Chronic kidney disease (CKD) arising from hypertension or other etiologies often progresses to ESRD despite treatment. One of the mainstays of treatment for CKD is blockade of the renin-angiotensin system (RAS). RAS blockers - angiotensin converting enzyme inhibitors (ACE-Is) and angiotensin receptor blockers (ARBs) - have the unique ability to decrease urine albumin excretion independent of systemic blood pressure. Despite their clinical effectiveness, RAS blockers do not completely stop CKD progression, thus there exists a need for new therapies. The association between proteinuria and an over-active RAS is well described and is mediated by angiotensin II (ang II) via the AT1 angiotensin receptor. This suggests that ang II, via AT1 receptors, promotes proteinuria and that this may be an important pathway in the pathogenesis of CKD. Yet, the mechanism and cellular site of action where ang II causes proteinuria have not been clearly demonstrated. To investigate the role of AT1 in podocytes we used cell-specific gene targeting to generate mice lacking all AT1 receptors in the podocyte (PodKOs). PodKOs were then crossed with mice expressing a renin transgene (RenTg) to generate PodKO-RenTg mice. RenTg mice are hypertensive and provide an effective genetic model in which to study RAS over-activation. We hypothesized that AT1 signaling is a critical mediator of albuminuria in hypertensive kidney disease and that actions of AT1 receptors in the podocyte mediate kidney injury. PodKO mice develop normally and there is no difference in kidney weight between Cre- and Cre+ mice (6.9 ± 0.5 mg/g BW vs 7.0 ± 0.3 mg/g BW). At baseline, there was no significant difference in albumin excretion between 24 week old RenTg and PodKO-RenTg mice (210 ± 70.9 μg vs 228.7 ± 37.6 μg). When the mice were subjected to uninephrectomy to induce CKD, both RenTg and PodKO-RenTg mice developed similar degrees of albuminuria (279.9 ± 105.8 μg vs 366.8 ± 105.9 μg). However, kidneys from PodKO-RenTg mice had higher levels of glomerulosclerosis and mesangial expansion. Taken together, these data suggest that AT1 receptors in podocytes do not promote albuminuria and may have protective effects.
The objective of this study was to assess the clinical and financial impact of a quality improvement project that utilized a modified Early Warning Score (mEWS)-based clinical decision support intervention targeting early recognition of sepsis decompensation.
BACKGROUND Academic medical centers have expanded their inpatient medicine services with advanced practice clinicians (APCs) or nonteaching hospitalists in response to patient volumes, residency work hour restrictions, and recently, COVID‐19. Reports of clinical outcomes, cost, and resource utilization differ among inpatient team structures. OBJECTIVE Directly compare outcomes among resident, APC, and solo hospitalist inpatient general medicine teams. DESIGN Retrospective cohort study using multivariable analysis adjusted for time of admission, interhospital transfer, and comorbidities that compares clinical outcomes, cost, and resource utilization. SUBJECTS Patients 18 years or older discharged from an inpatient medicine service between July 2015 and July 2018 (N = 12,716). MAIN MEASURES Length of stay (LOS), 30‐day readmission, inpatient mortality, normalized total direct cost, discharge time, and consultation utilization. KEY RESULTS Resident teams admitted fewer patients at night (32.0%; P < .001) than did APC (49.5%) and hospitalist (48.6%) teams. APCs received nearly 4% more outside transfer patients ( P = .015). Hospitalists discharged patients 26 minutes earlier than did residents (mean hours after midnight [95% CI], 14.58 [14.44‐14.72] vs 15.02 [14.97‐15.08]). Adjusted consult utilization was 15% higher for APCs (adjusted mean consults per admission [95% CI], 1.00 [0.96‐1.03]) and 8% higher for residents (0.93 [0.90‐0.95]) than it was for hospitalists (0.85 [0.80‐0.90]). No differences in LOS, readmission, mortality, or cost were observed between the teams. CONCLUSION We observed similar costs, LOS, 30‐day readmission, and mortality among hospitalist, APC, and resident teams. Our results suggest clinical outcomes are not significantly affected by team structure. The addition of APC or hospitalist teams represent safe and effective alternatives to traditional inpatient resident teams.
Results of a research project to quantify and improve the accuracy of point-of-care (POC) International Normalized Ratio (INR) values are reported.The accuracy of POC INR values relative to laboratory-measured INR values was retrospectively assessed in a cohort of patients with same-day INR determinations by both methods. Univariate linear regression was performed to derive a correction factor for POC INR values of >3; this correction factor was validated in a second cohort.In the derivation cohort (259 patients and 344 paired INR results), agreement of POC values with corresponding laboratory INR values at two specified thresholds (±15% and ±25%) was 51.2% and 66.6%, respectively; for POC INR values of >3 (n = 205), agreement was lower (24.9% and 44.9%, respectively). Univariate linear regression yielded a coefficient of 0.77 (95% confidence interval, 0.76-0.79; p < 0.001). Applying a correction factor of 0.8 to POC INR values in a validation cohort (169 patients and 209 paired INR values) significantly improved the accuracy of POC INR values of >3 relative to laboratory values (from 7% to 71.1% at the lower threshold and from 23.5% to 88.8% at the higher threshold, p < 0.0001 for both comparisons).Agreement between POC and laboratory INR results in one institution was poor, especially when POC INR values exceeded 3. Application of an institution-specific correction factor to POC INR values of >3 improved agreement with laboratory INR results but would not have significantly reduced differences in protocol-based warfarin dosage adjustments.
Older adults have a significantly greater risk of venous thromboembolism ( VTE ), including deep vein thrombosis and pulmonary embolism, than younger adults. The cause of this greater risk is thought to be multifactorial, including age‐related changes in hemostatic factors and greater comorbid conditions and hospitalizations, but is not completely understood. Moreover, VTE remains underrecognized in older adults and may present atypically. Thus, a low index of clinical suspicion is essential when evaluating older adults with possible VTE . Despite this underrecognition in older adults, the diagnostic approach remains similar for all age groups and includes estimation of pretest probability, measurement of the D‐dimer, and imaging. Antithrombotic agents are the mainstay of VTE treatment and, when used appropriately, substantially reduce VTE recurrence and complications. The approval of novel oral anticoagulants ( NOAC s), including dabigatran, rivaroxaban, apixaban, and edoxaban, provide clinicians with new therapeutic options. In some individuals, NOAC s may offer advantages over warfarin, including fewer drug interactions, more‐predictable anticoagulation, and lower risk of bleeding. Nevertheless, anticoagulation of VTE in older adults should always be performed cautiously, because age is a risk factor for bleeding complications. Identifying modifiable bleeding risk factors and balancing the risks of VTE recurrence with hemorrhage are important considerations when using anticoagulants in older adults.
Source Citation Wallentin L, Yusuf S, Ezekowitz MD, et al. Efficacy and safety of dabigatran compared with warfarin at different levels of international normalised ratio control for stroke prevention in atrial fibrillation: an analysis of the RE-LY trial. Lancet. 2010;376:975-83. 20801496
