Gender bias in access to healthcare in Nigeria: a study of end-stage renal disease

Sexual inequalities exist in most societies. Women are discriminated against in almost every sphere of life (i.e. in politics, inheritance, etc.) from childhood, especially in communities where there is a preference for the male child. Women have limited access to assets and services such as education and health care, resulting in their being socio-economically dependent on men.     

Living well with kidney disease by patient and care-partner empowerment: kidney health for everyone everywhere

Clinical and Experimental Nephrology - Living with chronic kidney disease (CKD) is associated with hardships for patients and their care partners. Empowering patients and their care partners,...     

Atypical antipsychotics for the treatment of ICU delirium

Delirium is commonly described in critically ill patients as 1 factor contributing to increased length of intensive care unit and hospital stay, secondary complications, and increased mortality. Initial screening tools for delirium in hospitalized patients are generally easy to use; however, many centers have struggled with implementing these tools in a consistent and systematic manner. Haloperidol has traditionally been prescribed as the primary agent of choice for the treatment of delirium in critically ill patients. Clinicians have been challenged to consider alternative agents due to adverse effects such as extrapyramidal symptoms, QTc prolongation, and possible torsades de pointes with haloperidol use. The atypical antipsychotics are attractive alternatives to haloperidol with improved safety profiles but are flawed by limited data to support dosing and efficacy in this patient population. Future studies that provide large, prospective, double-blinded, placebo-controlled data to support the implementation of these agents as standard therapy over haloperidol are needed.     

A data-driven approach to optimized medication dosing: a focus on heparin

Purpose

To demonstrate a novel method that utilizes retrospective data to develop statistically optimal dosing strategies for medications with sensitive therapeutic windows. We illustrate our approach on intravenous unfractionated heparin, a medication which typically considers only patient weight and is frequently misdosed.

Methods

We identified available clinical features which impact patient response to heparin and extracted 1,511 patients from the multi-parameter intelligent monitoring in intensive care II database which met our inclusion criteria. These were used to develop two multivariate logistic regressions, modeling sub- and supra-therapeutic activated partial thromboplastin time (aPTT) as a function of clinical features. We combined information from these models to estimate an initial heparin dose that would, on a per-patient basis, maximize the probability of a therapeutic aPTT within 4–8 h of the initial infusion. We tested our model’s ability to classifying therapeutic outcomes on a withheld dataset and compared performance to a weight-alone alternative using volume under surface (VUS) (a multiclass version of AUC).

Results

We observed statistically significant associations between sub- and supra-therapeutic aPTT, race, ICU type, gender, heparin dose, age and Sequential Organ Failure Assessment scores with mean validation AUC of 0.78 and 0.79 respectively. Our final model improved outcome classification over the weight-alone alternative, with VUS values of 0.48 vs. 0.42.

Conclusions

This work represents an important step in the secondary use of health data in developing models to optimize drug dosing. The next step would be evaluating whether this approach indeed achieves target aPTT more reliably than the current weight-based heparin dosing in a randomized controlled trial.     

Low-Dose Intradermal Infection with Trypanosoma congolense Leads to Expansion of Regulatory T Cells and Enhanced Susceptibility to Reinfection

BALB/c mice are highly susceptible to experimental intraperitoneal Trypanosoma congolense infection. However, a recent report showed that these mice are relatively resistant to primary intradermal low-dose infection. Paradoxically, repeated low-dose intradermal infections predispose mice to enhanced susceptibility to an otherwise noninfectious dose challenge. Here, we explored the mechanisms responsible for this low-dose-induced susceptibility to subsequent low-dose challenge infection. We found that akin to intraperitoneal infection, low-dose intradermal infection led to production of interleukin-10 (IL-10), IL-6, IL-12, tumor necrosis factor alpha (TNF-α), transforming growth factor β (TGF-β), and gamma interferon (IFN-γ) by spleen and draining lymph node cells. Interestingly, despite the absence of parasitemia, low-dose intradermal infection led to expansion of CD4⁺ CD25⁺ Foxp3⁺ cells (T regulatory cells [Tregs]) in both the spleens and lymph nodes draining the infection site. Depletion of Tregs by anti-CD25 monoclonal antibody (MAb) treatment during primary infection or before challenge infection following repeated low-dose infection completely abolished the low-dose-induced enhanced susceptibility. In addition, Treg depletion was associated with dramatic reduction in serum levels of TGF-β and IL-10. Collectively, these findings show that low-dose intradermal infection leads to rapid expansion of Tregs, and these cells mediate enhanced susceptibility to subsequent infection.