Iron Deficiency Anemia Associated With Acid-Modifying Medications: Two Cases and Literature Review

Iron deficiency anemia is often listed among potential adverse effects of gastric acid-suppressive medications, given that gastric acidity promotes intestinal absorption of nonheme iron. Additionally, the antacid calcium carbonate can inhibit iron absorption. However, there is little direct clinical evidence that proton-pump inhibitors, histamine-2 receptor antagonists, or calcium carbonate cause iron deficiency anemia. Most case reports have had substantial limitations (e.g., minimal follow-up and presence of other causes of iron deficiency), and retrospective cohort studies have lacked sufficient patient-specific detail to make strong causal inferences. We present 2 cases—both with detailed, prospective 10-year follow-up—in which combinations of proton-pump inhibitors, histamine-2 receptor antagonists and calcium carbonate were clearly associated with development of iron deficiency anemia. Overt iron-deficiency anemia is probably uncommon in patients who use acid-modifying medications and who have no other conditions that predispose to iron deficiency. Nevertheless, clinicians should be aware of this potential complication, given widespread use of these agents.     

Daily skin-to-skin contact in full-term infants and breastfeeding: Secondary outcomes from a randomized controlled trial

This randomized controlled trial evaluated the effect of a 5-week daily skin-to-skin contact (SSC) intervention between mothers and their full-term infants, compared with care-as-usual, on exclusive and continued breastfeeding duration during the first post-natal year. Healthy pregnant women (n = 116) from a community sample were enrolled and randomly allocated to the SSC or care-as-usual condition. SSC mothers were requested to provide one daily hour of SSC for the first five post-natal weeks. Twelve months post-partum, mothers indicated the number of exclusive and continued breastfeeding months. Multiple regression analyses were conducted using intention-to-treat, per-protocol and exploratory dose–response frameworks. In intention-to-treat analyses, exclusive and continued breastfeeding duration was not different between groups (exclusive: 3.61 ± 1.99 vs. 3.16 ± 1.77 months; adjusted mean difference 0.28, 95% confidence interval [CI] ?0.33 to 0.89; p = 0.36; continued: 7.98 ± 4.20 vs. 6.75 ± 4.06 months; adjusted mean difference 0.81, 95% CI ?0.46 to 2.08; p = 0.21). In per-protocol analyses, exclusive and continued breastfeeding duration was longer for SSC than care-as-usual dyads (exclusive: 4.89 ± 1.26 vs. 3.25 ± 1.80 months; adjusted mean difference 1.28, 95% CI 0.31–2.24; p = 0.01; continued: 10.81 ± 1.97 vs. 6.98 ± 4.08 months; adjusted mean difference 2.33, 95% CI 0.13–4.54; p = 0.04). Exploratory dose–response effects indicated that more SSC hours predicted longer exclusive and continued breastfeeding duration. This study demonstrates that for the total group, the 5-week daily SSC intervention did not extend exclusive and continued breastfeeding duration. However, for mothers performing a regular daily hour of SSC, this simple and accessible intervention may extend exclusive and continued breastfeeding duration by months. Future studies are required to confirm these promising findings. Trial registration: Netherlands Trial Register (NTR5697).     

Isolated Anisocoria as a Presenting Stroke Code Symptom is Unlikely to Result in Alteplase Administration

Background

Acute stroke codes may be activated for anisocoria, but how often these codes lead to a final stroke diagnosis or alteplase treatment is unknown. The purpose of this study was to assess the frequency of anisocoria in stroke codes that ultimately resulted in alteplase administration.

Application of the adverse outcome pathway framework to genotoxic modes of action

In May 2017, the Health and Environmental Sciences Institute's Genetic Toxicology Technical Committee hosted a workshop to discuss whether mode of action (MOA) investigation is enhanced through the application of the adverse outcome pathway (AOP) framework. As AOPs are a relatively new approach in genetic toxicology, this report describes how AOPs could be harnessed to advance MOA analysis of genotoxicity pathways using five example case studies. Each of these genetic toxicology AOPs proposed for further development includes the relevant molecular initiating events, key events, and adverse outcomes (AOs), identification and/or further development of the appropriate assays to link an agent to these events, and discussion regarding the biological plausibility of the proposed AOP. A key difference between these proposed genetic toxicology AOPs versus traditional AOPs is that the AO is a genetic toxicology endpoint of potential significance in risk characterization, in contrast to an adverse state of an organism or a population. The first two detailed case studies describe provisional AOPs for aurora kinase inhibition and tubulin binding, leading to the common AO of aneuploidy. The remaining three case studies highlight provisional AOPs that lead to chromosome breakage or mutation via indirect DNA interaction (inhibition of topoisomerase II, production of cellular reactive oxygen species, and inhibition of DNA synthesis). These case studies serve as starting points for genotoxicity AOPs that could ultimately be published and utilized by the broader toxicology community and illustrate the practical considerations and evidence required to formalize such AOPs so that they may be applied to genetic toxicity evaluation schemes. Environ. Mol. Mutagen. 61:114–134, 2020. © 2019 Wiley Periodicals, Inc.