Proton Pump Inhibitors Versus Histamine-2 Receptor Antagonists Likely Increase Mortality in Critical Care: An Updated Meta-Analysis

BackgroundUpper gastrointestinal bleeding is common among the critically ill. Recently, the Proton Pump Inhibitors (PPIs) vs. Histamine-2 Receptor Blockers for Ulcer Prophylaxis Therapy in the Intensive Care Unit (PEPTIC) trial suggested PPIs might increase mortality. We performed an updated meta-analysis to further inform discussion.MethodsWe leveraged 2 recent systematic reviews to identify randomized controlled trials directly comparing PPIs and H-2 Receptor Antagonists (H2RAs) for stress ulcer prophylaxis in critically ill patients and reporting mortality. We extracted mortality data from each study and meta-analyzed them with the PEPTIC trial using a random effects model.ResultsOf 28,559 total patients, 14,436 (50.5%) were allocated to PPI and 14,123 to H2RAs (49.5%). Compared to H2RAs, the pooled relative risk for mortality was 1.05 (95% confidence interval 1.00-1.10) with an estimated risk difference for mortality of 9 additional deaths per 1000 patients exposed to PPI (95% confidence interval 0-18); heterogeneity was low (I² = 0%; P = 0.826).ConclusionsStress ulcer prophylaxis with PPIs likely increases mortality compared to H2RAs. Whether stress ulcer prophylaxis is beneficial in critical care remains open to further study.     

Sera from patients with heparin-induced thrombocytopenia generate platelet-derived microparticles with procoagulant activity: an explanation for the thrombotic complications of heparin-induced thrombocytopenia

Heparin-induced thrombocytopenia is characterized by moderate thrombocytopenia and thrombotic complications, whereas quinine/quinidine-induced thrombocytopenia usually presents with severe thrombocytopenia and bleeding. Using flow cytometry and assays of procoagulant activity, we investigated whether sera from patients with these immune drug reactions could stimulate normal platelets to generate platelet-derived microparticles with procoagulant activity. Sera or purified IgG from patients with heparin-induced thrombocytopenia stimulated the formation of platelet-derived microparticles in a heparin-dependent fashion. Further studies showed that heparin-induced thrombocytopenia sera also produced a marked increase in procoagulant activity. In contrast, sera from patients with quinine- or quinidine-induced thrombocytopenia did not generate platelet-derived microparticles nor generate increased procoagulant activity. However, quinine/quinidine-induced thrombocytopenia sera produced a significant increase in the binding of IgG to platelets in a drug-dependent fashion, whereas sera from patients with heparin-induced thrombocytopenia demonstrated no drug-dependent binding of IgG to platelets. We also observed increased levels of circulating microparticles in patients with acute heparin-induced thrombocytopenia compared with control patients. Our observations indicate that the generation of procoagulant platelet-derived microparticles in vivo is a plausible explanation for the thrombotic complications observed in some patients with heparin-induced thrombocytopenia.     

Exploring the disclosure decisions made by physiotherapists with a specific learning difficulty

Objectives

To explore the disclosure decisions made in the workplace by physiotherapy staff with a specific learning difficulty (SpLD).

Iron status and anemia in the elderly: new findings and a review of previous studies

Iron status was determined in 280 free-living and healthy elderly men (n = 131) and women (n = 149) by assessing dietary and supplemental iron intake as well as ten biochemical measures of iron nutriture (erythrocyte count, hemoglobin level, hematocrit, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, plasma iron level, total iron-binding capacity, per cent transferrin saturation, and ferritin level). Subject ages ranged from 60 to 93 years with a median age of 72 years for both women and men. For comparison purposes, iron status measures in an unselected group of younger men (n = 107) and women (n = 164) between the ages of 20 and 39 years were also obtained. None of the elderly women and only two (1.2 per cent) of the younger women had low hemoglobin levels (less than 12.0 g/dl). Three (2.3 per cent) of the elderly men and none of the younger men had low hemoglobin levels (less than 14 g/dl). Other iron status measures revealed that anemia or iron deficiency was no more prevalent in the healthy elderly population than in the younger adult population when identical criteria were used to assess iron nutriture. The genesis of anemia often seen in the elderly is not completely understood. Reported evidence suggests the presence of anemia in the elderly is a result of overall reduction of hematopoietic reserves. Because of the potentially serious consequences of this assumption about anemia to the treatment of the elderly, the authors critically review some of the studies that have been designed in the past to determine the prevalence and etiology of anemia in the aged. They suggest that health status, race, socioeconomic status, diet, and region are more important than age as explanations for the high prevalence of anemia seen in many previous studies.     

Altered muscle metabolism in rats after thermal injury

Burn injury is associated with an elevation in total body oxygen consumption, increased hepatic alanine uptake and conversion to glucose, and a negative nitrogen balance. The primary source of the alanine used for gluconeogenesis by the liver and of the nitrogen lost as urea is believed to be from skeletal muscle. Selected muscle regulatory enzymes and pyruvate and oleate oxidation rates were assayed for maximal activity during the postburn period. Male Sprague-Dawley rats that received 50% total body surface scald burns on the dorsum and abdomen were examined for citrate synthase (CS), phosphofructokinase (PFK), and glutamate-pyruvate transaminase (GPT) activity in uninjured muscle at 3, 7, 13, and 20 days postburn, and the ability of muscle to oxidize pyruvate and oleate was measured at 3 and 13 days after injury. CS, PFK, and GPT activities increased significantly (p < 0.05) by 13–20 days after injury in the soleus and diaphragm. The epitrochlearis showed no change in CS, but PFK and GPT were elevated within this time frame. The gastrocnemius muscle showed an elevated oleate oxidation rate at 13 days after injury, but no change at 3 days postburn. Pyruvate oxidation rates were unaltered.The results of this study indicate that during the postburn period several metabolic alterations occur in muscle. These adaptations include: (1) elevated CS activity which may be associated with increased oxidative capactiy, (2) increased PFK activity which implies that more substrate is being shuttled through the glycolytic pathway, (3) increased GPT activity which may reflect increased pyruvate conversion to alanine, and (4) increased oleate oxidation rates which demonstrate that muscle is utilizing more fatty acid substrates during the postburn period.     

Thyroid storm in a child following radioactive iodine (RAI) therapy: a consequence of RAI versus withdrawal of antithyroid medication

A 7.5-yr-old boy with Graves' disease, difficult to control with antithyroid medication and radioactive iodine (RAI) therapy, developed thyroid storm encephalopathy on day 13 after withdrawal of methimazole therapy, 4 days after iodine-131 treatment. We attributed his thyroid storm to withdrawal of antithyroid medication as opposed to RAI therapy. We interpret this case as indicating that there may be a need to reevaluate the duration of antithyroid medication withdrawal before RAI therapy for hyperthyroid children at increased risk for thyroid storm.