Effect on longitudinal growth and anemia of zinc or multiple micronutrients added to vitamin A: a randomized controlled trial in children aged 6-24 months

<p>Abstract</p> <p>Background</p> <p>The benefits of zinc or multiple micronutrient supplementations in African children are uncertain. African children may differ from other populations of children in developing countries because of differences in the prevalence of zinc deficiency, low birth weight and preterm delivery, recurrent or chronic infections such as HIV, or the quality of complementary diets and genetic polymorphisms affecting iron metabolism.</p> <p>The aim of this study was to ascertain whether adding zinc or multiple micronutrients to vitamin A supplementation improves longitudinal growth or reduces prevalence of anemia in children aged 6-24 months.</p> <p>Methods</p> <p>Randomized, controlled double-blinded trial of prophylactic micronutrient supplementation to children aged 6-24 months. Children in three cohorts - 32 HIV-infected children, 154 HIV-uninfected children born to HIV-infected mothers, and 187 uninfected children born to HIV-uninfected mothers - were separately randomly assigned to receive daily vitamin A (VA) [n = 124], vitamin A plus zinc (VAZ) [n = 123], or multiple micronutrients that included vitamin A and zinc (MM) [n = 126].</p> <p>Results</p> <p>Among all children there were no significant differences between intervention arms in length-for-age Z scores (LAZ) changes over 18 months. Among stunted children (LAZ below -2) [n = 62], those receiving MM had a 0.7 Z-score improvement in LAZ versus declines of 0.3 in VAZ and 0.2 in VA (P = 0.029 when comparing effects of treatment over time). In the 154 HIV-uninfected children, MM ameliorated the effect of repeated diarrhea on growth. Among those experiencing more than six episodes, those receiving MM had no decline in LAZ compared to 0.5 and 0.6 Z-score declines in children receiving VAZ and VA respectively (P = 0.06 for treatment by time interaction). After 12 months, there was 24% reduction in proportion of children with anemia (hemoglobin below 11 g/dL) in MM arm (P = 0.001), 11% in VAZ (P = 0.131) and 18% in VA (P = 0.019). Although the within arm changes were significant; the between-group differences were not significant.</p> <p>Conclusions</p> <p>Daily multiple micronutrient supplementation combined with vitamin A was beneficial in improving growth among children with stunting, compared to vitamin A alone or to vitamin A plus zinc. Effects on anemia require further study.</p> <p>Trial registration</p> <p>This study is registered with ClinicalTrials.gov, number .NCT00156832.</p

Omecamtiv mecarbil in chronic heart failure with reduced ejection fraction, GALACTIC‐HF: baseline characteristics and comparison with contemporary clinical trials

Aims: The safety and efficacy of the novel selective cardiac myosin activator, omecamtiv mecarbil, in patients with heart failure with reduced ejection fraction (HFrEF) is tested in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTIC‐HF) trial. Here we describe the baseline characteristics of participants in GALACTIC‐HF and how these compare with other contemporary trials. Methods and Results: Adults with established HFrEF, New York Heart Association functional class (NYHA) ≥ II, EF ≤35%, elevated natriuretic peptides and either current hospitalization for HF or history of hospitalization/ emergency department visit for HF within a year were randomized to either placebo or omecamtiv mecarbil (pharmacokinetic‐guided dosing: 25, 37.5 or 50 mg bid). 8256 patients [male (79%), non‐white (22%), mean age 65 years] were enrolled with a mean EF 27%, ischemic etiology in 54%, NYHA II 53% and III/IV 47%, and median NT‐proBNP 1971 pg/mL. HF therapies at baseline were among the most effectively employed in contemporary HF trials. GALACTIC‐HF randomized patients representative of recent HF registries and trials with substantial numbers of patients also having characteristics understudied in previous trials including more from North America (n = 1386), enrolled as inpatients (n = 2084), systolic blood pressure &lt; 100 mmHg (n = 1127), estimated glomerular filtration rate &lt; 30 mL/min/1.73 m2 (n = 528), and treated with sacubitril‐valsartan at baseline (n = 1594). Conclusions: GALACTIC‐HF enrolled a well‐treated, high‐risk population from both inpatient and outpatient settings, which will provide a definitive evaluation of the efficacy and safety of this novel therapy, as well as informing its potential future implementation

Defusing the Bug Bomb: Legal Strategies to Combat Antibiotic Resistant Infections

The overuse of antibiotics has created a potential public health menace—the growth of microbial infections resistant to them. Antibiotic resistance stems from many causes that include the use of antibiotics in animal feed, medical practitioners’ over-prescription, the general public’s misuse of the drugs, and the failure to develop new antibiotics. This has led to the development of so called “super bugs” that are often immune to first line antibiotic therapies, such as penicillin, and to more powerful, broad-spectrum treatments. The CDC considers the primary source of antibiotic resistant infections in humans to come from our overuse of antibiotics and the failure to develop new antibiotics. In the words of the director of the CDC, “[t]he most resistant organisms in hospitals are emerging in those settings because of poor anti-microbial stewardship among humans.” Thus, this Article focuses on legal strategies both to control the use of antibiotics, and to develop antibiotic drug therapies to halt the spread of antibiotic resistant infections from person to person

Multi-omic longitudinal study reveals immune correlates of clinical course among hospitalized COVID-19 patients

The IMPACC cohort, composed of &gt;1,000 hospitalized COVID-19 participants, contains five illness trajectory groups (TGs) during acute infection (first 28&nbsp;days), ranging from milder (TG1-3) to more severe disease course (TG4) and death (TG5). Here, we report deep immunophenotyping, profiling of &gt;15,000 longitudinal blood and nasal samples from 540 participants of the IMPACC cohort, using 14 distinct assays. These unbiased analyses identify cellular and molecular signatures present within 72&nbsp;h of hospital admission that distinguish moderate from severe and fatal COVID-19 disease. Importantly, cellular and molecular states also distinguish participants with more severe disease that recover or stabilize within 28&nbsp;days from those that progress to fatal outcomes (TG4 vs. TG5). Furthermore, our longitudinal design reveals that these biologic states display distinct temporal patterns associated with clinical outcomes. Characterizing host immune responses in relation to heterogeneity in disease course may inform clinical prognosis and opportunities for intervention

Cardiac myosin activation with omecamtiv mecarbil in systolic heart failure

BACKGROUND The selective cardiac myosin activator omecamtiv mecarbil has been shown to improve cardiac function in patients with heart failure with a reduced ejection fraction. Its effect on cardiovascular outcomes is unknown. METHODS We randomly assigned 8256 patients (inpatients and outpatients) with symptomatic chronic heart failure and an ejection fraction of 35% or less to receive omecamtiv mecarbil (using pharmacokinetic-guided doses of 25 mg, 37.5 mg, or 50 mg twice daily) or placebo, in addition to standard heart-failure therapy. The primary outcome was a composite of a first heart-failure event (hospitalization or urgent visit for heart failure) or death from cardiovascular causes. RESULTS During a median of 21.8 months, a primary-outcome event occurred in 1523 of 4120 patients (37.0%) in the omecamtiv mecarbil group and in 1607 of 4112 patients (39.1%) in the placebo group (hazard ratio, 0.92; 95% confidence interval [CI], 0.86 to 0.99; P = 0.03). A total of 808 patients (19.6%) and 798 patients (19.4%), respectively, died from cardiovascular causes (hazard ratio, 1.01; 95% CI, 0.92 to 1.11). There was no significant difference between groups in the change from baseline on the Kansas City Cardiomyopathy Questionnaire total symptom score. At week 24, the change from baseline for the median N-terminal pro-B-type natriuretic peptide level was 10% lower in the omecamtiv mecarbil group than in the placebo group; the median cardiac troponin I level was 4 ng per liter higher. The frequency of cardiac ischemic and ventricular arrhythmia events was similar in the two groups. CONCLUSIONS Among patients with heart failure and a reduced ejection, those who received omecamtiv mecarbil had a lower incidence of a composite of a heart-failure event or death from cardiovascular causes than those who received placebo. (Funded by Amgen and others; GALACTIC-HF ClinicalTrials.gov number, NCT02929329; EudraCT number, 2016 -002299-28.)