Publications

Hepcidin, the master regulator of bioavailable iron, is a key mediator of anemia and also plays a central role in host defense against infection. We hypothesized that measuring hepcidin levels in cord blood could provide an early indication of interindividual differences in iron regulation with quantifiable implications for anemia, malaria, and mortality-related risk. Hepcidin concentrations were measured in cord plasma from a birth cohort (N = 710), which was followed for up to 4 years in a region of perennial malaria transmission in Muheza, Tanzania (2002-2006). At the time of delivery, cord hepcidin levels were correlated with inflammatory mediators, iron markers, and maternal health conditions. Hepcidin levels were 30% (95% confidence interval [CI]: 12%, 44%) lower in children born to anemic mothers and 48% (95% CI: 11%, 97%) higher in placental malaria-exposed children. Relative to children in the lowest third, children in the highest third of cord hepcidin had on average 2.5 g/L (95% CI: 0.1, 4.8) lower hemoglobin levels over the duration of follow-up, increased risk of anemia and severe anemia (adjusted hazard ratio [HR] [95% CI]: 1.18 [1.03, 1.36] and 1.34 [1.08, 1.66], respectively), and decreased risk of malaria and all-cause mortality (adjusted HR [95% CI]: 0.78 [0.67, 0.91] and 0.34 [0.14, 0.84], respectively). Although longitudinal measurements of hepcidin and iron stores are required to strengthen causal inference, these results suggest that hepcidin may have utility as a biomarker indicating children's susceptibility to anemia and infection in early life.

BACKGROUND

ST-segment elevation myocardial infarction (STEMI) in patients with concomitant multivessel (MV) coronary artery disease (CAD) is associated with poor outcomes. Percutaneous coronary intervention (PCI) of the culprit-lesion only (CLO) as compared with a MV PCI approach to revascularization remains uncertain. Our objective is to gain a better understanding of the efficacy and safety of CLO as compared with MV PCI in patients with STEMI by conducting an updated meta-analysis.

METHODS

A comprehensive search of PubMed, CENTRAL, EMBASE, The Cochrane Central Register, the ClinicalTrials.gov Website, and Google Scholar databases of randomized controlled trials (RCTs) was performed.

RESULTS

Seven RCTs were included, enrolling a total of 2006 patients. We found that there was a significant reduction in major adverse cardiovascular events (MACE) (OR, 0.62; 95% CI, 0.43-0.90), cardiovascular mortality (OR, 0.46; 95% CI, 0.27-0.80), and repeat revascularization (RRV) (OR, 0.39; 95% CI, 0.30-0.51) favoring MV over the CLO approach for patients undergoing primary PCI. The number needed to treat in order to prevent one CV mortality, RRV, or MACE event is 47, 11, and 16 patients, respectively. No differences were observed between MV vs. CLO PCI for subsequent myocardial infarction (OR, 0.74; 95% CI, 0.40-1.39), all-cause mortality (OR, 0.78; 95% CI, 0.53-1.15), non-cardiovascular mortality (OR, 1.35; 95% CI, 0.74-2.48), all-bleeding events (OR, 0.82; 95% CI, 0.40-1.65), contrast-induced nephropathy (OR, 0.72; 95% CI, 0.33-1.54), and stroke (OR, 1.28; 95% CI, 0.47-3.46).

CONCLUSIONS

MV PCI significantly reduces the rate of MACE, CV mortality, and RRV without significant harm as compared to CLO PCI.

There is an increasing recognition of the immune system as an important mediator in the pathogenesis of Alzheimer's disease (AD). As immune system modulators, non-steroidal anti-inflammatory drugs (NSAIDs) garnered initial enthusiasm from pre-clinical and epidemiologic studies as agents to reduce the risk of AD. Areas covered: This article will examine the evidence for the use of NSAIDs in AD by discussing the proposed mechanism of action, results from epidemiologic studies, and data from randomized controlled trials. In addition, a survey of several novel approaches to targeting inflammatory pathways currently in pre-clinical and clinical phases of development is presented. These agents primarily act to modulate microglial functioning, enhance amyloid-β phagocytosis, suppress potentially harmful pro-inflammatory responses, or enhance systemic immunity. Expert commentary: While long-term use of NSAIDs is associated with a reduced incidence of AD in epidemiologic studies, randomized controlled trials have not replicated these findings. Thus, NSAID use cannot currently be recommended either for primary prevention or treatment of AD. However, the available evidence does suggest that cognitively normal patients taking long-term courses of NSAIDs for other indications likely have a decreased risk of AD, which represents an important finding given the high prevalence of NSAID use among older adults.

BACKGROUND

Previous emergency contraception studies have excluded women who report >1 episode of unprotected or underprotected intercourse. Thus, clinical recommendations are based on exposure to a single episode of underprotected intercourse.

OBJECTIVE

We sought to assess the prevalence and timing of underprotected intercourse episodes among women requesting emergency contraception and to examine the probability of pregnancy following an emergency contraception regimen including placement of either a copper intrauterine device or a levonorgestrel intrauterine device with simultaneous administration of an oral levonorgestrel pill in women reporting multiple underprotected intercourse episodes, including episodes beyond the Food and Drug Administration-approved emergency contraception time frame (6-14 days).

STUDY DESIGN

Women seeking emergency contraception who had a negative pregnancy test and desired either a copper intrauterine device or levonorgestrel emergency contraception regimen enrolled in this prospective observational study. At enrollment, participants reported the number and timing of underprotected intercourse episodes in the previous 14 days. Two weeks later, participants reported the results of a self-administered home pregnancy test.

RESULTS

Of the 176 women who presented for emergency contraception and received a same-day intrauterine device, 43% (n = 76) reported multiple underprotected intercourse episodes in the 14 days prior to presenting for emergency contraception. Women with multiple underprotected intercourse episodes reported a median of 3 events (range 2-20). Two-week pregnancy data were available for 172 (98%) participants. Only 1 participant had a positive pregnancy test. Pregnancy occurred in 0 of 97 (0%; 95% confidence interval, 0-3.7%) women with a single underprotected intercourse episode and 1 of 75 (1.3%; 95% confidence interval, 0-7.2%) women reporting multiple underprotected intercourse episodes; this includes 1 of 40 (2.5%; 95% confidence interval, 0-13.2%) women reporting underprotected intercourse 6-14 days prior to intrauterine device insertion.

CONCLUSION

Women seeking emergency contraception from clinics commonly reported multiple recent underprotected intercourse episodes, including episodes occurring beyond the Food and Drug Administration-approved emergency contraception time frame. However, the probability of pregnancy was low following same-day intrauterine device placement.