Unresolved legal and ethical issues in research of adults with severe traumatic brain injury: analysis of an ongoing protocol

This paper synthesizes federal and state laws and bioethics literature with observations from an ongoing research protocol to identify, define, and clarify the unresolved legal and ethical issues regarding research involving adults with traumatic brain injury (TBI). Solutions that protect rights and minimize unnecessary impediments to valuable clinical and scientific inquiry are also illustrated using the same protocol. Research was performed at intensive care, inpatient rehabilitation, and long-term acute chronic hospitals. Our research protocol identified five areas of law impacting adults with TBI: advanced directives, healthcare surrogacy acts, probate acts, power of attorney acts, and the Health Insurance Portability and Accountability Act. The published bioethics literature and responses from local human subject institutional review boards (IRBs) suggest that some of the unresolved ethical issues in research include defining vulnerability, defining informed voluntary consent, determining competency and/or decision-making capacity, using caregivers as subjects, and conducting multisite cooperative studies. Collaboration with IRB members and administrators as well as legal and research ethic scholars developed procedures that protect rights while avoiding unnecessary impediments to research. Investigations of persons with TBI and other cognitive impairments are governed by complicated and inconsistent regulations within the Common Rule and federal and state statues. A need for clear and consistent regulatory guidance regarding multisite studies of TBI persists. In lieu of regulatory guidance, carefully researched solutions for critical peer review are needed to guide future multisite investigations of TBI.     

NIH peer review of grant applications for clinical research

Context  Support of research to facilitate translation of scientific discoveries to the prevention and treatment of human disease is a high priority for the US National Institutes of Health (NIH). Nevertheless, a perception exists among clinical investigators that the NIH peer review process may discriminate against clinical research. Objective  To describe recent trends and outcomes of peer review of grant applications to NIH requesting support for clinical research. Design and Setting  Peer review outcomes of grant applications submitted to NIH by MDs were compared with those of non-MDs, and outcomes of applications involving inclusion of human subjects were compared with those not involving human subjects. Analyses were carried out using an inclusive definition of clinical research and after stratifying clinical research into specific categories. Main Outcome Measures  Median priority scores and funding rates. Results  Between 1997 and 2002, on average, 25.2% of total grant applications (ranging from 27 607 to 34 422 per year) were submitted by MDs, and 27.5% of awards (ranging from 8495 to 10 769 awards per year) were made to MDs. Median priority scores (239.0 vs 250.0) and funding rates (31.4% vs 29.1%) reviewed in 2 grant cycles in 2002 were more favorable for MDs than for non-MDs (P<.001). However, median priority scores (254.0 vs 244.0) and funding rates (23.9% vs 28.1%) were less favorable (P<.001) for R01 applications for clinical research (n = 7227 applications) than for nonclinical research (n = 10 209). This trend was most convincingly observed for clinical research categorized as mechanisms of disease (P = .006) or clinical trials and interventions (P = .001). Similar trends were observed for grant mechanisms other than R01. Concerns about safety and privacy of human subjects may have contributed to the less favorable outcomes of clinical research applications. Conclusion  Although physicians compete favorably in the peer review process, review outcomes are modestly less favorable for grant applications for clinical research than for laboratory research.      

Human granulocytic ehrlichiosis co-incident with Lyme borreliosis in pregnant woman--a case study

A case of 25 years old woman, living in an endemic area for Lyme borreliosis was examined. In 29 th week of pregnancy thrombocytopenia, fever and fatigue were observed, in the last 7 weeks erythema migrans was present. The woman was not treated by that time. The infant presented thrombocytopenia in the first few weeks of life. 3 months after delivery erythema migrans disseminata was observed, by that time Lyme borreliosis and HGE were serologically confirmed. It was not confirmed that the infection was transferred to the infant, but it is possible that thrombocytopenia was caused by the infection with A. phagocytophila.     

Multiple micronutrient supplements during pregnancy do not reduce anemia or improve iron status compared to iron-only supplements in Semirural Mexico

The impact of iron-only supplements (FE) versus multiple micronutrient supplements containing iron (MM) during pregnancy on iron status was assessed in a subsample (n = 453) of women who participated in a randomized double-blind trial in Mexico. Compliance, monitored by observation, was high (>85%). The two groups were similar at recruitment (<13 wk gestation) for various sociodemographic characteristics and for mean hemoglobin (Hb) concentrations and prevalence of anemia (Hb < 110 g/L; 11%). However, mean serum ferritin was higher (P < 0.05) in the MM group (n = 142) compared to the FE group (n = 148) and the prevalence of iron deficiency (serum ferritin < 12 micro g/L) was lower in the MM group (44.4%) compared to the FE group (57.4%). By the third trimester, almost half the women were anemic in both groups, and mean Hb (g/L) was lower for the MM group (104.2; 95% CI: 102.5, 106.0) compared to the FE group (108.1; 95% CI: 106.4, 109.8) after adjusting for baseline serum ferritin. In contrast, there were no differences in Hb concentrations at 1 mo postpartum or in mean ferritin and prevalence of iron deficiency at 32 wk gestation and 1 mo postpartum (90.9 and 45.1% for the MM group; 92.6 and 47.3% for the FE group, respectively). In conclusion, rather than improve Hb or iron status relative to FE-only supplements as hypothesized, MM supplements may have slightly reduced Hb concentrations during pregnancy. Neither supplement was able to meet iron needs as evidenced by dramatic increases in anemia and iron deficiency by the end of pregnancy.