Access to preventive care by immigrant populations

Mark FORT Harris — 2012-05-31T00:00:00Z

Many Immigrant populations lack access to primary health care. A recently published study on cholesterol screening among immigrant populations in the US found disparities in cholesterol screening in those originating from Mexico, largely due to limited access to health care. This inverse care affects immigrants in many destination countries despite their greater health need.Please see related article: http://www.equityhealthj.com/content/11/1/22

Effects of phlebotomy-induced reduction of body iron stores on metabolic syndrome: Results from a randomized clinical trial

Khosrow S Houschyar — 2012-05-30T00:00:00Z

Background: Metabolic syndrome (METS) is an increasingly prevalent but poorly understood clinical entity characterized by insulin resistance, glucose intolerance, dyslipidemia, hypertension and obesity. Increased oxidative stress catalyzed by accumulation of iron in excess of physiologic requirements has been implicated in the pathogenesis of METS but cause-and-effect relationships remain uncertain. The hypothesis that phlebotomy-induced reduction of body iron stores would alter clinical manifestations of METS was tested by a randomized trial. Methods: In a randomized-controlled single-blinded clinical trial 64 patients with METS were randomly assigned to iron reduction by phlebotomy (n=33) or to a waiting-list control group (n=31). Iron reduction patients had 300ml of blood removed at entry and between 250-500ml removed after 4 weeks depending on entry ferritin levels. Primary outcomes were change of systolic blood pressure and of insulin sensitivity as measured by HOMA-Index after 6 weeks. Secondary outcomes included HbA1c, plasma-glucose, blood lipids and heart rate. Results: Systolic blood pressure decreased from 148.5+/-12.3 mmHg to 130.5+/-11.8 mm Hg in the phlebotomy group and from 144.7+/-14.4 mmHg to 143.8+/-11.9 mmHg in the control group (difference -16.6 mmHg;95%-CI:-20.7;-12.5;p<0.001). No significant effect on the HOMA-Index was observed. Among secondary outcomes, blood glucose, HbA1c, LDL/HDL ratio and heart rate were significantly decreased by phlebotomy. Changes in blood pressure and HOMA-Index were correlated with reduction of ferritin. Conclusions: In patients with METS, phlebotomy with consecutive reduction of body iron stores lowered blood pressure and resulted in improvements of markers of cardiovascular risk and glycemic control. Blood donation may have beneficial effects for donating subjects with METS.Trial registration: ClinicalTrials.gov: NCT01328210Please see related article: http://www.biomedcentral.com/1741-7015/10/53

Back to past leeches: repeated phlebotomies and cardiovascular risk

Melania Manco — 2012-05-30T00:00:00Z

In patients with metabolic syndrome, body iron overload exacerbates insulin resistance, impairment of glucose metabolism, endothelium dysfunction and coronary artery responses. Conversely, iron depletion is effective to ameliorate glucose metabolism and dysfunctional endothelium. Most of its effectiveness seems to occur through the amelioration of systemic and hepatic insulin resistance.In a study published by BMC Medicine, Michalsen et al demonstrated a dramatic improvement of blood pressure, serum glucose and lipids after removing 550-800 ml of blood in subjects with metabolic syndrome. This effect was apparently independent of changes in insulin resistance, in contrast to previous cross-sectional and cohort studies investigating the association between iron overload, insulin resistance and cardiovascular disease.Despite drawbacks in the study design, its findings may lead the way to investigations aimed at exploring iron-dependent regulatory mechanisms of vascular tone in healthy individuals and patients with metabolic disease, thus providing a rationale for novel preventive and therapeutic strategies to counteract hypertension.Please see related article: http://www.biomedcentral.com/1741-7015/10/54

Statistical challenges in the development and evaluation of marker-based clinical tests

Lisa M McShane — 2012-05-29T00:00:00Z

Exciting new technologies for assessing markers in human specimens are now available to evaluate unprecedented types and numbers of variations in DNA, RNA, proteins, or biological structures such as chromosomes. These markers, whether viewed individually, or collectively as a "signature", have the potential to be useful for disease risk assessment, screening, early detection, prognosis, therapy selection, and monitoring for therapy effectiveness or disease recurrence. Successful translation from basic research findings to clinically useful test requires basic, translational, and regulatory sciences and a collaborative effort among individuals with varied types of expertise including laboratory scientists, technology developers, clinicians, statisticians, and bioinformaticians. The focus of this commentary is the many statistical challenges in translational marker research, specifically in the development and validation of marker-based tests that have clinical utility for therapeutic decision making.

Reporting recommendations for tumor marker prognostic studies (REMARK): explanation and elaboration

Douglas G Altman — 2012-05-29T00:00:00Z

Background: The Reporting Recommendations for Tumor Marker Prognostic Studies (REMARK) checklist consists of 20 items to report for published tumor marker prognostic studies. It was developed to address widespread deficiencies in the reporting of such studies. In this paper we expand on the REMARK checklist to enhance its use and effectiveness through better understanding of the intent of each item and why the information is important to report. Methods: REMARK recommends including a transparent and full description of research goals and hypotheses, subject selection, specimen and assay considerations, marker measurement methods, statistical design and analysis, and study results. Each checklist item is explained and accompanied by published examples of good reporting, and relevant empirical evidence of the quality of reporting. We give prominence to discussion of the 'REMARK profile', a suggested tabular format for summarizing key study details.SummaryThe paper provides a comprehensive overview to educate on good reporting and provide a valuable reference for the many issues to consider when designing, conducting, and analyzing tumor marker studies and prognostic studies in medicine in general.To encourage dissemination of the Reporting Recommendations for Tumor Marker Prognostic Studies (REMARK): Explanation and Elaboration, this article has also been published in PLoS Medicine.

New insights into the health effects of dietary saturated and omega-6 and omega-3 polyunsaturated fatty acids

Michel DE Lorgeril — 2012-05-21T00:00:00Z

Cardiovascular diseases and cancers are leading causes of morbidity and mortality. Reducing dietary saturated fat and replacing it with polyunsaturated fat is still the main dietary strategy to prevent cardiovascular diseases, although major flaws have been reported in the analyses supporting this approach. Recent studies introducing the concept of myocardial preconditioning have opened new avenues to understand the complex interplay between the various lipids and the risk of cardiovascular diseases. The optimal dietary fat profile includes a low intake of both saturated and omega-6 fatty acids and a moderate intake of omega-3 fatty acids. This profile is quite similar to the Mediterranean diet. On the other hand, recent studies have found a positive association between omega-6 and breast cancer risk. In contrast, omega-3 fatty acids do have anticancer properties. It has been shown that certain (Mediterranean) polyphenols significantly increase the endogenous synthesis of omega-3 whereas high intake of omega-6 decreases it. Finally, epidemiological studies suggest that a high omega-3/omega-6 ratio may be the optimal strategy to decrease breast cancer risk. Thus, the present high intake of omega-6 in many countries is definitely not the optimal strategy to prevent CVD and cancers. A moderate intake of plant and marine omega-3 in the context of the traditional Mediterranean diet (low in saturated and omega-6, but high in plant monounsaturated fat) appears to be the best approach to reduce the risk of both cardiovascular diseases and cancers, in particular breast cancer.

Common variants in mismatch repair genes associated with increased risk of sperm DNA damage and male infertility

Guixiang Ji — 2012-05-17T00:00:00Z

Background: The mismatch repair (MMR) pathway plays an important role in the maintenance of the genome integrity, meiotic recombination and gametogenesis. This study investigated whether genetic variations in MMR genes are associated with an increased risk of sperm DNA damage and male infertility. Methods: We selected and genotyped 21 tagging single nucleotide polymorphisms (SNPs) in five MMR genes (MLH1, MLH3, PMS2, MSH4 and MSH5) using the SNPstream 12-plex platform in a case-control study of 1,292 idiopathic infertility patients and 480 fertile controls in a Chinese population. Sperm DNA damage levels were detected with the Tdt-mediated dUTP nick end labelling (TUNEL) assay in 450 cases. Fluorescence resonance energy transfer (FRET) and co-immunoprecipitation techniques were employed to determine the effects of functional variants. Results: One intronic SNP in MLH1 (rs4647269) and two non-synonymous SNPs in PMS2 (rs1059060, Ser775Asn) and MSH5 (rs2075789, Pro29Ser) seem to be risk factors for the development of azoospermia or oligozoospermia. Meanwhile, we also identified a possible contribution of PMS2 rs1059060 to the risk of male infertility with normal sperm count. Among patients with normal sperm count, MLH1 rs4647269 and PMS2 rs1059060 were associated with increased sperm DNA damage. Functional analysis revealed that the PMS2 rs1059060 can affect the interactions between MLH1 and PMS2. Conclusions: Our results provide evidence supporting the involvement of genetic polymorphisms in MMR genes in the aetiology of male infertility.

Novel regulatory therapies for prevention of Graft-versus-host disease

Joseph Leventhal — 2012-05-15T00:00:00Z

Graft-versus-host disease is one of the major transplant-related complications in allogeneic hematopoietic stem cell transplantation. Continued efforts have been made to prevent the occurrence of severe graft-versus-host disease by eliminating or suppressing donor-derived effector T cells. Conventional immunosuppression does not adequately prevent graft-versus-host disease, especially in mismatched transplants. Unfortunately, elimination of donor-derived T cells impairs stem cell engraftment, and delays immunologic reconstitution, rendering the recipient susceptible to post-transplant infections and disease relapse, with potentially lethal consequences. In this review, we discuss the role of dynamic immune regulation in controlling graft-versus-host disease, and how cell-based therapies are being developed using regulatory T cells and other tolerogenic cells for the prevention and treatment of graft-versus-host disease. In addition, advances in the design of cytoreductive conditioning regimens to selectively target graft-versus-host disease-inducing donor-derived T cells that have improved the safety of allogeneic stem cell transplantation are reviewed. Finally, we discuss advances in our understanding of the tolerogenic facilitating cell population, a phenotypically and functionally distinct population of bone marrow-derived cells which promote hematopoietic stem cell engraftment while reducing the risk of graft-versus-host disease.

Lifestyle interventions for overweight and obese pregnant women to improve pregnancy outcome: systematic review and meta-analysis

Eugene Oteng-Ntim — 2012-05-10T00:00:00Z

Background: Overweight and obesity pose a big challenge to pregnancy as they are associated with adverse maternal and perinatal outcome. Evidence of lifestyle intervention resulting in improved pregnancy outcome is conflicting. Hence the objective of this study is to determine the efficacy of antenatal dietary, activity, behaviour or lifestyle interventions in overweight and obese pregnant women to improve maternal and perinatal outcomes. Methods: A systematic review and meta-analyses of randomised and non-randomised clinical trials following prior registration (CRD420111122 http://www.crd.york.ac.uk/PROSPERO) and PRISMA guidelines was employed. A search of the Cochrane Library, EMBASE, MEDLINE, CINAHL, Maternity and Infant care and eight other databases for studies published prior to January 2012 was undertaken. Electronic literature searches, study selection, methodology and quality appraisal were performed independently by two authors. Methodological quality of the studies was assessed according to Cochrane risk of bias tool. All appropriate randomised and non-randomised clinical trials were included while exclusions consisted of interventions in pregnant women who were not overweight or obese, had pre-existing diabetes or polycystic ovarian syndrome, and systematic reviews. Maternal outcome measures, including maternal gestational weight gain, gestational diabetes and Caesarean section, were documented. Fetal outcomes, including large for gestational age and macrosomia (birth weight > 4 kg), were also documented. Results: Thirteen randomised and six non-randomised clinical trials were identified and included in the meta-analysis. The evidence suggests antenatal dietary and lifestyle intervention in obese pregnant women reduces maternal pregnancy weight gain (10 randomised clinical trials; n = 1228; -2.21 kg (95% confidence interval -2.86 kg to -1.59 kg)) and a trend towards a reduction in the prevalence of gestational diabetes (six randomised clinical trials; n = 1,011; odds ratio 0.80 (95% confidence interval 0.58 to 1.10)). There were no clear differences reported for other outcomes such as Caesarean delivery, large for gestational age, birth weight or macrosomia. All available studies were assessed to be of low to medium quality. Conclusion: Antenatal lifestyle intervention is associated with restricted gestational weight gain and a trend towards a reduced prevalence of gestational diabetes in the overweight and obese population. These findings need to be interpreted with caution as the available studies were of poor to medium quality.

The regulation of mobile health applications

Amy J Barton — 2012-05-08T00:00:00Z

In July 2011, the United States Food and Drug Administration issued draft guidance concerning the regulation of mobile medical applications (applications on a wireless device that are used as accessories to medical devices or to convert a mobile platform to a medical device). While the suggestion of regulation is rooted in patient safety, concerns about limits on innovation and discovery as well as the evolving nature of both mobile health and current healthcare delivery have emerged. This article discusses the prevalence of mobile health, the context of regulation concerning mobile medical applications, and implications for the future.

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