BMC Medicine - Latest Articles

Can racial disparities in optimal gout treatment be reduced? Evidence from a randomized trial

Jasvinder Singh — 2012-02-09T00:00:00Z

There is a disproportionate burden of gout in African-Americans in the U.S. due to a higher disease prevalence and lower likelihood of receiving urate-lowering therapy (ULT), compared to Caucasians. There is an absence of strong data as to whether the response to ULT differs by race/ethnicity. BMC Musculoskeletal Disorders recently published a secondary analyses of the CONFIRMS trial, a large randomized controlled, double-blind trial of 2,269 gout patients. The authors reported that the likelihood of achieving the primary study efficacy end-point of achieving serum urate < 6 mg/dl was similar between African-Americans and Caucasians, for all three treatment arms (Febuxostat 40 mg and 80 mg and allopurinol 300/200 mg). More importantly, rates were similar in subgroups of patients with mild or moderate renal insufficiency. Adverse event rates were similar, as were the rates of gout flares. These findings constitute a convincing evidence to pursue aggressive ULT in gout patients, regardless of race/ethnicity. This approach will likely help to narrow the documented racial disparities in gout care.Please see related article : http://www.biomedcentral.com/1471-2474/13/15

Zinc adjunct therapy reduces case fatality in severe childhood pneumonia: a randomized double blind placebo-controlled trial

Maheswari Srinivasan — 2012-02-08T00:00:00Z

Background: Pneumonia is a leading cause of child deaths in developing countries and hinders achievement of the fourth Millennium Development Goal. This goal aims to reduce the under-five mortality rate, by two thirds, between 1990 and 2015. Few studies have examined the impact of zinc adjunct therapy on the outcome of childhood pneumonia. We determined the effect of zinc as adjunct therapy on time to normalization of respiratory rate, temperature and oxygen saturation. We also studied the effect of zinc adjunct therapy on case fatality of severe childhood pneumonia (as a secondary outcome) in Mulago hospital, Uganda. Methods: In this double blind randomised placebo-controlled clinical trial, 352 children aged 6-59 months, with severe pneumonia were randomized to zinc (20mg for children [greater than or equal to] 12 months, and 10mg for those below 12 months) or placebo once daily for seven days, in addition to standard antibiotics for severe pneumonia. Children were assessed every 6 hours. Oxygen saturation was normal if it was above 92% (breathing room air) for more than 15 minutes. The respiratory rate was normal if it was consistently (more than 24 hours) below 50 breaths per minute in infants and 40 breaths per minute in children above 12 months of age. Temperature was normal if consistently below 37.5oC. The difference in case fatality was expressed by the risk ratio between the two groups. Results: Time to normalization of the respiratory rate, temperature and oxygen saturation was not significantly different between the two arms.Case fatality was 7/176 (4.0%) in the zinc group and 21/176 (11.9%) in the placebo group: Relative Risk 0.33 (95% CI 0.15-0.76). Relative Risk Reduction was 0.67 (95% CI 0.24-0.85) while the number needed to treat was 13. Among HIV infected children, case fatality was higher in the placebo (7/27) than the zinc (0/28) group; RR 0.1 (95% CI 0.0, 1.0).Among 127 HIV uninfected children receiving placebo, case fatality was 7/127 (5.5%); versus 5/129 (3.9%) among HIV uninfected group receiving zinc: RR 0.7 (95% CI 0.2, 2.2). The excess risk of death attributable to the placebo arm (Absolute Risk Reduction or ARR) was 8/100 (95% CI: 2/100, 14/100) children. This excess risk was substantially greater among HIV positive children than in HIV negative children [ARR: 26 (95% CI: 9, 42) per 100 versus 2 (95% CI: -4, 7) per 100]; p-value for homogeneity of risk differences = 0.006. Conclusion: Zinc adjunct therapy for severe pneumonia had no significant effect on time to normalization of the respiratory rate, temperature and oxygen saturation. However zinc supplementation in these children significantly decreased case fatality.The difference in case fatality attributable to the protective effect of zinc therapy was greater among HIV infected than HIV uninfected children. Given these results, zinc could be considered for use as adjunct therapy for severe pneumonia, especially among HAART naive HIV infected children in our environment. Clinical trials registration number: clinicaltrials.gov NCT00373100

Spectrum of gluten-related disorders: consensus on new nomenclature and classification

Anna Sapone — 2012-02-07T00:00:00Z

A decade ago celiac disease was considered extremely rare outside Europe and, therefore, was almost completely ignored by health care professionals. In only 10 years, key milestones have moved celiac disease from obscurity into the popular spotlight worldwide. Now we are observing another interesting phenomenon that is generating great confusion among health care professionals. The number of individuals embracing a gluten free diet appears much higher than the projected number of celiac disease patients, fueling a global market of gluten free products approaching the $2.5 billion in global sales in 2010. This trend is supported by the notion that along with celiac disease, other conditions related to the ingestion of gluten have emerged as health care concerns. This review will summarize our current knowledge about the three main forms of gluten reactions, i.e. allergic (wheat allergy), autoimmune (celiac disease, dermatitis herpetiformis, and gluten ataxia), and possibly immune-mediated (gluten sensitivity), outlining pathogenic, clinical, and epidemiological differences and proposing new nomenclature and classifications.

Treatment of Enterohemorrhagic E. coli (EHEC) infection and Hemolytic Uremic Syndrome (HUS)

Paul Goldwater — 2012-02-02T00:00:00Z

Verotoxigenic E. coli (VTEC) are a specialised group of E. coli, that cause severe colonic disease and renal failure. Their pathogenicity derives from virulence factors which enable the bacteria to colonise the colon and deliver extremely powerful toxins known as verotoxins (VT) or Shiga toxins (Stx) to the systemic circulation. The recent devastating E. coli O104:H4 epidemic in Europe has shown how helpless we are in terms of offering effective therapies. By examining the sources and distribution of these bacteria, and how they cause disease , we will be in better shape to prevent and treat the inevitable future cases of sporadic disease and victims of common-source outbreaks. Due to the complexity of pathogenesis, it is likely a multi-targeted approach is warranted. Developments in terms these treatments are discussed.See related article: http://www.biomedcentral.com/1741-7015/10/11

Outbreaks of virulent diarrhoeagenic Escherichia coli - are we in control?

Dirk Werber — 2012-02-02T00:00:00Z

Shiga toxin-producing E. coli (STEC) are the most virulent diarrhoeagenic E. coli known to date. They can be spread with alarming ease via food as exemplified by a large sprout-borne outbreak of STEC O104:H4 in 2011 that was centered in northern Germany and affected several countries. Effective control of such outbreaks is an important public health task and necessitates early outbreak detection, fast identification of the outbreak vehicle and immediate removal of the suspected food from the market, flanked with consumer advice and measures to prevent secondary spread.In our view, opportunities to improve control of STEC outbreaks lie in early clinical suspicion for STEC infection, timely diagnosis of all STEC at the serotype-level and integrating molecular subtyping information into surveillance systems. Furthermore, conducting analytic studies that supplement patients' imperfect food history recall and performing, as an investigative element, product tracebacks, are pivotal but underutilised tools for successful epidemiologic identification of the suspected vehicle in food-borne outbreaks. As a corollary, these tools are amenable to tailor microbiological testing of suspected food.Please see related article: http://www.biomedcentral.com/1741-7015/10/12

Cost -effectiveness analysis for clinicians.

Suzanne Hill — 2012-02-01T00:00:00Z

In a climate of economic uncertainty, cost effectiveness analysis is a potentially important tool for making choices about health care interventions. Methods for such analyses are well established, but the results need to be interpreted carefully and are subject to bias. Making decisions based on results of cost-effectiveness analyses can involve setting thresholds, but for individual patients, there needs to be disaggregation of benefits and harms included in a quality adjusted life year to ensure appropriate consideration of benefits and harms as well as personal preferences and circumstances.

Diindolylmethane suppresses ovarian cancer growth and potentiates the effect of cisplatin in tumor mouse model by targeting signal transducer and activator of transcription 3 (STAT3)

Prabodh Kandala — 2012-01-26T00:00:00Z

Background: STAT-3 is activated in majority of ovarian tumors and confers resistance to cisplatin treatment in patients with ovarian cancer. We have reported previously that Diindolylmethane (DIM) inhibits the growth of ovarian cancer cells. However, the exact mechanism by which DIM induces growth suppressive effects was not yet understood and hence evaluated in this report. Methods: Six human ovarian cancer cells and ovarian tumor xenograft animal model were used to study the effect of diindolylmethane alone or in combination of cisplatin. Results: Diindolylmethane treatment induced apoptosis in all the six ovarian cancer cells. Phosphorylation of STAT3 at Tyr-705 and Ser-727 was reduced by DIM in a concentration-dependent manner. In addition, diindolylmethane treatment inhibited nuclear translocation, DNA binding, and transcriptional activity of STAT3. IL-6-induced phosphorylation of STAT3 at Tyr-705 was significantly blocked by DIM. Overexpression of STAT3 by gene transfection blocked DIM-induced apoptosis. In addition, diindolylmethane treatment reduced the levels of IL-6 in ovarian cancer cells and in the tumors. Diindolylmethane treatment also inhibited cell invasion and angiogenesis by suppressing HIF-1alpha and VEGF. Importantly, diindolylmethane treatment potentiated the effects of cisplatin in SKOV-3 cells by targeting STAT3. Oral administration of 3 mg diindolylmethane per day and subsequent administration of cisplatin substantially inhibited in vivo tumor growth. Western blotting analysis of tumor lysates indicated increased apoptosis and reduced STAT3 activation. Conclusion: These findings provide a rationale for further clinical investigation of diindolylmethane alone or in combination for chemoprevention and/or chemotherapy of ovarian cancer.

Clinical evaluation of iron treatment efficiency among non-anemic but iron-deficient female blood donors: a randomized controlled trial

Sophie Waldvogel — 2012-01-24T00:00:00Z

Iron deficiency without anemia (IDWA) is related to adverse symptoms that can be relieved by supplementation. Since a blood donation can induce such an iron deficiency, we investigated the clinical impact of an iron treatment after blood donation. Methods: One week after donation, we randomly assigned 154 female donors with IDWA aged <50 years to a 4-week oral treatment of ferrous sulfate vs. placebo. The main outcome was the change in the level of fatigue before and after the intervention. Also evaluated were aerobic capacity, mood disorder, quality of life, compliance and adverse events. Biological markers were hemoglobin and ferritin. Results: Treatment effect from baseline to 4 weeks for hemoglobin and ferritin were 5.2 g/L (p < 0.01) and 14.8 ng/mL (p < 0.01) respectively. No significant clinical effect was observed for fatigue (-0.15 points, 95% confidence interval -0.9 to 0.6, p = 0.697) or for other outcomes. Compliance and interruption for side effects was similar in both groups. Additionally, blood donation did not induce overt symptoms of fatigue in spite of the significant biological changes it produces. Conclusions: These data are valuable as they enable us to conclude that donors with IDWA after a blood donation would not clinically benefit from iron supplementation.Trial registration: NCT00689793

The role of copeptin as a diagnostic and prognostic biomarker for risk stratification in the emergency department

Christian Nickel — 2012-01-20T00:00:00Z

The hypothalamic-pituitary-adrenal axis is activated in response to stress. One of the activated hypothalamic hormones is arginine vasopressin, a hormone involved in hemodynamics and osmoregulation. Copeptin, the C-terminal part of the arginine vasopressin precursor peptide, is a sensitive and stable surrogate marker for arginine vasopressin release. Measurement of copeptin levels has been shown to be useful in a variety of clinical scenarios, particularly as a prognostic marker in patients with acute diseases such as lower respiratory tract infection, heart disease and stroke. The measurement of copeptin levels may provide crucial information for risk stratification in a variety of clinical situations. As such, the emergency department appears to be the ideal setting for its potential use. This review summarizes the recent progress towards determining the prognostic and diagnostic value of copeptin in the emergency department.

Systematic review and meta-analysis of the value of initial biomarkers in predicting adverse outcome in febrile neutropenic episodes in children and young people with cancer

Robert Phillips — 2012-01-18T00:00:00Z

Background: Febrile neutropenia is a frequently occurring and occasionally life-threatening complication of treatment for childhood cancer. Many biomarkers have been proposed as predictors of adverse events. We aimed to undertake a systematic review and meta-analysis to summarise evidence on the discriminatory ability of initial serum biomarkers of febrile neutropenic episodes in children and young people. Methods: The review was conducted in accordance with Centre for Reviews and Dissemination methods, using three random effects models to undertake meta-analysis. It was registered with the HTA Registry of systematic reviews, CRD32009100485. Results: We found 25 studies exploring 14 different biomarkers assessed in 3585 episodes of FNP. CRP, PCT, and IL6 were subject to quantitative meta-analysis, and these revealed huge inconsistencies and heterogeneity in the studies included. Only CRP has been evaluated in assessing its' value over the predictive value of simple clinical decision rules. Conclusions: The limited data available describing the predictive value of biomarkers in the setting of paediatric febrile neutropenia mean firm conclusions can yet be reached, although the use of IL6, IL8 and procalcitonin warrant further study.