Significant Reduction In Overall Mortality Research Articles

Selenium supplementation for critically ill adults.

Selenium is a trace mineral essential to health and has an important role in immunity, defence against tissue damage and thyroid function. Improving selenium status could help protect against overwhelming tissue damage and infection in critically ill adults. This Cochrane review was originally published in 2004 updated in 2007 and again 2015. The primary objective was to examine the effect of nutrition supplemented with selenium or ebselen on mortality in critically ill patients.The secondary objective was to examine the relationship between selenium or ebselen supplementation and number of infections, duration of mechanical ventilation, length of intensive care unit stay and length of hospital stay. In this update, we searched the current issue of the Cochrane Central Register of Controlled Trials, the Cochrane Library (2014, Issue 5); MEDLINE (Ovid SP, to May 20, 2014), EMBASE (Ovid SP, to May 20, 2014), CAB, BIOSIS and CINAHL. We handsearched the reference lists of the newest reviews and cross-checked with our search in MEDLINE. We contacted the main authors of included studies to request any missed, unreported or ongoing studies. The latest search was performed up to 21 May 2014. The search is now from inception until 21 May 2014. We included randomized controlled trials (RCTs) irrespective of publication status, date of publication, blinding status, outcomes published or language. We contacted the trial investigators and authors in order to retrieve relevant and missing data. Two review authors independently extracted data and we resolved any disagreements by discussion. Our primary outcome measure was all-cause mortality. We performed several subgroup and sensitivity analyses to assess the effects of selenium in critically ill patients. We presented pooled estimates of the effects of intervention as risk ratios (RRs) with 95% confidence intervals (CIs). We assessed the risk of bias through assessment of trial methodological components and the risk of random error through trial sequential analysis. We included six new RCTs in this review update. In total we included 16 RCTs (2084 participants) in this review. Most trials were at high risk of bias. The availability of outcome data was limited and trials involving selenium supplementation were, with the exception of one trial, small regarding sample size. Thus the results must be interpreted with caution.Thirteen trials of intravenous sodium selenite showed a statistically significant reduction in overall mortality (RR 0.82, 95% CI 0.72 to 0.93, 1391 participants, very low quality of evidence). However, the overall point estimate on mortality is primarily influenced by trials of high risk of bias. Meta-analysis of three trials of ebselen had a RR of 0.83 (95% CI 0.52 to 1.34, 693 participants, very low quality of evidence).Nine trials of intravenous sodium selenite were analysed for 28 days mortality with no statistically significant difference (RR 0.84, 95% CI 0.69 to 1.02, 1180 participants, very low quality of evidence) while three trials were analysed for 90 days mortality with similar findings (RR 0.96, 95% Cl 0.78 to 1.18, 614 participants, very low quality of evidence).Two trials of ebselen were analysed for 90 days mortality and were not found to yield any benefit (RR 0.72, 95% Cl 0.42 to 1.22, 588 participants, very low quality of evidence).For mortality among intensive care patients selenium supplementation failed to indicate any statistically significant advantage (RR 0.88, 95% CI 0.77 to 1.01, nine trials, 1168 participants, very low quality of evidence).Six trials of intravenous sodium selenite found no statistically significant difference for participants developing infection (RR 0.96, 95% CI 0.75 to 1.23, 934 patients, very low quality of evidence). Similarly, three trials of ebselen provided data for participants developing infections (pyrexia, respiratory infections or meningitis) with no obvious benefit (RR 0.60, 95% CI 0.36 to 1.02, 685 participants, very low quality of evidence).Our analyses showed no effect of selenium or ebselen on adverse events (Selenium: RR 1.03, 95% Cl 0.85 to 1.24; six trials, 925 participants ; Ebselen: RR 1.16, 95% CI 0.40 to 3.36; two trials, 588 participants, very low quality of evidence).No clear evidence emerged in favour of selenium supplementation for outcomes such as number of days on a ventilator (mean difference (MD) -0.86, 95% CI -4.39 to 2.67, four trials, 191 participants, very low quality of evidence), length of intensive care unit stay (MD 0.54, 95% CI -2.27 to 3.34, seven trials, 934 participants, very low quality of evidence) or length of hospital stay (MD -3.33, 95% Cl -5.22 to -1.44, five trials, 693 participants, very low quality of evidence).The quality of trial methodology was low. Due to high risk of bias in the included trials, results must be interpreted with caution. Despite publication of a number of trials, the current evidence to recommend supplementation of critically ill patients with selenium or ebselen remains disputed. Trials are required which overcome the methodological inadequacies of the reviewed studies, particularly in relation to sample size, design and outcomes.

A qualitative and quantitative evaluation of the Advancing Quality pay-for-performance programme in the NHS North West

BackgroundAdvancing Quality (AQ) is a voluntary programme providing financial incentives for improvement in the quality of care provided to NHS patients in the north-west of England.Objectives(1) To identify the impact of AQ on key stakeholders and clinical practice; (2) to assess its cost-effectiveness; (3) to identify key factors that assist or impede its successful implementation; and (4) to provide lessons for the wider implementation of pay-for-performance schemes across the NHS.DesignWe tested whether or not the financial incentives of AQ had an impact on mortality using two methods: a between-region difference-in-differences analysis comparing the North West region and the rest of England for the incentivised and non-incentivised conditions and a triple-difference analysis comparing performance on the incentivised conditions, as well as the non-incentivised conditions, in the North West region and the rest of England. A cost-effectiveness analysis of AQ based on the first 18 months of the programme was also undertaken. We used interviews and observation to explore how and why changes occurred.ResultsRisk-adjusted mortality rates for all three of the conditions we studied (pneumonia, heart failure and myocardial infarction) decreased in both the North West region and the rest of England during the first 18 months of the scheme. The reduction in mortality for incentivised conditions was greater in the North West region than in the rest of England. Compared with non-incentivised conditions within the North West region, there was a significant reduction in overall mortality for incentivised conditions, comprising a statistically significant reduction in pneumonia and non-significant reductions in the other two conditions. Comparing mortality for the incentivised conditions with mortality for these conditions in other regions, there was a significant reduction in overall mortality in the North West region, again made up of individually significant reductions in pneumonia and non-significant reductions in the other two conditions. The reduction in mortality over the 18-month period studied for non-incentivised conditions was not significantly different between the North West region and the rest of England. The between-region difference-in-differences analysis after 42 months showed that risk-adjusted mortality for the incentivised conditions fell in the rest of England and the North West region. This reduction in the rest of England was significantly larger than in the North West region and was concentrated in pneumonia. However, the reductions in mortality were larger for the non-incentivised conditions in the North West region than in the rest of England between these periods. For incentivised conditions, the triple-difference analysis shows a larger reduction in mortality for the rest of England than in the North West region between the short- and long-term periods.ConclusionsBased on the first 18 months, the AQ programme was a relatively effective and cost-effective intervention. However, findings at 42 months are open to interpretation. One interpretation is that the short-term improvements were not sustained and that the observed improvements in mortality in the non-incentivised conditions within hospitals participating in AQ were unrelated to the programme. An alternative interpretation is that these improvements are related to the positive spillover effect of AQ. Further research should be undertaken to determine the explanation for the findings.FundingThe National Institute for Health Research Health Services and Delivery Research programme.

Current challenges in the management of heart failure.

The management of chronic heart failure (HF) with low ejection fraction (EF) has changed considerably over the past 30 years: the introduction of angiotensin-converting enzyme inhibitors (ACEIs), β-blockers, angiotensin-receptor blockers, mineralocorticoid-receptor antagonists and recently, the Ifblocker, ivabradine, has led to a significant reduction in overall mortality and HF mortality. Recently, a trial testing a dual inhibitor blocking the angiotensin-II receptor and neprylisin, the enzyme responsible for B-type natriuretic peptide degradation, showed that this complex molecule improved clinical outcomes compared with the ACEI enalapril. However, challenges remain in the management of HF, with suboptimal implementation of guideline-recommended therapies, a changing profile of patients who are older and have multiple comorbidities and a high rate of early rehospitalization for HF. Use of devices such as implantable cardiac defibrillators and cardiac resynchronization therapy are also associated with an improvement in outcomes in this condition. HF with preserved EF (HFpEF), a growing fraction of the HF population, remains a clinical dilemma: no pharmacological intervention has so far demonstrated any convincing benefit on outcome. Heterogeneity of the populations tested, role of comorbidities, difficulties in identifying patients with HFpEF, as well as a mismatch between the clinical phenotypes and the treatments tested, can explain the failure to find beneficial interventions. Overall, the management of HF after discharge remains fragmented and concerted action by all professionals concerned is needed.

Prophylactic lamivudine to improve the outcome of HBsAg-positive lymphoma patients during chemotherapy: A systematic review and meta-analysis

Hepatitis B viral (HBV) reactivation in lymphoma patients undergoing chemotherapy is associated with significant morbidity and mortality. Increasingly, lamivudine is being used to prevent hepatitis B reactivation. To assess the effects of prophylactic lamivudine on reactivation and mortality following chemotherapy in lymphoma patients who are hepatitis B surface antigen (HBsAg)-positive, we searched Medline/PubMed, Ovid MEDLINE, EMBASE, Web of Knowledge and the Cochrane Library for studies through November 2013. Statistical analysis was performed using REVMAN. Fourteen studies consisting of 636 patients were included in the analysis. The rate of HBV reactivation, incidence of hepatitis and incidence of hepatitis due to HBV reactivation in patients with lamivudine prophylaxis was significantly lower than those with no prophylaxis. Risk ratios [RRs] were 0.25 (95% confidence intervals [CI] 0.13-0.51; P=0.0001), 0.40 (95% CI 0.26-0.63; P<0.0001), and 0.21 (95% CI 0.09-0.51; P=0.0005) respectively. In addition, patients given prophylactic lamivudine had significant reductions in overall mortality and mortality attributable to HBV reactivation compared with control group. Risk ratios [RRs] were 0.45 (95% CI 0.29-0.70; P=0.0004) and 0.41 (95% CI 0.20-0.84; P=0.01) respectively. Chemotherapy disruption was not significantly different between the two groups. Risk ratios [RRs] were 0.34 (95% CI 0.09-1.26; P=0.11). Prophylactic therapy with lamivudine for HBsAg-positive lymphoma patients who are undergoing chemotherapy may reduce the risk for HBV reactivation, hepatitis due to HBV reactivation, overall mortality and mortality attributable to HBV reactivation. Additionally, patients with preventive lamivudine had a trend towards the decreased incidence of chemotherapy disruption.

Actigraphy-measured sleep disruption as a predictor of survival among women with advanced breast cancer.

Poor sleep, prevalent among cancer survivors, is associated with disrupted hormonal circadian rhythms and poor quality of life. Using a prospective research design, this study aimed to clarify the relationship between objective measures of sleep efficiency and sleep disruption with survival among women with advanced breast cancer. We examined sleep quality and duration via wrist-worn actigraphy and sleep diaries for 3 days among 97 women in whom advanced breast cancer was diagnosed (age = 54.6 ± 9.8 years). Sleep efficiency was operationalized using actigraphy as the ratio of total sleep time to total sleep time plus wake after sleep onset. As hypothesized, better sleep efficiency was found to predict a significant reduction in overall mortality (hazard ratio [HR], 0.96; 95% confidence interval [CI], 0.94-0.98; P < 0.001) at median 6 y follow-up. This relationship remained significant (HR, 0.94; 95% CI, 0.91-0.97; P < 0.001) even after adjusting for other known prognostic factors (age, estrogen receptor status, cancer treatment, metastatic spread, cortisol levels, and depression). Secondary hypotheses were also supported (after adjusting for baseline prognostic factors) showing that less wake after sleep onset (HR, 0.41; 95% CI, 0.25-0.67; P < 0.001), fewer wake episodes, (HR, 0.93; 95% CI, 0.88-0.98; P = 0.007); and shorter wake episode duration (HR, 0.29; 95% CI, 0.14-0.58; P < 0.001) also contributed to reductions in overall mortality. These findings show that better sleep efficiency and less sleep disruption are significant independent prognostic factors in women with advanced breast cancer. Further research is needed to determine whether treating sleep disruption with cognitive behavioral and/or pharmacologic therapy could improve survival in women with advanced breast cancer.

Use of Metformin and Survival of Diabetic Women with Breast Cancer

Objective: This study was set out to determine whether metformin use influences survival in breast cancer patients treated with antidiabetic drugs as compared to non-users.Research Design and Methods: We used data from the Danish national registries (1996-2008) to identify adult female patients diagnosed with breast cancer who were prescribed antidiabetic medication. We performed multivariate Cox-proportional hazard regression to assess all-cause and breast cancer-specific mortality risks associated with metformin exposure. In a secondary analysis, we stratified use of metformin according to the cumulative number of prescriptions.Results: Of the 1058 breast cancer patients 349 died during follow-up, with breast cancer listed as the primary cause of death for 152 cases. Compared to non-use, current metformin treatment was associated with a significant reduction in overall mortality (adjusted HR 0.74, 95% CI, 0.58-0.96). For breast cancer-specific mortality, a non-significant risk reduction (adjusted HR 0.88, 95% CI, 0.59-1.29) was observed, which became significant after stratification according to cumulative number of prescriptions. An increased risk of both overall and breast cancer-specific mortality was observed in the first 12 months after discontinuation of metformin.Conclusions: We observed a nonsignificant reduction in breast cancer-specific mortality associated with metformin exposure among breast cancer patients treated with antidiabetic drugs. However, our findings suggest that long-term metformin use may have a beneficial effect on survival in patients with breast cancer. Further confirmation of these findings is needed.

Surveillance for Hepatocellular Carcinoma: Long Way to Achieve Effectiveness

Surveillance for hepatocellular carcinoma (HCC) in high risk groups including those with cirrhosis as well as with chronic HBV infection is recommended by several practice guidelines including those by the Asian Pacific Association for the Study of Liver (APASL) [1], the American Association for the Study of Liver Disease (AASLD) and the European Association for Study of The Liver (EASL). The evidence supporting the surveillance recommendations in these guidelines is based on evidence of intermediate strength, although arguably the evidence is strongest for HCC surveillance in individuals infected with HBV in Southeast Asia. For example, two randomized controlled trials were conducted in China among individuals with chronic HBV infection with and without cirrhosis. In one placebo-controlled randomized study of nearly 19,000 HBV-infected patients, it was shown that HCC surveillance with both abdominal ultrasound and serum AFP repeated at 6-month intervals resulted in a 37 % reduction in HCCrelated mortality [2]. However, the other randomized controlled trial of 5,581 HBV-infected patients reported that serum AFP repeated at 6-month intervals did not result in a significant reduction in overall mortality [3]. The latter study was smaller and had detected HCC less frequently than the first study and therefore could have suffered from a lack of adequate statistical power. In addition to these two randomized trials, a population-based surveillance program using serum AFP every 6-months among HBVinfected patients in Alaska reported that, during a 16-year follow-up period, patients with HCC who received surveillance had significantly longer 5-year survival compared with historical controls (42 vs. 0 %, respectively) [4]. Last in the evidence hierarchy, several nonrandomized trials and observational cohort and case–control studies have reported that patients who undergo HCC surveillance are diagnosed at an earlier stage of HCC, are more likely to receive potentially curative therapy, and have a significant reduction in cancer-specific mortality compared with patients detected with symptomatic HCC [5, 6]. The ‘‘efficacy’’ of HCC surveillance reflects the degree to which surveillance produces the expected result under controlled conditions chosen to maximize the likelihood of observing an effect if it exists. By contrast, ‘‘effectiveness’’ addresses the extent to which HCC surveillance is beneficial when deployed in medical practice settings [7]. Effectiveness takes into account external factors such as individual patient characteristics, health system features, and societal influences. For HCC surveillance to be effective, several steps need to be enacted. These include (1) identification of high risk patients who are appropriate for surveillance (HBV and HCV with advanced fibrosis/ cirrhosis), (2) availability and accessibility of HCC surveillance to patients at risk in appropriate health care settings, (3) recommendation of the intervention by health care providers, (4) acceptance of HCC surveillance by patients, (5) adherence to surveillance, recall and follow-up at the recommended intervals, the benefits of therapy, (6) availability of appropriate diagnostic test follow-up for abnormal surveillance, and (7) availability of efficacious curative or palliative treatment once HCC is diagnosed. Given the multiplicity of components involved with determining HCC surveillance effectiveness, one could assess the interactions between these factors to arrive with an estimate of how one particular intervention would H. B. El-Serag (&) Dan L Duncan Professor of Medicine, Michael E DeBakey VA Medical Center, Houston Center for Quality of Care and Utilization Studies, Baylor College of Medicine, Houston, TX, USA e-mail: hasheme@bcm.edu

Reducing Bias in the Assessment of Treatment Effectiveness

Indication bias is the major challenge in assessing treatment effectiveness in observational studies. We explored the potential advantages of using an instrumental variable approach in the context of primary androgen deprivation therapy (ADT) for prostate cancer. We identified 31,930 men in the linked Surveillance, Epidemiology, and End Results-Medicare database with a diagnosis of prostate cancer who were not treated definitively with radical prostatectomy or radiation in the years 1992 through 2002, with follow-up through 2005. The association between use of primary ADT and overall, prostate cancer-specific, and nonprostate cancer survival was assessed using multivariable regression and instrumental variable methods. Two instrumental variables, based on region and urologist prescribing preference, were constructed and analyzed using exogenous probit models. Prespecified subgroup analyses in patients with lower-risk and higher-risk prostate tumors were also carried out. In the overall cohort, standard multivariable regression analyses showed a significantly increased risk of prostate cancer-related death, whereas the instrumental variable approaches showed a protective effect of primary ADT, which was significant for the urologist preference instrument (hazard ratio: 0.74; 95% confidence interval, 0.60-0.93). In the high-risk subgroup, using urologist preference for primary ADT as the instrument, there was a significant reduction in overall mortality (hazard ratio: 0.75; 95% confidence interval, 0.57-0.99), driven by a large reduction in prostate cancer-specific mortality. Instrumental variable analysis appears to provide better control of bias when assessing the effectiveness of primary ADT for prostate cancer, although the results may be more applicable to policy rather than to clinical decisions.

Comparative analysis of treatments, utilization, and survival benefit in HCC patients: A real-world analysis of SEER Medicare.

214 Background: We explore various treatments at all stages of Hepatocellular Carcinoma (HCC), in a SEER (Surveillance, Epidemiology and End-Results Program) Medicare population and assess their impact on HCC-specific and overall survival. Methods: Medicare enrollees, older than 65, with an initial diagnosis of a primary HCC between 2000-07 were followed up through end of 2009. Data are from the SEER and linked Medicare databases, with claims generated from Medicare parts A and B. Using multivariate Cox-proportional hazards models, we assessed overall and HCC-related mortality in relation to receipt of treatment/no treatment, adjusting for demographics, general health status (CCI), cancer stage and liver conditions. Results: Out of the 9054 HCC patients, older than 65, who did not get a liver transplant, 76% were Caucasian, 8% African American (AA), 63% male, and 37% got treatment [12% transarterial chemoembolization (TACE), 12% systemic chemotherapy, 1.5% selective internal radiation therapy (SIRT), 9% external beam radiation therapy (EBRT), 8% surgical resection and 9% ablative therapy]. Treatment was associated with a reduction of overall (HR=0.35, P= &lt;0.001) and HCC-related (0.33, &lt;0.001) mortality. HCC-related mortality was significantly reduced in those getting resection (0.38, &lt;0.001), ablation (0.59, &lt;0.001), TACE (0.76, &lt;0.001), EBRT (0.85, 0.017), or chemotherapy (0.85, 0.013). Significant reduction in overall mortality was seen with resection, ablation and TACE but not with chemotherapy, EBRT or SIRT. No particular treatment was associated with greater mortality reduction in early vs advanced stages. Patients with poor underlying health status (CCI&gt;1) had higher mortality (1.27, &lt;0.001). Alcohol related disease, Hep C, and moderate/severe liver dysfunction were not significantly associated with overall or HCC related mortality. Caucasians and non-African Americans had lower overall mortality (0.87, &lt;0.001). Conclusions: In HCC SEER Medicare patients, all treatments except SIRT were associated with a significant reduction in HCC related mortality. A limitation of this study is that, through the data, we cannot accurately depict the severity of the disease.

Antioxidant micronutrients in the critically ill: a systematic review and meta-analysis

IntroductionCritical illness is characterized by oxidative stress, which is a major promoter of systemic inflammation and organ failure due to excessive free radical production, depletion of antioxidant defenses, or both. We hypothesized that exogenous supplementation of trace elements and vitamins could restore antioxidant status, improving clinical outcomes.MethodsWe searched computerized databases, reference lists of pertinent articles and personal files from 1980 to 2011. We included randomized controlled trials (RCTs) conducted in critically ill adult patients that evaluated relevant clinical outcomes with antioxidant micronutrients (vitamins and trace elements) supplementation versus placebo.ResultsA total of 21 RCTs met inclusion criteria. When the results of these studies were statistically aggregated (n = 20), combined antioxidants were associated with a significant reduction in mortality (risk ratio (RR) = 0.82, 95% confidence interval (CI) 0.72 to 0.93, P = 0.002); a significant reduction in duration of mechanical ventilation (weighed mean difference in days = -0.67, 95% CI -1.22 to -0.13, P = 0.02); a trend towards a reduction in infections (RR= 0.88, 95% CI 0.76 to 1.02, P = 0.08); and no overall effect on ICU or hospital length of stay (LOS). Furthermore, antioxidants were associated with a significant reduction in overall mortality among patients with higher risk of death (>10% mortality in control group) (RR 0.79, 95% CI 0.68 to 0.92, P = 0.003) whereas there was no significant effect observed for trials of patients with a lower mortality in the control group (RR = 1.14, 95% 0.72 to 1.82, P = 0.57). Trials using more than 500 μg per day of selenium showed a trend towards a lower mortality (RR = 0.80, 95% CI 0.63 to 1.02, P = 0.07) whereas trials using doses lower than 500 μg had no effect on mortality (RR 0.94, 95% CI 0.67 to 1.33, P = 0.75).ConclusionsSupplementation with high dose trace elements and vitamins may improve outcomes of critically ill patients, particularly those at high risk of death.

Utilization and Outcomes of Palliative Therapy for Hepatocellular Carcinoma

To evaluate the utilization and determinants of receiving palliative treatment for hepatocellular carcinoma (HCC), and its effect on survival. Palliative treatment for HCC, including transarterial chemoembolization (TACE) and systemic chemotherapy, is available for patients who do not receive potentially curative therapy. The utilization and outcomes of these therapies in clinical practice are unknown. We conducted a population-based cohort study using the Surveillance, Epidemiology, and End-Results Registry data linked to Medicare claims of HCC patients aged above 65 years diagnosed during 2000 to 2005 who did not receive liver transplant, resection, or ablation. The proportions of patients who received TACE or systemic chemotherapy were calculated by tumor stage, liver disease status, and non-HCC comorbidity. Determinants of receiving palliative therapy were examined in logistic regression models and propensity scores were calculated. Cox proportional hazards models were used to evaluate mortality risk. We identified 3163 HCC patients (median age, 75 y; 67% men) who did not receive potentially curative treatment. Approximately 12.5% of patients received TACE and 11.0% received chemotherapy. In patients with early or intermediate stage HCC, no liver decompensation, and little or no comorbidity, only 22.8% received TACE and 13.8% received chemotherapy. Median survival was significantly higher among patients who received TACE (14.0 mo) compared with who received chemotherapy (5.0 mo) or no therapy (2.0 mo). A significant reduction in overall mortality was observed for TACE (54%) and chemotherapy (33%). Utilization of palliative treatment for HCC is low, which could not be explained by clinical features. However, misclassification could have occurred due to the data source. Receipt of TACE or systemic chemotherapy was associated with a reduction in mortality.

Overall Survival of Lymphoma Patients In Randomized Controlled Trials Comparing Primary G-CSF Chemotherapy Support to Control.

AbstractAbstract 1502 BackgroundRandomized controlled trials (RCTs) have shown that granulocyte colony-stimulating factor (G-CSF) can reduce the risk of neutropenic complications as well as early mortality (Kuderer et al. JCO 2007). The impact of G-CSF support of chemotherapy on overall survival in patients with lymphoma is assessed here in a systematic review of RCTs of chemotherapy with versus without G-CSF in studies with at least 2 years of follow up. MethodsA systematic review of RCTs of patients with malignant lymphoma receiving chemotherapy with versus without primary G-CSF support and reporting overall mortality by study arm identified 16 eligible studies. Data extraction was conducted by two independent reviewers. Heterogeneity was evaluated using Cochran's Q-statistic and the Inconsistency Index (I2). Weighted summary estimates of relative risk (RR) and absolute risk (AR) were based on the method of Mantel and Haenszel. Chemotherapy relative dose intensity (RDI) with G-CSF support compared to control was meta-regressed on the logarithm of RR for mortality. Egger's regression intercept was utilized to assess publication bias. ResultsSixteen (16) eligible RCTs of patients receiving chemotherapy with (n=2,731) versus without (n=2,757) primary G-CSF support were identified. Deaths were reported in 927 patients randomized to receive primary G-CSF and in 1,064 controls. No significant heterogeneity was observed (Q=12.50, P=.641; I2=0%). Overall RR for mortality with versus without G-CSF support of chemotherapy was 0.876 [95% CI: 0.822 – 0.935; P<.001]. The AR reduction for mortality in G-CSF-supported patients versus control was 4.8% [95% CI: 2.4% - 7.15; P<.001]. An inverse trend was observed between the difference in RDI between treatment arms and RR for mortality [Slope = -0.39; 95% CI: -0.78 – 0.01; P=.057]. The greatest reduction in mortality was observed in the 5 RCTs of dose dense chemotherapy [RR=0.830; 95% CI:0.742-0.930; P=.001]. Significant treatment effect was observed in 7 studies limited to older patients [RR=0.910;95% CI: 0.847–0.978;P=.010] and 9 permitting all adult age groups [RR=0.813;95% CI: 0.715–0.926;P=.002]. No difference in treatment effect was observed based on study funding source and no evidence for publication bias was observed. ConclusionsA highly significant reduction in overall mortality was associated with G-CSF support compared to control in 16 RCTs of lymphoma patients receiving chemotherapy. Patients receiving greater RDI with G-CSF support, especially those receiving dose dense regimens, experienced the greatest reduction in mortality. Disclosures:Lyman:Amgen: Research Funding. Crawford:Amgen: Consultancy. Dale:Amgen: Consultancy, Research Funding.

Antiviral prophylaxis in haematological patients: Systematic review and meta-analysis

Purpose Antiviral prophylaxis is commonly prescribed to haematological cancer patients. We conducted a systematic review and meta-analysis to quantify its overall benefit in specific clinical scenarios. Methods Randomised controlled trials assessing antiviral prophylaxis versus placebo, no treatment, pre-emptive treatment or another antiviral drug were included. Patients undergoing haematopoietic stem cell transplantation (HSCT) or intensive chemotherapy for acute leukaemia or high-grade lymphoma were included. No restrictions on language, year or publication status were applied. Overall mortality, herpes simplex virus (HSV) and cytomegalovirus (CMV) diseases were assessed as primary outcomes. Pooled relative risks (RRs) and numbers needed to treat (NNT) with 95% confidence intervals (CI) are reported. Results HSCT was the condition assessed in 22 trials and intensive chemotherapy in 5 trials. In the pre-engraftment setting of autologous or allogeneic HSCT, antiviral prophylaxis (mainly acyclovir for HSV seropositive recipients) significantly reduced HSV (NNT 2, 2–2, control event rate (CER) 61.9%) and CMV disease, with no effect on overall mortality. In the allogeneic post-engraftment setting (mainly CMV-seropositive recipients/donors), antiviral prophylaxis resulted in a significant reduction in overall mortality, RR 0.79 (0.65–0.95), NNT 12 (7–50, CER 39.4%) and all viral-related outcomes. In this setting, acyclovir significantly reduced overall mortality (RR 0.71, 0.53–0.96, 4 trials) and ganciclovir/maribavir significantly reduced CMV disease (RR 0.26, 0.14–0.48, 5 trials). During chemotherapy, acyclovir significantly decreased HSV disease (NNT 3, 2–4, CER 37.4%) and infection rates, with no effect on mortality. Conclusions Antiviral prophylaxis reduced mortality with a small NNT in the post-engraftment setting of allogeneic HSCT. In the pre-engraftment phase and during chemotherapy only viral-related morbidity was reduced.

Circulating 25-Hydroxyvitamin D Levels and Survival in Patients With Colorectal Cancer

Higher plasma 25-hydroxyvitamin D(3) (25(OH)D) levels are associated with a decreased incidence of colorectal cancer, but the influence of plasma 25(OH)D on the outcome of patients with established colorectal cancer is unknown. We prospectively examined the association between prediagnosis 25(OH)D levels and mortality among 304 participants in the Nurses' Health Study (NHS) and the Health Professionals Follow-Up Study (HPFS) who were diagnosed with colorectal cancer from 1991 to 2002. Participants diagnosed within 2 years of blood collection were excluded. Patients were observed until death, June 2005 (NHS), or January 2005 (HPFS), whichever came first. The primary end point was overall mortality. Cox proportional hazards models were used to calculate hazard ratios (HR) adjusted for other risk factors for cancer survival. Higher plasma 25(OH)D levels were associated with a significant reduction in overall mortality (P for trend = .02). Compared with the lowest quartile, participants in the highest quartile had an adjusted HR of 0.52 (95% CI, 0.29 to 0.94) for overall mortality. A trend toward improved colorectal cancer-specific mortality was also seen (HR = 0.61; 95% CI, 0.31 to 1.19). The results remained unchanged after excluding patients diagnosed within 5 years of blood collection (P for trend = .04); the multivariate HR for overall mortality comparing extreme quartiles was 0.45 (95% CI, 0.19 to 1.09). Among patients with colorectal cancer, higher prediagnosis plasma 25(OH)D levels were associated with a significant improvement in overall survival. Further study of the vitamin D pathway and its influence on colorectal carcinogenesis and cancer progression is warranted.

Venous thromboembolism and all-cause mortality in cancer patients receiving chemotherapy

9521 Background: Venous thromboembolism (VTE) is a common complication of cancer occurring with increasing frequency. A recent meta-analysis of anticoagulation as a form of cancer treatment reported a significant reduction in overall mortality (Kuderer et al. Cancer 2007). The aim of this analysis is to evaluate the impact of VTE on early mortality in cancer patients receiving chemotherapy. Methods: A prospective study of 4,458 adult cancer patients with solid tumors or malignant lymphoma initiating a new chemotherapy regimen was conducted between 2002 and 2006 at 115 randomly selected U.S. practice sites. Demographic, clinical and treatment-related measures were captured at baseline and during the first 4 cycles of chemotherapy including rates of documented VTE and deaths from all causes. Overall survival (OS) was estimated by the method of Kaplan-Meier and adjusted hazard ratios (HR) for OS were based on a Cox regression model incorporating VTE as a time-dependent covariate. Results: Average patient age was 60 years (range: 18 to 97). VTE occurred in 93 (2.1%) patients at a median of 38 days following initiation of chemotherapy. 137 patients died during the period of observation (median follow-up, 75 days). In multivariate analysis after adjusting for major confounders for mortality, including ECOG performance status, Charlson comorbidity index, age, body mass index, cancer type, stage, delivered chemotherapy dose intensity, study year and practice site, the occurrence of VTE was a significant independent predictor of early all-cause mortality [HR=6.98, 95%CI: 2.83–17.21; P<.0001]. Following additional adjustment for baseline laboratory abnormalities, including elevated serum creatinine, alkaline phosphatase or decreased serum protein, VTE remained significantly associated with early mortality [HR=4.50; 95%CI: 1.61–12.53; P=.004]. While 298 (6.7%) patients progressed or recurred during the period of observation, no significant relationship between VTE and tumor progression was observed. Conclusions: VTE is strongly associated with increased early all-cause mortality during the course of cancer chemotherapy. Further studies of the effect of anticoagulant treatment on cancer mortality are needed. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Eisai Eisai, sanofi-aventis

A decline in hospital mortality in acute myocardial infarct during the last 10 years. An effect of acute intervention?

The decline in hospital mortality after myocardial infarction was analyzed retrospectively in a cohort of 2147 consecutive patients with acute myocardial infarction, admitted to an University Hospital between 1978 and 1987. During this period the percentage of patients who had acute active interventions (thrombolysis, aortocoronary bypass surgery, percutaneous transluminal coronary angioplasty) increased from 6% (in 1978/79) to 50% (in 1986/87). During that same period, conventional treatment of acute myocardial infarction and the provisions for emergency admission and intensive care remained unchanged. At the same time there was a significant reduction in overall mortality from 29% (1978/79) to 17% (1986/87) (P less than 0.001). This decrease was especially marked for males (from 27% to 13% in the respective periods), and in patients with anterior-wall infarction (34% and 16%, respectively). These changes cannot be explained by differences in group characteristics. The main cause for the distinct reduction in hospital mortality of this cohort was the introduction and expansion of acute interventions.

Adherence to Mediterranean diet and health status: meta-analysis

Objective To systematically review all the prospective cohort studies that have analysed the relation between adherence to a Mediterranean diet, mortality, and incidence of chronic diseases in a primary prevention...

Follow-Up After Curative Resection of Colorectal Cancer: A Meta-Analysis

This is a systematic review to evaluate the impact of various follow-up intensities and strategies on the outcome of patients after curative surgery for colorectal cancer. All randomized trials up to January 2007, comparing different follow-up intensities and strategies, were retrieved. Meta-analysis was performed by using the Forest plot review. Eight randomized, clinical trials with 2,923 patients with colorectal cancer undergoing curative resection were reviewed. There was a significant reduction in overall mortality in patients having intensive follow-up (intensive vs. less intensive follow-up: 21.8 vs. 25.7 percent; P = 0.01). Regular surveillance with serum carcinoembryonic antigen (P = 0.0002) and colonoscopy (P = 0.04) demonstrated a significant impact on overall mortality. However, cancer-related mortality did not show any significant difference. There was no significant difference in all-site recurrence and in local or distant metastasis. Detection of isolated local and hepatic recurrences was similar. Intensive follow-up detected asymptomatic recurrence more frequently (18.9 vs. 6.3 percent; P < 0.00001) and 5.91 months earlier than less intensive follow-up protocol; these were demonstrated with all investigation strategies used. Intensive surveillance program detected recurrences that were significantly more amenable to surgical reresection (10.7 vs. 5.7 percent; P = 0.0002). The chance of curative reresection were significantly better with more intensive follow-up (24.3 vs. 9.9 percent; P = 0.0001), independent of the investigation strategies used. Intensive follow-up after curative resection of colorectal cancer improved overall survival and reresection rate for recurrent disease. However, the cancer-related mortality was not improved and the survival benefit was not related to earlier detection and treatment of recurrent disease.

What’s new in the other journals?

What’s new in the other journals?

Primary Prevention of Cardiovascular Diseases With Statin Therapy

While the role of hydroxymethyl glutaryl coenzyme A reductase inhibitors (statins) in secondary prevention of cardiovascular (CV) events and mortality is established, their value for primary prevention is less clear. To clarify the role of statins for patients without CV disease, we performed a meta-analysis of randomized controlled trials (RCTs). MEDLINE, EMBASE, Cochrane Collaboration, and American College of Physicians Journal Club databases were searched for RCTs published between 1966 and June 2005. We included RCTs with follow-up of 1 year or longer, more than 100 major CV events, and 80% or more of the population without CV disease. From each trial, demographic data, lipid profile, CV outcomes, mortality, and adverse outcomes were recorded. Summary relative risk (RR) ratios with 95% confidence intervals (CIs) were calculated using a random effects model. Seven trials with 42,848 patients were included. Ninety percent had no history of CV disease. Mean follow-up was 4.3 years. Statin therapy reduced the RR of major coronary events, major cerebrovascular events, and revascularizations by 29.2% (95% CI, 16.7%-39.8%) (P<.001), 14.4% (95% CI, 2.8%-24.6%) (P = .02), and 33.8% (95% CI, 19.6%-45.5%) (P<.001), respectively. Statins produced a nonsignificant 22.6% RR reduction in coronary heart disease mortality (95% CI, 0.56-1.08) (P = .13). No significant reduction in overall mortality (RR, 0.92 [95% CI, 0.84-1.01]) (P = .09) or increases in cancer or levels of liver enzymes or creatine kinase were observed. In patients without CV disease, statin therapy decreases the incidence of major coronary and cerebrovascular events and revascularizations but not coronary heart disease or overall mortality.