Data Submission Standards and Evidence Requirements

Presented are recommendations of the Data Submission Standards and Evidence Requirements panel from the Conference on Clinical Cancer Research along with the U.S. Food and Drug Administration's response to these recommendations

A multicenter retrospective cohort analysis of therapeutic hypothermia in acute liver failure

Cerebral edema is a severe and life-threatening complication in acute liver failure (ALF). Concerns exist that therapeutic hypothermia (TH) may increase the risk of infection, worsen coagulopathy and inhibit hepatic regeneration. We therefore reviewed the experience in use of TH in participating US Acute Liver Failure Study Group (ALFSG) centers. The aims were to determine utilization of TH in ALF patients at high risk for cerebral edema (grade III or IV hepatic encephalopathy (HE)) and to determine its effect on survival and complication rates

From caution to urgency: the evolution of HIV testing and counselling in Africa.

OBJECTIVE: To describe recent changes in policy on provider-initiated testing and counselling (PITC) for human immunodeficiency virus (HIV) infection in African countries and to investigate patients' experiences of and views about PITC. METHODS: A review of the published literature and of national HIV testing policies, strategic frameworks, plans and other relevant documents was carried out. FINDINGS: Of the African countries reviewed, 42 (79.2%) had adopted a PITC policy. Of the 42, all recommended PITC for the prevention of mother-to-child HIV transmission, 66.7% recommended it for tuberculosis clinics and patients, and 45.2% for sexually transmitted infection clinics. Moreover, 43.6% adopted PITC in 2005 or 2006. The literature search identified 11 studies on patients' experiences of and views about PITC in clinical settings in Africa. The clear majority regarded PITC as acceptable. However, women in antenatal clinics were not always aware that they had the right to decline an HIV test. CONCLUSION: Policy and practice on HIV testing and counselling in Africa has shifted from a cautious approach that emphasizes confidentiality to greater acceptance of the routine offer of HIV testing. The introduction of PITC in clinical settings has contributed to increased HIV testing in several of these settings. Most patients regard PITC as acceptable. However, other approaches are needed to reach people who do not consult health-care services

Challenges and Opportunities to Updating Prescribing Information for Longstanding Oncology Drugs.

A number of important drugs used to treat cancer-many of which serve as the backbone of modern chemotherapy regimens-have outdated prescribing information in their drug labeling. The Food and Drug Administration is undertaking a pilot project to develop a process and criteria for updating prescribing information for longstanding oncology drugs, based on the breadth of knowledge the cancer community has accumulated with the use of these drugs over time. This article highlights a number of considerations for labeling updates, including selecting priorities for updating; data sources and evidentiary criteria; as well as the risks, challenges, and opportunities for iterative review to ensure prescribing information for oncology drugs remains relevant to current clinical practice

Steroid use in acute liver failure

Drug-induced and indeterminate acute liver failure (ALF) might be due to an autoimmune-like hepatitis that is responsive to corticosteroid therapy. The aim of this study was to evaluate whether corticosteroids improve survival in fulminant autoimmune hepatitis, drug-induced, or indeterminate ALF, and whether this benefit varies according to the severity of illness. We conducted a retrospective analysis of autoimmune, indeterminate, and drug-induced ALF patients in the Acute Liver Failure Study Group from 1998-2007. The primary endpoints were overall and spontaneous survival (SS, survival without transplant). In all, 361 ALF patients were studied, 66 with autoimmune (25 steroids, 41 no steroids), 164 with indeterminate (21 steroids, 143 no steroids), and 131 with drug-induced (16 steroids, 115 no steroids) ALF. Steroid use was not associated with improved overall survival (61% versus 66%, P = 0.41), nor with improved survival in any diagnosis category. Steroid use was associated with diminished survival in certain subgroups of patients, including those with the highest quartile of the Model for Endstage Liver Disease (MELD) (\u3e40, survival 30% versus 57%, P = 0.03). In multivariate analysis controlling for steroid use and diagnosis, age (odds ratio [OR] 1.37 per decade), coma grade (OR 2.02 grade 2, 2.65 grade 3, 5.29 grade 4), MELD (OR 1.07), and pH \u3c 7.4 (OR 3.09) were significantly associated with mortality. Although steroid use was associated with a marginal benefit in SS overall (35% versus 23%, P = 0.047), this benefit did not persistent in multivariate analysis; mechanical ventilation (OR 0.24), MELD (OR 0.93), and alanine aminotransferase (1.02) were the only significant predictors of SS. CONCLUSION: Corticosteroids did not improve overall survival or SS in drug-induced, indeterminate, or autoimmune ALF and were associated with lower survival in patients with the highest MELD scores

Silicate Treatment to Inhibit Corrosion of Hot, Potable Water Systems, Phase I

Research has been conducted to determine the variables involved in the use of the sodium silicate treatment technique and in the design of a system which utilizes or controls these variables for the efficient control of corrosion of steel, galvanized steel, and copper piping exposed to hot, potable water. Test loops were designed and constructed at nine selected sites to investigate the influence that temperature flow velocity, water chemistry, and silicate formulation and dosage have on the effectiveness of sodium silicate as a corrosion inhibitor for steel, galvanized steel, and copper piping exposed to heat (140°F and 180°F) in aggressive, potable water of four different compositions. Recommendations are made to conduct further research to determine ( 1) silicate treatment variables involved in treating low alkalinity and low hardness water; {2) the practicality of employing silicate treatment of hard water; (3) the effectiveness of zinc salts as a supplement to silicate; and (4) the corrosion resistance of ASTM A-268 Grade 409 stainless steel.AIR FORCE WEAPONS LABORATORY - Air Force Systems Command - Kirtland Air Force Base, New MericoOpe

Global Challenges for Cancer Imaging

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

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

The association of sport and exercise activities with cardiovascular disease risk: The Atherosclerosis risk in Communities (ARIC) study

Background: This study assessed the independent associations between participation in self-reported sport and exercise activities and incident cardiovascular disease (CVD). Methods: Data were from 13,204 participants in the Atherosclerosis Risk in Communities Study cohort (1987–2015). Baseline sport and exercise activities were assessed via the modified Baecke questionnaire. Incident CVD included coronary heart disease, heart failure, or stroke. Multivariable-adjusted Cox proportional hazard models assessed the association of participation in specific sport and exercise activities at enrollment with risk of CVD. Results: During a median follow-up time of 25.2 years, 30% of the analytic sample (n = 3966) was diagnosed with incident CVD. In fully adjusted models, participation in racquet sports (hazard ratio [HR] 0.75; 95% confidence interval [CI], 0.61–0.93), aerobics (HR 0.75; 95% CI, 0.63–0.88), running (HR 0.68; 95% CI, 0.54–0.85), and walking (HR 0.89; 95% CI, 0.83–0.95) was significantly associated with a lower risk of CVD. There were no significant associations for bicycling, softball/baseball, gymnastics, swimming, basketball, calisthenics exercises, golfing with cart, golfing with walking, bowling, or weight training. Conclusions: Participation in specific sport and exercises may substantially reduce the risk for CVD