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Genetic testing is a rapidly expanding area with many clinical applications. While the introduction of new genetic tests creates tremendous potential for improving patient care, it is essential to adequately evaluate these tests to ensure their accuracy and utility for clinical practice. This article describes a general approach to the evaluation of genetic tests and discusses common challenges that evaluators face. This article's goal was to provide a starting point for those who are concerned with the safety and utility of genetic tests to develop an overall strategy to perform the assessment.

Complications from hospital-acquired pressure ulcers cause 60,000 deaths and significant morbidity annually in the United States. The objective of this systematic review is to review evidence regarding multicomponent strategies for preventing pressure ulcers and to examine the importance of contextual aspects of programs that aim to reduce facility-acquired pressure ulcers. CINAHL, the Cochrane Library, EMBASE, MEDLINE, and PreMEDLINE were searched for articles published from 2000 to 2012. Studies (any design) that implemented multicomponent initiatives to prevent pressure ulcers in adults in U.S. acute and long-term care settings and that reported pressure ulcer rates at least 6 months after implementation were selected. Two reviewers extracted study data and rated quality of evidence. Findings from 26 implementation studies (moderate strength of evidence) suggested that the integration of several core components improved processes of care and reduced pressure ulcer rates. Key components included the simplification and standardization of pressure ulcer-specific interventions and documentation, involvement of multidisciplinary teams and leadership, use of designated skin champions, ongoing staff education, and sustained audit and feedback.

Delirium, an acute decline in attention and cognition, occurs among hospitalized patients at rates estimated to range from 14% to 56% and increases the risk for morbidity and mortality. The purpose of this systematic review was to evaluate the effectiveness and safety of in-facility multicomponent delirium prevention programs. A search of 6 databases (including MEDLINE, EMBASE, and CINAHL) was conducted through September 2012. Randomized, controlled trials; controlled clinical trials; interrupted time series; and controlled before-after studies with a prospective postintervention portion were eligible for inclusion. The evidence from 19 studies that met the inclusion criteria suggests that most multicomponent interventions are effective in preventing onset of delirium in at-risk patients in a hospital setting. Evidence was insufficient to determine the benefit of such programs in other care settings. Future comparative effectiveness studies with standardized protocols are needed to identify which components in multicomponent interventions are most effective for delirium prevention.

Topic development and structuring a systematic review of diagnostic tests are complementary processes. The goals of a medical test review are to identify and synthesize evidence to evaluate the impacts alternative testing strategies on health outcomes and to promote informed decision making. A common challenge is that the request for a review may state the claim for the test ambiguously. Due to the indirect impact of medical tests on clinical outcomes, reviewers need to identify which intermediate outcomes link a medical test to improved clinical outcomes. In this paper, we propose the use of five principles to deal with challenges: the PICOTS typology (patient population, intervention, comparator, outcomes, timing, setting), analytic frameworks, simple decision trees, other organizing frameworks and rules for when diagnostic accuracy is sufficient.

Objectives: The purpose of this report is to systematically examine the possible causal mechanism(s) that may explain the association between alcohol (ethanol) consumption and the risk of developing breast and colorectal cancers., Data Sources: We searched 11 external databases, including PubMed® and Embase, for studies on possible mechanisms. These searches used Medical Subject Headings and free text words to identify relevant evidence., Review Methods: Two reviewers independently screened search results, selected studies to be included, and reviewed each trial for inclusion. We manually examined the bibliographies of included studies, scanned the content of new issues of selected journals, and reviewed relevant gray literature for potential additional articles., Results: Breast Cancer. Five human and 15 animal studies identified in our searches point to a connection between alcohol intake and changes in important metabolic pathways that when altered may increase the risk of developing breast cancer. Alterations in blood hormone levels, especially elevated estrogen-related hormones, have been reported in humans. Several cell line studies suggest that the estrogen receptor pathways may be altered by ethanol. Increased estrogen levels may increase the risk of breast cancer through increases in cell proliferation and alterations in estrogen receptors. Human studies have also suggested a connection with prolactin and with biomarkers of oxidative stress. Of 15 animal studies, six reported increased mammary tumorigenesis (four administered a co-carcinogen and two did not). Other animal studies reported conversion of ethanol to acetaldehyde in mammary tissue as having a significant effect on the progression of tumor development. Fifteen cell line studies suggested the following mechanisms: Increased hormonal receptor levels. Increased cell proliferation. A direct stimulatory effect. DNA adduct formation. Increase cyclic adenosine monophosphate (camp). Change in potassium channels. Modulation of gene expression. Colorectal Cancer. One human tissue study, 19 animal studies (of which 12 administered a co-carcinogen and seven did not), and 10 cell line studies indicate that ethanol and acetaldehyde may alter metabolic pathways and cell structures that increase the risk of developing colon cancer. Exposure of human colonic biopsies to acetaldehyde suggests that acetaldehyde disrupts epithelial tight junctions. Among 19 animal studies the mechanisms considered included: Mucosal damage after ethanol consumption. Increased degradation of folate. Stimulation of rectal carcinogenesis. Increased cell proliferation. Increased effect of carcinogens. Ten cell line studies suggested: Folate uptake modulation. Tumor necrosis factor modulation. Inflammation and cell death. DNA adduct formation. Cell differentiation. Modulation of gene expression. One study used a combination of animal and cell line and suggested intestinal cell proliferation and disruption of cellular signals as possible mechanisms., Conclusions: Based on our systematic review of the literature, many potential mechanisms by which alcohol may influence the development of breast or colorectal cancers have been explored but the exact connection or connections remain unclear. The evidence points in several directions but the importance of any one mechanism is not apparent at this time.

Unlabelled: This document reports the consensus of an interdisciplinary panel of research and clinical experts charged with reviewing the use of opioids for chronic noncancer pain (CNCP) and formulating guidelines for future research. Prescribing opioids for chronic noncancer pain has recently escalated in the United States. Contrasting with increasing opioid use are: 1) The lack of evidence supporting long-term effectiveness; 2) Escalating misuse of prescription opioids including abuse and diversion; and 3) Uncertainty about the incidence and clinical salience of multiple, poorly characterized adverse drug events (ADEs) including endocrine dysfunction, immunosuppression and infectious disease, opioid-induced hyperalgesia and xerostomia, overdose, falls and fractures, and psychosocial complications. Chief among the limitations of current evidence are: 1) Sparse evidence on long-term opioid effectiveness in chronic pain patients due to the short-term time frame of clinical trials; 2) Insufficiently comprehensive outcome assessment; and 3) Incomplete identification and quantification of ADEs. The panel called for a strategic interdisciplinary approach to the problem domain in which basic scientists and clinicians cooperate to resolve urgent issues and generate a comprehensive evidence base. It offered 4 recommendations in 3 areas: 1) A research strategy for studying the effectiveness of long-term opioid pharmacotherapy; 2) Improvements in evidence-generation methodology; and 3) Potential research topics for generating new evidence., Perspective: Prescribing opioids for CNCP has outpaced the growth of scientific evidence bearing on the benefits and harms of these interventions. The need for a strong evidence base is urgent. This guideline offers a strategic approach to creating a comprehensive evidence base to guide safe and effective management of CNCP., (Copyright 2010 American Pain Society. All rights reserved.)

Background: Opioid therapy for chronic noncancer pain (CNCP) is controversial due to concerns regarding long-term effectiveness and safety, particularly the risk of tolerance, dependence, or abuse., Objectives: To assess safety, efficacy, and effectiveness of opioids taken long-term for CNCP., Search Strategy: We searched 10 bibliographic databases up to May 2009., Selection Criteria: We searched for studies that: collected efficacy data on participants after at least 6 months of treatment; were full-text articles; did not include redundant data; were prospective; enrolled at least 10 participants; reported data of participants who had CNCP. Randomized controlled trials (RCTs) and pre-post case-series studies were included., Data Collection and Analysis: Two review authors independently extracted safety and effectiveness data and settled discrepancies by consensus. We used random-effects meta-analysis' to summarize data where appropriate, used the I(2) statistic to quantify heterogeneity, and, where appropriate, explored heterogeneity using meta-regression. Several sensitivity analyses were performed to test the robustness of the results., Main Results: We reviewed 26 studies with 27 treatment groups that enrolled a total of 4893 participants. Twenty five of the studies were case series or uncontrolled long-term trial continuations, the other was an RCT comparing two opioids. Opioids were administered orally (number of study treatments groups [abbreviated as "k"] = 12, n = 3040), transdermally (k = 5, n = 1628), or intrathecally (k = 10, n = 231). Many participants discontinued due to adverse effects (oral: 22.9% [95% confidence interval (CI): 15.3% to 32.8%]; transdermal: 12.1% [95% CI: 4.9% to 27.0%]; intrathecal: 8.9% [95% CI: 4.0% to 26.1%]); or insufficient pain relief (oral: 10.3% [95% CI: 7.6% to 13.9%]; intrathecal: 7.6% [95% CI: 3.7% to 14.8%]; transdermal: 5.8% [95% CI: 4.2% to 7.9%]). Signs of opioid addiction were reported in 0.27% of participants in the studies that reported that outcome. All three modes of administration were associated with clinically significant reductions in pain, but the amount of pain relief varied among studies. Findings regarding quality of life and functional status were inconclusive due to an insufficient quantity of evidence for oral administration studies and inconclusive statistical findings for transdermal and intrathecal administration studies., Authors' Conclusions: Many patients discontinue long-term opioid therapy (especially oral opioids) due to adverse events or insufficient pain relief; however, weak evidence suggests that patients who are able to continue opioids long-term experience clinically significant pain relief. Whether quality of life or functioning improves is inconclusive. Many minor adverse events (like nausea and headache) occurred, but serious adverse events, including iatrogenic opioid addiction, were rare.