Screening patients in general practice for advanced chronic liver disease using an innovative IT solution: The Liver Toolkit.

BACKGROUND: Identifying patients with undiagnosed advanced chronic liver disease (ACLD) is a public health challenge. Patients with advanced fibrosis or compensated cirrhosis have much better outcomes than those with decompensated disease and may be eligible for interventions to prevent disease progression. METHODS: A cloud-based software solution ("the Liver Toolkit") was developed to access primary care practice software to identify patients at risk of ACLD. Clinical history and laboratory results were extracted to calculate aspartate aminotransferase-to-platelet ratio index and fibrosis 4 scores. Patients identified were recalled for assessment, including Liver Stiffness Measurement (LSM) via transient elastography. Those with an existing diagnosis of cirrhosis were excluded. RESULTS: Existing laboratory results of more than 32,000 adults across nine general practices were assessed to identify 703 patients at increased risk of ACLD (2.2% of the cohort). One hundred seventy-nine patients (26%) were successfully recalled, and 23/179 (13%) were identified to have ACLD (LSM ≥10.0 kPa) (10% found at indeterminate risk [LSM 8.0-9.9 kPa] and 77% low risk of fibrosis [LSM <8.0 kPa]). In most cases, the diagnosis of liver disease was new, with the most common etiology being metabolic dysfunction-associated steatotic liver disease (n=20, 83%). Aspartate aminotransferase-to-platelet ratio index ≥1.0 and fibrosis 4 ≥3.25 had a positive predictive value for detecting ACLD of 19% and 24%, respectively. Patients who did not attend recall had markers of more severe disease with a higher median aspartate aminotransferase-to-platelet ratio index score (0.57 vs. 0.46, p=0.041). CONCLUSIONS: This novel information technology system successfully screened a large primary care cohort using existing laboratory results to identify patients at increased risk ACLD. More than 1 in 5 patients recalled were found to have liver disease requiring specialist follow-up.

State Level Point-of-Sale Policy Priority as a Result of the FSPTCA.

The Family Smoking Prevention and Tobacco Control Act (FSPTCA) give the U.S. Food and Drug Administration (FDA) unprecedented power to regulate tobacco products. One of the most significant provisions of the law allows state and local governments to adopt and enforce tobacco control legislation restricting the time, place, and manner (but not the content) of tobacco advertising. However, there is still reluctance among states and localities for mass adoption of laws due to challenges associated with legal feasibility and lack of U.S.-based evidence in effectiveness. The Center for Public Health Systems Science conducted interviews with key tobacco control contacts in 48 states at two time points (2012 and 2014) since the passage of the FSPTCA to assess the influence of the law on point-of-sale policy development in their state tobacco programs. Logistic regression results show that point-of-sale policy importance is growing post-FSPTCA, and that key influencers of this importance are states' tobacco control histories and environments, including that related to excise taxes and smoke free air policies. The adoption of smokefree and tax policies has become commonplace across the U.S., and the quality and extent of these laws and prevailing political will increasingly impact the ability of states to work in emerging tobacco control policy areas including those directed at the point of sale.

Managing Health Care After Cancer Treatment: A Wellness Plan.

Many patients and health care providers lack awareness of both the existence of, and treatments for, lingering distress and disability after treatment. A cancer survivorship wellness plan can help ensure that any referral needs for psychosocial and other restorative care after cancer treatment are identified.

The diagnosis of acute mesenteric ischemia: A systematic review and meta-analysis.

OBJECTIVES: Acute mesenteric ischemia is an infrequent cause of abdominal pain in emergency department (ED) patients; however, mortality for this condition is high. Rapid diagnosis and surgery are key to survival, but presenting signs are often vague or variable, and there is no pathognomonic laboratory screening test. A systematic review and meta-analysis of the available literature was performed to determine diagnostic test characteristics of patient symptoms, objective signs, laboratory studies, and diagnostic modalities to help rule in or out the diagnosis of acute mesenteric ischemia in the ED. METHODS: In concordance with published guidelines for systematic reviews, the medical literature was searched for relevant articles. The Quality Assessment Tool for Diagnostic Accuracy Studies-2 (QUADAS-2) for systematic reviews was used to evaluate the overall quality of the trials included. Summary estimates of diagnostic accuracy were computed by using a random-effects model to combine studies. Those studies without data to fully complete a two-by-two table were not included in the meta-analysis portion of the project. RESULTS: The literature search identified 1,149 potentially relevant studies, of which 23 were included in the final analysis. The quality of the diagnostic studies was highly variable. A total of 1,970 patients were included in the combined population of all included studies. The prevalence of acute mesenteric ischemia ranged from 8% to 60%. There was a pooled sensitivity for l-lactate of 86% (95% confidence interval [CI] = 73% to 94%) and a pooled specificity of 44% (95% CI = 32% to 55%). There was a pooled sensitivity for D-dimer of 96% (95% CI = 89% to 99%) and a pooled specificity of 40% (95% CI = 33% to 47%). For computed tomography (CT), we found a pooled sensitivity of 94% (95% CI = 90% to 97%) and specificity of 95% (95% CI = 93% to 97%). The positive likelihood ratio (+LR) for a positive CT was 17.5 (95% CI = 5.99 to 51.29), and the negative likelihood ratio (-LR) was 0.09 (95% CI = 0.05 to 0.17). The pooled operative mortality rate for mesenteric ischemia was 47% (95% CI = 40% to 54%). Given these findings, the test threshold of 2.1% (below this pretest probability, do not test further) and a treatment threshold of 74% (above this pretest probability, proceed to surgical management) were calculated. CONCLUSIONS: The quality of the overall literature base for mesenteric ischemia is varied. Signs, symptoms, and laboratory testing are insufficiently diagnostic for the condition. Only CT angiography had adequate accuracy to establish the diagnosis of acute mesenteric ischemia in lieu of laparotomy.

Implementing a dedicated education unit: a practice partnership with oncology nurses.

An urgent need exists to identify innovative and evidence-based educational methods to help oncology nurses provide safe and high-quality patient care. One promising solution is the dedicated education unit (DEU) educational model, which partners nursing faculty and skilled nursing clinicians to facilitate the clinical experience of undergraduate baccalaureate nursing students. This article describes the collaborative DEU initiative developed between a university school of nursing and a tertiary cancer center to provide senior nursing students with an innovative method to develop their competencies in oncology nursing practice and care.

Assessing the role of patient support services on adherence rates in patients using glatiramer acetate for relapsing-remitting multiple sclerosis.

OBJECTIVE: To assess predictors of achievement of 80% Medication Possession Ratio (MPR) in patients receiving manufacturer-provided self-management services for relapsing-remitting multiple sclerosis (RRMS) patients taking glatiramer acetate (Copaxone). METHODS: De-identified patient records were selected for study inclusion if patients had been (1) continuously enrolled in one or more aspects of the self-management program for a minimum of 24 months and had adherence measured by MPR between the values of zero and one. Baseline patient univariate measures were assessed using chi-squared statistics for categorical variables and Analysis of Variance (ANOVA) for continuous variables. Bivariate logistic regression models were used to assess predictors of 80% MPR. RESULTS: A total of 5825 patients met the study inclusion criteria. About 70% of patients received manufacturer-provided injection training and 75% were eligible for, and utilized, copayment assistance; 74.3% of patients accessing sponsor provided support achieved a desired MPR of greater than or equal to 80%. Patients were 40% more likely to reach goal if injection training was provided by the manufacturer (OR = 1.435; 95% CI = 1.258-1.636) and were 30.6% more likely to achieve goal when eligible patients utilized copayment assistance programs (OR = 1.306; 95% CI = 1.109-1.570). Patients reinitiating treatment were at risk of lower adherence rates (OR = 0.605; CI = 0.476-0.769) compared to those who were new to therapy. CONCLUSIONS: Manufacturer-provided patient support programs improve adherence to glatiramer acetate therapy.

Signal activation and inactivation by the Gα helical domain: a long-neglected partner in G protein signaling.

Heterotrimeric guanine nucleotide-binding proteins (G proteins) are positioned at the top of many signal transduction pathways. The G protein α subunit is composed of two domains, one that resembles Ras and another that is composed entirely of α helices. Historically most attention has focused on the Ras-like domain, but emerging evidence reveals that the helical domain is an active participant in G protein signaling.

The crystal structure of a self-activating G protein alpha subunit reveals its distinct mechanism of signal initiation.

In animals, heterotrimeric guanine nucleotide-binding protein (G protein) signaling is initiated by G protein-coupled receptors (GPCRs), which activate G protein α subunits; however, the plant Arabidopsis thaliana lacks canonical GPCRs, and its G protein α subunit (AtGPA1) is self-activating. To investigate how AtGPA1 becomes activated, we determined its crystal structure. AtGPA1 is structurally similar to animal G protein α subunits, but our crystallographic and biophysical studies revealed that it had distinct properties. Notably, the helical domain of AtGPA1 displayed pronounced intrinsic disorder and a tendency to disengage from the Ras domain of the protein. Domain substitution experiments showed that the helical domain of AtGPA1 was necessary for self-activation and sufficient to confer self-activation to an animal G protein α subunit. These findings reveal the structural basis for a mechanism for G protein activation in Arabidopsis that is distinct from the well-established mechanism found in animals.

Cancer-related pain management: a report of evidence-based recommendations to guide practice.

OBJECTIVES: Cancer may be associated with many symptoms, but pain is the one most feared by patients. Pain is experienced by one-third of patients receiving treatment for cancer and about two-thirds of those with advanced cancers. To aid in providing quality care and pain relief for cancer patients, Cancer Care Ontario's Cancer-related Pain Management Guideline Panel conducted a systematic review of guidelines to provide evidence-based and consensus recommendations for the management of cancer-related pain to guide the practice of healthcare providers. METHODS: Published and unpublished cancer-related pain management guidelines were sought by conducting an Internet search, which included health organizations and the National Guidelines Clearinghouse, the Guideline International Network, and the McMillan Group. Also, MEDLINE searches were conducted for guidelines published between the years 2000 and May 2006. RESULTS: Twenty-five guidelines were found and the quality of each guideline was evaluated using the Appraisal of Guideline Research and Evaluation Instrument and the utility of the guideline for recommendations was assessed. Using these 2 criteria, 8 relevant and high-quality pain guidelines were identified. From these guidelines, the Panel articulated core principles of the management of cancer pain and selected or adapted specific recommendations through consensus to become a part of the cancer-related pain guide for practice. DISCUSSION: The domains on which recommendations were drafted include: assessment of pain; assessors of pain; time and frequency of assessment; components of pain assessment; assessment of pain in special populations; plan of care; pharmacologic intervention; nonpharmacologic intervention; documentation; education; and outcome measures of cancer-pain management.

Expanding the functional repertoire of CTD kinase I and RNA polymerase II: novel phosphoCTD-associating proteins in the yeast proteome.

CTD kinase I (CTDK-I) of Saccharomyces cerevisiae is required for normal phosphorylation of the C-terminal repeat domain (CTD) on elongating RNA polymerase II. To elucidate cellular roles played by this kinase and the hyperphosphorylated CTD (phosphoCTD) it generates, we systematically searched yeast extracts for proteins that bound to the phosphoCTD made by CTDK-I in vitro. Initially, using a combination of far-western blotting and phosphoCTD affinity chromatography, we discovered a set of novel phosphoCTD-associating proteins (PCAPs) implicated in a variety of nuclear functions. We identified the phosphoCTD-interacting domains of a number of these PCAPs, and in several test cases (namely, Set2, Ssd1, and Hrr25) adduced evidence that phosphoCTD binding is functionally important in vivo. Employing surface plasmon resonance (BIACORE) analysis, we found that recombinant versions of these and other PCAPs bind preferentially to CTD repeat peptides carrying SerPO(4) residues at positions 2 and 5 of each seven amino acid repeat, consistent with the positional specificity of CTDK-I in vitro [Jones, J. C., et al. (2004) J. Biol. Chem. 279, 24957-24964]. Subsequently, we used a synthetic CTD peptide with three doubly phosphorylated repeats (2,5P) as an affinity matrix, greatly expanding our search for PCAPs. This resulted in identification of approximately 100 PCAPs and associated proteins representing a wide range of functions (e.g., transcription, RNA processing, chromatin structure, DNA metabolism, protein synthesis and turnover, RNA degradation, snRNA modification, and snoRNP biogenesis). The varied nature of these PCAPs and associated proteins points to an unexpectedly diverse set of connections between Pol II elongation and other processes, conceptually expanding the role played by CTD phosphorylation in functional organization of the nucleus.

Southern Ocean iron enrichment experiment: carbon cycling in high- and low-Si waters.

The availability of iron is known to exert a controlling influence on biological productivity in surface waters over large areas of the ocean and may have been an important factor in the variation of the concentration of atmospheric carbon dioxide over glacial cycles. The effect of iron in the Southern Ocean is particularly important because of its large area and abundant nitrate, yet iron-enhanced growth of phytoplankton may be differentially expressed between waters with high silicic acid in the south and low silicic acid in the north, where diatom growth may be limited by both silicic acid and iron. Two mesoscale experiments, designed to investigate the effects of iron enrichment in regions with high and low concentrations of silicic acid, were performed in the Southern Ocean. These experiments demonstrate iron's pivotal role in controlling carbon uptake and regulating atmospheric partial pressure of carbon dioxide.