196 research outputs found
Whose Goals? Whose Aspirations?: Learning to Teach Underprepared Writers across the Curriculum
Ever since Horace Mann promoted state supported schooling in the 1850s, the aims of U.S. public education have been the subject of heated national debate. Whose Goals? Whose Aspirations? joins this debate by exploring clashing educational aims in a discipline-based university classroom and the consequences of these clashes for underprepared writers. In this close-up look at a White middle-class teacher and his ethnically diverse students, Fishman and McCarthy examine not only the role of Standard English in college writing instruction but also the underlying and highly charged issues of multiculturalism, race cognizance, and social class.https://digitalcommons.usu.edu/usupress_pubs/1137/thumbnail.jp
A primary care, multi-disciplinary disease management program for opioid-treated patients with chronic non-cancer pain and a high burden of psychiatric comorbidity
BACKGROUND: Chronic non-cancer pain is a common problem that is often accompanied by psychiatric comorbidity and disability. The effectiveness of a multi-disciplinary pain management program was tested in a 3 month before and after trial. METHODS: Providers in an academic general medicine clinic referred patients with chronic non-cancer pain for participation in a program that combined the skills of internists, clinical pharmacists, and a psychiatrist. Patients were either receiving opioids or being considered for opioid therapy. The intervention consisted of structured clinical assessments, monthly follow-up, pain contracts, medication titration, and psychiatric consultation. Pain, mood, and function were assessed at baseline and 3 months using the Brief Pain Inventory (BPI), the Center for Epidemiological Studies-Depression Scale scale (CESD) and the Pain Disability Index (PDI). Patients were monitored for substance misuse. RESULTS: Eighty-five patients were enrolled. Mean age was 51 years, 60% were male, 78% were Caucasian, and 93% were receiving opioids. Baseline average pain was 6.5 on an 11 point scale. The average CESD score was 24.0, and the mean PDI score was 47.0. Sixty-three patients (73%) completed 3 month follow-up. Fifteen withdrew from the program after identification of substance misuse. Among those completing 3 month follow-up, the average pain score improved to 5.5 (p = 0.003). The mean PDI score improved to 39.3 (p < 0.001). Mean CESD score was reduced to 18.0 (p < 0.001), and the proportion of depressed patients fell from 79% to 54% (p = 0.003). Substance misuse was identified in 27 patients (32%). CONCLUSIONS: A primary care disease management program improved pain, depression, and disability scores over three months in a cohort of opioid-treated patients with chronic non-cancer pain. Substance misuse and depression were common, and many patients who had substance misuse identified left the program when they were no longer prescribed opioids. Effective care of patients with chronic pain should include rigorous assessment and treatment of these comorbid disorders and intensive efforts to insure follow up
Statistical design of personalized medicine interventions: The Clarification of Optimal Anticoagulation through Genetics (COAG) trial
<p>Abstract</p> <p>Background</p> <p>There is currently much interest in pharmacogenetics: determining variation in genes that regulate drug effects, with a particular emphasis on improving drug safety and efficacy. The ability to determine such variation motivates the application of personalized drug therapies that utilize a patient's genetic makeup to determine a safe and effective drug at the correct dose. To ascertain whether a genotype-guided drug therapy improves patient care, a personalized medicine intervention may be evaluated within the framework of a randomized controlled trial. The statistical design of this type of personalized medicine intervention requires special considerations: the distribution of relevant allelic variants in the study population; and whether the pharmacogenetic intervention is equally effective across subpopulations defined by allelic variants.</p> <p>Methods</p> <p>The statistical design of the Clarification of Optimal Anticoagulation through Genetics (COAG) trial serves as an illustrative example of a personalized medicine intervention that uses each subject's genotype information. The COAG trial is a multicenter, double blind, randomized clinical trial that will compare two approaches to initiation of warfarin therapy: genotype-guided dosing, the initiation of warfarin therapy based on algorithms using clinical information and genotypes for polymorphisms in <it>CYP2C9 </it>and <it>VKORC1</it>; and clinical-guided dosing, the initiation of warfarin therapy based on algorithms using only clinical information.</p> <p>Results</p> <p>We determine an absolute minimum detectable difference of 5.49% based on an assumed 60% population prevalence of zero or multiple genetic variants in either <it>CYP2C9 </it>or <it>VKORC1 </it>and an assumed 15% relative effectiveness of genotype-guided warfarin initiation for those with zero or multiple genetic variants. Thus we calculate a sample size of 1238 to achieve a power level of 80% for the primary outcome. We show that reasonable departures from these assumptions may decrease statistical power to 65%.</p> <p>Conclusions</p> <p>In a personalized medicine intervention, the minimum detectable difference used in sample size calculations is not a known quantity, but rather an unknown quantity that depends on the genetic makeup of the subjects enrolled. Given the possible sensitivity of sample size and power calculations to these key assumptions, we recommend that they be monitored during the conduct of a personalized medicine intervention.</p> <p>Trial Registration</p> <p>clinicaltrials.gov: NCT00839657</p
Modulation of the Akt/Ras/Raf/MEK/ERK pathway by A3 adenosine receptor
Downstream A3 receptor signalling plays an important role in the regulation of cell death and proliferation. Therefore, it is important to determine the molecular pathways involved through A3 receptor stimulation. The phosphatidylinositide-3-OH kinase (PI3K)/Akt and the Raf/mitogen-activated protein kinase (MAPK/ERK) kinase (MEK)/mitogen-activated protein kinase (MAPK) pathways have central roles in the regulation of cell survival and proliferation. The crosstalk between these two pathways has also been investigated. The focus of this review centres on downstream mediators of A3 adenosine receptor signalling
Adenosine and lymphocyte regulation
Adenosine is a potent extracellular messenger that is produced in high concentrations under metabolically unfavourable conditions. Tissue hypoxia, consequent to a compromised cellular energy status, is followed by the enhanced breakdown of ATP leading to the release of adenosine. Through the interaction with A2 and A3 membrane receptors, adenosine is devoted to the restoration of tissue homeostasis, acting as a retaliatory metabolite. Several aspects of the immune response have to be taken into consideration and even though in general it is very important to dampen inflammation, in some circumstances, such as the case of cancer, it is also necessary to increase the activity of immune cells against pathogens. Therefore, adenosine receptors that are defined as ‘sensors–of metabolic changes in the local tissue environment may be very important targets for modulation of immune responses and drugs devoted to regulating the adenosinergic system are promising in different clinical situations
Predictors of opioid misuse in patients with chronic pain: a prospective cohort study
BACKGROUND: Opioid misuse can complicate chronic pain management, and the non-medical use of opioids is a growing public health problem. The incidence and risk factors for opioid misuse in patients with chronic pain, however, have not been well characterized. We conducted a prospective cohort study to determine the one-year incidence and predictors of opioid misuse among patients enrolled in a chronic pain disease management program within an academic internal medicine practice. METHODS: One-hundred and ninety-six opioid-treated patients with chronic, non-cancer pain of at least three months duration were monitored for opioid misuse at pre-defined intervals. Opioid misuse was defined as: 1. Negative urine toxicological screen (UTS) for prescribed opioids; 2. UTS positive for opioids or controlled substances not prescribed by our practice; 3. Evidence of procurement of opioids from multiple providers; 4. Diversion of opioids; 5. Prescription forgery; or 6. Stimulants (cocaine or amphetamines) on UTS. RESULTS: The mean patient age was 52 years, 55% were male, and 75% were white. Sixty-two of 196 (32%) patients committed opioid misuse. Detection of cocaine or amphetamines on UTS was the most common form of misuse (40.3% of misusers). In bivariate analysis, misusers were more likely than non-misusers to be younger (48 years vs 54 years, p < 0.001), male (59.6% vs. 38%; p = 0.023), have past alcohol abuse (44% vs 23%; p = 0.004), past cocaine abuse (68% vs 21%; p < 0.001), or have a previous drug or DUI conviction (40% vs 11%; p < 0.001%). In multivariate analyses, age, past cocaine abuse (OR, 4.3), drug or DUI conviction (OR, 2.6), and a past alcohol abuse (OR, 2.6) persisted as predictors of misuse. Race, income, education, depression score, disability score, pain score, and literacy were not associated with misuse. No relationship between pain scores and misuse emerged. CONCLUSION: Opioid misuse occurred frequently in chronic pain patients in a pain management program within an academic primary care practice. Patients with a history of alcohol or cocaine abuse and alcohol or drug related convictions should be carefully evaluated and followed for signs of misuse if opioids are prescribed. Structured monitoring for opioid misuse can potentially ensure the appropriate use of opioids in chronic pain management and mitigate adverse public health effects of diversion
Exploring the relationship between chronic undernutrition and asymptomatic malaria in Ghanaian children
<p>Abstract</p> <p>Background</p> <p>A moderate association has been found between asymptomatic parasitaemia and undernutrition. However, additional investigation using the gold standard for asymptomatic parasitaemia confirmation, polymerase chain reaction (PCR), is needed to validate this association. Anthropometric measurements and blood samples from children less than five years of age in a rural Ghanaian community were used to determine if an association exists between chronic undernutrition and PCR-confirmed cases of asymptomatic malaria.</p> <p>Methods</p> <p>This was a descriptive cross-sectional study of 214 children less than five years of age from a community near Kumasi, Ghana. Blood samples and anthropometric measurements from these children were collected during physical examinations conducted in January 2007 by partners of the Barekuma Collaborative Community Development Programme.</p> <p>Results</p> <p>Findings from the logistic model predicting the odds of asymptomatic malaria indicate that children who experienced mild, moderate or severe stunting were not more likely to have asymptomatic malaria than children who were not stunted. Children experiencing anaemia had an increased likelihood (OR = 4.15; 95% CI: 1.92, 8.98) of asymptomatic malaria. Similarly, increased spleen size, which was measured by ultrasound, was also associated with asymptomatic malaria (OR = 2.17; 95% CI: 1.44, 3.28). Fast breathing, sex of the child, and age of the child were not significantly associated with the asymptomatic malaria.</p> <p>Conclusions</p> <p>No significant association between chronic undernutrition and presence of asymptomatic malaria was found. Children who experience anaemia and children who have splenomegaly are more likely to present asymptomatic malaria. Programmes aimed at addressing malaria should continue to include nutritional components, especially components that address anaemia.</p
Genetics of Sputum Gene Expression in Chronic Obstructive Pulmonary Disease
Previous expression quantitative trait loci (eQTL) studies have performed genetic association studies for gene expression, but most of these studies examined lymphoblastoid cell lines from non-diseased individuals. We examined the genetics of gene expression in a relevant disease tissue from chronic obstructive pulmonary disease (COPD) patients to identify functional effects of known susceptibility genes and to find novel disease genes. By combining gene expression profiling on induced sputum samples from 131 COPD cases from the ECLIPSE Study with genomewide single nucleotide polymorphism (SNP) data, we found 4315 significant cis-eQTL SNP-probe set associations (3309 unique SNPs). The 3309 SNPs were tested for association with COPD in a genomewide association study (GWAS) dataset, which included 2940 COPD cases and 1380 controls. Adjusting for 3309 tests (p<1.5e-5), the two SNPs which were significantly associated with COPD were located in two separate genes in a known COPD locus on chromosome 15: CHRNA5 and IREB2. Detailed analysis of chromosome 15 demonstrated additional eQTLs for IREB2 mapping to that gene. eQTL SNPs for CHRNA5 mapped to multiple linkage disequilibrium (LD) bins. The eQTLs for IREB2 and CHRNA5 were not in LD. Seventy-four additional eQTL SNPs were associated with COPD at p<0.01. These were genotyped in two COPD populations, finding replicated associations with a SNP in PSORS1C1, in the HLA-C region on chromosome 6. Integrative analysis of GWAS and gene expression data from relevant tissue from diseased subjects has located potential functional variants in two known COPD genes and has identified a novel COPD susceptibility locus
- …