553 research outputs found

    Cost effectiveness analysis of cervical cancer screening in women until age 70

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    Background: 2017 US Preventive Services Task Force guidelines for screening cervical cancer and pre-malignant lesions advise that screenings cease for women over age 65, with qualifications. Recent literature has identified significant discrepancies in rates of cervical cancer in older women – if hysterectomies in this patient population is accounted for, cervical cancer incidence does not decline with age as previously established. This adjusted incidence of cervical cancer necessitates a re-examination of current practice.Methods: This study seeks to demonstrate the utility of extending the cervical cancer screening age recommendations to age 70. Cost effectiveness will be estimated, from a payer perspective, of extending screening to age 70 for the United States women’s population in those who have not undergone hysterectomy or otherwise been treated for past cervical cancer or premalignancy. A Markov model was constructed to project outcomes in a hypothetical cohort of 10 000 women aged 65 to 70, with a time horizon of lifetime. A Probability Sensitivity Analysis determined the robustness of the result, and the Incremental Cost-effectiveness Ratio (ICER) is charted.Results: The economic evaluation of screening compared to none in this population was determined to be cost effective, with an ICER demonstrating a cost benefit, and Quality Adjusted Life Year (QALY) benefit, to extended screening.Conclusions: The sensitivity analysis confirms the robustness of this result. Implementing extended screening guidelines could potentially be a significant gain for both patients and society

    Computational purification of individual tumor gene expression profiles leads to significant improvements in prognostic prediction.

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    Tumor heterogeneity is a limiting factor in cancer treatment and in the discovery of biomarkers to personalize it. We describe a computational purification tool, ISOpure, to directly address the effects of variable normal tissue contamination in clinical tumor specimens. ISOpure uses a set of tumor expression profiles and a panel of healthy tissue expression profiles to generate a purified cancer profile for each tumor sample and an estimate of the proportion of RNA originating from cancerous cells. Applying ISOpure before identifying gene signatures leads to significant improvements in the prediction of prognosis and other clinical variables in lung and prostate cancer

    Overestimation of minimal model glucose effectiveness in presence of insulin response is due to undermodeling

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    Glucose effectiveness is an important determinant of glucose tolerance that can be derived from minimal model analysis of an intravenous glucose tolerance test (IVGTT). However, recent evidence suggests that glucose effectiveness is overestimated by minimal model analysis. Here we compare a new model-independent estimate of glucose effectiveness with the minimal model estimate by reanalyzing published data in which insulin-dependent diabetic subjects were each given IVGTTs under two conditions (Quon, M. J., C. Cochran, S. I. Taylor, and R. C. Eastman. Diabetes 43: 890-896, 1994). In one case, a basal insulin level was maintained (BI-IVGTT). In the second case, a dynamic insulin response was recreated (DI-IVGTT). Our results show that minimal model glucose effectiveness is very similar to the model- independent measurement during a BI-IVGTT but is three times higher during a DI-IVGTT. To investigate the causes of minimal model overestimation in the presence of a dynamic insulin response, Monte Carlo simulation studies on a two-compartment model of glucose kinetics with various insulin response patterns were performed. Results suggest that minimal model overestimation is due to single-compartment representation of glucose kinetics that results in a critical oversimplification in the presence of increasingly dynamic insulin secretion patterns

    ISOpureR: an R implementation of a computational purification algorithm of mixed tumour profiles

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    Background Tumour samples containing distinct sub-populations of cancer and normal cells present challenges in the development of reproducible biomarkers, as these biomarkers are based on bulk signals from mixed tumour profiles. ISOpure is the only mRNA computational purification method to date that does not require a paired tumour-normal sample, provides a personalized cancer profile for each patient, and has been tested on clinical data. Replacing mixed tumour profiles with ISOpure-preprocessed cancer profiles led to better prognostic gene signatures for lung and prostate cancer. Results To simplify the integration of ISOpure into standard R-based bioinformatics analysis pipelines, the algorithm has been implemented as an R package. The ISOpureR package performs analogously to the original code in estimating the fraction of cancer cells and the patient cancer mRNA abundance profile from tumour samples in four cancer datasets. Conclusions The ISOpureR package estimates the fraction of cancer cells and personalized patient cancer mRNA abundance profile from a mixed tumour profile. This open-source R implementation enables integration into existing computational pipelines, as well as easy testing, modification and extension of the model.Prostate Cancer CanadaMovember Foundation (Grant RS2014-01

    A Prospective Observational Study of Antihemophilic Factor (Recombinant) Prophylaxis Related to Physical Activity Levels in Patients with Hemophilia A in the United States (SPACE)

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    Introduction: High collision-risk physical activity can increase bleeding risk in people with hemophilia A, as can increasing the time between factor VIII (FVIII) administration and physical activity. FVIII prophylaxis may be tailored to planned activities to prevent activity-related bleeding. Aim: To explore the relationship between physical activity levels, FVIII infusion timing, and occurrence of bleeding in patients with severe/moderately severe hemophilia A without FVIII inhibitors receiving antihemophilic factor (recombinant) (rAHF; ADVATE®; Baxalta US Inc., a Takeda company, Lexington, MA, USA). Methods: SPACE was a 6-month, prospective, multicenter, observational outcomes study (NCT02190149). Enrolled patients received an eDiary application and a wearable activity tracker, which recorded physical activity, rAHF infusion, and occurrence of bleeding. Physical activity risks were ranked using National Hemophilia Foundation criteria. Results: Fifty-four patients aged 11– 58 years (n = 47 prophylaxis, n = 7 on-demand) were included in the analysis. Patients had a mean (SD) 8.14 (10.94) annualized bleeding rate, and recorded 4980 intervals between an rAHF infusion and physical activity; 1759 (35.3%) of these intervals were ≤ 24 hours. Analysis of recorded eDiary data showed that the risk of activity-related bleeding did not significantly increase with time between last infusion and activity, but did increase with higher-risk physical activities. Analysis of activity tracker recorded data showed that the risk of bleeding reported by patients as spontaneous increased with prolonging time (≤ 24 to \u3e 24 hours) from last infusion to physical activity start (odds ratio 2.65, p \u3c 0.05). Joint health data collected at baseline were not included in the regression analysis because of small sample size; therefore the study could not assess whether patients with more joint disease at baseline were at higher risk of injury-related and reported spontaneous occurrence of bleeding. Conclusion: These results show that activities with a high risk of collision lead to an increased risk of bleeding. Further investigation is warranted to explore potential benefits of FVIII infusion timing to reduce the risks of activity-related occurrence of bleeding

    Socioeconomic inequalities in health among Swedish adolescents - adding the subjective perspective

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    Abstract Background Socioeconomic inequalities in adolescent health predict future inequalities in adult health. Subjective measures of socioeconomic status (SES) may contribute with an increased understanding of these inequalities. The aim of this study was to investigate socioeconomic health inequalities using both a subjective and an objective measure of SES among Swedish adolescents. Method Cross-sectional HBSC-data from 2002 to 2014 was used with a total sample of 23,088 adolescents aged 11–15 years. Three measures of self-rated health (dependent variables) were assessed: multiple health complaints, life satisfaction and health perception. SES was measured objectively by the Family Affluence Scale (FAS) and subjectively by “perceived family wealth” (independent variables). The trend for health inequalities was investigated descriptively with independent t-tests and the relationship between independent and dependent variables was investigated with multiple logistic regression analysis. Gender, age and survey year was considered as possible confounders. Results Subjective SES was more strongly related to health outcomes than the objective measure (FAS). Also, the relation between FAS and health was weakened and even reversed (for multiple health complaints) when subjective SES was tested simultaneously in regression models (FAS OR: 1.03, CI: 1.00;1.06 and subjective SES OR: 0.66, CI: 0.63;0.68). Conclusions The level of socioeconomic inequalities in adolescent health varied depending on which measure that was used to define SES. When focusing on adolescents, the subjective appraisals of SES is important to consider because they seem to provide a stronger tool for identifying inequalities in health for this group. This finding is important for policy makers to consider given the persistence of health inequalities in Sweden and other high-income countries

    I smoke to cope with pain: patients\u27 perspectives on the link between cigarette smoking and pain

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    BACKGROUND: For people with chronic pain, cigarette smoking is associated with greater pain intensity and impairment. Researchers have hypothesized a reciprocal relationship in which pain and smoking exacerbate each other, resulting in greater pain and increased smoking. This study aimed to qualitatively examine patient perspectives on this association. METHODS: A retrospective thematic analysis of smoking cessation counseling notes for 136 veterans in the Pain and Smoking Study, a tailored smoking cessation trial, was conducted. A validated codebook was applied to each counseling note by four independent coders using Atlas.ti (Atlas.ti, Berlin, Germany). Coders participated in a consensus-forming exercise with salient themes validated among the wider research team. KEY RESULTS: Participants averaged 60 years of age (range 28-77 years) and were 9% female. The median number of cigarettes smoked per day was 15, with a mean pain intensity score in the last week (from 0-10) of 5.1. While not all patients acknowledged a connection between pain and smoking, we found that (1) pain motivates smoking and helps manage pain-related distress, as a coping strategy and through cognitive distraction, and (2) pain motivates smoking but smoking does not offer pain relief. Concerns about managing pain without smoking was identified as a notable barrier to cessation. CONCLUSION: Many patients with chronic pain who smoke readily identified pain as a motivator of their smoking behavior and are reluctant to quit for this reason. Integrated interventions for smokers with pain should address these perceptions and expectancies and promote uptake of more adaptive self-management strategies for pain
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