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Objective: Lung cancer is the most common type of cancer around the world, and it represents the main cause of death in the USA. Surgical treatment is the optimal therapeutic strategy for resectable non-small cell lung cancer. The principal factor for long-term survival after complete resection is the anatomic extension of the neoplasm. However, other factors also have adverse effects on operative mortality, and influence long-term outcome. In this paper we propose an algorithmic solution for the estimation of 5-years survival rate in lung cancer patients undertaking pulmonary resection. Materials and methods: We address the issue of survival analysis through decision-making techniques based on fuzzy and soft set theories. We develop an expert system based on clinical and functional data of lung cancer resections in patients with cancer that can be used to predict the survival of patients. Results: The evaluation of surgical risk in patients undertaking pulmonary resection is a primary target for thoracic surgeons. Lung cancer survival is influenced by many factors. The computational performance of our algorithm is critically analyzed by an experimental study. The correct survival classification is achieved with an accuracy of 79.0%. Our novel soft-set based criterion is an effective and precise diagnosis application for the determination of the survival rate. [ABSTRACT FROM AUTHOR]

Background: Intense interest surrounds the recent expansion of US National Institutes of Health (NIH) budgets as part of economic stimulus legislation. However, the relationship between NIH funding and cardiovascular disease research is poorly understood, making the likely impact of this policy change unclear. Methods: The National Library of Medicine's PubMed database was searched for articles published from 1996 to 2006, originating from U.S. institutions, and containing the phrases ''cardiolog,'' ''cardiovascular,'' or ''cardiac,'' in the first author's department. Research methodology, journal of publication, journal impact factor, and receipt of NIH funding were recorded. Differences in means and trends were tested with t-tests and linear regression, respectively, with P≤0.05 for significance. Results: Of 117,643 world cardiovascular articles, 36,684 (31.2%) originated from the U.S., of which 10,293 (28.1%) received NIH funding. The NIH funded 40.1% of U.S. basic science articles, 20.3% of overall clinical trials, 18.1% of randomizedcontrolled, and 12.2% of multicenter clinical trials. NIH-funded and total articles grew significantly (65 articles/year, P<0.001 and 218 articles/year, P<0.001, respectively). The proportion of articles receiving NIH funding was stable, but grew significantly for basic science and clinical trials (0.87%/year, P<0.001 and 0.67%/year, P = 0.029, respectively). NIH-funded articles had greater journal impact factors than non NIH-funded articles (5.76 vs. 3.71, P<0.001). Conclusions: NIH influence on U.S. cardiovascular research expanded in the past decade, during the period of NIH budget doubling. A substantial fraction of research is now directly funded and thus likely sensitive to budget fluctuations, particularly in basic science research. NIH funding predicts greater journal impact. [ABSTRACT FROM AUTHOR]

There is strong epidemiological evidence that poor diet is associated with depression. The reverse has also been shown, namely that eating a healthy diet rich in fruit, vegetables, fish and lean meat, is associated with reduced risk of depression. To date, only one randomised controlled trial (RCT) has been conducted with elevated depression symptoms being an inclusion criterion, with results showing that a diet intervention can reduce clinical levels of depression. No such RCTs have been performed in young adults. Young adults with elevated levels of depression symptoms and who habitually consume a poor diet were randomly allocated to a brief 3-week diet intervention (Diet Group) or a habitual diet control group (Control Group). The primary and secondary outcome measures assessed at baseline and after the intervention included symptoms of depression (Centre for Epidemiological Studies Depression Scale; CESD-R; and Depression Anxiety and Stress Scale– 21 depression subscale; DASS-21-D), current mood (Profile of Mood States), self-efficacy (New General Self-Efficacy Scale) and memory (Hopkins Verbal Learning Test). Diet compliance was measured via self-report questionnaires and spectrophotometry. One-hundred-and-one individuals were enrolled in the study and randomly assigned to the Diet Group or the Control Group. Upon completion of the study, there was complete data for 38 individuals in each group. There was good compliance with the diet intervention recommendations assessed using self-report and spectrophotometry. The Diet group had significantly lower self-reported depression symptoms than the Control Group on the CESD-R (p = 0.007, Cohen’s d = 0.65) and DASS-21 depression subscale (p = 0.002, Cohen’s d = 0.75) controlling for baseline scores on these scales. Reduced DASS-21 depression subscale scores were maintained on follow up phone call 3 months later (p = .009). These results are the first to show that young adults with elevated depression symptoms can engage in and adhere to a diet intervention, and that this can reduce symptoms of depression. The findings provide justification for future research into the duration of these benefits, the impacts of varying diet composition, and their biological basis. [ABSTRACT FROM AUTHOR]

The Model for End-Stage Liver Disease (MELD) score has been successfully used to prioritize patients on the United States liver transplant waiting list since its adoption in 2002. The United Network for Organ Sharing (UNOS)/Organ Procurement Transplantation Network (OPTN) allocation policy has evolved over the years, and notable recent changes include Share 35, inclusion of serum sodium in the MELD score, and a ‘delay and cap’ policy for hepatocellular carcinoma (HCC) patients. We explored the potential of a registrant’s change in 30-day MELD scores (ΔMELD30) to improve allocation both before and after these policy changes. Current MELD and ΔMELD30 were evaluated using cause-specific hazards models for waitlist dropout based on US liver transplant registrants added to the waitlist between 06/30/2003 and 6/30/2013. Two composite scores were constructed and then evaluated on UNOS data spanning the current policy era (01/02/2016 to 09/07/2018). Predictive accuracy was evaluated using the C-index for model discrimination and by comparing observed and predicted waitlist dropout probabilities for model calibration. After the change to MELD-Na, increased dropout associated with ΔMELD30 jumps is no longer evident at MELD scores below 30. However, the adoption of Share 35 has potentially resulted in discrepancies in waitlist dropout for patients with sharp MELD increases at higher MELD scores. Use of the ΔMELD30 to add additional points or serve as a potential tiebreaker for patients with rapid deterioration may extend the benefit of Share 35 to better include those in most critical need. [ABSTRACT FROM AUTHOR]

Introduction: The past decade has witnessed adoption of conservative gynecologic treatments, including minimally invasive surgery (MIS), alongside steady declines in inpatient hysterectomies. It remains unclear what factors have contributed to trends in outpatient benign hysterectomy (BH), as well as whether these trends exacerbate disparities. Materials and methods: Retrospective cohort of 527,964 women ≥18 years old who underwent BH from 2008 to 2014. BH surgical approaches included: open/abdominal hysterectomy (AH), vaginal hysterectomy (VH), laparoscopic hysterectomy (LH), and robotic-assisted hysterectomy (RH). Quarterly frequencies were calculated by care setting and surgical approach. We used multilevel logistic regression (MLR) using the most recent year of data (2014) to examine the influence of patient-, physician-, and hospital-level preoperative factors and surgical approaches on outpatient migration. Results: From 2008–2014, surgical approaches for LH and RH increased, which coincided with decreases in VH and AH. Overall, a 44.2% shift was observed from inpatient to outpatient settings (P<0.0001). Among all outpatient visits MIS increased, particularly for RH (3.6% to 41.07%). We observed increases in the proportion of non-Hispanic Black and Medicaid patients who obtained MIS in 2014 vs. 2008 (P<0.001). Surgical approach (51.8%) and physician outpatient MIS experience (19.9%) had the greatest influence on predicting outpatient BH. Compared with LH, RH was associated with statistically significantly higher likelihood of outpatient BH overall (OR 1.23; 95% CI, 1.16–1.31), as well as in sub-analyses of more complex cases and hospitals that performed ≥1 RH (P<0.05). Conclusion: From 2008–2014, rates of LH and RH significantly increased. A significant shift from inpatient to outpatient setting was observed. These findings suggest that RH may facilitate the shift to outpatient BH, particularly for patients with complexities. The adoption of MIS in outpatient settings may improve access to disadvantaged patient groups. [ABSTRACT FROM AUTHOR]

Background: The incidence of well-differentiated thyroid cancer (WDTC) is increasing rapidly. Many authors feel that this increase is due to over-diagnosis and that one of the contributing factors is the increasing use of various imaging studies. The rate of obesity has also been increasing in the United States. It has been suggested that patients with an increased body mass index (BMI kg/m2) have a higher incidence of WDTC than patients with normal BMI. One might hypothesize that thyroid nodules are more difficult to palpate in obese patients and that as more cancers are detected by imaging the apparent rate of increase in WDTC in obese patients would appear to be greater than in non-obese patients. This study was undertaken to evaluate this hypothesis by determining if there is any difference in the way thyroid cancers are initially detected in obese and non-obese patients. Methods: The medical records of all 519 patients with a postoperative diagnosis of WDTC who underwent thyroidectomy at NYU Langone Medical Center from January 1, 2007 through August 31, 2010 by the three members of NYU Endocrine Surgery Associates were reviewed. Patients were divided into Non-obese (BMI<30 kg/m2) and Obese (BMI≥30 kg/m2) groups. Patients were also divided by the initial method of detection of their tumor into Palpation, Imaging, and Incidental groups. Results: The final study group contained 270 patients, 181(67%) of whom were in the Non-obese Group and 89(33%) were in the Obese Group. In the Non-obese group, 81(45%) of tumors were found by palpation, 72(40%) were found by imaging, and 28(16%) were found incidentally. In the Obese group, 40(45%) were found by palpation, 38(43%) were found by imaging, and 11(12%) were found incidentally. These differences were not statistically significant (p-value 0.769). Conclusion: We show that BMI does not play a role in the method of initial detection in patients with WDTC. This suggests that the prevalence of WDTC detected by imaging is not an artifact caused by an increasingly obese population and that any association of WDTC and obesity is not related to the way in which these tumors are detected. [ABSTRACT FROM AUTHOR]

Lung cancer remains the leading cause of cancer deaths in the US with >150,000 deaths per year. In order to more effectively reduce lung cancer mortality, more sophisticated screening paradigms are needed. Previously, our group demonstrated the use of low-coherence enhanced backscattering (LEBS) spectroscopy to detect and quantify the micro/nano-architectural correlates of colorectal and pancreatic field carcinogenesis. In the lung, the buccal (cheek) mucosa has been suggested as an excellent surrogate site in the “field of injury”. We, therefore, wanted to assess whether LEBS could similarly sense the presence of lung. To this end, we applied a fiber-optic LEBS probe to a dataset of 27 smokers without diagnosed lung cancer (controls) and 46 with lung cancer (cases), which was divided into a training and a blinded validation set (32 and 41 subjects, respectively). LEBS readings of the buccal mucosa were taken from the oral cavity applying gentle contact. The diagnostic LEBS marker was notably altered in patients harboring lung cancer compared to smoking controls. The prediction rule developed on training set data provided excellent diagnostics with 94% sensitivity, 80% specificity, and 95% accuracy. Applying the same threshold to the blinded validation set yielded 79% sensitivity and 83% specificity. These results were not confounded by patient demographics or impacted by cancer type or location. Moreover, the prediction rule was robust across all stages of cancer including stage I. We envision the use of LEBS as the first part of a two-step paradigm shift in lung cancer screening in which patients with high LEBS risk markers are funnelled into more invasive screening for confirmation. [ABSTRACT FROM AUTHOR]

Objective: Recent treatment patterns and cost data associated with HIV in the United States are limited. This study assessed first-line persistence and healthcare costs of HIV-1 in patients by treatment line and CD4 cell count. Methods: MarketScan Commercial Claims and Encounters Database (2007–2011) and Lab Database (2007–2010) were used to construct two HIV-1 cohorts: 1) newly treated HIV-1–infected patients with ≥6 months' continuous enrollment prior to first third-agent drug claim (Newly Treated Cohort) and 2) CD4 cell count test results (CD4 Measurements Cohort). All patients were ≥18 years old and without hepatitis co-infection. The Kaplan-Meier method was used to measure treatment switch rates. Generalized linear models (gamma distribution, log link) were used to compare healthcare costs by treatment line and CD4 cell count controlling for potential confounders. Results: Newly treated patients (n = 8,617) had mean age of 41, 82% were male, and 20% had experienced AIDS-defining events at baseline. Over 20% of newly treated patients switched initial treatment regimen within 2 years. Average unadjusted (and covariate-adjusted) total healthcare cost/year was $33,674 ($28,861) for first-line, $39,191 ($35,805) for second-line, and $39,882 ($40,804) for third-line treatment. Covariate-adjusted costs of care on second- and third-line treatments were significantly more expensive than first-line treatment (24% [p<0.001] and 41% [p = 0.006] higher, respectively). The CD4 Measurements Cohort included 803 CD4 measurements (mean age 49, 76% male, 8% experienced an AIDS-defining event). Costs associated with CD4 measurements <100 cells/µL were 92% higher than those with >350 cells/µL (p<0.001). For higher CD4 cell counts, the majority of expenditures were for antiretrovirals (64% of total for CD4 >350 cells/µL). Conclusions: Despite modern advances in antiretroviral therapy and medical care, direct medical costs of HIV-1–infected patients increase after treatment switch and with lower CD4 counts, consistent with previous costing studies. [ABSTRACT FROM AUTHOR]

Background: The extent to which patients with COPD are receiving indicated treatment with medications to improve lung function and recent trends in the use of these medications is not well documented in the United States. The objective of this study was to examine trends in prescription medications for COPD among adults in the United States from 1999 to 2010. Methods: We performed a trend analysis using data from up to 1426 participants aged ≥20 years with self-reported COPD from six national surveys (National Health and Nutrition Examination Survey 1999–2010). Results: During 2009–2010, the age-adjusted percentage of participants who used any kind of medication was 44.2%. Also during 2009–2010, the most commonly used medications were short-acting agents (36.0%), inhaled corticosteroids (ICS) (18.3%), and LABAs (16.7%). The use of long-acting beta-2 agonists (LABAs) (p for trend <0.001), ICS (p for trend = 0.013) increased significantly over the 12-year period. Furthermore, the use of tiotropium increased rapidly during this period (p for trend <0.001). For the years 2005–2010, the use of LABAs, ICS and tiotropium increased with age. Compared with whites, Mexican Americans were less likely to use short-acting agents, LABAs, ICS, tiotropium, and any kind of COPD medication. Among participants aged 20–79 years with spirometry measurements during 2007–2010, the use of any medication was reported by 19.0% of those with a moderate/severe obstructive impairment and by 72.6% of those with self-reported COPD and any obstructive impairment. Conclusion: The percentages of adults with COPD who reported having various classes of prescription medications that improve airflow limitations changed markedly from 1999–2000 to 2009–2010. However, many adults with COPD did not report having recommended prescription medications. [ABSTRACT FROM AUTHOR]

Background: Previous studies have found that up to 60% of children with neurologic conditions have tried complementary and alternative medicine (CAM). Objective: To assess the use of CAM among patients presenting to neurology clinics at two academic centers in Canada. Methods: A survey instrument was developed to inquire about use of CAM products and therapies, including reasons for use, perceived helpfulness, and concurrent use with conventional medicine, and administered to patients or their parents/guardians at the Stollery Children's Hospital in Edmonton and the Children's Hospital of Eastern Ontario (CHEO) in Ottawa. Results: Overall CAM use at the Stollery was 78%, compared to 48% at CHEO. The most common CAM products used were multi-vitamins (84%), vitamin C (37%), homeopathic remedies (24%), and fish oil/omega 3 s (22%). The most common CAM practices used were massage (47%), chiropractic (37%), faith healing (18%), aromatherapy (16%), homeopathy (16%), and relaxation (16%). Many patients used CAM products at the same time as conventional medicine but just over half (57%) discussed this concurrent use with their physician. Conclusion: CAM use is common in pediatric neurology patients and most respondents felt that it was helpful, with few or no harms associated. However, this use is often undisclosed, increasing possibility of interactions with conventional drugs. We urge clinicians to inquire about CAM use during routine history taking at every patient visit. Parents would clearly like more information about CAM from their specialty clinics; such information would be easier to share if more primary data were available about the safety and effectiveness of commonly used therapies. [ABSTRACT FROM AUTHOR]

Cigarette smoking remains the most preventable cause of death and excess health care costs in the United States, and is a leading cause of death among alcoholics. Long-term tobacco abstinence rates are low, and pharmacotherapeutic options are limited. Repositioning medications approved by the U.S. Food and Drug Administration (FDA) may efficiently provide clinicians with new treatment options. We developed a drug-repositioning paradigm using larval zebrafish locomotion and established predictive clinical validity using FDA-approved smoking cessation therapeutics. We evaluated 39 physician-vetted medications for nicotine-induced locomotor activation blockade. We further evaluated candidate medications for altered ethanol response, as well as in combination with varenicline for nicotine-response attenuation. Six medications specifically inhibited the nicotine response. Among this set, apomorphine and topiramate blocked both nicotine and ethanol responses. Both positively interact with varenicline in the Bliss Independence test, indicating potential synergistic interactions suggesting these are candidates for translation into Phase II clinical trials for smoking cessation. [ABSTRACT FROM AUTHOR]

Background: The ClinicalTrials.gov registry provides information regarding characteristics of past, current, and planned clinical studies to patients, clinicians, and researchers; in addition, registry data are available for bulk download. However, issues related to data structure, nomenclature, and changes in data collection over time present challenges to the aggregate analysis and interpretation of these data in general and to the analysis of trials according to clinical specialty in particular. Improving usability of these data could enhance the utility of ClinicalTrials.gov as a research resource. Methods/Principal Results: The purpose of our project was twofold. First, we sought to extend the usability of ClinicalTrials.gov for research purposes by developing a database for aggregate analysis of ClinicalTrials.gov (AACT) that contains data from the 96,346 clinical trials registered as of September 27, 2010. Second, we developed and validated a methodology for annotating studies by clinical specialty, using a custom taxonomy employing Medical Subject Heading (MeSH) terms applied by an NLM algorithm, as well as MeSH terms and other disease condition terms provided by study sponsors. Clinical specialists reviewed and annotated MeSH and non-MeSH disease condition terms, and an algorithm was created to classify studies into clinical specialties based on both MeSH and non-MeSH annotations. False positives and false negatives were evaluated by comparing algorithmic classification with manual classification for three specialties. Conclusions/Significance: The resulting AACT database features study design attributes parsed into discrete fields, integrated metadata, and an integrated MeSH thesaurus, and is available for download as Oracle extracts (.dmp file and text format). This publicly-accessible dataset will facilitate analysis of studies and permit detailed characterization and analysis of the U.S. clinical trials enterprise as a whole. In addition, the methodology we present for creating specialty datasets may facilitate other efforts to analyze studies by specialty groups. [ABSTRACT FROM AUTHOR]

Background: The $1.1 billion investment in comparative effectiveness research will reshape the evidence-base supporting decisions about treatment effectiveness, safety, and cost. Defining the current prevalence and characteristics of comparative effectiveness (CE) research will enable future assessments of the impact of this program. Methods: We conducted an observational study of clinical trials addressing priority research topics defined by the Institute of Medicine and conducted in the US between 2007 and 2010. Trials were identified in ClinicalTrials.gov. Main outcome measures were the prevalence of comparative effectiveness research, nature of comparators selected, funding sources, and impact of these factors on results. Results: 231 (22.3%; 95% CI 19.8%-24.9%) studies were CE studies and 804 (77.7%; 95% CI, 75.1%-80.2%) were non-CE studies, with 379 (36.6%; 95% CI, 33.7%-39.6%) employing a placebo control and 425 (41.1%; 95% CI, 38.1%-44.1%) no control. The most common treatments examined in CE studies were drug interventions (37.2%), behavioral interventions (28.6%), and procedures (15.6%). Study findings were favorable for the experimental treatment in 34.8% of CE studies and greater than twice as many (78.6%) non-CE studies (P<0.001). CE studies were more likely to receive government funding (P = 0.003) and less likely to receive industry funding (P = 0.01), with 71.8% of CE studies primarily funded by a noncommercial source. The types of interventions studied differed based on funding source, with 95.4% of industry trials studying a drug or device. In addition, industry-funded CE studies were associated with the fewest pediatric subjects (P<0.001), the largest anticipated sample size (P<0.001), and the shortest study duration (P<0.001). Conclusions: In this sample of studies examining high priority areas for CE research, less than a quarter are CE studies and the majority is supported by government and nonprofits. The low prevalence of CE research exists across CE studies with a broad array of interventions and characteristics. [ABSTRACT FROM AUTHOR]

Background: Treatment strategies for the highly invasive brain tumor, glioblastoma multiforme, require that cells which have invaded into the surrounding brain be specifically targeted. The inherent tumor-tropism of neural stem cells (NSCs) to primary and invasive tumor foci can be exploited to deliver therapeutics to invasive brain tumor cells in humans. Use of the strategy of converting prodrug to drug via therapeutic transgenes delivered by immortalized therapeutic NSC lines have shown efficacy in animal models. Thus therapeutic NSCs are being proposed for use in human brain tumor clinical trials. In the context of NSC-based therapies, MRI can be used both to non-invasively follow dynamic spatio-temporal patterns of the NSC tumor targeting allowing for the optimization of treatment strategies and to assess efficacy of the therapy. Ironlabeling of cells allows their presence to be visualized and tracked by MRI. Thus we aimed to iron-label therapeutic NSCs without affecting their cellular physiology using a method likely to gain United States Federal Drug Administration (FDA) approval. Methodology: For human use, the characteristics of therapeutic Neural Stem Cells must be clearly defined with any pertubation to the cell including iron labeling requiring reanalysis of cellular physiology. Here, we studied the effect of ironloading of the therapeutic NSCs, with ferumoxide-protamine sulfate complex (FE-Pro) on viability, proliferation, migratory properties and transgene expression, when compared to non-labeled cells. FE-Pro labeled NSCs were imaged by MRI at tumor sites, after intracranial administration into the hemisphere contralateral to the tumor, in an orthotopic human glioma xenograft mouse model. Conclusion: FE-Pro labeled NSCs retain their proliferative status, tumor tropism, and maintain stem cell character, while allowing in vivo cellular MRI tracking at 7 Tesla, to monitor their real-time migration and distribution at brain tumor sites. Of significance, this work directly supports the use of FE-Pro-labeled NSCs for real-time tracking in the clinical trial under development: ''A Pilot Feasibility Study of Oral 5-Fluorocytosine and Genetically modified Neural Stem Cells Expressing Escherichia coli Cytosine Deaminase for Treatment of Recurrent High-Grade Gliomas''. [ABSTRACT FROM AUTHOR]