A survey of individual preference for colorectal cancer screening technique

BACKGROUND: Due to the low participation in colorectal cancer screening, public preference for colorectal cancer screening modality was determined. METHODS: A cross-sectional survey was performed of healthy ambulatory adults in a pediatrics primary care office and neighboring church. Overall preference was ranked for each of four colorectal cancer screening modalities: Faecal Occult Blood, Fiberoptic Sigmoidoscopy, Barium Enema and Colonoscopy. Four additional domains of preference also were ranked: suspected discomfort, embarrassment, inconvenience and danger of each exam. RESULTS: 80 surveys were analyzed, 57 of which were received from participants who had experienced none of the screening tests. Fecal Occult Blood Testing is significantly preferred over each other screening modality in overall preference and every domain of preference, among all subjects and those who had experienced none of the tests. CONCLUSIONS: Efforts to increase public participation in colorectal cancer screening may be more effective if undertaken in the context of public perceptions of screening choices

Application of adaptive design and decision making to a phase II trial of a phosphodiesterase inhibitor for the treatment of intermittent claudication

Background: Claudication secondary to peripheral artery disease (PAD) is associated with substantial functional impairment. Phosphodiesterase (PDE) inhibitors have been shown to increase walking performance in these patients. K-134 is a selective PDE 3 inhibitor being developed as a potential treatment for claudication. The use of K-134, as with other PDE 3 inhibitors, in patients with PAD raises important safety and tolerability concerns, including the induction of cardiac ischemia, tachycardia, and hypotension. We describe the design, oversight, and implementation of an adaptive, phase II, dose-finding trial evaluating K-134 for the treatment of stable, intermittent claudication. Methods: The study design was a double-blind, multi-dose (25 mg, 50 mg, and 100 mg of K-134), randomized trial with both placebo and active comparator arms conducted in the United States and Russia. The primary objective of the study was to compare the highest tolerable dose of K-134 versus placebo using peak walking time after 26 weeks of therapy as the primary outcome. Study visits with intensive safety assessments were included early in the study period to provide data for adaptive decision making. The trial used an adaptive, dose-finding strategy to efficiently identify the highest dose(s) most likely to be safe and well tolerated, based on the side effect profiles observed within the trial, so that less promising doses could be abandoned. Protocol specified criteria for safety and tolerability endpoints were used and modeled prior to the adaptive decision making. The maximum target sample size was 85 subjects in each of the retained treatment arms. Results: When 199 subjects had been randomized and 28-day data were available from 143, the Data Monitoring Committee (DMC) recommended termination of the lowest dose (25 mg) treatment arm. Safety evaluations performed during 14- and 28-day visits which included in-clinic dosing and assessments at peak drug concentrations provided core data for the DMC review. At the time of review, no subject in any of the five treatment arms (placebo, three K-134-containing arms, and cilostazol) had met pre-specified definitions for resting tachycardia or ischemic changes on exercise ECG. If, instead of dropping the 25-mg K-134 treatment arm, all arms had been continued to full enrollment, then approximately 43 additional research subjects would have been required to complete the trial. Conclusions: In this phase II, dose-finding trial of K-134 in the treatment of stable intermittent claudication, no concerning safety signals were seen at interim analysis, allowing the discontinuation of the lowest-dose-containing arm and the retention of the two highest-dose-containing arms. The adaptive design facilitated safe and efficient evaluation of K-134 in this high-risk cardiovascular population

Educating Cancer Prevention Researchers in Emerging Biobehavioral Models: Lessons Learned

To increase the adoption of transdisciplinary research methods among future cancer prevention investigators, faculty members from The University of Texas MD Anderson Cancer Center developed a graduate-level course in biobehavioral methods in cancer prevention research. Two instructors paired by topic and area of expertise offered an hour-long lecture-based seminar every week for 15 weeks during the spring semester of 2010. Students and presenters both evaluated the overall course content and delivery method, as well as each session. A total of 11 students and 22 presenters participated in the course. In each class session, one presenter was from a behavioral science background,and the other was from a biological sciences background. Both presenters and students expressed overall satisfaction with the content and format of the course. The presentation of topics from a transdisciplinary perspective and interaction with presenters from both biological and behavioral sciences are valuable and can help junior researchers prepare to meet the emerging challenges in cancer prevention research

Clinical and surgical data of affected members of a classic CFEOM 1 family

BACKGROUND: Congenital fibiosis of the extraocular muscles (CFEOM1) refers to a group of congenital eye movement disorders that are characterized by non-progressive restrictive ophthalmoplegia. We present clinical and surgical data on affected members of a classic CFEOM1 family. METHODS: Ten members of a fifteen-member, three-generation Italian family affected by classic CFEOM participated in this study. Each affected family member underwent ophthalmologic (corrected visual acuity, pupillary function, anterior segment and fundus examination), orthoptic (cover test, cover-uncover test, prism alternate cover test), and preoperative examinations. Eight of the ten affected members had surgery and underwent postoperative examinations. Surgical procedures are listed. RESULTS: All affected members were born with varying degrees of bilateral ptosis and ophthalmoplegia with both eyes fixed in a hypotropic position (classic CFEOM). The affected members clinical data prior to surgery, surgery procedures and postoperative outcomes are presented. On 14 operated eyes to correct ptosis there was an improvement in 12 eyes. In addition, the head position improved in all patients. CONCLUSIONS: Surgery is effective at improving ptosis in the majority of patients with classic CFEOM. However, the surgical approach should be individualized to each patient, as inherited CFEOM exhibits variable expressivity and the clinical features may differ markedly between affected individuals, even within the same family

Classic Kaposi's sarcoma in morocco: clinico -epidemiological study at the national institute of oncology

<p>Abstract</p> <p>Background</p> <p>Classic Kaposi's sarcoma (CKS) is a rare disease likely associated with human herpes virus 8 (HHV-8) infection, and occurs predominantly in Jewish, Mediterranean and middle eastern men .There is a dearth of data in Moroccan patients with CKS regarding epidemiology, clinical characteristics and outcomes. This report examines a cohort of patients with CKS evaluated at the national institute of oncology over 11-year period.</p> <p>Methods</p> <p>A retrospective analysis of patients referred to the national institute of oncology with classical Kaposi sarcoma, between January 1998 and February 2008, was performed. Reviewed information included demographics, clinical and pathological staging, death or last follow-up.</p> <p>Results</p> <p>During the study period, 56 patients with a diagnosis of CKS have been referred to our hospital. There were 11(19,7%) females and 45 (80,3%) males (male-to-female ratio: 4:1). Mean age at diagnosis was 61,7 ± 15 (range: 15- 86 years). Nodules and/or plaques were the most frequent type of lesion. The most common location was the lower limbs, particularly the distal lower extremity (90%). In addition to skin involvement, visceral spread was evident in 9 cases. The most common visceral involvement sites were lymph nodes (44%), lung (22%), and gastrointestinal tract (22%). Associated lymphoedema was seen in 24 (42%) of the patients. There were 18 stage I patients (32,14%), 8: stage II (14,28%), 21 stage III(37,5%) and 9 stage IV (16,07%). A second primary malignancy was diagnosed in 6 cases (10,7%), none of the reticuloendothelial system.</p> <p>With a median follow-up of 45 months, 38 (67,8) patients are alive, of whom 25 (65,78%) patients with stable disease, five with progressive disease currently under systemic chemotherapy and 8(21,05%) are alive and free of disease, over a mean interval of 5 years.</p> <p>Conclusion</p> <p>This is the largest reported series in our context. In Morocco, CKS exhibits some special characteristics including a disseminated skin disease at diagnosis especially in men, a more common visceral or lymph node involvement and a less frequent association with second malignancies.</p

Investigating the complex genetic architecture of ankle-brachial index, a measure of peripheral arterial disease, in non-Hispanic whites

<p>Abstract</p> <p>Background</p> <p>Atherosclerotic peripheral arterial disease (PAD) affects 8–10 million people in the United States and is associated with a marked impairment in quality of life and an increased risk of cardiovascular events. Noninvasive assessment of PAD is performed by measuring the ankle-brachial index (ABI). Complex traits, such as ABI, are influenced by a large array of genetic and environmental factors and their interactions. We attempted to characterize the genetic architecture of ABI by examining the main and interactive effects of individual single nucleotide polymorphisms (SNPs) and conventional risk factors.</p> <p>Methods</p> <p>We applied linear regression analysis to investigate the association of 435 SNPs in 112 positional and biological candidate genes with ABI and related physiological and biochemical traits in 1046 non-Hispanic white, hypertensive participants from the Genetic Epidemiology Network of Arteriopathy (GENOA) study. The main effects of each SNP, as well as SNP-covariate and SNP-SNP interactions, were assessed to investigate how they contribute to the inter-individual variation in ABI. Multivariable linear regression models were then used to assess the joint contributions of the top SNP associations and interactions to ABI after adjustment for covariates. We reduced the chance of false positives by 1) correcting for multiple testing using the false discovery rate, 2) internal replication, and 3) four-fold cross-validation.</p> <p>Results</p> <p>When the results from these three procedures were combined, only two SNP main effects in <it>NOS3</it>, three SNP-covariate interactions (<it>ADRB2 </it>Gly 16 – lipoprotein(a) and <it>SLC4A5 </it>– diabetes interactions), and 25 SNP-SNP interactions (involving SNPs from 29 different genes) were significant, replicated, and cross-validated. Combining the top SNPs, risk factors, and their interactions into a model explained nearly 18% of variation in ABI in the sample. SNPs in six genes (<it>ADD2, ATP6V1B1, PRKAR2B, SLC17A2, SLC22A3, and TGFB3</it>) were also influencing triglycerides, C-reactive protein, homocysteine, and lipoprotein(a) levels.</p> <p>Conclusion</p> <p>We found that candidate gene SNP main effects, SNP-covariate and SNP-SNP interactions contribute to the inter-individual variation in ABI, a marker of PAD. Our findings underscore the importance of conducting systematic investigations that consider context-dependent frameworks for developing a deeper understanding of the multidimensional genetic and environmental factors that contribute to complex diseases.</p

Little evidence for an epidemic of myopia in Australian primary school children over the last 30 years

BACKGROUND: Recently reported prevalences of myopia in primary school children vary greatly in different regions of the world. This study aimed to estimate the prevalence of refractive errors in an unselected urban population of young primary school children in eastern Sydney, Australia, between 1998 and 2004, for comparison with our previously published data gathered using the same protocols and other Australian studies over the last 30 years. METHODS: Right eye refractive data from non-cycloplegic retinoscopy was analysed for 1,936 children aged 4 to 12 years who underwent a full eye examination whilst on a vision science excursion to the Vision Education Centre Clinic at the University of New South Wales. Myopia was defined as spherical equivalents equal to or less than -0.50 D, and hyperopia as spherical equivalents greater than +0.50 D. RESULTS: The mean spherical equivalent decreased significantly (p < 0.0001) with age from +0.73 ± 0.1D (SE) at age 4 to +0.21 ± 0.11D at age 12 years. The proportion of children across all ages with myopia of -0.50D or more was 8.4%, ranging from 2.3% of 4 year olds to 14.7% of 12 year olds. Hyperopia greater than +0.50D was present in 38.4%. A 3-way ANOVA for cohort, age and gender of both the current and our previous data showed a significant main effect for age (p < 0.0001) but not for cohort (p = 0.134) or gender (p = 0.61). CONCLUSIONS: Comparison of our new data with our early 1990s data and that from studies of over 8,000 Australian non-clinical rural and urban children in the 1970's and 1980's provided no evidence for the rapidly increasing prevalence of myopia described elsewhere in the world. In fact, the prevalence of myopia in Australian children continues to be significantly lower than that reported in Asia and North America despite changing demographics. This raises the issue of whether these results are a reflection of Australia's stable educational system and lifestyle over the last 30 years

Vitamin D exposure and Risk of Breast Cancer: a meta-analysis

The relationship between vitamin D and breast cancer is still controversial. The present meta-analysis examines the effects of the 25(OH)D, 1,25(OH)2D and vitamin D intake on breast cancer risk. For this purpose, a PubMed, Scopus and Web of Science-databases search was conducted including all papers published with the keywords "breast cancer" and "vitamin D" with at least one reported relative risk (RR) or odds ratio (OR). In total sixty eight studies published between 1998 and 2018 were analyzed. Information about type of study, hormonal receptors and menopausal status was retrieved. Pooled OR or RR were estimated by weighting individual OR/RR by the inverse of their variance Our study showed a protective effect between 25 (OH) D and breast cancer in both cohort studies (RR?=?0.85, 95%CI:0.74-0.98) and case-control studies (OR?=?0.65, 95%CI: 0.56-0.76). However, analyzing by menopausal status, the protective vitamin D - breast cancer association persisted only in the premenopausal group (OR?=?0.67, 95%CI: 0.49-0.92) when restricting the analysis to nested case-control studies. No significant association was found for vitamin D intake or 1,25(OH)2D. CONCLUSION: This systematic review suggests a protective relationship between circulating vitamin D (measured as 25(OH) D) and breast cancer development in premenopausal women

Severe traumatic injury during long duration spaceflight: Light years beyond ATLS

Traumatic injury strikes unexpectedly among the healthiest members of the human population, and has been an inevitable companion of exploration throughout history. In space flight beyond the Earth's orbit, NASA considers trauma to be the highest level of concern regarding the probable incidence versus impact on mission and health. Because of limited resources, medical care will have to focus on the conditions most likely to occur, as well as those with the most significant impact on the crew and mission. Although the relative risk of disabling injuries is significantly higher than traumatic deaths on earth, either issue would have catastrophic implications during space flight. As a result this review focuses on serious life-threatening injuries during space flight as determined by a NASA consensus conference attended by experts in all aspects of injury and space flight