Radiological staging in breast cancer: which asymptomatic patients to image and how.

BACKGROUND: Approximately 4% of patients diagnosed with early breast cancer have occult metastases at presentation. Current national and international guidelines lack consensus on whom to image and how. METHODS: We assessed practice in baseline radiological staging against local guidelines for asymptomatic newly diagnosed breast cancer patients presenting to the Cambridge Breast Unit over a 9-year period. RESULTS: A total of 2612 patients were eligible for analysis; 91.7% were appropriately investigated. However in the subset of lymph node negative stage II patients, only 269 out of 354 (76.0%) investigations were appropriate. No patients with stage 0 or I disease had metastases; only two patients (0.3%) with stage II and or =4 positive lymph nodes), III and IV disease, respectively. CONCLUSION: These results prompted us to propose new local guidelines for staging asymptomatic breast cancer patients: only clinical stage III or IV patients require baseline investigation. The high specificity and convenience of computed tomography (chest, abdomen and pelvis) led us to recommend this as the investigation of choice in breast cancer patients requiring radiological staging

Public Availability of Published Research Data in High-Impact Journals

BACKGROUND: There is increasing interest to make primary data from published research publicly available. We aimed to assess the current status of making research data available in highly-cited journals across the scientific literature. METHODS AND RESULTS: We reviewed the first 10 original research papers of 2009 published in the 50 original research journals with the highest impact factor. For each journal we documented the policies related to public availability and sharing of data. Of the 50 journals, 44 (88%) had a statement in their instructions to authors related to public availability and sharing of data. However, there was wide variation in journal requirements, ranging from requiring the sharing of all primary data related to the research to just including a statement in the published manuscript that data can be available on request. Of the 500 assessed papers, 149 (30%) were not subject to any data availability policy. Of the remaining 351 papers that were covered by some data availability policy, 208 papers (59%) did not fully adhere to the data availability instructions of the journals they were published in, most commonly (73%) by not publicly depositing microarray data. The other 143 papers that adhered to the data availability instructions did so by publicly depositing only the specific data type as required, making a statement of willingness to share, or actually sharing all the primary data. Overall, only 47 papers (9%) deposited full primary raw data online. None of the 149 papers not subject to data availability policies made their full primary data publicly available. CONCLUSION: A substantial proportion of original research papers published in high-impact journals are either not subject to any data availability policies, or do not adhere to the data availability instructions in their respective journals. This empiric evaluation highlights opportunities for improvement

Why we need easy access to all data from all clinical trials and how to accomplish it

International calls for registering all trials involving humans and for sharing the results, and sometimes also the raw data and the trial protocols, have increased in recent years. Such calls have come, for example, from the Organization for Economic Cooperation and Development (OECD), the World Health Organization (WHO), the US National Institutes of Heath, the US Congress, the European Commission, the European ombudsman, journal editors, The Cochrane Collaboration, and several funders, for example the UK Medical Research Council, the Wellcome Trust, the Bill and Melinda Gates Foundation and the Hewlett Foundation

Checkerboard Patterns, Interspecific Competition, and Extinction: Lessons from Distribution Patterns of Tarsiers (Tarsius) and Slow Lorises (Nycticebus) in Insular Southeast Asia

Tarsiers (Tarsius) and slow lorises (Nycticebus) are the only extant nocturnal primates occurring in Southeast Asia. Harcourt (1999) hypothesized that in insular Southeast Asia, slow lorises and tarsiers showed a checkerboard distribution on 12 small (<12,000 km2) islands, i.e., only one or the other occurs, and attributed this to extreme levels of competition between these 2 largely faunivorous primates. Further, he predicted slow lorises were able to persist on smaller islands than tarsiers. We re-evaluated these findings using an expanded dataset including 49 islands where tarsiers or slow lorises occur. Tarsiers and slow lorises live on islands of similar size (median size of ca. 300–900 km2), and both taxa inhabit an equal proportion of small, medium, and large islands. On small islands within their area of sympatry tarsiers occur on 1 island, slow lorises on 8, both genera on 3, and we can assume they have become extinct from 11 small islands since the Last Glacial Maximum. Sizes of islands where tarsiers or slow lorises have become extinct do not differ from islands where they are still extant. We show that slow lorises occur on more islands in insular Southeast Asia than perhaps previously assumed, but these islands are not smaller on average than islands where tarsiers occur. A checkerboard distribution between these taxa is not evident. More studies are needed at the macroecological level to assess the importance of biogeographic history in explaining their present-day distribution patterns

Differential response effects of data collection mode in a cancer screening study of unmarried women ages 40–75 years: A randomized trial

<p>Abstract</p> <p>Background</p> <p>Little is known about the impact of data collection method on self-reported cancer screening behaviours, particularly among hard-to-reach populations. The purpose of this study is to examine the effects of data collection mode on response to indicators of cancer screenings by unmarried middle-aged and older women.</p> <p>Methods</p> <p>Three survey methods were evaluated for collecting data about mammography and Papanicolaou (hereafter, Pap) testing among heterosexual and sexual minority (e.g., lesbian and bisexual) women. Women ages 40–75 were recruited from June 2003 – June 2005 in Rhode Island. They were randomly assigned to receive: Self-Administered Mailed Questionnaire [SAMQ; N = 202], Computer-Assisted Telephone Interview [CATI; N = 200], or Computer-Assisted Self-Interview [CASI; N = 197]. Logistic regression models were computed to assess survey mode differences for 13 self-reported items related to cancer screenings, adjusting for age, education, income, race, marital status, partner gender, and recruitment source.</p> <p>Results</p> <p>Compared to women assigned to CATI, women assigned to SAMQ were less likely to report two or more years between most recent mammograms (CATI = 23.2% vs. SAMQ = 17.7%; AOR = 0.5, 95% CI = 0.3 – 0.8) and women assigned to CASI were slightly less likely to report being overdue for mammography (CATI = 16.5% vs. CASI = 11.8%; AOR = 0.5, 95% CI = 0.3 – 1.0) and Pap testing (CATI = 14.9% vs. CASI = 10.0%; AOR = 0.5, 95% CI = 0.2 – 1.0). There were no other consistent mode effects.</p> <p>Conclusion</p> <p>Among participants in this sample, mode of data collection had little effect on the reporting of mammography and Pap testing behaviours. Other measures such as efficiency and cost-effectiveness of the mode should also be considered when determining the most appropriate form of data collection for use in monitoring indicators of cancer detection and control.</p

New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk.

Levels of circulating glucose are tightly regulated. To identify new loci influencing glycemic traits, we performed meta-analyses of 21 genome-wide association studies informative for fasting glucose, fasting insulin and indices of beta-cell function (HOMA-B) and insulin resistance (HOMA-IR) in up to 46,186 nondiabetic participants. Follow-up of 25 loci in up to 76,558 additional subjects identified 16 loci associated with fasting glucose and HOMA-B and two loci associated with fasting insulin and HOMA-IR. These include nine loci newly associated with fasting glucose (in or near ADCY5, MADD, ADRA2A, CRY2, FADS1, GLIS3, SLC2A2, PROX1 and C2CD4B) and one influencing fasting insulin and HOMA-IR (near IGF1). We also demonstrated association of ADCY5, PROX1, GCK, GCKR and DGKB-TMEM195 with type 2 diabetes. Within these loci, likely biological candidate genes influence signal transduction, cell proliferation, development, glucose-sensing and circadian regulation. Our results demonstrate that genetic studies of glycemic traits can identify type 2 diabetes risk loci, as well as loci containing gene variants that are associated with a modest elevation in glucose levels but are not associated with overt diabetes

Intimal Hyperplasia in Balloon Dilated Coronary Arteries is Reduced by Local Delivery of the NO Donor, SIN-1 Via a cGMP-Dependent Pathway

<p>Abstract</p> <p>Background</p> <p>To elucidate the mechanism by which local delivery of 3-morpholino-sydnonimine (SIN-1) affects intimal hyperplasia after percutaneous transluminal coronary angioplasty (PTCA).</p> <p>Methods</p> <p>Porcine coronary arteries were treated with PTCA and immediately afterwards locally treated for 5 minutes, with a selective cytosolic guanylate cyclase inhibitor, 1 H-(1,2,4)oxadiazole(4,3-alpha)quinoxaline-1-one (ODQ) + SIN-1 or only SIN-1 using a drug delivery-balloon. Arteries were angiographically depicted, morphologically evaluated and analyzed after one and eight weeks for actin, myosin and intermediate filaments (IF) and nitric oxide synthase (NOS) contents.</p> <p>Results</p> <p>Luminal diameter after PCI in arteries treated with SIN-1 alone and corrected for age-growth was significantly larger as compared to ODQ + SIN-1 or to controls (p < 0.01). IF/actin ratio after one week in SIN-1 treated segments was not different compared to untreated segments, but was significantly reduced compared to ODQ + SIN-1 treated vessels (p < 0.05). Expression of endothelial NADPH diaphorase activity was significantly lower in untreated segments and in SIN-1 treated segments compared to controls and SIN-1 + ODQ treated arteries (p < 0.01). Restenosis index (p < 0.01) and intimal hyperplasia (p < 0.01) were significantly reduced while the residual lumen was increased (p < 0.01) in SIN-1 segments compared to controls and ODQ + SIN-1 treated vessels.</p> <p>Conclusions</p> <p>After PTCA local delivery of high concentrations of the NO donor SIN-1 for 5 minutes inhibited injury induced neointimal hyperplasia. This favorable effect was abolished by inhibition of guanylyl cyclase indicating mediation of a cyclic guanosine 3',5'-monophosphate (cGMP)-dependent pathway. The momentary events at the time of injury play crucial role in the ensuring development of intimal hyperplasia.</p

Volunteer Bias in Recruitment, Retention, and Blood Sample Donation in a Randomised Controlled Trial Involving Mothers and Their Children at Six Months and Two Years: A Longitudinal Analysis

BACKGROUND: The vulnerability of clinical trials to volunteer bias is under-reported. Volunteer bias is systematic error due to differences between those who choose to participate in studies and those who do not. METHODS AND RESULTS: This paper extends the applications of the concept of volunteer bias by using data from a trial of probiotic supplementation for childhood atopy in healthy dyads to explore 1) differences between a) trial participants and aggregated data from publicly available databases b) participants and non-participants as the trial progressed 2) impact on trial findings of weighting data according to deprivation (Townsend) fifths in the sample and target populations. 1) a) Recruits (n = 454) were less deprived than the target population, matched for area of residence and delivery dates (n = 6,893) (mean [SD] deprivation scores 0.09[4.21] and 0.79[4.08], t = 3.44, df = 511, p<0.001). b) i) As the trial progressed, representation of the most deprived decreased. These participants and smokers were less likely to be retained at 6 months (n = 430[95%]) (OR 0.29,0.13-0.67 and 0.20,0.09-0.46), and 2 years (n = 380[84%]) (aOR 0.68,0.50-0.93 and 0.55,0.28-1.09), and consent to infant blood sample donation (n = 220[48%]) (aOR 0.72,0.57-0.92 and 0.43,0.22-0.83). ii) Mothers interested in probiotics or research or reporting infants' adverse events or rashes were more likely to attend research clinics and consent to skin-prick testing. Mothers participating to help children were more likely to consent to infant blood sample donation. 2) In one trial outcome, atopic eczema, the intervention had a positive effect only in the over-represented, least deprived group. Here, data weighting attenuated risk reduction from 6.9%(0.9-13.1%) to 4.6%(-1.4-+10.5%), and OR from 0.40(0.18-0.91) to 0.56(0.26-1.21). Other findings were unchanged. CONCLUSIONS: Potential for volunteer bias intensified during the trial, due to non-participation of the most deprived and smokers. However, these were not the only predictors of non-participation. Data weighting quantified volunteer bias and modified one important trial outcome. TRIAL REGISTRATION: This randomised, double blind, parallel group, placebo controlled trial is registered with the International Standard Randomised Controlled Trials Register, Number (ISRCTN) 26287422. Registered title: Probiotics in the prevention of atopy in infants and children

Assessing hospitals' clinical risk management: Development of a monitoring instrument

<p>Abstract</p> <p>Background</p> <p>Clinical risk management (CRM) plays a crucial role in enabling hospitals to identify, contain, and manage risks related to patient safety. So far, no instruments are available to measure and monitor the level of implementation of CRM. Therefore, our objective was to develop an instrument for assessing CRM in hospitals.</p> <p>Methods</p> <p>The instrument was developed based on a literature review, which identified key elements of CRM. These elements were then discussed with a panel of patient safety experts. A theoretical model was used to describe the level to which CRM elements have been implemented within the organization. Interviews with CRM practitioners and a pilot evaluation were conducted to revise the instrument. The first nationwide application of the instrument (138 participating Swiss hospitals) was complemented by in-depth interviews with 25 CRM practitioners in selected hospitals, for validation purposes.</p> <p>Results</p> <p>The monitoring instrument consists of 28 main questions organized in three sections: 1) Implementation and organizational integration of CRM, 2) Strategic objectives and operational implementation of CRM at hospital level, and 3) Overview of CRM in different services. The instrument is available in four languages (English, German, French, and Italian). It allows hospitals to gather comprehensive and systematic data on their CRM practice and to identify areas for further improvement.</p> <p>Conclusions</p> <p>We have developed an instrument for assessing development stages of CRM in hospitals that should be feasible for a continuous monitoring of developments in this important area of patient safety.</p