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Background Little is known about publication agreements between industry and academic investigators in trial protocols and the consistency of these agreements with corresponding statements in publications. We aimed to investigate (i) the existence and types of publication agreements in trial protocols, (ii) the completeness and consistency of the reporting of these agreements in subsequent publications, and (iii) the frequency of co-authorship by industry employees. Methods and Findings We used a retrospective cohort of randomized clinical trials (RCTs) based on archived protocols approved by six research ethics committees between 13 January 2000 and 25 November 2003. Only RCTs with industry involvement were eligible. We investigated the documentation of publication agreements in RCT protocols and statements in corresponding journal publications. Of 647 eligible RCT protocols, 456 (70.5%) mentioned an agreement regarding publication of results. Of these 456, 393 (86.2%) documented an industry partner's right to disapprove or at least review proposed manuscripts; 39 (8.6%) agreements were without constraints of publication. The remaining 24 (5.3%) protocols referred to separate agreement documents not accessible to us. Of those 432 protocols with an accessible publication agreement, 268 (62.0%) trials were published. Most agreements documented in the protocol were not reported in the subsequent publication (197/268 [73.5%]). Of 71 agreements reported in publications, 52 (73.2%) were concordant with those documented in the protocol. In 14 of 37 (37.8%) publications in which statements suggested unrestricted publication rights, at least one co-author was an industry employee. In 25 protocol-publication pairs, author statements in publications suggested no constraints, but 18 corresponding protocols documented restricting agreements. Conclusions Publication agreements constraining academic authors' independence are common. Journal articles seldom report on publication agreements, and, if they do, statements can be discrepant with the trial protocol., Author(s): Benjamin Kasenda 1, Erik von Elm 2,*, John J. You 3,4, Anette Blümle 5, Yuki Tomonaga 6, Ramon Saccilotto 1, Alain Amstutz 1, Theresa Bengough 2,7, Joerg J. Meerpohl [...]

Background: Optimal end-of-life care requires identifying patients that are near the end of life. The extent to which attending physicians and trainee physicians agree on the prognoses of their patients is unknown. We investigated agreement between attending and trainee physician on the surprise question: "Would you be surprised if this patient died in the next 12 months?", a question intended to assess mortality risk and unmet palliative care needs. Methods: This was a multicentre prospective cohort study of general internal medicine patients at 7 tertiary academic hospitals in Ontario, Canada. General internal medicine attending and senior trainee physician dyads were asked the surprise question for each of the patients for whom they were responsible. Surprise question response agreement was quantified by Cohen's kappa using Bayesian multilevel modeling to account for clustering by physician dyad. Mortality was recorded at 12 months. Results: Surprise question responses encompassed 546 patients from 30 attending-trainee physician dyads on academic general internal medicine teams at 7 tertiary academic hospitals in Ontario, Canada. Patients had median age 75 years (IQR 60–85), 260 (48%) were female, and 138 (25%) were dependent for some or all activities of daily living. Trainee and attending physician responses agreed in 406 (75%) patients with adjusted Cohen's kappa of 0.54 (95% credible interval 0.41 to 0.66). Vital status was confirmed for 417 (76%) patients of whom 160 (38% of 417) had died. Using a response of "No" to predict 12-month mortality had positive likelihood ratios of 1.84 (95% CrI 1.55 to 2.22, trainee physicians) and 1.51 (95% CrI 1.30 to 1.72, attending physicians), and negative likelihood ratios of 0.31 (95% CrI 0.17 to 0.48, trainee physicians) and 0.25 (95% CrI 0.10 to 0.46, attending physicians). Conclusion: Trainee and attending physician responses to the surprise question agreed in 54% of cases after correcting for chance agreement. Physicians had similar discriminative accuracy; both groups had better accuracy predicting which patients would survive as opposed to which patients would die. Different opinions of a patient's prognosis may contribute to confusion for patients and missed opportunities for engagement with palliative care services. [ABSTRACT FROM AUTHOR]

Background: The association between fetal exposure to major radiodiagnostic testing in pregnancy--computed tomography (CT) and radionuclide imaging-and the risk of childhood cancer is not established. Methods and Findings: We completed a population-based study of 1.8 million maternal-child pairs in the province of Ontario, from 1991 to 2008. We used Ontario's universal health care-linked administrative databases to identify all term obstetrical deliveries and newborn records, inpatient and outpatient major radiodiagnostic services, as well as all children with a malignancy after birth. There were 5,590 mothers exposed to major radiodiagnostic testing in pregnancy (3.0 per 1,000) and 1,829,927 mothers not exposed. The rate of radiodiagnostic testing increased from 1.1 to 6.3 per 1,000 pregnancies over the study period; about 73% of tests were CT scans. After a median duration of follow-up of 8.9 years, four childhood cancers arose in the exposed group (1.13 per 10,000 person-years) and 2,539 cancers in the unexposed group (1.56 per 10,000 person-years), a crude hazard ratio of 0.69 (95% confidence interval 0.26-1.82). After adjusting for maternal age, income quintile, urban status, and maternal cancer, as well as infant sex, chromosomal or congenital anomalies, and major radiodiagnostic test exposure after birth, the risk was essentially unchanged (hazard ratio 0.68, 95% confidence interval 0.25-1.80). Conclusions: Although major radiodiagnostic testing is now performed in about 1 in 160 pregnancies in Ontario, the absolute annual risk of childhood malignancy following exposure in utero remains about 1 in 10,000. Since the upper confidence limit of the relative risk of malignancy may be as high as 1.8 times that of an unexposed pregnancy, we cannot exclude the possibility that fetal exposure to CT or radionuclide imaging is carcinogenic. Please see later in the article for the Editors' Summary., Introduction Cancer remains the second leading cause of hospitalization and death among children aged 14 y and younger in industrialized nations [1-3]. Fewer than 10% of childhood cancers are attributable [...]

Background: Patients with serious illness, and their families, state that better communication and decision-making with healthcare providers is a high priority to improve the quality of end-of-life care. Numerous communication tools to assist patients, family members, and clinicians in end-of-life decision-making have been published, but their effectiveness remains unclear. Objectives: To determine, amongst adults in ambulatory care settings, the effect of structured communication tools for end-of-life decision-making on completion of advance care planning. Methods: We searched for relevant randomized controlled trials (RCTs) or non-randomized intervention studies in MEDLINE, EMBASE, CINAHL, ERIC, and the Cochrane Database of Randomized Controlled Trials from database inception until July 2014. Two reviewers independently screened articles for eligibility, extracted data, and assessed risk of bias. Grading of Recommendations Assessment, Development, and Evaluation (GRADE) was used to evaluate the quality of evidence for each of the primary and secondary outcomes. Results: Sixty-seven studies, including 46 RCTs, were found. The majority evaluated communication tools in older patients (age >50) with no specific medical condition, but many specifically evaluated populations with cancer, lung, heart, neurologic, or renal disease. Most studies compared the use of communication tools against usual care, but several compared the tools to less-intensive advance care planning tools. The use of structured communication tools increased: the frequency of advance care planning discussions/discussions about advance directives (RR 2.31, 95% CI 1.25–4.26, p = 0.007, low quality evidence) and the completion of advance directives (ADs) (RR 1.92, 95% CI 1.43–2.59, p<0.001, low quality evidence); concordance between AD preferences and subsequent medical orders for use or non-use of life supporting treatment (RR 1.19, 95% CI 1.01–1.39, p = 0.028, very low quality evidence, 1 observational study); and concordance between the care desired and care received by patients (RR 1.17, 95% CI 1.05–1.30, p = 0.004, low quality evidence, 2 RCTs). Conclusions: The use of structured communication tools may increase the frequency of discussions about and completion of advance directives, and concordance between the care desired and the care received by patients. The use of structured communication tools rather than an ad-hoc approach to end-of-life decision-making should be considered, and the selection and implementation of such tools should be tailored to address local needs and context. Registration: PROSPERO [ABSTRACT FROM AUTHOR]

Gangliosides serve as receptors for internalization and infection by members of the polyomavirus family. Specificity is determined by recognition of carbohydrate moieties on the ganglioside by the major viral capsid protein VP1. For the mouse polyomavirus (MuPyV), gangliosides with terminal sialic acids in specific linkages are essential. Although many biochemical and cell culture experiments have implicated gangliosides as MuPyV receptions, the role of gangliosides in the MuPyV-infected mouse has not been investigated. Here we report results of studies using ganglioside-deficient mice and derived cell lines. Knockout mice lacking complex gangliosides were completely resistant to the cytolytic and pathogenic effects of the virus. Embryo fibroblasts from these mice were likewise resistant to infection, and supplementation with specific gangliosides restored infectibility. Although lacking receptors for viral infection, cells from ganglioside-deficient mice retained the ability to respond to the virus. Ganglioside-deficient fibroblasts responded rapidly to virus exposure with a transient induction of c-fos as an early manifestation of a mitogenic response. Additionally, splenocytes from ganglioside-deficient mice responded to MuPyV by secretion of IL-12, previously recognized as a key mediator of the innate immune response. Thus, while gangliosides are essential for infection in the animal, gangliosides are not required for mitogenic responses and innate immune responses to the virus. [ABSTRACT FROM AUTHOR]

Background: Activity-based funding (ABF) of hospitals is a policy intervention intended to re-shape incentives across health systems through the use of diagnosis-related groups. Many countries are adopting or actively promoting ABF. We assessed the effect of ABF on key measures potentially affecting patients and health care systems: mortality (acute and post-acute care); readmission rates; discharge rate to post-acute care following hospitalization; severity of illness; volume of care. Methods: We undertook a systematic review and meta-analysis of the worldwide evidence produced since 1980. We included all studies reporting original quantitative data comparing the impact of ABF versus alternative funding systems in acute care settings, regardless of language. We searched 9 electronic databases (OVID MEDLINE, EMBASE, OVID Healthstar, CINAHL, Cochrane CENTRAL, Health Technology Assessment, NHS Economic Evaluation Database, Cochrane Database of Systematic Reviews, and Business Source), hand-searched reference lists, and consulted with experts. Paired reviewers independently screened for eligibility, abstracted data, and assessed study credibility according to a pre-defined scoring system, resolving conflicts by discussion or adjudication. Results: Of 16,565 unique citations, 50 US studies and 15 studies from 9 other countries proved eligible (i.e. Australia, Austria, England, Germany, Israel, Italy, Scotland, Sweden, Switzerland). We found consistent and robust differences between ABF and no-ABF in discharge to post-acute care, showing a 24% increase with ABF (pooled relative risk = 1.24, 95% CI 1.18–1.31). Results also suggested a possible increase in readmission with ABF, and an apparent increase in severity of illness, perhaps reflecting differences in diagnostic coding. Although we found no consistent, systematic differences in mortality rates and volume of care, results varied widely across studies, some suggesting appreciable benefits from ABF, and others suggesting deleterious consequences. Conclusions: Transitioning to ABF is associated with important policy- and clinically-relevant changes. Evidence suggests substantial increases in admissions to post-acute care following hospitalization, with implications for system capacity and equitable access to care. High variability in results of other outcomes leaves the impact in particular settings uncertain, and may not allow a jurisdiction to predict if ABF would be harmless. Decision-makers considering ABF should plan for likely increases in post-acute care admissions, and be aware of the large uncertainty around impacts on other critical outcomes.