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In this article, I argue that many of the ethical problems associated with the authorship of journal literature can usefully be clarified if authorship is placed within the broader concept of attribution, which extends beyond the author byline to encompass everything that readers are told about the work’s origination and the parties responsible. I also suggest that as the attribution of literature has grown more complex, and the opportunities for misattribution have become more subtle and multifarious, attribution has become increasingly vulnerable to systematic bias. Accordingly, I define “credit bias” as the systematic distortion of attribution, frequently in the interests of those with influence over the publication. I present a four-step framework for evaluating publications, discuss misattribution in drug industry literature as an illustration of credit bias, and examine the role of editorial standards in mitigating, but also in assisting, credit bias. I also argue for an independent scientific standard to promote ethical conduct in the medical journal sector.

Although research indicates that developing new public housing typically does not increase neighborhood crime, little is known about the impact of revitalizing existing public housing properties, also known as redevelopment. This study evaluates the effect of a multi-component physical and social redevelopment project on reports and perceptions of neighborhood crime in Seattle, Washington. We compare administrative police data with findings from a community survey to assess trends during early-to-mid redevelopment. While perceptions of safety improved over the study period, most crime-specific trends were not significantly different at the redevelopment site relative to comparison sites where no redevelopment occurred. Results suggest that this project did not have obvious adverse effects on crime rates. Although this redevelopment may have had a positive effect on perceptions of crime and safety in the short-term, it may take longer to realize beneficial effects on actual experiences or reports of crime.

In response to the growing regional (and national) focus on health and housing intersections, two public housing authorities (PHAs) in Washington—the King County Housing Authority and the Seattle Housing Authority—joined with Public Health–Seattle & King County to form the Housing and Health (H&H) partnership in 2016. H&H linked Medicaid health claims with PHA administrative data to create a sustainable public-facing dashboard that informs health and housing stakeholders such as an Accountable Community of Health (a governing body that oversees local Medicaid transformation projects), managed care organizations, and PHAs, allowing insights into the low-income communities they serve.

Meta-analysis based on individual participant data (IPD) is a powerful methodology for synthesizing evidence by combining information drawn from multiple trials. Hitherto, its principal application has been in questions of clinical management, but an increasingly important use is in clarifying trials methodology, for instance in the selection of endpoints, as discussed in this review. In oncology, the Aide et Recherche en Cancerologie Digestive (ARCAD) Metastatic Colorectal Cancer Database is a leader in the use of IPD-based meta-analysis in methodological research. The ARCAD database contains IPD from more than 38 000 patients enrolled in 46 studies and continues to collect phase III trial data. Here, we review the principal findings of the ARCAD project in respect of endpoint selection and examine their implications for cancer trials. Analysis of the database has confirmed that progression-free survival (PFS) is no longer a valid surrogate endpoint predictive of overall survival in the first-line treatment of colorectal cancer. Nonetheless, PFS remains an endpoint of choice for most first-line trials in metastatic colorectal cancer and other solid tumors. Only substantial PFS effects are likely to translate into clinically meaningful benefits, and accordingly, we advocate an oncology research model designed to identify highly effective treatments in carefully defined patient groups. We also review the use of the ARCAD database in assessing clinical response including novel response metrics and prognostic markers. These studies demonstrate the value of IPD as a tool for methodological studies and provide a reference point for the expansion of this approach within clinical cancer research. SL was supported by the US National Cancer Institute Cancer Center Support Grant, award number: P30CA008748. AS was supported by AIRC, grant number IG2018. We thank our ARCAD colleagues Daniel G Haller, MD, for guidance and helpful revisions to the text, and Lama Sharara, PhD, Director General of ARCAD, for expertly coordinating this multi-author review. We also thank the many ARCAD members who commented on this article at the outline stage. AIRCFondazione AIRC per la ricerca sul cancro [IG2018]

The incidence and spread of dengue virus (DENV) have increased rapidly in recent decades. Dengue is underreported in Africa, but recent outbreaks and seroprevalence data suggest that DENV is widespread there. A lack of ongoing surveillance limits knowledge about its spatial reach and hinders disease control planning. We sought to add data on dengue distribution in Kenya through diagnostic testing of serum specimens from persons with an acute febrile illness (AFI) attending an outpatient clinic in rural western Kenya (Asembo) during rainy seasons. Patients with symptoms not likely to be misclassified as dengue (e.g., diarrhea and anemia), those with a positive diagnostic laboratory results which explained their febrile illness, or those with serum collected more than 5 days after fever onset were excluded. However, febrile patients with a positive malaria smear were included in the study. We used reverse transcription polymerase chain reaction (RT-PCR) to test for DENV and IgM anti-DENV to test for recent infection. Of the 615 serum specimens available for testing, none were dengue positive by either RT-PCR or IgM anti-DENV testing. Dengue did not appear to be a cause of febrile illness in this area of western Kenya, although our relatively small sample size may not have identified DENV infections occurring at low incidence. A more widespread AFI surveillance system that includes dengue diagnostic testing by RT-PCR and antibody-based methods is required to more definitively gauge the size and geographic distribution of DENV infection in western Kenya.

There is growing evidence supporting comprehensive community development efforts that focus on multiple determinants of well-being. Yet evaluation has been limited by a lack of longitudinal studies...

Much medical journal literature is developed by the pharmaceutical and device industries, sometimes with assistance from marketing agencies, writers, and academics. This literature is vulnerable to commercial bias. The publications trade issues self-regulatory ethical guidelines for its production, called "Good Publication Practice" (GPP). I evaluated the most recent iteration, GPP3. The most progressive recommendations in GPP3 call for complete publication of all clinical trials, and full data sharing. GPP3 makes numerous further recommendations more directly concerning the publications trade. Many of these repeat existing editorial requirements, chiefly those of the International Committee of Medical Journal Editors, but readers are not adequately advised of this. Despite its emphasis on ethical and transparent reporting, the detail of GPP3 enables continued use of academic medical literature for drug marketing, on the basis of commercial steerage of content, coupled with the attribution of published articles to collaborating academic authors. As such, GPP3 provides a de facto manual for how marketing through academic journal content can be conducted in compliance with contemporary editorial standards. Consequently, the self-regulatory GPP3 guidelines are not a sound basis for the production of unbiased industry-financed medical journal literature. I suggest improvements for future iterations of these influential guidelines.

The best studies on the relationship between pharmaceutical corporations and medicine have recognized that it is an ambiguous one. Yet most scholarship has pursued a simpler, more saleable narrative in which pharma is a scheming villain and medicine its maidenly victim. In this article, I argue that such crude moral framing blunts understanding of the murky realities of medicine's relationship with pharma and, in consequence, holds back reform. My goal is to put matters right in respect to one critical area of scholarly interest, the medical journal publication. Pharma relies on peer advocacy to sell its wares to prescribing doctors. This is an arrangement in which clinicians' qualified colleagues, including "key opinion leaders," are recruited by pharmaceutical corporations and marketing agencies to deliver commercially expedient content to their professional fellows. Precisely how this practice works in the setting of publications is not well understood because ethicists studying the problem have made too much of the narrative of corporate villainy and medical victimhood. Accordingly, criticism of industry publications has been preoccupied with the crudely dishonest practices of ghostwriting, ghost authorship, and "ghost management," vices condemned as "dirty little secrets" perpetrated from "behind the scenes" with the connivance of academic "shills" or "guest authors," in contempt of standards set by the International Committee of Medical Journal Editors. This account is appealing, and yet it is wrong or, at the very least, seriously incomplete, with only limited relevance to the actualities of contemporary industry practices. In truth, many commercial publications are not developed in secret but fashioned within a culture of open collaboration, where academic authors make substantial, independent contributions; pharmaceutical companies are showcased rather than hidden; and medicine's editorial standards assist rather than impede the workings of commerce.

Strong data quality (DQ) is a precursor to strong data use. In resource limited settings, routine DQ assessment (DQA) within electronic medical record (EMR) systems can be resource-intensive using manual methods such as audit and chart review; automated queries offer an efficient alternative. This DQA focused on Haiti's national EMR - iSanté - and included longitudinal data for over 100,000 persons living with HIV (PLHIV) enrolled in HIV care and treatment services at 95 health care facilities (HCF).This mixed-methods evaluation used a qualitative Delphi process to identify DQ priorities among local stakeholders, followed by a quantitative DQA on these priority areas. The quantitative DQA examined 13 indicators of completeness, accuracy, and timeliness of retrospective data collected from 2005 to 2013. We described levels of DQ for each indicator over time, and examined the consistency of within-HCF performance and associations between DQ and HCF and EMR system characteristics.Over all iSanté data, age was incomplete in1% of cases, while height, pregnancy status, TB status, and ART eligibility were more incomplete (approximately 20-40%). Suspicious data flags were present for3% of cases of male sex, ART dispenses, CD4 values, and visit dates, but for 26% of cases of age. Discontinuation forms were available for about half of all patients without visits for 180 or more days, and60% of encounter forms were entered late. For most indicators, DQ tended to improve over time. DQ was highly variable across HCF, and within HCFs DQ was variable across indicators. In adjusted analyses, HCF and system factors with generally favorable and statistically significant associations with DQ were University hospital category, private sector governance, presence of local iSante server, greater HCF experience with the EMR, greater maturity of the EMR itself, and having more system users but fewer new users. In qualitative feedback, local stakeholders emphasized lack of stable power supply as a key challenge to data quality and use of the iSanté EMR.Variable performance on key DQ indicators across HCF suggests that excellent DQ is achievable in Haiti, but further effort is needed to systematize and routinize DQ approaches within HCFs. A dynamic, interactive "DQ dashboard" within iSanté could bring transparency and motivate improvement. While the results of the study are specific to Haiti's iSanté data system, the study's methods and thematic lessons learned holdgeneralized relevance for other large-scale EMR systems in resource-limited countries.

Purpose System use is a key criterion of success in an electronic medical record (EMR) implementation, and there is little research on long-term use of systems following implementation. The aim of the paper was to describe the development, implementation and use of iSante, Haiti's national HIV care and treatment EMR. Methods To build a picture of the history of iSante, we interviewed 11 staff involved with the development and implementation of the EMR, and reviewed organization records. Data entry and report use were ascertained by querying the central patient database. Results By the end of 2010 there were 67 sites with iSante installed, and the scope of the system had been expanded to include primary care and obstetrics and gynecology. New functionality includes data forms specific to subpopulations, the ability to transfer patient records among clinics, and integration with an electronic laboratory system. We observed fluctuations in use over time, with substantial reductions in the number of active sites during times of large-scale disruptions in Haiti. A surge in report use following the January 2010 earthquake suggests that clinics found the EMR to be a valuable source of data during the recovery phase. Conclusion There is real potential for EMRs in developing countries to improve clinical practice and make data available for efficient reporting, quality improvement and other population health uses. An approach of continuous system improvement, combined with regular assessments of use, is necessary for achieving an effective, national implementation of a standardized EMR. We have achieved successes in terms of rolling out new functionality and expanding to new sites, but more work remains to be done to improve perceptions of data quality and increase use of population data for accurate and timely reporting.

Parker and colleagues discuss ethical drug marketing.1 One simple, potent yardstick for distinguishing acceptable from bad drug marketing derives from the perspective of the prescribing doctor. When treatment decisions are made, the clinician’s reasoning should be free from interference, evidence based, cost aware, and appropriate to the needs and wishes of the patient. This basic principle of medicine leads to two fundamental marketing requirements. Firstly, the only acceptable form of marketing should be the provision of information …

Aimery de Gramont, Hopital Saint Antoine, Paris, France Daniel G. Haller, Abramson Cancer Center at the University of Pennsylvania, Philadelphia, PA Daniel J. Sargent, Mayo Clinic, Cancer Center Statistics, Rochester, MN Josep Tabernero, Vall d’Hebron University Hospital, Medical Oncology Service, Barcelona, Spain Alastair Matheson, Foundation ARCAD, Paris, France Richard L. Schilsky, University of Chicago, Biological Sciences Division, Chicago, IL

This article analyses the role of the pharmaceutical and medical device industries (‘pharma’) in the construction of scientific and medical knowledge. Pharma's activities are part of the broader dispositif of institutions, enterprises, regulations and constituencies within which medical-scientific knowledge is generated, but pharma's contributions exhibit a specific character reflecting commercial pressures. As drug development proceeds, research and marketing activities coalesce around ‘product canons’ that integrate scientific truth-claims and commercial positioning, generating knowledge with implicit commercial functionality. From this platform, pharma stamps consensus-building ‘narratives’ into medical-scientific discourse, in which ‘problems’ arise and are ‘solved’ by drugs. Concurrently, pharma modulates the structure of discourse and the social networks through which discourse proceeds. Implicit within these activities is a meta-science whose goal is to understand and technologize the operation of science to an external end. This mode of knowledge production can be viewed as a normative transformation of Kuhnian normal science, characterized by the attachment (and at times subordination) of paradigmatic tenets to extrinsic goals; exaggerated control of belief, research and consensus formation; and a capacity for infringement of traditional norms of scientific truthfulness. An International Standard of Integrity in Science would strengthen pharma's contributions to medical and scientific knowledge.

Background The International Committee of Medical Journal Editors (ICMJE) Recommendations set ethical and editorial standards for article publication in most leading medical journals. Here, I examine the strengths and weaknesses of the Recommendations in the prevention of commercial bias in industry-financed journal literature, on three levels – scholarly discourse, article content, and article attribution. Discussion With respect to overall discourse, the most important measures in the ICMJE Recommendations are for enforcing clinical trial registration and controlling duplicate publication. With respect to article content, the ICMJE promotes stringent author accountability and adherence to established reporting standards. However, the ICMJE accepts the use of commercial editorial teams to produce manuscripts, which is a potential source of bias, and accepts private company ownership and analysis of clinical trial data. New ICMJE guidance on data sharing will address but not eliminate problems of commercial data access. With respect to attribution, the Recommendations oppose guest authorship and encourage clear documentation of author contributions. However, they exclude writers from coauthorship; provide no specific advice on the attribution of commercial literature, for instance with respect to company authorship, author sequence or prominent commercial labeling; and endorse the use of fine print and euphemism. The ICMJE requires detailed author interest disclosures, but overlooks the interests of non-authors and companies, and does not recommend that interests most salient to the publication are highlighted. Together, these weaknesses facilitate “advocacy”-based marketing, in which literature planned, financed and produced by companies is fronted by academics, enabling commercial messages to be presented to customers by their respected clinical peers rather than companies themselves. Conclusions The ICMJE Recommendations set important research and reporting standards, without which commercial bias would likely be a significantly greater problem than it is today. However, they also support practices of commercial data control, content development and attribution that run counter to science’s values of openness, objectivity and truthfulness. These weaknesses could be addressed with appropriate modifications to the Recommendations. The ICMJE should also disclose its own commercial interests and funding – not least because publishing organizations that finance it and pay the salaries of some member editors derive substantial revenues from industry.

Background Enteric fever due to Salmonella Typhi (typhoid fever) occurs in urban areas with poor sanitation. While direct fecal-oral transmission is thought to be the predominant mode of transmission, recent evidence suggests that indirect environmental transmission may also contribute to disease spread. Methods Data from a population-based infectious disease surveillance system (28,000 individuals followed biweekly) were used to map the spatial pattern of typhoid fever in Kibera, an urban informal settlement in Nairobi Kenya, between 2010–2011. Spatial modeling was used to test whether variations in topography and accumulation of surface water explain the geographic patterns of risk. Results Among children less than ten years of age, risk of typhoid fever was geographically heterogeneous across the study area (p = 0.016) and was positively associated with lower elevation, OR = 1.87, 95% CI (1.36–2.57), p, Author Summary Typhoid fever, a serious bloodstream infection caused by the bacterium Salmonella Typhi, is commonly associated with direct, person-to-person transmission as a result of improper hygiene and unsafe food/water handling practices. Recent evidence, however, suggests that individuals may be indirectly exposed to typhoid through contact with fecal contamination in their immediate environment. In this study we investigated the role of environmental sources in the transmission of typhoid fever across an urban slum in Kenya by mapping the occurrence of cases in both children and adults. We tested the hypothesis that cases (relative to non-cases) cluster in low elevation areas as a result of the downstream flow and accumulation of fecal waste. We found that cases of typhoid fever among children tended to be concentrated in the downstream area. In adolescents and adults, on the other hand, there was little evidence of a geographic pattern in the risk of typhoid fever. These results provide evidence that environmental transmission of typhoid fever contributes to the risk of disease in children but not adults and adolescents, an observation most likely attributed to the fact that children are more likely to be exposed to fecal contamination through outside play. Interventions to improve local sanitation may therefore provide particular benefit to children who are at most risk of exposure to and acquisition of typhoid fever from environmental sources.

Background Pneumonia and diarrhea are leading causes of death for children under five (U5). It is challenging to estimate the total number of deaths and cause-specific mortality fractions. Two major efforts, one led by the Institute for Health Metrics and Evaluation (IHME) and the other led by the World Health Organization (WHO)/Child Health Epidemiology Reference Group (CHERG) created estimates for the burden of disease due to these two syndromes, yet their estimates differed greatly for 2010. Methods This paper discusses three main drivers of the differences: data sources, data processing, and covariates used for modelling. The paper discusses differences in the model assumptions for etiology-specific estimates and presents recommendations for improving future models. Results IHME’s Global Burden of Disease (GBD) 2010 study estimated 6.8 million U5 deaths compared to 7.6 million U5 deaths from CHERG. The proportional differences between the pneumonia and diarrhea burden estimates from the two groups are much larger; GBD 2010 estimated 0.847 million and CHERG estimated 1.396 million due to pneumonia. Compared to CHERG, GBD 2010 used broader inclusion criteria for verbal autopsy and vital registration data. GBD 2010 and CHERG used different data processing procedures and therefore attributed the causes of neonatal death differently. The major difference in pneumonia etiologies modeling approach was the inclusion of observational study data; GBD 2010 included observational studies. CHERG relied on vaccine efficacy studies. Discussion Greater transparency in modeling methods and more timely access to data sources are needed. In October 2013, the Bill & Melinda Gates Foundation (BMGF) hosted an expert meeting to examine possible approaches for better estimation. The group recommended examining the impact of data by systematically excluding sources in their models. GBD 2.0 will use a counterfactual approach for estimating mortality from pathogens due to specific etiologies to overcome bias of the methods used in GBD 2010 going forward. Electronic supplementary material The online version of this article (doi:10.1186/s12879-014-0728-4) contains supplementary material, which is available to authorized users.

Objectives To help stakeholders identify and prioritise countries with the best opportunities for implementation of an integrated prevention campaign (IPC) focused on diarrhoea, malaria and HIV prevention. Design Cross-sectional analysis of country-specific epidemiological data using an index tool developed for this purpose. Setting We calculated the total disability-adjusted life years (DALYs) attributed to diarrhoea, malaria and HIV for 214 World Bank economies. Criteria for inclusion were: low-income and middle-income countries, and total annual DALY burden in the top tertile (≥87 000 DALYs). 70 countries met inclusion criteria and were included in our opportunity analysis. Outcome measures We synthesised data on 10 indicators related to the potential reduction in burden and new coverage achievable by an IPC. We scored and ranked countries based on three summary opportunity metrics: DALYs per capita across the diseases, a composite score of tertile rankings of burden for each disease, and a score combining burden and intervention opportunity. Results We estimated the total annual global burden attributable to diarrhoea, malaria and HIV at 135 million DALYs. All of the countries with the highest opportunity for implementation of a diarrhoea, malaria and HIV IPC are in sub-Saharan Africa, regardless of opportunity metric used. Although the overall rank order changes, 16 countries rank among the top 23 highest opportunity countries for all three metrics. Conclusions Stakeholders can use this objective metric-based approach to prioritise countries for IPC scale-up. Priority countries are largely robust to the opportunity metric chosen.

SUMMARY Treatment of tuberculosis (TB) remains challenging, with lengthy treatment durations and complex drug regimens that are toxic and difficult to administer. Similar to the vast majority of antibiotics, drugs for Mycobacterium tuberculosis are directed against microbial targets. Although more effective drugs that target the bacterium may lead to faster cure of patients, it is possible that a biological limit will be reached that can be overcome only by adopting a fundamentally new treatment approach. TB regimens might be improved by including agents that target host pathways. Recent work on host-pathogen interactions, host immunity, and host-directed interventions suggests that supplementing anti-TB therapy with host modulators may lead to shorter treatment times, a reduction in lung damage caused by the disease, and a lower risk of relapse or reinfection. We undertook this review to identify molecular pathways of the host that may be amenable to modulation by small molecules for the treatment of TB. Although several approaches to augmenting standard TB treatment have been proposed, only a few have been explored in detail or advanced to preclinical and clinical studies. Our review focuses on molecular targets and inhibitory small molecules that function within the macrophage or other myeloid cells, on host inflammatory pathways, or at the level of TB-induced lung pathology.

Alastair Matheson describes how the pharmaceutical publications industry seeks to legitimise ghostwriting by changing its definition while deflecting attention from wider marketing practices in academic publishing

It is widely accepted that traditional models of clinical investigation are becoming unsustainable in oncology and that trials must become more efficient in matching effective treatments to the patients most likely to benefit. In 2008, gastrointestinal oncologists from many countries began a collaboration to improve the design and conduct of clinical trials in their field, through the auspices of a French/U.S. charitable foundation, ARCAD. Whether this model of academic collaboration will be judged a success will depend on the quality of its scientific output during the next few years and whether this output, alongside that of other scientists, groups, and institutions, ultimately leads to more efficient trials and improved treatment options for patients.

Biomarkers have a growing role in clinical trials. With the advent of the targeted therapy era, molecular biomarkers in particular are becoming increasingly important within both clinical research and clinical practice. This article focuses on biomarkers that anticipate the prognosis of individual patients ('prognostic' biomarkers) and on biomarkers that predict how individual patients will respond to specific treatments ('predictive' biomarkers, also called 'effect modifiers'). Specific Phase II and III clinical trial designs are discussed in detail for their ability to validate the biomarker and/or to establish the effect of an experimental therapy in patient populations defined by the presence or absence of the biomarker. Contemporary biomarker-based clinical trials in oncology are used as examples.

Despite advances in the prevention and early detection of cancer and the treatment of some malignancies, clinical research has not yet delivered treatment benefits of the magnitude anticipated after the launch of imatinib, which established highly effective new treatment standards. The primary impediments to progress are scientific, but the efficiency of research is also affected by structural deficiencies relating to where and by whom it is conducted, as well as how it is organized and regulated. To optimize the research environment and maximize the benefits of improved funding, adjustments in the roles of government, industry, the academic community, national research bodies, and regulatory authorities are needed. A patchwork of reforms that are enabling in character and build on existing expertise can deliver substantial progress without the need for radical intervention.

Background As new interventions to reduce childhood mortality are identified, careful consideration must be given to identifying populations that could benefit most from them. Promising reductions in childhood mortality reported in a large cluster randomized trial of mass drug administration (MDA) of azithromycin (AZM) prompted the development of visually compelling, easy-to-use tools that synthesize country-specific data on factors that would influence both potential AZM benefit and MDA implementation success. Methodology/Principal Findings We assessed the opportunity to reduce mortality and the feasibility of implementing such a program, creating Opportunity and Feasibility Indices, respectively. Countries with high childhood mortality were included. A Country Ranking Index combined key variables from the previous two Indices and applied a scoring system to identify high-priority countries. We compared four scenarios with varying weights given to each variable. Twenty-five countries met inclusion criteria. We created easily visualized tools to display the results of the Opportunity and Feasibility Indices. The Opportunity Index revealed substantial variation in the opportunity for an MDA of AZM program to reduce mortality, even among countries with high overall childhood mortality. The Feasibility Index demonstrated that implementing such a program would be most challenging in the countries that could see greatest benefit. Based on the Country Ranking Index, Equatorial Guinea would benefit the most from the MZA of AZM in three of the four scenarios we tested. Conclusions/Significance These visually accessible tools can be adapted or refined to include other metrics deemed important by stakeholders, and provide a quantitative approach to prioritization for intervention implementation. The need to explicitly state metrics and their weighting encourages thoughtful and transparent decision making. The objective and data-driven approach promoted by the three Indices may foster more efficient use of resources.

In 2005 the American Diabetes Association and European Association for the Study of Diabetes questioned the value of the metabolic syndrome as a diagnostic category(1). In the same year, Reaven delivered a noted “obituary” for the metabolic syndrome in this journal, while defending the insulin resistance syndrome as a pathophysiologic entity(2). But despite these broadsides, the concept of the metabolic syndrome is attracting continued support. PubMed lists 1775 articles with “metabolic syndrome” in the title or abstract published during 2005, 2566 during 2006, and 1689 for the first 6 months of 2007. Clearly, rumors of the syndrome’s demise have been greatly exaggerated. There are several reasons why the metabolic syndrome continues to thrive as a concept. First, there is a widespread sense that its components are sufficiently coupled mechanistically to suggest some kind of disease entity. Second, the term and concept retain utility simply for want of a fuller description of the underlying pathology. Third, the …

3557 Background: Since post-progression therapy influences overall survival (OS), PPS is of interest as a determinant of OS. We quantified the relationship between several median times to event in ACC: progression-free survival (PFS), PPS and OS. We looked for factors with an impact on these times. Methods: We searched PubMed for phase III trials published between January 1998 and December 2010 in 12 leading journals. PPS is the difference between median OS and median PFS or time to tumor progression. The statistics of interest (median times [PFS, OS and PPS] and the ratio of PPS/OS) were compared using t-tests. Results: We retrieved 70 trials that yielded 71 comparisons and 156 arms (one trial was factorial) involving 38,504 patients. Trials from the period 2005-10 enrolled more patients than trials from the period 1998-2004 (medians of 246 vs 174 per arm; P=.026). PPS could be calculated for 60 trials and 135 arms (Table). Treatment type did not have an impact on any statistic. Treatment line had a significant impact on all times and on the ratio of PPS/OS, although the difference on the latter statistic was small. Treatment period had a significant impact on all times but not on the ratio of PPS/OS. Conclusions: None of the factors examined have a major impact on the ratio of PPS/OS. This suggests that in ACC, gains in PFS are translated into proportional gains in OS, one of the conditions required for PFS to be considered a surrogate for OS. [Table: see text]

An idea far more revolutionary than the drastic land reform decrees introduced in Peru by the military Government after the 1968 coup d'etat was one concerning children that education should start in the cradle and not in the classroom. So determined was the Revolutionary Government to introduce drastic educational reforms to parallel the sweeping agrarian reforms that it gave the measure equally high priority, despite the misgivings of some critics. In fact, the special Committee for Educational Reform, which began work shortly after the new regime was installed, had to endure many jokes at its own expense. Some teachers asked if they would have classes of new-born babies, other if they were expected to be nurses instead of educators. A few even mockingly inquired if they were expected to give toilet training in the new curriculum. The Peruvian Government soon showed it was no joke, but a policy to be applied in deadly earnest, as part of a deliberate strategy to wrest power from the landed oligarchy of that time and place it in the hands of the people, creating a more egalitarian society. The measures were aimed especially at bringing the Indian population of Peru more into the mainstream of public life and to ensure that they were no longer an under-privileged group, as had been the case ever since Pizarro and the Conquistadores crushed the Inca's power early in the 16th Century.