Expanding Disease Definitions in Guidelines and Expert Panel Ties to Industry:A Cross-sectional Study of Common Conditions in the United States

BACKGROUND: Financial ties between health professionals and industry may unduly influence professional judgments and some researchers have suggested that widening disease definitions may be one driver of over-diagnosis, bringing potentially unnecessary labeling and harm. We aimed to identify guidelines in which disease definitions were changed, to assess whether any proposed changes would increase the numbers of individuals considered to have the disease, whether potential harms of expanding disease definitions were investigated, and the extent of members' industry ties. METHODS AND FINDINGS: We undertook a cross-sectional study of the most recent publication between 2000 and 2013 from national and international guideline panels making decisions about definitions or diagnostic criteria for common conditions in the United States. We assessed whether proposed changes widened or narrowed disease definitions, rationales offered, mention of potential harms of those changes, and the nature and extent of disclosed ties between members and pharmaceutical or device companies. Of 16 publications on 14 common conditions, ten proposed changes widening and one narrowing definitions. For five, impact was unclear. Widening fell into three categories: creating “pre-disease”; lowering diagnostic thresholds; and proposing earlier or different diagnostic methods. Rationales included standardising diagnostic criteria and new evidence about risks for people previously considered to not have the disease. No publication included rigorous assessment of potential harms of proposed changes. Among 14 panels with disclosures, the average proportion of members with industry ties was 75%. Twelve were chaired by people with ties. For members with ties, the median number of companies to which they had ties was seven. Companies with ties to the highest proportions of members were active in the relevant therapeutic area. Limitations arise from reliance on only disclosed ties, and exclusion of conditions too broad to enable analysis of single panel publications. CONCLUSIONS: For the common conditions studied, a majority of panels proposed changes to disease definitions that increased the number of individuals considered to have the disease, none reported rigorous assessment of potential harms of that widening, and most had a majority of members disclosing financial ties to pharmaceutical companies. Please see later in the article for the Editors' Summar

A systematic review of associations between environmental exposures and development of asthma in children aged up to 9 years

Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.Peer reviewedPublisher PD

How well does B-type natriuretic peptide predict death and cardiac events in patients with heart failure: systematic review

Objective To assess how well B-type natriuretic peptide (BNP) predicts prognosis in patients with heart failure. Design Systematic review of studies assessing BNP for prognosis m patients with heart failure or asymptomatic patients. Data sources Electronic searches of Medline and Embase from January 1994 to March 2004 and reference lists of included studies. Study selection and data extraction We included all studies that estimated the relation between BNP measurement and the risk of death, cardiac death, sudden death, or cardiovascular event in patients with heart failure or asymptomatic patients, including initial values and changes in values in response to treatment. Multivariable models that included both BNP and left ventricular ejection fraction as predictors were used to compare the prognostic value of each variable. Two reviewers independently selected studies and extracted data. Data synthesis 19 studies used BNP to estimate the relative risk of death or cardiovascular events in heart failure patients and five studies in asymptomatic patients. In heart failure patients, each 100 pg/ml increase was associated with a 35% increase in the relative risk of death. BNP was used in 35 multivariable models of prognosis. In nine of the models, it was the only variable to reach significance-that is, other variables contained no prognostic information beyond that of BNP. Even allowing for the scale of the variables, it seems to be a strong indicator of risk. Conclusion Although systematic reviews of prognostic studies have inherent difficulties, including die possibility of publication bias, the results of the studies in this review show that BNP is a strong prognostic indicator for both asymptomatic patients mid for patients with heart failure at all stages of disease

On the Quantization of the Chern-Simons Fields Theory on Curved Space-Times: the Coulomb Gauge Approach

We consider here the Chern-Simons field theory with gauge group SU(N) in the presence of a gravitational background that describes a two-dimensional expanding ``universe". Two special cases are treated here in detail: the spatially flat {\it Robertson-Walker} space-time and the conformally static space-times having a general closed and orientable Riemann surface as spatial section. The propagator and the vertices are explicitely computed at the lowest order in perturbation theory imposing the Coulomb gauge fixing.Comment: 15 pp., Preprint LMU-TPW 93-5, (Plain TeX + Harvmac

Kidney trajectory charts to assist general practitioners in the assessment of patients with reduced kidney function: a randomised vignette study

OBJECTIVE: To investigate the decisional impact of an age-based chart of kidney function decline to support general practitioners (GPs) to appropriately interpret estimated glomerular filtration rate (eGFR) and identify patients with a clinically relevant kidney problem. DESIGN AND SETTING: Randomised vignette study PARTICIPANTS: 372 Australian GPs from August 2018 to November 2018. INTERVENTION: GPs were given two patient case scenarios: (1) an older woman with reduced but stable renal function and (2) a younger Aboriginal man with declining kidney function still in the normal range. One group was given an age-based chart of kidney function to assist their assessment of the patient (initial chart group); the second group was asked to assess the patients without the chart, and then again using the chart (delayed chart group). MAIN OUTCOME MEASURES: GPs’ assessment of the likelihood—on a Likert scale—that the patients had chronic kidney disease (CKD) according to the usual definition or a clinical problem with their kidneys. RESULTS: Prior to viewing the age-based chart GPs were evenly distributed as to whether they thought case 1—the older woman—had CKD or a clinically relevant kidney problem. GPs who had initial access to the chart were less likely to think that the older woman had CKD, and less likely to think she had a clinically relevant problem with her kidneys than GPs who had not viewed the chart. After subsequently viewing the chart, 14% of GPs in the delayed chart group changed their opinion, to indicate she was unlikely to have a clinically relevant problem with her kidneys. Prior to viewing the chart, the majority of GPs (66%) thought case 2—the younger man—did not have CKD, and were evenly distributed as to whether they thought he had a clinically relevant kidney problem. In contrast, GPs who had initial access to the chart were more likely to think he had CKD and the majority (72%) thought he had a clinically relevant kidney problem. After subsequently viewing the chart, 37% of GPs in the delayed chart group changed their opinion to indicate he likely had a clinically relevant problem with his kidneys. CONCLUSIONS: Use of the chart changed GPs interpretation of eGFR, with increased recognition of the younger male patient’s clinically relevant kidney problem, and increased numbers classifying the older female patient’s kidney function as normal for her age. This study has shown the potential of an age-based kidney function chart to reduce both overdiagnosis and underdiagnosis

Expanding disease definitions in guidelines and expert panel ties to industry: A cross-sectional study of common conditions in the United States

Background: Financial ties between health professionals and industry may unduly influence professional judgments and some researchers have suggested that widening disease definitions may be one driver of over-diagnosis, bringing potentially unnecessary labeling and harm. We aimed to identify guidelines in which disease definitions were changed, to assess whether any proposed changes would increase the numbers of individuals considered to have the disease, whether potential harms of expanding disease definitions were investigated, and the extent of members' industry ties. Methods and Findings: We undertook a cross-sectional study of the most recent publication between 2000 and 2013 from national and international guideline panels making decisions about definitions or diagnostic criteria for common conditions in the United States. We assessed whether proposed changes widened or narrowed disease definitions, rationales offered, mention of potential harms of those changes, and the nature and extent of disclosed ties between members and pharmaceutical or device companies. Of 16 publications on 14 common conditions, ten proposed changes widening and one narrowing definitions. For five, impact was unclear. Widening fell into three categories: creating "pre-disease''; lowering diagnostic thresholds; and proposing earlier or different diagnostic methods. Rationales included standardising diagnostic criteria and new evidence about risks for people previously considered to not have the disease. No publication included rigorous assessment of potential harms of proposed changes. Among 14 panels with disclosures, the average proportion of members with industry ties was 75%. Twelve were chaired by people with ties. For members with ties, the median number of companies to which they had ties was seven. Companies with ties to the highest proportions of members were active in the relevant therapeutic area. Limitations arise from reliance on only disclosed ties, and exclusion of conditions too broad to enable analysis of single panel publications. Conclusions: For the common conditions studied, a majority of panels proposed changes to disease definitions that increased the number of individuals considered to have the disease, none reported rigorous assessment of potential harms of that widening, and most had a majority of members disclosing financial ties to pharmaceutical companies

The association of dyslexia and developmental speech and language disorder candidate genes with reading and language abilities in adults

Reading and language abilities are critical for educational achievement and success in adulthood. Variation in these traits is highly heritable, but the underlying genetic architecture is largely undiscovered. Genetic studies of reading and language skills traditionally focus on children with developmental disorders; however, much larger unselected adult samples are available, increasing power to identify associations with specific genetic variants of small effect size. We introduce an Australian adult population cohort (41.7–73.2 years of age, N = 1505) in which we obtained data using validated measures of several aspects of reading and language abilities. We performed genetic association analysis for a reading and spelling composite score, nonword reading (assessing phonological processing: a core component in learning to read), phonetic spelling, self-reported reading impairment and nonword repetition (a marker of language ability). Given the limited power in a sample of this size (~80% power to find a minimum effect size of 0.005), we focused on analyzing candidate genes that have been associated with dyslexia and developmental speech and language disorders in prior studies. In gene-based tests, FOXP2, a gene implicated in speech/language disorders, was associated with nonword repetition (p < .001), phonetic spelling (p = .002) and the reading and spelling composite score (p < .001). Gene-set analyses of candidate dyslexia and speech/language disorder genes were not significant. These findings contribute to the assessment of genetic associations in reading and language disorders, crucial for understanding their etiology and informing intervention strategies, and validate the approach of using unselected adult samples for gene discovery in language and reading

Rates, costs and determinants of lumbar spine imaging in population-based women born in 1973-1978: Data from the Australian Longitudinal Study on Women's Health

ObjectiveThere are concerns that lumbar spine imaging represents low value care. Our aim was to examine the use of lumbar spine imaging [radiography, computed tomography (CT), magnetic resonance imaging (MRI)] over 20 years, and costs and person-level characteristics of imaging in a large cohort of Australian women.MethodsThe Australian Longitudinal Study on Women's Health (ALSWH) is a longitudinal population-based survey of women randomly selected from national health insurance scheme (Medicare) database. This study examined 13458 women born in 1973-1978 who consented to link their ALSWH and Medical Benefits Scheme records. Self-reported data on demographics, body mass index, depression, physical and mental health, and back pain were collected in each survey performed in 1996, 2000, 2003, 2006, 2009, 2012, and 2015. Data on lumbar spine imaging from 1996 to 2015 were obtained from the Medical Benefits Scheme database.Results38.9% of women underwent some form of lumbar spine imaging over 20 years. While radiography increased from 1996 to 2011 and decreased thereafter, CT and MRI continued to increase from 1996 to 2015. In women with self-reported back pain, depression and poorer physical health were associated with imaging, with no significant differences in types of imaging. Based on imaging rates in ALSWH, the estimated costs for Australian women aged 30-39 years were AU$51,735,649 over 2011-2015.ConclusionsLumbar spine imaging was common in population-based Australian women, with rates increasing over 20 years. Depression and poor physical health were associated with lumbar spine imaging. Raising awareness of this in clinicians is likely to result in significant cost savings if clinical guidelines are followed, with the potential of freeing resources for high value care and health outcomes

Globally, functional traits are weak predictors of juvenile tree growth, and we do not know why

1. Plant functional traits, in particular specific leaf area (SLA), wood density and seed mass, are often good predictors of individual tree growth rates within communities. Individuals and species with high SLA, low wood density and small seeds tend to have faster growth rates. 2. If community-level relationships between traits and growth have general predictive value, then similar relationships should also be observed in analyses that integrate across taxa, biogeographic regions and environments. Such global consistency would imply that traits could serve as valuable proxies for the complex suite of factors that determine growth rate, and, therefore, could underpin a new generation of robust dynamic vegetation models. Alternatively, growth rates may depend more strongly on the local environment or growth-trait relationships may vary along environmental gradients. 3. We tested these alternative hypotheses using data on 27352 juvenile trees, representing 278 species from 27 sites on all forested continents, and extensive functional trait data, 38% of which were obtained at the same sites at which growth was assessed. Data on potential evapotranspiration (PET), which summarizes the joint ecological effects of temperature and precipitation, were obtained from a global data base. 4. We estimated size-standardized relative height growth rates (SGR) for all species, then related them to functional traits and PET using mixed-effect models for the fastest growing species and for all species together. 5. Both the mean and 95th percentile SGR were more strongly associated with functional traits than with PET. PET was unrelated to SGR at the global scale. SGR increased with increasing SLA and decreased with increasing wood density and seed mass, but these traits explained only 3.1% of the variation in SGR. SGR-trait relationships were consistently weak across families and biogeographic zones, and over a range of tree statures. Thus, the most widely studied functional traits in plant ecology were poor predictors of tree growth over large scales. 6. Synthesis. We conclude that these functional traits alone may be unsuitable for predicting growth of trees over broad scales. Determining the functional traits that predict vital rates under specific environmental conditions may generate more insight than a monolithic global relationship can offer.Additional co-authors: Hervé Jactel, Xuefei Li, Kaoru Kitajima, Julia Koricheva, Cristina Martínez-Garza, Christian Messier, Alain Paquette, Christopher Philipson, Daniel Piotto, Lourens Poorter, Juan M. Posada, Catherine Potvin, Kalle Rainio, Sabrina E. Russo, Mariacarmen Ruiz-Jaen, Michael Scherer-Lorenzen, Campbell O. Webb, S. Joseph Wright, Rakan A. Zahawi, and Andy Hecto

Sonography of ruptured appendicitis

Three girls and 4 boys with the final diagnosis of ruptured appendicitis underwent 19 sonographic studies, 5 before any therapy was instituted and 14 follow-up studies. Four abscesses identified before treatment and 2 seen postoperatively were ovoid, irregularly marginated, and contained lowamplitude echoes. Gastrointestinal ileus with gas- and fluid-filled loops of bowel made the studies technically difficult. Follow-up studies also showed fluid collections distant from the original abscesses. The complete resolution of the abscess was followed sonographically in 1 patient treated with antibiotics. Ultrasound can be useful in confirming or suggesting the diagnosis of ruptured appendicitis in the child with abdominal pain, but careful attention to detail is necessary in these technically difficult studies.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/48131/1/261_2005_Article_BF02035110.pd