Tag: PLoS Medicine

Using Evidence to Combat Overdiagnosis and Overtreatment: Evaluating Treatments, Tests, and Disease Definitions in the Time of Too Much


English: A Collection of Articles on Disease M...
English: A Collection of Articles on Disease Mongering in PLoS Medicine Español: Portada del monográfico publicado en Public Library of Science – Medicine sobre promoción de enfermedades (Photo credit: Wikipedia)

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PLOS Medicine. 

  • Ray Moynihan

As a matter of urgency, the potential for overdiagnosis and related overtreatment should be routinely considered for inclusion in the introduction and discussion sections of reports of studies of therapies, studies of diagnostic test accuracy, systematic reviews of those studies, clinical guidelines, and changes to disease definitions (Box 1). Second, there is a clear need for more research—both original studies and reviews of studies—into the nature and extent of overdiagnosis and related overtreatment within specific conditions—as, for example, has occurred with studies on the risks associated with mammography [5]. Third, the potential harms associated with new treatments and tests, or expanded disease definitions, demand much greater attention in primary studies and reviews.

Box 1. Summary of Suggestions for Improving the Evidence Base to Combat Overdiagnosis and Related Overtreatment

  1. Routine consideration of overdiagnosis and related overtreatment in the introduction and discussion sections of primary studies and systematic review articles about tests and treatments
  2. More condition-specific studies and reviews on the risk of overdiagnosis and related overtreatment—e.g., diagnosis of pulmonary embolism
  3. More rigorous routine evaluation of potential harms of treatments, tests, and changes to disease definitions
  4. In studies and reviews of studies of therapies, clearer stratification by baseline risk, to better identify treatment thresholds where benefits are likely to outweigh harms
  5. In studies and reviews of studies of test accuracy, more clarity about which target condition or spectrum of a disease is being considered, with a shift from a dichotomous “disease/no disease” frame to a “spectrum of disease severity” frame, and a linking of test accuracy to consequences for treatment and patient outcomes
  6. Panels that review and change disease definitions that are free of conflicts, and routinely consider evidence for potential harms as well as potential benefits of the changes they propose

For evaluation of treatments, more clarity is required about the specific definitions of diseases being treated in primary treatment studies and subsequent systematic reviews. As per the recommendations of Kent and colleagues [11], clearer stratification of groups at varying degrees of baseline risk or disease stage is needed, to better identify treatment thresholds at which the harms of treatment start to outweigh benefits. Sometimes this will require re-analysis of large (e.g., pooled individual participant) datasets, underscoring the need for access to raw data from trials.

For primary studies and reviews of studies of diagnostic test accuracy, there is a need to make explicit exactly which stages or spectrum of a target disease is being considered—also referred to as the “target condition” [14]. Where possible, it may be desirable to shift the paradigm from a dichotomous frame—disease presence versus absence—to thinking about a spectrum of disease severity. Moreover, when diagnostic studies show improved detection (or exclusion) of specific disease stages, researchers should try to link the consequences of such improved diagnostic accuracy to subsequent treatment decisions. Ideally, the consequences of such changed treatment decisions for patient outcomes might also be addressed [16]. Such elaborations to conventional diagnostic test accuracy studies would help identify at what diagnostic disease spectrum thresholds subsequent treatments will do more good than harm.

And, finally, the need to improve the process of disease definition—with awareness of the dangers of overdiagnosis and overtreatment—is being increasingly accepted, with international organisations, including the Guidelines International Network, currently looking to develop new guidance. While a detailed debate will ensue in coming years, we believe several key principles might underpin the reform of how disease definitions are changed: panel members should be free of financial and reputational conflicts of interest; strong evidence, ideally from randomised trial data, should demonstrate that the use of new criteria will meaningfully reduce mortality and/or morbidity; and potential benefits and potential harms of labelling and treatment using the new criteria should be explicitly investigated and reported.

Conclusions

We offer these suggestions as part of the wider scientific debate underway on how to safely and fairly wind back the harms of too much medicine [17]. We are hopeful that a heightened attention to the dangers of overdiagnosis and related overtreatment may lead to an enhanced evidence base on these topics. This, in turn, will help produce fairer, more rational, and less wasteful health care systems, built on a reformed process of disease definition that offers diagnostic labels and medical interventions only to those likely to benefit from them.

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Poca gripe en Africa


  • Un articulo en PLoS afirma que en este continente la gripe se confunde con otras enfermedades

El mundo.es no deja de asombrar, o quizas el mundo cientifico no deja de asombrar. Hace unos meses escribimos varias veces, que los pocos casos en Africa no se debe a que no haya gripe. Sino al hecho que los centros de vigilancia de la OMS son pocos. A esta altura ya parece poco relevante, visto que la pandemia ha alcanzado su pico en los paises que a la prensa puede importarle (que son los mismos que a la OMS y a las farmaceuticas). El trabajo de PLoS al que se hace mencion se puede acceder desde aqui.

Interesante tambien como el mismo periodico resaltó en estos dias que han muerto mas de 10 mil personas por la gripe, claro que en letras mas pequeñas aclara que por año mueren entre 250 y 500 mil personas en el mundo por esta causa. O sea que si estos numeros son ciertos, estamos hablando de un virus que seria 25 veces mas benigno que el que nos acompaño durante tantos años.

Aunque, y en personal opinion, creo que tendremos para largo con esto, ya que con tanto antiviral que se ha dado, y barbijos inutiles, el CDC reporto al menos 4 casos de mutaciones del virus, todas distintas entre ellas. Si la prensa no se entera, seguramente no habra mas pandemia. Por si acaso, la prensa se deleita con un terrorista en EE.UU. que nos hará recordar nuevamente que las guerras no pararon, aunque si la crisis financiera gracias, en parte, a la deuda que pagamos los que vivimos en esta parte del mundo.

Actualizado lunes 21/12/2009 09:07 (CET)
NURIA BAENA

MADRID.- También en cuestiones de gripe el continente africano vuelve a ser el gran olvidado. Esto es, al menos, lo que expone un ensayo publicado en la revista ‘PloS Medicine’ que sostiene que esta dolencia (en todas sus variantes) está circulando por África aunque prácticamente no se recibe información sobre el problema ni se le concede la atención necesaria.

Según este trabajo, mientras en áreas templadas la gripe despliega un patrón estacional con picos marcados en invierno (diciembre-marzo) esta enfermedad está presente todo el año en zonas tropicales y subtropicales como Brasil o Hong Kong.

La red de vigilancia de la gripe de la Organización Mundial de la Salud (WHO Flu Net en sus siglas en inglés), bien establecida en Europa o Norteamérica, proporciona de forma continua datos acerca del problema de la gripe y la propagación de sus tipos y subtipos virales. Además, la reciente amenaza de pandemia de gripe A ha provocado una monitorización activa similar en zonas del sudeste asiático y de Latinoamérica. Sin embargo, la prevalencia e incidencia de la gripe en la mayoría de los países tropicales, especialmente en África, son, en gran parte, desconocidas.

Los autores del escrito, María Yazdanbakhsh, del Departamento de Parasitología del Centro Médico de la Universidad de Leiden (Holanda) y Peter G. Kremsner, del Instituto de Medicina Tropical de la Universidad de Tübingen (Alemania), mantienen que los datos procedentes de estudios realizados de forma esporádica sugieren que la gripe es prevalente en África y tiene un impacto considerable en la morbilidad y mortalidad de este continente, pudiendo causar epidemias de forma regular. Sin embargo, la falta de vigilancia podría estar provocando que este problema esté siendo incorrectamente considerado como insignificante en el continente africano.

Como ejemplo de esta falta de atención los autores citan la actualización de la OMS en mayo de 2009 respecto a la gripe A (H1N1), que reflejaba contagios en muchos países, aunque ninguno en África. No obstante, dos informes de octubre 2009 confirmaban la existencia de casos en Sudáfrica y Kenia. Esto indica “que el virus estaba circulando en África, pero debido a la carencia de un sistema de vigilancia riguroso no fue notificado tan fácilmente”, argumentan los científicos.

En opinión de los investigadores una de las causas del problema radica en que la gripe no se distingue clínicamente de otras enfermedades infecciosas tropicales que cursan con fiebre. En este contexto destaca el papel de la malaria, a la que se atribuye la mayor parte de episodios febriles sufridos por niños. Sin embargo, tal y como denuncia el ensayo, pese a haberse observado una disminución de la incidencia de malaria en algunos países africanos, el viejo hábito de tratar la fiebre de los niños con medicamentos antimaláricos persiste y como en muchas enfermedades infecciosas la temperatura disminuye sin tratamiento la creencia errónea de que se está atajando correctamente la enfermedad continúa.

¿Una reacción distinta a la vacuna?

Además, los científicos denuncian que no exista información acerca de la eficacia de la vacuna de la gripe en África ni se haya estudiado si el sistema inmunológico de las gentes que viven en la zona tropical reaccionarían de forma similar a una inmunización que ha sido principalmente desarrollada para otras poblaciones.

Tal y como analizan los autores, las enfermedades parasitarias que devastan el continente africano y el consiguiente estado nutricional de la población podrían provocar un funcionamiento alterado del sistema inmunológico. Esta hipótesis habría sido corroborada por un reciente estudio que señaló la existencia de claras diferencias en la respuesta inmune a la vacuna en niños de entornos rurales africanos frente a otros que vivían en entornos semi-urbanos (la respuesta de los anticuerpos frente a las cepas de los virus A-H1N1 y B fue significativamente menor en los niños de un entorno rural).

“Una creciente conciencia de la presencia de enfermedades febriles comunes como la gripe es esencial para el tratamiento clínico de los pacientes. Para conseguir este fin, deben ser puestos en marcha sistemas de vigilancia apropiados en centros de investigación clínica ya existentes y bien establecidos que permitan entender la epidemiología de la gripe en África, lo que, por otra parte, puede ayudar en el proceso de toma de decisiones en lo que respecta a la vacunación de gripe en el continente y tendría un gran impacto en la salud en África”, concluyen los investigadores.

Association of Mild Anemia with Cognitive, Functional, Mood and Quality of Life Outcomes in the Elderly: The “Health and Anemia” Study


Asociacion de anemia leve con calidad de vida en ancianos. Estudio “Health and Anemia”.

Texto en PDF

Ugo Lucca1*, Mauro Tettamanti1, Paola Mosconi2, Giovanni Apolone3, Francesca Gandini1, Alessandro Nobili1, Maria Vittoria Tallone4, Paolo Detoma4, Adriano Giacomin5, Mario Clerico6, Patrizia Tempia6, Adriano Guala7, Gilberto Fasolo8, Emma Riva1

1 Laboratory of Geriatric Neuropsychiatry, Istituto di Ricerche Farmacologiche “Mario Negri”, Milano, Italy2 Laboratory for Medical Research & Consumer Involvement, Istituto di Ricerche Farmacologiche “Mario Negri”, Milano, Italy3 Laboratory of Translational and Outcome Research in Oncology, Istituto di Ricerche Farmacologiche “Mario Negri”, Milano, Italy4 Laboratory of Analysis, Ospedale degli Infermi, Biella, Italy5 County Cancer Registry, Local Health Authority, ASL12, Biella, Italy6 Department of Oncology, Ospedale degli Infermi, Biella, Italy7 Department of Medicine & Geriatrics, Ospedale degli Infermi, Biella, Italy8 Community Medicine, Local Health Authority, ASL12, Biella, Italy

Abstract

Background

In the elderly persons, hemoglobin concentrations slightly below the lower limit of normal are common, but scant evidence is available on their relationship with significant health indicators. The objective of the present study was to cross-sectionally investigate the association of mild grade anemia with cognitive, functional, mood, and quality of life (QoL) variables in community-dwelling elderly persons.

Methods

Among the 4,068 eligible individuals aged 65–84 years, all persons with mild anemia (n = 170) and a randomly selected sample of non-anemic controls (n = 547) were included in the study. Anemia was defined according to World Health Organization (WHO) criteria and mild grade anemia was defined as a hemoglobin concentration between 10.0 and 11.9 g/dL in women and between 10.0 and 12.9 g/dL in men. Cognition and functional status were assessed using measures of selective attention, episodic memory, cognitive flexibility and instrumental and basic activities of daily living. Mood and QoL were evaluated by means of the Geriatric Depression Scale-10, the Short-Form health survey (SF-12), and the Functional Assessment of Cancer Therapy-Anemia.

Results

In univariate analyses, mild anemic elderly persons had significantly worse results on almost all cognitive, functional, mood, and QoL measures. In multivariable logistic regressions, after adjustment for a large number of demographic and clinical confounders, mild anemia remained significantly associated with measures of selective attention and disease-specific QoL (all fully adjusted p<.046). When the lower limit of normal hemoglobin concentration according to WHO criteria was raised to define anemia (+0.2 g/dL), differences between mild anemic and non anemic elderly persons tended to increase on almost every variable.

Conclusions

Cross-sectionally, mild grade anemia was independently associated with worse selective attention performance and disease-specific QoL ratings.

Citation: Lucca U, Tettamanti M, Mosconi P, Apolone G, Gandini F, et al. (2008) Association of Mild Anemia with Cognitive, Functional, Mood and Quality of Life Outcomes in the Elderly: The “Health and Anemia” Study. PLoS ONE 3(4): e1920. doi:10.1371/journal.pone.0001920

Editor: Bernhard Baune, James Cook University, Australia

Received: October 3, 2007; Accepted: February 27, 2008; Published: April 2, 2008

Copyright: © 2008 Lucca et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Funding: This study was supported by a research grant from Amgen Italy. The sponsor of the study had no role in the conception and design of the study; collection, management, analysis, and interpretation of data; preparation and writing of the report or in the decision to submit the manuscript for publication.

Competing interests: The authors have declared that no competing interests exist.

* To whom correspondence should be addressed. E-mail: lucca@marionegri.it

Introduction

Mean blood concentrations of hemoglobin progressively decline with aging [1]. In the elderly persons, hemoglobin concentrations slightly below the lower limit of normal are common and are usually viewed by the physician as having no clinical significance or as a chronic disease marker with no independent effect on health. In recent years however, anemia has been increasingly shown to be associated with a number of health indicators. Fatigue and weakness are common consequences of anemia. Several cross-sectional studies in the elderly persons have reported the association of anemia with functional disability and poorer physical performance [2], decreased muscular strength [3], fall injury events at home [4], and increased frailty risk [5]. Two longitudinal studies suggested that elderly persons with anemia are at increased risk of physical decline and recurrent falls [6], [7]. Anemia can thus have a relevant effect on healthcare needs and, with the increasing rate of growth of the elderly population, become a significant healthcare burden [8], [9].

The hypoxic condition caused by anemia may not only negatively affect physical function but also the cognitive performance, mood, and quality of life (QoL) of the elderly person. Very few studies in community-dwelling elderly persons have explored the relationship of anemia with cognitive performance or mood, and none with QoL. Moreover, those few studies did not exclude moderate to severe anemic individuals from the analyses whose scores likely affected the results.

The main aim of the study was to investigate the association of mild grade anemia with significant health-related variables such as cognitive performance, functional status, mood, and QoL in a sample of community-dwelling elderly persons.

A Randomised, Blinded, Placebo-Controlled Trial in Dementia Patients Continuing or Stopping Neuroleptics (The DART-AD Trial)


Clive Ballard1*, Marisa Margallo Lana2, Megan Theodoulou3, Simon Douglas4, Rupert McShane5, Robin Jacoby3, Katja Kossakowski1, Ly-Mee Yu6, Edmund Juszczak6, on behalf of the Investigators DART AD

1 Wolfson Centre for Age-Related Diseases, King’s College London, London, United Kingdom, 2 Northgate Hospital, Morpeth, Northumberland, United Kingdom, 3 Department of Psychiatry, University of Oxford, The Warneford Hospital, Oxford, United Kingdom, 4 Department of Psychiatry, Newcastle University, Newcastle upon Tyne, United Kingdom, 5 Oxfordshire and Buckinghamshire Mental Health NHS Trust and University of Oxford, Department of Psychiatry, Fulbrook Centre, Oxford, United Kingdom, 6 Centre for Statistics in Medicine, University of Oxford, Oxford, United Kingdom

Background

There have been increasing concerns regarding the safety and efficacy of neuroleptics in people with dementia, but there are very few long-term trials to inform clinical practice. The aim of this study was to determine the impact of long-term treatment with neuroleptic agents upon global cognitive decline and neuropsychiatric symptoms in patients with Alzheimer disease.

Methods and Findings

Design: Randomised, blinded, placebo-controlled parallel two-group treatment discontinuation trial.

Setting: Oxfordshire, Newcastle and Gateshead, London and Edinburgh, United Kingdom.

Participants: Patients currently prescribed the neuroleptics thioridazine, chlorpromazine, haloperidol trifluoperazine or risperidone for behavioural or psychiatric disturbance in dementia for at least 3 mo.

Interventions: Continue neuroleptic treatment for 12 mo or switch to an identical placebo.

Outcome measures: Primary outcome was total Severe Impairment Battery (SIB) score. Neuropsychiatric symptoms were evaluated with the Neuropsychiatric Inventory (NPI).

Results: 165 patients were randomised (83 to continue treatment and 82 to placebo, i.e., discontinue treatment), of whom 128 (78%) commenced treatment (64 continue/64 placebo). Of those, 26 were lost to follow-up (13 per arm), resulting in 51 patients per arm analysed for the primary outcome. There was no significant difference between the continue treatment and placebo groups in the estimated mean change in SIB scores between baseline and 6 mo; estimated mean difference in deterioration (favouring placebo) −0.4 (95% confidence interval [CI] −6.4 to 5.5), adjusted for baseline value (p = 0.9). For neuropsychiatric symptoms, there was no significant difference between the continue treatment and placebo groups (n = 56 and 53, respectively) in the estimated mean change in NPI scores between baseline and 6 mo; estimated mean difference in deterioration (favouring continue treatment) −2.4 (95% CI −8.2 to 3.5), adjusted for baseline value (p = 0.4). Both results became more pronounced at 12 mo. There was some evidence to suggest that those patients with initial NPI ≥ 15 benefited on neuropsychiatric symptoms from continuing treatment.

Conclusions

For most patients with AD, withdrawal of neuroleptics had no overall detrimental effect on functional and cognitive status. Neuroleptics may have some value in the maintenance treatment of more severe neuropsychiatric symptoms, but this benefit must be weighed against the side effects of therapy.

Trial registration: Cochrane Central Registry of Controlled Trials/National Research Register (#ISRCTN33368770).

Funding: The DART-AD project was made possible by a grant from The Alzheimer’s Research Trust, Cambridge, UK (http://www.alzheimers-research.org.uk) to Profs Ballard and Jacoby and to RM. The peer review process undertaken by the funder did result in some modifications to the study design. The funder has no other role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing Interests: CB has received honoraria from Novartis, Pfizer, Shire, Lundbeck, Myriad, Janssen, Astra Zeneca, and Servier pharmaceutical companies and research grants from Novartis, Lundbeck, Astra-Zeneca, and Janssen pharmaceuticals. The remaining authors have declared that they have no competing interests.

Academic Editor: Carol Brayne, University of Cambridge, United Kingdom

Citation: Ballard C, Lana MM, Theodoulou M, Douglas S, McShane R, et al. (2008) A Randomised, Blinded, Placebo-Controlled Trial in Dementia Patients Continuing or Stopping Neuroleptics (The DART-AD Trial) . PLoS Med 5(4): e76 doi:10.1371/journal.pmed.0050076

Received: May 31, 2007; Accepted: February 15, 2008; Published: April 1, 2008

Copyright: © 2008 Ballard et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abbreviations: AD, Alzheimer disease; ANCOVA, analysis of covariance; BADLS, Bristol Activities of Daily Living Scale; CGIC, Clinician’s Global Impression of Change; CI, confidence interval; DMC, data-monitoring committee; EPS, extrapyramidal signs and symptoms; FAS, Verbal Fluency Task; FAST, Functional Assessment Staging; IQR, interquartile range; NPI, Neuropsychiatric Inventory; SD, standard deviation; SIB, Severe Impairment Battery; (S)MMSE, (Standardised) Mini Mental State Examination; STALD, Sheffield Test for Acquired Language Disorders; UPDRS, Unified Parkinson’s Disease Rating Scale

* To whom correspondence should be addressed. E-mail: clive.ballard@kcl.ac.uk

Editors’ Summary

Background

The number of people with dementia (currently 25 million worldwide) is expected to increase by 5 million each year. The risk of dementia, including Alzheimer disease, increases sharply with age: Alzheimer’s Disease International estimates that 1.4% of people 65–69 have dementia, whereas almost a full quarter of those over the age of 85 years are affected. Almost all older dementia patients will experience, along with the cognitive and functional decline typical of the illness, some neuropsychiatric symptoms. These symptoms can include agitation, aggression, and psychosis, and are often devastating for the older patient and his or her family and caregiver. Managing these symptoms is often a prime concern for health-care providers and families. Neuroleptics (sometimes called antipsychotics) are the class of drugs often used to manage or control neuropsychiatric problems, but there have been questions about their safety and appropriateness. Safety concerns involve risk of stroke, parkinsonism, sedation, edema, and chest infections but also include a worsening of cognitive decline with prolonged use of neuroleptics.

Why Was the Study Done?

Previous studies on the effectiveness and safety of neuroleptics in older people have been short term. Ballard and colleagues wanted to study over a longer period of time the impact of neuroleptic drugs on elderly patients with dementia. Specifically, they wanted to know if being on a neuroleptic was associated with more cognitive decline than coming off the drug. They also wanted to investigate whether discontinuing the drug exacerbated any neuropsychiatric symptoms, Parkinson disease-like symptoms, or other functional, language, and cognition difficulties frequently associated with dementia.

What Did the Researchers Do and Find?

The researchers recruited older patients with Alzheimer disease from across England who had been on neuroleptics for at least three months. They randomised patients to one of two groups: the first group continued taking the same neuroleptic at the same dosage level while the second group was switched to an identical-looking placebo. The researchers assessed the patients’ cognitive status and neuropsychiatric symptoms upon their entry into the study. Six and 12 months later the researchers assessed any cognitive decline and the level of neuropsychiatric and other problems that patients were experiencing.

At both 6 and 12 months, the researchers found that there were no differences between the two groups (continued treatment and placebo) in terms of cognitive decline. The placebo group may have had less cognitive decline, but this was not statistically significant. They also found no overall differences between the two groups in the change in the number of neuropsychiatric symptoms over these time periods. Patients with severe neuropsychiatric problems at the outset of the trial did better on continued neuroleptic therapy, but this advantage was not statistically significant. There was a significant decline on the verbal fluency language tests among the patients who continued on their neuroleptic.

What Do these Findings Mean?

The researchers report perhaps the first trial of this duration on continued versus withdrawn neuroleptic treatment among older dementia patients. The findings do not indicate any benefit of continuing neuroleptic therapies in older patients on either cognitive or neuropsychiatric outcomes. The researchers conclude that neuroleptics, with their known safety issues, should not be used as first-line treatment to manage problems such as agitation or aggression. For older dementia patients whose neuropsychiatric symptoms are not remedied by nonpharmaceutical treatments, the researchers advise caution. More studies are urgently needed to find better solutions to help older patients with dementia who have agitation, aggression, and psychosis.

Additional Information

Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0050076.

Articulo completo en PLoS

Estimating Incidence from Prevalence in Generalised HIV Epidemics: Methods and Validation


Fuente: PLoS Medicine

Timothy B. Hallett1*, Basia Zaba2,3, Jim Todd4, Ben Lopman1, Wambura Mwita3, Sam Biraro4, Simon Gregson1,5, J. Ties Boerma6, on behalf of the ALPHA Network

1 Imperial College London, London, United Kingdom, 2 London School of Hygiene and Tropical Medicine, London, United Kingdom, 3 National Institute for Medical Research, Mwanza, Tanzania, 4 Medical Research Council/Uganda Virus Research Institute, Uganda Research Unit on AIDS, Entebbe, Uganda, 5 Biomedical Research and Training Institute, Harare, Zimbabwe, 6 World Health Organization, Geneva, Switzerland

Background

HIV surveillance of generalised epidemics in Africa primarily relies on prevalence at antenatal clinics, but estimates of incidence in the general population would be more useful. Repeated cross-sectional measures of HIV prevalence are now becoming available for general populations in many countries, and we aim to develop and validate methods that use these data to estimate HIV incidence.

Methods and Findings

Two methods were developed that decompose observed changes in prevalence between two serosurveys into the contributions of new infections and mortality. Method 1 uses cohort mortality rates, and method 2 uses information on survival after infection. The performance of these two methods was assessed using simulated data from a mathematical model and actual data from three community-based cohort studies in Africa. Comparison with simulated data indicated that these methods can accurately estimates incidence rates and changes in incidence in a variety of epidemic conditions. Method 1 is simple to implement but relies on locally appropriate mortality data, whilst method 2 can make use of the same survival distribution in a wide range of scenarios. The estimates from both methods are within the 95% confidence intervals of almost all actual measurements of HIV incidence in adults and young people, and the patterns of incidence over age are correctly captured.

Conclusions

It is possible to estimate incidence from cross-sectional prevalence data with sufficient accuracy to monitor the HIV epidemic. Although these methods will theoretically work in any context, we have able to test them only in southern and eastern Africa, where HIV epidemics are mature and generalised. The choice of method will depend on the local availability of HIV mortality data.

Funding: TBH, SG, BL, and WM thank the Wellcome Trust; BZ was supported by a grant from Global Fund to Fight AIDS, Tuberculosis and Malaria; JT and SB were supported by UK MRC. The funders had no role in the study design, analysis, and preparation of the manuscript or the decision to publish.

Competing Interests: The authors have declared that no competing interests exist.

Academic Editor: Peter Ghys, Joint United Nations Programme on HIV/AIDS, Switzerland

Citation: Hallett TB, Zaba B, Todd J, Lopman B, Mwita W, et al. (2008) Estimating Incidence from Prevalence in Generalised HIV Epidemics: Methods and Validation. PLoS Med 5(4): e80 doi:10.1371/journal.pmed.0050080

Received: May 21, 2007; Accepted: February 15, 2008; Published: April 8, 2008

Copyright: © 2008 Hallett et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abbreviations: ART, antiretroviral therapy; DHS, Demographic and Health Surveys; PYAR, person-years at risk

* To whom correspondence should be addressed. E-mail: timothy.hallett@imperial.ac.uk

It's the Network, Stupid: Why Everything in Medicine Is Connected


The PLoS Medicine Editors

 

Citation: The PLoS Medicine Editors (2008) It’s the Network, Stupid: Why Everything in Medicine Is Connected. PLoS Med 5(3): e71 doi:10.1371/journal.pmed.0050071

Published: March 25, 2008

Copyright: © 2008 The PLoS Medicine Editors. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

The PLoS Medicine Editors are Virginia Barbour, Jocalyn Clark, Larry Peiperl, Emma Veitch, and Gavin Yamey.

E-mail: medicine_editors@plos.org

One need look no further than Facebook to appreciate the significance and power of social networking. (Even PLoS has its own thriving Facebook community, which you can join at http://www.facebook.com/group.php?gid=2401713690.) But social networking is about more than just friends reunited; it’s a framework for understanding even the most basic of biological processes. Two papers in this month’s PLoS Medicine illustrate the insight that network theory brings to basic science, and the valuable interdisciplinarity that social network analysis can inspire.

Once the domain of social scientists—who have used social network analysis to study such diverse phenomena as kinship ties, organizational behavior, rumor spreading, and global air traffic—network theory has now entered the purview of health scientists. Network theory is concerned with mapping the links between entities, and social network analysis is the application of that theory to the social sciences. Searching for more social and environmental explanations for the obesity epidemic in America, for example, Christakis and Fowler [1] showed that obesity can spread from person to person, and that this spread depends on the nature of social ties: a person’s chance of becoming obese increased by 171% if he or she had a mutual friend who had become obese (even if they lived far away). Their risk increased by 40% if it was their sibling or spouse who became obese. Christakis and Fowler concluded that the social network is a crucial component—perhaps more so than genetics—in explaining obesity, a problem normally thought of as solely biological and behavioral.

Similarly, a major advance in stemming an outbreak of early syphilis in San Francisco was accomplished through understanding social networks. Klausner and colleagues found that the outbreak was tied to a network of sexual contacts who were meeting through Internet chat rooms [2]. The public health department was then able to initiate an electronic awareness and partner notification campaign using the same Web-based sexual network; 42% of named partners were identified and evaluated.

The observation that social relations and interdependency play a part in health is not surprising. But what network theory teaches us is that connections, even within the most complex systems, are not random (that is, they are not unpredictable). Instead, networks behave in ways that we can theorize, model, and predict.

In network analysis, the network becomes more important than the individual entity.

In its simplest form, network analysis can map ties between entities (whether elephants, humans, or genes). The same principles that allowed researchers to characterize the role of matriarchs in the social organization of the endangered African elephant species [3] also illuminated the collective dynamics fueling individual donations to the 2004 tsunami relief fund [4], and provided the techniques to model the gene network that controls T cell activation in humans [5].

But beyond identifying simple links, network analysis also helps to illustrate the structure of those ties—the nature of the relationships, the rules that govern them, and how we might predict various relationships or outcomes under various conditions. The network becomes more important than the individual entity. In this month’s PLoS Medicine paper by Lewis and colleagues [6], for example, investigating the transmission network (and its episodic nature) provides insights into HIV prevention that would not emerge from studying individual behavior.

Lewis and colleagues conducted their study because of a seeming contradiction. Genetic studies of HIV transmission networks have not corresponded well with the social contact networks revealed through interview data. The authors’ use of phylodynamics—a mix of genetics, epidemiology, and evolutionary biology—allowed a more sophisticated look. By examining and dating the genetic sequences of men attending an HIV clinic in central London, Lewis and colleagues found large clusters comprising ten or more individuals, a quarter of whom had transmitted the virus within several months of being infected. This information is valuable for understanding HIV transmission dynamics, not least because rapid transmission within clusters may result in the spread of drug-resistant strains.

Network analysis is also used in Mossong and colleagues’ study on the dynamics of influenza transmission, reported in this month’s PLoS Medicine [7]. Using paper diaries completed by over 7,000 Europeans documenting their daily physical and nonphysical contacts, Mossong and colleagues found varied mixing patterns, duration of contacts, and types of contacts. This information allowed the researchers to produce a mathematical model that suggests that 5–19-year-olds will suffer the highest burden of respiratory infection during any initial spread. Mossong and colleagues’ work illustrates how the patterning of social contacts—between and within groups, and in different social settings—and not just contact rates can influence how new emerging diseases spread. Physical exposure to an infectious agent, the authors conclude, is thus best modeled by taking into account the social network of close contacts and its patterning.

The physicist Albert-László Barabási argues in his book, Linked, that “there is a path between any two neurons in our brain, between any two companies in the world, between any two chemicals in our body. Nothing is excluded from this highly interconnected web of life” [8]. As health professionals, we might find network analysis useful in helping us describe and explain the connections in matters of health, whether they be at the cellular or population level. But we will also want to act.

Indeed, the greatest value in understanding networks lies in what they can tell us about taking action. The same insights generated from social network analysis about the spread of disease hold the key to developing effective interventions to halt that spread. The nature of social networks that drive transmission of syphilis and other sexually transmitted infections, for example, demonstrate that the Internet is an appropriate place to deliver safe sex education [9–11]. Exploiting the peer influences that feed the social network of obesity (or smoking, or substance abuse) could be a meaningful way to spread healthy behaviors. Even in diseases that appear intractable to our campaigns and controls, we might best inform policy makers and health promoters by considering: It’s the network, stupid.

References

  1. Christakis NA, Fowler JH (2007) The spread of obesity in a large social network over 32 years. N Engl J Med 357: 370–379. Find this article online
  2. Klausner JD, Wolf W, Fischer-Ponce L, Zolt I, Katz MH (2000) Tracing a syphilis outbreak through cyberspace. JAMA 284: 447–449. Find this article online
  3. McComb K, Moss C, Durant SM, Baker L, Sayialel S (2001) Matriarchs as repositories of social knowledge in African elephants. Science 292: 491–494. Find this article online
  4. Schweitzer F, Mach R (2008) The epidemics of donations: Logistic growth and power-laws. PLoS ONE 3: e1458. doi:10.1371/journal.pone.0001458.
  5. Palacios R, Goni J, Martinez-Forero I, Iranzo J, Sepulcre J, et al. (2007) A network analysis of the human t-cell activation gene network identifies jagged1 as a therapeutic target for autoimmune diseases. PLoS ONE 2: e1222. doi:10.1371/journal.pone.0001222.
  6. Lewis F, Hughes GJ, Rambaut A, Pozniak A, Leigh Brown AJ (2008) Episodic sexual transmission of HIV revealed by molecular phylodynamics. PLoS Med 5: e50. doi:10.1371/journal.pmed.0050050. Find this article online
  7. Mossong J, Hens N, Jit M, Beutels P, Auranen K, et al. (2008) Social contacts and mixing patterns relevant to the spread of infectious diseases. PLoS Med 5: e74. doi:10.1371/journal.pmed.0050074. Find this article online
  8. Barabási A-L (2003) Linked: How everything is connected to everything else and what it means New York: Plume. 304 p.
  9. Benotsch EG, Kalichman S, Cage M (2002) Men who have met sex partners via the Internet: Prevalence, predictors, and implications for HIV prevention. Arch Sex Behav 31: 177–183. Find this article online
  10. Bolding G, Davis M, Hart G, Sherr L, Elford J (2005) Gay men who look for sex on the Internet: Is there more HIV/STI risk with online partners. AIDS 19: 961–968. Find this article online
  11. Curioso WH, Blas MM, Nodell B, Alva IE, Kurth AE (2007) Opportunities for providing web-based interventions to prevent sexually transmitted infections in Peru. PLoS Med 4: e11. doi:10.1371/journal.pmed.0040011. Find this article online

It’s the Network, Stupid: Why Everything in Medicine Is Connected


The PLoS Medicine Editors

 

Citation: The PLoS Medicine Editors (2008) It’s the Network, Stupid: Why Everything in Medicine Is Connected. PLoS Med 5(3): e71 doi:10.1371/journal.pmed.0050071

Published: March 25, 2008

Copyright: © 2008 The PLoS Medicine Editors. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

The PLoS Medicine Editors are Virginia Barbour, Jocalyn Clark, Larry Peiperl, Emma Veitch, and Gavin Yamey.

E-mail: medicine_editors@plos.org

One need look no further than Facebook to appreciate the significance and power of social networking. (Even PLoS has its own thriving Facebook community, which you can join at http://www.facebook.com/group.php?gid=2401713690.) But social networking is about more than just friends reunited; it’s a framework for understanding even the most basic of biological processes. Two papers in this month’s PLoS Medicine illustrate the insight that network theory brings to basic science, and the valuable interdisciplinarity that social network analysis can inspire.

Once the domain of social scientists—who have used social network analysis to study such diverse phenomena as kinship ties, organizational behavior, rumor spreading, and global air traffic—network theory has now entered the purview of health scientists. Network theory is concerned with mapping the links between entities, and social network analysis is the application of that theory to the social sciences. Searching for more social and environmental explanations for the obesity epidemic in America, for example, Christakis and Fowler [1] showed that obesity can spread from person to person, and that this spread depends on the nature of social ties: a person’s chance of becoming obese increased by 171% if he or she had a mutual friend who had become obese (even if they lived far away). Their risk increased by 40% if it was their sibling or spouse who became obese. Christakis and Fowler concluded that the social network is a crucial component—perhaps more so than genetics—in explaining obesity, a problem normally thought of as solely biological and behavioral.

Similarly, a major advance in stemming an outbreak of early syphilis in San Francisco was accomplished through understanding social networks. Klausner and colleagues found that the outbreak was tied to a network of sexual contacts who were meeting through Internet chat rooms [2]. The public health department was then able to initiate an electronic awareness and partner notification campaign using the same Web-based sexual network; 42% of named partners were identified and evaluated.

The observation that social relations and interdependency play a part in health is not surprising. But what network theory teaches us is that connections, even within the most complex systems, are not random (that is, they are not unpredictable). Instead, networks behave in ways that we can theorize, model, and predict.

In network analysis, the network becomes more important than the individual entity.

In its simplest form, network analysis can map ties between entities (whether elephants, humans, or genes). The same principles that allowed researchers to characterize the role of matriarchs in the social organization of the endangered African elephant species [3] also illuminated the collective dynamics fueling individual donations to the 2004 tsunami relief fund [4], and provided the techniques to model the gene network that controls T cell activation in humans [5].

But beyond identifying simple links, network analysis also helps to illustrate the structure of those ties—the nature of the relationships, the rules that govern them, and how we might predict various relationships or outcomes under various conditions. The network becomes more important than the individual entity. In this month’s PLoS Medicine paper by Lewis and colleagues [6], for example, investigating the transmission network (and its episodic nature) provides insights into HIV prevention that would not emerge from studying individual behavior.

Lewis and colleagues conducted their study because of a seeming contradiction. Genetic studies of HIV transmission networks have not corresponded well with the social contact networks revealed through interview data. The authors’ use of phylodynamics—a mix of genetics, epidemiology, and evolutionary biology—allowed a more sophisticated look. By examining and dating the genetic sequences of men attending an HIV clinic in central London, Lewis and colleagues found large clusters comprising ten or more individuals, a quarter of whom had transmitted the virus within several months of being infected. This information is valuable for understanding HIV transmission dynamics, not least because rapid transmission within clusters may result in the spread of drug-resistant strains.

Network analysis is also used in Mossong and colleagues’ study on the dynamics of influenza transmission, reported in this month’s PLoS Medicine [7]. Using paper diaries completed by over 7,000 Europeans documenting their daily physical and nonphysical contacts, Mossong and colleagues found varied mixing patterns, duration of contacts, and types of contacts. This information allowed the researchers to produce a mathematical model that suggests that 5–19-year-olds will suffer the highest burden of respiratory infection during any initial spread. Mossong and colleagues’ work illustrates how the patterning of social contacts—between and within groups, and in different social settings—and not just contact rates can influence how new emerging diseases spread. Physical exposure to an infectious agent, the authors conclude, is thus best modeled by taking into account the social network of close contacts and its patterning.

The physicist Albert-László Barabási argues in his book, Linked, that “there is a path between any two neurons in our brain, between any two companies in the world, between any two chemicals in our body. Nothing is excluded from this highly interconnected web of life” [8]. As health professionals, we might find network analysis useful in helping us describe and explain the connections in matters of health, whether they be at the cellular or population level. But we will also want to act.

Indeed, the greatest value in understanding networks lies in what they can tell us about taking action. The same insights generated from social network analysis about the spread of disease hold the key to developing effective interventions to halt that spread. The nature of social networks that drive transmission of syphilis and other sexually transmitted infections, for example, demonstrate that the Internet is an appropriate place to deliver safe sex education [9–11]. Exploiting the peer influences that feed the social network of obesity (or smoking, or substance abuse) could be a meaningful way to spread healthy behaviors. Even in diseases that appear intractable to our campaigns and controls, we might best inform policy makers and health promoters by considering: It’s the network, stupid.

References

  1. Christakis NA, Fowler JH (2007) The spread of obesity in a large social network over 32 years. N Engl J Med 357: 370–379. Find this article online
  2. Klausner JD, Wolf W, Fischer-Ponce L, Zolt I, Katz MH (2000) Tracing a syphilis outbreak through cyberspace. JAMA 284: 447–449. Find this article online
  3. McComb K, Moss C, Durant SM, Baker L, Sayialel S (2001) Matriarchs as repositories of social knowledge in African elephants. Science 292: 491–494. Find this article online
  4. Schweitzer F, Mach R (2008) The epidemics of donations: Logistic growth and power-laws. PLoS ONE 3: e1458. doi:10.1371/journal.pone.0001458.
  5. Palacios R, Goni J, Martinez-Forero I, Iranzo J, Sepulcre J, et al. (2007) A network analysis of the human t-cell activation gene network identifies jagged1 as a therapeutic target for autoimmune diseases. PLoS ONE 2: e1222. doi:10.1371/journal.pone.0001222.
  6. Lewis F, Hughes GJ, Rambaut A, Pozniak A, Leigh Brown AJ (2008) Episodic sexual transmission of HIV revealed by molecular phylodynamics. PLoS Med 5: e50. doi:10.1371/journal.pmed.0050050. Find this article online
  7. Mossong J, Hens N, Jit M, Beutels P, Auranen K, et al. (2008) Social contacts and mixing patterns relevant to the spread of infectious diseases. PLoS Med 5: e74. doi:10.1371/journal.pmed.0050074. Find this article online
  8. Barabási A-L (2003) Linked: How everything is connected to everything else and what it means New York: Plume. 304 p.
  9. Benotsch EG, Kalichman S, Cage M (2002) Men who have met sex partners via the Internet: Prevalence, predictors, and implications for HIV prevention. Arch Sex Behav 31: 177–183. Find this article online
  10. Bolding G, Davis M, Hart G, Sherr L, Elford J (2005) Gay men who look for sex on the Internet: Is there more HIV/STI risk with online partners. AIDS 19: 961–968. Find this article online
  11. Curioso WH, Blas MM, Nodell B, Alva IE, Kurth AE (2007) Opportunities for providing web-based interventions to prevent sexually transmitted infections in Peru. PLoS Med 4: e11. doi:10.1371/journal.pmed.0040011. Find this article online

Cochrane Child Health Field


The Cochrane Child Health Field, whose tag line is “promoting best evidence in child health,” has announced that a trials register will shortly be available.

The register will be a searchable database of over 30,000 pediatric RCTs and CCTs published from 1948 onwards.

One valuable aspect of the register, says Denise Thomson, Cochrane Child Health Field Administrator, is that “it will facilitate study of the development of paediatric research over the past sixty-odd years.”

With this in mind, Denise has put out a call for nominations for “classic” RCTs in paediatrics.

The criteria for being a “classic,” she says, are innovation in design characteristics, the consequence of their results on medical practice, or the fact that, in their absence, patients would have been denied access to beneficial treatments or would have been exposed to deleterious or ineffective approaches to treatment.

If you’ve got ideas for a classic, send her your nominations by Friday, October 12 at denise.thomson@ualberta.ca.

Meanwhile, if you are ready to report the results of a recently completed paediatric trial, please do submit the trial report to PLoS. Along with the report (which, if it is an RCT, should follow the CONSORT reporting guidelines), please also submit the original protocol. All of the PLoS journals support the International Committee of Medical Journal Editors (ICMJE) statement on trial registration.