Conflict of interest (COI) of clinical practice guideline (CPG) sponsors and authors is an important potential source of bias in CPG development. The objectives of this study were to describe the COI policies for organizations currently producing a significant number of CPGs, and to determine if these policies meet 2011 Institute of Medicine (IOM) standards.We identified organizations with five or more guidelines listed in the National Guideline Clearinghouse between January 1, 2009 and November 5, 2010. We obtained the COI policy for each organization from publicly accessible sources, most often the organization's website, and compared those polices to IOM standards related to COI. 37 organizations fulfilled our inclusion criteria, of which 17 (46%) had a COI policy directly related to CPGs. These COI policies varied widely with respect to types of COI addressed, from whom disclosures were collected, monetary thresholds for disclosure, approaches to management, and updating requirements. Not one organization's policy adhered to all seven of the IOM standards that were examined, and nine organizations did not meet a single one of the standards.COI policies among organizations producing a large number of CPGs currently do not measure up to IOM standards related to COI disclosure and management. CPG developers need to make significant improvements in these policies and their implementation in order to optimize the quality and credibility of their guidelines. Clinical practice guidelines (CPGs) are “statements that include recommendations intended to optimize patient care that are informed by a systematic review of evidence and an assessment of the benefits and harms of alternative care options,” according to the Institute of Medicine (IOM) Conflict of interest (COI) is an important potential source of bias in the development of CPGs. A COI is a set of conditions in which professional judgment concerning a primary interest , is unduly influenced by a secondary interest Recent IOM reports highlight the importance of COI in healthcare http://www.guideline.gov) that were published between January 1, 2009 and the date of our search . We selected this cohort in order to examine the policies of organizations that have the potential for a major effect on physician behavior and patient outcomes. The NGC, funded by the Agency for Healthcare Research and Quality (AHRQ), was established in January of 1999, “to provide physicians and other health professionals, health care providers, health plans, integrated delivery systems, purchasers, and others an accessible mechanism for obtaining objective, detailed information on clinical practice guidelines and to further their dissemination, implementation, and use” We identified organizations that had five or more guidelines listed in the National Guideline Clearinghouse (NGC)  independently searched for each organization's COI policy on the organization's website and through a general internet search. Only policies that were specific to CPG development were examined further: the policy was required to either include a statement specifically regarding CPGs or be included in a CPG development handbook, and at a minimum address COI for CPG panel members. Policies that covered a variety of organizational activities were not examined further because such general policies did not address adequately address the issues of COI relevant to CPG development. If the guideline developer was US-based, the authors also determined if the CPG organization was signed onto the Council of Medical Specialty Societies' (CMSS) Code for Interactions with Companies, by examining the CMSS website We did not include information contained within the CPG or in the summary provided by the NGC as the former was invariably insufficient to assess the organization's policy and the latter was information provided by the organization to the NGC after the guideline was completed. We did not contact organizations for additional information, nor did we try to obtain information from organizations with protected websites for members only, because we wanted to include only information that was publicly available to users of CPGs, and our past experiences trying to obtain unpublished COI policies suggested that such an approach was not likely to be productive.One author abstracted information on each organization's COI policy into a pre-specified template in Excel®, and those data were checked by a second author. The data abstracted from each policy included when disclosures were obtained, from whom, over what time period, the types of COI , and how disclosures were managed. Data were synthesized across guidelines using descriptive statistics and a qualitative synthesis. We used a logistic regression model to explore the association between whether an organization had a CPG-specific COI policy and pre-specified predictors included type of organization, the number of CPGs produced between 2009 and our search date, and whether or not the organization was based in the US.We compared the COI policy of each guideline organization to the COI-related standards in the 2011 IOM report  [1] for Three authors  independently made a determination as to whether each organization's policy met each IOM standard and then consensus was achieved through discussion. Inter-rater reliability was assessed by using Kappa statistics for each standard and overall for the seven standards combined.We then explored pre-specified predictors for organizations fulfilling these IOM standards, using the same variables that we used in our examination of whether each organization had a COI policy or not. The association between meeting each standard or at least one standard and the predictors was assessed using a logistic regression model. The association between meeting any IOM standard and the predictors was assessed using a logistic generalized estimating equation (GEE) model, accounting for correlation among multiple standards within each organization. The association between the proportion of standards met in each organization and the predictors was explored using a linear regression model.596 CPGs were published in NGC between 2009 and the date of our search in 2010, by 118 organizations listing at least one guideline. Of these organizations, 37 fulfilled our inclusion criteria, publishing 392 guidelines  . The majSeventeen of the 37 organizations (45.9%) had a COI policy that was publicly accessible and applicable to the development of CPGs . The remTwelve COI was variably defined across the 17 policies , of whicThe types of non-financial COI described in the policies also varied . Eleven All organizations required disclosure from all guideline development group members . The ediDisclosures are collected at various time points across the organizations,  most comSeven organizations (41.2%) limited the disclosure to only those that were relevant to the content of the CPG  [25], [2Eleven organizations (64.7% of 17) delineated strategies to manage COI after disclosure, with considerable variation in these approaches . AdvisorNone of the 17 organizations with a CPG-specific COI policy met all seven IOM standards specific to COI . The polThe agreement among the three assessors for all seven IOM standards across all 17 policies was 94.1% . Agreement for specific standards ranged from 76.5% (standard 4a) to 100.0% . The overall Kappa statistic for inter-rater reliability among the three reviewers was 0.88.Fewer than half of organizations that have recently listed a large number of guidelines in the NGC have a COI policy directly related to CPGs. Of organizations with such policies, these vary widely with respect to types of COI addressed, from whom disclosures are collected, monetary thresholds for disclosure, approaches to management, and updating requirements. Not one organization's policy adhered to all seven of the IOM 2011 standards applicable to COI policies for CPGs, and approximately half of these organizations do not adhere to a single one of these standards.There is a need for extensive improvements in COI policies for organizations producing CPGs. Every developer must have a COI policy specific to CPGs: a general COI policy for the organization or a policy that relates to research subjects, for example, is not adequate to address the issues of secondary interests relevant to guideline development. Guidelines involve multiple groups of individuals and processes, and the COI of all of these must be disclosed: authors of the systematic review, the guideline panel members, and other individuals involved in the formulation and approval processes. COI policies for CPGs must also address management of the disclosures, starting with the requirement that the guideline panel chair and co-chair have no relevant COI.There are important implications of our findings for users of CPGs. Given the evidence that financial relationships of researchers are associated with study findings Nonfinancial COI may be an important source of bias, and two-thirds of organizations make some mention of this type of COI in their policies. Definitions are variable, however, and often vague and difficult to interpret, potentially leading to inconsistent and incomplete reporting. The current knowledge base on the impact of nonfinancial COI on decision making is sparse, so that the development of evidence-based guidance on the disclosure and management of nonfinancial COI is difficult at the present time.The IOM standards related to COI do not address all of the important issues for CPG developers and users. In particular, these standards do not address accessibility of COI policies, the relevance of secondary interests to the primary interest, and the optimal presentation of disclosures. We often encountered a great deal of difficulty locating COI policies: these policies should be readily accessible from the guideline organization's website. Policies on disclosures should address both relevance and an appropriate level of detail. Inadequate guidance within COI policies on these issues may reflect lack of evidence on both the relationship between specific types of conflicts and risk of bias, and what constitutes optimal disclosures for the reader. IOM standards also do not address accountability for accurate disclosures and adherence to the policy within the organization. In other words, adherence to these seven IOM standards does not ensure an optimal COI policy.There are limitations to our approach. Most importantly, we did not assess if and how these policies were applied during CPG development and publication. Nor did we examine the impact of each organization's policy on their processes, disclosures, recommendations, and the use and interpretation of the guidelines by healthcare providers. Our descriptive work provides the basis for these important next steps in evaluating the nature and effect of COI policies in CPG development.It is possible that our summary of these organizations' policies is not up to date. Given the current attention to COI policies by biomedical journals We did not contact organizations for additional, unpublished information, nor did we try to obtain information from organizations with protected websites. We felt that if the guideline was in the public domain the COI policy should be there also, given the presumed importance of transparency in COI processes and disclosures. We also encountered challenges in determining if an organization's COI policy was specific to CPGs. Two independent reviewers made this assessment and then came to consensus, but it is possible that some of the organizations that we assessed as not having a CPG-specific policy would consider themselves to have such a policy. We would counter that these policies need to be more transparent and to address the processes and individuals involved in CPGs specifically.The applicability of our findings to other organizations producing CPGs may be limited. The COI policies of organizations producing a small number of CPGs (less than 5) may differ from the policies that we examined. In addition, we focused only on CPGs published in English and those listed in NGC: the policies of other organizations may differ from our findings. The IOM standards were developed by a US-based group of experts, and thus encompass the American perspective on guideline topics, methodology, available resources, and the standards target U.S. patient populations and health care providers. The evidence base examined in the IOM report encompasses studies from a variety of international settings, and thus the IOM standards are likely applicable to guideline development in the Western world.The IOM standards The IOM standards were not intended to be a quality assessment tool, thus implementing them as such was problematic. Standard 2.1 addresses both financial and nonfinancial COI, thus the two types of COI are not distinguished. Many of the standards are too vague to implement as quality assessment criteria: for example, standard 2.4a .COI policies among organizations producing a large number of CPGs currently do not measure up to IOM standards. Policy-makers, guideline funders, sponsors, and developers, as well as users need to address and demand improvements. Patients and populations need trustworthy CPGs, and the accurate disclosure and subsequent management of COI is essential to achieve that goal.


In the history of public health, HIV/AIDS is unique; it has widespread and long-lasting demographic, social, economic and political impacts. The global response has been unprecedented. AIDS exceptionalism - the idea that the disease requires a response above and beyond "normal" health interventions - began as a Western response to the originally terrifying and lethal nature of the virus. More recently, AIDS exceptionalism came to refer to the disease-specific global response and the resources dedicated to addressing the epidemic. There has been a backlash against this exceptionalism, with critics claiming that HIV/AIDS receives a disproportionate amount of international aid and health funding.This paper situations this debate in historical perspective. By reviewing histories of the disease, policy developments and funding patterns, it charts how the meaning of AIDS exceptionalism has shifted over three decades. It argues that while the connotation of the term has changed, the epidemic has maintained its course, and therefore some of the justifications for exceptionalism remain. In the 30 years since it was first recognized, HIV has spread globally. An estimated 25 million people have died, and about 33 million people are currently living with HIV/AIDS. The epidemic is not homogenous; the global picture is diverse. In wealthy countries, most of Latin America, Asia, north Africa and the Middle East, infections are concentrated in particular geographical locations and among specific population groups. These are often socially and politically marginalized populations, including injecting drug users, men who have sex with men, and commercial sex workers.Generalized epidemics are found in eastern, central and southern Africa, where between 5% and 30% of adults are infected. However, even here, specific groups, such as women, remain disproportionately at risk. The development of HIV "risk environments"  has beenIn the history of public health, HIV/AIDS is unique in terms of how it is spread and attacks the body and because of its widespread and long-lasting demographic, social, economic and political impacts. HIV/AIDS is a long-wave event: an epidemic that, where it is most prevalent, will have consequences that will be felt for generations . Just asAIDS exceptionalism began as a Western response to the originally terrifying and lethal nature of the virus, which disproportionately affected specific groups. The first activists argued that HIV/AIDS required an exceptional response in order to protect the rights of those infected, to generate resources to assist them and to curb a then mysterious epidemic. More recently, AIDS exceptionalism came to refer to the disease-specific global response. This international response was unprecedented, as the commitment of resources exceeded any other health cause.International organizations, such as the Joint United Nations Programme on HIV/AIDS (UNAIDS), the Global Fund to Fight AIDS, Tuberculosis and Malaria  and the US President's Emergency Plan for AIDS Relief (PEPFAR), were formed to specifically address HIV/AIDS. In the past few years, there has been a backlash against this exceptionalism, with critics claiming that HIV/AIDS receives a disproportionate amount of international aid and health funding, and that this has implications for other health issues.This paper reviews the histories of the disease, policy developments and funding patterns to chart how the meaning of AIDS exceptionalism has shifted over three decades. It argues that, while the connotation of the term has changed, the epidemic has maintained its course, and therefore some of the justifications for exceptionalism remain.In the early 1980s, when previously healthy, mostly homosexual young men began dying, the unknown cause and rising numbers of deaths combined with homophobia to generate a response of blame and fear. Extreme religious right-wing advocates spoke of divine punishment for "sinful" lifestyles . The disAs haemophiliacs, women and children in the West increasingly presented with the same symptoms, it became clear that the cause of illness was not related to sexual orientation. In 1983, the human immunodeficiency virus (HIV) was identified as the cause of AIDS. The realization that HIV could spread to the general public, and that it was linked to the life-giving and pleasurable acts of sexual intercourse, resulted in increased hysteria. Governments, the media and scientists sought a quick response: "A sense of urgency defined the problem, and the public information materials developed in this period often emphasized danger at the expense of clear information about prevention measures" . Even asThe gay rights movement, building on the momentum it had gained in the preceding decades, began campaigning for HIV/AIDS to be viewed as a human rights issue. Advocates argued that infection was not the only risk; if found positive, individuals also faced harmful discrimination . In thisAvoiding compulsory measures such as isolation and quarantine, which were so much a part of the public health tradition, was all the more crucial, since the people with increased risk -- gay and bisexual men, drug users, and their sexual partners -- were already socially vulnerable ... Policies and practices that appeared to threaten such persons could only drive the epidemic underground and make it more difficult to work with the populations within which HIV was spreading .Recognizing the unique needs of populations at risk of HIV infection, an exceptionalist alliance, including the gay community, liberal and left-wing parties, and the healthcare and psychosocial professions, was formed to advocate for a unique response. Bayer writes, "The embrace of exceptionalism must be understood in broad political terms, as representing in large measure, a singular victory on the part of gay men, their community-based organisations and their allies" . The allDuring the 1980s, public health adopted a human rights framework that took societal-based vulnerability into consideration and increasingly became involved in societal transformation efforts . HIV/AIDDescriptively, exceptionalism posited that in the early years of the HIV epidemic, HIV was considered so different, so "exceptional" in comparison to other communicable diseases that advocates and public health officials agreed that HIV policy should cater to the uniqueness of the epidemic rather than treat it like all other communicable diseases. Supposedly, the argument goes, public fear was so great, the political power of gay men so substantial, and concern over stigmatization so real, that public health authorities abandoned "traditional" approaches to communicable disease control in favor of a civil liberties approach .This public health approach helped contain the epidemic among those groups most at risk, and meet, to varying degrees, their specific needs. New infections in the United States fell from approximately 130,000 in 1984 to about 60,000 in 1991 . The feaThe hysteria surrounding HIV/AIDS faded; the media and public policy lost interest. The human rights approach that had previously been revolutionary was integrated into existing public health traditions that included education, technical solutions and regular testing. In 1991, Bayer wrote, "As AIDS has become less threatening, the claims of those who argued that the exceptional threat would require exceptional policies have begun to lose their force" . Highly When antiretroviral treatment (ART) was unveiled at the 1996 International AIDS Conference in Vancouver, Canada, AIDS was transformed into a treatable disease. The advent of treatment shifted Western priorities of response: "The availability of more advanced antiretroviral therapies has made it possible to treat effectively those with HIV infection, thereby increasing the importance of early identification and tracking. These developments establish a strong case for moving beyond HIV exceptionalism and treating HIV antibody tests like other blood tests" .As technical solutions of testing and treatment gained priority, the social movement that had spurred the early HIV/AIDS response continued to fade from public awareness. This shift was assisted by a rapid fall in the price of the drugs. Had they remained expensive, AIDS exceptionalism would have been perpetuated. As Casaratt and Lantos noted, "Medical therapy has become more effective but also prohibitively expensive. A medical tragedy has been transformed into a financial crisis and society has responded by establishing special programs and sources of funding for AIDS. These manoeuvres parallel earlier approaches to HIV testing and reporting that have collectively come to be known as exceptionalism" . The mobThroughout the rise and fall of Western AIDS exceptionalism, the growing global epidemic remained largely ignored by the international community . During The Global Programme on AIDS in the World Health Organization (WHO) lacked both the funding and capacity to respond to the epidemic. Outside of WHO, HIV/AIDS was not on the agenda of other United Nations (UN) agencies. International responses between 1986 and 1996 were characterized by denial, underestimation and over-simplification . AIDS exIn 1996, UNAIDS was formed as a joint programme of UN agencies engaged in the AIDS response . In 1998The Global Infectious Disease Threat and Its Implications for the United States  threatens not just individual citizens, but the very institutions that define and defend the character of a society ... It strikes at the military, and subverts the forces of order and peacekeeping" [d States . Six mond States . In 2001d States .The Pretoria-based Institute for Security Studies wrote, "The severe social and economic impact of HIV/AIDS, and the infiltration of the epidemic into the ruling political and military elites and middle classes of developing countries may intensify the struggle for political power to control scarce state resources. Such dynamics, even singularly, have the potential to lead to political instability" .It was argued that HIV/AIDS could hinder processes of democratization by undermining social development and intensifying the struggle for resources. It was further suggested that AIDS orphans could contribute to social unrest as they made likely recruits for terror and rebel groups: "Bluntly put, those who are orphaned may be indifferent to prevailing norms and values, may look for salvation to millenarian and fundamentalist beliefs of one kind or another, and may ultimately do this with assistance from a Kalashnikov or a bomb" .While there was little evidence to actually link HIV/AIDS prevalence and security issues , the disHowever, as policy and activists spoke of a global HIV/AIDS epidemic, it became apparent that, like many diseases that are expensive to treat, how this epidemic was experienced differed drastically by region. ART, available from 1996, proved effective in curbing AIDS deaths in those regions that could afford the high costs of medications . In those countries with mid to high HIV/AIDS prevalence, ART remained unaffordable, even while costs dropped to about $10,000 per patient per year by 2000 and to less than $100 by 2010. A mid to high disease burden combined with lack of health resources in much of the developing world, making the benefits of ART beyond the reach of most domestic health budgets. While AIDS had become a chronic disease in the West, in most of the developing world. it was still a death sentence.What made this discrepancy unique was the international mobilization that occurred around it, positioning the inequity of treatment access for people living with HIV and AIDS (PLHIV) as an international human rights cause. The International AIDS Conference in Durban in 2000 called for treatment to be rolled out in the developing world and for prices of ART be cut. Activists in South Africa demanded that their government provide universal access to ART, despite political resistance and denial. The governments of India and Brazil took on the World Trade Organization, arguing for compulsory licensing that would enable them to manufacture cheaper generic medications. Activists in the United States, largely led by the PLHIV organization, ActUp, began a sustained campaign against the US government's support for pharmaceutical companies' patent legislation .Arguments that ART could not be provided in the developing world due to limited capacity and poverty were challenged by the successful implementation of such programmes by health organizations like Médecins Sans Frontières . ResearcIn 2002, Botswana implemented the first universal access programmes in sub-Sahara Africa. In 2003, the South African Government gave in to local and international pressure and announced its public treatment programme. The World Health Organization launched the "3 × 5" campaign, aiming to place 3 million people on treatment by 2005. In 2006, 111 countries committed to achieving universal access to prevention, treatment, care and support by 2010 .The development of international AIDS programmes combined with a favourable political environment to create a new discourse of AIDS exceptionalism. At the 2001 UN General Assembly Special Session on AIDS, 189 nations agreed that HIV/AIDS was a national and international development issue of the highest priority . This trIn 2004, at the Copenhagen Consensus, a policy think tank in Denmark, a panel of eight prominent economists ranked controlling HIV/AIDS as the number one economic priority in terms of a cost-benefit analysis in health and nutrition . UNAIDS The Invisible Cure focused on the African epidemic, suggesting that one of the main drivers of the epidemic in hyper-epidemic countries was concurrent sexual partnering, but that such sensitive social issues had not been openly or adequately addressed, despite the resources mobilized for curbing the epidemic [Arguments against exceptionalism began to gain attention in 2007. The amount of funding allocated to HIV/AIDS was called into question, as were the types of programmes being implemented. Three important books put forward new arguments. Chin and Pisani focused on the Asian experience, suggesting that scientists, UNAIDS and AIDS activists accept certain myths about HIV epidemiology to maintain the political profile of AIDS, and their own jobs . Pisani epidemic .British Medical Journal, Roger England argued that HIV/AIDS was not the "global catastrophe" claimed by "AIDS exceptionalists", and that donor aid for HIV/AIDS was disproportionate to the contribution of HIV/AIDS to the global disease burden [The strongest argument against AIDS exceptionalism has centred on the claim that responses undermined health systems in developing countries. In a series of opinion pieces in the e burden . Englande burden . He wrotIt is no longer heresy to point out that far too much is spent on HIV relative to other needs and that this is damaging health systems. Although HIV causes 3.7 percent of mortality, it receives 25 percent of international healthcare aid and a big chunk of domestic expenditure ... Until we put HIV in its place, countries will not get the delivery systems they need .England and others' commentaries highlighted that many diseases and health issues  resulted in more deaths than those related to AIDS in many parts of the world, but were receiving less funding. Whether or not this neglect was because of the prioritization of the AIDS response or due to other factors was hotly contested.et al argued that HIV/AIDS funding actually increased access to other health resources in many underserved areas [UNAIDS and WHO responded defensively, noting that those against AIDS exceptionalism attributed the UN agencies more power than they had to address the epidemic . Researced areas . A 2007 ed areas . These ded areas ; here, tThe emergence of the most recent exceptionalism debate is concurrent to a shift in donor country spending and priorities. Some donor countries have begun redirecting HIV/AIDS funding; in 2009, the UK Department for International Development reassigned a portion of its AIDS funds to maternal and child mortality programmes and health system strengthening . Médecinet al argue for transforming the Global Fund from a disease-specific fund into a "Global Health Fund" [As these changes take place, proposals are emerging to reorganize disease-specific funds in new ways. Sachs and Pronyk argue that the Global Fund should increase its mandate to include health systems, maternal and child mortality and neglected tropical diseases . Similarth Fund" . HIV/AIDth Fund" ; here, tWhile the debate on the global exceptionality of AIDS continues, HIV/AIDS will prevent many sub-Saharan African countries from achieving the Millennium Development Goals (MDGs) . In highThe number of new HIV infections each year remains unacceptably high, and models of effective prevention programmes are few and far between. In the endemic countries, mass behaviour-change campaigns, such as the ABC  strategy, have failed to achieve their intended impacts. Advocates are stressing the need to address the systemic contributors to risk and vulnerability.In South Africa, where one of the largest epidemics continues to unfold, Venter writes that prevention efforts are failing: "500 000 South Africans are infected each year, and there is no sign that this is letting up. In 8 to 10 years' time, as they enter the AIDS stage, these 500 000 South Africans will need ARVs, and this will continue forever until a prevention strategy that works is implemented" .et al write from the American perspective:In Western countries, though the epidemic is concentrated in specific population groups, infection rates among these groups are stable (but not declining). El-Sadre For the past decade, however, progress has been stalled. It had been anticipated that effective antiretroviral therapy, with its suppressive effect on viral replication, would reduce the overall rate of new infections, but this expectation has not been realized. More than half a million Americans became infected with HIV in the past decade, including about 56,000 in the past year .The authors advocate for interventions that "address the socioeconomic milieu in which HIV transmission occurs" . The socMeanwhile, more than half of those in need still do not have access to treatment, and treatment is posing new challenges for sustainable funding. Most countries with mid to high prevalence cannot afford the cost of treatment without international aid; as aid is reduced or cancelled, treatment programmes are threatened, drug resistance develops and large numbers of PLHIV die. In countries like Uganda, patients are being turned away from treatment clinics due to lack of resources; 300,000 Ugandans in need of treatment are denied their right to health . These nThe gap between resources required to implement HIV/AIDS programmes and those available has continued to grow over the past three years . In 2009De Waal writes, "Normalization in the sense of adjusting reality to take account of the miseries of AIDS can be found in many places, when it is looked for. Even the statistics become numbing, and when lower-than-expected HIV prevalence is reported, as recently in Kenya and Zimbabwe, it can give the impression that things are 'not so bad' - when 7 to 10 percent of an adult population is living with HIV" . While iThe concept of AIDS exceptionalism developed as a Western response to an epidemic that threatened the lives and rights of specific populations in the developed world. As that epidemic was contained and effective treatment became available, the case for exceptionalism shifted to the international stage, where resources and organizations were mobilized to respond to the extreme need in developing countries. As a result, the numbers of PLHIV on treatment has increased each year. Infection rates in much of the world have stabilized.These gains have been accompanied by criticisms of the type and size of response. It is argued that the HIV/AIDS response has done harm, as well as good, particularly by creating vertical programmes for a single disease, which may have diverted resources. As donor countries shift priorities, and in the context of the economic recession, the urgency around the HIV/AIDS response is once again declining.This shift in policy and international priorities does not change the reality of an epidemic that, after three decades, is still unfolding. In southern Africa, the demographic effects of the generalized epidemic will shape societies for generations. In other parts of the world, HIV/AIDS continues to mark inequalities: one in 40 blacks, one in 10 men who have sex with men, and one in eight injection drug users in New York City are HIV positive [The Lancet, "We are not overspending on AIDS but underspending on the rest ... The choice is not between AIDS, health systems, and other Millennium Development Goals. We can and must support them all" [Both the human rights approach, originally adopted by the HIV/AIDS response, and the more recent demands for universal access to treatment, remain relevant to the 33 million people living with HIV/AIDS and to their communities; these issues should also remain pertinent within global health policy. Meanwhile new challenges are developing, not the least of which is the need to successfully integrate the HIV/AIDS response within broader public health responses to the benefit of all. As Sachs notes in a commentary in hem all" .As how to best approach such challenges is debated, we must not lose sight of the approximate 2 million AIDS-related deaths that occur each year. Defining these deaths as either exceptional or unexceptional seems both callous and arbitrary.The authors declare that they have no competing interests.Both authors contributed to the research and writing of this paper, and read and approved the final manuscript.


The extraordinary increase of the elderly in developed countries underscore the importance of studies on ageing and longevity and the need for the prompt spread of knowledge about ageing in order to satisfactorily decrease the medical, economic and social problems associated to advancing years, because of the increased number of individuals not autonomous and affected by invalidating pathologies.Centenarians are equipped to reach the extreme limits of human life span and, most importantly, to show relatively good health, being able to perform their routine daily life and to escape fatal age-related diseases. Thus, they are the best example of extreme longevity, representing selected people in which the appearance of major age-related diseases, such as cancer, and cardiovascular diseases among others, has been consistently delayed or escaped. To discuss the relevance of genetics and life style in the attainment of longevity, five papers mostly focused on Italian centenarians have been assembled in this series. The aim is to realize, through a” positive biology” approach  how to prevent and/or reduce elderly frailty and disability. During the last century, life expectancy at birth rose by a remarkable 30 years in Western countries and in Japan, initially because of reductions in infant, child, and maternal mortality and then because of declining mortality in middle and old age. So, during the past century, humans have gained more years of average life expectancy than in the last 10,000 years: we are now living in a rapidly ageing world. The sharp rise in life expectancy, coupled to a steady decline in birth rates in all developed countries, has led to an unprecedented demographic revolution characterized by an explosive growth in the number and proportion of older people. In 1900, about 40% of babies born in Western countries were expected to live beyond age 65. Today in these same countries more than 88% of all newborns will live past age 65 and at least 44% will live beyond age 85. The number of people aged 60 years or older exceeded 635 million in 2002, and is expected to grow to nearly 2 billion by 2050. The proportion of people aged 60 and over stands about 1 in 4 in many Western countries as well as in Japan. Should the present trend continues, this ratio is expected to reach 1 in 3 by 2050. So, many countries have rising ageing populations and are facing an increased prevalence of age-related diseases and increasing healthcare costs, since the rapid rise in older people is accompanied by an increase in the number of people with chronic age-related diseases. However, the improvement in public health has reduced the principal causes of mortality in the elderly, allowing an increasing number of individuals to reach the maximum lifespan age. Indeed, around the 1950s, in all industrialized countries, the progressive decline of mortality in oldest old people has increased, so that the number of centenarians has augmented about 20 times .The increased ability to reach 100 years in industrialized countries over the last 150 years most likely reflects a rise in life expectancy as a consequence of improvements in diet and a reduced exposure to infection and inflammation  and the The extraordinary increase of the elderly in developed countries underscore the importance of studies on ageing and longevity and the need for the prompt spread of knowledge about ageing in order to satisfactorily decrease the medical, economic and social problems associated to advancing years for the increase of the subjects which are not autonomous and are affected by invalidating pathologies .Recently, it has been pointed out that most biomedical research should be termed ‘negative biology’, because the study of disease is its central heart, reflecting the prevalence of pathology-oriented negative biology, so focusing on the causes of pathology. By contrast, the Author invites to focus on a different approach, named “positive biology”. Rather than making diseases the central focus of research, positive biology seeks to understand the causes of positive phenotypes, trying to explain the biological mechanisms of health and well-being . In partThe model of centenarians is not simply an additional model with respect to well-studied organisms, since the study of humans has revealed characteristics of ageing and longevity as geographical and sex differences, role of antigenic load and inflammation, which did not emerge from studies in laboratory model systems and organisms. So, scientists have focused their attention on centenarians as optimal model to address the biological mechanisms of successful ageing ,18.Centenarians are equipped to reach the extreme limits of human life span and, most importantly, to show relatively good health, being able to perform their routine daily life and to escape fatal age-related diseases. Thus, they are the best example of extreme longevity, representing selected peope in which the appearance of major age-related diseases, such as cancer, and cardiovascular diseases among others, has been consistently delayed or escaped ,18.The ageing process and longevity are multi-factorial events. Genetic, epigenetic, stochastic and environmental factors seem to have a crucial role in ageing and longevity. As well known, life expectancy is a familial trait and longevity is determined by different factors. Epidemiological evidence for a genetic component to variation in human lifespan comes from twin studies and family studies. By comparing life span in twins, researchers have found that approximately 25% of the overall variation in human lifespan can be attributed to genetic factors, which become more relevant for extreme longevity -24. CondTo discuss the relevance of genetics and life style in the attainment of longevity, five papers mostly focused on Italian centenarians have been assembled in this series with aim to understand, through a “positive biology” approach, how to prevent and/or reduce elderly frailty and disability.As it is known, healthy ageing and longevity in humans result from a number of factors, including genetic background, favorable environmental and social factors and chance. So, in their paper Montesanto et al., discuss the role of epidemiological, genetic and epigenetic factors in the variation of quality of ageing and lifespan, including the most promising candidate genes investigated so far. Epigenetic modifications indicate the sum of heritable changes, such as DNA methylation, histone modification and miRNA expression, that affect gene expression without changing the DNA sequence. So, they outlined some recent advance in the epigenetic studies of ageing, as epigenetics, a bridge between genetics and environment, might explain many aspects of ageing and longevity.In their review, Ferrario et al,. point out that the genetic origin of exceptional longevity and the more recently observed environment-driven increase in the average age of the population could possibly be explained by the same genetic variants and environmentally modulated mechanisms. The potential overlap of hits for environmentally and genetically mediated predisposition for extreme longevity in centenarians is highlighted by the association of genetic variants of genes that regulate, or that are regulated by, nutrient metabolism. They conclude that the adoption of innovative study designs combined with novel genetic platforms and innovative statistical methods hopefully will bring to the identification of new intervention points at which to modulate ageing and the diseases of ageing.In their review, Balistreri et al., report their data gathered for over 10 years in Sicilian centenarians. Based on their findings, they suggest longevity as the result of an optimal performance of immune system and an over-expression of anti-inflammatory sequence variants of immune/inflammatory genes. The data from Sicilian investigation add another piece to complex puzzle of genetic and environmental factors involved in the control of life span expectancy in humans, showing a complex network of trans-inactive genes able to influence the type and strength of immune responses to environmental stressors, and as final result, conditioning individual life expectancy.The paper of Vasto et al., pays attention on the modifiable lifestyle factors such as diet and nutrition to achieve extension of health span. Previous data reported that in Sicily, the biggest Mediterranean island, there are some mountain regions where there is a high frequency of male centenarians with respect to the Italian average. The present data show that in Sicani Mountain zone there are more centenarians with respect to the Italian average. In fact, in five villages of Sicani Mountains, there where 19 people with age ranging from 100–107 years old, on the total population of 18,328 inhabitants. So, the centenarian number was more than 4.32-fold higher the national average ; the female/male ratio was 1.1:1 in the study area, while the national ratio is 4.54:1. Unequivocally, their nutritional assessment showed a high adherence to the Mediterranean nutritional profile with low glycemic index food consumed.In their paper, Davinelli et al., focus on dietary patterns of centenarians and nutrient-sensing pathways that have a pivotal role in the regulation of life span. They point out that the realization of healthy longevity is possible but to achieve a longer and a healthier life, increased attention must be placed on lifestyle choices, particularly the diet. To date the main dietary intervention that may retard the ageing process is calorie restriction and a typical example is the Okinawan population in Japan. Many of the genes that act as key regulators of lifespan also have known functions in nutrient sensing, thus called nutrient-sensing longevity genes and variant associated to longevity have been described.Success in increasing longevity in laboratory organisms has shown that ageing is not an immutable process . Hence, Centenarians, despite being exposed to the same environmental conditions as members of the average population, manage to live much longer; moreover, as a consequence of demographic selection, centenarians have a compression of morbidity and mortality towards the end of their life-span . On the Regarding immunological aspects, studying centenarian offspring reveal that several B cell immune parameters are better preserved than in age-matched controls, and together with their genetic background could contribute to their healthier ageing. This suggests the idea of the “familiar youth” of the immune system ,38.Concerning life style, it is out of doubt that healthy centenarians live surrounded by a solid support network of friends and family. However, diet plays a key role in successful ageing. Specific dietary factors that may be involved include a high intake of fruit and vegetables, and in the property of phytochemicals to activate specific nutrient sensing pathways. Centenarians have a very high intake of phytochemicals in the diet. All plants contain these natural compounds and the elderly have significantly lower levels of lipid peroxidation and they suffer less free-radical-induced damage -41. FromIn conclusion, the development of strategies that will lead to the extension of healthy life and that would result in slowing the rate of ageing may be part of the new paradigm for the medical sciences that is the ‘positive biology’.The authors declare that they have no competing interests.CC wrote the paper. All authors edited the paper and approved its final version.


Chronic diseases are posing an increasing challenge to society, with the associated burden falling disproportionally on more deprived individuals and geographical areas. Although the existence of a socioeconomic health gradient is one of the main concerns of health policy across the world, health information systems commonly do not have reliable data to detect and monitor health inequalities and inequities. The objectives of this study were to measure the level of socioeconomic-related inequality in prevalence of chronic diseases and to investigate the extent and direction of inequities in health care provision.A dataset linking clinical and administrative information of the entire population living in the Basque Country, Spain  was used to measure the prevalence of 52 chronic conditions and to quantify individual health care costs. We used a concentration-index approach to measure the extent and direction of inequality with respect to the deprivation of the area of residence of each individual.Most chronic diseases were found to be disproportionally concentrated among individuals living in more deprived areas, but the extent of the imbalance varies by type of disease and sex. Most of the variation in health care utilization was explained by morbidity burden. However, even after accounting for differences in morbidity, pro-poor horizontal inequity was present in specialized outpatient care, emergency department, prescription, and primary health care costs and this fact was more apparent in females than males; inpatient costs exhibited an equitable distribution in both sexes.Analyses of comprehensive administrative clinical information at the individual level allow the socioeconomic gradient in chronic diseases and health care provision to be measured to a level of detail not possible using other sources. This frequently updated source of information can be exploited to monitor trends and evaluate the impact of policy reforms. The existence of a socioeconomic health gradient is one of the main concerns of public sectors in the European Union and otheIn Spain, the organization of the health care system is devolved to the autonomous regions, which has led to the development of 17 separate regional health services. Financed through taxes, regional health services in Spain provide primary and specialized care, free of charge  to all residents. Each person has an assigned general practitioner, who acts as a gatekeeper to the rest of the system. Health care services at all levels of care are predominantly public in most regions, and most health professionals are employees with civil servant status. In general, health care services in each region are owned by a public organization, which centrally oversees the regional health service. In the Basque Country, one of the autonomous regions located in the north of Spain, this organization is called Osakidetza  and was created in 1983.Nevertheless, the existence of a National Health Service covering all the population and almost free at the point of use does not prevent there being social inequalities in health within the system; indeed, these are known to be present in the Basque Country and in SThe focus of the aforementioned strategy is a new framework, in which the phenomenon of chronicity is considered central, due to the implications of chronic health conditions and multimorbidity for both patients, their families and caregivers, and health systems and societies. Under tThe aim of this study is to exploit this dataset to measure inequalities and inequities in health and health care delivery for the entire population living in the Basque Country. The richness of this dataset and its systemic scope is one of the strengths of this study, because it overcomes the limitations of most survey-based research and other studies using databases that do not provide a comprehensive picture of prevalence and expenditures across a health system, being limited to certain age groups, diseases or record systems .i) to estimate, from data in clinical and administrative records from the Basque Health Service, the prevalence of chronic diseases in the population, ii) to measure the level of socioeconomic-related inequality in these prevalences, and iii) to investigate the extent and direction of inequities in health care provision with respect to socioeconomic deprivation in the Basque Country. Finally, we analyze the implications of our findings for health policies in aged societies.Our aims are Ethics statement: This study is a part of a project that was approved by the Ethics Committee of the Basque Country. We used databases that employ an opaque identifier to ensure patient confidentiality.This study utilized the database prepared by the population stratification program (PREST) of the Basque Health Service. This program was launched in 2010 with the aim of classifying all citizens of the autonomous region in terms of their future care needs. To this end, data recorded since 2007 were collected from various sources, for the following variables: diagnoses , prescriptions, procedures and costs of care. A more detailed description is available elsewhere.st August 2011 was covered by public health insurance in the Basque Country and who had been covered for at least 6 months in the previous year, regardless of whether or not they had used or had any contact with the Basque Health Service.The study population included every individual who on 31The Spanish National Health System provides almost universal (99.5%) coverage to Spanish citizens and foreign nationals within the Spanish national territory. Only 0.The database includes individual-level information on age, sex, health care utilization by type of service and diagnosis, Adjusted Clinical Group (ACG) categories, a small area of residence indicator based on census tracts, and the general practice at which they are registered.We analyzed a comprehensive list of chronic diseases as well as the presence of multimorbidity. In the Basque Health Service, in accordance with the policy of the Ministry of Health, Social Services and Equality of Spain, diagnoses on hospital discharge forms, emergency department databases and primary care medical records are coded according to ICD-9-CM, while tst September 2007 onwards. Out of the remaining individuals, 95,714 had shorter follow-up periods because they were born after September 2007 or for other reasons, such as, moving house, changes in type of insurance or administrative factors.In the present study, we analyzed a four-year period of data for each of the patients. For this, we adapted a methodology previously applied in the literature: we deveMultimorbidity was defined, for the purposes of this study, as the coexistence of more than one health problem in the same patient considering the 52 conditions under study.st September 2010 to 31st August 2011). We consider separately the cost of the following types of services: primary care , specialized outpatient care , inpatient stays, emergency department attendances, and prescribing.We measured health care provision in terms of cost-weighted utilization of health care. Health care use was estimated for a 12-month period . Information on some services was not available and these were therefore excluded from the analysis: admission to psychiatric hospitals, home hospitalization and day care services (except the procedures and services listed above), health care transport, prostheses and other equipment provided to patients at home.The deprivation index of the census tract  of residence proposed by the MEDEA project was usedWe use a concentration index (CI) as our measure of socioeconomic-related inequality. CIs aren is the sample size; hi is the health/health care measure; μ is the average health/health care measure; andth person, where i =1 for the poorest and i = n for the richest. The CI takes a positive (negative) value when there is socioeconomic-related inequality favoring the rich (poor).where One of the main advantages of CIs is that they make it possible to summarize the extent of inequality in a single measure that can be used to compare inequality levels across time, areas or, as in our case, disease groups and types of services.A problem with CIs of binary variables is that they are mean dependent. To accoinequity as they do not take into account differences in needs between individuals[horizontal inequity as the difference between the CI of actual health care costs and the CI of need-predicted health care costs[With respect to the analysis of health care costs, socioeconomic inequalities in health care simply reflect that different individuals receive different amounts of care, but they tell us very little about potential ividuals. For insre costs. Need-prre costs). The efWe utilized the variables available in our dataset as need and non-need indicators. Classifying variables as need or non-need variables requires making value judgments about which factors ought to affect use and which factors ought not to. Empirical analyses of equity in health service use have commonly classified socioeconomic variables as non-need indicators, and the common practice involves using data on age, gender and morbidity indicators as need measures. We follow this convention in this study. The indicators of need in our models included: sex, age  and Adjusted Diagnosis Groups (ADGs), which are a component of the ACG case-mix system. ADGs are 32 categories, specifically designed to aggregate diagnoses into groups with similar severity, duration of condition, and needs for health care treatment. We usedAll CIs were adjusted for clustering at level of the general practice where the individual was registered.The total population was 2,262,686, of which 50.90% were female. The proportion of children age <18 years) was 15%, and 20% of individuals were over 65. Table 8 years wThe average number of chronic diseases per person was 0.97 and the percentage of the population with two or more of such diseases was 23.61%.Figure Figure Table CIs of observed health care are negative in every case, suggesting that health care provision was disproportionally concentrated among those living in poorer areas for every type of use. After accounting for the differences in the levels of need, the indices of horizontal inequity continued to be pro-poor in most cases, although the magnitude of the indices decreased dramatically and in some cases become non-significant. The values of the indices of horizontal inequity also indicated that the pro-poor bias is greater for specialized outpatient care and emergency department attendance, while the indices were lower for primary care and prescriptions. Among males, inpatient stays appeared to be disproportionally concentrated among richer individuals after accounting for needs, although the horizontal inequity estimate is very small and non-significant. Similar to analysis of inequalities in chronic diseases, we found inequities in health care were also larger among females.The contribution of each factor to explaining the inequalities in observed health care costs are summarized in Figure The exploitation of administrative health databases in the Basque Country has allowed us to describe the prevalence of chronic diseases, level of multimorbidity and use of health care resources in the entire population and to analyze differences by socioeconomic deprivation and sex. The prevalence of the great majority of the observed chronic diseases is concentrated among the most disadvantaged social groups who also have higher rates of multimorbidity. These inequalities in morbidity burden account for most of the differences found in use of health resources and there is only a small degree of horizontal inequity , in most cases this being pro-poor.Analyzing chronic diseases individually, the largest inequalities are found in pathologies related to high-risk behaviors, substance misuse  and sedentary life-style, and to exposure to environmental and work-related factors. However, the two sexes do not show analogous patterns in all the conditions and, in general, greater differences were observed in women than men.Although the methodology used in this study is, in several respects, different to that employed by other authors, our results partially agree with studies in the literature. In a previous study on socioeconomic inequality in the Basque Country, Esnaola et al. found that the greatest differences in causes of mortality between socioeconomic groups were in overdoses of illegal drugs, cirrhosis, AIDS and COPD. FurtherOn the other hand, for some diseases our results differ from previously published findings. One of the most striking cases is that of skin conditions, which in our study were relatively strongly concentrated in more deprived communities, while other authors have found no relationship between poor socioeconomic conditions and this type of health problem,29. NeveIt is well known that the inequalities between social groups in many risk factors vary between the sexes in magnitude and even direction. For example, there are greater inequalities related to level of education for obesity in women, and for smoking and alcoWe also found inequity in the prevalence of multimorbidity and this was greater the larger the number of diseases diagnosed in same person. In addition, in all cases, the inequality was larger in women. Although for many years it has been known that the number of people with multiple apparently unconnected conditions is higher than would be expected by chance, the intIn the Basque Country, people with poor socioeconomic status use more health resources, especially females. This inequality is mostly explained by the fact that these deprived groups have greater health care needs given their greater morbidity burden. Nevertheless, we still detected a certain degree of pro-poor inequity in the case of specialized outpatient care and emergency services, and to a lesser extent also in primary care and prescriptions, while no inequity was detected in inpatient care. These results are not in agreement with those of other studies that used surveys,40-42 orOne factor that may partly explain the different use of specialized care observed in our data is that some of the Spanish population, in general those with higher incomes, is covered by private medical insurance as well as the Public Health System,45. SpecOur study has the following strengths. First, it includes almost the entire population of the geographical area studied, thus avoiding selection bias. Second, it exploits a database containing information from primary, specialized outpatient and inpatient care, as well as prescriptions; as other authors have established, the use of a single source can produce inaccurate estimates,50, whilOur study also has certain limitations. Firstly, administrative databases only contain information about problems for which people seek medical attention. Therefore, the prevalence of diseases can only reflect known cases and excludes the presence of diseases that are present but not known of by the patients or their doctors. The distribution of undiagnosed cases might be influenced by factors including accessibility to health care services and help seeking behavior of patients. Secondly, our database contains information from primary and specialized care, emergency departments and hospital admissions, but not psychiatric hospitals; even though patients admitted in such hospitals are also usually cared for by primary care doctors, given their special characteristics, it is feasible that their health records were not as complete as for the rest of the population. Moreover, as previously noted, we do not have access to information from the health services in the private sector as they are not under the management of the Basque Health Service. As a consequence, in this research we were not able to explore the effect of the existence of double insurance. Thirdly, regarding the cost of care per patient, our health service has no direct data and, hence, costs were calculated from the standard pricing of the services provided and in some specific cases the costs were not available . Finally, being based on socioeconomic indicators at the level of area of residence, our study has the limitations common to ecological studies. Although there is known to be a relationship between socioeconomic deprivation and poor health, the contributions of individual and context-related factors have not been clearly established. In any case, the area-based measures, reflecting community-wide characteristics, turn out to be indicators with their own characteristics and do not behave solely as proxy measures for individual socioeconomic variables. The depAlthough the relationship between low socioeconomic status and poorer health status is complex, and the underlying mechanisms have not been clearly established, the existence of health inequalities is well recognized. Most people in the world aspire to greater solidarity in the field of health and wish their governments to introduce policies that guarantee health protection and promote equity. To faceCommonly, health information systems do not have reliable data to detect health inequalities and inequities in health care, to assess changes in these over time and to monitor the impact of related policies. Exploiting a huge dataset that links all the clinical and administrative information available  for each resident in the Basque Country, we observed the prevalence of 52 chronic conditions, quantified individual health care costs and estimated the extent and direction of inequality with respect to socioeconomic deprivation. Analyses of comprehensive administrative clinical information at the individual level allow the socioeconomic gradient in chronic diseases and health care provision to be measured to a level of detail not possible using other sources.ACG: Adjusted clinical group; ADG: Adjusted diagnosis group; ATC: Anatomical therapeutic chemical classification system; CI: Concentration index; COPD: Chronic obstructive pulmonary disease; DRG: Diagnosis-related group; EU: European union; ICD-9-C: International classification of diseases, ninth revision, clinical modification.The authors declare that they have not competing interests.All authors contributed to the design of the study, and participated in the interpretation of data, as well as critically reviewing the manuscript and approving the final version.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2458/13/870/prepubDefinition of chronic conditions.Click here for file


Artemisinin-based combination therapy (ACT), the treatment of choice for uncomplicated falciparum malaria, is unaffordable and generally inaccessible in the private sector, the first port of call for most malaria treatment across rural Africa. Between August 2007 and May 2010, the Uganda Ministry of Health and the Medicines for Malaria Venture conducted the Consortium for ACT Private Sector Subsidy (CAPSS) pilot study to test whether access to ACT in the private sector could be improved through the provision of a high level supply chain subsidy.Four intervention districts were purposefully selected to receive branded subsidized medicines - “ACT with a leaf”, while the fifth district acted as the control. Baseline and evaluation outlet exit surveys and retail audits were conducted at licensed and unlicensed drug outlets in the intervention and control districts. A survey-adjusted, multivariate logistic regression model was used to analyse the intervention’s impact on: ACT uptake and price; purchase of ACT within 24 hours of symptom onset; ACT availability and displacement of sub-optimal anti-malarial.At baseline, ACT accounted for less than 1% of anti-malarials purchased from licensed drug shops for children less than five years old. However, at evaluation, “ACT with a leaf” accounted for 69% of anti-malarial purchased in the interventions districts. Purchase of ACT within 24 hours of symptom onset for children under five years rose from 0.8% at baseline to 26.2% (95% CI: 23.2-29.2%) at evaluation in the intervention districts. In the control district, it rose modestly from 1.8% to 5.6% (95% CI: 4.0-7.3%). The odds of purchasing ACT within 24 hours in the intervention districts compared to the control was 0.46  at baseline and significant increased to 6.11  at evaluation. Children less than five years of age had “ACT with a leaf” purchased for them more often than those aged above five years. There was no evidence of price gouging.These data demonstrate that a supply-side subsidy and an intensive communications campaign significantly increased the uptake and use of ACT in the private sector in Uganda. Malaria is a parasitic disease that mostly affects the poorest populations of the world, with sub-Saharan Africa experiencing the heaviest disease burden,2. EarlyIn response to the likelihood of an emerging threat of artemisinin resistance, the Institute of Medicine (IOM) released a 2004 expert report proposing that the price of ACT, the most effective malaria treatment, would have to be subsidized at the factory-gate to make them as affordable and as available as sub-optimal monotherapies such as chloroquine. The IOMIn 2007, the Uganda Ministry of Health (Ug-MoH) and the Medicines for Malaria Venture (MMV), in consultation with national and international stakeholders, designed the Consortium for ACT Private Sector Subsidy (CAPSS) pilot study to test the viability of the AMFm approach. The Ugandan pilot was one of two designed to assess the overall feasibility of providing affordable treatment through the private sector,16. The Here the findings from the CAPSS pilot study are reported, that demonstrate that the AMFm strategy is feasible and can improve access to life saving medicines in the private sector in rural Uganda.Four contiguous intervention pilot districts  were selected to receive the subsidized medicines, while the fifth district (Soroti) acted as the control. To limit leakage of the intervention to the control area, the control and intervention areas had two intervening buffer districts (Bukedea and Kumi) or a lake between them Figure . The pil.The baseline household survey provided a comprehensive picture of malaria treatment, which subsequently shaped the pilot’s design. One of the baseline household survey’s findings was that access to effective treatment was extremely low. In 2007, in the most vulnerable age group, of children under the age of five years, only 3% of those contracting a fever received effective treatment (ACT) within 24 hours of symptom onset. This figure rose to just 4% after 48 hours of symptoms onset. The contextual information suggests that there was better availability of ACT in the public sector in the control district because of improvements that had been made in the procurement and distribution system, based on a push instead of a pull system for the lower-level health units. However, this was not the case in the intervention districts. Consequently, slightly more than half of the public health facilities in Pallisa and Kaliro had no public sector ACT packs in stock at the time of the surveys; and the situation in Budaka was distressingly inadequate, with three quarters of public sector facilities having no ACT in stock. Second, the intervention made by another group (Living Goods) to improve access to ACT at community level in the control district had an impact on ACT supply there. These findings make us believe that the effect differences could have been bigger had these developments not taken place or had the public sector supply chain not failed in the intervention districts.The private sector’s role in ensuring access to medicines is largely complementary to that of the public sector: the nature of this role is determined primarily by the level of availability in public sector outlets. When there are stock-outs in the public sector, the private sector’s role inevitably shifts from a complementary one to primary. Whether the private sector played a complementary or primary role therefore varied greatly during the different rounds of data collection. For example, in Kaliro, Pallisa and Budaka, access to ACT was largely assured through the availability of the subsidized ACT in the private sector, because stock-outs in the public sector were very frequent. However, in Kamuli, private sector availability complemented existing public sector availability. ACT access through the private sector was very low in the control district. Based on these findings, we believe that moving forward; the AMFm strategy should be tailored to the local context. There aWhile the CAPPS pilot study was very successful, there are several challenges that need to be addressed to ensure adequate availability in poor and remote rural areas. This requires a number of specific actions, such as incentivising suppliers to deliver medicines to such areas, or strengthening community based systems, such as that of Uganda’s village health teams. Ensuring there are sufficient licensed outlets to meet demand is also critical. In the more developed areas of Uganda, where private businesses flourish, a sufficiently large number of private outlets are able to achieve the required licensing standards. However, in other less developed areas, where there are currently few or no private licensed outlets, there is insufficient coverage. In addition, the outlets that do exist in these areas are often severely constrained, since many of the smaller outlets rely on the immediate cash flow from sales to pay for their next orders. These cash flow constraints result in the smaller outlets placing very small orders with the distributors, since they cannot afford to tie up significant amounts of money in stock. Prices in the more remote rural areas are often even higher than in urban/suburban centres, largely due to the additional costs of distribution. Enhancing access to ACTs in poorer, more remote areas requires overcoming these distribution challenges.A second challenge is the difficulty of maintaining the maximum recommended retail price in the face of currency exchange fluctuations. The Ugandan Shilling faced ongoing devaluation during the course of this study. This resulted in the importers of “ACT with a leaf” facing higher landed costs, costs which are normally passed on to the consumers in terms of higher prices. Moreover, national drug regulatory agencies in many countries, particularly in East Africa, do not attempt to control market prices in view of price liberalization policies. Rather than imposing a maximum price, therefore, a more pragmatic approach might be to issue a “recommended retail price range” (RRPR). This would be effective in setting price expectations. The maintenance of the ACT price is also subject to the availability of the continuing subsidy; this price is consequently vulnerable to changes in the global funding landscape.A third challenge, applying to both the public and private sectors, is the need to avoid stock-outs. Ensuring uninterrupted availability of ACT is critical to guaranteeing access to effective treatment. In this regard, the two sectors can work synergistically to improve access to treatment. A concerted effort needs to be made to ensure that more caregivers of children under five seek treatment within 24 hours of the onset of fever and have access to ACT. The introduction of rapid diagnostic tests in the public sector and subsequently in the private sector could help ensure targeting of ACT. Such an approach would ensure that patients quickly get access to the correct treatment for malaria based on parasite-based diagnosis as per current WHO recommendations.The results of the independent evaluation of the AMFm from Uganda validate the CAPSS findings of affordability driving stocking and uptake as availability of quality assured ACTs (AQ-ACT) across all outlets increased from 21% at baseline to 67% at endline. The recCertain limitations in the design of this study need to be noted. First, the districts were purposefully selected and only one district was used as a control. This could have increased the potential for discordance between the populations included in the study. Some discordance was observed between the intervention and control districts at baseline in terms of drug consumption habits. Fortunately, the observed disparities did not include the use of ACT. Generating survey-adjusted outputs was intended to provide a more reasonable range of likely values that accounted for this prior to executing tests of significance. Second, only respondents leaving drug outlets at specific times and who consented to the interview were analysed. This could lead to both a selection and response bias. Different groups are likely to visit drug stores at different times during the day. As an example, people who are employed full-time may be more likely to visit an outlet at night. Also, we did not collect detailed information about potential respondents who refused to be interviewed. It is possible that their characteristics differed from the study sample. However, the rate of refusal was generally small (not exceeding 10%) and any effect due to refusal probably did not impact significantly on the outcome measures. Further, the wide range of times at which interviews were conducted, in combination with survey-adjustment, minimized the influence of these possible biases. Finally, a possible observer bias could arise from the fact that the interviewers were not blinded to the intervention status of the respondents. To mitigate this risk, a week long training session was administered prior to each round of data collection to instil strict processes for conducting interviews and to prevent - to the extent possible - deviation from the script. It is unlikely that this lack of blinding could influence the primary outcome in this study, as it was obligatory for the interviewer to observe and record the details of the actual medicine purchased.These findings provide evidence that a subsidy high up in the supply chain coupled with an intensive communication campaign leads to increased ACT uptake, making a compelling case for AMFm in Uganda and potentially other African settings with similar private sector use. The approach will need to be customized by country to respond to specific national access challenges. The approach adopted has been effective in extending uptake in the most vulnerable category, the youngest segment of the population. Further, it is reassuring that customers purchase the right dose, consistent with observations reported elsewhere in Uganda.All of the CAPSS pilot study’s multiple data platforms – the cross-sectional outlet exit surveys with observation and verification of medicines and audits of all retail outlets and public health facilities - confirm that the subsidy of ACT increases access through the private sector to these life-saving medicines.AOT, PGD, AB, TE, BP, RC, ML, GB, JB and JG were at the time of the study affiliated with MMV a product development partnership-PDP for different anti-malaria drugs. KN, KR, ND work for Surgipharm Pharmaceuticals, which at the time of the pilot study was the company designated to distribute Coartem in Uganda. All the other authors declare no competing interest.The members of the Consortium for ACT Private Sector Subsidy-CAPSS are the designated authors of this paper: AOT and PG (MMV) conceptualized the CAPSS pilot study, were the overall leaders of the management team and drafted the manuscript; JB, AB, GB, ML, RC and JG (MMV) were involved in the design and implementation of the pilot study and reviewed the manuscript; GBR, RN, MB, PK, FS and FK (Ug-MoH) were involved in the design and implementation of the CAPSS study and reviewed the manuscript; DN and AB (NDA) were involved in the regulatory aspects of CAPSS, training on safety monitoring and reviewed the manuscript; SMM, PB, JL, and AB (PACE) designed and implemented the secondary packaging and communications programme and reviewed the manuscript; GN and JT (MC) were responsible for the design and implementation of the training programme; KN, KR and ND  were involved in the design and management of the supply aspects of CAPSS; SR (I+Solutions) was involved in supply side and logistics training, SK  was involved in the design of the study and policy oversight and reviewed the manuscript; BP and TE (MMV) provided substantial input in the implementation of the field surveys and performed the geographical information system (GIS) and statistical analysis and reviewed the manuscript. All authors read and approved the final manuscript.


Barriers and bridges to implement policies about sustainable development and sustainability commonly depend on the past development of social–ecological systems. Production of metals required integration of use of ore, streams for energy, and wood for bioenergy and construction, as well as of multiple societal actors. Focusing on the Swedish Bergslagen region as a case study we (1) describe the phases of natural resource use triggered by metallurgy, (2) the location and spatial extent of 22 definitions of Bergslagen divided into four zones as a proxy of cumulative pressure on landscapes, and (3) analyze the consequences for natural capital and society. We found clear gradients in industrial activity, stream alteration, and amount of natural forest from the core to the periphery of Bergslagen. Additionally, the legacy of top-down governance is linked to today’s poorly diversified business sector and thus municipal vulnerability. Comparing the Bergslagen case study with other similar regions in Russia and Germany, we discuss the usefulness of multiple case studies.The online version of this article (doi:10.1007/s13280-012-0369-z) contains supplementary material, which is available to authorized users. Man’s impact on landscapes creates path dependence effects of importance both for sustainable development as a societal governance process, and for sustainability. Already Marsh  stressedEnvironmental history has been addressed by both cultures, however, with limited integration between them Merchant . WorsterAnother relevant discipline is economic history. This is a broad human science discipline with its main emphasis on empirical studies  and several hybrid fields  Balée . The neeThe importance of understanding the history of resource use, economy, and social issues for contemporary landscapes can be seen in the production of metals. Historically, this required integration of use of ore, water, and wood for bioenergy and construction, as well as of societal actors  with a history of industrial landscape use that began with production of metals more than 2000 years ago Nelson . The nam2 of catchment area using the Swedish Water Archive’s data base hosted by Swedish Meteorological and Hydrological InstituteFocusing on the use of ore, forests, and water, we first reviewed literature about the historic phases of the economic and social development in the Bergslagen region. To map the location of Bergslagen, 22 different maps defining the spatial location and extent of Bergslagen  were produced using ArcGis. Printed maps were scanned and rectified, and the border of Bergslagen then digitized. The locations of the different definitions were then delimited with parishes as the minimum mapping unit. This was made to minimize errors linked to the variable quality of maps. Then the number of spatial definitions of Bergslagen per parish was counted and presented as a map showing the gradient in four zones from the core of Bergslagen , to the periphery of Bergslagen . The number of definitions was thus used as a proxy for the gradient from stronger impact of metallurgy on social–ecological systems in the center of the region to weaker in the periphery. To understand some consequences for landscapes in the core and periphery of Bergslagen, we compiled proxy data linked to metallurgy, forests, and water, as well as for societal development. Regarding mining we compiled data from the Swedish National Heritage Board about the location of historical mines and furnaces . They had special privileges that included tax reductions and sometimes exemption from military service. The entire family was engaged with farming during the cultivation season and with mining and pig iron production the rest of the year. Thus, Swedish iron production was co-operatively organized  paralleled the “Bergsmän” cooperative organizations. Subsequently the former gradually took over the bar iron production, which was the most profitable part. Large ironworks were established in Bergslagen. Swedish ironmasters who wanted to increase their production of bar iron were obliged to buy privileged quantities from other ironmasters, or build new ironworks outside the core of Bergslagen Furuskog . The spaUp to the mid-twentieth century the mining region of Bergslagen was a working landscape Ågren . The farThis long landscape history of industrial use of natural resources, that once provided many local jobs, resulted in relatively low levels of entrepreneurship and education among local people compared to regions with more diversified livelihoods , 704 parishes with different number of spatial definitions were identified. These data were used to define four spatial zones from the core to the periphery of Bergslagen , and climate change are current issues that affect landscape management and governance in Bergslagen. Additionally, with increasing mineral prices internationally there is a renewed interest to resume mining operations in Bergslagen. This requires collaboration among actors from the prospecting phase to the establishment of a new mine to its closing, including minimizing the environmental impact, and restoring the mining site after ore extraction. However, the realization of sustainable mining includes not only mines themselves, but also a need to support societal infrastructures in general Richards . To dealDevelopment is generally considered to be supported by improved social capital and an associated level of entrepreneurship Below is the link to the electronic supplementary material.