Lifestyle and behaviour change are important factors in the prevention of cardiovascular disease and reduction of premature mortality. Public health initiatives have focused on opportunities for healthcare staff to deliver lifestyle advice routinely in primary and secondary care but there is no consistent approach to onward referrals and the rate of uptake of advice remains low. We do not know if advice is more effective in supporting behaviour change when a systematic approach is taken that includes identification of barriers to change, directing patients toward services, referral to services, and feedback on outcome.This is a single-centre, randomized, unblinded feasibility trial in an acute hospital setting which aims to assess the feasibility of a definitive trial and provide proof of concept for the systematic delivery of individualized lifestyle advice in patients managed through an acute cardiology in-patient service.Patients will be recruited before discharge and randomized to two groups. A control group will receive the usual lifestyle assessment and referral, while an intervention group will receive the usual assessment plus the new individualized lifestyle assessment and referral. The new assessment will inform assignment of each patient to one of three categories based on personal barriers to change. Patients may be referred to a formal lifestyle-change programme, through the ‘Leeds Let’s Change’ website, or they may be guided in self-management, using goal setting, or they may be assigned to a ‘deferment’ category, for reassessment at follow-up. These latter patients will be given a contact card for the ‘Leeds Let’s Change’ service.Lifestyle change is an important mechanism for improving health and wellbeing across the population but there are widely acknowledged difficulties in addressing lifestyle factors with patients and supporting behaviour change. A systematic approach to assessment would facilitate audit and provide an indicator of the quality of care. The new assessment template has been designed to be quick and easy to use in practice and could, for example, be added to a primary care consultation or form part of a nursing discharge assessment in an acute setting.ISRCTN41781196.Current Controlled Trials  Cardiovascular disease is a global killer; it is a major cause of premature death and morbidity, and is responsible for over 4 million deaths in Europe annually . It is cRecent guidance from the UK’s National Institute for Health and Clinical Excellence (NICE)  states tPublic health initiatives have focused on the opportunities to deliver lifestyle advice . Healthc• Low mood, especially anxiety and depression.• Poor knowledge about healthy lifestyles and poor education.• Little support from family and friends.• Financial and transport difficulties (where cost and travel is required for attendance at a lifestyle programme).• A belief that changing lifestyle will have little impact on health.The intervention to be tested will therefore consist of a new referral assessment for patients. The assessment will address these barriers to change and will be used to identify suitable services for patients.Incentivizing individuals to encourage healthy living was recently discussed by the National Institute for Health and Clinical Excellence (NICE) Citizen’s Council . This apIncentives are becoming more common in public health interventions for encouraging healthy behaviour, and some positive results have been reported for increasing weight loss , and levThis randomized feasibility trial is being conducted as part of the vascular research theme: Improving Prevention of Vascular Events (IMPROVE) in the National Institute for Health Research Collaboration for Leadership in Applied Health Research and Care (CLAHRC) for Leeds, York and Bradford. It will examine feasibility and provide proof-of-concept evidence for a larger-scale trial to test the hypothesis that the rate of uptake of lifestyle behaviour change can be increased by use of a systematic assessment that tailors the level of lifestyle support offered to individuals according to personal barriers and facilitators to lifestyle behaviour change. It is exploratory in nature rather than a scaled-down, pilot version of the main trial. The design of the main trial may be modified based on the findings of the feasibility trial.Leeds Let’s Change[The intervention  is based on evidence about key factors that are known to predict uptake of lifestyle behaviour change ,4, and i’s Change, a localThis study was approved by the committee of the National Research Ethics Service for Yorkshire and the Humber (Leeds East) on 12 March 2012. REC Reference number: 12/YH/0086.The main aim of the study is to assess the feasibility of conducting a definitive trial in terms of recruitment, use and acceptability of the intervention, follow-up at 3 and 6 months, and data collection methods. The following criteria will be used to assess success:1. Favourable difference shown in referrals and participation.2. Favourable changes made through self-management.3. Recruitment target met in time available.4. Retention rate at 75% or more at 6 months follow-up.5. Missing data at 10% or less, including 6 months follow-up.6. Included participants are representative of the target population.In addition, the study aims to establish suitable procedures for delivering the intervention and conducting assessments and procedures for ensuring recruitment and retention in the study. Finally, the study aims to discover whether using a structured, individualized approach to lifestyle assessment and referral will improve uptake and participation in lifestyle- and behaviour-change interventions;The study will also examine, qualitatively, the acceptability of the assessment tool to patients in an acute cardiology setting as well as patients’ experiences of making lifestyle changes in order to develop effective recruitment and retention strategies.The study will have a number of quantitative objectives:1. To determine how many patients accept referral to a formal lifestyle programme;2. To determine how many patients participate in a lifestyle-change intervention or initiate self-managed change;3. To investigate the uptake of lifestyle intervention in relation to subsequent behaviour change and impact on health-related quality of life, mood and social satisfaction;4. To estimate feasible eligibility, recruitment and refusal rates, and 3- and 6-months follow-up rates;5. To measure key outcome domains  for patients including clinical indicators and patient-reported measures of social satisfaction; health-related quality of life; and mood;6. To synthesize data to inform the sample size of a definitive trial;7. To determine the acceptability (and factors influencing this) of financial incentives as a method to encourage behaviour change, their pricing and factors influencing this.This study is being conducted in cardiology wards at the Leeds Teaching Hospitals Trust with patients admitted to hospital, who are subsequently referred to the cardiac rehabilitation team or discharged with no confirmed diagnosis of cardiac event.The study is designed as a single-centre, randomized, unblinded feasibility trial in an acute hospital setting Figure .A sub-study will explore the acceptability and potential usefulness of using financial incentives to help patients overcome motivational and financial barriers to changing their health behaviour. Incentives will not be offered within the trial but we will explore theoretical aspects, such as the pricing and type of incentives offered, and the association of type and magnitude of incentive with perceived difficulty of change. A survey questionnaire specifically designed to explore attitudes to incentives will form part of the study assessments.Participants are randomized, using block randomization with randomly varying block sizes, in equal proportions, with no stratification, to receive either usual lifestyle assessment or an enhanced lifestyle assessment using an automated 24-hour telephone randomization service provided by the clinical trials research unit. The usual lifestyle assessment comprises a series of questions that identify lifestyle factors  that contribute to an increased risk of vascular events. The enhanced lifestyle assessment includes the usual assessment but also contains an evidence-based lifestyle referral assessment based on factors that predict change [Men or women aged between 40 and 74 years of age at the time of screening, who are willing and able to give written informed consent, and have been admitted to hospital with a diagnosis of acute coronary event, myocardial infarction or symptoms of a cardiac nature will be eligible for inclusion in the study.Patients who are currently receiving specialist treatment with a primary focus on alcohol, smoking, diet or exercise, or who have no modifiable risk factors for vascular events will be excluded from the study. In addition, patients who will be unavailable for follow-up because they have no fixed abode, are mainly resident abroad, or are currently serving a sentence in prison or have outstanding legal issues likely to lead to imprisonment will be excluded, as will patients who are unable to take part in either intervention using spoken English or are unable to complete the English-language outcome measure tools without assistance.Based on figures available at the planning stage, we can estimate that cardiology services in the Leeds Teaching Hospitals Trust receive around 800 admissions per month; on average approximately 300 of these admissions are people who have had an acute myocardial infarction and 150 are people who have experienced an acute cardiac event; the remainder are elective admissions for cardiac-related procedures such as stenting. It is therefore estimated that ten patients per week could take part in the study. This estimate is also based on local knowledge and previous experience of recruiting patients with acute stroke in a similar setting .All patients admitted to the selected wards are considered potential participants. Potentially eligible patients are identified by research staff from the ward admissions register or by direct referral from ward staff. These patients are approached by the research team or ward staff to determine willingness to participate and an eligibility checklist is completed. Assessment of psychological status and cognitive capacity to participate is made in consultation with ward staff. All patients meeting the eligibility criteria are provided with an explanation of the study and a patient information sheet, and have an opportunity to ask questions. If willing to continue, they are invited to participate in the study and give written consent. Participation in the study does not alter their usual care. Reasons for nonparticipation, date of birth, sex and postcode are recorded whenever possible.The rates of recruitment to the trial are given in Figure This is a longitudinal study with two follow-up points. Data Table  are collChange in lifestyle will be determined by self-reported changes in alcohol consumption , smokingPatients will also complete a questionnaire developed specifically for the trial as part of the incentives sub-study. The Valuing Health Change Questionnaire asks about the perceived difficulty in changing health behaviour, willingness to accept financial (dis)incentives (and minimum acceptable incentive amounts) and some supplementary questions required for the analysis in order to analyze the incentive, including attitudinal and time preference questions.There are no suitable quantitative measures of uptake, participation and maintenance of behaviour change. Information about participants’ acceptance of lifestyle advice, motivation to change and experience of effecting change will therefore be collected using qualitative methods in a structured interview, which will be conducted at the three and six-month follow-up points. Interviews will be conducted face-to-face or by telephone. The primary endpoints for the trial will be coded from this information and analyzed quantitatively. The interview data will be analyzed using a thematic framework approach and will be used to inform the development of a larger-scale trial.t test with a 2-sided 5% significance level, there would be an 80% power of detecting a standardized effect size of 0.6 in any outcome variable with 90 patients at analysis. As this is larger than the clinically meaningful effect of 0.4, our results will be classed as inconclusive rather than negative if no statistically significant difference is found. We will report 95% confidence intervals and interpret the level of uncertainty based on these.We planned to recruit a minimum of 120 patients over four months, randomized equally between intervention and control groups. Assuming that loss to follow-up will be no greater than 25% at 6 months, this will leave 90 patients for our study. This study is designed to assess the feasibility of conducting a definitive trial; because effectiveness is not being evaluated, a formal power calculation would not usually be considered necessary for the primary objectives. However, there is a secondary proof-of-concept element to the study. Based on a two-sample Student’s The primary analysis will be conducted on the intention-to-treat sample, including all randomized participants in the groups to which they were randomized. Analysis will focus on descriptive statistics and confidence interval estimation rather than formal hypothesis testing. The primary outcome of successful uptake of lifestyle advice is made up of two components: accepting referral or self-referral and participation in lifestyle interventions or self-management. The first is a binary outcome  while the second is ordinal . Both will be summarized in each group, along with 95% confidence intervals to provide evidence of proof of concept.n (%), mean (standard deviation) or median (interquartile range), as appropriate, both overall and by randomized group, to characterize the sample and look for any imbalances. Risk factors for vascular events will be summarized, together with the frequency at which patients seek help. Referral choice will then be summarized by randomized group. Responses to the new assessment will be explored, including any changes between first and second assessments. Protocol violations will be reported, including an exploration of the predictors of any missing data. The primary outcomes will be summarized descriptively by behaviour change in relation to risk factors and by health-related quality of life, mood and social satisfaction to assess the relationship between the process and the clinical endpoints. Completion rates and missing item data will be summarized for key secondary outcomes, together with estimates and variances to aid calculation of sample size for a definitive trial.A standard CONSORT-approved diagram will depict the flow of patients through the study from screening to analysis  benefitted greatly from the involvement of the CLAHRC vascular theme patient and public involvement (PPI) group. The group comprises people with a range of experience of vascular and chronic respiratory conditions, either as patients or as carers. The outcome of the consultation with the PPI group was summarized in an appendix to the full trial protocol (available on request) and submitted to the local research ethics committee. We will undertake further consultation with a wider group of service users during the later phase of the trial, specifically, at the dissemination stage.Reducing demands on the NHS by giving advice and information to people to enable them to manage and maintain their own health was one of the tenets of the Wanless report . This haIf the results of this preliminary work are positive, and our success criteria are met, we intend to develop a large-scale trial to evaluate the clinical and cost effectiveness of systematized lifestyle assessment on reducing risk factors for cardiovascular disease and improving health status. Other associated effects, such as social functioning and emotional wellbeing, would be considered secondary outcomes. This study is designed to demonstrate that such a trial could be implemented in an acute cardiac setting and to develop an optimized, practicable protocol; secondly, to show that the assessment is viable and can be implemented with patients; and thirdly, to provide an estimate, and a confidence interval, for the efficacy of the assessment, to determine whether a definitive, large-scale trial would be warranted. These aims constitute a balance between, on the one hand, feasibility work and, on the other, proof of concept.This is the first study of this type of intervention, to our knowledge, in an acute hospital setting, and the first in cardiology. This study paves the way for a larger-scale trial by giving us insight into operational procedures, such as recruitment and follow-up of patients; and the assumptions necessary to calculate the required sample sizes. It also allows us to test and refine methods of data collection and intervention provision. Our larger-scale trial would be multicentre and would require us to consider training hospital staff to deliver the assessment on the ward, as well as introduce different methods of directing patients toward locally available formal programmes. This preliminary work provides a case-study for wider roll-out and generalization and will give a useful indication as to whether there is benefit in approaching different lifestyle behaviours in different ways.Given current emphasis on lifestyle change as a mechanism for improving health and wellbeing across the population, the significance of the larger-scale trial to which this would lead is important. The difficulties of addressing lifestyle factors and supporting behaviour change are widely acknowledged; therefore, we consider that the results from this study will be of value both to the acute setting and to primary care. A systematic approach to assessment would facilitate audit and provide an indicator of the quality of care. It would also facilitate feedback to clinical commissioners and enable service improvement measures to be implemented where required. The new assessment template has been designed to be quick and easy to use in practice and could, for example, be added to a primary care consultation or form part of a nursing discharge assessment in an acute setting.The trial is on-going.CLAHRC: Collaboration for applied health research and care; IMPROVE: Improving prevention of vascular events; NICE: National Institute for Health and Clinical Excellence; PPI: Patient and public involvement.The authors declared that they have no competing interests.KH wrote the study protocol, managed the trial and took the lead in writing the manuscript. REAW designed the statistical analysis and assisted in writing the manuscript. DC implemented the protocol, collected data, refined the study processes and reviewed the manuscript. DM designed the health economics component and contributed to the manuscript. GR provided guidance on clinical aspects of the trial. AJF contributed to writing the protocol, supervised the statistical aspects of the trial and data management and reviewed the manuscript. JYM designed the lifestyle assessment tested in the trial and reviewed the manuscript. AH conceived the trial and contributed to writing the protocol and the manuscript preparation. All authors have read and approved the final manuscript.KMH: BSc, MSc, PhD, Senior Research Fellow.REAW: BSc, MSc, PhD, Principal Medical Statistician.DCC: BSc, MSc, Research Officer.DMM: BA, MSc, Lecturer and Doctoral Student.JYM: BSc, MSc, PhD, Senior Research Fellow.GR: MBBS, FRCP, Consultant Cardiologist; Clinical Director, Cardiology and Respiratory Medicine.AJF: BSc, MSc, Professor of Clinical Trials & Evaluation of Complex Interventions.AOH: BSc, MBBS, MRCP, MRCPsych, DM, Professor of Liaison Psychiatry.


Surveillance systems often present data by means of summary measures, like age-standardised rates. In this study, we aimed at comparing information derived from commonly used measures of smoking with that presented in modified population pyramids (PPs), using the example of the diffusion of smoking in Italy over the past two decades.Data were derived from four National Health Interview Surveys carried out in 1983, 1990 to 1991, 1999 to 2000, and 2004 to 2005. After computing both age-specific and age-standardised rates of current, former, and never smoking, we constructed modified PPs by stratifying the male and female populations according to smoking status and educational level.Modified PPs showed several features of the smoking epidemic in Italy that were not apparent from conventional surveillance techniques. First, they showed that the population of smokers is aging, with most current smokers in 2005 being males aged 25 to 39 and females aged 40 to 49, whereas in 1983 most smokers belonged to the youngest age groups. Second, they showed that in 2005 most smokers were found among subjects with middle and higher education, whereas two decades earlier most smokers were  subjects with the lowest education.Modified PPs were able to show how absolute numbers of smokers were distributed by age and sex, how these numbers varied between population subgroups, and how they changed over time. PPs may help provide information on past and future trends in the absolute number of smokers and in their sociodemographic characteristics, which may be missed using only traditional surveillance methods. Tobacco smoking largely contributes to premature death and disease in developed countries. It is eIn the UK, smoking reached its peak among men in the 1940s and among women two decades later-8.Subjects at the top of the social hierarchy were the first to take up the habit of cigarette smoking, but afterwards the social pattern reversed, with higher smoking rates among the worst off. SmokingMonitoring the prevalence and distribution of smoking is essential in order to assess how smoking diffuses over time as well as to identify in which population groups smoking is more common. Monitoring is also needed to evaluate the effectiveness of tobacco control policies. To thesSurveillance systems often present data by means of summary measure like age-standardised rates. Age-standardised prevalence rates are used in order to compare populations with different age structures. It is aPopulation pyramids (PPs), also known as age-sex pyramids, may be easily adapted to provide relevant information on such absolute numbers. A PP describes the age and gender structure of a population by means of two juxtaposed histograms, one for each gender. The absolute number of subjects in each age and gender subgroup is shown. The shaIn this exploratory study, we compare information on the absolute number of smokers presented in modified PPs with that coming from commonly used smoking prevalence rates. We use the illustrative example of the diffusion of smoking in Italy, a country in which the epidemic has moved towards the later stages only in recent years,18. OverWe used data deriving from four National Health Interview Surveys carried out in Italy in 1983 , 1990 to 1991 , 1999 to 2000 , and 2004 to 2005 . Each survey collected information on representative samples of the non-institutionalized Italian population using multistage sampling. Response rates were 90%, 89%, 87%, and 84%, respectively. Data on smoking were collected through the use of interviewer-administered questionnaires in the first two surveys and self-compiled questionnaires in the most recent ones.The National Institute of Statistics (ISTAT) provided anonymous electronic datasets of the four surveys. From these datasets, we extracted data on age, gender, education, and smoking status for subjects aged 20 to 99. These individual-level variables were selected because they are strong determinants of smoking and are routinely collected in smoking surveillance systems. On the Individuals were classified as current smokers, former smokers, and never smokers on the basis of the question “Do you currently smoke?” Response options were “Yes”, “No and I never smoked,” and “No and I used to smoke.” Occasional smokers, as well as pipe and cigar smokers, were classified as never smokers. The same questions were used throughout the four surveys.st of each year were derived from the same institute[Age (by 10-year categories) and gender-specific rates of current/former/never smoking were computed for subjects aged 20 to 99 at the time of each survey, taking into account individual survey weights provided by ISTAT. Combining these prevalence rates with population estimates, we were able to estimate the actual number of subjects in each sex and smoking category by single year of age. Population estimates of the age and gender distribution of the Italian population on January 1nstitute,20. Age PPs were constructed by stratifying each bar of the two histograms that compose the PP  according to individual smoking status . All statistical analyses were carried out using Stata 11. The code used to produce PPs was presented at the 2008 Italian Stata users meeting.The age-standardised rates of current and ever smoking in Italy between 1983 and 2005 are shown in Table The age-specific rates of current and ever smoking in 1983 and 2005 are shown in Figure The modified PPs for year 1983, 1990, 2000, and 2005 are shown in Figure The relationship between education and smoking, and how it evolved over time, is shown in Figure The modified PPs in 1983 and 2005 are shown in Figure This study is mainly limited by the use of cross-sectional surveys. This implies that nonresponse and underreporting of smoking may affect our findings. However, nonresponse rates were generally small in the Italian National Health Interview Surveys, and self-reports of smoking are considered adequate. Severalth century in Italy among young adults, following several reforms in the educational system[A good graph tells a story. Although the PP is a snapshot of basic demographic data, it tells the story of how the structure of an entire population is changing over time. Both long-term trends and sudden changes in fertility and mortality rates influence the shape of the PP. For instance, the marked reduction observed at the bottom of the PP between 1983 and 2005 was caused by declining fertility rates during the 1970s and 1980s in Italy, whereasl system.To the best of our knowledge, hardly any use has been made of PPs outside the realm of demography. PPs were used to describe marital status according to age and sex in the UK, but no PPs convey information that is not provided by common surveillance methods. First, the large asymmetry between males and females in smoking behaviour in 1983 and the fact that smokers were mostly young adults are both more visible with the PPs than with traditional representations. Absolute numbers are sometimes more relevant than relative numbers  from a public health point of view. This applies to smoking cessation services, which need to plan their resources and activities according to the number of smokers. Population subgroups with the largest number of smokers do not necessarily have the highest prevalence rate of smoking. In the case of males in 2005, the age profile of the number of current smokers and that of current smoking rates did not exactly match: males who were 80 to 89 years old in 2005 had the highest rates of ever smoking, but the absolute number of these subjects was extremely small compared to other age groups.Second, changes over time in the age and sex distribution of smokers become evident when PPs are made for different time periods: these changes are the result of both the underlying demographic processes  as well as the dynamic processes that regulate the flow of subjects into and out of the “pool” of smokers . With the use of PPs, we were able to show that, between 1983 and 2005, the population of smokers had a less skewed age distribution.Third, PPs may be useful for comparing population subgroups that strongly differ in their age distribution. Stratifying the PPs by educational level, we were able to show that in 1983 most smokers were found among middle-aged males with the lowest education, whereas two decades later most smokers were found among young adults with higher educational levels. In the case of education, the story told by the PP is rather different compared with that displayed by the age-specific rates of current smoking: an inspection of these rates indeed suggests that, among young adults, the educational gap in smoking increased over time among young males, and that there was a reversal of the association between smoking and education among young females. Policy interventions aiming at reducing smoking behaviour within young adults with the lowest educational level, which is the subgroup with the highest smoking rate, would in fact provide only minor public health benefits, because there were very few smokers in this group, especially in 2005.Finally, PPs may inform on future trends in the absolute number of smokers. PPs made clear that the population of smokers is likely to be aging within the next 20 years in Italy, as a result of the inevitable decline in the number of people younger than 40 years. Moreover, PPs made clear that, within about 20 years, smokers with a low educational level will start to be extinguished and they will be replaced by smokers with higher levels of education.This study has a few implications for tobacco control policies. The first one relates to smoking surveillance, which is one of the pillars of tobacco control. In addiModified PPs are able to show how absolute numbers are distributed by gender and age, how these numbers change over time, and how they vary between population subgroups. We argue that the visual information provided by the modified PP make it a natural complement in surveillance to other statistical methods, such as the presentation of age-specific and age-standardised rates. We also suggest that this graphical representation may be of value to show trends over time in the absolute number of people exposed to other risk factors or health conditions, such as overweight and obesity, alcohol abuse, or physical disability.The authors declare that they have no competing interests.BF and GCapelli conceived the study and they performed statistical analyses. GCosta provided data and helped in the interpretation of the study findings. AEK and JPM participated in the design of the study and they critically revised the manuscript. BF drafted the manuscript. All authors read and approved the final manuscript.


Since 2000, access to antiretroviral drugs to treat HIV infection has dramatically increased to reach more than five million people in developing countries. Essential to this achievement was the dramatic reduction in antiretroviral prices, a result of global political mobilization that cleared the way for competitive production of generic versions of widely patented medicines.Global trade rules agreed upon in 1994 required many developing countries to begin offering patents on medicines for the first time. Government and civil society reaction to expected increases in drug prices precipitated a series of events challenging these rules, culminating in the 2001 World Trade Organization's Doha Declaration on the Agreement on Trade-Related Aspects of Intellectual Property Rights and Public Health. The Declaration affirmed that patent rules should be interpreted and implemented to protect public health and to promote access to medicines for all. Since Doha, more than 60 low- and middle-income countries have procured generic versions of patented medicines on a large scale.Despite these changes, however, a "treatment timebomb" awaits. First, increasing numbers of people need access to newer antiretrovirals, but treatment costs are rising since new ARVs are likely to be more widely patented in developing countries. Second, policy space to produce or import generic versions of patented medicines is shrinking in some developing countries. Third, funding for medicines is falling far short of needs. Expanded use of the existing flexibilities in patent law and new models to address the second wave of the access to medicines crisis are required.One promising new mechanism is the UNITAID-supported Medicines Patent Pool, which seeks to facilitate access to patents to enable competitive generic medicines production and the development of improved products. Such innovative approaches are possible today due to the previous decade of AIDS activism. However, the Pool is just one of a broad set of policies needed to ensure access to medicines for all; other key measures include sufficient and reliable financing, research and development of new products targeted for use in resource-poor settings, and use of patent law flexibilities. Governments must live up to their obligations to protect access to medicines as a fundamental component of the human right to health. A decade ago, the world prepared to gather in Durban, South Africa, for the first International AIDS Conference to be held on the continent most devastated by HIV. At the time, the statistics were grim: only one in a thousand people living with HIV in Africa had access to AIDS treatment . AntiretWith civil society at the forefront -8, a joiThis achievement required some essential ingredients: first, civil society had to put access to treatment for HIV/AIDS on the global political agenda; second, innovative healthcare providers had to demonstrate that delivering treatment was safe and effective and thus feasible in resource-poor settings; and third, the price of medicines had to come down. Once these ingredients were in place, increased funding for ARVs followed, and investment in strengthening health systems to deliver treatment and care for all - both HIV positive and HIV negative - was made possible. Civil society, alongside courageous leaders willing to take risks, made it happen.While the achievements have been enormous, huge challenges remain to sustain the progress made to date and to meet future needs.The past 10 years have shown how ARV treatment can reduce HIV/AIDS-related illness and death in developing countries. But in the current climate of wavering support for achieving universal access to treatment, prevention, care and support - a commitment that Member States made at the UN General Assembly just five years ago ,17 - it 3 rather than 200 [3 or above [Overall, ARVs are still underused relative to need, and they still reach people with too much delay. The latest World Health Organization (WHO) guidelines for HIV treatment in resource-poor settings recommend that people should start treatment when their CD4 cell counts are above 350 cells/mmthan 200 ,19. Receor above . HoweverIn order to address this challenge, ARVs should be more affordable, meet current medical standards, and be developed or adapted for use in the contexts where they are needed: that is, in settings with minimal or no monitoring available , where refrigeration may be scarce, and where health workers are in short supply.What role do intellectual property rules and practices play in this equation? The AIDS crisis has radically changed conceptions of and policy approaches to patents on medicines. This shift is reflected in changes in international treaties, national law, public policies, and the business practices of pharmaceutical companies. In order to understand current thinking on HIV medicines patents, we need to look back at least to the 1990s.In 1996, a group of health non-governmental organizations (NGOs) met in Bielefeld, Germany, to discuss the public health implications of new intellectual property rules created by the World Trade Organization (WTO). The Agreement on Trade-Related Aspects of Intellectual Property Rights (TRIPS) was part of the set of treaties that established the WTO in 1994, and had just come into force in 1995. The negotiations leading to TRIPS had been primarily driven by the trade and commercial interests of the industrialized nations ,8. WhileTRIPS required that all WTO Members, which today number 153, provide a minimum standard of intellectual property protection, and was enforceable through the WTO dispute settlement procedures. The standards for intellectual property protection that were globally harmonized through the TRIPS Agreement derived primarily from practices in the industrialized countries, where national patent systems had evolved over many years. While proponents argued that TRIPS would increase foreign direct investment, technology transfer and research in the developing countries, critics argued that it would retard industrialization, hamper technology transfer and increase the prices of essential goods, such as medicines and agricultural inputs ,22-36.Before TRIPS, pharmaceutical patent policies and practices were diverse. For example, many countries did not consider patents on such products as medicines and food to be in the public interest. Half of the 98 countries that were members of the 1883 Paris Convention on the Protection of Industrial Property  actively excluded pharmaceutical (product) patenting altogether . Some coTRIPS put an end to this diversity when it required all Members to introduce 20-year patents in all fields of technology; in practice, this requirement meant that many developing countries had to begin offering patents on pharmaceutical products for the first time. Because TRIPS was part of the WTO package, countries that wished to remain Members of the WTO could not opt out of TRIPS or make reservations to the treaty . The ensuing years saw a wave of intellectual property reforms in most developing countries in response to TRIPS obligations . The polIn the late 1990s, the potential effect of these new intellectual property rules on access to medicines was little understood, and interest in intellectual property issues among the public health community was still rare.In early 1998, 41 drug companies and their representative body sued the new democratic post-apartheid government of South Africa over amendments made in 1997 to its Medicines Act, which aimed to make low-cost medicines more readily available. The companies asserted that it was neither constitutional nor in compliance with the TRIPS Agreement .This lawsuit was brought against the backdrop of the growing AIDS crisis. It came two years after the 1996 International AIDS Conference in Vancouver, Canada, where the world had learned that highly active antiretroviral therapy could transform HIV infection from a disease with a certain death sentence into a chronic, manageable condition. However, while ARVs were becoming available in the industrialized countries, they remained far out of reach of most South Africans and others living in developing countries. At the time, South Africa was (and remains today) home to the largest estimated number of PLHIV in the world.Big Pharma vs. Nelson Mandela shocked the world's conscience. It was a call to action that pulled many different actors onto the stage.In 1999, at the United Nations in Geneva, a group of NGOs and AIDS activists held a conference on compulsory licensing for HIV medicines. A compulsory licence is a way to remedy problems caused by a patent, whereby a government body  grants a licence to an entity other than the patent holder, allowing them to produce the patented product in exchange for "adequate remuneration". It is allowed under the TRIPS Agreement, which sets out some procedural requirements but leaves countries free to determine the grounds for issuing a compulsory licence. Industrialized countries have repeatedly used compulsory licensing, including to purchase low-cost medicines. For example, from 1969 until 1992, when Canada changed its system as a requirement of the North American Free Trade Agreement, Canada granted 613 compulsory licences for the production or import of generic medicines, leading to some of the lowest medicines prices in the industrialized world .  to a standstill. Had the demonstrators not disrupted the gathering, the forecast for global pharma might be much cloudier ."At the time, an editorial in the The period between the failed Seattle WTO Ministerial conference in 1999 and the 2001 WTO meeting in Doha saw a number of developments that had a profound effect on intellectual property rules and access to medicines.Developing countries that were at the forefront of providing ARV therapy began to experience the consequences of pharmaceutical patents on HIV/AIDS drugs. For example, in Thailand and Brazil, patents significantly limited the legal space to produce lower-cost generics, resulting in a heavy burden on public health budgets.Brazil was the first developing country to provide widespread access to HIV/AIDS treatment through its national programme; the Brazilian programme demonstrated to the world that ARVs could be provided safely even with limited toxicity and efficacy monitoring . InitialAt the same time that awareness of the public health implications of TRIPS was growing, the AIDS crisis also began to attract greater political attention at the global level. In 2000, the Group of 8 countries paid unprecedented attention to health and the need for action to increase access to medicines. At the International AIDS Conference in Durban, the Treatment Action Campaign and its partners organized the Global March for Treatment, squarely placing access to ARVs on the political agenda.In December of that year, a three-day global summit in Okinawa, Japan, on infectious diseases outlined an agenda to prevent the spread of AIDS, provide treatment and care for those affected, and to enhance research and development (R&D) for international public goods, including new approaches to managing intellectual property. Most importantly, Okinawa witnessed the birth of the Global Fund to Fight AIDS, Tuberculosis and Malaria , a result of extensive efforts by many advocates to create a new approach to financing the international response to HIV and other global health concerns.Under increasing public pressure to support rather than hinder efforts to combat the epidemic, the patent-holding pharmaceutical industry began to respond. In May 2000, five pharmaceutical companies announced the Accelerating Access Initiative, offering price discounts on HIV-related medicines and diagnostics in developing countries . HoweverGeneric production of ARVs in India was possible because the Indian Patents Act did not provide for patents on pharmaceutical products until required by TRIPS to do so in 2005. Generic producers competed with each other to make medicines at prices far lower than the originators. Indian firms also combined two or more medicines into one pill in "fixed-dose combinations" (FDCs), a type of innovation facilitated by the absence of medicines product patents. FDCs are thought to facilitate patient adherence, reduce the risk of resistance and simplify supply chain management -47. Althdifferent companies was the combination of tenofovir, emtricitabine and efavirenz (brand name Atripla). First approved by the US Food and Drug Administration in 2006, this product has become the standard of care in recent recommendations in high-income countries.In high-income countries, the patents on these three medicines were controlled by three different companies , which raised the transaction costs of developing this product. In high-income countries, the first three-in-one FDC comprised of medicines on which patents were controlled by In early 2001, the Indian generic medicines producer, Cipla, offered a triple-combination of ARVs for US$350 per patient per year - or HIV/AIDS treatment for less than a dollar a day . At the Also in 2001, controversy had broken out over the cost of the drug stavudine , which came to a head on the Yale University campus in March. Stavudine was developed by researchers at Yale University, which held the patent on the drug. The price of the generic version of stavudine in South Africa was 34 times less than the price of the brand-name product from Bristol Myers Squibb, but the patent prevented its use in South Africa. Under pressure from researchers, students and access advocates, Yale renegotiated its licence with Bristol Myers Squibb to ensure the availability of generic stavudine in developing countries ,52.amicus curiae brief filed by the AIDS Law Project on behalf of the Treatment Action Campaign put the spotlight on access to ARV treatment and brought the matter to the international stage. In April 2001, after a global public outcry that built on the Treatment Action Campaign's legal intervention and domestic advocacy campaign, the drug companies dropped their case against the South African Government. The landscape had dramatically changed.Meanwhile, the Medicines Act court case in South Africa was progressing. In early 2001, an Access to medicines and the need to revisit the patent rules that govern them had become part of a larger political agenda, and was no longer the exclusive domain of trade negotiators or intellectual property lawyers.In November 2001, governments at the WTO Ministerial Conference, in an unprecedented move, adopted the Doha Declaration on TRIPS and Public Health. The Doha Declaration made clear that the TRIPS Agreement "can and should be interpreted and implemented in a manner supportive of WTO Members' right to protect public health and, in particular, to promote access to medicines for all ".This landmark event represented the first significant push back to the relentless march to strengthen private intellectual property rights without regard for societal consequences in poor countries.The 500-word Doha Declaration on TRIPS and Public Health has been essential in making lower-cost generic versions of patented medicines available on a large scale.th decision" in an attempt to find a remedy for legal barriers to exporting sufficient amounts of medicines produced under a compulsory licence, and to ensure that countries that rely on import for their medicines supply could benefit from compulsory licences. Most developing countries do not have domestic manufacturing capacity for ARVs. Although some argued that the absence of ARV patents in a number of African countries meant that intellectual property did not pose a barrier to HIV treatment, this perspective did not take into account the industrial reality that patents in a few producing countries (such as India) could hinder access to generic medicines in scores of importing countries [bis amendment, which has yet to come into force, is the sole amendment agreed since 1994 not only to TRIPS itself, but to the full set of WTO agreements. Public health concerns in general, and the AIDS crisis in particular, made this happen.In 2003, the WTO adopted the "August 30ountries ,55. WhilOn 1 December 2003, WHO and the Joint United Nations Programme on HIV/AIDS declared the lack of HIV/AIDS treatment to be a global public health emergency and announced the launch of a drive to get three million people on ART by 2005; this was the "3 by 5" campaign. The political momentum of the campaign, combined with newly available funding from governments, the Global Fund and the US President's Emergency Plan for AIDS Relief (PEPFAR), allowed countries to begin purchasing HIV/AIDS medicines in significant volumes.By 2010, such purchases were predominantly generic drugs . For exaHow did countries manage the potential barriers posed by patents? While Thailand and Brazil's compulsory licences for ARVs in 2006 and 2007 have been widely publicized, it is perhaps less widely known that over 60 developing countries have procured lower-cost medicines on a large scale using TRIPS flexibilities ,43,59. OIn other cases, the policy space for countries to use such flexibilities is being constrained by stringent intellectual property requirements that exceed TRIPS and are contained in bilateral or regional free trade agreements, investment treaties and/or WTO accession agreements . Middle-Many countries could import generic ARVs, largely because India could produce and export them . There wCompanies have also responded to patent challenges by agreeing to voluntary licences to their patents. For example, GlaxoSmithKline and Boehringer-Ingelheim expanded their voluntary licences in South Africa as part of a settlement reached after the AIDS Law Project, acting on behalf of the Treatment Action Campaign and others, had filed a successful complaint with the South African Competition Commission ,65. CompIn short, the AIDS crisis has been an engine for change. These changes extend beyond the field of intellectual property and access to medicines, and also include:• Increasing political attention for global health well beyond HIV and AIDS• Strengthening the role of civil society in decision making in health policy• Bringing about new financing mechanisms, such as the Global Fund, PEPFAR and UNITAID, whose beneficiaries go beyond HIV and AIDS• Catalyzing other innovative approaches to financing development, such as the "Robin Hood tax" • Expanding healthcare delivery through task shifting from doctors to nurses and/or community health workers ,70• Empowering patients through treatment literacy, and putting PLHIV at the centre of their own treatment• Catalyzing the establishment of access strategies by the pharmaceutical industry• Establishing the WHO Prequalification Programme, which helped create the market for low-cost generics by providing quality-assurance and a level playing field for competitors • Improving the standard of care for chronic conditions in resource-limited settings.The HIV/AIDS crisis and AIDS activists also impacted the way R&D for new medicines is carried out. Since the 1980s, when the US National Institutes of Health was investing in the development of the first AIDS drugs, PLHIV developed scientific expertise on the virus, clinical trials, research methods and promising candidates for drug development. For example, activists demanded greater freedom to decide which risks they were willing or unwilling to take with experimental therapies, and challenged what they saw as the slow pace of regulatory decisions at the US Food and Drug Administration . In addiA patent can be understood as a type of social contract: in exchange for exclusive rights, patent holders are expected to provide benefits, such as innovation, to society. If, however, these benefits are not forthcoming or not widely available, the contract is not being fulfilled . In the Between 1975 and 2004, of the 1556 new chemical entities marketed globally, only 20 (1.3%) new drugs were for tropical diseases and tuberculosis, diseases that account for 12% of the total disease burden . In 2006A number of new initiatives have been launched to address the problem of insufficient research into the neglected diseases. These include more than two dozen public-private product development partnerships, such as the Drugs for Neglected Diseases initiative  and a "pPrescrire International found that 68% of the 3096 new products approved in France between 1981 and 2004 offered "nothing new" over previously available medicines. Furthermore, an analysis of more than 1000 new drugs approved by the US FDA between 1989 and 2000 found that more than three-fourths have no therapeutic benefit over existing products [The search is on for new ways to generate needs-driven medical innovation that will meet the needs of both the world's rich and poor. Indeed, the crisis in innovation is not limited to developing countries or neglected diseases alone. While globally, the level of patent protection has increased over the past 20 years, the rate of pharmaceutical innovation has fallen, with an increasing number of "me-too drugs" of little or no therapeutic gain. products .While patents can provide incentives for innovation if sufficient market prospects exist, granting too many intellectual property rights may also impede rather than accelerate innovation by creating a "tragedy of the anti-commons" ,81. At tFurthermore, recent improvements in access to first-line ARVs should not mask the need for additional research in this field. The gold standard three-in-one FDC  still cannot be used during early pregnancy because of the potential first trimester teratogenicity of efavirenz. In addition, the current widely used regimen (which is nevirapine-based) is not suitable for treatment in the early stages of HIV infection due to increased toxicity.While tuberculosis (TB) remains the most frequent opportunistic infection of HIV/AIDS, using ARVs in combination with TB drugs is still a challenge. Regimens for patients for whom first-line therapy is failing are still expensive, inconvenient and carry side effects and potential interactions with multiple other drugs, making their use impractical. Economic incentives are insufficient for the industry to develop child-friendly drug formulations. Finally, implementing WHO's new recommendations for earlier initiation of ARV therapy in both children and adults will require an expanded drug formulary geared towards addressing a generalized epidemic. Products should ideally be heat stable, require minimal monitoring, and offer simplified dosing and other features that facilitate adherence.How can we address these interrelated problems of market-driven R&D priority setting, declining innovation and high medicines prices? A number of new proposals have been put on the table, and are being debated and/or pilot tested, including: rewarding innovation based on therapeutic value; prize funds to attract new "solvers" to a problem; guaranteeing markets for end products; open-source collaborative drug discovery; and an R&D treaty -88. WhilFirst, competitive production of medicines has consistently proven to be the most powerful and reliable way to reduce drug prices to their lowest sustainable levels ,89. New Second, public involvement in and funding for research plays a key role in accelerating scientific progress. Governments need to invest sufficiently in medical R&D. For example, additional funding is needed to conduct further research on promising tenofovir-containing vaginal microbicides to reduce the risk of HIV transmission - a product that offers the important benefit of being woman-initiated and controlled .Third, PLHIV engagement played a central role in overcoming both innovation and access barriers with respect to treatment for HIV/AIDS. New approaches to generating innovation and ensuring widespread access to the fruits of scientific progress should prioritize the engagement of people directly affected by a disease.With all of the progress of the past decade in scaling up access to ARVs, what is the problem? Unfortunately, the challenges ahead are formidable and many.First, the cost of treatment is increasing again because new ARVs are likely to be more widely patented in developing countries and thus more expensive. Even with the high patentability standards implemented in India and other countries, some of the new ARVs are likely to be patented. Without production sources, the countries that rely on importation will find it hard to source low-cost medicines. In addition, patents on individual medicines can make it more difficult to develop new FDCs.Second, increasing numbers of people will need access to new-generation ARVs: an expanded drug formulary is urgently needed. In addition, about two-thirds of people in need of treatment still do not receive first-line medicines today. ARV prices, particularly in some middle-income developing countries, can still put them out of reach of the people who need them. There is wide variation in the voluntary licensing practices of the patent-holding companies, and such licences too often come with limitations that hamper the full effect of generic competition and the ability to develop FDCs.Third, advances in research on newer drugs and combinations need to be available worldwide. For example, tenofovir is a promising newer drug that is finally becoming available in resource-limited settings, but experience on how to use it without monitoring or in specific populations  is lacking. To avert such situations, research should be carried out in the specific contexts, and taking into account the specific co-morbidities of the target populations where medicines are needed. Some drugs, such as raltegravir, elvitegravir or rilpivirine, are promising, but long-term follow up regarding adverse events is lacking, and the feasibility of their use for treating TB co-infected patients is unclear at this stage.Fourth, the policy space to produce or import generic versions of patented medicines is shrinking in some developing countries. Stringent intellectual property provisions exceeding TRIPS requirements ("TRIPS-plus") have been negotiated into free trade agreements between industrialized and developing countries, and/or investment and WTO accession agreements. Measures, such as patent term extensions, data exclusivity, patent-registration linkage and border enforcement requirements, can all delay access to generics by lengthening, strengthening or broadening monopolies on medicines ,92-94. IFifth, we are faced with a serious financial crisis that risks setting back the treatment achievements of the past 10 years.In July 2009, the United Kingdom All Party Parliamentary Group on AIDS called this situation a "treatment timebomb" and called for "political activism" to "ensure that the next generation of drugs is available to the world's poorest in future ".We need to go further than where we are today. We need expanded use of the existing flexibilities in patent law and new models to address the second wave of the access crisis. Without generic competition, prices for newer drugs will not come down the same way that they did for the first generation of medicines. One promising new mechanism is the Medicines Patent Pool, established with the support of UNITAID.UNITAID is a new financing mechanism based on a small solidarity levy on airline tickets, and is supported by 29 countries, the Bill & Melinda Gates Foundation, NGOs and communities. Its mission is to increase access to treatment for HIV/AIDS, TB and malaria by making markets work better for health. UNITAID has raised approximately US$1.5 billion, and seeks to be innovative in the way that it both raises and spends funds ,104.It is UNITAID's overarching principle to make markets work better for health that made it a natural birthplace for the Medicines Patent Pool Initiative, which became operational in mid-2010. The idea for an HIV medicines patent pool was first launched at the 2002 International AIDS Conference in Barcelona, Spain, by James Love from Knowledge Ecology International. He had studied the US airplane patent pool that was established in 1917 by the US Government to overcome patent barriers to the mass production of airplanes needed for the military . He suggThe Medicines Patent Pool is a response to the changed global intellectual property environment in which medicines are being more widely patented in developing countries. It is built on the principle of relying on market competition to bring medicines prices down. However, robust competition is possible only if licences are available.The Pool is expected to work as follows:Patent holders will make licences available through the Pool that will allow others to produce low-cost generic versions of patented ARVs for use in developing countries. It will be important that the licences cover as many developing countries as possible, both to maximize public health benefit and to ensure economies of scale in generic drug production. The licences are also intended to facilitate the development of FDCs and other formulations adapted for use in resource-poor settings, such as special formulations for treating children, by ensuring that patents do not block generic companies or product development initiatives from carrying out follow-on R&D.Companies that receive licences from the pool will pay royalties on their sales to the patent holders. The Pool will be a systematic and predictable way of making voluntary licences available, offering legal certainty to all parties involved. No change in international or national law is required for the Pool to work; what is required is a change in mindset from the patent holders, without whose collaboration this initiative cannot succeed. In other words, the Patent Pool will work only if patent holders are willing to collaborate to make their intellectual property available to the Pool. Several major leading patent holders have expressed an interest and willingness to engage with the Pool.In addition, companies have increasingly adopted voluntary licensing practices as part of their access policies; voluntary measures, such as the Pool, may provide an attractive alternative to non-voluntary measures for patent holders, and can be understood as one outcome of the decade-long evolution in approaches to managing intellectual property and access to medicines. In September 2010, the US National Institutes of Health became the first patent holder to licence its patents (related to a class of ARVs) to the newly established Medicines Patent Pool .Despite these recent developments, the Pool faces many challenges and many key factors have yet to be determined -111. NevNew approaches to achieving innovation and access to medicines are possible today because of the previous decade of activism that demanded a change in the way we approach intellectual property and public health. The political and civil society mobilization catalyzed by HIV/AIDS was at the forefront of these changes. But three warnings merit attention at this point.First, initiatives such as the Pool are only one approach to addressing access issues, and must be seen as complements to a broad set of other policies that are needed to ensure access to medicines for all. The Pool is not a panacea, and governments must live up to their responsibilities to protect the health of their populations.Second, overcoming intellectual property barriers to innovation and competitive production is critical, but is only one piece of the complex machinery required to ensure that we achieve our shared objective of universal access to treatment, care and prevention services for HIV/AIDS. Improving access to medicines also requires addressing regulatory issues, strengthening procurement and supply chains, and establishing pharmacovigilence systems, among other measures. In particular, sufficient levels of funding are critical. Without a market for even the lowest-cost medicines, we cannot expect that anyone will be ready to develop and produce these products.Third, while there may be progress in key aspects of HIV treatment, needs for the development of new products (such as microbicides) and access to medicines for other diseases remain immense. For example, treatment is often unavailable in many developing countries for both acute infectious diseases and chronic diseases, such as diabetes and cancer -114. ProThe struggle for improved access to medicines has been and will be a continuous fight, sometimes an uphill battle, and not always easy to win. But the lessons of the past 10 years show what can be achieved if we mobilize.We are at a crucial point in time: not only do we need to protect what has been achieved, but we also need to be ambitious and go further. It is feasible that with better-adapted, more affordable ARVs, we can double or triple the number of people on treatment without doubling or tripling the cost. We can also ensure that people have access to better and better-tolerated medicines.High prices simply cannot be legitimate grounds for withholding lifesaving treatment from people. Access to medicines is a fundamental human right ,115, whiARV: antiretroviral; FDC: fixed-dose combination; NGO: non-governmental organization; PEPFAR: US President's Emergency Plan for AIDS Relief; PLHIV: people living with HIV/AIDS; R&D: research and development; TB: tuberculosis; The Global Fund: The Global Fund to Fight AIDS, Tuberculosis and Malaria; TRIPS: Agreement on Trade-Related Aspects of Intellectual Property Rights; WHO: World Health Organization; WTO: World Trade OrganizationEtH is the Executive Director of the Medicines Patent Pool and a former employee of UNITAID. SM is a consultant for the Medicines Patent Pool and has been a consultant for UNITAID.EtH was involved in the conception and design of the study, analysis and interpretation of data, drafting the manuscript, and revising it critically for important intellectual content. JB was involved in drafting the manuscript and revising it critically for important intellectual content. AC was involved in drafting the manuscript and revising it critically for important intellectual content. SM was involved in the conception and design of the study, analysis and interpretation of data, drafting the manuscript, and revising it critically for important intellectual content. All authors read and approved the final manuscript.


The demand for health professionals continues to increase, partially due to the aging population and the high proportion of practitioners nearing retirement. The University of British Columbia (UBC) has developed a program to address this demand, by providing support for internationally trained Physiotherapists in their preparation for taking the National Physiotherapy competency examinations.The aim was to create a program comprised of the educational tools and infrastructure to support internationally educated physiotherapists (IEPs) in their preparation for entry to practice in Canada and, to improve their pass rate on the national competency examination.The program was developed using a logic model and evaluated using program evaluation methodology. Program tools and resources included educational modules and curricular packages which were developed and refined based on feedback from clinical experts, IEPs and clinical physical therapy mentors. An examination bank was created and used to include test-enhanced education. Clinical mentors were recruited and trained to provide clinical and cultural support for participants.The IEP program has recruited 124 IEPs, with 69 now integrated into the Canadian physiotherapy workforce, and more IEPs continuing to apply to the program. International graduates who participated in the program had an improved pass rate on the national Physiotherapy Competency Examination (PCE); participation in the program resulted in them having a 28%  greater possibility of passing the written section than their counterparts who did not take the program. In 2010, 81% of all IEP candidates who completed the UBC program passed the written component, and 82% passed the clinical component.The program has proven to be successful and sustainable. This program model could be replicated to support the successful integration of other international health professionals into the workforce. Health-care education around the world varies in educational standards, curriculum, and evaluation methods. The increasing demographic presence of ‘visible minorities’ and internationally-trained professionals, demands equal access to employment opportunities that support practice in occupational roles according to their qualifications and work experience. Support for this transition is essential to maximize skilled contribution to the development of a country . Canada In order to obtain a license to practice Physiotherapy in Canada, in all provinces except Québec, Physiotherapists educated outside Canada must complete the two-part national Physiotherapy Competency Exam (PCE). In 2005 there was a notable discrepancy in pass rates between internationally trained Physiotherapists and Canadian graduates; less than 50% of internationally trained Physiotherapists exam attempts translated into passes, compared to greater than 92% of Canadian educated candidate attempts . The chaThere is some literature about internationally trained health professionals; this literature mainly reflects the process of examining the credentials, competency, demographic characteristics and distribution of international medical graduates (IMGs) -11. TherTo meet the demand for licensed Physiotherapists in Canada, and more specifically British Columbia (BC), and to provide support for internationally-trained physiotherapists who wish to continue to practice their skills and gain licensure, the “Internationally Educated Physiotherapists (IEP) Program Project” was established at the University of British Columbia.The aim of this project was to create the educational tools, curriculum, and infrastructure needed to sustain a program supporting internationally trained Physiotherapists applying for licensure in BC. The primary objective of the program was to increase the pass rate of internationally trained Physiotherapists taking the PCE. The UBC ethics board states that ethical approval is not needed for program evaluation.The project team used a conceptual framework to map the program components, clarify the nature of program goals, and guide the program development . To thisThe IEP project was developed in a partnership with key BC Physiotherapy stakeholders  which provided oversight, guidance, communication services, advertising and marketing support, identification and recruitment of mentors and content experts. A key role in the management of the program was the Program Coordinator, who was a trained and licensed Physiotherapist with over 40 years of practice experience. The Program Coordinator was responsible for all activities of the program, including recruiting, scheduling, data collection, communication and feedback sessions related to exam modules. All inputs and activities are shown in Figure The program consists of two separate streams to assist IEPs in the preparation for the PCE: one in preparing for the written component (QE), and the other to prepare for the clinical component (PNE) of the national exam. IEPs had the option to participate in both streams of the program, or to receive support for the preparation of only one component of the PCE (the written (QE) component or the clinical (PNE) component). The QE consists of 200 multiple-choice questions (MCQs) and the PNE is an objective structured clinical examination (OSCE) to evaluate candidate’s interactions in controlled scenarios with standardised clients. The primary objective of the program is to assist IEPs with their preparation for taking these exams. To achieve this objective, modules including examination writing skills, content area review, and practice exam experiences (using tested-enhanced learning theory) were developed . Many reContent experts developed initial versions of the curricular modules covering the four primary areas of Physiotherapy practice using the DACUM (Developing a Curriculum) model . All modAccess to Physiotherapy mentors was initially identified as important to provide IEPs with the acquisition and reinforcement of practical skills in a Canadian context. Mentors were recruited from the clinical community based on area of clinical expertise, and experience teaching and supervising students. Three mentor-training workshops that focussed on facilitation techniques to support the learning of entry-level physiotherapy skills were offered to interested physiotherapists across the province. IEPs were matched with mentors who specialize in the primary areas of practice. The responsibilities of the mentors were to facilitate the development of the knowledge, clinical skills and clinical reasoning in each content area as expected in Physiotherapy practice in Canada. Mentors were also responsible for supporting the IEPs to achieve the competencies, as outlined in each module.The program evolved since inception as a result of feedback from a variety of sources, including data collected from the IEPs, mentors and the IEP Advisory committee through focus groups and interviews. Feedback indicated that sample exam questions and practice exams were not perceived to accurately reflect the final PCE exam, and that there was a lack of detailed feedback after practice exams. Furthermore, IEPs suggested that modules were not specific enough and that IEPs were unfamiliar with terminology used within the Canadian Physiotherapy context. In response, study questions and a glossary of terms were added to each module, more complex vignette-based questions were developed, and based on the results of their exams IEPs are provided with guidance to further resources and study suggestions.Several new initiatives resulted from the interviews with IEPs, including: clinical skills lab reviews; written tutorial workshops; mobile mentors; small group mentorship; delivery of written exam modules to remote communities; and transitioning the written program to an on-line platform. In addition, the written exam preparation was transitioned to a fully on-line program, so all aspects of the module was accessible to IEPs throughout BC, across Canada and even internationally.The first step of the Program Evaluation was the formation of a program logic model followed by analysis of the outcomes defined in the model. Data for IEP candidates, all international Physiotherapy graduates, and Canadian graduates is shown for the PCE across time Table . The difSeven modules, based on the PCE blueprint and the core competencies of entry level physiotherapy in Canada, were developed and trialled.More than 500 MCQs and 22 OSCE questions were developed, reviewed and, stored in the exam bank with marking guides and patient model instructions where appropriate. This supported the administration of internal written tests and internal clinical tests.Initially 35 mentors were trained and paid for a maximum of 10 hours per IEP to provide one-on-one support and expertise during the exam preparation. The number of mentors trained was sufficient for the number of IEPs residing in the Lower Mainland of British Columbia, however, there were challenges pairing mentors with IEPs who resided out of the Lower Mainland, particularly those IEPs in rural areas. To address this, mobile and small group mentorship models were developed, which involved mentors from the Lower Mainland travelling to meet with IEPs in remote areas. This model proved to be cost effective and time efficient. In addition, higher IEP to mentor ratios , maximised the mentor time and provided a more “dynamic” session for the IEPs. Feedback from IEPs and mentors, indicated that few IEPs utilized the allocated time with mentors, and that IEPs found the other components of the program  of more benefit. The mentorship model therefore moved to self-regulated access; that is, IEPs were given contact details for mentors and were encouraged to make independent arrangements to meet with mentors according to need.The first cohort of nine IEPs was admitted into the program in July 2008. Figure Table Of the 65 IEPs taking the QE exam 65% had English as their first language, of these 63% passed the exam. Of the 35% who did not have English as their first language, 40% passed the QE. IEP candidates who have English as their first language have a non-statistically significant 58% increased risk of passing the QE, RR = 1.58 . Of the 83 IEPs taking the PNE exam, 74% had English as their first language, of these 93% passed the exam. Of the 26% who did not have English as their first language, 67% passed the PNE. For the PNE, IEP candidates who have English as their first language have a statistically significant, 40% increased risk of passing with an RR = 1.4.Of the 124 people who entered the IEP program 69 are known to have entered the Canadian physiotherapy workforce, with 34 of these known to be working in the public sector, five people are temporarily not in the Canadian workforce, due to child care or visa problems, and 20 are awaiting immigration approval for entry to Canada.The aim of the IEP Program was to create the educational tools and infrastructure needed to sustain a program supporting internationally trained Physiotherapists applying for licensure in BC. Consideration was given to developing a program that included the necessary curriculum, resources, mentorship and practice opportunities to assist IEPs in their preparation for the exams and entering the Canadian workforce. As many resources as possible were made available on-line to serve the needs of IEPs from clinical practice sites distant from Vancouver. Evaluation was built into the program to inform continuing program improvements and the development of additional program initiatives. This has resulted in the Program attracting greater numbers of IEPs than projected, and providing the flexibility to support and accommodate these greater numbers. Projections identified the capacity to support and accommodate 8 IEPs per year in the practical and 16 in the written, and over the first 4 years of the program (2008–2011), 124 IEPs have participated. The program now recovers its expenses through charging the IEPs, and although participation has declined relative to the funded program, enrolment has been sufficient to cover costs. Using a framework to build the modules, gaining regular feedback and, making the necessary changes to develop an internationally educated health professional program has proven highly successful. Only 24 health professionals (19%) who entered the program were unable to succeed in national examinations and join the Canadian physiotherapy workforce. However, these professionals may retake the examination and enter the workforce in the future. The long-term data regarding entry of IEPs into practice indicates that at least 69 IEPs, who completed the IEP Program, entered the Canadian Physiotherapy workforce, with 34 of these working in the public sector.The IEPs who participated appear to be representative of the population of Canadian immigrants; in the Canadian general populace the ratio of European to Asian immigrants is changing over time. In our population 58% of students came from the UK in 2009 and 12% in 2011, versus 10% of students from India in 2009 and 40% in 2011. The top four countries for physiotherapist immigrants practicing in Canada to have received their basic physiotherapy education, from 2007 to 2009, were UK (21%), India (15%), USA (10%) and Australia (8%) . The IEPThe primary objective of this program was to increase the pass rate of internationally trained Physiotherapists taking the PCE. The success of the program in increasing the pass rate of IEPs taking the PCE has been achieved with international graduates who took the program having a 28% greater possibility of passing the written section than their counterparts who did not take the program. The results for the clinical exam are even more impressive with the IEP program students having a 39% increase in risk of passing. A greater percentage of Canadian-educated candidates for the PCE continue to pass both elements of the PCE but the gap is closing, particularly in the clinical component. The program was developed partially due to the observation that in 2005 less than 50% of PCE attempts translated into passes in IEPs ; the stuIt may be expected that those who do not have English as their first language would have more difficulty with participating in the course and passing the exams, in particular, the written element. This appears to be false for the QE, the relative risk is 1.58 but the confidence interval is very wide, crossing 1  and is not significant. However, in the slightly larger number of people taking the PNE (n = 81), the relative risk demonstrates that those with English as their first language have a significant, 40% greater risk of passing the clinical element. The IEP success rate on the PNE indicates a slight decrease over time, when more candidates who did not have English as their first language participated.Although the IEP program targets internationally trained Physiotherapists, this model could be transferred to other health professions given the identified need to support internationally trained health professionals transitioning into the Canadian workforce , and theAs this is a relatively new program, there are not sufficient numbers of IEPs who have participated to enable sub-analyses of the data and examination of particular elements of the program. Collecting more qualitative data will allow for more in-depth analysis of the IEPs integration into Canadian practice and the impacts on acculturation and socialization.Potentially this program model could be applied to support integration of international health graduates from any background into the workforce. While this program used as a primary outcome measure improved performance on national competency examinations, many program elements also support international practitioner’s integration into the Canadian health care system and practice. Further examination of the role specific program elements may have on improving internationally educated health professional’s understanding of the cultural context of Canadian practice is needed.GP received reimbursement for her work coordinating the IEP program.AG conceived of the study and participated in its design and coordination and helped to draft the manuscript. DD carried out the analyses and drafted the manuscript. SM participated in study design and coordination. GP participated study coordination. BL oversaw study concept, design and coordination. All authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1472-6920/13/140/prepub


In this brief review, I argue that the impact of a stimulus on behavioral control increase as the distance of the stimulus to the body decreases. Habituation, i.e., decrement in response intensity repetition of the triggering stimulus, is the default state for sensory processing, and the likelihood of habituation is higher for distal stimuli. Sensitization, i.e., increment in response intensity upon stimulus repetition, occurs in a state dependent manner for proximal stimuli that make direct contact with the body. In Pavlovian conditioning paradigms, the unconditioned stimulus (US) is always a more proximal stimulus than the conditioned stimulus (CS). The mechanisms of associative and non-associative learning are not independent. CS−US pairings lead to formation of associations if sensitizing modulation from a proximal US prevents the habituation for a distal anticipatory CS. Identification of the necessary and sufficient conditions for the formation of associations has been a driving influence on learning theory and research. In Pavlovian conditioning, a conditioned stimulus (CS) acquires the ability to trigger a new response by virtue of being paired with an unconditioned stimulus (US), which by definition is biologically important and capable of triggering an innate reflex. Starting with British associationism, early theories of conditioning were based on the premise that temporal contiguity was both necessary and sufficient for stimulus associations  would eventually lead to the habituation of the response that is initially triggered by the odor. I say eventually, because depending on the parameters of the stimulation protocol , a temporary increment in responsiveness might initially be observed. If, however, an appetitive gustatory stimulus  is repeated with the same ISI, depending again on the concentration of sugar, frequency of stimulation, and the physiological state of the organism, this protocol is likely to result in an increment in the probability of responding, i.e., sensitization. Finally if odor and sugar are paired instead of being presented separately, the standard paradigm for Pavlovian conditioning would ensue, where the two stimuli would now be termed conditioned (CS) and unconditioned stimuli (US), respectively. Hence, associative learning can be suggested to entail an evasion from habituation for the CS as it signals the arrival of a sensitizing event, the US, and a conditioned response (CR) would then be triggered during the CS in anticipation of the US.de novo during Pavlovian pairings. Indeed, the strength of associations decreases if organisms are pre-exposed to the CS before conditioning  exerts a modulatory influence to prevent the habituation for another stimulus (CS) begs the identification of stimulus characteristics that determine whether habituation or sensitization will occur upon repetition. So, are there any independent criteria for predicting Only a small number of model paradigms for Pavlovian conditioning endured the test of time in vertebrate and invertebrate species. The limiting factor is the scarcity of stimuli that can function as a US. In all paradigms that yield reliable conditioning, the US is a proximal stimulus that comes into direct contact with the body. For example, in appetitive conditioning paradigms, food is the most frequently used US which supports conditioned approach or discrimination via its gustatory or nutritive properties. In aversive conditioning, the US is most often a pain inflicting stimulus  that is delivered via the tactile domain. In contrast, the CS's consist of distal inputs from the visual, auditory, or olfactory domains. Distal stimuli are conspicuously ineffective as US's even after they have acquired the potential to support conditioned responding through higher-order conditioning  are detectable via distal cues  before they contact the body to activate proximal senses , and associative learning is sensitive to this temporal order  is a probabilistic process that is modulated by stimulus properties  are bilateral multi-modal sensory integration sites  input that provides information about the concentration of food, and it can facilitate the associability of mushroom body olfactory representations for minutes via OA modulation. More stable memories require sensitizing modulation from an internal source: DA neurons that relay the impact of the nutritive quality of food can support olfactory memories for hours. Hence, following conditioning, when animals encounter distal olfactory stimuli, they learn to anticipate the sequential arrival of progressively more proximal inputs with positive valence, namely sweetness and nutritive value, through the DA-mediated olfactory associations .Notice that the hierarchical modulation of olfactory representations in downstream multi-modal association areas confers flexibility and context-dependence to conditioned responding  stimuli by the signaling the valence of proximal inputs . Interestingly, olfactory conditioning in fruit flies has recently been shown to involve post-synaptic plasticity in the dendrites of MB output neurons that express NMDA receptors  has been the principal model of memory formation in the mammalian brain since its discovery by Bliss and Lomo . In the In this brief review, I argued that the impact of a stimulus on behavior and its potential to modulate the effects of other stimuli increase as its distance from the body decreases, and the body-centered hierarchy of stimulus impact applies to the organization of behavior as well as its experience dependent change. For example, the likelihood of habituation, i.e., the inability of a perceivable stimulus to control behavior is higher for distal stimuli, whereas the likelihood of sensitization is higher for stimuli that come into direct contact with the body to activate gustatory and/or mechanoreceptors. Further, I argued that mechanisms of associative learning are not independent from those of habituation and sensitization. Pavlovian conditioning ensues when internal state  up-regulates the sensitizing potential of the proximal US , which in turn prevents habituation to the distal CS . According to the argument being raised here, CS−US pairings should fail to yield associative learning if sensitization does not occur to the US. In this short review, I gave examples from olfactory learning in fruit flies, but I believe that a similar hierarchy of body-centered stimulus impact exists in the vertebrate brain as well. The idea that sensitization from proximal inputs and the internal milieu drives associative learning might help our understanding of phenomena such as the development of chronic pain (Agroff et al., The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.