This paper reports on income generation practices among civil servants in the health sector, with a particular emphasis on dual practice. It first approaches the subject of public–private overlap. Thereafter it focuses on coping strategies in general and then on dual practice in particular.To compensate for unrealistically low salaries, health workers rely on individual coping strategies. Many clinicians combine salaried, public-sector clinical work with a fee-for-service private clientele. This dual practice is often a means by which health workers try to meet their survival needs, reflecting the inability of health ministries to ensure adequate salaries and working conditions.Dual practice may be considered present in most countries, if not all. Nevertheless, there is surprisingly little hard evidence about the extent to which health workers resort to dual practice, about the balance of economic and other motives for doing so, or about the consequences for the proper use of the scarce public resources dedicated to health.In this paper dual practice is approached from six different perspectives: (1) conceptual, regarding what is meant by dual practice; (2) descriptive, trying to develop a typology of dual practices; (3) quantitative, trying to determine its prevalence; (4) impact on personal income, the health care system and health status; (5) qualitative, looking at the reasons why practitioners so frequently remain in public practice while also working in the private sector and at contextual, personal life, institutional and professional factors that make it easier or more difficult to have dual practices; and (6) possible interventions to deal with dual practice. Doctors and nurses in government employment are labelled "unproductive", "poorly motivated", "inefficient", "client-unfriendly", "absent" or even "corrupt". These labels are often associated with coping strategies associated with widespread "demotivation", due partly to "unfair public salaries". These are presented as the de facto justification of "inevitable" predatory behaviour and public-to-private brain drain -6. In maThis paper reports on income generation practices among civil servants in the health sector, with a particular emphasis on dual practice. It first approaches the subject of public–private overlap. Thereafter it focuses on coping strategies in general and on dual practice in particular.Private providers capture a significant and growing share of the service delivery market for health care, and ensure an important part of the uptake of services. For a sample of 40 developing countries, an average of 55% of physicians worked in the private sector and an average of 28% of health care beds were private beds  [Asia has more than 60% of private sector contributions to health care financing (excluding China and India) and is the part of the world where the private sector normally plays the dominant role. In Malaysia, for example, the proportion of physicians in private practice increased from 43% in 1975 to 70% in 1990. In Indonesia half of the hospitals are privately run. In Thailand the share of beds in private hospitals grew from 5% in 1970 to 14% in 1989.The contribution of the private sector to health care financing in Africa is 50%, with a significant preponderance of private, not-for-profit, nongovernmental (PNFP-NGO) entities, particularly church organizations. In Zimbabwe church missions provide nearly 70% of all beds in rural hospitals and in Tanzania they run 40% of the hospitals. In Kenya, about one third of the total health services and 40%–50% of the family planning services are provided by PNFP-NGOs. In Latin America the private sector finances 40% to 60% of the health sector .For many populations, especially in rural areas, these PNFP-NGOs are the main – if not the only – providers of health care. For example, in a mail survey of 88 nongovernmental hospitals in sub-Saharan Africa at the end of the 1980s, 39 were the only service provider in their district ,11. It iIn urban areas PNFP-NGOs usually share the work with private, for-profit (PFP) providers and government services. In Alexandra, South Africa – a poor periurban township – for example, a PNFP university clinic, a municipal clinic and PFP "general dispensing cash practices" worked side by side ,15. But PFP health providers are no doubt an important source of ambulatory care throughout the developing world, but tend to concentrate on the more profitable niches of the market. The development of private practice in most developing countries is notoriously unregulated. Private practices are not easily forthcoming with information, at times for fear of tax implications, at times because existing regulations are not respected, often because of a lack of respect for discredited ministries of public health and not infrequently because of the non-existence of information systems. In transitional countries, such as Tunisia, the growth of the entrepreneurial sector is well documented.Although hard data are hard to come by for the poorer countries, it is sufficient to walk around Luanda or Dar es Salaam or to look at the advertising sections of any newspaper in Maputo to see that private health care provision is a thriving growth industry. If there are ever more private providers on the market, not all provide the whole range of health services. They tend to select niches according to demand and competition rather than providing comprehensive care.There are huge differences between and within countries. This (patchy and scarce) evidence confirms that both PFP and PNFP providers have a significant and growing share of the market of health care, but this statement needs qualification. There are wide differences between and within countries. Overall, the market share of the private sector is smaller for inpatient than for ambulatory care, and limited for preventive and public health services .Individual coping strategies represent the health professionals' ways of dealing with unsatisfactory living and working conditions. In many countries their prevalence has increased over recent years. The notion of the full-time civil servant exclusively dedicated to his/her public sector job is disappearing. Were this without consequences for the performance of the public health sector, it would not be much of a problem. Not all coping strategies can be classified as predatory behaviour or corruption, and their effects on the health care system can be positive as well as negative. They cannot, however, be ignored as, in many countries – particularly the poorest – the situation has gotten out of hand.Most would agree that public sector salaries are most often "unfair". For example, in 1999 a Mozambican nurse's salary was only 10% to 15% of what it had been 15 years before . In SierTo compensate for unrealistically low salaries, health workers rely on individual coping strategies ,18,20-54In Thailand 37% of patients pay their public sector obstetricians "gratitude money" . In FranAnother example is fee splitting, whereby a specialist shares a fee with the referring physician . In 1998Patients and practitioners may collude to deceive a third agent: in Kazakhstan, for example, it is reported that doctors regularly provide false health reports in return for a fee, so that patients can obtain driving licenses . A furthDrugs are – in the current context of scarce resources, health care reform, promotion of generics, the HIV epidemic and growing demand for health care – a sensitive issue, as in many low-income countries, pharmaceuticals make up 50% or more of health care costs . With heIn other settings, such as hospitals and health centres, misappropriation is a widespread practice by all categories of professionals. This is infrequently acknowledged explicitly or documented, even in studies that have looked into the coping strategies of health professionals ,41,44,45In Uganda, for example, misuse of pharmaceuticals was reported by facility health workers as well as by the District Health Teams and the Health Unit Management Committees; resale of drugs represented the greatest single source of income for health workers in most units ,43. In mWe have stated that many clinicians combine salaried public-sector clinical work with a fee-for-service private clientele ,44,45,53In this paper dual practice is approached from six different perspectives: (1) conceptual, regarding what is meant by dual practice; (2) descriptive, trying to develop a typology of dual practices; (3) quantitative, trying to determine its prevalence; (4) impact on personal income, the health care system and health status; (5) qualitative, looking at reasons for its prevalence and for staying in public practice while working in the private sector and at contextual, personal life, institutional and professional factors that make it easier or more difficult to have dual practices; and (6) possible interventions to deal with dual practice.Dual practice is approached in the literature with great diversity. It can mean health professionals with multiple specializations – for example, among Egyptian physicians the most popular areas of multiple specializations are "cardiology and internal medicine, internal medicine and fever and cardiology and chest" .It can also mean health professionals working within different paradigms of health . It may involve combining different forms of health-related practice – clinical with research, with teaching or with management. It can also mean health professionals combining their professional health practice with an economic activity not related to health (such as agriculture).In this paper, dual practice will be used to describe multiple health-related practices in the same or different sites.Therefore, in terms of sector location, dual practice may be public on public, public on private or private on private Table .Overtime may be considered a form of dual employment. It is increasing because of cost-containment measures or shortages of staff. In 1992, the German Union of Salaried Employees estimated that the overtime worked by health workers was equivalent to 20 000 extra full-time staff posts. Today, trade unions in Canada and the United Kingdom express particular concern about the use of overtime to substitute for recruitment and about the increase in unpaid overtime .As mentioned and supported by the limited literature available Table , dual prDual practice may lead to predatory behaviour  by healtThis hypothesis, controversial for some practices such as caesarean sections, seems consensual regarding other surgical practices . In ThaiThe predatory behaviour of individual clinicians constitutes, in many cases, a de facto financial barrier to access to health care . More imA more insidious problem is that of conflicts of interest. Effects on the system can best be looked at separately for each type of side activity. When health officials set up in dual practice to improve their living conditions – or merely to make ends meet – this may not interfere with their work as civil servants . When they take up teaching as an extra job, usually in public sector institutions, that may actually be beneficial to the public agenda, as it reinforces the contact of trainees with the realities of the health services.For doctors who are basically managers, moonlighting in private practice presents less of a conflict of interest than for clinicians. The latter must compete for patients with themselves, and thus they have an incentive (and the opportunities) to lower the quality of the care they provide in the public services. This is not the case for managers: involvement in NGO projects or work for donors can foster better coordination in the provision of services, but may constitute a conflict of interest when NGO or project policies are not necessarily congruent with national health policies or the agenda of the public service ,44,52,55Other business activities, such as agriculture, are neutral towards health services, although they may constitute a de facto internal brain drain .Dual practice is to a large extent a question of creating and making use of opportunities. The pursuit of such opportunities contributes also to brain drain.Brain drain of health professionals is often thought of only in terms of intercountry migration . But faiThis public-to-private migration compounds the rural-to-urban migration because cities also offer more opportunities to diversify income generation ,29. The Coping strategies, including dual practice, also affect access, but through competition for time. In many countries, civil service medical staff is available only nominally full-time to fulfil its assigned tasks. This has been well described regarding Colombia, Costa Rica and Venezuela. In Venezuela doctors and head nurses missed about one third of their contracted service hours, 37% and 30% respectively, while resident doctors and nurses were absent about 7% and 13% of the time, respectively . In PeruIf public sector medical staff is moonlighting in private practice, this evidently limits access by public patients. This corresponds to a net flow of resources out of the public sector. Competition for time is also something that concerns managers, whose coping strategies are often more oriented towards collaboration with development agencies ,45.Competition for time is a nagging problem for many development agencies and ministries of health. At times it is blatant. In Mali, for example, regional health staff was found to spend 34% of its total working time in (income-generating) workshops and supervision missions supported by international agencies; for chief medical officers it was 48% . The 73% of working time spent on official duties that was self-reported by the respondents to one of the surveys reviewed may well be an overly optimistic estimate ,45.In Egypt the number of hours worked in the private clinic falls as the number of a physician's jobs increases, indicating that the physician replaces hours away from the private clinic with other employment. Secondly, as the number of jobs increases, the amount of time spent in the second job, usually a government job, decreases. This reduces the access of low-income people to medical care, as they cannot afford to seek care in the private sector.Econometric analysis of the data also found that physicians replace hours they should be working at the government job by hours in the private clinic. This has important policy implications, as multiple employment is not increasing the access of the population to medical care. On average, physicians see one patient per hour in their private clinic. This increases to 3.2 patients per hour in the second job, 4.4 in the third job and 2.9 in the fourth job. An extreme example is that of general practitioners who see one patient per hour in their private clinic, approximately four in the second job and 12 in their third job. In general, the number of patients seen per hour increases with the job number. This is true for physicians as well as dentists .Competition for time automatically results in a transfer of salary resources out of the public sector through reduced availability – at least the equivalent of 27% of the salary mass ,45.Besides competition for time, in many cases the use of the public sector's means of transportation, office infrastructure and personnel represent additional hidden outflows of resources, often in association with dual practice. The overall impact of this outflow of resources is hard to quantify in any country. Reports from Moscow suggest that up to 30% of the federal budget is not accounted for ,34; in tThe loss to the public sector associated with redirection of diagnostic and therapeutic resources, such as pharmaceuticals, to private practice or into the black market is obviously difficult to assess. In Uganda, for example, it results in a significant loss to the public health facilities: the median drug leakage in health facilities was estimated at 78% ,43. In tIn Costa Rica, 71% of doctors and 83% of the nurses reported that equipment and materials had been stolen in their hospital . In the Competition for time and transfer of resources are compounded by the fact that the best-trained and most competent officials are also the most likely to divert their time to other activities outside the health sector (a de facto brain drain). This in turn reinforces the attraction of what starts out as a job-on-the-side, and quickly becomes not only more rewarding financially but also professionally and in terms of social prestige.The impact of these coping strategies is seen as negative. These strategies weaken the public sector health structure and damage people's health ,88.Individual income topping-up strategies allow professionals a standard of living that is closer to what they expect. In one study, these strategies more than doubled the median income of public sector health managers, and brought it from 20% to 42% of that of a full-time private practice ,45  , but witAnother problem with current research is its treatment of corruption as something that would be the same everywhere, with essentially the same causes and implications wherever it occurs .A third problem is that of the moralistic and criminal connotations of the word "corruption". It should be kept in mind that not all that is illegal is corrupt and not all that is corrupt is illegal, and that also a distinction should be maintained between corrupt transactions and those that are immoral .The literature tends to focus on the "corrupt", failing to acknowledge that contexts that generate so-called corrupt behaviours generate them across the whole spectrum of society, to the extent that they become an ingrained and acceptable part of society, a necessary evil to survive in a very harsh environment. This shift from focusing on the persons involved to the system in which the professionals are integrated has taken place in other areas, such as in quality management  and in tCorruption has a negative impact on development in general. It hits the poor the hardest, directly and indirectly by, inter alia, reducing their access to public services such as education and health care ,106.This negative impact is also felt in indicators of health status. There is an inverse relationship between indices of corruption and ratio of public health spending to GDP and child mortality rates . As suchWhen compared with other sectors, health is frequently classified as being of median to high levels of corruption, with sectors such as public works contracts and construction, arms and defence, energy and industry appearing as more corrupt .The professional literature hardly touches on corruption in the health sector. It is anecdotal    teaching, or in unpaid NGO work shows that other factors – social responsibility, self-realization, professional satisfaction, working conditions and prestige – still play a significant role ,4,44,45.The gap between income and expectations makes it unavoidable that managers, like other health care workers, will seize opportunities that are rewarding, professionally and financially. Some are of the opinion that dual practice can at times be justified. Health workers in Mozambique and Cape Verde rationalize it: "... to help a sick neighbour" or to help patients "because there are patients that, on account of the long waiting times, do not go to the hospital, they will rather go to these persons in order to avoid wasting their time in the hospitals" .Most, however, implicitly or explicitly condemn such practices while still attempting to explain and/or justify them in various ways. An obvious explanation is that of "serious lack of motivation" and insufficient salaries: "economic reasons, and low salaries ... those are the reasons ... it is a means of surviving" .The reasons for dual practice are not well studied. A number of Portuguese case studies ,74-76 suThis limited evidence suggests that being a migrant worker, being on temporary contracts and doing shift work are important determinants. This evidence is not conclusive or generalizable, but is welcome as it suggests that dual practice depends not so much on the personal (age and sex), social  and professional characteristics of health workers – although these are not insignificant – but on factors that are manageable.Sometimes dual practice may be the unexpected result of health care reform. In Canada, within the public system, designating sites for different levels of surgical acuity during the early stages of regionalization has resulted in a 3.5-fold increase in the number of surgeons working in more than one setting after this restructuring compared to before, as most surgeons do both high- and low-acuity surgeries. This resulted in interference with continuity of care, increased commuting time for both surgeons and medical residents and increased reliance on house staff (with whom surgeons spent less time and are thus less familiar with the limits of their skills) .Another area where provider strain was reported as high was among paid home care staff: low wages, irregular hours, inadequate training and high turnover resulted in lack of continuity of care, staff shortages, waiting lists, health risks to both workers and recipients and impoverishment. Some home workers reported working several jobs to make ends meet .Reforms frequently result in the increase of staff employed on fixed term and temporary contracts . This trAt the core of the reliance on individual coping strategies, including dual practice, is a very strong motor: the gap between the professional's financial  expectations and what public service can offer.Most public responses to individual coping strategies, including dual practice, fail to acknowledge the obvious: that individual employees are reacting individually to the failures of the organizations in which they work, and that these de facto choices and decisions become part of what the organization is.Adequate responses also imply that the main underlying reason for the observed dual practice can be identified. They call for an understanding of how endemic are the practices observed: Are they isolated, individual cases? Are they specific to the health sector? Or are they widespread in other sectors of society? It is equally important to identify the impact of these practices, particularly the impact in terms of reduced access, inequity and other dangers for the health of the public.Dual practices have, in some countries, become so prevalent that it has been widely assumed that the very notion of a civil service ethos has completely – and possibly irreversibly – disappeared. But some of the literature reviewed reflects, from the health workers themselves, a conflict between what it means to be an honest civil servant who wants to do a decent job, and the brute facts of life that make them betray that image. The manifest unease that this provokes is an important observation as such. It suggests that even in the difficult circumstances observed in many countries, behaviours that depart from traditional civil servant duty and ethics have not been interiorized as a norm. This ambiguity suggests that interventions to mitigate the erosion of proper conduct would be welcome.The most relevant conclusion is that there is no single recipe to address the reality of dual practice. Its cause and logic vary, and the resulting differences among situations need to be taken into account in the design of corrective measures .Pretending that the problem does not exist or that it is a question merely of individual ethics, or approaching it as a problem merely of corruption, does not do justice to the complex nature of the problem and will not make it go away.Prohibition is equally unlikely to meet with success, certainly if the salary scales remain blatantly insufficient. In situations where it is difficult to keep staff performing adequately for want of decent salaries and working conditions, those who are supposed to enforce such a prohibition are usually in the same situation as those who have to be disciplined. As an isolated measure, restrictive legislation, when not blatantly ignored, only drives dual practice underground and makes it difficult to avoid or correct negative effects . DespiteClosing the salary gap by raising public sector salaries to "fair" levels may not be enough to break the vicious circle. This was attempted by Louro, in Greece, in his restructuring of the health sector in 1945. When public-sector doctors were prohibited by law from pursuing private practice, their average remuneration was raised to take account of their lost income. But there was great resistance by doctors not prepared to give up private practice and professional autonomy . The 198The 1990–1994 reform again allowed doctors to become part-timers if they wished to practice simultaneously in private surgeries or to treat on a per-case basis, but in this case their salaries would be reduced. Notably, though the Ministry of Health expected that around 2500 doctors would become part-timers, only 150 opted for it.In 1994 an international committee chaired by Abel-Smith reopened this issue, recommending that either rights to private practice would be denied to all doctors working for the NHS or they would be confined to senior doctors for a limited number of sessions. Higher salaries were to be paid to professors to compensate them for their loss of unlimited private practice rights.In 1997 this still had not been implemented . And it Downsizing central bureaucracies and delinking health service delivery from civil service  would maLastly, a mere increase in salary would not automatically reinstate the sense of purpose that is required to make public services function: as such it would not be enough to make moonlighting disappear spontaneously ,120. ThaA prerequisite is to address the problem of dual practice openly. Where it is not realistic to expect health care workers to dedicate 100% of their time to their public service job, this should be acknowledged. That is the only way to create the possibility of containing and discouraging income-generating activities that present conflicts of interest, in favour of safety valves with less potential for negative impact on the functioning of the health services.Besides minimizing conflicts of interest, open discussion can diminish the feeling of unfairness among colleagues. It then becomes possible to organize things in a more transparent and predictable way.There are indications that the newer generations of professionals have more modest expectations and are realistic enough to see that the market for dual practice is finite and to a large extent occupied by their elders. This gives scope for the introduction of systems of incentives that are coherent with the organization's social goals .Where, for example, financial compensation for work in deprived areas is introduced in a context that provides a clear sense of purpose and the necessary recognition, this may help to reinstate lost civil service values . The samIt makes no sense to expect health workers to perform well in circumstances where the equipment and resources are patently deficient. But improving working conditions involves more than providing an adequate salary and the right equipment. It also means developing career prospects and providing perspectives for training ,120. PerHowever ill-defined they may be, the value systems of the professionals are a major determinant in making the difference between good service to the public and bad. It would be naïve to think this could be achieved through mere bureaucratic regulation by governments or donor agencies. With the building up of pressure from donors and from peers as well as from users, civil servant health professionals will be more likely to invest in patterns of behaviours and practices that visibly uphold the professional value system ,120.The social and professional culture within a profession may have a major impact on the practice ,120,121.The effect of peer pressure may be positive or negative. Pressure from local practice styles is particularly relevant in situations where there is the most uncertainty concerning the most appropriate treatment protocol . This rePractice styles can be changed through "peer influence meetings", particularly if the change is seen as building up public reputation and status, once more showing that simple income topping-up is not the principal driving force of professional behaviour . This poA further possibility is workers' forming peer pressure groups to reduce undesirable coping strategies associated with dual practice. These groups could function to support members to maintain their personal stance as well as to inform the public of their rights. Making public the membership of such a group could be a way of identifying the non-members, an indirect way of increasing pressure .A significant problem with individual coping strategies associated with dual practice is the difficulty of assigning individual responsibilities in situations where these are endemic. In these circumstances it might be relevant to introduce legislation that makes the head of an organization or department legally responsible for the actions of that body. This would be a further means of increasing peer pressure and accountability .Civil society has a particularly important role, specifically in linking reform measures to the experiences and expectations of real people. But civil society must not be seen as a neutral body, particularly in developing countries where patron–client networks or kinship networks have a strong influence on the state and on the patterns of corruption and/or of coping strategies observed. In these situations the reform of civil society itself should be an objective of the interventions to correct such strategies.In many countries, users/clients/patients are not protected against the consequences of the asymmetry of information they face – with health and financial consequences. From the history of the workers' movement in Europe and as the recent evolution in a number of middle-income countries – such as Thailand's National Forum on Health Care Reform  – pointsCreating opportunities for users to voice their discontent effectively implies that patient's rights must be clear, channels for complaints must be simple, regulatory agencies must be strong and trusted by the public, processes must be explicit and transparent and the judiciary system must be strengthened .International development agencies, even when they do not have formal, explicit policies regarding dual practice, have become more sensitized to the problem over recent years. This has resulted in a number of recommendations to help minimize the problem. To limit the brain drain due to their own employment policies, organizations such as the World Bank, Norwegian Agency for Development Cooperation (NORAD), German Technical Cooperation (GTZ) or the World Health Organization in principle implement human resources recruitment policies that emphasize the employment of task-specific and short-term consultants, with a commitment of national institutions to retain such staff -92,130.The anti-corruption literature, without the necessary empirical evidence to support such claims, actually blames government monopoly of service provision as one of the key determinants of the emergence of some of the coping strategies reviewed above . It has The claims for a greater role for the private sector in the provision of health care are based on a number of assumptions that are not all based on empirical evidence and ignore that private practice, in most developing countries, is notoriously unregulated. The fragmentary evidence shows that blanket recommendations regarding the role of the private sector are inappropriate .There is a case for public sector support of the private sector where this serves the public's interest and allows redirection of scarce resources. If that is not the case, support has no rationale. Support, but also mere control, carries costs for the public sector administrative machinery. The costs of the "new" state responsibilities must be compensated for by savings resulting from gains in efficiency and from complementarity ,131,132.A key policy question is whether doctors should be allowed to work in both the public and private sectors. As discussed before, prohibition is unlikely to be effective. The real issue is what types of private practice should be allowed in order to minimize conflicts of interest, and what forms of regulatory mechanisms can be introduced to isolate coping strategies that are associated mostly with lack of regulation rather than just with low income . It seemRegulation is one important factor influencing the coping strategies that result from the interface with the private sector ,124. EveInternational collaboration is seen as particularly important regarding the support of international development agencies for actions such as: good-governance interventions in specific domains; supporting methods to curb corruption, including policy dialogue, capacity building, documentation and analysis of best practices and support to national programmes; and making reformers aware of the importance of country conditions in programme development .Anti-corruption strategies have also been approached by donors with different objectives: to reduce poverty, to improve the functioning of democratic institutions, to sustain economic development, political stability and social justice. The lesson for the management of coping strategies and dual practice is that international collaboration cannot be neglected, as donors may be important inducers of coping strategies and dual practice as well as essential partners in the search for solutions.One way to increase donors' and governments' commitment to deal with the causes of individual coping strategies as well as dual practice might be to include a formal "human resources impact assessment" as a condition for the approval of health projects or components of sector-wide approaches. This could force governments and their partners to face the problems caused by dual practice before it becomes part of the public organization's culture. This would not be a guarantee that it would be effectively dealt with, but might limit the damage .In terms of sector location, dual practice may be public-on-public, public-on-private or private-on-private. Dual practice is probably present in all countries regardless of income, even in settings where there are major regulatory restrictions, such as China.Dual practice may lead to predatory behaviour by health workers. This constitutes, in many cases, a de facto financial barrier to access to health care. It delegitimizes public sector health service delivery and jeopardizes the necessary relation of trust between user and provider. Clinicians in dual practice have to compete for patients with themselves, which is an incentive to lower the quality of the care they provide in the public services.Dual practice contributes also to brain drain, specifically public-to-private brain drain. If public sector medical staff is moonlighting in private practice, this limits access. Besides competition for time, in many cases, the use of the public sector's means of transportation, office infrastructure and personnel represent additional hidden outflows of resources, often in association with dual practice.This is not the case for managers: involvement in NGO projects or work for donors can foster better coordination in the provision of services, but may constitute a conflict of interest when NGO or project policies are not necessarily congruent with national health policies or the agenda of the public service.On the other hand, dual practice allows professionals a standard of living that is closer to what they expect, as well as a standard of practice closer to their own perceptions of good professional practice, resulting in higher professional satisfaction.There is no evidence that dual practice by public sector health professionals complements public practice or promotes greater equity of health care distribution.The reasons for dual practice are contextual. The extent of dual practice seems to vary according to urban or rural residence, according to professional group  and even within a professional group, according to specialty or occupation. The limited evidence suggests that being a migrant worker, being on temporary contracts and doing shift work are important determinants. This evidence suggests that dual practice depends not so much on the personal (age and sex), social  and professional characteristics of health workers, although these are not insignificant, but on factors that are manageable.Sometimes dual practice may be the unexpected result of health care reform. Reforms frequently result in the increase of staff employed on fixed-term and temporary contracts. This trend seems to encourage dual employment.Therefore, at the core of the reliance on dual practice is the gap between the professional's expectations and what public service can offer. Adequate responses imply the identification of the main underlying reason for the observed dual practice. The most relevant conclusion is that there is no single recipe to address the reality of dual practice.The author(s) declare that they have no competing interests.AB, IF, FH were responsible for the Portuguese case studies. PF and WVLconceived of the study and participated in its design and coordination. All authors read and approved the final manuscript.


All of these receptors, based on the kappa opioid receptor, were modified to be receptors activated solely by synthetic ligands (RASSLs). This modification allows us to compare receptors that have the same ligands and effectors, but differ only in desensitization and internalization.The physiological regulation of G protein-coupled receptors, through desensitization and internalization, modulates the length of the receptor signal and may influence the development of tolerance and dependence in response to chronic drug treatment. To explore the importance of receptor regulation, we engineered a series of GRemoval of phosphorylation sites in the C-terminus of the RASSL resulted in a mutant that was resistant to internalization and less prone to desensitization. Replacement of the C-terminus of the RASSL with the corresponding portion of the mu opioid receptor eliminated the induction of AC superactivation, without disrupting agonist-induced desensitization or internalization. Surprisingly, removal of phosphorylation sites from this chimera resulted in a receptor that is constitutively internalized, even in the absence of agonist. However, the receptor still signals and desensitizes in response to agonist, indicating normal G-protein coupling and partial membrane expression.i-receptor signals, are independently regulated. Furthermore, specific mutations can radically alter superactivation or internalization without affecting the efficacy of acute Gi signaling. These mutant RASSLs will be useful for further elucidating the temporal dynamics of the signaling of G protein-coupled receptors in vitro and in vivo.These studies reveal that internalization, desensitization and adenylyl cyclase superactivation, all processes that decrease chronic G It is becoming clear that the regulation of the GPCR itself – its location, stability, and signal duration – is a key component of the signaling process ,2 The letivation . Such retivation .mu opioid receptors (MOR) in response to different ligands [The complex effects of drugs at multiple receptor subtypes in multiple tissues have made it difficult to isolate the relative contributions of GPCR regulation, ligand binding, effector coupling, drug metabolism, and cellular downregulation machinery. Even if two receptors couple to the same signaling pathway, the physiological effects of their activation could vary tremendously depending on the pharmacokinetics of the ligands, the cell type expressing the receptors, and the interactions with desensitization mechanisms. An engineered family of receptors that share the same ligand binding and effector coupling, yet have discrete mutations that cause them to internalize or desensitize differentially, would help pinpoint the physiological consequences of GPCR desensitization. This is especially important in the light of recent evidence showing dramatically different endocytosis and signaling profiles of  ligands ,6. In ad ligands ,8 and io ligands -11.i-coupled receptor that is insensitive to endogenous ligands but can still respond to the synthetic small-molecule agonist spiradoline [receptor activated solely by a synthetic ligand (RASSL) was based on the kappa opioid receptor (KOR). In the original RASSLs, exchanging the second extracellular loop of the KOR with the corresponding sequence from the delta opioid receptor, and making an additional point mutation (Q297E), resulted in a receptor with 1/2,000 of the response to dynorphin and other endogenous peptides relative to the wild-type KOR. However, the response of this RASSL to spiradoline was not altered. RASSLs can be expressed in a tissue-specific manner in transgenic mice, allowing direct control of Gi-mediated physiological responses such as heart rate [RASSL opioid green). Given the well-documented role of the C-terminal region in the desensitization and internalization of GPCRs [Our laboratory has engineered a Gradoline ,13. Thisart rate . It has art rate . To inveof GPCRs -18, we mi-coupled RASSL alters the receptor's internalization, desensitization, and induction of AC superactivation. Since it is well established that the endogenous mu and kappa opioid receptors differ in these properties, we also explore the regulation of kappa opioid RASSLs bearing specific portions of the mu opioid receptor C-terminal sequence. The cell culture experiments presented here provide a basis for in vivo studies in complex tissues such as the nervous system. Insight gained through these experiments may help explain the differences seen in vivo between different endogenous Gi-coupled receptors, improving our understanding of the contribution of receptor regulation to the physiological response to agonists and our overall understanding of GPCR signal regulation.This novel receptor system offers an opportunity to test specific hypotheses about the relationship between receptor sequence and receptor regulation, without requiring the use of multiple ligands that might have different effects on the signal and the regulation of receptors. Because RASSLs lack endogenous agonists, they allow greater control of the timing and specificity of activation than is possible with endogenous receptors. In these studies, we test how the removal of phosphorylation sites from the C-terminal regions of a Gqi5 protein [i-coupled receptors but signals through the Gq pathway and therefore stimulates calcium release. Using this transient calcium response as a measure of Gi activation, we showed by FLIPR assay that Rog responded dose-dependently to spiradoline, but not to a range of doses of dynorphin, the endogenous ligand that activates the wild-type KOR  and a main effect of receptor type . As observed with Rog, maximal internalization of Rog-A in response to 1 μM spiradoline occurred after 20 min of drug treatment , a main effect of receptor type , and an interaction between receptor type and treatment length . These results suggest that C-terminal phosphorylation promotes receptor internalization. Activation of Rog-A inhibits cAMP as fully as Rog  and an interaction between receptor type and drug dose . Post-hoc Scheffé analysis shows significant differences between Rog and Rog-μ at 0.01 μM (p = .024) and 0.1 μM (p = .016) doses of spiradoline. When cells were treated with 1 μM spiradoline for differing lengths of time, there was no detectable difference in the time course of internalization of Rog and Rog-μ , with no effect of receptor type. There was also no difference in cAMP inhibition after spiradoline activation of Rog and Rog-μ (Table Since the mu opioid receptor (MOR) internalizes more readily than the KOR, we made Rog-μ, a chimeric receptor in which the entire intracellular portion of the C-terminus was replaced with the corresponding MOR sequence Figure . Rog-μ wμ Figure . ANOVA iA variant of Rog-μ, known as Rog-μA, also has MOR sequence at the C-terminus, but five serine and glutamic acid residues at the C-terminus were mutated Figure . These m1,6 = 27.00). It also increased the cell-surface expression of Rog-μ, but to a lesser degree . In contrast, it had no effect on the cell-surface expression of Rog. The increase in membrane expression of Rog-μA after antagonist treatment was confirmed by confocal microscopy. Under basal conditions, little Rog-μA was seen in the plasma membrane, although the receptor was readily detected in other areas of the cell . A similar degree of superactivation was seen in cells transfected with the wild-type KOR, indicating the same cellular response to prolonged Gi signaling through both Rog and KOR. Overnight treatment of Rog-A-expressing cells with spiradoline, followed by stimulation with 10 μM forskolin, resulted in a slightly smaller increase in cAMP . Notably, cells expressing Rog-μ and Rog-μA receptors showed no evidence of AC superactivation after 18 h of spiradoline pretreatment. These data show that receptors that desensitize and internalize more readily at the receptor level, such as Rog-μ and Rog-μA, do not induce compensations in an opposing signaling pathway.Chronic treatment of cells expressing Gorskolin . We exam1,18 = 8.22, p < 0.01), but no effect of receptor type (p > 0.99).Although little internalization of these RASSLs has been observed at these low doses of spiradoline, we wanted to ensure that the AC superactivation data could not be explained by differences in receptor internalization. Therefore, we performed an analysis of cell-surface receptor expression in parallel with the cAMP response experiment. Cells were plated and treated with 10 nM spiradoline for 18 hours exactly as described above. Then the cells were fixed and a cell-surface ELISA was performed. In general, 7–10% of the receptors were internalized by this treatment, but there were no significant differences between receptor types Figure . ANOVA sWe have engineered a series of RASSLs that inhibit cAMP after acute activation by spiradoline with equal efficacy but differ dramatically in cellular location and responses to chronic drug treatment.Mutation of phosphorylation sites on the C-terminus to alanines resulted in a receptor that was relatively resistant to internalization in the presence of moderate doses of agonist , but their properties may change in specific cell types or under specific physiological conditions. One potentially fruitful avenue for future investigations would be to target different RASSLs to particular cell types The development of a toolbox of engineered RASSLs that differ in internalization and desensitization raises several possibilities for future research and clinical investigations. Growing evidence points to a link between receptor dynamics and the potential for drugs to elicit tolerance or dependence, especially for opioid receptors ,34. Herein vivo signal engineering. The basic RASSL, Ro2, shows rapid and extensive physiological desensitization [in vivo will help solidify the elusive links between the receptor amino acid sequence, cell biology, and complex physiology.A family of engineered GPCRs that do not respond to endogenous ligands has enormous potential for selectively controlling G protein signaling in specific tissues without interfering with endogenous processes. Rog-A, a long-signaling RASSL, has several interesting implications for tization , making RASSL opioid with GFP tag. Rog was made by inserting the coding sequence for emerald GFP (Packard) at the N-terminus of the receptor, after a FLAG tag (DYKDDDDV) and the first eight amino acids of the RASSL. To create Rog-A, two serines and two threonines in the C-terminal region of the receptor were mutated to alanines  of Rog were replaced by 47 C-terminal residues from the rat mu opioid receptor (MOR). Rog-μA contains the following additional modifications to the rat MOR C-terminus: T383A, E388Q, E391Q, E393Q and T394A. For each receptor, a schematic design and a C-terminal amino acid sequence alignment is shown in Figure All receptors were based on the human kappa-opioid RASSL called Ro2 . The GFPs Figure . In the HEK293 cells were grown in culture to 60–80% confluence and then transfected using Lipofectamine Plus . The RASSL construct contained a cytomegalovirus promoter to drive mammalian expression, and a neomycin-resistance gene to allow selection of stable cell lines. Experiments on transiently transfected cells were performed approximately 48 h after transfection. To create stable cell lines, transfected cells were selected with G418  for 10–14 days. Individual colonies showing green fluorescence were selected and grown under maintenance doses of G418 (250 μg/ml). Receptor expression was confirmed visually by fluorescence microscopy, and by an enzyme-linked immunoadsorbent assay .2 and incubated for 30 min at room temperature in secondary antibody , then washed three times in PBS plus CaCl2. To develop the reaction, 0.25 ml of 2,2-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) liquid substrate (Sigma) was added to each well. After 15–60 min, 200 μl from each well was transferred to a 96-well plate and the optical density was read at 410 nm. To quantify agonist-induced internalization, cells were treated with various doses of spiradoline in medium for 10–120 min. The medium was removed and the cells were fixed and processed as described above. Vehicle treated cells on each plate were used to calculate a "maximum" cell-surface expression for that plate. All other treatment conditions on that plate were then normalized to this maximum to determine "percent internalization." Each experiment included 3–6 replicates per condition and was repeated at least 3 times. After values for cell-surface expression of each receptor were calculated and normalized, receptor expression was compared using two-way ANOVA . For dose response studies, receptor and dose were independent factors. For time course studies, receptor and length of treatment were independent factors.Cell-surface expression of receptors was confirmed by an ELISA that detects only extracellular FLAG tag, which labels the N terminus of all RASSLs. This assay therefore quantifies only receptors that are in the membrane at the time of labeling, without providing detailed localization data about those receptors. Cells were plated at 100,000 cells/well on to 24-well plates coated with poly-d-lysine. Cultured cells were fixed in 4% paraformaldehyde for 10 min at 4°C, washed in phosphate-buffered saline (PBS), and then incubated in 1 μg/ml M1 anti-FLAG antibody  for 1 h at room temperature. They were washed again in PBS with 1 mM CaCl4/well into 96-well plates coated with poly-d-lysine. The next day, cells were rinsed in Krebs-Ringer bicarbonate buffer with glucose . Cells were then incubated in pre-stimulation buffer containing a phosphodiesterase inhibitor (0.75 mM 3-isobutyl-1-methylxanthine in KRBG buffer) for 10 min at room temperature to inhibit cAMP degradation. cAMP production was stimulated by the addition of 50 μM forskolin to all cells. At the same time, various doses of spiradoline in PBS were added to cells to establish a dose-response curve. After a 15-min drug treatment at 37°C, the cells were lysed and cAMP accumulation was assayed according to the CatchPoint protocol. Inhibition of cAMP by spiradoline was determined by comparison to cells treated with forskolin alone. For each experiment, 3–6 wells per condition were averaged, and EC50 and percent inhibition values for each receptor were determined by fitting curves for each independent experiment using SOFTmax PRO v. 4.0.1 (Molecular Devices). Data for 3–8 independent experiments were averaged to determine the EC50 and maximum cAMP inhibition for each receptor and condition. For desensitization assays, a pretreatment dose (1 nM) of spiradoline diluted in sterile PBS was added to the cells, which were then incubated for 10 min at 37°C. The cells were rinsed 4 times in KRBG and then stimulated and assayed for cAMP as described above. AC superactivation was determined by measuring forskolin-stimulated (10 μM) cAMP after treatment with either 10 nM spiradoline or vehicle for 18 h. AC superactivation data were expressed as a percent increase in forskolin-stimulated cAMP relative to vehicle-pretreated cells expressing the same receptor. Conditions and receptors were compared using a two-way ANOVA with receptor and treatment condition as independent factors.The degree of cAMP inhibition in spiradoline-treated HEK-293 cells transiently expressing RASSL variants was measured with the CatchPoint cAMP ELISA kit . Cells were plated at 5 × 10HEK293 cells stably expressing receptor constructs were plated at a density of 500,000 cells/ml onto glass Labtek II chamber slides  coated with poly-d-lysine. The following day, the cells were treated with agonist (spiradoline or dynorphin A 1–13) for typically one hour, or antagonist (NorBNI) overnight and briefly washed in PBS. The PBS was removed and replaced with 1 ml of cold 4% paraformaldehyde in PBS. The cells were fixed at room temperature for 10 min, washed with PBS, and then mounted in Vectashield  under cover slips. For confocal imaging on a Bio-Rad MRC 600 microscope, typical images were taken with a 40–60× oil immersion objective lens, subject to 5× Kalman filtering. The microscope operator was blind to both cell line and treatment condition.qi5 [qi5 is a chimeric G protein alpha subunit that has the Gαq wild-type sequence except for the C-terminal 5 residues, which were changed to the corresponding Gαi sequence. This allows Gi-coupled receptors to signal through the Gq pathway, resulting in a signal that can be detected using calcium-sensitive reagents. The following day, the cells were plated in a 96-well plate  and allowed to grow for 24 h before being incubated with the calcium-sensitive dye fura-3 for 1 h. The assay was performed as described [All receptors tested were transiently transfected using Lipofectamine into CHO cells in conjunction with the chimeric G protein Gqi5  in a 5:1escribed  using a KSL and MDL created the constructs and cell lines used here, designed and conducted the experiments; analyzed the data; and drafted the manuscript. HHE maintained cell lines and participated in making constructs, internalization assays and confocal microscopy. BRC conceived of the study and participated in its design and interpretation. All authors read and approved the final manuscript.


Osteoporosis is a systemic skeletal disorder, characterized by reduced bone mass, deterioration of bone structure, increased bone fragility, and increased fracture risk. It is more frequent to find among women than men at a 4:1 ratio. Evidence suggests that to adopt changes on some life habits can prevent or delay development of osteoporosis. Several osteoporosis-risk factors have been confirmed in the US and western Europe, but in El Salvador there are neither reliable epidemiological statistics about this skeletal disorder nor studies addressing osteoporosis-risk factors in women. The aim of this study was to determinate the extent of osteoporosis knowledge, the levels of both daily calcium intake and weight-bearing physical activity, and the influence of several osteoporosis-risk factors on these variables in three age groups of Salvadorean women.In this exploratory cross-sectional study, an osteoporosis knowledge assessment questionnaire incluiding a food frequency and a physical activity record section were used to collect data and it was delivered through a face-to-face interview. A convenience sample (n = 197) comprised of three groups of women aged 25–35 years, 36–49 years, and over 49 years was taken. Among-group comparisons of means were analyzed by two-way ANOVA. To determinate the overall influence of osteoporosis-risk factors, the multivariate analysis was used.Study results indicated that better educated women had more knowledge about osteoporosis than women with a low education level, regardless of age, even though this knowledge was rather fair. Older women got more weight-bearing physical activity at home and less at place of employment than reported by the younger women; however, neither group performed sufficient high-intensity WBPA to improve bone mass. Regardless of age, the most women consumed 60% or less than the Dietary Reference Intake of calcium and depend on household income, lactose intolerance and coffee rather than milk consumption.In summary, the majority of women in this study have modest knowledge on osteoporosis. The knowledge base is not linked to preventive health habits, including sufficient calcium intake and performance of weight-bearing physical activities. They are thus at increased risk for low bone mass. Osteoporosis is a systemic skeletal disorder, characterized by reduction of bone mass, deterioration of bone structure, increasing bone fragility, and increasing fracture risk -4. It isSeveral risk factors for osteoporosis have been identified, these include female sex; Caucasian or Asiatic race; advancing age; family history of osteoporosis or fragility fractures; a low body mass index; menopause before age 45 years; prolonged amenorrhea unrelated to menopause; nulliparity; prolonged lactation; diet low in calcium and vitamin D; poor intestinal absorption of calcium; lactose intolerance; excessive caffeine or alcohol consumption; smoking; sedentary lifestyle; and prolonged treatment with thyroid hormones, glucocorticoids (e.g. cortisone), anticonvulsants, aluminum antiacids, and use of anticoagulants ,3-6,8.Approximately 20% of bone mass is genetically determined; however, the risk of osteoporosis can be reduced by optimizing bone mass increasing during youth, conserving bone mass during adulthood, and minimizing bone mass loss during advancing age -7. AmongA study on US women aged over 25 years found that knowledge about osteoporosis was limited, irrespective of age . CalciumThere have been three related studies reported in Hispanic women: a study performed in Mexico , and twoAt present, the Salvadorean Public Health and Social Assistance Ministry does not maintain a specific record of this disease in adults, and most cases are likely classified as dorsalgy, that includes several musculoskeletal diseases such as radiculopathies, cervicalgy, lumbalgy, sciatica, spinal derived pain, and unspecified back pain . This reBearing in mind the lack of reliable epidemiological data, the present study wished to investigate osteoporosis-related life habits  and knowledge about osteoporosis among Salvadorean women aged ≥ 25 years. We investigated possible relationships of these variables with age, educational level, household income, family history of osteoporosis, menopause before age 45 years, fecundity (children per woman), lactose intolerance, caffeine consumption, low in calcium diet, and use of aluminum antiacids.This was an exploratory study with a cross-sectional design performed between May and September 2003, and it was used to survey a convenience sample comprised of 197 women  from urban areas within 6 main municipalities in El Salvador. All subjects were randomly sampled and recruited by personal contact through to visit homes, churches, schools, primary healthcare centers, hospitals, supermarkets, shopping centers, and parks. It was not necessary to obtain any proper informed consent from interviewed women. The participation rate of women was 87.5% (197 out of 225).We selected three age groups of women attending following criterions: women aged 25 – 35 years are at the period when higher peak of bone mass is reached [Data were obtained at the time of interview, which were performed by a member of the research team. Prior training in interview techniques was obtained for study. Each staff interviewer subsequently participated in several practice sessions, with an evaluation component to confirm accurate transcription of responses, and comparison and adjustment to ensure good inter-interviewer concordance.The data collection instrument incorporated a personal interview guide comprising five sections, validated through a prior pilot study performed in 12 women (4 in each age group).Among the demographic information was household income. It was classified by the criteria of the Salvadorean Economy Ministry as "below poverty line" if monthly income was below the cost of two basic shopping baskets (i.e. < $254), and otherwise as "above poverty line" .The second survey section generated information on family history of osteoporosis, and asked about the use of aluminum antiacids.Section 3 addressed weight-bearing physical activity  both at place of employment and at home, and included questions on weight-bearing exercises including jogging, swimming, aerobics, and isometrics. This survey section was adopted from a previous study . A test/Section 4 produced information on diet: for each of a list of 31 dietary and non-dietary items , the subjects were asked to estimate frequency of consumption . Similar checklists have been used in related previous studies . Given tFinal section (5) comprised eight open questions designed to assess nine knowledge dimensions about osteoporosis in subjects. The nine knowledge dimensions regarding osteoporosis, their specific questions and corresponding scores (from 0 to 42) are shown in Table Each subject's responses to the questions in the fifth section were analyzed by the principal researcher, who compared the answers with a semantic map Fig.  developeThe total score achievable was 42 points. The total number of hours of weight-bearing physical activity was estimated by adding the subtotals for activities at home, activities at worksite, and that of weight-bearing exercises.Total calcium intake was estimated by adding the estimated subtotals for consumed dairy products, other dietary intake, and calcium supplements, including calcium content per portion × the number of portions per day. Obtained values were compared with reference values .Data are cited in the text as means ± standard errors. For variables with homogeneous variance, means were compared by two-way analysis of variance and by Tukey tests for pairwise comparisons. For variables with non-homogenous variance, data were compared by the Kruskal-Wallis test (ANOVA on ranks) followed by Dunn's test for pairwise comparisons. These analyses were performed using SigmaStat version 2.03. Correlation analysis was used to determine relationships between knowledge scores and WBPA including exercise and calcium intake. To develop predictive models, we used a multivariate analysis based on multiple linear regression as contained in the program AMOS version 5 .The participant characteristics of each age group are shown in Table In all age groups, more than 44% of interviewed women reported a family history of osteoporosis, which included extended family: grandmothers, mothers, aunts, elder sisters, and cousins. Median, mean (SEM), and range of age of menopause in interviewed women were: 44, 42.3 (± 0.8), and 27–53 years, respectively. About 20% of interviewed women had lactose intolerance or ingested aluminum antiacids, both of these characteristics were unrelated of age. In addition, most women (> 69%) were coffee-consumers and the consumption of this drink increased with age.The sub-scores per knowledge dimensions about osteoporosis and age groups are shown in Table Most of interviewed women (75%) had enough knowledge about osteoporosis regarding the concept of disorder and its risk factors, sex-related factor, and prevention behaviours, irrespective of age Table . ConversF = 22.46, p < 0.001) than women with lower educational level . Only 5% of the women with higher education obtained total scores of less than 12 points, and 75% of them obtained total scores of more than 25   explained only about 37% of variance in total score . Analysis of variance with factors of age and family history of osteoporosis indicated that neither factor produced a significant effect , nor the interaction between them was significant.p < 0.001; Fig. H = 10.25, p = 0.069).The amount of weight-bearing physical activity reported at the worksite was markedly and significantly lower in over 49 years than in the other two age groups . Use of dependent variable of physical activity at worksite explained about 26% of variance ; the most effective predictor was family history of osteoporosis .Multivariate analysis employing dependent variable of amount of total physical activity and candidate predictors age, educational level, household income, family history of osteoporosis, early menopause and fecundity, appeared to explain only 5% of total variance , at home  or during exercise , squared correlations were rather low in all of cases.Total osteoporosis knowledge score was not predicted on the amount of weight-bearing exercise . Although, total osteoporosis knowledge scores were significantly associated with WBPA at worksite  and significantly more dairy calcium  than women in all other age/income groups Figs. .Supplementary calcium intake did not vary significantly among the age/income groups , neither was there any significant interaction between these factors.2 = 0.191, p < 0.001)   Fig. . With th01) Fig. . In both2 = 0.06, p < 0.001) or dairy calcium intake  or non-dairy calcium intake  or calcium supplements , squared correlations were rather low in all cases.Women who had moderate osteoporosis knowledge had an increase in their intake of calcium that was significant . Although total osteoporosis knowledge scores were significantly associated with total calcium intake . The greatest predictors were a woman's use of aluminum antiacids  and her educational level .With the addition of calcium supplement intake only 12% of total variance was accounted for  out of a possible 42 points. A similar study found Taiwanese women got a mean score of 15 out of 44 points related to six osteoporosis knowledge dimensions , whereasThe present results also indicate that Salvadorean women with secondary or higher education have significantly better knowledge of osteoporosis than women with a low educational level, regardless of age. Similarly, other study found that better educated Chinese women in Singapore seem to know more about osteoporosis than those ones worst educated . A previBesides, short counselling sessions about preventive aspects of osteoporosis are given by some physician's private clinics, because there is not a settled public health education program about osteoporosis in El Salvador. This country is not only case in Latin America, since Mexican women got more osteoporosis information from mass communication media than health education activities of public institutions . HoweverOur data on physical activity in the three age groups indicate that the amount of physical activity engaged in paid work currently declines with increasing age, whereas the amount of physical activity during housework appears to increase with increasing age. This trend was confirmed by multivariate analysis, which indicates that the most effective predictors of amount of physical activity at worksite or at home were age and educational level. Educational level attained likely increases the likelihood of obtaining paid work. However, recreational activities and other health-preventive behaviours such as to do isometric exercises may also determine total physical activity.Considering all subjects together, most reported physical activity 96%) was performed in the course of daily housework, walking to work or shops, or standing at work or at home; only 4% was directly applicable to weight-bearing exercise. About 50% of women in the youngest age group did more than 2 hours of physical activity per week, but the amount of physical activity in the older women was markedly lower, and even in the youngest age group very few women performed the recommended daily minimum of 30 minutes of exercise per day % was per.Very few of the women interviewed for the present study employ any of the weight-bearing physical activities that are known to be especially effective for increasing bone mass and thus perhaps reducing the risk of osteoporosis, such as isometrics . SimilarIndependent of age and income, most women interviewed (50 – 75%) have a daily calcium intake of less than 60% of the recommended level, thus increasing the risk of osteoporosis. Similarly, in another studies of Caucasian and African-American and Hispanic women in the US ,16, and The difference between our results in El Salvador and those obtained in the study of Caucasian women in the US  may, at The average proportion of calcium intake as dairy products was 57% in women below the poverty line and 68% in women above the poverty line; both values are close to those reported for Caucasian women in the US . These aThe consumption of caffeine-containing drinks, especially coffee, has been shown to influence calcium intake, since these beverages often replace milk and milk-based beverages due to dairy products are relatively expensive in El Salvador and many Salvadorean families 42.9%) have a low purchasing power, and live below the poverty line . Excessi% have a et al. also suggested that Hispanic women (particularly adolescents and young women) in general tend to reject dairy products more than Anglosaxon and Asiatic women.Calcium intake also varied with age, being significantly less among younger women. Similarly, most of interviewed Caucasian and African-American young adult women in the US did not get recommended calcium intake per day . This maThe key practical implications of this study relate to suggest set up of primary healthcare programs regarding osteoporosis for Salvadorean women as it has also suggested for Taiwanese women , and Hisa) The type and frequency of physical exercise.b) Diet-related risk factors, including inadequate intake of calcium, vitamin D, and phosphorus; also the adverse effects of drinking coffee or other low-calcium drinks instead of milk or milk-based drinks.c) The importance of monitoring menstruation frequency, since normal circulating estrogen levels and normal menstrual cycles are important for maintaining normal bone metabolism.In addition, it is clearly important to set up health education programs to focus on integration and internalization of knowledge about osteoporosis.Although our results indicate that many women have modest knowledge about osteoporosis concerning risk factors and preventive behaviours, this knowledge often does not translate to appropriate changes in healthy life habits as it is shown through a weak association between total osteoporosis scores and exercise or calcium intake, so that osteoporosis knowledge is not well internalized among interviewed Salvadorean women. The lack of time to practice most adequate osteoporosis preventive exercise may accounts for the weak association between foregoing variables since majority of interviewed women perform WBPA (> 8 hours/day), but as labour activities or housework. The low calcium intake among subjects may be explained through they have a low purchasing power and do not have the habit to ingest enough dairy products, the main diet calcium source . Non-daiFinally, we would suggest that osteoporosis education campaigns should be directed at families as well as individuals, with the aim of fomenting within-family education of children about the importance of calcium in the diet, whether as dairy products or in other calcium-rich products such soya milk and oat-based drinks and desserts.It showed that Salvadorean women with secondary or higher education have significantly better knowledge about osteoporosis than women with lower educational level, regardless of age. However, this knowledge does not appear to lead to improved life style or preventive habits of osteoporosis.The amount of weight bearing physical activity  during paid work or housework was high in the three age groups of interviewed women (over 8 hours/day). However, very few of the women interviewed for this study did not perform any of the weight-bearing physical activities that are known to be especially effective for increasing bone mass and thus reducing the risk of osteoporosis, such as going up and down stairs, jogging, aerobics, swimming, and isometrics.Most Salvadorean interviewed women have a daily calcium intake of 60% or less than the recommended level depending of lactose intolerance, household income, age, and coffee consumption. The former variables directly affect both calcium source diversity and intake frequency. Age would influence dairy calcium intake, since younger women tend to perceive dairy products as having a high animal fat content, and thus reject them. The coffee consumption would affect calcium intake, since this beverage often replace milk. Therefore, all these factors together may be increasing the risk to develop osteoporosis among Salvadorean women.WBPA: Weight-bearing physical activityANOVA: Analysis of VarianceSEM: Standard error of meanNone declared.RHR performed the design of the study, coordinated the study, performed data analysis, and drafted the paper. SMG participed in the design of the study and provided input into the paper.The pre-publication history for this paper can be accessed here:


Infectious complications are the major cause of death in acute pancreatitis. Small bowel bacterial overgrowth and subsequent bacterial translocation are held responsible for the vast majority of these infections. Goal of this study is to determine whether selected probiotics are capable of preventing infectious complications without the disadvantages of antibiotic prophylaxis; antibiotic resistance and fungal overgrowth.PROPATRIA is a double-blind, placebo-controlled randomised multicenter trial in which 200 patients will be randomly allocated to a multispecies probiotic preparation (Ecologic 641) or placebo. The study is performed in all 8 Dutch University Hospitals and 7 non-University hospitals. The study-product is administered twice daily through a nasojejunal tube for 28 days or until discharge. Patients eligible for randomisation are adult patients with a first onset of predicted severe acute pancreatitis: Imrie criteria 3 or more, CRP 150 mg/L or more, APACHE II score 8 or more. Exclusion criteria are post-ERCP pancreatitis, malignancy, infection/sepsis caused by a second disease, intra-operative diagnosis of pancreatitis and use of probiotics during the study. Administration of the study product is started within 72 hours after onset of abdominal pain. The primary endpoint is the total number of infectious complications. Secondary endpoints are mortality, necrosectomy, antibiotic resistance, hospital stay and adverse events. To demonstrate that probiotic prophylaxis reduces the proportion of patients with infectious complications from 50% to 30%, with alpha 0,05 and power 80%, a total sample size of 200 patients was calculated.The PROPATRIA study is aimed to show a reduction in infectious complications due to early enteral use of multispecies probiotics in severe acute pancreatitis. Infection of pancreatic necrosis is the major cause of death in acute pancreatitis -4 Small Lactobacillus plantarum in patients with acute pancreatitis showed very interesting results: a significant reduction of infected pancreatic necrosis (1/22 versus 7/23 infected necrosis)[Several trials with enteral probiotics have shown a significant reduction of infectious complications both in acute pancreatitis and in patients undergoing major abdominal surgery -21 A welnecrosis). Howeverin vitro data, a selection of 6 out of 75 probiotic strains was made by Winclove Bio Industries  in co-operation with the Departments of Paediatric Immunology and Surgery, of the UMC Utrecht . This paper describes the rationale of this product and the design of the study.It has been suggested that multispecies probiotics are more effective, because effects are strain specific. Combinations of probiotics can be designed so that strain-specific properties are additive or synergistic. Based on The bacteria responsible for infection of (peri-)pancreatic necrosis most often originate from the gut ,5,27 ThePrevention of UGID, SBBO and BT may lead to prevention of infected pancreatic necrosis and the resulting systemic complications. Intravenous antibiotic prophylaxis is considered an option to prevent pancreatic infection, but results from randomised clinical trials are conflicting -14.Escherichia Coli or Enterococcus species. The combination of these probiotics, in vitro, inhibits the growth of all relevant PMO's known to infect pancreatic necrosis [Probiotics are living micro-organisms that upon oral delivery exert a range of health promoting properties. For a growing number of inflammatory diseases  probiotics are being used, with variable clinical outcome. It is hypothesised that probiotics have an effect on different levels. We developed a multispecies probiotic preparation that aims to prevent SBBO and BT in ANP through (1) stimulation of the production of anti-inflammatory cytokines, especially interleukin-10, at the level of the intestinal mucosa, (2) stinecrosis .The study objective is to show that probiotics are effective in reducing the number of infectious complications during the course of acute pancreatitis.The primary endpoint is the total numbers of infectious complications during the hospital stay for acute pancreatitis, see table 1.Secondary endpoints are mortality, necrosectomy, use of antibiotics, total hospital stay, intensive care stay, side effects, abdominal complaints by a patient visual analogue scale questionnaire, sequential organ failure assessment (SOFA) scores, bacterial resistance and total costs.PROPATRIA is a double-blind, placebo-controlled randomised multicenter trial. The randomisation is stratified according to the aetiology of the acute pancreatitis (ie. biliary versus non-biliary), also block-randomisation per hospital is used. Its design and timing of the investigations are presented in Figure Patients will be enrolled from all 8 Dutch University Hospitals and 7 non-University hospitals.A total of 200 adult patients with a first episode of predicted severe acute pancreatitis will be randomised.• age equal to or above 18 years• first episode of acute pancreatitis• written and oral informed consent• post-ERCP pancreatitis• malignancy• infection/sepsis caused by a second disease• intra-operative diagnosis• immunocompromised patients• use of probiotics during admissionAfter inclusion in the study, patients with predicted severe acute pancreatitis, represented by at least one of the following scores: 3 Imrie criteria, CRP 150 mg/L, APACHE II score 8, are randomised within the first 72 hours after the onset of abdominal pain. Patients with a predicted mild attack of acute pancreatitis do not receive the study product. They do give informed consent and are monitored.This study is conducted in accordance with the principles of the Declaration of Helsinki and 'good clinical practice' guidelines. The independent ethics committee of all 15 participating hospitals approved the final protocol. Oral and written informed consent in form is obtained from the patient before inclusion in the trial.All the probiotics used in this study have a long history of use in the food industry. Probiotics have been studied in many critical ill and immunocompromised patients without any serious adverse events being noted. There is one trial that studied probiotics in acute pancreatitis patients and no serious advents were noted. If an infection with one of the administered probiotics might occur, this could be treated with antibiotics. During administration of the study-product both the patient and the nursing staff are asked to register any potential side effect or adverse event. An independent monitoring committees will discuss all reported (serious) adverse events.The analysis will be performed on the basis of an intention-to-treat (ITT) population and with respect to ITT principles. Also a per-protocol analysis and an analysis for necrotising versus non-necrotising pancreatitis will be performed.For ethical reasons it is desirable to end a therapeutic experiment once a statistical significant difference in treatment results has been reached. This study uses the stopping-rules according to Snapinn . An inteIt is anticipated that probiotics will lead to a reduction of infectious complications from 50% (% of patients) to 30%. The sample size calculation is based on α = 0.05, and a power of 80% This leads to a required sample size of 188 patients. Taking into account a 5% loss-to-follow up, a total of 2 × 100 patients will be randomised. Based on hospital data of 2002 about 500 patients have to be included in order to randomise 200 patients with predicted severe acute pancreatitis. There is one post-discharge follow-up after three months. The expected study end is in 2006 (2 years inclusion period).. According to this list a stratified random allocation of probiotics and placebo was performed. Each participating hospital received a series of subsequently numbered identical containers with probiotics or placebo. Patients with biliary cause of the pancreatitis are allocated to the lowest possible number available whereas patients with non-biliary cause are allocated to the highest possible number available (stratification).The randomisation list was generated by using the website Randomization.com Both the probiotics and placebo are packed in identical, numbered sachets. These sachets are packed in identical, numbered containers. The probiotics and placebo are identical in weight, colour, smell and taste. All doctors, nurses, research staff and patients involved are unaware of the treatment administered to the patient.® 641, Winclove Bio Industries, Amsterdam, The Netherlands) and fibre enriched tube feeding  is started. Ecologic® 641 consists of 6 strains of viable and freeze-dried bacteria, namely 4 lactobacilli: Lactobacillus acidophilus, Lactobacillus casei, Lactobacillus salivarius, Lactococcus lactis, and 2 bifidobacteria: Bifidobacterium bifidum and Bifidobacterium lactis in a total daily dose of 1010 bacteria. The study-product is administered twice daily through a nasojejunal tube for a maximum of 28 days. The treatment is stopped when a patient is diagnosed with infected pancreatic necrosis, is discharged or dies. A standard protocol for the treatment of acute pancreatitis is followed. During ERC with sphincterotomy in case of biliary pancreatitis antibiotic prophylaxis is allowed. Prophylactic use of proton pump inhibitors is only allowed in case of a clinical history of peptic diseases like peptic ulcer disease and reflux esophagitis. Prophylactic use of antibiotics is not allowed. At 7–10 days after admission, a routine CT scan is performed to detect pancreatic necrosis. Fine needle aspiration in (peri)pancreatic collections is performed only in case of clinical suspicion of infected necrosis. Further culturing, imaging and treatment are all based on clinical findings.Patients eligible for inclusion are followed during 72 hours after onset of the abdominal pain. When a patient meets a randomisation criteria (preferably within 24 hours), a nasojejunal feeding tube is passed and administration of the study product , MGH Besselink , HM Timmerman, LMA Akkermans, VB Nieuwenhuijs, E Buskens, UMC Utrecht; H van Goor, GT Bongaerts, UMC St. Radboud Nijmegen.Monitoring Committee-IHM Borel Rinkes (chairman), B Oldenburg, Y van der Graaf, W Renooij, UMC Utrecht; E Stobberingh, University Hospital Maastricht.MGH Besselink , VJM Zeguers , J Oors (auditor), HG Rijnhart (data manager), HM Timmerman, LMA Akkermans, HG Gooszen, UMC Utrecht.The last investigator per hospital is the local principal investigator. University Hospital Groningen: RJ Ploeg, MR Kruijt Spanjer, HS Hofker; University Medical Center St. Radboud Nijmegen: H Buscher, A Nooteboom, H van Goor; University Hospital Maastricht: JP Rutten; CHC De Jong; St. Elisabeth Hospital Tilburg: T Drixler; C van Laarhoven; Erasmus Medical Center Rotterdam: G van ’t Hof, EJ Kuipers CHJ van Eijck; Canisius Wilhelmina Hospital Nijmegen: B Houben, L Ootes, A Tan, C Rosman; Medical Center Rijnmond Zuid Rotterdam: N Wijffels, L van Walraven, J Lange; Leiden University Medical Center: A Haasnoot, S Schaapherder; Gelderse Vallei Hospital Ede: B Witteman; St. Antonius Hospital Nieuwegein: TL Bollen, B van Ramshorst; University Medical Center Utrecht: KJ van Erpecum; Meander Medical Center Amerfoort: R Frankhuisen, MA Brink; Vrije Universiteit Medical Center Amsterdam: CJ Mulder, MA Cuesta; Rijnstate Hospital Arnhem: E Spillenaar Bilgen, P Wahab; Academic Medical Center Amsterdam: DJ Gouma, O van Ruler, MA Boermeester.CRP c-reactive proteinAPACHE II Acute Physiology and Chronic Health Evaluation IIERC endoscopic retrograde cholangiographyCT scan computer tomographic scanThe pre-publication history for this paper can be accessed here: