Envenoming resulting from snakebites is an important public health problem in many tropical and subtropical countries. Few attempts have been made to quantify the burden, and recent estimates all suffer from the lack of an objective and reproducible methodology. In an attempt to provide an accurate, up-to-date estimate of the scale of the global problem, we developed a new method to estimate the disease burden due to snakebites.The global estimates were based on regional estimates that were, in turn, derived from data available for countries within a defined region. Three main strategies were used to obtain primary data: electronic searching for publications on snakebite, extraction of relevant country-specific mortality data from databases maintained by United Nations organizations, and identification of grey literature by discussion with key informants. Countries were grouped into 21 distinct geographic regions that are as epidemiologically homogenous as possible, in line with the Global Burden of Disease 2005 study . Incidence rates for envenoming were extracted from publications and used to estimate the number of envenomings for individual countries; if no data were available for a particular country, the lowest incidence rate within a neighbouring country was used. Where death registration data were reliable, reported deaths from snakebite were used; in other countries, deaths were estimated on the basis of observed mortality rates and the at-risk population. We estimate that, globally, at least 421,000 envenomings and 20,000 deaths occur each year due to snakebite. These figures may be as high as 1,841,000 envenomings and 94,000 deaths. Based on the fact that envenoming occurs in about one in every four snakebites, between 1.2 million and 5.5 million snakebites could occur annually.Snakebites cause considerable morbidity and mortality worldwide. The highest burden exists in South Asia, Southeast Asia, and sub-Saharan Africa. Janaka de Silva and colleagues estimate that globally at least 421,000 envenomings and 20,000 deaths occur each year due to snakebite. Of the 3,000 or so snake species that exist in the world, about 600 are venomous. Venomous snakes—which exist on every continent except Antarctica—immobilize their prey by injecting modified saliva (venom) that contains toxins into their prey's tissues through their fangs—specialized, hollow teeth. Snakes also use their venoms for self defense and will bite people who threaten, startle or provoke them. Snakebites caused by the families Viperidae  and Elapidae  are particularly dangerous to people. The potentially fatal effects of being “envenomed” (having venom injected) by these snakes include widespread bleeding, muscle paralysis, and tissue destruction (necrosis) around the bite site. Bites from these snakes can also cause permanent disability. For example, snakebite victims, who tend to be young and male, may have to have a limb amputated because of necrosis. The best treatment for any snakebite is to get the victim to a hospital as soon as possible where antivenoms  can be given.Although snakebites occur throughout the world, envenoming snakebites are thought to pose a particularly important yet largely neglected threat to public health. This is especially true in rural areas of tropical and subtropical countries where snakebites are common but where there is limited access to health care and to antivenoms. The true magnitude of the public-health threat posed by snakebites in these countries (and elsewhere in the world) is unknown, which makes it hard for public-health officials to optimize the prevention and treatment of snakebites in their respective countries. In this study, therefore, the researchers develop and apply a new method to estimate the global burden of snakebite.The researchers systematically searched the scientific literature for publications on snakebites and deaths from snakebites and extracted data on snakebite deaths in individual countries from the World Health Organization (WHO) mortality database. They also contacted Ministries of Health, National Poison Centers, and snakebite experts for unpublished information (“grey” literature) on snakebites. Together, these three approaches provided data on the number of snakebite envenomings and deaths for 135 and 162 countries, respectively. The researchers then grouped the 227 countries of the world into 21 geographical regions, each of which contained countries with similar population characteristics, and used the results of studies done in individual countries within each region to estimate the numbers of snakebite envenomings and deaths for each region. Finally, they added up these estimates to obtain an estimate of the global burden of snakebite. Using this method, the researchers estimate that, worldwide, at least 421,000 envenomings and 20,000 deaths from snakebite occur every year; the actual numbers, they suggest, could be as high as 1.8 million envenomings and 94,000 deaths. Their estimates also indicate that the highest burden of snakebite envenomings and death occurs in South and Southeast Asia and in sub-Saharan Africa, and that India is the country with the highest annual number of envenomings  and deaths .These findings indicate that snakebites cause considerable illness and death around the world. Because of the careful methods used by the researchers, their global estimates of snakebite envenomings and deaths are probably more accurate than previous estimates. However, because the researchers had to make many assumptions in their calculations and because there are so few reliable data on the numbers of snakebites and deaths from the rural tropics, the true regional and global numbers of these events may differ substantially from the estimates presented here. In particular, the regional estimates for eastern sub-Saharan Africa, a region where snakebites are very common and where antivenoms are particularly hard to obtain, are likely to be inaccurate because they are based on a single study. The researchers, therefore, call for more studies on snakebite envenoming and deaths to be done to provide the information needed to deal effectively with this neglected public-health problem.http://dx.doi.org/10.1371/journal.pmed.0050218.Please access these Web sites via the online version of this summary at PLoS MedicinePerspective by ChippauxThis study is further discussed in a snakebites (in English and Spanish)The MedlinePlus Medical Encyclopedia has a page on snakebitesThe UK National Health Service Direct health encyclopedia has detailed information about all aspects of venomous snakes and on snakebites Wikipedia has pages on antivenoms and about efforts to increase access to antivenoms in developing countries The World Health Organization provides information about PLoS Medicine also discusses the neglected problem of snakebite envenoming: Gutiérrez JM, Theakston RDG, Warrell DA (2006) Confronting the Neglected Problem of Snake Bite Envenoming: The Need for a Global Partnership. PLoS Med 3(6): e150A previous article in  Venomous snakes are found throughout most of the world (including many oceans), except for a few islands, frozen environments, and high altitudes . EnvenomFew reliable incidence data are available from the rural tropics where snakebites occur most commonly; reliable data are mostly limited to a few developed countries where bites are rare. Thus, the true global incidence of snakebite envenoming, its impact, and characteristics in different regions remain largely unknown. However, information on the number of bites, envenomings, and deaths and on the frequency of long-term sequelae due to snakebites are essential for assessing the magnitude of the problem, drawing up guidelines for management, planning health care resources (particularly antivenom), and training medical staff to treat snakebites.Recent estimates, which are fragmentary, variously suggest that worldwide, venomous snakes cause “5.4 million bites, about 2.5 million envenomings and over 125,000 deaths annually” , “more tThe objective of this article is to review the currently available literature on snakebite worldwide, and to attempt to make scientifically robust estimates of the current burden. Toward that end, we developed a method to obtain global estimates of envenoming and deaths due to snakebites; these global estimates were based on regional estimates, which were, in turn, derived from data available for countries within a defined region.The methodology consisted of two components, data retrieval and estimation.The data retrieval process consisted of three main strategies: electronic searching for publications on snakebite; extraction of relevant country specific data required for estimation from databases maintained by the World Health Organization (WHO), United Nations (UN), World Bank (WB), and Food and Agriculture Organization (FAO); and identification of grey literature by discussion with key informants.The keywords used for this search were “snakebite and epidemiology,” “snakebite and incidence,” “snakebite and morbidity,” “snakebite and mortality,” “snakebite and envenomation,” “snakebite and envenoming,” and “snakebite and deaths.” The languages of publications included English, French, and Spanish. The process of the published literature review is shown in The data were extracted from the publications, transcribed into data extraction forms, and entered into a database in Microsoft Excel by one researcher. Data from work done earlier than 1985 were excluded from this database. The main variables extracted were: the number of snakebites estimated or reported for a country, nationally, or subnationally; the incidence rate of snakebite; the number of deaths due to snakebite estimated or reported for the entire country; the mortality rate of snakebite; and the percentage of venomous bites out of all snakebites where available. This database was independently cross-checked with the original publications for accuracy and completeness by two other researchers.When more than one value was available for the same country from a number of sources, only the lowest and the highest values were used. When different rates were quoted in the same publication, the lowest and the highest rates were used. Data for calculation of the number of snakebite envenomings were obtained for 46 countries –60 whileThe WHO Headquarters in Geneva, Switzerland, permitted us access to the WHO mortality database  and the Regional Offices and several country offices of the WHO were contacted to request information on incidence and mortality of snakebite. After the primary review of literature, the countries that did not have reliable published data on snakebite were identified. We contacted Ministries of Health, National Poison Centres, researchers, and experts on snakebite in these countries for information on the incidence of, and mortality due to, snakebite in their countries.A second search on the internet using the Google search engine was conducted for all countries still without data. The keywords used for this search were the “(country name) and snakebite.” This search included sources in English, Japanese, and Russian.Two hundred twenty-seven countries were grouped into 21 distinct geographical regions in this study, according to the classification used for the Global Burden of Disease (GBD) 2005 study  . This laA country was considered free of snakebites  if no literature (published or unpublished) indicated the occurrence of snakebite since 1985. A country was considered to have no mortality due to snakebites, even though snakebites have been reported, if no mortality statistics have been reported to the WHO mortality database from 1990 to date, provided that the country has a HDI 0.750 or higher and vital registration coverage of deaths 75% or higher. The most recent incidence or mortality rate that had been calculated after 1985 was assumed to be the current rate for a country. If the HDI was 0.750 or higher and coverage of vital registration of deaths was 75% or higher, the average number of deaths reported over the last 5 y to the WHO mortality database in the respective category of the ICD code was assumed to be the total number of deaths due to snakebite for the country.The assumptions made on the representativeness of data were based on the national coverage of the data. It was assumed that the different types of data (data originating from different sources) were representative in the following order of priority. (1) Published community-based national data; (2) published hospital-based national data; (3) unpublished national data ; (4) published community-based subnational data; (5) unpublished community based subnational data; and (6) published subnational hospital data where the population served was known.High and low estimates of the number of envenomings and deaths due to snakebite for each GBD region were derived from the highest and lowest estimated number of envenomings and deaths for countries within a region. Regional estimates were summed up to arrive at global estimates.Four types of data were available to be used for calculation of the incidence rate of snakebite envenoming  for each country. These data were prioritised as follows. (1) Published data or estimates of the absolute number of annual snakebites in a country and the number of persons seeking treatment for snakebite each year, reported by National Ministries of Health, National Poison Centres, or the entire hospital system in a country;(2) unpublished data or estimates of the absolute number of annual snakebites in a country and the number of persons seeking treatment for snakebite each year, reported by National Ministries of Health, National Poison Centres, or the entire hospital system in a country; (3) number of snakebites based on the incidence reported in published community-based studies at the subnational level; and (4) number of snakebites based on the incidence reported in published hospital-based studies at the subnational level.Incidence rates calculated from nationwide community-based studies were not available in the literature. Where the absolute annual number of envenomings for a given country was available, the incidence rate was calculated using the country population for the reporting year as the denominator. For subnational data, the incidence rate was calculated using the population surveyed or the population served by the hospitals, as the denominator.The following steps were then followed. For countries where snakebites do not occur, a zero incidence was used. For countries having a single national incidence rate, the rate was applied to the total population to estimate the number of snakebites for the country. For countries having a single subnational incidence rate, the rate was applied to the subnational study population, and the number obtained was considered the number of snakebites for the entire country.Two incidence rates (high and low) were calculated for countries for which more than one rate was available. The lower rate was applied to the total population of the country for the low estimate. The high estimate was obtained by summing the estimates obtained after applying the higher incidence rate to the rural population and the lower rate to the urban population of that country.For countries where snakebite is known to occur, but which did not have data, two estimates of the number of snakebites occurring within the country were calculated as follows. The low estimate was calculated by applying the lowest incidence rate reported by another country within the same GBD 2005 region to the given country's population. The high estimate was calculated by summing the estimates obtained after applying the highest incidence rate reported within the same GBD 2005 region to the given country's rural population and the lowest incidence rate reported within the same region to the given country's urban population.For countries where snakebites do not occur the number of deaths due to snakebites was estimated as zero. For countries that had a HDI of 0.750 or more in 2005 , and theThe following steps were used in the estimation of deaths due to snakebites. Mortality rates  were calculated using the country populations of the reporting year as the denominator. If only one mortality rate was available, it was considered the lower mortality rate. If more than one mortality rate was available for the same country, the lowest and the highest reported rates were considered the low and high mortality rates. For subnational data, the mortality rate was calculated using the population surveyed, or the population served by the hospitals, as the denominator. Within each GBD 2005 region the lowest and the highest mortality rates reported were applied to countries without data.The following method was used for estimation of the number of deaths due to snakebite for each country. For countries where snakebites do not occur, zero mortality was used. For countries having national mortality rates, the rate was applied to the total population of that country to arrive at the estimate of the number of deaths due to snakebites. For countries having subnational mortality rates, the higher mortality rate was applied to the rural population of that country and the lower mortality rate was applied to the urban population of that country, and the two estimates were summed to arrive at the high estimate for that country.n = 14) described both total snakebite and snakebite resulting in envenoming. A considerable number (n = 32) did not make a distinction between bites resulting in envenoming and bites not resulting in envenoming. Although our prime estimate was snakebite envenomings, we also estimated the total number of snakebites, using figures for the percentage of bites with envenoming out of total bites reported in a few publications. The calculated number of bites without envenoming was added to the number of bites with envenoming estimated originally.The majority (70%) of the published papers on snakebite described only snakebite envenomings, while a very few  by looking at the literature in different continents to enable us to extrapolate from the number of envenomings. In Asia, various studies suggest that envenomed bites constitute between 12% and 50% of the total number of bites ,84,85. TThese data indicate that the relationship of the total number of snakebites to envenoming is highly variable and may be influenced by a number of factors. To give an indication of the total number of bites, we have assumed that the total number of snakebites would be two to three times the number of envenomings. This estimate combined with our estimate that the number of envenomings ranges from 421,000 to as high as 1,841,000 annually, we estimate 1,200,000 to 5,500,000 snakebites may occur globally per year., we estimate that 1,200,000–5,500,000 snakebites may occur globally. The vast majority of the estimated burden of snakebite is in South and Southeast Asia, sub-Saharan Africa, and Central and South America, as identified in previous estimates of the global burden. Despite accounting for nearly one-fourth of the global snakebite incidence, mortality due to snakebite is relatively lower in Central and South America when compared to other high incidence regions. Mortality may be lower because of better snakebite management systems, including the development of locally effective antivenoms, in many Latin American countries. The lower estimates of snakebite incidence in sub-Saharan Africa are probably a reflection of under-reporting from many parts of this region; we found it particularly difficult to find reliable data for this region, especially for East Africa. India, with its population of over a billion people, accounted for the highest estimated number of bites and deaths for a single country.We estimate that at least 421,000 envenomings and 20,000 deaths occur worldwide from snakebite annually. These figures may be as high as 1,841,000 envenomings and 94,000 deaths. On the basis of the estimation that the total number of snakebites is two to three times the number of envenomingsThe most often quoted currently available estimates of the global burden of snakebite ,4 are suThe true global incidence of snakebite, envenomings, and its associated mortality are difficult to estimate. The overwhelming majority of bites occur in rural areas of resource-poor countries. Reporting and record-keeping in such situations are generally poor. Snakebite varies seasonally and geographically within countries; i.e., high incidences are reported during agricultural activity . Many esConversely, many of the few published community surveys of snakebite have been performed in areas where the problem is endemic and perhaps a major public health problem, and incidence and mortality figures then extrapolated to represent the entire country or region; this would lead to an overestimation of the burden. To circumvent this problem we applied the higher rates identified for a particular country only to the rural population of that country if the rates were reported at subnational level. This would have resulted in considerable underestimation, because some of the published subnational studies have reportedly been conducted in regions where snakebite is not considered a high priority public health problem ,60,90,91The most important issue we faced was the paucity of good-quality published data, particularly from nationwide community-based studies. Despite this deficiency, we have given priority to national estimates derived from the national health systems and related services over rates available from subnational studies to try to avoid overestimation of national incidence or mortality rates. Data generated from hospital-based studies were used in a few instances where no other data were available, provided that the catchment population was known.We considered only data reported after 1985 to make the estimates as current as possible. More than 70% of the data that were utilised in arriving at the estimates were, in fact, reported after 1995. Most regions lacked either population-based studies or surveillance systems that might measure snakebite incidence at the population level. In some cases, many countries in a region lacked data. For example, data were available for only one country in eastern sub-Saharan Africa, where snakebite is known to be an important public health problem. Population-based studies of incidence and mortality are urgently needed to describe the epidemiology of snakebite in these areas. In some countries that encompass large geographical areas and have large populations such as India, China, Indonesia, and Russia, country estimates had to be calculated on the basis of single or few regional incidence or mortality figures. This also means that relatively small changes in the incidence rates could lead to considerable differences in the estimation of the total burden in terms of the number of envenomings and deaths. The proportion of the population that is rural, and therefore exposed to the risk of snakebites, can also considerably affect estimates for these countries.On the rare occasions where multiple studies were reported for the same country, we selected the most conservative incidence and mortality rates for our low estimates. We followed this principle when extrapolating data for countries within a region. That is, where no data were available for a country in which bites were likely to occur, we selected the most conservative rate available from a country within the region as the rate for the country without data . This waMost previous estimates of snakebite morbidity and mortality appear to have been derived from studies that were done in such high incidence areas within regions or countries, and extrapolated to whole countries and regions. Our approach minimised this effect, although in some regions, such as the Caribbean, lack of data still meant that we were forced to use very high rates in our calculations of the high estimate. These methodological differences may have played a substantial role in accounting for the differences between the previous estimates and our low estimate . The casAnother plausible reason is that we used very recent incidence and mortality data from India and Pakistan that are considerably lower than previous estimates. Our estimate of about 81,000 envenomings and nearly 11,000 deaths due to snakebite in India is much lower than the 200,000 bites and up to 50,000 deaths quoted in previous estimates . Given tEstimation of the total number of snakebites (both with and without envenoming) is difficult because of the scarcity of literature that differentiates the two and variation in the distribution of venomous snakes in the regions; few community-based studies address this. The true burden of snakebites may not be reflected in hospital data, because a considerable proportion of people with asymptomatic bites may not seek treatment at hospitals; in some settings, snakebite victims may preferentially attend traditional healers. It was also not possible to ascertain whether “all bites,” especially in community surveys, included bites of nonvenomous snakes and dry bites of venomous snakes. These non-envenoming bites would arguably not contribute much to the burden of disease, although the opportunity cost of the bite may affect the victims and the households adversely. We estimated the total number of snakebites using data on the proportion of snakebites with envenoming from studies in different parts of the world. The proportion envenomed varied considerably, most probably because of both the effects of different snake species and variation in methodology. This heterogeneity means that we have only a crude estimate of the total number of snakebites. Our main focus was to estimate snakebite envenoming, as it is envenoming that causes most of the burden due to snakebite: requirement for antivenom, hospital and intensive care unit care, and surgery; complications; permanent sequelae; and even death.The WHO mortality database was the main source of information used for estimation of the mortality due to snakebite, providing nearly 70% of the data used. The reliability of the data reported to this database by countries was assessed on the basis of two criteria: the HDI and the coverage of vital registration of deaths. Only code X20 of ICD10 was considered snakebite to minimise inclusion of deaths caused by other venomous animals. Code X20 does not differentiate between deaths due to snakes and lizards. However, lizard bites, unlike venomous snakebites, are not known to be fatal; in fact, in the last 50 y only a few cases of envenoming and no deaths have been reported as due to lizard bites. Thus, from an epidemiological point of view lizard bites are legible and have no public health implications.In any estimation, assumptions have to be made and the robustness and validity of the estimate depends on how well the assumptions are met. The assumptions we made included considering a country as free of snakebites  if there was no literature (published or unpublished) indicating the occurrence of snakebite since 1985, and assuming that the mortality data reported to the WHO mortality database to be accurate and representative of the national data for countries with a high HDI and a high vital registration coverage of deaths. We did not make any adjustments to arrive at the final estimate of deaths for countries with less than 100% vital registration coverage to prevent an apparent unrealistic precision to the estimate. The most recent incidence or mortality rate reported after 1985 was assumed to be the current rate for a country.We estimated the numbers of snakebites and deaths only. No reliable data were available on the long-term physical and psychological consequences of surviving snakebite, but as most snakebite victims are in the economically productive age group, the economic impact of disability is likely to be high. Although the socioeconomic burden of snakebite cannot be stressed strongly enough, in this study we did not attempt to quantify this burden. Global health resource allocation is often based on DALYs (disability-adjusted life-years), and other socioeconomic markers rather than on the number of patients and deaths, despite the limitations of each of these measures of burden. Future assessments of the burden of snakebite will draw greater attention to the problem, which in turn will help win resources to tackle this neglected issue.In conclusion, data from several new sources and the development and application of a scientifically robust method that can be replicated has enabled us to generate a revised estimate of the global disease burden due to snakebite, although the inadequacy of available data and the consequent need to rely upon extrapolation mean that this estimate is still far from perfect. The burden is considerable, especially in South and Southeast Asia, sub-Saharan Africa, and Central and South America. Given the high burden, the paucity of reliable snakebite data, particularly in some of these areas, is both surprising and worrying. The fact that snakebite varies geographically and seasonally, that it is mainly a rural tropical phenomenon where reporting and record keeping is poor, and that health-seeking behaviour is diverse with traditional treatments being sometimes preferred to Western medicine, all contribute to the difficulties faced when studying its epidemiology.To address this problem, population-based studies of incidence and mortality in countries that appear to have the highest case load and mortality rates are urgently required to clarify the situation. The quality of reporting and recordkeeping on morbidity and mortality due to snakebite in health facilities should be optimised. Data sources should include traditional medical practitioners and rural health workers, because high morbidity and mortality due to snakebite can be encountered in geographically isolated communities . AccuratTable S1(427 KB DOC)Click here for additional data file.Table S2(478 KB DOC)Click here for additional data file.


Anticipating physician supply to tackle future health challenges is a crucial but complex task for policy planners. A number of forecasting tools are available, but the methods, advantages and shortcomings of such tools are not straightforward and not always well appraised. Therefore this paper had two objectives: to present a typology of existing forecasting approaches and to analyse the methodology-related issues.A literature review was carried out in electronic databases Medline-Ovid, Embase and ERIC. Concrete examples of planning experiences in various countries were analysed.Four main forecasting approaches were identified. The supply projection approach defines the necessary inflow to maintain or to reach in the future an arbitrary predefined level of service offer. The demand-based approach estimates the quantity of health care services used by the population in the future to project physician requirements. The needs-based approach involves defining and predicting health care deficits so that they can be addressed by an adequate workforce. Benchmarking health systems with similar populations and health profiles is the last approach. These different methods can be combined to perform a gap analysis. The methodological challenges of such projections are numerous: most often static models are used and their uncertainty is not assessed; valid and comprehensive data to feed into the models are often lacking; and a rapidly evolving environment affects the likelihood of projection scenarios. As a result, the internal and external validity of the projections included in our review appeared limited.There is no single accepted approach to forecasting physician requirements. The value of projections lies in their utility in identifying the current and emerging trends to which policy-makers need to respond. A genuine gap analysis, an effective monitoring of key parameters and comprehensive workforce planning are key elements to improving the usefulness of physician supply projections. The health care sector is labour-intensive and human resources are the most important input into the provision of health care, as well as accounting for the largest proportion of health care expenditure . PlanninFirst, current workforce supply is estimated, and the adequacy of current supply (compared to current requirements) should be assessed. This gap analysis permits identification of current imbalances, provided that the population segment under scrutiny  is precisely defined . Second,An oversupply may inflate healthcare costs through a possible supplier-induced demand  and may To address the question, policy planners have a number of forecasting tools at hand, but the methods, advantages and shortcomings of such tools are not straightforward and not always well appraised. Therefore, this paper has two objectives: (1) to present a typology of existing forecasting approaches, taking the physician workforce planning as an illustrative case; and (2) to analyse methodological challenges of such models and discuss potential paths for improvement.A literature review was carried out in electronic databases Medline-Ovid, Embase and ERIC with the following search terms: health AND (workforce OR manpower OR physicians OR human resources) AND (forecast OR planning OR models). The search was restricted to documents published in Dutch, English, French or Spanish, during the years 1997 to 2007. Documents reporting on physician supply planning in developing countries were excluded. Concrete examples of planning experiences in various countries were analysed.Four main approaches for physician supply forecast were identified .Also called the trend model, this relies on physician-per-population ratios and takes into account health care services currently delivered by the total pool of practising physicians. This approach assumes that future requirements for physicians will need to match the volume of services currently provided on a per capita basis. This approach is based on three assumptions: the current level, mix, and distribution of providers in the population are adequate; the age and sex-specific productivity of providers remain constant in the future; the size and demographic profile of the providers change over time in ways projected by currently observed trends . In suchAlthough conceptually straightforward, such a model can gain complexity. First, the supply-based model often integrates parameters of demand. Possible changes in demographic features and the delivery system are sometimes factored into the projections. Second, the model is not necessarily based on a simple headcount of providers, but can integrate parameters linked to professional productivity. The model can also serve to create scenarios, such as changes in the skill mix. In such instances, the model is called by some authors a substitution model ,11. The Also called the requirement model or the utilization-based approach, this examines the quantity of health care services demanded by the population. Demand refers here to amounts of the various types of health services that the population of a given area will seek and has the means to purchase at the prevailing prices within a given period. Physician requirements are estimated based on the number and type of projected services and on the physician-per-population ratios in the reference population (population at baseline or benchmarking). This information can be derived from analysis of billing data  or from Demand can be estimated through at least three methods :1. The service utilization method: Data on current service utilization serve as a proxy of satisfied demand. This approach is the most commonly used.2. The workforce-to-population ratio method: A ratio is established between the population (segmented into different age categories) and the requirement for health practitioners. Future projections are based on estimated service need per unit of population and forecast population scenarios. For example, Morgan et al. assessed the adequacy of the oncologist workforce in Australia by using the reference ratio of seven oncologists per million inhabitants. This reference ratio was derived from international benchmarking and expert evaluation .3. The economic demand method: An assessment is made of the current and future social, political and economic circumstances, and how consumers, service providers and employers will behave as a result of those circumstances. Cooper suggested that economic projections could serve as a gauge for projecting the future utilization of physician services .The demand-based approach has been used in various countries such as the United States ,31-33, CAlso called the epidemiological approach, this involves defining and projecting health care deficits along with appropriate health care services. Needs refers here to the number of workers or quantity of services necessary to provide an optimum standard of service and to keep the population healthy. This planning method combines information on the health status of the population with disease prevalence, demographics and appropriate standards of care. The information is essentially provided by professionals.This approach was used in the United States in the early 1980s, by the Graduate Medical Education National Advisory Committee (GMENAC). Its model used epidemiological evidence for each specialty, modified by professional opinion on the need and appropriateness of care for various conditions to estimate physician need . The folThis approach relies on three assumptions: all health care needs can and should be met; cost-effective methods of addressing needs can be identified and implemented; health care resources are used in accordance with relative levels of needs .An important limiting factor of the needs-based approach is the unavailability of extensive epidemiological data, leading some authors to use an alternative approach based on utilization data. A neat example of this was given by Persaud et al. for ophthalmologists in Ontario ,11. The Moreover, the needs-based approach is more useable when projecting numbers in a specific care specialty, because incidence of the diseases managed within that care specialty can be approximated with more accuracy. An example is the radiologists forecast in Australia. One radiation oncologist is expected to treat 250 new patients per year. The number of radiation oncologists required is thus determined by calculating the number of patients with newly diagnosed cancer during that year and dividing the assumed treatment rate by 250 .This is based on identifying regions or countries that are similar in their demographic and health profiles but are markedly different in their costs and deployment of health care resources. Municipalities and health plans that achieve low levels of deployment of clinically active physicians without a measured loss of patient welfare are considered benchmarks. Those benchmarks are then used as a current best estimate of a reasonable physician workforce active in patient care for planning . BenchmaIn benchmarking, the extrapolation methodology is crucial. To draw relevant lessons from a reference model to a specific situation, adjustments are necessary for population demography, population health, patients' insurance, physicians' productivity and health system organization . ObviousOur model's typology has been set up to ease understanding Table . In realThe most common mix encountered in the literature associates supply-based and requirement-based parameters, which permits the performance of gap analysis for future years and taking action to make physician supply match requirements. Again, the supply-to-health care utilization ratio at baseline is assumed to be appropriate and serves as a reference for any gap analysis in the future ,40.The Effective Demand-based approach is another example of a mixed model. In this approach, the epidemiological principles of the needs-based approach are complemented by economic considerations, i.e. fiscal constraints are integrated in the model . Under tThe Effective Infrastructure approach is also based on needs assessment but is complemented by infrastructure considerations. The reasoning is that there is little point in having a workforce greater than the physical capacity of the health system to gainfully employ or use that workforce . AnotherIssues relating to human resources are complex in essence, and this complexity will be only partially captured in static models, based on a deterministic approach, such as the majority of the models reviewed above. Even when physician-to-population ratios, population-based rates and utilization-based rates were used as the basis of computerized simulations, these models lacked the capacity to examine the dynamic relationships between inputs and outcomes. There are alternatives to this bounded approach.First, regression modeling could be a more appropriate approach. Theoretically, regression models can be fit for health workforce projections. Such models allow to adjust for the effect of various parameters and to estimate the importance of each of those parameters to the supply and requirements for health care professionals. It would also be possible to compute confidence intervals around the required numbers. Such models have been used in the United States by Angus et al.  and by LRegression models can also serve as a basis for indirect standardization, as was the case for general-practice workforce modeling in Australia . In thatA slightly different methodology was used in the United States by Lipscomb et al., who determined physician requirements through empirically based models. Those models were then used to yield estimates of future staffing requirements conditional on future workload, but also to compare current physician staffing in a given setting with system wide norms, i.e. detect under- and over-supply .Second, uncertainty in health projections must be assessed, so that planners can anticipate possible variations and adapt the planning of human resources in consequence. This was rarely the case in the examples presented in the first part of this paper. The two common approaches that can be used are deterministic sensitivity analysis and stochastic simulation.In sensitivity analysis, a sensitive variable is detected when changes in its input value result in considerable changes in the outcome . In stocSong and Rathwell, who developed a simulation model to estimate the demand for hospital beds and physicians in China between 1990 and 2010, used the two approaches . Their fMore recently, Joyce et al. , AndersoReliability is defined in the present framework as the capacity of a model to correctly project the health workforce deemed to be adequate at some identified future time. We used three means for exploring models reliability: (1) to compare how a set of models applied to the same setting and the same period produced matching projections ; (2) to examine how projections are sensitive to parameters inserted into the models ; (3) to confront projections and actual figures .Different models used for projection of health human resource requirements will produce different estimates. Anderson et al., who forecasted the requirement of otolaryngologists in the United States by means of three methods  provided a nice example of such a discrepancy . The besAnderson et al. considered the managed-care approach the most appealing because it reflected the workforce staffing ratios of managed-care organizations that operate efficiently in the marketplace. However, in each of the models, it was possible to show a shortage or surplus of physicians by altering one or more key assumptions.Persaud et al. also tested the projections yielded by a range of models ,11. TheiInterestingly, Politzer et al. reviewed five projection methods for generalist and specialist care requirements in the United States and reached the same conclusion: that different models yielded different figures. But they took advantage of these differences to conduct a type of meta-analysis and to derive requirement bands, instead of one unique requirement figure .The results of projections differ because the models are based on different assumptions. The supply model assumes that existing trends, policies and training positions will be maintained, thus expecting and accounting for no future changes in market factors. The demand model assumes that physician numbers can increase in response to an expected rate of economic growth. The needs-based model assumes that the number of physicians should match the calculated number required to provide adequate medical services to the future population. The first two types of models are based on extrapolation, while the third is based on expert scenarios. The first two types of models aim at projecting a likely future given the current parameters, although some changes can be factored in the models; the third relies on a normative approach. The models also differ in limitations, implications for population health outcomes and resource costs.Whatever the modeling approach, estimates for requirements will not be exact numbers but instead a range of numbers, as several authors have suggested ,33,46. SA Markov-population model can provide a valid projection of the future workforce, provided that the error present in the projection is small and quantifiable, i.e. the inflow and outflow parameters are known with certainty. However, a number of difficulties are also present: (1) small uncertainties in inflow and outflow parameters might result in great inaccuracy; (2) trends, which are often considered to keep on developing infinitely, present plausible limits that must be accounted for; and (3) calculation of statistical confidence intervals is impossible, although there have been attempts to apply those models in a more probabilistic sense ,33,44.Although appealing because of its simplicity, benchmarking also presents a number of drawbacks. A similar physician density can provide very different levels of care according to care accessibility, provider productivity, task sharing or prevailing health care delivery model (e.g. the role of a family practitioner can vary greatly across countries). Finally, determinants of population health itself, such as environmental health hazards or lifestyles, can affect the results. For those reasons, it is recommended to use regional benchmarks that are comparable in demographic characteristics and have a similar health system .Attention should be paid to three sets of factors influencing the model's validity: (1) parameter uncertainty, i.e. the quality of available data; (2) the plausibility of projection scenarios, i.e. the likelihood of the underlying assumptions as regards future requirements; and (3) the goodness of fit of the model, i.e. the comprehensiveness of the model and its adjustments for confounding and/or interacting factors.Data quality is one of the key challenges. Easily accessible clinical, administrative and provider databases are often lacking to conduct complex modeling activities. Even the number of active physicians can be difficult to assess, with important variations between national databases. Moreover, the forecasts usually focus on headcounts, with loose translation into effective workforce. Another example of a loose evidence base is the gender difference of productivity. It is generally estimated that women produce 20% fewer medical services than their male counterparts, an estimate that feeds many models . HoweverThe likelihood of the underlying assumptions is also an important consideration. In 1998 an undersupply of physicians in Canada was projected for the next 25 years, based on an estimated 31% reduction in the physician-to-population ratio . HoweverLastly, the goodness of fit of the model must be assessed. In the models reviewed earlier, adjustment for confounding and/or interacting factors is generally minimal . Macroeconometric and microeconometric models of the health care system can be used to draw a more comprehensive view of health workforce planning. However, such models require considerable amounts of data .Ultimately, the reliability of the forecasting models can be addressed by analysing the success of past projections in either projecting or modifying the future, i.e. reaching a balance between supplies and requirements. This evaluation is difficult. On the one hand, there are no direct means to assess whether the target was effectively realized . On the It is nevertheless possible to test the realization of projected supply headcounts. We performed the exercise for various countries Table  for whicThere was a margin of error in all the projected physician headcounts, and the error size increased with the time lag between projection and assessment. For instance, in Australia, workforce projections have been computed with baseline year 2001 to 2012, on the basis of a supply-based approach . For thePlanning the health workforce is aimed at having the right number of people with the right skills in the right place at the right time to provide the right services to the right people. It involves comparing estimates of future requirements for and supplies of human resources. However, a major weakness of the examples retrieved in peer-reviewed journals and included in our review was the lack of gap analysis in the reference year, most of the forecasts implicitly making the assumption of an adequate health workforce at baseline. The objective of the projection exercise was therefore to compute the future workforce required to maintain the current equilibrium by taking into account evolving supply and demand trends. However, assessing the adequacy of the workforce and determining the existence of imbalances at baseline is central to workforce planning.Rizza et al. attempted to apprehend the level of balance between supply and demand at baseline . The autMorgan et al. accounted for the deficit in radiation oncologists at baseline to compute projected requirements . The speSome indicators can be helpful in performing a gap analysis, such as employment indicators , activity indicators (e.g. overtime), monetary indicators (e.g. wages), and normative population-based indicators (e.g. doctors/populations ratios) . The AMWHowever, none of the proposed indicators are unambiguous. For instance, Zurn et al.  emphasizIt is suggested that a range of indicators should be considered, to allow for a more accurate measurement of imbalances, and to differentiate between short-term and long-term indicators. In addition, further efforts should be devoted to improving and facilitating the collection of data. Moreover, it remains necessary to determine at what level an indicator suggests workforce surplus or shortage, e.g. when a waiting time becomes unacceptable.We have shown that in most of the reviewed examples, important determinants of supply and demand were not fed into the planning models, most probably because relevant data were not collected and/or not available. The focus to date has very much been on the impact of demographic change on individual health professions, i.e. mainly the effect of an ageing population on the service requirements, and the effect of an ageing workforce on the capacity to meet requirements . As a reThere is no single accepted approach to forecasting physician requirements . This isTable It is also crucial to anticipate the implications of adopting emerging technologies  and redefining the roles of all available health professionals . Decision-makers must also review professionals' working conditions and their remuneration (fee-for-service or not) as well as incentives and regulations adopted to attract and retain health professionals in the health sector. How quality of practice would be monitored and ensured is also an important issue to consider. Those choices would have to be validated by the various stakeholders  to ensure a reasonable degree of feasibility in their implementation.International migrations of health professionals in Belgium are a good example of rapidly evolving and challenging key factors to be closely monitored. Since 1997, 100 new yearly incomers were accounted for in the projections, on the basis of a secular trend. The total number of new physicians licensed to practice per year was 700. However, since 2004 there has been a sharp increase in migration influx, with new visas delivered to foreign physicians rising from 138 in 2005 to 430 in 2007.Before 2004, the inflow originated largely from the neighbouring countries  and to a lesser extent from Spain and Italy. Since 2004, the larger group of immigrant doctors has come from the eastern part of European Union (Poland and Romania). The enlargement of the European Union since 2004, as well as the implementation of the internal market for services and the mutual recognition of professional qualifications between Member States, favoured the increase.numerus clausus) in Belgium, resulting in a decrease in medical assistants and less staff in hospitals. Whatever the causes, this international inflow makes any forecasting of the supply of national health professionals quite difficult and plausibly irrelevant.Another contributing factor has been the limitation of medical trainees  who will stay in Belgium, turnover rates or activity profiles, are poorly documented. So far, this recent sharp increase in immigrant physicians has not been taken into account in Belgian projections, although it represents more than a 50% excess over the scheduled national numbers and modifies deeply the parameters of the planning.There is no unambiguous "right" number and mix of health professionals, as fundamental societal and institutional dimensions are affecting health workforce production directly and indirectly ,54. DuboHealth provider requirements are determined by broader societal decisions about the level of commitment of resources to health care, organization of the delivery and funding of health care programmes, and level and mix of health care services. We have already underlined the importance of appropriate modeling methods fed with good-quality data. To replace the medical workforce planning in a system-wise approach is also crucial, as other policy initiatives will shape the medical workforce and practice, such as organizational or financial reforms of the health system .to maintain practice volumes comparable to today, pediatricians of the future may need to provide expanded services to the children currently under their care, expand their patient population to include young adults, and/or compete for a greater share of children currently cared for by non pediatricians".However, forecasting the medical workforce is much too often an isolated exercise. Most of the published studies on workforce projections in specific specialties were produced by members of the specialty under consideration. Such a narrow focus may cast some doubt on the validity of the approach and interpretations. Probably the most striking example is given in Shipman et al. . As the Such a comprehensive approach is not an easy task for planners. It requires a system-level perspective, integrating medical workforce planning with workforce planning for other health professionals, and with workforce development, service planning and financial planning for the health care system. This broader approach has also been advocated by other authors ,42,53.There is no accepted approach to forecasting physician requirements. Each of the approaches relies on a number of assumptions and limitations that should be acknowledged because of their large influence on the model outputs.The value of projections lies not in their ability to get the numbers exactly right but in their utility in identifying the current and emerging trends to which policy-makers need to respond. The requirements for health providers are endogenously determined through the political or social choices that underlie the health care system. Only where the social and political choices about the access to and delivery of care are explicit, can scientific methods be used systematically to derive requirements for health care providers in a particular population . HoweverAMWAC: Australian Medical Workforce Advisory Committee; FTE: full-time equivalent; GDP: gross domestic product; GP: general practitioner; HMO: health maintenance organization; HRH: human resources for health; SID: supplier-induced demandThe authors declare that they have no competing interests.DR reviewed the literature and drafted the paper. CL and SS critically reviewed the data and contributed substantially to the writing. All authors read and approved the final manuscript.


Considering the costs of multiple sclerosis (MS), it is crucial that the health-related services supplied are in accordance with needs as they are perceived by people with MS (PwMS). Satisfaction with care is related to quality of care and can provide health care providers with the means for improvement. The aim was to explore the perceived needs and satisfaction with care amongst PwMS over a two-year period, also taking sex and disease severity into consideration.The sample consisted of 219 outpatients at a MS specialist clinic. Data on perceived needs and satisfaction with care were collected every six months using a questionnaire which included various dimensions of care. The data was analysed for the whole sample and on an individual level, as well as in subgroups with regard to sex and disease severity.There were no statistically significant variations in the proportion of PwMS with perceived needs concerning different health-related services during the study period. However, individual variations were found with regard to both perceived needs and satisfaction with care. Few PwMS perceived a continuous need for a specific service. However, the majority perceived a need for rehabilitation, assistive devices, transportation service for the disabled, psychosocial support/counselling and information on social insurance/vocational rehabilitation at least sometimes. Severe MS was associated with a greater perceived need for almost all the services studied and women experienced a need for psychosocial support/counselling to a greater extent than men. In relation to the different categories of health care staff, PwMS were most satisfied with nurses with regard to all dimensions of care. They were least satisfied with the availability of psychosocial support/counselling; and information about social insurance/vocational rehabilitation.Despite the large proportion of individuals with mild disease severity in our sample, a considerable number of needs were identified of which many, on an individual level, varied over time. Key services demanded by PwMS were identified. Also the level of satisfaction with care varied and areas with a potential for improvement were identified such as the availability of rehabilitation services including an increase in the supply of psychosocial support and counselling. Multiple sclerosis (MS) is a chronic, neurological disease, the onset of which usually occurs between the ages of 20–40 years. The disease results in a wide range of symptoms, but does not alter the life span substantially . ConsequA recent study revealed that the great majority of PwMS in Stockholm make parallel use of hospital specialist care and primary care and that neurology care contacts constitute only 20% of all outpatient care . ConsideSatisfaction with care is a complicated, multidimensional concept that includes both affective and cognitive components . It is rThe International Classification of Functioning, Disability and Health (ICF) aims to provide a scientific basis for the study of health conditions and is also useful for the study of health care systems, in terms of outcomes and the cost-effectiveness of services, the assessment of needs and consumer satisfaction . The ICFThe aim of the present study was to explore perceived needs in relation to different health-related services, also taking sex and disease severity into consideration, and to explore PwMS's satisfaction with care over a two-year period.The study was carried out in the context of a prospective, observational study of functioning and perceived health amongst PwMS . Those eThe neurologist responsible determined disease course and assessed disease severity by means of the Expanded Disability Status Scale (EDSS) . EDSS-scData regarding perceived needs and satisfaction with care was collected using a questionnaire that has previously been used in studies of people with stroke , GuillaiThe study was approved by the ethical committee of Karolinska Institutet in Stockholm, Sweden.Descriptive statistics were used to present perceived need and satisfaction with care. Satisfaction with care was dichotomised into satisfied  or not satisfied . The Cohran Q test was performed for analyses of the changes in the proportion of PwMS with perceived needs during the study period with regard to different health-related services for the whole sample and for the subgroups, with regard to sex and disease severity. Chi square statistics were used for the analyses of differences in sex and disease severity between PwMS with perceived needs for different health-related services and those with no perceived need, and between PwMS who were satisfied with availability and those who were not. A p value ≤ 0.05 was considered statistically significant. The statistical analyses were performed in Statistica 7.Of 255 eligible PwMS, 36 declined and 219 were included in the study. During the study period seven PwMS died and 12 withdrew, leaving 200 who were followed for two years. Demographic and clinical characteristics on inclusion are summarised in Table Perceived need and PwMS's satisfaction with care on inclusion are presented in Table Despite the fact that most of the PwMS in the sample had mild EDSS, a high proportion perceived a need for physiotherapy (61%); occupational therapy (41%); and rehabilitation periods  (42%). However, more than one third of those who perceived a need were not satisfied with these areas of rehabilitation. The costs of care were considered burdensome by 75%. The vast majority wanted to participate in planning their care but only 63% of those who perceived a need to participate were satisfied. Regarding continuity and efficacy/outcomes of care, the majority were satisfied.During the study period there were no statistically significant variations over time in the proportion of PwMS with perceived needs concerning different health-related services; either in the whole sample or with regard to sex. In those with severe EDSS, a statistically significant variation was found concerning occupational therapy (p = 0.007). Table Women experienced a need for psychosocial support/counselling to a greater extent than men (p = 0.04). Between PwMS with mild and severe EDSS there were statistically significant differences with more people among those with severe EDSS perceiving needs. PwMS with moderate EDSS did not differ in perceived needs from those with mild or those with severe EDSS. A severe state of MS was associated with a greater perceived need and a mild state of MS was associated with a smaller perceived need for the availability of almost all the health-related services studied: physiotherapy (p = 0.004), occupational therapy (p = 0.01), rehabilitation periods (p = 0.008), assistive devices (p = 0.002), home adaptation (p = 0.04), transportation service for the disabled (p = 0.002) and home help/personal assistants (p < 0.001). However, there were no associations between disease severity and perceived need for workplace adaptation, psychosocial support/counselling and information on social insurance/vocational rehabilitation; nor was there any association between satisfaction with care and sex or disease severity.This study explored the perceived needs and satisfaction with care over a period of two years at a MS specialist outpatient clinic, taking sex and disease severity into consideration. Individual variations were found with regard both to perceived needs and satisfaction with care. However, the majority of the participants perceived a need for rehabilitation, assistive devices, transportation service for the disabled, psychosocial support/counselling and information on social insurance/vocational rehabilitation at all times or sometimes. A severe state of MS was associated with a greater perceived need for almost all the health-related services studied and women experienced a need for psychosocial support/counselling to a greater extent than men.The majority preferred an early diagnosis, a result which tallies with previous studies ,24. HoweRegarding contacts with the different health care providers, the PwMS were least satisfied with the psychologists with regard to such matters as information about the disease, art of care  and accessibility. One possible explanation can be that contacts with psychologists will most likely include an assessment of cognitive functioning, which, for the individual, may be associated with feeling ill-at-ease .Despite the fact that the PwMS met a neurologist every six months, as many as 35% of them were not satisfied with the physicians' accessibility; this is a result in line with a previous study . This fiAs far as the professional health care staff is concerned, the PwMS were most satisfied with nurses with regard to all the dimensions studied. A plausible reason for this result may be that the majority of these PwMS received immunomodulatory treatment, entailing repeated contacts with nurses for instructions and assistance with the injections. This frequent contact may lead to the nurses becoming care coordinators.Regardless of disease severity, the majority of those who indicated a need for information regarding social insurance/vocational rehabilitation had not received this service to the extent that they perceived necessary. In a country like Sweden, with a public social insurance system, an improved information service regarding these issues as well as access to vocational rehabilitation services that respond to individual needs  might beOnly half of those who perceived a need for psychosocial support/counselling reported that they had received this service to the extent that they perceived necessary; this is in line with results from a previous study  and possThe cost of rehabilitation is relatively small. Nevertheless, a recent study of the costs of MS in Sweden revealed that the expenditure on rehabilitation was reduced from 8.6% in 1998 to 7.2% in 2005 . ConsideThe fact that the majority were burdened by the costs of care is probably primarily explained by the high proportion of individuals in our sample who were receiving immunomodulatory treatment. In addition, the costs of care are probably especially burdensome for the 42% in the sample who were not working.The results derived from previous studies which reveal that PwMS exhibit high participation preferences ,30 were During the study period there were no statistically significant variations in the proportion of PwMS with perceived needs with regard to various health-related services. However, over time, individual variations in perceived needs and in satisfaction with care were found. The reasons for these variations are not clear but might indicate that some needs are met or disappear while others vary as a consequence of the varying MS disease. All the same, variations in needs and satisfaction with care coincide with previous results concerning significant variations in functioning and disability in PwMS . The resIn accordance with the NICE guidelines , a regulPwMS who perceived a need at all times or sometimes, were most satisfied with the availability of assistive devices; workplace adaptation; home adaptation; and transportation service for the disabled, which indicates that the availability of these services may be considered as reasonably satisfactory within the Swedish health care system. However, these PwMS were least satisfied with the availability of psychosocial support/counselling; and information on social insurance/vocational rehabilitation which suggests a need for an increase in the supply of these services.As can be expected, a severe state of MS was associated with a greater perceived need for almost all the health-related services studied; this result is in line with previous studies ,14. HoweThe present study's major strengths were the longitudinal design and the low dropout rate in contrast to many previous studies in which postal questionnaires have been used ,11,13,14The results are probably representative for a MS specialist outpatient clinic but there may be differences between countries or regions in Sweden due to different structures in the health care systems. The level of satisfaction with care in the present study may be influenced by higher demands made by PwMS attending a specialist clinic. On the other hand, at such a clinic the potential for meeting the needs of the PwMS ought to be most favourable and opportunities for improvements e.g., enhanced availability of rehabilitation services, are excellent.Despite the large proportions of individuals in our sample with mild disease severity, a considerable number of needs were identified of which many varied on an individual level over time. Rehabilitation, assistive devices, transportation service for the disabled, psychosocial support/counselling and information on social insurance/vocational rehabilitation, seem to be key services demanded by PwMS. Also the level of satisfaction with care varied and areas with a potential for improvement were identified e.g., availability of rehabilitation services including an increase in the supply of psychosocial support/counselling as well as information on social insurance/vocational rehabilitation. Future research is needed to explore how the different needs of PwMS best should be met in terms of outcome and cost-effectiveness and, within the different dimensions, what levels of satisfaction with care can be considered as acceptable.The authors declare that they have no competing interests.CY participated in the design and coordination of the study, performed the statistical analysis and drafted the manuscript. SJ participated in the design and coordination of the study, and helped to draft the manuscript. KG participated in the design of the study and helped to draft the manuscript. LWH participated in the design of the study and assisted in drafting the manuscript. LvK participated in the design and coordination of the study and helped to draft the manuscript. All authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:


Nausea and vomiting is a problem for children after neurosurgery and those requiring posterior fossa procedures appear to have a high incidence. This clinical observation has not been quantified nor have risk factors unique to this group of children been elucidated.A six year retrospective chart audit at two Canadian children's hospitals was conducted. The incidence of nausea and vomiting was extracted. Hierarchical multivariable logistic regression was used to quantify risk and protective factors at 120 hours after surgery and early vs. late vomiting.The incidence of vomiting over a ten day postoperative period was 76.7%. Documented vomiting ranged from single events to greater than 20 over the same period. In the final multivariable model: adolescents (age 12 to <17) were less likely to vomit by 120 hours after surgery than other age groups; those who received desflurane, when compared to all other volatile anesthetics, were more likely to vomit, yet the use of ondansetron with desflurane decre kelihood. Children who had intraoperative ondansetron were more likely to vomit in the final multivariable model . Children who started vomiting in the first 24 hours were more likely to be school age (groups 4 to <7 and 7 to <12) and receive desflurane. Nausea was not well documented and was therefore not analyzed.The incidence of vomiting in children after posterior fossa surgery is sufficient to consider all children requiring these procedures to be at high risk for POV. Nausea requires better assessment and documentation. The successful management of nausea and vomiting is an important component in the care of children after surgery. Postoperative nausea and vomiting (PONV) may cause discomfort and distress, put pressure on surgical incisions, cause dehydration and electrolyte imbalance, delay recovery, and prolong hospitalization ,2. ChildTramer  describe3 receptor antagonist, have estimates of 24 hour POV in children after craniotomy that range from 24% [POV and/or PONV after craniotomy in children have not been well described in the literature. Two small randomized controlled trials of ondansetron, a 5-HTfrom 24%  to 66% [from 24% . Althougfrom 24%  could noChildren who appear to be at high risk for nausea and vomiting are those who require posterior fossa craniotomy. Posterior fossa surgery takes place below the tentorium cerebelli in the posterior cranial fossa. The posterior cranial fossa houses structures that include: the cerebellum; brainstem; and cranial nerves III-XII. Although the reticulospinal tracts, diencephalon, limbic system, and discrete areas of the cerebral hemispheres may all be involved in nausea, retching, and vomiting, the coordination of the autonomic changes associated with retching and vomiting occurs at the level of the medulla oblongata in the posterior fossa -14. ThusChildren who require craniotomy form a heterogeneous group. By specifically studying children after posterior fossa surgery, the research questions can be focused on the unique risk and protective factors for PONV for this group of children, while limiting the heterogeneity in the sample. This approach has shown success in determining risk and protective factors specific to the location of the neurosurgery in adult studies -21. ThusThe hospital charts of children who required posterior fossa surgery at two Canadian children's hospital sites, the Stollery Children's Hospital in Edmonton and the Hospital for Sick Children in Toronto, were reviewed for the study. A retrospective study design was chosen as an efficient and cost effective way to describe nausea and vomiting in this group of children. Specifically, for the acute postoperative period, we sought to determine:1) The cumulative incidence of nausea and vomiting by: hours 4, 8, and 24; and during subsequent 24 hour periods.2) The frequency distribution of number of days that nausea and vomiting were experienced.3) The frequency distribution of number of vomiting events.4) The significant risk and protective factors for nausea and vomiting.5) The co-morbidities that children with nausea and vomiting experience.Following institutional ethical review and administrative approval at each centre, all patients under age seventeen who had posterior fossa surgery between March 1, 2001 and March 1, 2007 were identified for chart retrieval through two separate paediatric neurosurgeons' databases  and a central paediatric neurosurgery database . The upper limit for age was determined by the age of qualification for admission to both children's hospitals. Fourth ventricular shunt procedures, operations without dural openings (outside the brain), surgery for traumatic brain injury, and children requiring prolonged intubation (greater than 48 hours) were excluded. If more than one posterior fossa procedure was required for a child over the study period, the earliest one was included in the study. Prospectively, we estimated data from two sites to involve approximately 300 children. This would allow for an estimation of incidence within a 6% margin of error . It woulA case report form was developed specifically for the study in collaboration with a paediatric educator in surgery, a neurosurgeon, and clinical nurse specialists/advanced nurse practitioners in children's neurosurgery. Data were collected by review of the child's in-patient chart. The data collection period extended over the course of a child's neurosurgical postoperative hospital stay, up to ten days. Thus, data collection ended when the child went home, was transferred from neurosurgical care to rehabilitation care , was transferred from neurosurgery care to oncology care for further treatments, or at 240 hours after the recorded time that the anaesthetic was finished. The first ten postoperative days were chosen by the study team to ensure that an adequate length of time was captured for the exploratory analysis. The final outcomes for analysis of risk and protective factors were determined based on these exploratory results.One nurse with paediatric neurosurgical experience at each site collected data. To ensure reliability, the two data collectors trained on ten charts. Revisions to the data collection form were then made as necessary. For example, the child's activity and diet at each time period were initially part of the case report form. Due to gaps in charting, these data could not be collected reliably. Once the case report was finalized, each person then reviewed the same five randomly selected charts to establish inter-rater reliability: 100% inter-rater reliability was achieved for the main study outcomes, independent variables and adverse events. Weekly contact was maintained between the two sites to discuss issues that arose during data collection.PONV covers one or more of three symptoms: nausea; retching; and vomiting . Nausea Retching is the first phase of vomiting  and is cData on potential risk factors were collected from the admission records, physician notes, anaesthesia records, operative reports, and medication flow sheets. This data included age of child, gender, presenting symptoms, type of surgery, length of surgery, use of intraoperative dexamethasone and/or ondansetron (administration at any time after induction), and type of anaesthetic. For analysis, age was examined in quartiles rounded to the year: 0 to <4; 4 to <7; 7 to <12; and 12 to <17. A number of variables were dichotomized for analysis. The use of desflurane has been shown to be a risk factor in adults requiring retromastoid craniectomy, compared to other volatile anaesthetics . We therFinally, Potential co-morbidities, including development of a pseudomeningocele, wound failure or cerebral spinal fluid leak through the incision, and wound infection, were noted by examining the nursing notes, physician notes, discharge summary, and/or reasons for readmission to the neurosurgical service. Reports of postoperative imaging studies were also reviewed for possible documentation of a pseudomeningocele.Data analysis was conducted using SPSS Version 15.0 software. Demographic and study variables were summarized using descriptive statistics that were appropriate to their level of measurement. Cumulative incidence  was used to calculate outcomes at: 4, 8, and 24 hours, and for subsequent 24 hour periods until the end of the study period. The number of days that an outcome was experienced was calculated by subtracting the time of the first recorded event from the last recorded event, and was summarized using a frequency distribution. A frequency distribution was also used for counts of recorded events.Univariate logistic regression was first conducted to examine the relationships between each variable and the outcomes. Additionally, the clinical plausibility of an interaction effect of ondansetron and dexamethasone was tested using two steps. In the first step, the adjusted odds ratios of ondansetron and dexamethasone were estimated using multivariable logistic regression. Then, the interaction term of ondansetron and dexamethasone was entered in the second step.a-priori determined, hierarchical fashion based on sequential events . The clinical plausibility of dexamethasone and ondansetron administered together vs. either drug administered alone were again tested using an interaction term in the larger multivariable models at this time. Only statistically significant interactions were included in the final model. Multicollinearity, associations among the independent variables in the model, was reviewed by looking for correlations above 0.8 between any two variables.To finish the analysis, cross tabulations were used to examine the relationship between the final outcomes and other adverse events. The phi statistic (ϕ) for nominal by nominal variables was used to summarize these relationships. This statistic was also used to examine relationships between categorical confounding variables, whereas a Pearson's correlation (r) was used for continuous variables.Table The cumulative incidence of PON, POV and PONV over the first ten days is presented in Table Based on the initial exploratory data analysis, we decided to examine the risk and/or protective factors for two outcomes: POV in the first 120 hours (the acute postoperative period), and early (an event recorded by 24 hours or less) compared to late POV (the first event occurring after 24 hours up to 120 hours). The decision to make the cut-off for the acute postoperative period 120 hours, despite data collection that went up to 240 hours, was to control for confounding factors such as early discharge, the requirement for sedation for procedures or tests, or the need for further surgery that were emerging in the data after 120 hours. After data collection, it was clear that some potential risk factors could not be reliably collected due to lack of documentation or inconsistent documentation. These included: a history of PONV in the child or family member; a history or motion sickness; and pain rating.The initial univariate logistic regressions Table  indicateIn the first multivariable analysis Table , controlThere were a number of variables which appeared to confound the effects of previously entered variables in the model. When the factor of whether or not a child presented with vomiting was added (Model 3), the odds ratio for POV by 120 hours for Chiari I surgery increased. A greater proportion of children with brain tumours presented with vomiting than those with Chiari I malformations or other procedures  = .0.65, p < .001); thus, controlling for whether or not the child presented with vomiting proportionally decreased the odds of vomiting for children with brain tumours compared to those with Chiari I malformations. The combined surgery category of "other" was too small (n = 15) to determine if there was similar effect. The odds ratio for hospital site changed to being significantly greater for the Hospital for Sick Children after the intraoperative variables were entered (Model 4). Desflurane and intraoperative ondansetron were used proportionately more at the Stollery Children's Hospital than at the Hospital for Sick Children . There were no differences between the sites for the use of dexamethasone  or length of surgery (r = -0.02 p = .74). Thus, controlling for the combination of intraoperative risk factors, notably any use of desflurane and administration of intraoperative ondansetron, resulted in a proportionately higher reduction in the risk of vomiting by 120 hours at the Stollery Children's Hospital compared to the Hospital for Sick Children. These findings highlight the challenges that can be found in types of procedures and/or sites with different proportions of children exposed to potential risk and protective factors.Finally, the addition of the interaction term of any use of desflurane and the administration of ondansetron (Model 5) also showed a change in the odds of POV by 120 hours for children requiring Chiari I surgery to a statistically significant result. However, there were no differences in the proportion of children in the three surgery categories who received both ondansetron and desflurane . The interaction of intraoperative ondansetron and dexamethasone was not statistically significant when tested with this multivariable model.The second multivariable modelling procedure Table  was usedAssessment for multicollinearity Table , showed With the exception of infection, adverse events were frequently reported in the sample. Because posterior fossa syndrome is most commonly associated with brain tumours, the relationship between posterior fossa syndrome and POV by 120 hours was examined for brain tumours only. As shown in Table The results of this study support our clinical experience that POV is a common adverse outcome for children after posterior fossa surgery. Overall, POV is common enough to regard all children who require posterior fossa surgery as being at high risk for the development of POV. When POV occurred, counts of vomiting events formed a positively skewed distribution in this sample. These results are similar to those shown by the data collected by Rowley and Brown  in theirIn this study, some variables were related to POV in children after posterior fossa surgery. These results may lead to the development of predictive tools or the identification of areas for stratification for future research. They will also help to identify challenges for future research, especially multi-site studies. That one hospital site showed greater odds of POV by 120 hours, once intraoperative variables were entered, highlights the difficulty in comparing between sites that may have varying intraoperative practices. Type of surgery was significant, with children requiring surgery for Chiari I Malformation more likely to have POV by 120 hours than children requiring brain tumour craniotomies and "other" procedures. Within the category of brain tumour surgery, there may be children who are at much higher risk for POV, balanced out by those at lower risk. A secondary analysis of these data for children with posterior fossa brain tumours, in particular, would be useful.That the oldest age quartile (12 to <17 years) emerged as a protective factor for POV by 120 hours, once intraoperative variables were controlled for, is consistent with research in children following other types of surgery , but hasWhile not desflurane was commonly used in this sample, any use of desflurane was identified as a risk factor for early vomiting compared to the use of other volatile anaesthetics. This finding must be taken in the context of a small sample size and very wide confidence intervals when all other variables in the model were controlled for. The Stollery Children's Hospital site had a greater proportion of exposed children than the Hospital for Sick Children and the influence of individual clinicians was not accounted for. As previously discussed, the use of desflurane has been identified as a significant risk factor when compared to other volatile anaesthetics in a multivariable analysis of risk factors for PONV for adults requiring microvascular decompression of cranial nerves ; this is3 receptor antagonists, in preventing POV in this group of children might then include stratification for characteristics of the volatile anaesthetic used.Children who received intraoperative ondansetron were more likely to vomit by 120 hours those who did not. This finding may be due to use of clinical judgment in administering ondansetron, a drug which has not been shown to have efficacy in preventing vomiting in children after craniotomy ,11. ThusThe intraoperative use of dexamethasone was not shown to be a protective factor for POV by 120 hours. Like ondansetron, its use may have been targeted to children clinically perceived to be at high risk for POV, and so a protective effect might not emerge in a retrospective study. The lack of significance of the use of intraoperative dexamethasone and the lack of an interaction effect between dexamethasone and ondansetron may also be reflective of this limitation. Additionally, we did not control for the use of preoperative dexamethasone because preoperative dexamethasone was given to most of the children with brain tumours, and thus collinearity with the type of surgery would be a problem. However, Subramaniam and colleagues  did lookFinally, associations between POV by 120 hours and a number of negative consequences for recovery – the development of a pseudomeningocele, infection, wound failure/cerebral spinal fluid leak, and posterior fossa syndrome (in children with brain tumours) – could not be identified in the data. These outcomes may be better studied prospectively with consideration of the severity of POV. A prospective study would also aid in identifying a causal pathway in the relationship between negative outcomes and POV.The primary limitation of this study is its retrospective nature as it limits the researchers' control over the data that can be collected. For the outcomes of nausea, vomiting, and retching, the quality of the charting by health care professionals was paramount. The exact count of vomiting episodes was likely underestimated, as severe events were often identified as "+ + + vomiting," but the cumulative incidence of vomiting at the specified time period should be accurate. Additionally, retching may have only been charted if it occurred without vomiting, for example in the post-anaesthesia recovery room or paediatric intensive care. Once the child was cared for in the general nursing care unit, it may have been unobserved by the health care team and thus not documented. Subjective measures of nausea, expressed by the child, were rarely charted. In adults after craniotomy, risk factors for nausea may be different than those for vomiting . As we wThere were also challenges in conducting the study at two sites. Differences in the way that postoperative neurosurgical care was provided and the timing of transfer of the child either home, for rehabilitation, or for oncology treatment, varied between institutions. Different documentation styles and charting practices may have also affected data collection. Defining what constituted the acute postoperative period was also difficult and the outcomes for analysis of risk and protective factors were decided once the data were collected and descriptive statistics completed.Sample size issues also became apparent in the final stages of the multivariable analysis, as shown by the wide confidence intervals for some variables. Initially we had estimated a sample size of approximately 300. There were more children with exclusion criteria than expected, which decreased the final sample. The high incidence of vomiting, even when the outcome was limited to POV by 120 hours, resulted in five children without vomiting per variable for the final multivariable model. Therefore, the results of the multivariable analysis should be interpreted with caution and require further validation.Due to the retrospective nature of the data collection, the multivariable models developed in this study can be used to identify risk and protective factors for POV in children after posterior fossa surgery in general. The models were not developed for prognosis or risk scoring at the individual level. The study does not show the effect of treatments, only their contribution as possible risk or protective factors. The type of data that can be extracted is limited to what is charted in a retrospective study. For example, whether or not the administration of a postoperative anti-emetic was prophylactic or therapeutic could not be reliably determined and therefore was not used in the analysis. A further limitation of the study is that the outcomes examined for the risk and protective factors were one or more events of POV by 120 hours and early vs. late POV. Severity of POV, an important outcome that is often clinically observed in children after posterior fossa surgery, and may be inferred from the frequency of events and length of time that POV was experienced, was not quantified for the analysis of risk and protective factors.3 receptor antagonists and dexamethasone. Of particular note, is the current absence of evidence that any class of drug, including the combination of dexamethasone and ondansetron, is effective for preventing or treating POV in children after craniotomy. Overall, this is a unique but understudied population of children who are at risk for POV.The findings of risk and protective factors in this study support the suggestion that current prognostic models and risk scoring systems for POV should not be used in children after posterior fossa craniotomy  as they There have also not been any studies of particular anaesthetic protocols, such as TIVA with propofol, in children requiring posterior fossa surgery. Knowledge and treatment guidelines are currently limited to what is known in other patient populations. Translating current knowledge and treatment guidelines to children requiring posterior fossa surgery is challenging. For example, even the results of studies of TIVA in adults after craniotomy remain inconclusive . FinallyThe authors declare that they have no competing interests.SN Conceptualized the study, collected data at the Stollery Children's Hospital Site, entered and analyzed the data, and drafted the manuscript, revised and prepared the manuscript for publication. CNC Helped with the study design and methodology, critically revised the manuscript and approved the final version for publication. DS Developed the statistical plan for the manuscript, directed the statistical analysis and interpretation of the data, and critically revised the statistical portion of the manuscript. BD Helped with the conceptualization of the study, collected data at the Hospital for Sick Children, critically revised the manuscript and reviewed the final version for publication. HY Helped conceptualize the study, assisted in the development of the data collection tool, and was study coordinator at the Hospital for Sick Children. JD Helped with conceptualization of the study, critically revised the manuscript, and approved the final version for publication. All authors read and approved the final version of the manuscript.SM, BD, and HY are nurses who work in children's neurosurgery, where their clinical experience prompted them to identify the extent of postoperative nausea and vomiting on their units, not only to gain knowledge of the problem but to then identify ways to help these children and their families.The pre-publication history for this paper can be accessed here: