The University of Michigan Dioxin Exposure Study (UMDES) was undertaken in response to concerns that the discharge of dioxin-like compounds from the Dow Chemical Company facilities in Midland, Michigan, resulted in contamination of soils in the Tittabawassee River floodplain and areas of the city of Midland, leading to an increase in residents’ body burdens of polychlorinated dibenzodioxins and polychlorinated dibenzofurans.The UMDES is a hypothesis-driven study designed to answer important questions about human exposure to dioxins in the environment of Midland, where the Dow Chemical Company has operated for > 100 years, and in neighboring Saginaw, Michigan. In addition, the UMDES includes a referent population from an area of Michigan in which there are no unusual sources of dioxin exposure and from which inferences regarding the general Michigan population can be derived. A central goal of the study is to determine which factors explain variation in serum dioxin levels and to quantify how much variation each factor explains.In this article we describe the study design and methods for a large population-based study of dioxin contamination and its relationship to blood dioxin levels. The study collected questionnaire, blood, dust, and soil samples on 731 people. This study provides a foundation for understanding the exposure pathways by which dioxins in soils, sediments, fish and game, and homegrown produce lead to increased body burdens of these compounds. In addition, this facility was a major producer of 2,4-dichlorophenoxy-acetic acid and 2,4,5-trichlorophenoxyacetic acid during the Vietnam conflict era and has produced a number of products derived from chlorophenols. The contaminant distribution of the Tittabawassee River is currently undergoing extensive mapping, and heavily contaminated areas are being remediated.The University of Michigan Dioxin Exposure Study (UMDES) was undertaken in response to concerns that the discharge of dioxin-like compounds from the Dow Chemical Company facilities in Midland, Michigan, resulted in contaminated soils in the Tittabawassee River floodplain and areas of the city of Midland, leading to an increase in residents’ body burdens of poly-chlorinated dibenzodioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs). The Dow Chemical Company has operated in Midland since 1897 and is believed to have caused two major patterns of environmental contamination: The goals of the study focus on assessing the human body burdens of dioxins  aIn this article, we describe the hypotheses to be tested; the design of the multistage population sampling; the survey instruments used; methods for collection of soil and household dust samples; the analytical methods for measuring dioxins in serum, household dust, and soil; the survey methods used to calculate sample weights; and the methods used for imputing item missing values.The hypothesis to be tested is whether contamination of the environment by dioxins from the Dow Chemical Company’s operations in Midland, Michigan, is associated with increased body burdens of dioxins among some residents of the surrounding area of Midland, Saginaw, and southwestern Bay counties. For the purposes of this study, we use the term “contamination” to mean the presence of dioxins above background levels in environmental media, where “background” is defined as the concentration that would occur in an area without known point sources of that substance . The stuA number of studies of PCDDs, PCDFs, and PCBs in human serum lipids  show thaWe began developing the study protocol in the winter of 2004 and completed it in the summer of 2004. Field interviews, blood collection, soil sampling, and household dust collection were conducted in the summer and fall of 2004 and the spring and summer of 2005. All fieldwork ceased during the winter of 2005, when soil samples could not be collected because of frozen ground. Laboratory analyses of blood, soil, and household dust began as samples were collected and were completed in the spring of 2006. Statistical analyses of the data began in fall 2005.The sample design was a stratified, multistage area probability sample of households and persons. We defined the population as persons residing in Midland and Saginaw counties, Williams Township in Bay County, and Jackson and Calhoun counties, all of whom were > 18 years of age, had lived in their current residence continuously for at least 5 years, and currently lived in a residence outside the floodplains of the Shiawassee and Saginaw Rivers in Saginaw County. The sample used a two-stage area probability selection of housing units in the study area, and a third stage of selection of an eligible person within each sample housing unit. The first stage of selection employed stratified cluster sampling methods in which a sample was drawn from a list of all U.S. Census blocks in the study counties.a) blocks in Midland and Saginaw and parts of Bay counties that contained any land area in the Federal Emergency Management Administration–defined 100-year floodplain of the Tittabawassee River below the Dow Chemical Company facility in Midland, and above the point where the Tittabawassee and Shiawassee Rivers join and have a mixed floodplain; b) blocks in the area of deposition from emissions stacks at the Dow Chemical Company in Midland, as defined by environmental modeling of the plume of the historical emission data; c) blocks outside of the Tittabawassee floodplain (item a above) or the plume (item b above) and outside the flood-plain of the Shiawassee and Saginaw rivers; and d) blocks in Jackson and Calhoun counties (control area for the study).We divided the list into four groups : a) blocWe defined the aerosol plume by a geostatistical simulation-based method that combined the process-based modeling of atmospheric deposition from an incinerator with the probabilistic modeling of residual variability of field samples. We used the approach to delineate areas with high levels of dioxin around the Dow plant, accounting for 53 field data points and the output of the U.S. EPA Industrial Source Complex (ISC3) dispersion model. We simulated 100 realizations of soil toxic equivalent (TEQ) values on a grid with a 50-m spacing. We used these realizations to identify census blocks  that werWe recruited and hired interviewers from Midland and Saginaw counties. They were trained in general interviewing techniques, the specific study protocol and questionnaire, and refusal aversion techniques. Study staff monitored daily data collection progress, which achieved high response rates. Sample households were visited by interviewers multiple times, if necessary, to obtain cooperation. Interviewers also offered a financial incentive totaling $100 if the person participated in the interview and the blood, soil, and household dust sampling.Each household was screened to determine whether eligible persons lived in the household. If one or more eligible persons lived in the household, we chose one at random to interview. Each respondent eligible for the blood draw was asked to provide a blood sample collected through an in-home visit from a phlebotomist from a local health care facility. If the respondent owned the housing unit, she/he was asked to permit household dust to be collected by vacuuming. We asked respondents who owned the property to permit soil samples to be gathered from around the housing unit (excluding apartments and condominiums).In fall 2004, the first replicate in Midland and Saginaw counties was available for study. “Replicate” refers to random samples chosen from a target population, in which a first sample is taken and then a replicate sample is taken from the same target population. Replicate sampling is valuable in estimating the variances of parameter estimates. In spring 2005, the second replicate in Midland and Saginaw counties and the entire sample in Jackson and Calhoun (the control) counties were available for study.Between the fall 2004 and spring 2005 data collection, we converted the survey interview from paper-and-pencil format to computer-assisted format on laptop computers. The paper-and-pencil and computer-assisted interviews both asked the same questions, were subjected to the same quality controls, and were of comparable quality. The questionnaire response rates varied between 82% and 84% in the different study populations . HousehoA commonly used indicator of survey quality is the response rate. Cooperation rates were substantially higher than anticipated: 84% in the floodplain and 82% in the nonfloodplain and control areas. The overall interview response rate (74%) is lower than the cooperation rate because the response rate incorporates an estimate of the proportion of eligible persons in households that were not successfully screened. ith person, yi, and nonresponse adjusted weight, wi, we computed the weighted mean TEQ value for the population asSurveys often make adjustments to compensate for missing values, such as occurred in the UMDES. These models produced predicted probabilities of cooperation. The inverse of these predicted probabilities for respondents at each stage were then used as nonresponse adjustment factors and multiplied times the unequal probability of selection weight for each person. We “trimmed” extremely large values  because the weighted value could be overly influential in an estimate. We then used these weights in all analyses to compute weighted estimates that would be sound estimates for the population from which the sample was drawn . For exaWe used the same “global” weight for all analyses.We further adjusted the data to account for missing values for items or missing values for a single variable for an individual who otherwise provided data. Many analysts “ignore” the missing values in a variable by using “case-wise deletion” of missing data features in statistical software. Ignoring the missing values effectively imputes or assigns the mean of the cases without missing values to the value for each case for which the value is missing. In the careful population inference methods being used for the UMDES, we imputed the item missing values in the survey questionnaire, the household dust, and the soil samples. We used a sequential regression imputation procedure  to replaa) contact, given status as an occupied housing unit; b) screening, given initial contact; c) interview, given successful screening and eligibility for the interview; d) giving blood or not, conditional on being eligible to give blood; e) giving dust, conditional on being eligible to give dust; f) giving soil, conditional on being eligible to give soil; and g) giving blood, dust, and soil, conditional on being eligible to give all samples.For a subset of households that were not contacted or for which eligibility was not determined, or for which the selected respondent did not complete the questionnaire, we asked them again to participate in the UMDES. A shortened questionnaire, which collected information on key study variables, was administered to subjects who agreed to participate in this non-response follow-up study. We did not collect blood, soil, and household dust samples. These data permitted comparisons of nonrespondents and respondents on key study variables from the questionnaire to assess the degree of non-response bias. Nonresponse follow-up activities took place during January and February 2005 and October and November 2005, immediately after the end of main data collection. We constructed nonresponse adjustment weights using response propensity models, which use a logistic regression predicting the likelihood of being a respondent, conditional on being eligible for response. Models were run for each of the following stages of nonresponse: We used the inverse of predicted probabilities from each of these models as a non-response adjustment weight. We trimmed extremely small predicted probabilities from each of these models to minimize the influence of any single case on the overall estimation, while maintaining as much of the original predictions as possible.Survey questionnaires were developed through a process of writing or adopting questions from other surveys, review by project stakeholders and the scientific advisory board (SAB), and pretesting in a small sample of residents in Midland and Saginaw counties. All eligible adults gave written informed consent and completed a 1-hr standardized interview administered by the Survey Research Center at the University of Michigan.An important component of the questionnaire was an event history calendar (EHC), which collects significant time-varying information using cues from the respondent’s lifetime to assist in recall. The interviewer recorded major life events, such as marriage or childbirth, on the EHC, along with major national and local current events to help respondents anchor when events occurred. The questionnaire consisted of 10 sections, each of which contained lifetime recall questions. The respondent was asked to recall possible dioxin exposure pathways over their entire lifetime in 1-year intervals. Much of the interview was devoted to questions about consumption of fish, game, poultry, dairy, and produce and whether it came from contaminated areas; activities such as hiking, camping, picnicking, and water sports in the contaminated areas; occupational history, particularly work at Dow and in other settings where PCDD, PCDF, or PCB exposure would have been likely; and residential history. All questions included the historic periods when the activities occurred. The complete interview questionnaire is available on the UMDES website .The study was unusual in that it addressed the potential economic risks to subjects from participation. The Michigan Department of Environmental Quality considers any property with soil levels ≥ 90 ppt TEQ for dioxins, furans, and PCBs to be a “facility” for the purposes of state regulations , 2005. TAlthough there are no state regulations regarding the dioxin content of household dust (as there are for soil), and there are no medical guidelines for interpreting serum dioxin levels, participants were given the option to receive or not receive their results for each of their samples . This allowed participants to protect themselves from potential economic damages consequent to participation and awareness that their property was contaminated. Essentially, participants who did not know their soil and household dust results would be identical (with respect to economic risk) to subjects who were not selected for study or who chose not to participate after being selected. The text of all informed consent forms and written communications with potential subjects are available on the UMDES website . All staDuring the interview, each subject was asked questions that established eligibility for blood drawing [based on the Red Cross criteria for blood donors ]. Each eligible participant was asked to give an 80-mL sample of blood. Blood was usually drawn in the participant’s home by a mobile phlebotomy service in each community and was delivered on wet ice to the laboratory of either Mid-Michigan Medical Center  or Foote Hospital .13C12-labeled internal standards, and the analytes of interest were extracted with hexane and concentrated. The extracts were then fractionated using silica gel and activated alumina columns. An aliquot of each extract was injected into a gas chromatograph and the selected analytes were quantified by high-resolution mass spectrometry on a Waters Ultima magnetic-sector high-resolution mass spectrometer  using selected ion monitoring at 10,000 resolving power. The concentration of each analyte was then calculated based on a standard linear calibration specific to each congener. Each analytical run, which was blinded to the analyst, consisted of the unknown serum samples, a method blank , an ongoing precision and recovery sample , two solvent blanks, and two calibration standard solutions. After all quality assurance and quality control data were reviewed, the analytical results were calculated on both a whole-weight and a lipid-adjusted basis. Serum total lipids for each sample were calculated using Phillips formula summing triglycerides and total cholesterol.In the laboratory, blood was allowed to clot and then was centrifuged, and the serum was decanted. Serum was frozen at −20°C and was shipped by express mail on dry ice to Vista Analytical Laboratory . Vista performed analyses for the 29 dioxins, furans, and PCBs for which consensus toxic equivalency factors (TEFs) have been published , 2006, uDust sampling was conducted in the home of each respondent who had completed the interview and blood draw, after consent of the respondent, if the respondent was an owner of the residence. Participants who did not own the residence  did not have legal authority to give permission for sampling without the property owner’s consent. In consequence, their dust was not sampled, even though they otherwise participated in the study. All household dust samples were collected using high-volume small-surface samplers . Vacuums were equipped with a cyclone and a fine-particle filter capable of capturing 99.95% of particles > 0.3 μm in mean aerodynamic diameter. One composite sample was collected in each household from sampling locations that presented the highest potential for human contact with dust. Locations were generally a frequently occupied living space (living room or family room) and a high-traffic pathway . Samples were taken from both hard and soft surfaces, with carpets and area rugs being preferred sampling surfaces. Samples were not taken from undisturbed dust in generally inaccessible areas because there was no way to tell when such samples became contaminated or whether there had been any exposure by the participants. The sampling protocol was based, with minor modifications, on the American Society for Testing and Materials (ASTM) D 5438-00 method . The sam2) on a preprinted field data sheet, as well as the surface types where the sample was taken. Technicians transported samples on ice in a dedicated 4°C cooler until delivery to Vista Analytical Laboratory for analysis of the World Health Organization (WHO) 29 PCDD, PCDF, and PCB congeners using internal modifications of U.S. EPA method 8290 . We sampled a total of 764 residences for household dust  did not have legal authority to give permission for sampling without the property owner’s consent. In consequence, their soil was not sampled, even though they otherwise participated in the study. Each property was sampled in multiple locations by a sampling technician using a push core sampler to collect a core of soil from the surface to a depth of 6 in. (15 cm). Surface vegetation at the site of the core was also collected except in situations where garden plants might be damaged. For selection of locations for sampling, technicians followed a protocol that identified the house perimeter, property areas where skin contact was likely , and areas in or near the floodplain of the Tittabawassee River. The sampling protocol is portrayed schematically in Up to four sampling stations were located around the perimeter of the house . We determined locations where activities occurred that were likely to result in skin contact with soil from the interview responses. If the respondent worked in a flower garden, it was sampled. If there was a vegetable garden, it was sampled regardless of whether the participant worked in it, based on the assumption that the homegrown vegetables were consumed by all members of the household. Up to two gardens (soil contact areas) were sampled. For residences located in the floodplain, one additional station at the lowest, safely accessible location on the respondent’s property in the floodplain was sampled, referred to as the near-river sample. Thus, each residence had a maximum of seven sampling stations .Each sampling station was defined by laying out a 3-foot-diameter sampling ring, and three equally spaced cores were collected within the ring. All sample location coordinates were established using global positioning system procedures, for mapping purposes, and to relocate sample sites, if necessary. Technicians stored all sealed sample cores on wet ice (4°C) before transport to the University of Michigan Environmental and Water Resources Engineering laboratories, where they were extruded, separated into strata by depth, and composited across cores. Samples were stratified so that the top 0–1 in. (0–2.5 cm) could be examined separately from the 1–6 in. (2.5–15 cm) sample because surficial deposition of aerosols would be expected to affect only the top 1–2 cm of soil, whereas contamination from other pathways  would be expected to affect deeper soil. Ultimately, each residence yielded the following analytical samples: house perimeter set 0–1-in. (0–2.5 cm) depth composite; house perimeter set 1–6 in. (2.5–15 cm) depth composite; and house perimeter set surface vegetation composite.a) soil contact set 0–6 in. (0–15 cm) composite ; and b)soil contact set surface vegetation composite (if available). In addition, residences in the Tittabawassee River floodplain yielded the following samples: near-river set 0–1 in. (0–2.5 cm) depth composite; near-river set 1–6 in. (2.5–15 cm) depth composite; and near-river set surface vegetation composite.If there was a soil contact set, the residence yielded two additional samples: .A total of 766 residences were sampled in the five counties in Michigan from October through December 2004 and from March through September 2005. A total of 2,081 samples were analyzed for the 29 dioxin, furan, and PCB congeners  by VistaAll of the 0–1 in. (0–2.5 cm) house perimeter composite samples were analyzed. If any part of the property was in the floodplain, then we also analyzed all remaining composites . If the respondent did not live in the floodplain but had a vegetable garden or worked in a flower garden, we analyzed the 0–6 in. and vegetation composites for the soil contact set. If the TEQ of the 0–1 in. house perimeter composite for any property outside the floodplain was > 8 pg/g, then we analyzed the 1–6 in. and vegetation house perimeter composites. The trigger value of 8 pg/g TEQ represents the 75th percentile of the background distribution for the lower peninsula of Michigan .a) important changes to the questionnaire; b) addition of the Midland plume area as a separate study group; and c) addition of Jackson and Calhoun counties as control areas. Stakeholders did not participate in the selection of the study participants, sample collection, or laboratory or statistical analyses. Stakeholders were invited to all SAB meetings, and they had opportunities to discuss the study design, conduct, and analysis with the investigators and privately with the SAB. We treated the Dow Chemical Company in the same manner as all other stakeholders.Stakeholders, which we defined as entities that had a direct interest and that were actively involved in the dioxin issue in Midland/Saginaw  played a key role in the development of the study protocol. We held numerous face-to-face and telephone meetings with stakeholders to review the study goals, objectives, and draft protocol. Stakeholders submitted multiple sets of written comments, and the study team provided written responses that were posted on the UMDES website . The proa) reviewing and commenting on the draft study design; b) convening in person in Michigan twice yearly for 1–2 days each time to meet with the investigators, representatives of the Michigan Department of Community Health and other health officials, representatives of the community advisory panel (CAP), and stakeholders; c) monitoring the conduct of the UMDES; d) providing feedback to the investigators regarding the conduct of the UMDES; and e) reviewing and commenting on draft reports and manuscripts before they were released to the public and scientific community.We reported to an independent SAB made up of four scientists who were nominated by the stakeholders and appointed by the University of Michigan, with membership based on independence, qualifications in research relevant to dioxin issues, and scientific stature. Neither Dow nor any other stakeholders played any role in the selection of the SAB members. The members of the SAB are listed in the acknowledgments; their affiliations are posted on the UMDES website . The SABFunding for this research was available through an unrestricted grant from the Dow Chemical Company to the University of Michigan. We gave Dow periodic accounting reports to assure Dow that funds were properly spent on study activities. We reported research progress and results to Dow only in public settings at the SAB–stakeholder meetings, open scientific conferences, and meetings with county, state, and federal agencies and in public meetings in the Midland/Saginaw area. Dow played no role in the study design, data collection, data analysis, or data interpretation beyond providing written comments that the investigators posted to the UMDES website .Because potential exposures to environmental toxicants such as dioxins are a public health concern, residents and public health professionals in the Tittabawassee River area had a great interest in the design and execution of this study. The research team was committed to proactive community engagement in the design and implementation of the study. The research team’s community outreach efforts had three key areas:We conducted research and focus groups to clarify the concerns of the community. We identified key community leaders, including elected officials, school superintendents, clergy, members of the news media, and heads of nonprofit organizations, whom we selected for interviews. These investigations allowed identification of areas that could be addressed by the study team and helped to guide interactions with the community.We formed two CAPs  with membership based on independence, representation of community groups, and stature and respect in the community. We solicited nominees during focus groups and key-person interviews. The CAPs provided feedback to us regarding the concerns of the community, and they helped to inform the community about the conduct and progress of the study. The memberships of the CAPs are posted on the UMDES website .We developed a broad outreach/educational campaign to describe the efforts of the research team and to provide critical information to the public. The campaign involved media resources at the University of Michigan and in the communities, website development, area physicians, elected officials, public health officials, key community leaders, and regular, open meetings with the public. The outreach/educational campaign included descriptions of the research study, periodic updates on study progress, findings from the study as they became available for release, and interpretations of the findings [examples are available on the UMDES website ]. We conThis study has a number of unique features. First, informed consent for taking soil and household dust samples included discussion of the potential economic risks to subjects from participation in the research. Recent publications have highlighted the importance of this issue . This isWe considered household dust to be the property of the participant, provided that the participant owned the structure , whether or not the participant owned the land. In these instances, we asked the participant to consent to household dust sampling. In instances where the participant was the adult child (or other relative) of and lived with the property owner, we did not take soil or dust samples. Again, this would have violated the confidentiality of the participant.Almost all of the participants (> 98%) asked to receive the results of their blood dioxin analyses. In contrast, only 64% asked to receive their soil results. We believe this lower number reflected the potential economic risks to participants from knowing the contamination levels on their properties. Protection of the study participants included protection from economic risk consequent to their knowing the dust and soil results from their property. By not receiving their results, they could participate in the study yet be no different in terms of risk than nonparticipants.Our participation rates were high, even in the control areas ; in fact, these rates were higher than we anticipated when we planned the study. We believe this was due to the intense concern in the contaminated area regarding the risks of dioxin pollution and the widespread desire of the general public to participate in characterizing these risks and in taking appropriate actions to reduce risks. Communications with the affected population were a central part of this study and have been ongoing since the study planning began. Including the affected population in the study design, keeping them updated on study progress, and reporting the results in public meetings in a timely manner have led to widespread acceptance of the findings as providing a factual basis for addressing the dioxin pollution.We based our laboratory analyses on large samples of serum (~ 25 mL), household dust (10 g), and soil (10 g), which allowed us to achieve low LODs for all PCDD, PCDF, and PCB congeners. For the PCDD and PCDF congeners of greatest concern, we achieved low LODs, and few samples had unmeasured levels. This allowed us to make important inferences about the dioxin levels in the blood in the referent population, as well as to characterize the full range of the distribution for each congener in blood, household dust, and soil. Comparisons of mean and median values across populations, and inferences about differences in these measures between population groups, are greatly improved when they are based on measurements rather than assumptions about values < LOD. Our LODs for serum were substantially less than those reported for the National Health and Nutrition Examination Survey (NHANES) 2001–2002 data  primarilIn this study we collected complete questionnaire, blood, dust, and soil samples on 731 people  of the 1An important concern is often raised in the investigation of industrial contamination sites, as illustrated by this study. On the one hand, high-quality, expensive research is needed to identify the extent of the contamination and the impact on the human population, which should be paid for by the entities that created the pollution. On the other hand, there is often concern in the affected communities that research paid for by the industry will not fairly address the issues. In the present instance, there are also concerns in the affected communities that neither the government agencies nor the environmental groups will fairly address the issues. We set up our study to provide a credible method by which community concerns could be addressed, and to that end we sought extensive community input and participation, rigorously protected the confidentiality of our participants, set up an independent advisory board to which we reported, had no reporting relationship to Dow, kept our methods and results transparent, and built an extensive communications program. These methods have resolved a myriad of practical problems and are applicable across a broad range of settings.


During the last eight years, North and South Kivu, located in a lake area in Eastern Democratic Republic of Congo, have been the site of a major volcano eruption and of numerous complex emergencies with population displacements. These conditions have been suspected to favour emergence and spread of cholera epidemics.In order to assess the influence of these conditions on outbreaks, reports of cholera cases were collected weekly from each health district of North Kivu  and South Kivu  from 2000 through 2007. A geographic information system was established, and in each health district, the relationships between environmental variables and the number of cholera cases were assessed using regression techniques and time series analysis. We further checked for a link between complex emergencies and cholera outbreaks. Finally, we analysed data collected during an epidemiological survey that was implemented in Goma after Nyiragongo eruption. A total of 73,605 cases and 1,612 deaths of cholera were reported. Time series decomposition showed a greater number of cases during the rainy season in South Kivu but not in North Kivu. Spatial distribution of cholera cases exhibited a higher number of cases in health districts bordering lakes . Four epidemic reactivations were observed in the 12-week periods following war events, but simulations indicate that the number of reactivations was not larger than that expected during any random selection of period with no war. Nyiragongo volcanic eruption was followed by a marked decrease of cholera incidence.Our study points out the crucial role of some towns located in lakeside areas in the persistence of cholera in Kivu. Even if complex emergencies were not systematically followed by cholera epidemics, some of them enabled cholera spreading. With the number of cholera cases up to 73,000 during the last eight years and successive wars that have persisted for fifteen years, the North and South Kivu provinces of the Democratic Republic of Congo are currently heavily hit by both cholera outbreaks and war-related population displacements. Prior to this study, no research had been done to identify the sources of epidemics and the pathways used by cholera to spread throughout the Kivu provinces. Here we show that a few cities located on the lakeshore of Lake Kivu and Lake Tanganyika act as the main sources of cholera epidemics and that the number of cholera cases tends to increase during the rainy season. We also found that only a minority of population displacements were followed by cholera outbreaks. Finally, we think that the low number of cholera cases recorded after the Nyiragongo eruption is one more argument to implement programs aiming at restoring, and if possible improving, drinking water access following natural disasters Numerous factors have been postulated to increase the risk of cholera outbreaks in a given area where cholera is already circulating among the population. The main environmental risk factors identified include heavy rainfall, blooms of plankton, and an increase in sea surface temperatures The provinces of North and South Kivu, bordering Lake Kivu in the east of the DRC, present an exceptional accumulation of these risk factors. They have been the site of numerous dramatic events, including invasion and occupation by foreign forces, civil war, population displacements, a major volcano eruption and earthquakes. According to a recently published mortality survey, it is estimated that the conflicts and humanitarian crises, which ravaged the eastern part of the DRC, have taken the lives of 5.4 million people since 1998, and continue to leave as many as 45,000 dead every month Here, we present a study designed to describe epidemiological patterns of cholera outbreaks in the Kivu provinces and to elucidate the influence of specific environmental and geographical factors, CEs and disasters on outbreaks of cholera. This study and the previous work that described the patterns of cholera outbreaks in Katanga and Eastern Kasaï Vibrio cholera O1 from stool samples From January 2000 through December 2007, reports of cholera cases and deaths were collected weekly from each health district (HD) of North and South Kivu provinces. Case-patients of cholera were defined as recommended by the World Health Organization (WHO): “any person 5 years of age or older in whom severe dehydration develops or who dies from acute watery diarrhoea”, with an age limit lowered to 2 years for cases associated with confirmed cholera outbreaks 2, 4,667,699 inhabitants, 19 HDs) and South Kivu  are located in the Great Rift Valley, and border Lake Edward, Lake Kivu, and the north edge of Lake Tanganyika. In Kivu, the climate is characterized by a rainy season from October to the end of May and a dry season the rest of the year. However, the rainy season is partially interrupted by a short dryer period in January and February. The relief of the Kivu provinces is dominated by several volcanic chains. Nyiragongo, the most active volcano, is located approximately 20 kilometres north of the city of Goma  near Lake Kivu. Nyiragongo last major eruption occurred on January 17, 2002, when lava flow destroyed one third of the city of Goma North Kivu  and 3 from South Kivu (among 29 samples). Vibrio cholerae O1 El Tor Inaba was found only in South Kivu (6 positive samples among 29). In Bukavu (South Kivu), Ogawa and Inaba serotypes were isolated during the same outbreak of cholera in 2005. All isolates were found to be sensitive to ciprofloxacin, erythromycin and nalidixic acid, and resistant to tetracycline, ampicillin and cotrimoxazole.From January 2000 through December 2007 (416 weeks), a total of 73,605 cases and 1,612 deaths  from cholera were reported in North and South Kivu. During the eight-year study, both provinces experienced at least one outbreak of cholera per year, with peaks ranging from 130 to more than 700 cases a week . In SoutAccording to UN and NGOs reports, a total of 18 large-scale population displacements related to CEs has been recorded during the period. In six cases, these population displacements occurred during already ongoing cholera epidemics. Among the 12 remaining war events with displacements of population, four were followed by a cholera outbreak within a period of 12 weeks. Two of these cholera epidemics occurred in IDP camps, starting six and eight weeks after the arrival of the first IDPs in the settlements. However, simulations indicate that the number of reactivations was not larger than expected after any random selection of a week with no war event in a non-epidemic period .In 2002, the Nyiragongo volcanic eruption was not followed by any exacerbation of cholera incidence. A survey performed in five health centres located in the western area of Goma showed that, during this period, diarrhoeas accounted for only 6% of patients who were seen in the health centres. In the entire city of Goma, only 140 cholera cases (8 cases per week), without any deaths, were reported from January to April 2002. This low number of cases contrasts with an average of 29 cases per week usually encountered in Goma at this period of the year.Escherichia coli), which would have a similar clinical presentation to that of the cholera cases here Since the beginning of the 1990's, Kivu provinces have been identified as one of the most active foci of cholera in the world. In 1994, the refugee camps located around Goma and Bukavu experienced the deadliest cholera epidemics recorded during the last hundred years. This explosive outbreak of cholera, which affected Rwandan refugees, resulted in about 70,000 cases and 12,000 deaths First, our findings, obtained from a study performed in a lakeside region, are consistent with what was recently found in the province of Katanga, located on the south side of Kivu in the eastern part of the DRC V. choleraeV. cholerae is not formally established because no study has yet demonstrated a long term persistence of toxigenic V. cholerae in the East African Rift Valley lakes. Our results show that there is a need for further studies to explore the role of lake environments in the persistence of cholera in inland Africa. Indeed, some endemic V. cholerae strains have long been isolated from fresh water V. cholerae strains, which can rapidly grow in a free-living state in one natural lake water in Austria Here, the influence of seasons, and the effect that some lakeside areas have on the persistence of the disease, could make the epidemiological pattern of cholera in Kivu comparable to patterns studied more comprehensively in Asian coastal areas The eruption of Nyiragongo, the largest natural disaster reported during this period, was not followed by a cholera outbreak, or by any other disease outbreak. On the contrary, during the months that followed the disaster, the rates of cholera infection were among the lowest that have been recorded in the city of Goma during the 8 years of the study. Several hypotheses can be advanced to explain this low number of cholera cases. This can be due to the impact of the emergency program, but other possible explanations cannot be ruled out, including the fact that the volcanic eruption could have decreased the likelihood of a cholera outbreak secondary to the alterations in water sources and usage patterns. Our finding is in agreement with a recent study showing that earthquakes, tsunamis and volcano eruption were not usually followed by epidemics The search for the impact of the CEs indicates that they do not systematically represent a triggering factor for cholera outbreaks. However, in our study, we also saw that in four cases, the occurrence of a CE led to the exacerbation of cholera, including, in two cases a cholera outbreak, which started in a displaced settlement a few weeks after the arrival of IDPs. Actually, several conditions are necessary for a CE to father a cholera outbreak. Among these conditions, there is the fact that some of the IDPs fleeing from the conflict area should have a previously acquired cholera infection (symptomatic or in incubation), and/or the fact that the IDPs should move into areas where cases of cholera are already present. It would also be necessary for there to be insufficient or no assistance to the IDPs . These circumstances were met in 1994 when one million refugees coming from Rwanda settled in makeshift camps around Goma, overwhelming the capacities of humanitarian staff already present in the town. More recently, due to the insecurity that prevailed around Goma in the summer and fall of 2008, a cascade of cholera outbreaks that began in Rutshuru in the North of Goma have been recorded in North Kivu: Rutshuru (beginning on week 37), Goma and Karisimbi (beginning on week 40), Walikale and Birambizo (beginning on week 44). In each of these HDs, the outbreak was introduced by people escaping from battle-hit areas located North of Goma . Simultaneously, due to excessive danger for fieldworkers, numerous NGOs fled from Goma and neighbouring areas as cholera outbreaks started, leading to a disorganization of the programs aimed to limit the spread of the epidemic.In conclusion, the epidemiology of cholera in both Kivu provinces confirms our previous findings in Katanga and eastern Kasaï, and highlights the role of some towns located in lakeside areas as sources of cholera outbreaks. The results of this study show that, even if each CE with numerous IDPs is not systematically followed by a cholera outbreak, CEs may facilitate spreading of already existing outbreaks due to the fleeing of infected IDPs to new areas where NGOs cannot reach them due to an excessive danger for fieldworkers. By contrast, even in a context of CE and natural disaster, the occurrence of epidemics is not unavoidable. For example, the number of cholera cases was lower than expected after the partial destruction of the town by the Nyiragongo eruption followed by the implementation of an emergency program. We think that this low number of cholera cases is one more argument to implement programs aiming to restore, and if possible to improve, drinking water access following natural disasters.Alternative Language Article S1Translation of the Article into French.(0.96 MB PDF)Click here for additional data file.


There has been very little research on wellbeing, physical impairments and disability in older people in developing countries.A community survey of 1147 older parents, one per household, aged sixty and over in rural Thailand. We used the Burvill scale of physical impairment, the Thai Psychological Wellbeing Scale and the brief WHO Disability Assessment Schedule. We rated received and perceived social support separately from children and from others and rated support to children. We used weighted analyses to take account of the sampling design.Impairments due to arthritis, pain, paralysis, vision, stomach problems or breathing were all associated with lower wellbeing. After adjusting for disability, only impairment due to paralysis was independently associated with lowered wellbeing. The effect of having two or more impairments compared to none was associated with lowered wellbeing after adjusting for demographic factors and social support  but after adjusting for disability the coefficient fell and was non-significant. The parsimonious model for wellbeing included age, wealth, social support, disability and impairment due to paralysis . In this Thai setting, received support from children and from others and perceived good support from and to children were all independently associated with greater wellbeing whereas actual support to children was associated with lower wellbeing. Low received support from children interacted with paralysis in being especially associated with low wellbeing.In this Thai setting, as found in western settings, most of the association between physical impairments and lower wellbeing is explained by disability. Disability is potentially mediating the association between impairment and low wellbeing. Received support may buffer the impact of some impairments on wellbeing in this setting. Giving actual support to children is associated with less wellbeing unless the support being given to children is perceived as good, perhaps reflecting parental obligation to support adult children in need. Improving community disability services for older people and optimizing received social support will be vital in rural areas in developing countries. There is increasing interest worldwide in the study of wellbeing as a means to assess need and to evaluate positive dimensions of health care programs. Positive mental health "which allows individuals to realise their abilities, cope, and contribute to their communities"  and the Research on associations between physical impairments and wellbeing in older people has been limited -7 althouIn Thailand, the setting for this study, the proportion of adults 60 years of age and over rose from 4.5% in 1960 to 9.5% in 2000 and is predicted to be 25% in 2040. In the We nested the study within the Kanchanaburi Demographic Surveillance System in western Thailand . KanchanThe interviewing team visited each sampling unit and made contact with the village headman prior to visiting each selected household. The populations were mostly already well acquainted with the demographic surveillance system. If the selected older adult and the household head gave consent, the interviewer first interviewed the household head with the household questionnaire and then the older adult with the individual questionnaire.We carried out focus group discussions to explore experiences of rural ageing, health and wellbeing and exchanges with family members. This informed the development of the questionnaire which was pre-tested by a team of ten experienced interviewers on three separate occasions. After each pre-test we made modifications by consensus. The final version was back-translated to English and checked for consistency by a bilingual psychiatrist and a bilingual social scientist.Fluent Thai-speaking; aged 60 or over; parent of at least one living child ; residence in a demographic surveillance system village since at least 2004.Psychological well-being. We used the 15-item Thai well-being scale ,18, devePhysical Illnesses and Impairments: we used a modified version of the Burvill physical illness scale . Particiyears of education, number of household assets , and household wealth index. We used principal components analysis to develop the household wealth index from the list of assets and the interviewer's global rating of household quality. The first principal component (which accounted for 26% of the variance compared to 7% for the second next most important) was used to provide an overall socioeconomic index based on these 23 items. This final index comprised 15 items .We modified existing measures in the light of the importance in the Thai context of the family and of children. We measured size of neighbourhood family network, frequency of talking to a child, frequency of talking to friends, received support , actual support to children , perceived adequacy of support from and to children, and received support from others -22. The we used a learning task which has been used extensively in low and middle income countries which is drawn from the Consortium to Establish a Registry of Alzheimer's Disease (CERAD) ,24, compWe used the brief (12-item) questionnaire from the WHO Disability Assessment Schedule to rate disability over the past 30 days . We wereThe data collection team of four supervisors and twelve interviewers had at least a bachelor's degree. Most had previous experience with interviewing for the demographic surveillance system. Residential training took ten days and included presentations, role play and practice in pilot villages. The study was presented to the interviewers as a study of healthy ageing in Thailand. Purposefully, no possible links were discussed between psychological wellbeing, impairment, disability or social support from children in order to blind the interviewers to the research hypotheses and none of these sections of the interview immediately followed each other in sequence.The data collection team stayed in the villages at the headman's house or the temple. Quality control included checks on data completeness and consistency. Interviewers had to return to the participant if data were inadequate. Field station research managers (trained in the interview but blind to the hypothesis), and researchers were in frequent telephone contact and regularly visited the data collection teams. We conducted all interviews in Thai and gathered informed consent from all participants. We gained ethical approval from Kings College Research Ethics Committee (No. 05/05-68) and from Mahidol University Institutional Review Board.This was developed for the main longitudinal study which was designed to study the impact on older parents of out-migration of their adult children/offspring from the district . The samWe used Stata version 9 for Windows . We weighted the data using the product of two sets of probability weights to take account of differential sampling at neighbourhood and household levels. The weighting at neighbourhood level took account of the probability of the neighbourhood being selected from the total number of neighbourhoods in that stratum in the province. The weighting at household level took account of the probability of being selected if the older parent was or was not co-resident with one of their offspring. We used the survey commands in Stata (svyset) for analyses. We first described the unadjusted associations between wellbeing score and the socio-economic, social support and health variables. We modelled impairment in two ways: as individual impairments and as a total of different impairments (one impairment versus none and two or more versus none). We used multiple linear regressions to develop a model for the effect of impairment on wellbeing, carrying out tests of the effect of impairment after adding in potential confounding variables. We explored interactions between social support, specific impairments, total impairments and total disability in the multivariable model. All tests were Wald tests as appropriate for weighted survey data. Residuals were computed for the final multivariable model and plotted as histograms  and were also plotted against predicted values . Variance inflation factors (VIFs) were computed for all independent variables to check for collinearity.1620 older adults in 1620 households were sampled, of whom 1300 (80%) were eligible to take part. Reasons for not being eligible were having no biological or adopted children or step-children; having died since 2004, or moved out of the village. Out the 1300 eligible, 1147 (88%) agreed to take part and 153 (12%) were non -responders of whom 110 were unavailable for an interview (despite at least three visits to the household), 21 refused to take part and 22 were too unwell. Of the responders, data were incomplete for 43 due to the older adult being unwell or cognitively impaired. There were no significant differences between responders and non-responders in terms of age, gender, living alone, being married, or education.Table The three most common impairments were arthritis, pain, and eyesight problems. Approximately one-third (32%) of the older adults did not have any impairment, 18% had one and 50% had two or more impairments. Impairments due to arthritis, pain, paralysis, vision, stomach problems or breathing were all associated with lowered wellbeing. Paralysis, faints/blackout, breathlessness, and pain were the impairments with the highest effect size for less wellbeing. After adjusting the impairments for disability, only paralysis remained significantly associated with low wellbeing.As shown in Table Variables that were significantly associated with wellbeing either before and/or after adjustment are shown in Table There was an interaction between social support from children and paralysis – those with low received social support from children and with paralysis were especially likely to have low wellbeing .The key finding from this paper is that impairment due to paralysis was associated with lowered psychological wellbeing in older Thai people, even after controlling for eleven other physical impairments, disability, socio-economic factors and social support. A second key finding is that while an increasing number of impairments was also associated with less wellbeing, this association, and those with other individual impairments, were explained by disability. A third finding is that in this Thai setting, received support from adult child offspring, received support from others and perceived support from adult child offspring were all independently associated with greater wellbeing in older parents whereas actual support to children was associated with lower wellbeing.Chance is an unlikely explanation for the adjusted association between paralysis and low wellbeing, and for the adjusted association between disability and low wellbeing, as the associations were significant at a level of p = 0.001. We were able to adjust for a range of covariates so confounding is an unlikely explanation. All impairment and disability measures relied on subjective perception which may lead to misclassification of health status, although a high level of agreement has been reported between self-reported and objective health status measures . Bias isWhy was paralysis associated with a large and significant effect on wellbeing? Studies of older people in Western countries have reported low mood and depression particularly following stroke and that this association was independent of disability . Post-stOur finding that disability explains the association between number of impairments and low wellbeing echoes studies that have looked at impairment, disability and depression and at impairments and wellbeing in Western countries ,9,28,29.The model for greater wellbeing included other factors, notably received social support from children, perceived social support from children, received social support from others, financial remittances from children and wealth. As a number of associations were analysed in this study, a problem of multiple testing might have occurred. However, it is unlikely that this would explain our findings as most of the factors in the parsimonious model for wellbeing were significant at p < 0.001 or p = 0.001. Several possible mechanisms could explain the effect of received social support on wellbeing. Social support may reduce stress and consequently buffer the effect of negative events. Although received support is likely to reflect need, certain types of received support may be valuable in bringing about improved wellbeing.Greater social support might also aid older people with impairment to carry out daily tasks, encourage them to be physically active, increase medication compliance, decrease social restriction and enhance self-esteem . In the Some limitations of this study include its cross-sectional design. Secondly our measure of wellbeing is culture specific – although this may also be regarded as strength of the study. Thirdly, the findings from this study might lack generalisability to all older adults as the sample was restricted to parents with at least one living child, although in Thailand this excluded only 5% of older people as we included anyone with a biological, adopted or stepchild.In conclusion, disability may mediate most of the impact of chronic physical impairments on psychological wellbeing, although paralysis appears to have an independent effect. Received social support, perceived social support and wealth also have important positive effects on psychological wellbeing. Improving disability services and optimising social support will be vital in rural areas in developing countries which are likely to experience increasing depletion of younger adults in the next decade. While care is currently provided by family members, especially daughters and grand-daughters, we suggest that potentially valuable services in rural areas may include home care programmes for older people and their carers, home visits by health care volunteers in the village, day care, extending the existing network of 'elderly clubs', occupational therapy to enable aids and adaptations at home, and making a range of facilities more accessible to older disabled people,In conclusion, in this Thai rural setting, most of the association between physical impairments and lower wellbeing in older people is explained by disability. Received support from children and from others and perceived high support from and to children were all independently associated with greater wellbeing whereas giving actual support to children was associated with lower wellbeing. Improving community disability services for older people and optimizing received social support through families, neighbours and home care programs will be vital in rural areas in developing countries.The authors declare that they have no competing interests.All authors made substantial contributions to study design and interpretation of data. MA had main responsibility for analysing data and drafting the manuscript. SP and KT had main responsibility for acquisition of data. All authors were involved in revising the manuscript critically and have given final approval of the version to be published.


Although a sizeable budget is available for HIV/AIDS control in Thailand, there will never be enough resources to implement every programme for all target groups at full scale. As such, there is a need to prioritize HIV/AIDS programmes. However, as of yet, there is no evidence on the criteria that should guide the priority setting of HIV/AIDS programmes in Thailand, including their relative importance. Also, it is not clear whether different stakeholders share similar preferences.Criteria for priority setting of HIV/AIDS interventions in Thailand were identified in group discussions with policy makers, people living with HIV/AIDS (PLWHA), and community members ). On the basis of these, discrete choice experiments were designed and administered among 28 policy makers, 74 PLWHA, and 50 VHVs.In order of importance, policy makers expressed a preference for interventions that are highly effective, that are preventive of nature (as compared to care and treatment), that are based on strong scientific evidence, that target high risk groups , and that target both genders (rather than only men or women). PLWHA and VHVs had similar preferences but the former group expressed a strong preference for care and treatment for AIDS patients.The study has identified criteria for priority setting of HIV/AIDS interventions in Thailand, and revealed that different stakeholders have different preferences vis-à-vis these criteria. This could be used for a broad ranking of interventions, and as such as a basis for more detailed priority setting, taking into account also qualitative criteria. While the number of new HIV positive cases in Thailand decreases -3, HIV/AAlthough a sizeable budget for implementation of this plan is available - approximately US$193 million in 2008 derived from both the Thai government and the International Monetary Fund [A number of criteria can guide this priority setting process . First, It is clear that relying on a single criterion, e.g. efficiency, falls short to capture the important moral and ethical notions, and is unlikely to be acceptable for most policy makers -21 incluHowever, as of yet, there is no evidence on the criteria that should guide the priority setting of HIV/AIDS programmes in Thailand, including their relative importance. Also, it is not clear whether different stakeholders share similar preferences. It is against this background that this paper elicits preferences on the relative importance of criteria for priority setting of HIV/AIDS programmes in Thailand from policy makers, PLWHA and community members. The study uses discrete choice experiments (DCE) to elicit explicit preferences in HIV/AIDS area, and is the first study to do so in this area. The technique allows the assessment of the relative importance of different criteria that influence choice, in this case the priority setting of health interventions in HIV/AIDS control. The technique has shown promising results in a number of other disease areas in low-income settings -25. The Discrete choice experiments are a quantitative methodology for evaluating the relative importance of the different product attributes that influence consumer choice behavior . In suchWe employed DCE to determine the relative importance of criteria for priority setting, according to various stakeholders. In a DCE, respondents choose their preferred option from sets of hypothetical scenarios, each consisting of a bundle of criteria that describe the scenario in question. The criteria are constant in each scenario, but the levels that describe each criterion may vary across scenarios. Analysis of the options chosen by respondents in each scenario reveals the extent to which each criterion is important to the decision at hand ,28. RunnIn this study, we chose to explore the views of policy makers in comparison with two other groups of stakeholders, i.e. PLWHA, and community members represented by village health volunteers (VHVs).The policy makers were represented by 28 national - and province level decision makers strongly involved in health resource allocation decisions in Thailand specifically on HIV/AIDS. As a first step in the selection process, members of the National AIDS Committee were asked to participate. As a second step, they were asked to nominate other decision-makers meeting the above criterion. A total of 30 decision makers were invited, and 28 agreed to participate in the study. They were predominantly male 71.4%), and all being higher educated (bachelor degree or more)  with a minority being higher educated.The community members were represented by VHVs - these are community members who have been trained by public health providers in order to provide basic health care delivery including first aid and necessary health information to members of the village they reside in. In the selection process, we invited 100 VHVs in a semi-urban district of Samutprakan province, and out of these, 50 agreed to participate. They were predominantly female (88%), with a minority being higher educated.To define the criteria in DCE, group discussions were organized with each group of stakeholders including six representatives of that group. As an initial step, two HIV/AIDS interventions were presented. Then participants were asked to decide which intervention should be funded and reasons for the choices were discussed. The discussion was then broadened to discuss general reasons, or criteria, to fund HIV/AIDS interventions, and finally agreement was reached on a comprehensive set of criteria. Resulting criteria and associated levels from the three group discussions were compared. The final selection of criteria and levels included those that were identified by two or more discussion groups. This resulted in identification of one criterion at four levels, two criteria at three levels, and two criteria at two levels Table .1 × 32 × 22), a limited number is chosen on the basis of a fractional experimental designs catalogue produced by Hahn and Shapiro [The DCE was designed on the following principles. To avoid information overload from a full factorial of 144 possible scenarios based on identified criteria and levels  are the coefficients of the model indicating the probability of selection relative to the reference criterion level, and ε is the unobservable error term. To control for differences in attractiveness of DCE scenarios, dummies were added for scenarios to equation (1).where P is the probability of an intervention being selected by the respondents, βMarginal effects reflect the change in the probability of selection of an intervention. These were computed by taking the average difference in predicted probability of P with and without the variable, while holding the distribution of the other variables at their sample value, and then taking the sample mean of these differences.2[The relative contributions were calculated to signify the contribution of one criterion to the variation in preferences explained by the regression model and therefore describe the relative importance of the various criteria in the choice of interventions. This relative importance depends on the variation in the levels that are chosen for each of the attributes. Variation explained by the model is based on Efron R2,(2)i indicates the observed choice and 2of the above model minus Efron's R2of the model where the criterion is held constant at its sample mean. This procedure shows the contribution of criteria irrespective of the number of levels they have.where yTo test whether the decision makings on choice selections vary between perspectives, the likelihood ratio test was analyzed. At the end, as a validity check, the resulting rank ordering of attributes derived from DCE exercise was compared (presented by the relative contributions) to those derived from a simple rank ordering.This study was approved by Institute for the Development of Human Research Protections (IHRP), Ministry of Public Health, Thailand. All participants provided their written informed consent for the discussion and the interview.Table Second, PLWHA had similar preferences as policy makers with some exceptions. Most notably, PLWHA expressed a strong preference for treatment or care for AIDS patients, and the probability of selection of these interventions is 24.5% higher than treatment and care for HIV-infectious people. Moreover, they expressed a strong preference for targeting both genders rather than one gender only. Third, VHVs preferences cohered largely with that of policy makers.2, and Hosmer-Lemeshow chi-square. The likelihood ratio test presents that the preferences on the criteria of each group of stakeholders are significantly different.The different models for policy makers, PLWHA and VHVs demonstrate a good fit as indicated by the pseudo R2 indicates the overall importance of criteria  are well reflected through decisions made by policy makers. This study also highlights the differences in preferences between PLWHA and the other stakeholder groups. The preferences of the former for care and treatment may reflect self-interests, whereas the preferences of the latter may reflect preferences for the society at large.Thirdly, our findings show overlap between the ranking of criteria resulting from DCE and as obtained from simple ranking for policy makers, but less so for other stakeholders. This may indicate validity and hence usefulness of DCE for (well-educated) policy makers, but possibly less so for other (less-educated) stakeholders.Recently, a number of empirical priority setting studies have included the views of different stakeholders, such as patients and community members, besides those of policy makers . InclusiThe DCE in this study only includes the criteria that were found to overlap from the focus group discussions. The rationale for doing so was to accommodate comparability of study findings  on the one hand, while maintaining the number of criteria to a manageable number  on the other hand. However, this choice may have led to the omission of important criteria for some groups of stakeholders, and may have reduced the validity of study findings. Next studies should seek to strike a balance between comparability and validity.Our study findings are based on small sample sizes , and should therefore be interpreted with caution. This also indicates the explorative character of our study. A proper sample size calculation is difficult in the absence a prior information on the variances on the responses - we based our sample sizes on previous similar studies, e.g. in Ghana  and NepaIntervention utility can be calculated by assuming a main effects additive utility model on the basis of a linear combination of the weights of each level of all criteria . This utThe present study findings, and associated rank ordering of HIV/AIDS interventions, can be considered as general principles to prioritization of HIV/AIDS interventions in Thailand. Since the DCE design only involves a set of criteria amendable to quantification, it ignores a range of non-quantifiable considerations - e.g. ethical, political, and social concerns ,35. As sThis exploratory study has shown the feasibility of eliciting explicit preferences on the criteria for prioritization of HIV/AIDS interventions in Thailand. Further studies should refine methodological aspects, and interpret the findings in terms of the prioritization of interventions.The authors declare that they have no competing interests.SY and RB conceptualized the study. SY carried out the data collection, and drafted the manuscript. RB, ST and YT participated in the study design, made substantial contributions to the data interpretation and writing of the paper. XK participated in data analysis. All authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1472-6963/10/197/prepubThe DCE questionnaire. The questionnaire presents the DCE questions and explanatory notes used in the survey (10 pages)Click here for file


The Longitudinal Analysis of Nursing Education (LANE) study was initiated in 2002, with the aim of longitudinally examining a wide variety of individual and work-related variables related to psychological and physical health, as well as rates of employee and occupational turnover, and professional development among nursing students in the process of becoming registered nurses and entering working life. The aim of this paper is to present the LANE study, to estimate representativeness and analyse response rates over time, and also to describe common career pathways and life transitions during the first years of working life.Three Swedish national cohorts of nursing students on university degree programmes were recruited to constitute the cohorts. Of 6138 students who were eligible for participation, a total of 4316 consented to participate and responded at baseline (response rate 70%). The cohorts will be followed prospectively for at least three years of their working life.Sociodemographic data in the cohorts were found to be close to population data, as point estimates only differed by 0-3% from population values. Response rates were found to decline somewhat across time, and this decrease was present in all analysed subgroups. During the first year after graduation, nearly all participants had qualified as nurses and had later also held nursing positions. The most common reason for not working was due to maternity leave. About 10% of the cohorts who graduated in 2002 and 2004 intended to leave the profession one year after graduating, and among those who graduated in 2006 the figure was almost twice as high. Intention to leave the profession was more common among young nurses. In the cohort who graduated in 2002, nearly every fifth registered nurse continued to further higher educational training within the health professions. Moreover, in this cohort, about 2% of the participants had left the nursing profession five years after graduating.Both high response rates and professional retention imply a potential for a thorough analysis of professional practice and occupational health. The main current problem for healthcare organizations worldwide is the shortage of health service providers . This shNurses' health, working conditions, job satisfaction and occupational commitment affect nurse behaviour such as turnover, which in turn can influence quality of care and patient outcomes -13. As aThe multinational European Nurses Early Exit (NEXT) study showed that intention to leave the nursing profession  provided a good estimate of subsequent decisions to actually quit . Hayes aIn 2006, 12% of the nursing workforce in Sweden were not employed within the healthcare system . Nurses Numerous studies are either directed towards an investigation of student health outcomes , or workhttp://www.who.int/whosis/en/index.html (accessed 5 March 2009)). While the labour market is somewhat balanced in supply and demand, the nursing educational system has undergone major structural changes. One educational change that has occurred during the past 15 years is the transition from a non-academic and practically oriented education programme to higher education leading to an academic degree [In Sweden, the labour market demand for nurses is relatively good, with an unemployment rate of below 0.5% . The denc degree ,32. Concc degree . Since tc degree .Thus, the future retention and continuing professional development of nurses, and the provision of high quality care, may depend on the interaction of many factors, such as student engagement and commitment, outcome of higher educational studies, working conditions and occupational health. In order to address several of these issues, a nationwide study  was initiated in 2002, with the aim of longitudinally examining a wide variety of individual and work-related variables related to psychological and physical ill health and well-being, as well as risk and protective factors for mental ill health among nursing students in the process of becoming registered nurses and entering working life. The database, now under construction, will make it possible to study individual conditions, educational structures, and contextual factors in healthcare that affect health trends among new graduates in the transition from undergraduate studies to practice.Thus, the aim of the LANE study is to monitor the health status as well as retention, turnover rates  and professional development of newly qualified nurses in their first years of working life. The aims of this paper are to present the LANE study, to estimate representativeness and analyse response rates over time, and also to describe common career pathways  and life transitions during the first years of working life.th student is taking an undergraduate nursing programme . The three cohorts that comprise the LANE study include nursing students who were expected to graduate and receive their nursing degree in the autumn of 2002, 2004, and 2006, respectively. In the following text, these three cohorts are referred to as the EX2002, EX2004, and EX2006 cohorts. Participants eligible for the study were 6138 nursing students attending a predefined semester at any of the 26 Swedish universities offering nursing programmes in Sweden at that time (see Table In Sweden there are approximately 130 000 registered nurses (under 65 years of age), and another 40 000 new graduates will enter the labour market during this first decade of the century. In all, there are about 300 000 students in higher education and around every 20Students who were eligible for participation in EX2002 and EX2004 were informed about the study, either by attending an oral presentation given by a member of the research group at their university, and/or by an information letter sent to each student. At the presentation seminar, written information about the study and the survey instrument was available. Those who did not attend the information meeting, or for whom there was no record that they had received the written information at the seminar, were contacted by post. All EX2006 students were contacted by post. After two reminders (the last one including a new information letter and a copy of the questionnaire), the students who gave their consent (and thus constituted the cohorts) were defined. Since 2003, all data collections have been administered by Statistics Sweden. Data from the sampling frames for the LANE study are presented in Table The study has an observational longitudinal design , where tThe objectives for choosing a multiple-cohort observational design were: to measure and compare period and cohort effects, and to describe developmental change and temporal order of events in relation to health status and incidence of disease . The worThe following steps were taken to ensure an appropriate sample size that could give stable and correct estimates of main outcomes such as depression and later job burnout. The argument focuses on changes in mean levels of depression over time in an affected group. The strategy here was to find the power to perform a post-hoc test, where the increase in mean levels of depression could be detected in an affected group and compared with a non-affected group. To detect a small mean change in symptom levels (i.e. an effect size of 0.20 standard deviations) across two adjacent time points with a power of 80%, 199 affected subjects are required .According to data from community surveys addressing point estimates of depressive symptoms, up to 20% of the adult population are affected . MoreoveApproval for the initial study consisting of the two first cohorts was received from the regional Research and Ethics Committee at Karolinska Institutet, Sweden (Dnr 2005/1532-32). Additional permission regarding another cohort (EX2006) and subsequent data collections and questionnaires was received . Written informed consent was obtained from all study participants. To minimize the risk of ambiguity or distress, oral and written information was given, and a covering letter also accompanied each questionnaire. The covering letters kept the study participants updated and always included details of how to contact the research team. The research team was available to answer questions and concerns by phone and e-mail.All data in the LANE study are self-reported and collected by means of a postal survey, except for year of birth, sex and social security number, which were originally retrieved from the national registry of educational statistics and later validated by comparisons with data given by participants in their written informed consent. Also, to ensure quality over time, each survey was reviewed by the workers at the technical and language laboratory at Statistics Sweden (SCB). General background variables included civil status, household composition, previous education, social support and critical life events and were asked in each wave of data collection when appropriate. Most main outcomes were assessed repeatedly in all cohorts, but EX2002 had a unique focus on occupational values; EX2004 was specifically oriented towards a complete coverage of assessments related to education, personality factors and research utilization; and EX2006 had an extended focus on psychosocial factors at work, and was suitable for comparison with another project on teaching students.The main psychological health outcomes, i.e. depressive symptoms and job burnout, were measured by the Major Depression Inventory  and the Professional competence and practice was conceptualized as occupational self-efficacy  and reseItems from the National Survey of Student Engagement  were useAt the end of the 25-page questionnaire, two open-ended questions were added, where the respondents were invited to write comments on subjects of current importance to them. Initially, the open-ended questions primarily focused on encouraging participants to outline important areas that had not yet been covered in the questionnaires. Subsequently, the general question was phrased: "If you have any thoughts about yourself, or the LANE study, that you would like to share with us, and which have not been covered in the questionnaire, please write your comments below!" In addition, an open-ended question suitable for the specific time point was generally asked, covering areas such as: expectations of the nursing profession; experience of a) incongruity or agreement between the theoretical and practical part of the study programme; b) the introduction to establishing a professional nursing role in working life, c) factors important for the transition from education to practice, d) significant events related to nursing work.Background variables, employee status, and items concerning life events and intention to leave the nursing profession will be analysed in the present paper.th and final semester in the autumn of 2002, 2004, and 2006, respectively. Point estimates as well as confidence intervals for these data in the three cohorts were computed and compared with population values. As these data from the national registers are not available to the research group, these comparisons were performed by Statistics Sweden.Cohort representativeness was evaluated using data from population-based national registers. Demographic characteristics of the total population of nursing students and the ones who consented to participate were compared. From the national register population, values of age, gender, country of birth, residency (large city), marital status, and parenthood, were defined for nursing students in their 6A longitudinal analysis of response rate was performed (where response or non-response was measured at every follow-up assessment). Because so few data collections have been conducted on the EX2006 cohort up to this point, analyses were only performed on the EX2002 and EX2004 cohorts. Factors influencing participants' response rates across time were evaluated using self-reported data from the baseline questionnaires as predictors of participation. Age, gender, country of birth, civil status (cohabiting or not), as well as self-rated health were used as time-invariant predictors of the longitudinal change in participation rates. Data were analysed using a regression procedure referred to as 'longitudinal logistic regression' , 'marginBoth the robust and the model-based estimators were tried in combination with different structures of the working correlation matrix . Furthermore, of the 4316 that consented to participate, 10 (0.2%) did not subsequently complete the questionnaire at baseline. Response rates across the three cohorts varied between 68 and 73%, giving the highest response rate in the cohort recruited earlier in their education. Administrative data for eligible students from the sampling frame and consenting students are presented in Table Cohort representativeness was further evaluated by comparing point estimates as well as confidence intervals for consenting nursing students in their sixth and final semester in the autumn of 2002, 2004, and 2006 against national register population values on six different demographic variables among all nursing students registered for the sixth semester in those particular years . Table 004. TablThe response rates in all three cohorts one year after graduation , are presented in Table Data on nursing qualifications and employment one year after graduation are also presented in Table Percentages of nurses intending to leave the profession one year after graduation are presented across the three cohorts in Table Data collections for the EX2002 cohort were completed in 2008, more than five years after the former students had graduated. In this cohort the actual response rate varied between 81% and 92% across five years (c.f. 69% to 92% in EX2004). Only 38 respondents dropped out after the baseline assessment. Data reflecting retention and common life transitions across the years after graduation will be briefly summarized for this cohort below. Five years after graduation, at least 97% of all participants in the EX2002 cohort had worked as registered nurses at some time point. At this time, only a few persons had not completed their bachelor's degree. Moreover, every fifth nurse in the EX2002 cohort had returned to further higher educational training, and had graduated as a midwife, or gained a graduate diploma in specialist nursing. In addition, at least 2% of the participants in the EX2002 cohort had left the nursing profession. There are other common life events parallel to graduation and entering working life that are known to affect health. For example, data from the EX2002 cohort reveal that study participants give birth to approximately 100 babies each year up to three years after graduation. In addition, about 110 new marriages and 50 to 75 divorces were reported each year up to three years after graduation. Furthermore, 0.6% of the EX2002 cohort report a period of unemployment at some time during their first three years of working life.In the ongoing LANE study, a 70% response rate was found at baseline, when the three cohorts were established. Subsequent actual participant rates across data collection waves were high, ranging between 69% and 92%. In the sixth semester the three cohorts were found to be representative of the populations, as point estimates of sociodemographic data were close to population data, only differing about 0-3% from population values. Response rates were found to decline somewhat across time (11% units in EX2002 and 23% units in EX2004), and this decrease was present in all analysed subgroups. Importantly, self-rated health was not associated with attrition. The most consistent demographic variables showing any influence on recruitment and response rates were gender  and country of birth (non-Swedish-born being either underrepresented in two cohorts by 2 to 3% units or showing declining response rates across time).During the first year after graduation nearly all participants had qualified as nurses and had later also held a nursing position. The most common reason for not working was due to maternity leave. In the EX2002 and EX2004 cohorts about 10% intended to leave the profession one year after graduation, and in the EX2006 cohort the figure was almost twice as high. In all cohorts, intention to leave the profession was more common among young nurses. In EX2006, twice as many nurses reported having taken active measures to seek positions outside the profession as compared with the other two cohorts. In the first cohort (EX2002) nearly every fifth registered nurse moved on to further higher educational training within the health professions, e.g. midwifery or specialist nursing of some kind. Furthermore in this cohort, about 2% of the participants had left the nursing profession five years after graduating.The high rates of graduates in the LANE study that receive their nursing qualification, and eventually also hold a nursing position, reflect current trends in Sweden. In the first place, the dropout rate from nursing programmes is generally lower than from other undergraduate programmes in Sweden , and betThe high rate of new graduates that had held a nursing position at some point since graduation, as well as the fact that the main reason for not working one year after graduation was maternity leave, was in accordance with national statistics on entrance to the labour market . Data frDue to the increased number of students that have been accepted for undergraduate nursing programmes, there is currently a balance in supply and demand of nurses in Sweden. However, the present stability in the registered nursing workforce may change and turn into a shortage if issues regarding working conditions and intention to leave the profession are not addressed -64. In bInitially the LANE study comprised two cohorts, i.e. EX2002 and EX2004, in order to disclose potential cohort effects on the results. The basis for choosing year 2002 for initiation of the study was twofold. First, there was an urgent need to start the investigation in 2002 due to the increasing frequency of stress ,26 and lThe time frame selected in the LANE study for investigation of common career pathways, life transitions and change in psychological health, covers a period from studies to practice. This is a strength when evaluating the possible influence of educational, working and individual factors on health development and the retention of graduates in the profession. The number of time points in each cohort was chosen to maximize coverage before and after the adjustment and transitional process from student to graduate nurse. Described from a transitional perspective, our assessments were made at both ends of the transition to professional practice, i.e., before and after "the confusing nowhere of in-betweenness", where change is inevitable and the individual will need to develop approaches for dealing with it in one way or another . The traThe LANE study resembles other concurrent cohort studies on new graduates' transition to practice, such as the Australian e-cohort study (including 540 nursing students) , in thatWhen data collection and analyses are complete, the LANE study will add unique knowledge, since surprisingly few studies have actually collected information both during education and after entering nursing practice ,72,7. DuEven if the wave response rates are generally high, they decrease over time. The possible selection bias introduced by this phenomenon must be carefully scrutinized in relation to each particular research question. Specifically, we will compare and contrast attrition due to leaving the profession, embarking on specialist training or being on maternity leave. Although our findings were not constant over the three cohorts, the analyses in this paper generally indicated that gender and country of birth influenced participation and retention. Firstly, the lower male participation (2% units) in the EX2006 cohort, as compared with the population is a phenomenon that has been reported earlier in similar studies. For instance, in the European NEXT (Nurses' Early Exit) study, there was a smaller proportion of men in the study sample, as compared with the percentage in the national workforce, in eight out of eleven countries . SimilarThe number of immigrants consenting to participate in the EX2002 (6%) and the EX2006 (9%) cohorts was an underrepresentation as compared with the wider population (9% and 11% respectively). In this study, language difficulties cannot be ruled out as a reason for immigrant non-participation; however, this seems to be a less probable cause, since all participants were recruited from higher education. It is difficult to know whether cultural differences can explain the fact that immigrants were less likely to consent to participate, and whether respondents were more integrated into Swedish society than non-participants. In the EX2004 cohort, on the other hand, where the non-Swedish-born subgroup had lower response rates across time, this may be related to higher mobility and a tendency to move out of the country.When understanding and interpreting different outcome areas in the LANE study, it is important to remember that the population of students at two sites of learning could not be defined prior to the study, and that students from these universities had to personally take the initiative to become part of the sampling frame. Although this selection may not be a major problem (at least not for the EX2002 cohort), exclusion of the consenting students from these two universities will be optional when comparing educational outcomes across universities with regard to data from the EX2002 and EX2004 cohorts. This reservation does not concern the EX2006 cohort, where the total population of students attending the last semester of the nursing programme in the autumn of 2006 could be defined in advance and included in the sampling frame. This limitation will be controlled for when contrasting educational data among the universities.The main weakness of the study is that data are only collected through self-reports; thus, health data are not clinically validated. However, when data collection closes in 2010, additional data from national registers available for research will be used to form parallel cohorts; data on graduation, employment, maternity leave and sick leave will then be extracted and compared with LANE data.The LANE study will provide a unique opportunity to answer a variety of research questions about the transitional development of health and issues in early professional development. The establishment of longitudinal cohorts with high response rates and low attrition over time is necessary in order to estimate prevalence, incidence and factors associated with career pathways, life transitions during the first years of working life, as well as development of depression, burnout, subjective well-being and job engagement in the transition between undergraduate studies and practice.The use of multiple cohorts is one of the strengths of the LANE study, and this is important in order to disentangle possible cohort and period effects from the developmental trends that are one main focus. An additional strength is that all three cohorts comprise students from all 26 universities offering undergraduate nursing programmes within the higher education system in Sweden. Also, the relatively high response rate when the cohorts were formed, as well as subsequent high response rates and data suggesting high professional retention, imply a potential for a thorough analysis of professional practice and occupational health.The authors declare that they have no competing interests.AR contributed to the design of the study, participated in the acquisition and analysis of data, and drafted the manuscript. MOP contributed to the design of the study, participated in the acquisition of data, and in revising the manuscript. LW contributed to the design of the study, and participated in revising the manuscript. PG contributed to the design of the study, analysed the data and drafted an original version of this manuscript. All authors have read and approved the final manuscript.