Hounton et al.: Towards elimination of maternal deaths: maternal deaths surveillance and response. Reproductive Health 2013 10:1.

Publication date: 2013

REVIEW e y J rec os co m n t na m rm s m of an accountability framework that in countries is based on national oversight, accurate and comprehensive moni- surveillance, and considers the pre-requisites for wide- spread implementation. Hounton et al. Reproductive Health 2013, 10:1 http://www.reproductive-health-journal.com/content/10/1/1 an elimination strategy. The term elimination in this pa- per refers to a significantly lowered level to the point at 1UNFPA Technical Division, New York, USA Full list of author information is available at the end of the article toring of results, regular multi-stakeholder review of data and responses, all key features of traditional surveillance and response systems. Significant reduction of maternal mortality in countries will require counting every case and collection of information to permit an effective re- sponse that prevents future deaths [3]. Thus a maternal Eliminating maternal mortality The vision ‘no woman should lose her life when giving birth’ reflects the human rights perspective on maternal mortality and would require that 90% of maternal deaths (when diagnosed and treated in a timely manner) [5], be avoided, making maternal mortality a potential target for * Correspondence: hounton@unfpa.org Introduction Of all Millennium Development Goals (MDGs), impro- ving maternal health (MDG 5) is the least likely to be achieved. Despite knowledge on determinants and cau- ses, and effective clinical and public health strategies [1], the goal of reducing, the maternal mortality ratio (MMR) between 1990 and 2015 by three quarters is unlikely to be met. More than ever before, maternal and newborn health has received heightened attention from the United Nations, governments, non-governmental organizations, and civil society [2]. The Commission on Information and Accountability of the Global Strategy for Women’s and Children’s Health recommended the implementation death surveillance and response (MDSR) Technical Wor- king Group (TWG) has been established and chaired by the World Health Organization. The overall objectives of the MDSR are: 1) To provide information that effectively guides actions to eliminate preventable maternal morta- lity at health facilities and in the community; and 2) To count every maternal death, permitting an assessment of the true magnitude of maternal mortality and the impact of actions taken to reduce it [4]. The upcoming technical guidance of MDSR by the World Health Organization will provide comprehensive concepts of MDSR. This pa- per describes why MDSR is needed and what would be entailed, builds on lessons from communicable disease Towards elimination of m deaths surveillance and r Sennen Hounton1*, Luc De Bernis1, Julia Hussein2, Wend and Elizabeth M Mason5 Abstract Current methods for estimating maternal mortality lack p the short run. In addition, national maternal mortality rati where the greatest burden of mortality is located, who is what sub-national variations occur. This paper discusses a MDSR systems are not yet established in most countries a accountability and can build on existing efforts to conduc confidential enquiries. Accountability at national and sub- retrospective estimates periodically generated from acade counting, investigation, sub national data analysis, long te information systems. Establishing effective maternal death improve quality of maternity care and eliminate maternal © 2013 Hounton et al.; licensee BioMed Centr Commons Attribution License (http://creativec reproduction in any medium, provided the or ision, and are not suitable for monitoring progress in (MMRs) alone do not provide useful information on ncerned, what are the causes, and more importantly aternal death surveillance and response (MDSR) system. d have potential added value for policy making and maternal death reviews, verbal autopsies and tional levels cannot rely on global, regional and national ia or United Nations organizations but on routine investments in vital registration and national health urveillance and response will help achieve MDG 5, ortality (MMR ≤ 30 per 100,000 by 2030). Open Access aternal deaths: maternal sponse Graham2, Isabella Danel3, Peter Byass4 al Ltd. This is an Open Access article distributed under the terms of the Creative ommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and iginal work is properly cited. Hounton et al. Reproductive Health 2013, 10:1 Page 2 of 8 http://www.reproductive-health-journal.com/content/10/1/1 which maternal mortality ceases to be a major public health burden in countries (for example a goal of a MMR ≤ 30 per 100,000 by 2030 [5] although other tar- get dates such as 2035 or much closer 2025 are being considered). Although pregnancy is not a disease and maternal death is non-communicable, the good and bad outcomes (births, deaths, complications for mothers and newborns and subsequent disabilities) are all relevant to public health. All issues carrying the burdens of mortality and morbidity warrant public health surveillance systems, and although most have been established for communi- cable diseases, similar principles could be applied to ma- ternal events [6-8]. Paradigm shift: why MDSR and what is its added value? Rationale for MDSR Tracking progress on maternal mortality ratios or rates is notoriously difficult given the lack of reliable vital registration in developing countries and problems in the ascertainment of pregnancy status especially in its early stages. Current national MMR estimates are generated by United Nations agencies and academia despite the ab- sence of civil vital registration and the difficulties in capturing maternal deaths [9-11]. These estimates use aggregated national figures, which lack precision; are not timely, referring to the past; and are often not readily available in formats like simple maps or trend diagrams. Current methods in many developing countries use large- scale periodic surveys (national censuses, Demographic and Health Surveys, Multiple Indicator Cluster Surveys, etc.), which are expensive and data are retrospective and not released in a timely manner. These estimates carry wide confidence intervals and often provide no clues for action. Such estimates are often disputed by countries, and not acted upon. Efforts to generate national estimates have usually ignored the equity dimension of maternal mortality within countries, mainly because of large sample size errors that are associated with survey methodologies for relatively rare events [12]. MDSR would assist in com- puting national, country-owned maternal mortality data, as well as provide more reliable MMR at sub national le- vels, thereby showing where the greatest burden of mor- tality is located, who is concerned and what the causes are. MDSR can inform the actions needed to prevent ma- ternal deaths both in the community and in health facil- ities. MDSR can improve the quality of care provided to pregnant women by identifying gaps in health services that contributed to a maternal death. Data are needed to enable short term progress track- ing, intervention evaluation, timely actions and increased accountability of civil society, policy makers, managers and donors at national and sub-national levels. These data must be locally relevant, ‘fit for purpose’, inform an immediate response system and be presented in simple table and graphic formats with stories that are powerful and which catalyze action – hence creating accountability. This, together with improvements in health information systems, requires a paradigm shift in counting and responding to maternal deaths instead of solely providing numerical estimates. Added value of MDSR Public health surveillance involves continuous interpre- tation of data, essential for the planning, implementation and evaluation of public health practice [13,14]. Surveil- lance in principle can be either passive or active. Passive surveillance relies on routine reporting, is simple and is minimally burdensome to health care providers, but no- tification is usually not timely or complete enough to be useful. Active surveillance involves targeted searching for cases, and provides more timely and less variable data, which is clearly needed for maternal deaths. The immediate added value of active surveillance of maternal deaths would include timely notification of events, assessment and confirmation of cases, increased awareness and advocacy, and most importantly account- ability for health services, policy makers, managers and civil society for monitoring progress. The term ‘surveil- lance’ is not new and has been used with reference to maternal health to address maternal death reviews, audits, confidential enquiries, or at demographic surveillance sites [15-17]. However, converting surveillance systems and responses originally developed for communicable and non-communicable diseases for the purpose of elimina- ting maternal mortality has only recently been adopted as a framework with guidelines for implementation being developed. Not only is MDSR required for ac- countability, but a clear pre and post-MDG agenda to- wards eliminating maternal mortality is also needed such as a proposed goal of MMR ≤ 30 per 100,000 by 2030 [5]. What would MDSR entail? Pre-requisites for MDSR First and foremost MDSR requires a mandatory notifica- tion of maternal deaths. Steps towards such mandatory notification have taken place in several regions. The Inte- grated Disease Surveillance and Response (IDSR) guide- lines have been updated to include maternal deaths. Several sub Saharan African, Asian and Latin American countries (such as South Africa and Tamil Nadu state in India) have adopted mandatory notification of maternal deaths in the first 48 hours, although full implementation in the context of MDSR is yet to be achieved even in these relatively well developed systems. Second, for epidemic diseases control, most countries have a national management committee for epidemic and outbreak control: The national management committees are typically headed by a high-level Ministry of Health official with convening power, and includes stakeholders from civil society, community leaders, parliamentarians, security, news and media, finance and education, adminis- tration, the donor community, international and national NGOs and UN partners. As described in the recommen- dations of the Commission on Information and Account- ability [2], this type of national oversight mechanism for maternal, newborn and child health will recommend re- medial actions as required. The terms of reference of the national management committee include the development and validation of surveillance and response strategies, co- ordination of all partners’ contributions and actions, mon- itoring and evaluating responses. This multi-sector, data driven and action oriented model of national oversight has been missing in most maternal mortality committees. but one which integrates with existing mechanisms of reporting at country level. Second, provide case definitions (Table 2): This is a cornerstone of any surveillance system and although maternal mortality is not a communicable disease the rationale for case definition remains the same. A case definition needs to be simple and sensitive enough to avoid missing cases and should specify criteria for confirmation of cases. Third, develop data collection mechanisms and instruments. Figure 2 illustrates a sample data collection mecha- nism (to be adapted based on each country context). Data collection instruments at community level need to be very simple with few data requirements, for example, name of deceased, residence (village, districts, sub na- tional geographic area relevant to the country), time (date of death), place (death in health facility or not), and pregnancy status. Confirmation of the maternal e o R aly pre SR Hounton et al. Reproductive Health 2013, 10:1 Page 3 of 8 http://www.reproductive-health-journal.com/content/10/1/1 Establish th of the MDS Evaluate the MDSR system Develop dissemination mechanism s (incl. civil society) An and inter the MD Respond (use MDSR data to develop actions to prevent future deaths) Establishing a MDSR system Figure 1 describes classic steps in surveillance and res- ponse system (Figure 1) [14]. First, define the goals of the system, which is the elimination of maternal mortality. More specifically the system will confirm individual cases, identify causes and underlying factors, monitor levels and trends in maternal deaths and develop standard operating procedures (SOPs) and performance indicators for the system (Table 1). MDSR will define the guidelines, tools, mechanisms and indicators for its implementation. MDSR will build on existing surveillance and other information systems at country level. It is critical not to create a parallel system, Figure 1 Steps in Planning Maternal Deaths Surveillance and Response death could be challenging and additional tools will in- clude verbal autopsy, medical files and maternal death review tools. M Gregg [15] suggested the need to ‘re- member surveillance is a fluid process – as populations or health problems change. . .we need to overcome the real tendency to wait or postpone starting a surveillance system until everything is scientifically perfect’. In com- municable disease surveillance, data are usually genera- ted from health facilities from the lowest level of the health system to the central level. The MDSR should use the existing facility level notification and reporting sys- tems as well as community health workers from each health facility catchment areas for timely notification bjectives system Identify maternal deaths based on WHO case definitions Investigate causes and circumstances of deaths (maternal death reviews) sis tation of data Collect data (mechanisms and tools in facilities & Community) (MDSR) System (Adapted from Teutsch SM [14] and Gregg M [15]. Table 1 Sample performance indicators of a MDSR system* Indicators Targets Overall system indicators Maternal death is a notifiable event Yes National maternal death review committee exists Yes - that meets regularly At least quarterly National maternal mortality report published annually Yes % of districts with maternal death review committees 100% % of districts with someone responsible for MDSR 100% Identification and notification Health facility: All maternal deaths are notified Yes % within 24 hours >90% Community: % of communities with ‘zero reporting’ monthly 100% % of community maternal deaths notified within 48 hours >80% District % of expected maternal deaths that are notified >90% Review Health facility % of hospitals with a review committee 100% % of health facility maternal deaths reviewed 100% % of reviews that include recommendations 100% Community % of verbal autopsies conducted for suspected maternal deaths >90% % of notified maternal deaths that are reviewed by district >90% District District maternal mortality review committee exists Yes - and meets regularly to review facility and community deaths At least quarterly % of reviews that included community participation and feedback 100% Data Quality Indicators Cross-check of data from facility and community on same maternal death 5% of deaths cross-checked Sample of WRA deaths checked to ensure they are correctly identified as not maternal 1% of WRA rechecked Response Facility % of committee recommendations that are implemented >80% - quality of care recommendations >80% - other recommendations >80% District % of committee recommendations that are implemented >80% Reports National committee produces annual report Yes District committee produces annual report Yes - and discusses with key stakeholders including communities Yes Hounton et al. Reproductive Health 2013, 10:1 Page 4 of 8 http://www.reproductive-health-journal.com/content/10/1/1 and reporting of cases at the community level. There may be a need to improve identification of relevant deaths by introducing a systematic means of recording pregnancy status in women, including teenagers, in any hospital service, rather than confining data collection to maternity units [18]. The use of community health workers and the required timeliness of the maternal Organization seminal publication ‘Beyond the numbers’ [19]. The investigation is done by analysing cases of death and identifying clinical, community and health systems factors which have to be addressed to avoid sub- sequent deaths most importantly, at local (community and facility) level and also at regional and national levels [19,20]. The UK confidential enquiry into maternal Table 1 Sample performance indicators of a MDSR system* (Continued) Impact Quality of care (requires specific indicators, such as case fatality rates) District maternal mortality ratio Reduced by 10% annually Hospital maternal mortality ratio/lethality rates Reduced by 10% annually *To be adapted to each country context. ear po e gn Hounton et al. Reproductive Health 2013, 10:1 Page 5 of 8 http://www.reproductive-health-journal.com/content/10/1/1 death notification will likely involve the use of mobile technologies. Fourth, investigate through maternal death reviews, verbal autopsies and confidential enquiries. In a communicable disease surveillance, investigations aim to improve speed (to reduce the toll on mortality and morbidity), and certainty (by establishing determi- nants and confirming the cause) of causal mechanisms including the agent. In maternal and newborn health, speed is not paramount as there is no contagion, but the confirmation of the maternal death, the determination of causes, determinants and how to prevent future cases remain essential and has to be done in a reasonable time frame. The investigation function is fulfilled by verbal autopsies at community level, maternal death reviews at facility level, and including confidential enquiries into maternal deaths within national mechanisms [19]. The overall goal is to ascertain causes of adverse outcomes of pregnancies and to contribute to improvements in quality of care as summarized in the World Health Table 2 Maternal death case definitions Cases Definitions Death of a woman of reproductive age (WRA): Death of woman in reproductive y reference period years given the im should be investigated to determin pregnancy. Suspected case The death of any woman while pre where there is a suggestion of a preg the concept of ‘42 days’ may not be w ensure that all maternal deaths are ca Probable case All deaths of women while pregnant that are easily determined to be caus Confirmed case Probable case with ascertainment of c or probabilistic modelling of verbal au 42 days of pregnancy ending, irrespec to or aggravated by the pregnancy o Late maternal death Death of a woman from direct or ind termination of pregnancy *Confirmation of a maternal death is sometimes challenging, particularly for indirect dea deaths (CEMD) is one of the oldest systems which has been in place for over 50 years, and has been mooted as one of the reasons behind the UK’s success in reducing maternal mortality [16]. A number of other middle in- come countries, including Malaysia, Sri Lanka, South Africa, Jamaica and Egypt have successfully used confi- dential enquiries for several years and demonstrated co- incident reductions in maternal mortality [21-23]. The US CDC confidential enquiry system has looked to ans- wer specific questions like racial disparities [17]. In most of these countries, relatively reliable death registration systems are available, which have enabled identification of maternal deaths. In other developing countries, inves- tigation into maternal mortality has also been used, for example in The Gambia [24], in Malawi [25], and some- times referred to surveillance, such as in India [26]. The lack of a vital registration system will hamper efforts to identify maternal deaths. In countries with poor vital registration systems, maternal death reviews are used primarily at health facilities, but this may result in biases s, usually 15–49 years (although some countries may decide to use other rtance of teenage pregnancy and early marriage). All death of WRA whether the woman was pregnant or within 42 days of the end of a ant or within 42 days of the termination of pregnancy including deaths nancy even though it may not have been confirmed. In places where ell understood the time period can be extended to 2–3 months to ptured or within 42 days of the termination of pregnancy exception of those ed by incidental or accidental causes (e.g. motor vehicle accidents) ause of death (either using physician ascertainment of medical records topsy) and is defined by a death of a woman while pregnant or within tive of the duration and site of the pregnancy, from any cause related r its management, but not from accidental or incidental causes* irect obstetric causes more than 42 days but less than one year after ths. Final confirmation is generally done by a maternal mortality review committee. Hounton et al. Reproductive Health 2013, 10:1 Page 6 of 8 http://www.reproductive-health-journal.com/content/10/1/1 NOTIFICATION Health District Team (Health Information Staff) YES NOT SURE DEFINITELY NO Regional Health Team (Health Information Staff) VERBAL AUTOPSY DISTRICT MATERNAL DEATHS REVIEW TEAM STOP NO NOTIFICATION Suspect case (see Box 1 case definitions) Probable case of maternal death? (see Box 1 case definitions) Community Health Workers due to mortality outside health facilities, incomplete data retrieval, especially if registers are not well kept, case notes missing or misplaced and independent sources of verification of death not available. Setting up MDSR will benefit the identification of maternal deaths and there- fore provide an enabling environment for establishing solid denominators through birth and death registration systems and thus for maternal death reviews and confi- dential enquiries into all maternal deaths. The commit- tees will determine the factors that contributed to the maternal death and make recommendations to prevent similar deaths in the future. Fifth, analyse and interpret data. Data analysis and interpretation include a simple line listing, descriptive statistics (people, place and time of maternal deaths) as well as case reviews. Confirmation of cases is essential and will be done for deaths in faci- lities (using patients’ records) as well as in communities (using verbal autopsy data). The required timeliness of the MDSR is likely to involve probabilistic models of verbal autopsy (www.interva.net) [27-29], instead of traditional reliance on physicians to assign cause of death on the NATIONAL HEALTH INFORMATION SYSTEM NATIONAL MATERNAL DEATHS REVIEW COMMITTEE NATIONAL MANAGEMENT / RESPONSE COMMITTEE WEEKLY/MONTHLY DISSEMINATION (AS APPLICABLE) Figure 2 Sample flow diagram or decision tree for national MDSR system (to be adapted based on each country context). basis of VA data (difficult in most remote settings in high maternal mortality countries given scarcity of physi- cians and transaction costs of finding a third physician evaluation when the first two disagree on causes of death). Sixth, develop dissemination mechanisms. The availability of data is likely to change the dynamics of advocacy, resources mobilization, accountability, and effectiveness for preventing maternal mortality at national and sub-national levels. Having weekly/monthly/quarterly maternal death trends reported on a regular basis in a prominent national newspaper is a powerful instrument to move the agenda of maternal mortality reduction forward by mobilizing policy makers, but also to improve accoun- tability of governments, communities and professionals (Figure 3). The current existing mechanisms of briefing of high level decision makers should be used to update and engage on numbers of cases, place of occurrence, and causes. An important dimension whilst developing MDSR is related to communication. It is paramount to plan for communication before the system is established, the communication of results, the management of crisis (unintended consequences such as rebuttal, denial or denigration for political reasons) and communication for advocacy and resource mobilization. Seventh, respond by using the MDSR data to imple- ment preventive actions. This is the most important step, and given the mul- tiplicity of priorities media and governments are often more responsive to catastrophic and tangible news. Al- though communities, professionals and governments may agree that levels of maternal mortality are unacceptable, they may not have data that spur timely and routine ac- tion, or engage the community. Having regular (monthly, quarterly) figures on maternal deaths at facility or district levels and at national level, reviewed by the district level and national management committee for maternal health can prompt countries to set-up an alert system (Figure 3). This regular information should prompt responsiveness, accountability by comparison across years and areas, and between countries in a region of the world. This real-time data can prompt questions about the need for changes, why a community or health facility cannot do better, what the underlying causes are, or whether effective measures have been put in place and evaluated. Among other key issues, MDSR can identify critical gaps in the quality of care provided to pregnant and post-partum women that must be addressed to prevent maternal death. This is the necessary investment to make maternal mortality elimination a national agenda. Eighth, evaluate the MDSR system. Given the resources required to set-up and run MDSR, countries should start with basic features, building on existing health information systems. The system will need Hounton et al. Reproductive Health 2013, 10:1 Page 7 of 8 http://www.reproductive-health-journal.com/content/10/1/1 to be improved subsequently to increase efficiency, and evaluation will identify areas for improvement. In practice, following the classic framework of an evaluation of disease surveillance system is possible. The table below presents sample indicators and performance criteria for the MDSR system and could be adapted to each context. It could include keys steps such as a review of engagement of stakeholders to ensure buy-in and support, the description and review of the operation, attributes (simplicity, flexibi- lity, acceptability, sensitivity, specificity, predictive positive value, representativeness, timeliness), costs, the design of evaluation to be used, and description of data collection, data analysis, report writing, and follow-up of recommen- dations. The results of the evaluation will be examined by Source: Cambodia Maternal Mortality Surveillance (Courtesy of UNFPA country office in Cambodia) Trends of maternal deaths in three provinces in 0 1 2 3 4 5 6 Jan Feb Mar Apr May JuN um be r o f m at er n al d ea th s Year Figure 3 Sample mapping and trends of maternal deaths in Cambod the national oversight committee for maternal and new- born health and appropriate actions will be identified and implemented to improve the surveillance system. Conclusion Presentation, format and accuracy of data are critical for mobilising communities and stakeholders and ensuring accountability for reducing maternal deaths. One of the shortcomings of current maternal mortality estimates is the lack of precision, resulting in presentation of point estimates with large confidence intervals. These estimates are often misinterpreted in comparisons of point estimates of maternal mortality ratios with no reference to confi- dence intervals. Maternal mortality surveillance and Room, 2010 Cambodia, 2010 n Jul Aug Sep Oct Nov Dec 2010 Battambang Kampong Thom Takeo Khmer Soviet: 05 Chalmette: 09 MCH: 13 Phnom Penh: 01 ia, 2010. 8. Anya SE: Seasonal variation in the risk and causes of maternal death in Hounton et al. Reproductive Health 2013, 10:1 Page 8 of 8 http://www.reproductive-health-journal.com/content/10/1/1 response (MDSR) offers a way forward and will improve accurate identification, counting, and reporting of deaths in settings where vital registration systems have low cove- rage. Most importantly MDSR will improve current esti- mations of maternal mortality ratios, will provide data for action to improve quality of care and reduce maternal deaths. MDSR will enhance accountability mechanisms by providing information on whether policies and actions meant to reduce maternal mortality are effective. Having data at sub-national level for action and accountability will also provide better opportunities for equity-based inter- ventions. This paper presents the different components and steps for implementing MDSR. Countries are at vari- ous stages of health systems development and will imple- ment MDSR differently based on levels of mortality and health service factors. Regardless of the variations in coun- tries’ contexts, accountability requires a bold investment towards maternal mortality elimination with a pos- sible goal of an MMR ≤ 30 per 100,000 by 2030 [5]. Implementing and improving completeness of MDSR and establishing solid denominators through birth and death registration systems will be achieved over time, but a journey that does not get started can never be completed. Competing interests The authors declare that they have no competing interests. Authors’ contributions SH conceived and proposed the original draft. All authors designed, and participated in the writing and reviewing of the final manuscript. All authors read and approved the final manuscript. Acknowledgement The views expressed in this publication are solely those of the authors. Author details 1UNFPA Technical Division, New York, USA. 2Aberdeen University, Aberdeen, UK. 3US Centers for Disease Control and Prevention, Atlanta, USA. 4Umea University, Umea, Sweden. 5WHO, Geneva, Switzerland. Received: 5 October 2012 Accepted: 24 December 2012 Published: 2 January 2013 References 1. Ronsmans C, Graham WJ: Lancet Maternal Survival Series steering group: Maternal mortality: who, when, where, and why. Lancet 2006, 368(9542):1189–1200. 2. Commission on information and accountability for Women’s and Children’s Health. http://www.everywomaneverychild.org/images/content/files/ accountability_commission/final_report/Final_EN_Web.pdf. 3. Danel I, Graham WJ, Boerma T: Maternal death surveillance and response. 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Fottrell E, Kahn K, Tollman S, et al: Probabilistic Methods for Verbal Autopsy Interpretation: InterVA Robustness in Relation to Variations in A Priori Probabilities. PLoS One 2011, 6(11):e27200. 28. Fottrell E, Byass P, Ouedraogo TW, et al: Revealing the burden of maternal mortality: a probabilistic model for determining maternal causes of death from verbal autopsies. Popul Health Metr 2007, 8(5):1. 29. Byass P, Hounton S, Ouédraogo M, et al: Direct data capture using hand- held computers in rural Burkina Faso: experiences, benefits and lessons learnt. Trop Med Int Health 2008, 13(Suppl 1):25–30. doi:10.1186/1742-4755-10-1 Cite this article as: Hounton et al.: Towards elimination of maternal deaths: maternal deaths surveillance and response. Reproductive Health 2013 10:1. Abstract Introduction Eliminating maternal mortality Paradigm shift: why MDSR and what is its added value? Rationale for MDSR Added value of MDSR What would MDSR entail? Pre-requisites for MDSR Establishing a MDSR system Conclusion Competing interests Authors’ contributions Acknowledgement Author details References << /ASCII85EncodePages false /AllowTransparency false /AutoPositionEPSFiles true /AutoRotatePages /PageByPage /Binding /Left /CalGrayProfile (Dot Gain 20%) /CalRGBProfile (sRGB IEC61966-2.1) /CalCMYKProfile (U.S. Web Coated \050SWOP\051 v2) /sRGBProfile (sRGB IEC61966-2.1) /CannotEmbedFontPolicy /Error /CompatibilityLevel 1.4 /CompressObjects /Tags /CompressPages true /ConvertImagesToIndexed true /PassThroughJPEGImages true /CreateJobTicket false /DefaultRenderingIntent /Default /DetectBlends true /DetectCurves 0.0000 /ColorConversionStrategy /LeaveColorUnchanged /DoThumbnails true /EmbedAllFonts true /EmbedOpenType false /ParseICCProfilesInComments true /EmbedJobOptions true /DSCReportingLevel 0 /EmitDSCWarnings false /EndPage -1 /ImageMemory 1048576 /LockDistillerParams true /MaxSubsetPct 100 /Optimize true /OPM 1 /ParseDSCComments true 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deze instellingen om Adobe PDF-documenten te maken voor kwaliteitsafdrukken op desktopprinters en proofers. 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/ENU (Use these settings to create Adobe PDF documents for quality printing on desktop printers and proofers. 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