Cancer vaccines are a real application of the extensive knowledge of immunology to the field of oncology. Tumors are dynamic complex systems in which several entities, events, and conditions interact among them resulting in growth, invasion, and metastases. The immune system includes many cells and molecules that cooperatively act to protect the host organism from foreign agents. Interactions between the immune system and the tumor mass include a huge number of biological factors. Testing of some cancer vaccine features, such as the best conditions for vaccine administration or the identification of candidate antigenic stimuli, can be very difficult or even impossible only through experiments with biological models simply because a high number of variables need to be considered at the same time. This is where computational models, and, to this extent, immunoinformatics, can prove handy as they have shown to be able to reproduce enough biological complexity to be of use in suggesting new experiments. Indeed, computational models can be used in addition to biological models. We now experience that biologists and medical doctors are progressively convinced that modeling can be of great help in understanding experimental results and planning new experiments. This will boost this research in the future. Vaccines for cancer represent an alternative approach to the use of standard drugs. Differently from the traditional vaccines that prevent disease instructing the immune system on how to recognize and destroy a particular pathogen, cancer vaccines enlist the patient's immune system to destroy existing cancer cells. While simple in concept, the development of products has proven difficult. Problems specifically lie in eliciting sufficient, tumor-selective stimulation of an immune system that is already tolerant of cancer cells , 2.Revolutions in biotechnology and information technology have produced enormous amounts of data and are accelerating the extension of our knowledge of biological systems. These advances are changing the way biomedical research, development, and applications are done. Clinical data complement biological data, enabling detailed descriptions of various healthy and diseased states, progression, and responses to therapies. The availability of data representing various biological states, processes, and their time dependencies enable the study of biological systems at various levels of organization, from molecule to organism, and even population levels. Specific systems biology models, that is, applications of computer and mathematical models that enable the simulation of biological processes, can be used to investigate the physiology and pathology of the immune responses involved in vaccination and immunotherapy. This involves applications of computational simulations to the discovery, design, and optimization of vaccines and other immunotherapies. The term immunotherapies usually refers to the treatment of established disease while the term vaccine is restricted to prophylactic immune interventions. We will use “vaccines” to refer to generic immune intervention and will use terms “therapeutic vaccines” and “prophylactic vaccines” to distinguish between the two modalities. Vaccine design is amenable to the application of modeling techniques, for both the discovery and development of new and existing vaccines. In what follows, we first deal with a brief overview of different types of existing cancer vaccines; we then focus on modeling cancer vaccines and finally we draw our final remarks.The ultimate aim of a vaccine is to activate a component of the immune system such as B lymphocytes, which produce antibodies or T lymphocytes, which directly kill tumor cells. Antibodies must recognize antigens in the native protein state on the cell's surface. Once bound, antibodies are capable of destroying tumor cells by means of antibody-dependent cellular cytotoxicity or complement-mediated cytotoxicity. T lymphocytes recognize proteins as major histocompatibility complex complexed with peptides that can vary in size, presented on the surface of the cells recognized. Recent research  demonstrThe use of cytotoxic T cells (CTLs), dendritic cells (DC), and antibodies, actually represent well-known approaches in cancer immunotherapy .The use of anti-idiotype (Id) antibodies as vaccines to stimulate immune system response against tumors, have been demonstrated effective in preventing tumor growth and curing mice with established tumors . SeveralRecently it has been shown that prophylactic vaccines administered to transgenic mice prone to cancer development can completely prevent tumor onset and restore a normal life expectancy . Even thComputational models have been recognized as relevant for the understanding of biological systems. In particular, models are suitable for guiding biology from a qualitative to a quantitative, thus predictive, science. Pharmaceutical companies are starting to use models to optimize/predict therapeutic effects at the organism level, suggesting that computational biology can effectively play a key role in this field .Obviously to model the behavior of a cancer vaccine, one needs to model the immune system that is one of the most exciting challenges as it represents one of the most complex biological systems. It is, in fact, an adaptive learning system that operates at multiple levels . Immunological research, both basic and applied, needs to deal with this complexity.Computational immunologists increasingly use mathematical modeling and computer simulation to study the immune system and the immune responses to different pathogens . Thus, qOne of the first example in modeling a cancer vaccine is represented by the SimTriplex model. It is an agent-based model specifically tailored to simulate the effects of “Triplex” tumor-preventive cell vaccines in HER-2/neu transgenic mice prone to the development of mammary carcinoma , 12. TheSimTriplex includes a variety of cellular and molecular entities, including tumor and vaccine cells, B and plasma cells, helper and cytotoxic T cells, macrophages, dendritic cells, antigens, antibodies, and cytokines. The attributes of each cell entity include position, age, and state . Changes of state  are governed by a set of rules based on tumor immunology.Antigen-specific immune interactions (antibody or immunoglobulin/antigen (IG/Ag) and T cell receptor/peptide/MHC (TCR-pMHC)) are modeled with bit-strings (sequences of 0 s and 1 s). Hamming distances is used as a measure of affinity among receptors and co-receptors: the probability of an interaction depends on the number of matches.The simulation space is a two-dimensional triangular lattice (six neighbor sites) with periodic boundary conditions. Cells and molecules are free to move across the lattice sites. At each time step, representing 8 hours of real time, cells and molecules residing on the same lattice site can interact.To model the continuous carcinogenic process of HER-2/neu transgenic mice, new tumor cells appear in the lattice, and existing tumor cells replicate (and rarely die). The simulation stops if the total number of tumor cells exceeds a threshold, signifying the formation of a palpable tumor mass, or after a defined number of time steps, typically more than 1 year of real time.Probabilistic elements affect various starting variables  and interactions . The outcome of each run of the simulator, entailing the generation of a large number of pseudo-casual numbers, is taken to simulate the results of one mouse, thus reproducing experimental variability between individual mice. SimTriplex model coupled with optimization techniques  allowed to search for an optimal vaccination schedule to obtain the same efficacy of the Chronic protocol with a definitively reduced vaccine administrations. Simtriplex predictions has been verified in a in-vivo experiment (probably the first model results verified in vivo). Results show that in-silico predicted schedule does significantly reduce the tumors multiplicity on the ten mice mammary glands even if the vaccination efficacy for the first appearing of tumor was still overestimated. Further adjustment of the model is required to include evidence of immune aging which appeared from in vivo follow up results , 14.The Triplex vaccine proved to be effective also as a therapeutic vaccine, showing its ability to be used against induced lung metastases . BrieflyThe administration of the vaccine started one day after the intravenous injection of the metastatic cells and it is repeated twice weekly up to the end of the experiment (day 32), with lower but good prevention rates when the same cycle is started 7 days after the induction of the metastases (Triplex+7 protocol). The immunological responses in the immunoprevention and therapeutic experiments overlap only partially. A major goal of biologists is to better understand the biological behavior to improve the efficacy of the therapeutic treatment and to try to predict, for example, the outcomes of longer experiments in order to move faster towards clinical phase I trials. In a recent work , we deveThe MetastaSim model has been inspired by the SimTriplex model. MetastaSim has in common with SimTriplex the same modeling framework , 18 and An exhaustive search for any optimal protocol has been performed. Results showed that it is possible to obtain in silico a reduction of approximately 45% in the number of vaccinations. Most of the protocols presented there share a similar vaccination strategy that is composed by a boost of three vaccine injections, a period of rest, and then a series of vaccine recalls that are somewhat equally spaced. The model suggests that any optimal protocol for preventing lung metastases formation should be therefore composed by an initial massive vaccine dosage followed by few vaccine recalls. Even if this is a well-known vaccination strategy in immunology, since it is commonly used for many infectious diseases such as tetanus and hepatitisB, it can be still considered a relevant result in the field of cancer-vaccines immunotherapy.Unfortunately, the efficacy of available therapeutic strategies for cancer still remain poor. Moreover, widely adopted approaches to cure or, at least, delay cancer development that is, chemotherapy and radiotherapy, both still carry major side effects for individual patients. In order to better understand therapies, experimentalists and clinicians are increasingly appreciating mathematical and computational modeling, and in recent years several papers appeared in the literature: they have begun to investigate the various aspects of the immune system response to cancer from a computational and mathematical perspective –21.Particularly, in , the autDuring the numerical simulation of the model, it has been discovered that adoptive immunotherapy protocols have the potential to promote tumor growth instead of inhibiting it. Conversely, active vaccination with tumor-antigen pulsed APCs was shown to be generally more effective.DNA vaccination has been widely explored to develop new, alternative, and efficient vaccines for cancer immunotherapy. They offer several paybacks such as specific targeting, use of multiple genes to enhance immunity, and reduced risk compared to conventional vaccines.Fast advances in molecular biology and immunoinformatics allow logical design methodologies. These technologies allow construction of DNA vaccines encoding selected tumor antigens together with molecules to direct and amplify the desired effector pathways, as well as highly targeted vaccines aimed at specific epitopes. Reliable predictions of immunogenic T cell epitope peptides are crucial for rational vaccine design and represent a key problem in immunoinformatics , 24. For example, the authors in  explore Moreover they present two applications, namely prediction of novel T cell epitopes and epitope enhancement by sequence modification, and combined rationale design with bioinformatics for creation of new synthetic mini-genes.It is well known that the immune system is characterized by high combinatorial complexity, especially due to its wide potential repertoire. Consequently, the analysis of immunological data needs the use of specialized computational tools. A new way to select vaccine targets and reduce the number of necessary experiments is based on the use of machine learning (ML) algorithms in combination with classical experimentation. As the development of ML algorithms requires standardized data sets that are measured in a consistent way , there is a gap between the immunology community and the ML community. To overcome this problem and filling the gap, the authors in  present Detection of minimal residual disease, diagnosis, characterization of the profile of immunotherapies, and immune response tracking represent hot topics in cancer research. Flow cytometry (FCM) is widely used in these areas of interest. Circumventing spurious positive events and recognizing uncommon cells subsets delineate the challenge in all these applications. To accomplish this is task, the use of multiple markers simultaneously in the analysis of FCM data will help a lot. This because the additional information provided often lends a hand to minimize the number of false positive and false negative events, hence improving both sensitivity and specificity. With the use of the above explained strategy by manual gating, it is possible to analyze at most two markers in a single dot plot, often applying a sequential scheme. The sequential strategy is difficult to assess, as it gets rid of events that fall outside preceding gates at each stage.Model-based analysis is a promising computational technique that works using information from all marker dimensions simultaneously and offers an alternative approach to flow analysis that can usefully complement manual gating in the design of optimal gating strategies. In , the autThe authors' approach to model-based analysis is based on the use of statistical mixture models. Statistical mixture models are very widely used in the presence of problems where objects depicted in several or many dimensions need to be clustered or classified. Therapeutic interventions that stimulate tumor-specific immunity still remain rare. An improved understanding of patient-specific dynamic interactions of immunity and tumor progression, combined with personalized application of immune therapeutics, would increase the efficacy of immunotherapy. In  the authβ), in combination with vaccine treatments. The proposed mathematical model follows the dynamics of the tumor size, TGF-β concentration, activated cytotoxic effector cells, and regulatory T cells. Using numerical simulations and stability analysis, they have studied several scenarios: a control case of no treatment, anti-TGF-β treatment, vaccine treatment, and combined anti-TGF-β vaccine treatments. The model was able to capture experimental results, and hence has the potential to be used in designing future experiments involving this approach to immunotherapy.Recently, Wilson and Levy  have invThe investigation of vaccines and therapeutic approaches against cancer from the mathematical and computational point of view is still a new field of research. It has been shown that several papers have begun to propose models that have been appreciated by both clinicians and experimentalists and have been proven to be of great use in improving anti-cancer approaches research. We expect that an extensive use of mathematical/computational modeling into clinical practice will stimulate the clinical research of new and alternative protocols for cancer treatments with immune interventions.The possibility of the use of personalized approaches into the clinical practice is probably still far to come. However, virtual patient simulations can produce expected responses to the therapy for different class of patients . This can help the clinicians in deciding the best clinical approach for the specific patient. Finally, a thought on the future directions of the modeling cancer vaccines topic. We believe that models should be integrated during the entire cycle of cancer vaccine development line. This means that if a model has been used in the first line of the development (for example in the definition of epitopes targets), it should be used later in the optimization of the schedule and finally in the human response to the specific vaccine or immunotherapy. Presently, to the best of our knowledge, there is no model that has been applied to the three critical phases of vaccine development.


The objective of this research is to generate quality of care indicators from systematic reviews to assess the appropriateness of obstetric care in hospitals.A search for systematic reviews about hospital obstetric interventions, conducted in The Cochrane Library, clinical evidence and practice guidelines, identified 303 reviews. We selected 48 high-quality evidence reviews, which resulted in strong clinical recommendations using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. The 255 remaining reviews were excluded, mainly due to a lack of strong evidence provided by the studies reviewed.A total of 18 indicators were formulated from these clinical recommendations, on antepartum care (8), care during delivery and postpartum (9), and incomplete miscarriage (1). Authors of the systematic reviews and specialists in obstetrics were consulted to refine the formulation of indicators.High-quality systematic reviews, whose conclusions clearly claim in favour or against an intervention, can be a source for generating quality indicators of delivery care. To make indicators coherent, the nuances of clinical practice should be considered. Any attempt made to evaluate the extent to which delivery care in hospitals is based on scientific evidence should take the generated indicators into account. Quality of care has been defined as the degree to which health services increase the likelihood of desired health outcomes for individuals and populations and are consistent with current professional knowledge. Scientide novo the evidence relevant to each case. The establishment of a priori clinical indicators to be used as performance measures might be more efficient for systematically assessing the degree to which scientific evidence is applied in clinical practice.Too little attention has been paid to the correlation between the availability of scientific evidence and clinical practice. A series of studies-7 faced Development of indicators based on professional consensus has a long history,9, whileIn the present study, we restricted the source of indicators of quality of care to systematic reviews (SR), based on the assumption that they provide the highest degree of reliability, are incIn summary, we generated a set of quality indicators of obstetric care related to childbirth, based on SRs, which could be applicable in different settings and circumstances.The first phase of our project consisted of a literature search and generation of a set of recommendations based on sound evidence, either in favour or against interventions in delivery care; the second phase consisted of developing and validating a set of indicators.Table A literature search was conducted in the Cochrane Database of Systematic Reviews , the Database of Abstracts of Reviews of Effects, and Clinical Evidence to identify SRs assessing obstetric interventions performed in a hospital setting. To retrieve supplementary relevant SR, we consulted the available CPG from the main obstetrical medical societies  and CPG of obstetric care from main guideline producers , and the New Zealand Guidelines Group).Two researchers (MA and DR) independently applied selection criteria to the identified SR: pharmacological or non-pharmacological interventions, under the responsibility of the clinical team and registered at the clinical record or any other database. In case of disagreement, the criterion from a third author (XB) was applied.Two researchers (MA and DR) independently appraised each SR and restricted the inclusion to SR that met all internal validity items established by the Scottish Intercollegiate Guidelines Network (SIGN), as asseFor each selected SR, we classified the outcomes by relevance . Two authors (MA and DR) independently rated the quality of evidence and assessed the strength of recommendations based on the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. ApplicaTwo authors (MA and DR) independently selected recommendations that were considered strong (either in favour or against the application of a given intervention) and based on high quality evidence, at least for the most critical outcomes. In case of disagreements, a third author (XB) was consulted.From the selected clinical recommendations, we proceeded to construct indicators, following an adaptation of the methods proposed by the American College of Cardiology/American Heart Association (ACC/AHA) and the We subsequently consulted two specialists in obstetrics (CF and AV) to assess our design interpretation of the indicators, and the relevance of the indicators in current practice. This was followed by an email consultation with the authors of the SR on which the indicators were based, asking to what extent they agreed with the formulation of the indicator . The comments received from the review authors or consultants led us to modify or redefine various indicators.FigureThe selected reviews consisted exclusively of Cochrane reviews. No SR was excluded based on their quality assessment. In the following stage, 28 SR were excluded for not providing a base for any strong recommendation (either in favour or against an intervention). Thus, we generated 20 clinical recommendations that were both strong and based on high-quality evidence.Approximately 75% of the authors of the selected SR responded to our request to review the indicator. Overall, they agreed on the indicator proposal, and their comments were used for further improvement of their definition and formulation.Following advice of the obstetric consultants, two indicators were removed: the proportion of women with singleton pregnancies at risk of preterm delivery to be treated with a combination of corticosteroids with thyrotropin-releasing hormone, and theThe 18 indicators eventually accepted are shown in Table Indicators are expressed in proportions and refer to process of care, while none refer to structure or outcome. To illustrate the process  to conste.g., a clinical guideline) and the necessity of providing personalized care to individuals who are different. In our opinion, only with such an approach can the evaluation of quality of care provided be made, taking the existing evidence and the characteristics and values of each patient simultaneously into account.At the end of the process, 18 quality indicators for the delivery of obstetric care in hospitals were identified. Illustrated in Table The 18 generated indicators represent a conservative sample of the available evidence, since the criteria of consistency, meaningfulness and applicability had priority. We do not expect them to be unique; however, we propose that they should be included in any quality assessment or performance measurement that is made relating to the delivery of care. Since they have been formulated while taking criteria of flexibility and feasibility into account, they could be applied in very different hospital obstetric settings.e.g., assessing that an episiotomy was not performed unless justified). Second, the identified indicators reflect only those aspects of care that are supported by adequate evidence, which do not necessarily cover all the desirable dimensions; however, the reviews represented in the Cochrane Pregnancy and Childbirth Group encompass the most used interventions in the field. Therefore, the results of the present study are very specific  but probably less sensitive (some indicators could be lacking due to the aforementioned limitations) in relation to all possible cases. Third, the rigour applied in our methodology for defining indicators, necessary to guarantee its internal validity, might limit its external validity or applicability in clinical practice. Strictly defining the target population might reduce its applicability, leaving out large groups of people for whom an indicator is not suitable. Finally, calculation of detailed indicators in daily practice might involve the need for accurate information systems and is quite sensitive to the quality of clinical data registration. If clinicians know in advance the criteria applied for calculating quality indicators, they will likely be more aware of the actions that must be considered in each clinical scenario and the necessity of registering them or justifying an alternative. Indicators could not only be included in local clinical guidelines, but could also be part of electronic alarms or clinical reminders to be activated when the hospital information system detects one of the situations labelled as a priority . Future research should concentrate on establishing the corresponding standards for the proposed indicators and interpreting the influence of local circumstances and patient preferences on their observed values.Some potential limitations of the present study should be noted. First, since indicators help to identify quality problems over time, their applicability and usefulness may depend on the evolving needs of their potential users: policy-makers, health professionals, medical societies, etc., and, theoretically, indicators that specifically address all the issues that are relevant for different stakeholders should be available. However, one characteristic of our methodology is that we have generated indicators based on strong evidence, which should be equally important for all involved parties (The present study demonstrated that the generation of healthcare quality indicators from SRs is feasible and efficient. This is not a simple process, and not all reviews are equally useful in generating indicators. We believe that the thoroughness of the proposed methodology makes these indicators essential references to assess the extent to which the delivery of care is based on scientific evidence. We propose that this methodology be applied to other areas of care where there is sufficiently sound evidence.The authors declare that they have no competing interests.MA and DR carried out the search selection, data extraction, and evidence assessment. MR and DO helped to methodologically refine the indicators. AV and CF helped to interpret the clinical data and refine the quality indicators. XB conceived the study and participated in its design and coordination. MR, DR and XB drafted the manuscript. All authors read and approved the final manuscript.Adapted GRADE system for assessing clinical recommendations. Table presenting the adapted GRADE system used in this project to assess clinical recommendations derived from sound systematic reviews.Click here for fileExample of an indicator. Full text of a quality indicator developed in this project and an example of computation based on fictional data.Click here for file


German healthcare provides a very comprehensive benefits catalogue, high quality standards, low access barriers and in particular healthcare which is independent from one’s income. But at the same time it is one of the most expensive systems in the world. Reasons for the high costs of care are mainly due to the separation of the outpatient, inpatient and rehabilitation sectors, the poor information flow between the service providers and insufficient competition in healthcare provision. In the last 15 years the German government has introduced various reform acts and in doing so has followed a continual path of development: more competition for care concepts between health insurances, more options for the insured and more leeway for players in the various sectors of healthcare. The following article gives an overview of new forms of contracting that have been introduced and provides recommendations for the further development of integrated care in the German healthcare system. During the last 15 years, the German government has introduced various reform acts to improve quality and efficiency of medical provision. In this paper we describe the development of integrated care, new forms of contracting that have been introduced, and provide political recommendations.German healthcare provides a very comprehensive benefits catalogue, high quality standards, low access barriers and in particular healthcare which is independent from one’s income for the entire population. However, on the basis of their gross domestic product, this also places Germany among the most expensive healthcare systems worlwide. In addition, great challenges are to come. In the context of the demographic developments and progress in medical technology, the number of patients with chronic diseases is likely to increase remarkably. Thus the quality and economic efficiency of a healthcare system will always depend on how the care of people with complex disease patterns is organised. This is where German healthcare reaches its limits, as it makes few allowances for customised treatment processes. This is particularly due to the extensive separation of the outpatient, inpatient and rehabilitation sectors, the poor information flow between the service providers and the insufficient competition in healthcare provision. It is even more regrettable that the German government’s many attempts to provide integrated care have largely been unsuccessful and their spread has faltered since its start-up funding expired at the end of 2008. Thus there is a broad consensus that the German healthcare system must undergo structural reforms.The remaining inefficiency of German healthcare is not a new issue. Already in the 1970s the inadequate exchange of information between doctors was criticised as well as the ruptures in treatment when transitioning from one medical sector to another . Twenty-The great lack of the integration of technical processes and informational technology is the consequence of three fundamental problems in German healthcare. First, the competition for contracts and the provision of care is still very limited. Instead care is dominated by mutual and uniform contracts between the traditional associations of the statutory sickness funds and the service providers. There is too little room in this system for individualised, patient-orientated services. The lack of competition all too often leads to reliance on the familiar and thus results in a certain aversion to technology. Secondly, there is a lack of cooperation between disciplines. The field of activities of German physicians (in comparison to other countries) is characterised by its wide spectrum and tasks that more affordable and possibly even more suitable professions could execute just as well. Thirdly, medical care takes place in largely separate sectors with their own compensation systems, budgets, high market entry barriers and complex planning structures. A lack of transparency and false incentives lead to the fact that the diagnostic process is continually further developed without considering previous test results. This is not only a problem at the interface between outpatient and inpatient treatment, but also within sectors, such as the decision process between primary care physicians and specialists .In the last 15 years the German government has introduced various laws and in doing so has followed a continual path of development: more competition for care concepts between health insurances, more options for the insured and more leeway for players in the various sectors of healthcare [The German government has placed its hopes in managed care to a large extent. Since 2004 individual physicians and physician networks have been able to become direct contract partners with the health insurances for the first time through selective contracts. Combined with an attractive start-up financing of up to 1% of the entire compensation of physicians and hospitals, ca. €680 million, integrated care experienced a strong push. Within four years, approximately 6000 contracts were concluded.With the expiration of the start-up financing at the end of 2008, the success ebbed somewhat. Around 20% of the contracts were immediately dissolved or not renewed. At the end of 2009 it is assumed that there were approximately 5000 contracts and somewhat below 1% of the total expenses . AlthougToday, due to the conclusion of a series of new contracts in the mental illness field, rheumatology and also in full-care models, we estimate approximately 6000 contracts and an overall share of perhaps 1.5% of the total expenses.The healthcare reform which took effect on January 1st, 2012, the Versorgungsstrukturgesetz (care structure law), includes several good methods for interdisciplinary and cross-sector models of care. For example hospitals’ obligation to mandatory discharge management. The introduction of an outpatient specialist care sector, in which inpatient as well as SHI-authorized physicians can equally take part, can also contribute to lessening the frictional losses at sector boundaries. The change to § 87b SGB V is particularly important. It creates the opportunity to introduce separate compensation rules for network practices and to assign these their own fee volumes. In this way quality- and success-based forms of compensation (pay for performance) could receive new vigour. However, beyond these specific improvements the central blockades for integrated care are not addressed by the care structure law.If one goes looking for blockades in integrated care, one usually encounters the supposed inflexibility of traditional structures, the conflicts between statutory doctors and those working in inpatient care, as well as the fears of losing independence and worries about the transparency of quality shortcomings . These pCurrently the risks outweigh the advantages for the health insurance companies, since innovative forms of care usually require considerable investments. However, as a corporation under public law a statutory sickness fund is obligated to demand additional premiums from their policyholders when the insurance exceeds its budget. Experience with additional premiums has shown that these can occasionally have serious consequences in terms of price competition. The risk and the use of resources necessary for integrated care are thus often classified as unreasonably high. Instead it is often more attractive for health insurances to invest in comprehensive, widespread primary care physician contracts or in contracts which are not cross-sector and thus easier to manage. In order to change this, health insurances should be given more flexible entrepreneurial leeway which also allows them to invest in projects whose revenue may first accrue in three to five years. In addition, innovation budgets should be introduced in health insurances for the development of highly innovative forms of care and pilot projects. The appropriate use of funds can be determined by using standardised evaluations of the supported projects.There is also too little initiative from the service providers, as the economic pressure to be involved in selective contracts is rather low . AlthougThe insured are rather skeptical of new forms of care. Most of them are confident in the quality supposedly provided by the government in the standard provision of care. Since the advantages of innovative forms of care can first be recognised when they are made use of in cases of illness, the insured are not very willing to accept alternative forms of care which are designed for long-term use. Thus it is even more important to ensure more transparency. Currently the insured can hardly judge the different services of the health insurances due to a lack of information. Thus more standardised evaluations and the publication of results are absolutely necessary. With the rising level of transparency, new forms of care would become more significant as an instrument for competition for the health insurances and a dynamic development process would be set in motion.Comparable to the reluctance of the other participants, private partners—whether private insurances, the industry or also private financers, such as banks and private equity—have been rather cautious about investing in forms of integrated care up until now. There are individual cases of involvement, but the scale of engagement is nowhere close to the requirement for modernisation and increasing efficiency in German healthcare.In the future the efficiency of a healthcare system will be particularly assessed based on how the treatment of people with complex disease patterns is organised. The German healthcare system is not yet sufficiently equipped for this challenge. The far-reaching separation of the outpatient and inpatient sector, the inadequate flow of information between the service providers and competition in contract and care provision, which is still too weak, all allow too little room for customised treatment processes which are optimised throughout all of the stages of care. Thus it is all the more important to finally enable the breakthrough of cross-sector and interdisciplinary forms of care. For it is only through cooperation and holistic treatment workflows that unnecessary repeat examinations can be prevented, individual, custom therapies as well as an efficient form of innovation-based competition can be made possible. Selective contracts will only become established when three prerequisites are fulfilled: first, the policyholders must be convinced that the quality of the products offered by the health insurances differs from insurance to insurance. Secondly, they must be able to recognise these differences and to assess the advantages and disadvantages for themselves. Thirdly, the service providers, statutory health insurances and possibly third-party financers have to see a realistic chance to earn profits through the participation in innovative forms of care.Overcoming barriers in integrated care seems to be a never-ending story in the German healthcare system. Although politics have introduced more leeway for medical providers and insurances through various reform acts, the competition for contracts and the provision of care is still very limited. The separation of outpatient, inpatient, and rehabilitation sectors is stricter than in other countries. Nevertheless, we feel confident that we are on the right path in the direction of a more patient-oriented system. In the last decades, the number of physician networks has doubled from 200 to 400. By now, 30,000 doctors participate in cooperative forms of medical treatment. This builds the foundation for numerous population- and indication-based concepts of integrated care which have made remarkable progress. Yet, there is still a lot of work to do. At the end, integrated care will only become established when all stakeholders see a realistic chance to earn medical and economical profits through managed care.Prof. Dr. Volker E. Amelung is professor for international healthcare systems Research at the Medical University of Hannover, Germany. He is also the president of the German Managed Care Association (BMC), Berlin. His research activities concentrate on healthcare policy, managed care, healthcare management, and healthcare systems research. He has co-authored more than ten books, and has published over 100 papers on managed care, healthcare policy, new technologies, and integrated delivery systems.Helmut Hildebrandt is CEO and owner of OptiMedis AG, located in Hamburg, Germany. He holds a pharmacy diploma from Philipps-University, Marburg, Germany. He has worked intensively with the World Health Organization (Copenhagen) and with the institute for medicine-sociology of the University of Hamburg. Being President and CEO of a successful consulting firm for twenty years, he cooperated with a wide array of organizations in healthcare industry, such as leading hospitals, sickness funds, health insurances, physician networks, pharmaceutical and biomedical companies, ministries, and others. Mr. Hildebrandt is board member of the BMC.Dr. Sascha Wolf is Managing Director of the BMC. The BMC is one of the leading independent healthcare associations, elaborating innovative concepts in healthcare management and healthcare policy. It affiliates approximately 160 members from different areas in healthcare, such as leading sickness funds, health insurances, consultancy firms, pharmaceutical companies, biomedical companies, and others. Prior to this he was responsible for health politics at the Economic Council to the Christian Democratic Union of Germany (CDU).


Peter Agre, born in 1949 in Northfield Minnesota, shared the 2003 Nobel Prize in Chemistry with Roderick MacKinnon for his discovery of aquaporins, the channel proteins that allow water to cross the cell membrane.Agre's interest medicine was inspired by the humanitarian efforts of the Medical Missionary program run by the Norwegians of his home community in Minnesota. Hoping to provide new treatments for diseases affecting the poor, he joined a cholera laboratory during medical school at Johns Hopkins. He found that he enjoyed biomedical research, and continued his laboratory studies for an additional year after medical school.Agre completed his clinical training at Case Western Hospitals of Cleveland and the University of North Carolina, and returned to Johns Hopkins in 1981. There, his serendipitous discovery of aquaporins was made while pursuing the identity of the Rhesus (Rh) antigen.For a century, physiologists and biophysicists had been trying to understand the mechanism by which fluid passed across the cell's plasma membrane. Biophysical evidence indicated a limit to passive diffusion of water, suggesting the existence of another mechanism for water transport across the membrane. The putative "water channel," however, could not be identified.In 1988, while attempting to purify the 30kDa Rh protein, Agre and colleagues began investigating a 28 kDa contaminant that they believed to be a proteolytic fragment of the Rh protein. Subsequent studies over the next 3-4 years revealed that the contaminant was a membrane-spanning oligomeric protein, unrelated to the Rh antigen, and that it was highly abundant in renal tubules and red blood cells. Still, they could not assign a function to it.Xenopus oocytes, which typically have low water permeability. When the test oocytes were placed in a hypotonic solution, they swelled and exploded, thus revealing the function of the unknown protein as a water channel, which they named aquaporin.The breakthrough came following a visit with his friend and former mentor John Parker. After Agre described the properties of the mysterious 28 kDa protein, Parker suggested that it might be the long-sought-after water channel. Agre and colleagues tested this idea by expressing the protein in Anopheles mosquito, which both express aquaporins. In addition, since winning the Nobel Prize, he has enjoyed increased opportunities for bringing science to the public and for "encouraging young people to go into science."The Nobel Prize enabled Agre to take his research and scientific interests in new directions. He felt that over the years his work had continually taken him further from his original interests in third-world diseases, so he shifted his focus back in that direction. He now serves as the director of the Malaria institute at Johns Hopkins where he has applied his knowledge to the study of the malarial parasite and the


Sleep medicine is a relatively new specialty in the medical community. The practice of sleep medicine in Saudi Arabia (KSA) began in the mid to late nineties. Since its inception, the specialty has grown, and the number of specialists has increased. Nevertheless, sleep medicine is still underdeveloped in the KSA, particularly in the areas of clinical service, education, training and research. Based on available data, it appears that sleep disorders are prevalent among Saudis, and the demand for sleep medicine service is expected to rise significantly in the near future. A number of obstacles have been defined that hinder the progress of the specialty, including a lack of trained technicians, specialists and funding. Awareness about sleep disorders and their serious consequences is low among health care workers, health care authorities, insurance companies and the general public. A major challenge for the future is penetrating the educational system at all levels to demonstrate the high prevalence and serious consequences of sleep disorders. To attain adequate numbers of staff and facilities, the education and training of health care professionals at the level of sleep medicine specialists and sleep technologists is another important challenge that faces the specialty. This review discusses the current position of sleep medicine as a specialty in the KSA and the expected challenges of the future. In addition, it will guide clinicians interested in setting up new sleep medicine services in the KSA or other developing countries through the potential obstacles that may face them in this endeavor. The first was the description of narcolepsy by Jeane Baptiste Edouard Gélineau in 1880, and the second was the description of the main sleep disorder, obstructive sleep apnea (OSA), in 1836, not by a clinician but by the novelist Charles Dickens.[2Although sleep medicine is considered a relatively new specialty, interest in sleep and sleep disorders has existed since the beginning of mankind. Sleep is mentioned frequently in the Holy Quran, including a verse that says, “And among his signs is your sleep by night and by day” . Early descriptions of two of the main sleep pathologies appeared in the 19Dickens.2–8 The abDickens.2 In the KIn the early and mid-1990s, pulmonologists in the KSA used overnight pulse oximetry to diagnose OSA and titrated CPAP blindly to comfort patients and eliminate repetitive dips in oxygen saturation during sleep.–13 The uThis review aims to discuss the current position of sleep medicine as a specialty in the KSA and the expected challenges of the future by utilizing locally published data and data from other countries. In addition, it will help clinicians interested in setting up new sleep medicine services in the KSA or other developing countries to recognize the potential obstacles that may face them in this endeavor.2) in Saudi women between 40 and 49 years.[Studies that have addressed the prevalence of sleep disorders in the KSA are limited. However, based on available data and waiting lists for sleep studies, it appea1549 years. The prev49 years. In addit49 years.23 which 49 years.The prevalence of other sleep disorders has not been well explored among Saudis. Snoring has been reported in 17.9% of elementary school children. The esti26A recent national survey quantitatively assessed sleep medicine service in the KSA. It revea14Administratively, all surveyed sleep disorders facilities are under pulmonary medicine services. Sleep me24The per capita polysomnography rate in the KSA was 7.1 per year per 100,000 people, compared to 18.3–427 in developed countries .[143031314303134The practice of sleep medicine has grown significantly worldwide over the past two decades. The number of sleep centers and laboratories accredited by the American Academy of Sleep Medicine (AASM) has increased four-fold in the past decade.36 This gThe number of sleep medicine specialists in the KSA is relatively low. The number of trained qualified sleep medicine specialists in the KSA is reportedly 19 physicians located in a few hospitals in three major cities. This numA shortage of trained sleep technologists is a global problem, and in the KSA, this is considered the major obstacle facing sleep medicine. A nationSleep disorders and sleep medicine as a specialty are under-recognized by both the public and health care workers. The KSA public accepts information on sleep disorders from any source without criticism, even if the information is not authentic; therefore, they have developed their own ideas and myths about sleep. Some of the public think that sleep problems are part of their nature and do not think of these problems as medical issues that can be treated. They do not perceive sleep disorders to be as critical as other health problems and do not know about the serious comorbid conditions associated with sleep disorders. In addition, many patients do not know to which specialty they should go to present their sleep problems. Most patients seen in the clinic have gone to many doctors, particularly psychiatrists, before attending the sleep disorders clinic, thinking that all sleep disorders are handled by psychiatrists. In addition, practitioners face problems persuading patients to modify their sleep pattern or to apply good sleep hygiene. Due to under-recognition of the seriousness of disorders like OSA, patient compliance with CPAP in the KSA is less than that reported in developed countries, even when they have good objective and subjective responses to CPAP in the sleep disorders center.On the other hand, the knowledge of practicing physicians, particularly primary care physicians, about sleep disorders is limited. In gener411516Unfortunately, sleep medicine is not considered among the priorities or core competencies of decision makers in some hospitals. A national survey conducted recently revealed that “unconvinced administration” was one of the main obstacles facing the establishment of sleep disorders facilities in some hospitals. In addit62The lack of designated sleep disorders facilities may result in admitting patients with sleep disorders into valuable hospital beds that could be used to treat acutely ill patients who need inpatient care. Bahammam and Rahman demonstrated that in the absence of proper sleep disorders facilities, patients with OSA spend 4.5 nights on average as inpatients for the sake of CPAP titration, which costs around SR6750 per patient. A few st6466One major obstacle that faces practitioners in developing countries is the after-sale service. The perfEducation should be addressed at two levels: level I, education of medical and technical staff; and level II, education of the general public.There is no doubt that sleep disorders are under-recognized by practicing physicians. In a study in the US that examined more than 1,000,000 patient records, only 17 positive diagnoses of sleep disorders were made, which is less than 1/1000 of the expected number of sleep disorders based on the current estimates.–71 In ge39The education and training of physicians to become specialists in sleep medicine is another challenge. The number of qualified sleep medicine specialists in the country is very low and does not meet the increasing demand for service. The needSince the early 1970s, polysomnographic technologists have been the technical group trained to perform polysomnography for the diagnosis and treatment of sleep/arousal disorders, including the management of CPAP titration for OSA. In the KSA, sleep technologists usually come from a respiratory therapy, nursing, or electroencephalography technology background. To work Despite individual efforts by some sleep specialists to educate the public about sleep disorders through different media channels, the majority of the general public remains unaware of the serious consequences of sleep disorders, sleep deprivation and disturbances of biological rhythms. Sleep deprivation is a major problem among youths in the KSA.75 Many pSpecialty care has been shown to improve outcomes in several settings. For example, a number of studies in intensive care units have demonstrated that management of critically ill patients by qualified critical care specialists resulted in a reduction of mortality, hospital stay and health care utilization.–78 SimilThe accreditation process aims to ensure that the facility and its staff meet the highest quality standards. The accreditation standards describe the required structural, professional and human resources, clinical and technical standards, and emergency and quality assurance methods.82 The prThe accreditation process should assess the credentials of medical and technical staff. Therefore, there should be a licensing system to license sleep medicine specialists and sleep technologists. The Saudi Commission for Health Specialties should take on this role and develop guidelines and requirements for the licensing of medical specialists and sleep technologists. Nevertheless, the SSMG can initiate the process through direct communication with the Saudi Commission for Health Specialties to develop defined standards for the required education and training and the need for formal evaluation.Although the last three decades have witnessed significant growth and evolution in sleep research worldwide, sleep research remains underdeveloped in the KSA, which mirrors the underdevelopment in the clinical service overall. In 1994, the KSA published 10 papers on sleep and was ranked number 31 in the world in terms of number of publications. AlthoughSleep medicine in the KSA is underdeveloped at the levels of practice, education and research. It faces a number of obstacles that hinder its progress, including a lack of adequate specialized medical and technical staff and a lack of awareness about sleep disorders and their serious consequences among health care workers, health care authorities, insurance companies and the general public. A major challenge for the future is penetrating the educational system at all levels to demonstrate the high prevalence and serious consequences of sleep disorders. Educating and training health care professionals at the level of sleep medicine specialists and sleep technologists is another important challenge that faces the specialty to attain an adequate number of staff and facilities. Sleep research is mandatory to assess the size of the problem in the KSA and to help strategic health planners estimate the number of sleep specialists and sleep facilities needed to meet the increasing demand.


The latest generation of smartphones are increasingly viewed as handheld computers rather than as phones, due to their powerful on-board computing capability, capacious memories, large screens and open operating systems that encourage application development. This paper provides a brief state-of-the-art overview of health and healthcare smartphone apps (applications) on the market today, including emerging trends and market uptake. Platforms available today include Android, Apple iOS, RIM BlackBerry, Symbian, and Windows (Windows Mobile 6.x and the emerging Windows Phone 7 platform). The paper covers apps targeting both laypersons/patients and healthcare professionals in various scenarios, e.g., health, fitness and lifestyle education and management apps; ambient assisted living apps; continuing professional education tools; and apps for public health surveillance. Among the surveyed apps are those assisting in chronic disease management, whether as standalone apps or part of a BAN (Body Area Network) and remote server configuration. We describe in detail the development of a smartphone app within eCAALYX , an EU-funded project for older people with multiple chronic conditions. The eCAALYX Android smartphone app receives input from a BAN  and the GPS  location sensor in the smartphone, and communicates over the Internet with a remote server accessible by healthcare professionals who are in charge of the remote monitoring and management of the older patient with multiple chronic conditions. Finally, we briefly discuss barriers to adoption of health and healthcare smartphone apps , as well as some workarounds to mitigate those barriers. More than half of Americans aged 25-29 now live in households with mobile phones but no traditional landline telephones, a December 2010 report on phone use by the US National Center for Health Statistics at the CDC (Centers for Disease Control and Prevention) has found. The same study also found that the younger children are, the likelier they are to live in homes that only have wireless phones, suggesting that younger parents are becoming increasingly reliant on mobile phones even as they adjust from being single to a more settled family lifestyle   and location-enabled smartphones offer many additional application opportunities that can further assist the independent living of persons with disabilities and/or multiple chronic conditions ,23, as wKailas et al.  claim thThe eCAALYX Mobile Application is being developed under the scope of the eCAALYX EU-funded project , whiThere are many challenges to the development of the mobile platform. Most importantly, the mobile platform must be seamless and autonomous in its operation , in order to provide a usable service to a target group that usually does not have any familiarity with technology and might even be unconscious during times of medical emergency and not able to manually operate any device or software. System and service reliability is also an important issue to take into account, firstly due to the possible negative sensation that the application may give to the user in the case of malfunctioning, and, secondly, due to the physical distance between the technical maintenance teams and the users. From an implementation point of view, the issues regarding the implementation of intelligent mechanisms in a mobile resource-limited device should also be considered. Usability issues are further discussed in the following section.Usability is a critical issue for the target group of eCAALYX as, usually, users in this target group do not have any familiarity with technology and this is also often compounded by a range of physical  and/or cognitive disabilities  that such users might be suffering from that can further limit their use of the technology . Due to • Use of dock-stations to simplify the battery charging of the mobile device;• Use of a mobile phone without buttons and with large touch-screens, which allows the building of virtual buttons as large as needed, instead of the small buttons available on commercial mobile phones with conventional keypads and keyboards; and• All maintenance actions are performed either remotely and transparently to the user, or locally, by technicians.Concerning smartphone software usage, the following practical solutions were adopted:• The phone runs autonomously without the need of any mandatory interaction from the user from the time it is powered on. This includes the supressing of all enquiries of the operating system, such as pin negotiation and the automation of all necessary processes;• Rebooting has to be avoided, because it can be a difficult task to perform by the target users. The phone must therefore support prolonged periods of operation without the need to reboot the system;• All possible navigation has been reduced to two easily accessible screens, to avoid confusion of the user while navigating the software; and• All error pop-ups were supressed, to avoid showing any system errors to the user.The technological platform in the current prototype is the Google Nexus, running the Android 2.1 platform , with 1 There are not yet any clinical trials or evaluation results of the eCAALYX Mobile App to report (at the time of writing in January 2011); such details are expected to be available after project completion in July 2012. However, we think that the eCAALYX Mobile App we have briefly described here provides a unique opportunity to have a somewhat detailed 'under-the-hood' look at one current example from a rapidly growing class of smartphone apps for chronic disease management and telehealthcare.eCAALYX builds on the experience gained in a previous and closely related EU-funded project, CAALYX . MobiLens survey [Smartphone ownership in the developed world is rapidly increasing. ChangeWave Research  report as survey  estimatiany mobile phone. UK's National Statistics [We can perhaps extrapolate from ownership of atistics  report tatistics , so therAge is probably the major 'digital divide'. The Continuous Household Survey in Northern Ireland  providesTaking these two trends together we might estimate that 80-90% of the UK population will have a smartphone within 10 years. This might not be quite as rapid as some might suggest, but, in the context of other social changes brought about by the development of technology, is a massive change.Jane Sarasohn-Kahn reports "How smartphones are changing healthcare for consumers and providers" . ProbablConsidering that many apps now, especially those intended for chronic disease management, rely on the presence of an active Internet connection on the smartphone in order to function as intended, a question immediately arises about current Internet uptake levels among people with chronic diseases.one chronic disease go online compared to only 52% of adults living with two or more chronic diseases. The difference is even more marked when comparing use of text messages with only 23% of those with two or more chronic conditions compared to 60% of those with no conditions using a mobile to send text messages [Fox and Purcell  report tmessages .There are now many health promoting Internet interventions  but theyThere are now hundreds of smartphone apps focusing on wellness, fitness, and nutrition. Mobile and home monitoring can be carried out with body-worn and ambient sensors communicating with smartphones , including accelerometers measuring motion and gait, infrared detectors measuring body temperature and heart rate, and glucometers measuring blood glucose . However, Sarasohn-Kahn  describeAt the moment, Sarasohn-Kahn  cites EiWhat other barriers to smartphone use in health does Sarasohn-Kahn  see? SheNotwithstanding all of the benefits we should be aware that the use of the mobile phone in healthcare and clinical practice is not without its problems and limitations. In comparison to laptop computers, the small internal storage capacity, processing power and screen size of the mobile phone often requires apps that are running to be in reduced format . HoweverWhen used as a method for monitoring the health status of remote patients, mobile phones should be applied only after due consideration to patient perceptions and feelings. One study in Italy revealed that patients with implantable cardioverter-defibrillators for cardiac resynchronisation therapy welcomed the use of mobile technologies for remote monitoring, but did not want them to replace their personal contact with health workers . Other sKurniawan , Lorenz According to a recent MobiHealthNews report published in November 2010 , from FeDesk-based health researchers who rely on the telephone to gather their data are faced with a growing problem. Increasingly, respondents are replacing their landlines with mobile telephones, and in so doing, they create a problem for the researcher. Legislation in some countries requires researchers to manually dial mobile phone numbers, thereby incurring significantly more cost in both time spent on calling and in call costs. Further, calling a mobile phone on some tariffs may use up respondents' air time, and there may therefore be an ethical onus on the researcher to reimburse the costs incurred .It is clear from their rapid proliferation and deep penetration into society, that there are significant opportunities to exploit the potential of smartphones in healthcare . Mobile Some commentators ,41 suggeLater adopters of new technologies may not use them in the same way as early adopters. Developers of new smartphone health apps need to look 'at the margin', i.e., how the latest group of adopters are using smartphones and how the next group of new users may use it. Although there are hundreds of smartphone apps at the moment, the successful ones are, currently, likely to be for younger and healthier populations. The adoption of smartphones by older people and people with chronic disease will come with time, but also as the relative cost comes down, as apps become easier to use, as there is a greater awareness of what smartphones can do, with the establishment of more 'community knowledge' to deal with the complexity of the new technology , and perThe authors declare that they have no competing interests.MNKB conceived and drafted the manuscript with contributions from SW, CT and RJ. MNKB and CT (and their institutions) are both involved in the EU-funded eCAALYX project, with MNKB leading the University of Plymouth part of it. All authors read and approved the final version of the paper. (N.B.: All Web links in 'References' below have been last checked working on 16 March 2011.)


Joint pain is a highly prevalent condition in the older population. Only a minority of the older adults consult the general practitioner for joint pain, and during consultation joint pain is often poorly recognized and treated, especially when other co-existing chronic conditions are involved. Therefore, older adults with joint pain and comorbidity may have a higher risk of poor functional outcome and decreased quality of life (QoL), and possibly need more attention in primary care. The main purpose of the study is to explore functioning in older adults with joint pain and comorbidity, in terms of mobility, functional independence and participation and to identify possible predictors of poor functional outcome. The study will also identify predictors of decreased QoL. The results will be used to develop prediction models for the early identification of subgroups at high risk of poor functional outcome and decreased QoL. This may contribute to better targeting of treatment and to more effective health care in this population.The study has been designed as a prospective cohort study, with measurements at baseline and after 6, 12 and 18 months. For the recruitment of 450 patients, 25 general practices will be approached. Patients are eligible for participation if they are 65 years or older, have at least two chronic conditions and report joint pain on most days. Data will be collected using various methods . We will measure different aspects of functioning  and QoL. Other measurements concern possible predictors of functioning and QoL . Furthermore, health care utilization, health care needs and the meaning and impact of joint pain will be investigated from an older person's perspective.In this paper, we describe the protocol of a prospective cohort study in Dutch older adults with joint pain and comorbidity and discuss the potential strengths and limitations of the study. Almost half of the community dwelling older adults report daily pain , which mPoor recognition and treatment of joint pain is especially seen in older patients who also suffer from other chronic conditions, such as diabetes, cardiovascular disorders or respiratory diseases ,20,21 anTo optimize health care for this population, it could be relevant for health care providers to identify older adults at risk of poor functional outcome and decreased QoL. Early recognition of those at risk may facilitate better targeting of treatment, resulting in more effective and efficient health care for older adults with joint pain and comorbidity. To enable early recognition of poor functional outcome, it is important to obtain more insight in functioning and the course of functioning in the defined group. This provides the opportunity to make an appropriate distinction in subgroups based on functional prognosis and to understand the differences in functioning in older adults with joint pain and comorbidity. It also helps to identify possible risk factors that are associated with different patterns of functioning and therefore makes it possible to predict specific trajectories of functioning.Previous longitudinal studies on prognostic factors for functional decline in joint pain and/or osteoarthritis (OA) found evidence for various predictors of poor functional outcome, like older age, high pain intensity, longer duration of symptoms, comorbidity, high BMI, anxiety, depression and poor self efficacy -26. HoweApart from investigating functional outcomes, it is also important to obtain insight into health care utilization and health care needs in older people with joint pain and comorbidity ,12,28 anThe overall aim of the study is to explore functioning in older adults with joint pain and comorbidity, in terms of mobility, functional independence and participation and to identify possible predictors of poor functional outcome. The results will be used to develop prediction models for the identification of subgroups at high risk of poor functional outcome. Besides identifying predictors of functioning, we will also explore QoL and its possible predictors. Furthermore, the study examines health care use and health care needs in this population and explores the personal experiences and impact of joint pain in everyday life, from an older person's perspective.The study has been designed as an observational prospective cohort study, with measurements at baseline and after 6, 12 and 18 months. Various methods will be used to gather information, using questionnaires, physical tests, patient interviews and focus groups.The Medical Ethics Committee of the VU University Medical Center, Amsterdam, has approved the study protocol.Patients will be recruited from approximately 25 general practices, located in the Northwest of the Netherlands. Patients are eligible for participation in the study if they are aged 65 or older, have two or more chronic conditions  . When coICPC codes of symptoms or conditions that have been resolved are retained in the registration system of the general practitioner. If we would select patients based on ICPC codes of resolved conditions, this may lead to an incorrect selection in step 1. Therefore, in the second step, we ask the general practitioner to check if the selected chronic conditions of the patients are still up-to-date and active. A chronic condition is considered 'active' if it has the attention of the general practitioner, which for example involves additional diagnostic testing or monitoring, recent treatment or medication prescription, or if the condition is known to have a progressive course . SubsequThe third step is to send a study information leaflet, information letter and self-report screening questionnaire to all potential participants identified in the previous two steps. This screening questionnaire contains questions about the presence, frequency, duration and intensity of joint pain and also assesses the impact of joint pain on functioning. Additionally, patients are asked to consent to further contact. Reminders will be sent to non-responders after two weeks. Responders who report experiencing joint pain on most days in the last month and give permission to be re-contacted will be included in the study Figure .Measurements will be performed at baseline and after 6, 12 and 18 months. We will use various methods to collect data, i.e. questionnaires, physical tests, interviews and focus groups. To optimize the data collection, we have invited two older adults who represent the target population, to participate in our project team as patient experts. They will be asked to assess the information leaflet, letters and questionnaires for clarity and burden to patients and to give recommendations about relevant topics that we can incorporate in the focus group meetings.The baseline assessment will consist of a baseline questionnaire, several physical tests and an interview. The physical tests and interview will be performed at the participant's home, during a home visit. The baseline questionnaire will be sent to the participant's home two weeks before the visit, so that the participant has enough time to complete the questionnaire. An interviewer will contact eligible respondents by telephone to provide information about the project, to explain the procedure for the baseline assessment in more detail and to schedule an appointment for the baseline assessment. During the visit, written informed consent will be obtained. Then, the interviewer will conduct the short set of physical tests  as a framework for the measurements, as shown in Figure Functioning will be assessed with self-report questionnaires at baseline and after 6, 12 and 18 months, in terms of mobility, functional independence and participation, by using questionnaires , which consists of 10 items measuring difficulties in a hierarchical range of activities  and can be scored on an ordinal 3-point scale  [tations) . The Duttations) .Functional independence will be measured with the KATZ index of independence in activities of daily living [y living , which mParticipation restriction will be measured with the Keele Assessment of Participation questionnaire (KAP) [During the past four weeks, I have moved around my home, as and when I have wanted") [re (KAP) , which cwanted") . Responswanted") ."In general, how would you rate your quality of life?") on a 5-point scale  [QoL will be measured at baseline and after 6, 12 and 18 months with one item of the SF-36,  . Additiole, bad) .For the development of the prediction models, we will assess possible predictors of functioning and QoL at baseline, like pain, comorbidity, markers of frailty, physical performance, psychological factors, environmental factors and individual factors. Some time-dependent determinants will also be measured during the follow up period, such as psychological factors and living arrangements. Details are described in table To study health care utilization, we will obtain data on health care use in general and health care use for joint pain in particular, as shown in table To explore the personal experience and impact of joint pain in an older adult's everyday life, we will organize focus group meetings. Focus group meetings allow participants to share experiences and thus, enable exploration of the impact of joint pain, how joint pain interacts with other health problems, how people manage to lead their life despite pain and other health problems, which self management strategies they may use and how they could be supported by health care practitioners . ParticiOne of the main objectives of the study is to develop prediction models for poor functional outcome. This analysis demands the most statistical power and therefore, we calculated the sample size based on this analysis. Altman suggests using at least 10 'events'  per predictor in a multivariable model . Based oWe will use Latent Class Growth Mixture Modelling (LCGMM) to study functioning and quality of life over time . Based oWe expect to find different predictors for QoL, and therefore QoL will be analysed separately by using LCGMM and logistic regression analysis.Objective health care utilization will be described by using descriptive statistics. Frequency tables will be used to summarize health care needs on the different items of the CANE and the extent to which these needs are met or unmet. We will use a paired T test or a Wilcoxon signed rank test to analyse differences between the amount of received and desired health care, to quantify unmet needs. To study the relation between sociodemographic characteristics and health care needs, we will use the chi-square test or the t-test, depending on the variables under study. Further data on health care needs will be collected in focus groups. The processing of the focus groups is described below.The results of the focus groups will provide additional qualitative information on subjective health care needs and the meaning and consequences of joint pain in everyday living. This mixed methods approach enables us to generalise the quantitative results to the target population, while emphasising the personal perspective and experiences of older adults with joint pain and comorbidity. The results of the focus groups will be audio recorded and transcribed. Two independent researchers will code and group the data into categories for the identification of key points, by using ATLAS.ti. After the coding process, the two researchers will compare and discuss the categories, in order to achieve consensus.This protocol describes a prospective observational cohort study in which extensive information will be gathered about older adults with joint pain and comorbidity. Previous studies indicate that older adults with joint pain and comorbidity have a higher risk of poor functional outcome, as joint pain is often poorly recognized and treated in primary care. Therefore, the main purpose of the study is to explore functioning in older adults with joint pain and comorbidity, in terms of mobility, functional independence and participation and to develop prediction models for the early identification of subgroups at high risk of poor functional outcome. Furthermore, the study will identify predictors of QoL. Early identification of older adults at high risk of poor functional outcome and decreased QoL may facilitate appropriate recognition, assessment, and treatment of joint pain, resulting in more effective and efficient primary care for this population and maintenance of functioning in daily living.To strengthen our data collection and assimilation, we decided to extend our data resources by using various measuring methods. Besides quantitative methods for the exploration of functioning and QoL, the study design incorporates qualitative methods for the exploration of health care needs and the experiences and meaning of joint pain from the perspective of older adults, by organizing focus groups. The use of various measuring methods provides a more comprehensive understanding of joint pain in the older population, because the qualitative data are complementary to the quantitative data. The qualitative data further clarifies possible strengths and weaknesses in health care, and problems older people deal with in everyday life, which helps to optimize health care for this defined group. Another strength of this research protocol is that we incorporate the opinion and experiences of our target population into the different stages of the project. Two older adults who represent the target population have been recruited as members of the project team. They will be involved in the entire process and will provide input in several phases of the project, including the design and content of the information leaflet, letters and questionnaires and the objectives of the focus group meetings. We will also involve them in the presentation and dissemination of the results, in order to make sure that the results are clearly written and accessible for the target population, and all relevant professionals and stakeholders. A final strength is our selection procedure. We select patients based on self-report questionnaires for joint pain, instead of the medical records of the GP. The reason that we decided to screen on joint pain was because only a minority of the older people consults their GP for joint pain. Selection based on medical records would result in an underestimation of the number of people with joint pain and would provide a population sample which is not representative for the actual prevalence of joint pain in the older population.However, this selection procedure also has a limitation. Screening with self-report questionnaires raises the possibility that people answer the questions about pain problems other than joint pain, like nerve pain or muscle pain, which could result in incorrect selection of people with joint pain. To minimize this problem, participants are asked to clarify their joint pain problems during the telephone call that we make when scheduling the appointment for the baseline assessment. Another limitation is the short follow up period of 18 months. Some earlier studies recommend longer follow-up periods, because of the relatively small changes in functioning after 2 years ,46. HoweIn conclusion, the aim of the study is to obtain more insight into functioning and the different patterns of functioning and QoL in older adults with joint pain and comorbidity. This provides the opportunity to understand the differences in functioning and helps to identify possible risk factors that are associated with poor functional outcome and decreased QoL in the study population. Eventually, this could contribute to better recognition, assessment and treatment of joint pain and to more effective health care for older adults with joint pain and comorbidity.The authors declare that they have no competing interests.LH wrote the paper. SL has co-written the paper. DW designed the study and co-wrote the paper. MS has assisted in the design of the study and co-wrote the paper. JD has assisted in the design of the study and co-wrote the paper. HH has assisted in the design of the study and co-wrote the paper. All authors have been involved in revising the paper and have approved the final version.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2474/12/241/prepub


Health Professionals for a New Century, Frenk and Chen comment that, compared to medicine and nursing, public health has done the least to examine what and how it teaches (A well-educated workforce is essential to the infrastructure of a public health system . At a ti teaches . This do The overarching goal of this study is to examine the literature pertaining to the education of public health professionals in recent years in order to document the extent to which those preparing professionals of the public health workforce think about what they teach, how they teach, and what the results of the instruction are. The specific objectives are to (1) identify relevant peer reviewed literature, (2) analyze that literature for content, (3) characterize the literature according to teaching elements, and (4) draw conclusions and implications to enhance future pedagogical efforts related to the education of public health professionals.Identifying those who comprise the public health workforce can be a challenge, particularly if cross-national comparisons are involved. For the purposes of this study, “public health professional” is used to refer to professionals of any discipline working in any aspect of the field of public health, including in government and non-government sectors, on a full-time or part-time basis. “Professional” refers to characteristics that include formal academic training, the ability to work independently, a self-governing discipline, and adherence to a code of ethics . The stu“Pedagogy” is defined here as the study of the science of teaching, including content, format, compilation into curricula, and evaluation. Elements of pedagogy include learning objectives, KSAs , courses, curricula, competencies, instructional methods, and evaluation methodologies. Workforce analyses, needs assessments, and job placement outcomes are elements that affect education. “Accreditation” as defined by the US Department of Education is recognition granted by an authorized accrediting body that an educational program meets minimum standards specified by its field.The challenges of identifying literature on the pedagogy of public health workforce education include the broadness of the field and the vagueness of the terms. “Public health education” can be interpreted to mean the education of the public about health. A general literature search turns up articles on anti-smoking campaigns and condom use. The breadth of the field means that literature on pedagogy can be found on such diverse topics as epidemiology, sanitary engineering, and nutrition. Several health professions disciplines have specialties of public health within their academic training, such as public health nurses and physicians with specialty training in preventive medicine or occupational health. Additionally, because heretofore public health has not had a specific journal dedicated to its pedagogy, many potential contributions remain unpublished. Myriad reports about the status of the public health workforce are white papers or government reports and are not converted to publication in peer reviewed literature. In short, the challenges to finding the literature that analyzes and evaluates education for public health professionals is part of the reason that public health has been criticized for its pedagogy, or lack thereof.To identify critical thinking about the education of public health professionals as reflected in the published literature, a medical librarian conducted a detailed literature search using a sophisticated Boolean logic. Three major data bases were searched: PubMed, Scopus, and Education Full Text. The timeframe was limited to 2000 and forward, recognizing that the education of the professionals for public health practice is a centuries-old endeavor, and a number of seminal articles and reports pre-date this timeframe. The analysis was limited to literature published in peer review journals. White papers, institutional reports and “gray” literature were not included. The search requested articles published in English as the primary language.The search intentionally did not pursue sub-specialties within public health, such as environmental health, community health education, public health nursing, or nutrition. Sub-specialties, particularly ones that have specific certifications, licenses, or accreditations, might also well have a distinct body of literature on the pedagogy pertaining to that sub-specialty. Similarly, the search did not examine each distinct health professions discipline for articles pertaining to education about public health. If an article appeared in the general search for public health professions pedagogy, it was assumed to have widespread applicability or interest, even if emanating from a sub-specialty of public health or a separate health professions discipline.The articles were initially categorized using 10 themes generated from a previous pilot study of 110 articles. (These 110 articles were excluded from the retrieved articles.) The retrieved articles were also categorized by type of study: program description, commentary, evaluation, or original research. One of the authors reviewed the abstracts of all articles for (1) relevancy to the study, (2) appropriateness of theme category, (3) type of article. The articles were also examined for date of publication and the publishing journal.A total of 576 unique articles were identified from the three sources: PubMed – 478; Scopus – 49; Education Full Text – 49. The 110 articles from the pilot study, relevant to the overall body of literature, were excluded since they had been used to create the initial theme categories. Because the preponderance of articles came from PubMed, and the information available from the other two sources was in different formats, the analysis was limited to those articles published in PubMed. As noted, the abstract for each of the 478 articles was read to confirm appropriateness for the study and for the theme category. Four articles were shifted from one category to another. Fourteen articles were dropped as not directly related to the education of the public health workforce, leaving a total of 464 articles.Table Commentary: articles based on application of concepts, suggestions of theoretical frameworks, analyses without quantifiable data, opinions based on experience and wisdom.Program description: descriptions of a course, curricula, or other teaching approach used primarily by one organization.Evaluation: objective data gathered to evaluate a specific course, curriculum, or teaching approach that had already been implemented.Research: original research conducted to guide the development of a new educational program, such as needs assessment surveys, focus groups, descriptive information compiled across a number of programs.Table Many articles were descriptions of training programs or case studies of the education offered by a single university. Evaluations of training programs were called out separately, with any other type of quantitative analysis assigned the category of “research.” Commentaries included opinion pieces by thought leaders and analyses of educational trends.The types of articles were analyzed by theme. Table Articles within each theme were further analyzed by number of journals. Table Special topic issues and/or supplements brought together a number of papers on the same issue. Supplements and special issues tended to reflect an educational initiative , indicating the influence that a dedicated funding initiative can have on education and the need to document the results. Special topics covered themes such as emergency preparedness and the training of veterinarians about public health.In contrast to the assertion by Frenk and Chen that the field of public health has relatively few articles on its pedagogy, the initial search here identified 686 articles in peer review journals between 2000 and 2012 listed in four different sources (three bibliographic data bases and the pilot study). Publications listed in PubMed (464) were the focus of detailed analysis based on abstract and other information listed in the PubMed data base.Ten themes of primary content and four types of methods emerged. The themes encompassed articles on content of education , target audience , program descriptions , and others. The types of articles included commentaries and theoretical frameworks, program descriptions, evaluations, and original research. Many articles spanned more than one theme.the Journal of Public Health Management and Practice, the Journal of Veterinary Medicine, and the Journal of the American Public Health Association) resulted in an increase in papers in a single year.The 464 articles appeared in a total of 138 journals, reflecting the breadth of the field and the lack of a single journal focused on the pedagogy of public health. Each theme also had a number of journals, with no theme having a single dominant journal. The number of articles per year varied, but several supplements  became concerned about zoonotic diseases, an emphasis was put on educating veterinarians about public health. This produced curriculum innovations in a number of US universities. The current push toward translation and dissemination of new knowledge no doubt contributed to a desire to publish information about the initiative, and two separate journals ran special issues on veterinary public health education. Similarly, a CDC-funded program to recruit minority researchers to the study of health disparities produced a number of innovative university-based programs, subsequently described in a special issue of a journal. Thus, educational programs and the dissemination of information about them in formal peer review literature can be directly affected by funding sources and their expectations of translation and dissemination.Education of the professional workforce for public health practice is distinct from educating the lay public to engage in positive health practices, although there is overlap.Those teaching professionals for the field of public health clearly think about what they teach, how they teach, and what approaches are most effective for which purposes.Public health is a highly interdisciplinary field, with education incorporated into the education of various health professions as well as a distinct academic discipline of public health.Within public health, some sub-specialties are more advanced in their pedagogy than others. This is often tied to specific licensure or certification and accreditation by external accrediting bodies.As public health grows as a focus of education at the university undergraduate level, the pedagogy of public health should be used to guide instruction, curriculum articulation, career planning, and practice expectations. Published articles on undergraduate public health education tend to be unrelated to articles on general public health workforce education, graduate, or sub-specialty education.Practice is clearly a desired outcome yet it is difficult to measure the impact of education over time; additional work on evaluating public health professionals’ education is warranted. Licensure and certification data bases and content expectations offer one way to evaluate the effects of formal education.Relating public health education across national boundaries and education systems is complex given the diversity of public health education within a given country. More information about how public health education is approached in individual countries, perhaps shared through open access literature, would provide a basis of knowledge for sharing educational content and platforms across nations to achieve consistency in the education of a global public health workforce.A search term or way of identifying literature on education for public health professionals will facilitate access to peer reviewed information that can inform the pedagogy of public health professionals’ education.The literature pertaining to the pedagogy for public health professionals reflects the status of the field, as well as its approach to education. The analysis of the literature reported here reinforces the following:The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Serious efforts are taking place worldwide to attain universal health coverage (UHC). In India, although an unattained goal for long, recent recommendations of the High Level Expert Group (HLEG) instituted by the Planning Commission have brought the UHC agenda to its zenith . HoweverThe toolkits were developed by a multidisciplinary team of experts specialised in planning, implementation and evaluation of health systems. Each of the recommendations was elaborated into a set of action points, signifying the specific institutional reforms and measures required for their realization. In doing so, lessons were also drawn from comparable national and international experiences. The action points were verified by experts and implementers and developed in the form of a tabular framework, with sub-activities against each action point, a list of stakeholders and a timeframe. While articulating all necessary reforms clearly and specifically in the toolkit, we also accorded care to preserve the flexibility required at different implementation levels. This was to avoid being overtly prescriptive, while at the same time providing focused guidance for application in varying settings. It was also found to be important to provide guidance on the ‘how’ of the implementation, in addition to the ‘what’.The project is at an interim stage wherein we have finalised the toolkit for the recommendations on community participation and citizen engagement, out of all the recommendations of the HLEG. The work on other recommendations is progressing. We observe that a systematic analysis of each recommendation opens up a large horizon of implementation challenges. Each recommendation leads into several action points and numerous sub-activities at both national and state level. These include, but are not restricted to devising rules and norms, establishing institutions, employing personnel, undertaking trainings and securing and deploying finances. It is estimated that it will take 18-24 months at the national level, and 48-60 months at the state level, to institute preparatory reforms that are requisite for implementing the UHC recommendations. This may be exceeded in instances where capacities at state level are less developed, or for larger-than-average states. There is a simultaneous need to set into motion local and community-led processes, which in turn necessitate massive capacity-building efforts. The toolkit reflects a paradigm shift from the current trend of centralised technical assistance and out-sourcing, towards self-reliance.In the case of most nationally mandated programmes and reforms, it is widely observed that the lack of adequate detail in implementation guidelines or, conversely, overly top-down or prescriptive guidelines create varied challenges and limitations for the implementers. Crucially, the important step of dismantling or modifying existing institutions is rarely addressed, when institutional or structural reforms are propagated. Newer systems are often layered onto existing decision-making structures creating parallel implementation chains. Further, the establishment of systems of governance is seldom prioritised while instituting reforms, nor is the ethical basis of such governance typically articulated. All these deficits in the reform process result in poor health governance and eventually reflect in health outcomes. In the context of UHC, it is important to have a robust framework that guides governance in an integrated manner, and facilitates better implementation at central and state level. The governance toolkit is one such robust, sensitive and practical approach.The limitations of the toolkit in its present iteration include that it is restricted to the national and state/UT levels only - yet it contains the potential to be expanded to district, block and peripheral levels. The toolkit has potential to support all levels of decision makers to adopt measures and to ensure better implementation of UHC at their respective levels, and to ascertain the efficacy of these measures.Authors declare that they have no conflict of interest.The study was funded by Oxfam India, New Delhi for the Initial phase of “Preparing the Governance Toolkit for Universal Health Coverage” project.