Physiologically-based PK (PBPK) models in particular, based on mechanistic descriptions of the body anatomy and physiology, may also help to extrapolate in vitro or animal data to human.Computational pharmacokinetic (PK) modeling gives access to drug concentration Once in the systemic circulation, a chemical has access to the microvasculature of every organ or tissue. However, its penetration in the brain, retina, thymus, spinal cord, testis, placenta,… may be limited or even fully prevented by dynamic physiological blood-tissue barriers. Those barriers are both physical (involving tight junctions between adjacent cells) and biochemical (involving metabolizing enzymes and transporters).On those cases, correct mechanistic characterization of the passage (or not) of molecules through the barrier can be crucial for improved PBPK modeling and prediction.in vitro experimental models. Data from such assays are very useful to calibrate PBPK models.In parallel, attempts to understand and quantitatively characterize the processes involved in drug penetration of physiological barriers have led to the development of several in vitro and computational models, highlighting the challenges and perspectives for in vitro and computational models to better assess drug availability to target tissues.We review here those  Computational tools permit to go beyond the frontiers of feasible experiments  process , and wein vitro models have been developed, ranging from the determination of partition coefficients to more mechanistic experiments  and characterization . Tissue homogenates or slices can be used to estimate a drug’s partition coefficient between tissues and an extracellular medium  would be very useful.Yet, in vitro systems is the relevance of their results to in vivo settings, and the conditions for validity of their extrapolation to in vivo. Physiological barriers are most of time complexes of junction proteins and involve both physical and biochemical mechanisms. It is rarely possible to assess the effects of all this components on resulting permeability in a unique stand-alone in vitro experiment. Firstly, it has been shown that junctions are tighter in vivo than in vitro  is to sub-compartmentalize the PBPK model: organs get usually sub-divided into three  compartments Campbell . ExchangVTBis the vascular blood volume in the tissue, PSTthe apparent permeability-surface area product, fubthe unbound fraction of the compound in blood, futthe unbound fraction of the compound in tissue, XTIthe quantity of X in the interstitial and intracellular compartment and VTIthe volume of that compartment (VTI= VT – VTB).where, in addition to the parameters and variables defined in eq. XTI, the corresponding differential equation is:For J (nmol/min/mg protein) can be added to equation J is usually based on conventional Michaelis-Menten kinetics:To model active transport, a transport rate term Vmax is the maximum transport capacity (nmol/min/mg protein), and Km the half-saturation concentration. For efflux, the TB subscripts would be replaced by TI.where in vitro. Partition coefficients can be obtained either by model-based predictions according to the tissue composition (where the equation parameters are given by in vitro experiments on drug lipophilicity and plasma protein binding), or by in vitro direct determination of the drug's concentrations ratio in the buffer and tissue at steady-state :This leaves us with specific parameters to estimate. Such estimates can be obtained dQ/dt (mol/s) is the increase in the amount of drug/tracer molecule in the receiver compartment after a small time interval dt since time zero, S (cm2) the exchange surface, and C0 (mol/cm3) the initial drug/tracer molecule concentration in the donor chamber.where PST, is simply  , and mathematical models based on mechanistic description of biological processes.The above parameters can also be estimated by fitting the whole PBPK model to One way to estimate the permeability of drugs through a given barrier is to link their chemical structures to the property of interest: permeability. The principle of QSPR models is that similar chemical structures should lead to similar properties  and functional (metabolizing enzymes) barrier features, for mimicking the in vitro passive transport properties through cell monolayers. Model predictions of passive transport were validated across in vitro data, and were reasonable approximations.There have been several efforts to develop computational ways to gain mechanistic insight in permeability processes. For example, Garmire et al.  developeAnother computational development is that of Dolghih and Jacobson . They deA well thought conceptualization is the key for developing a useful model. We have seen that there are several ways to build a PBPK model, from description of few global compartments to precise compartmentalization at the tissue or even at the cell levels. The same is true for parameters which can be estimated at whole tissue level or at a finer level.One important thing in PBPK modeling is to have an integrated view of the whole body behavior. To model every detail is not feasible, and abstraction is essential to understand. Hence, an approach coupling general chemical behavior in the whole body and refinement through description at lower levels in tissues of special interest can give very useful insight about relevant mechanisms, while being predictive at a higher level.The success of QSPR-based models depends both on the accuracy of algorithms and on the quality of input data. Because of the methodological and experimental variability present in published data, QSPR models may be poorly predictive. This highlights the need of a balance between i) the understanding of the reality of complex physiologic events to provide accurate systems information and ii) the simplicity required for computational modeling feasibility.Different tools detailing each step of ADME processes are available and can be integrated into a coherent iterative approach  the time-course of concentration in blood and ii) the characterization of passage through those barriers. The first kind of information can be obtained from whole-body PBPK models, the second may come from several methods, in vitro models. Of course, the complexity of the living systems and the imperfect predictive power of computational models mean that in vitro assays will be still used for a long time.Both understanding of mechanisms and estimating model parameters in the field of barrier permeability can be done thanks to in vitro to in vivo, or from animal to human.As long as experimental evidence come and scientific hypotheses are validated, the mathematical models for predicting passage across biological barriers will tend to be increasingly complex and realistic. They should thus lead to better extrapolation, from


The assessment of quality of care is becoming increasingly important in healthcare, both globally and in the Netherlands. The Dutch Minister of Health declared 2015 to be the year of transparency, thereby aiming to improve quality of care by transparent reporting of outcome data. With the increasing importance of transparency, knowledge on quality measurement will be essential for a cardiologist in daily clinical care. To that end, this paper provides a comprehensive overview of the Dutch healthcare structure, quality indicators and the current and future assessment of quality of cardiac care in the Netherlands. The assessment of quality of care is becoming increasingly important in healthcare, both globally and in the Netherlands. With the transition into a regulated healthcare market system in 2006, insurance companies received a central role and the shared legal responsibility for the quality of cost-effective care. This responsibility created the legal need to develop a system in which quality of care can be measured and monitored . Currentdoing the right thing, at the right time, in the right way, for the right person—and having the best possible results [Quality of care has been defined by the Agency for Healthcare Research and Quality of the United States as  results . The aim results . Patient results ; Fig. 1)To accomplish all these goals, quality of care has to be measured. In 1966, Donabedian described three different types of measurable indicators for quality of care: structure, process and outcome indicators Structure indicators reflect the system and setting in which care is delivered and measurements relate directly or indirectly to staff expertise or the organisation. For cardiac care, examples are PCI volume, availability of a catheterisation laboratory and the educational level of the nursing staff. Structure indicators are less likely to be influenced by medical professionals and therefore less useful to monitor programs for quality improvement. They reflect the average results for large groups of providers, not individuals. The advantage of these structure indicators is that they are expedient and inexpensive to collect and can be used in plain hospital comparisons. Structure indicators are in general of limited use in clinical practice although recently a large study  was published in which a relationship was found between increased operator/institutional volume of PCI procedures and a decrease in adverse outcomes and cost of hospitalisation [n = 457,48 was pubProcess indicators describe the care patients actually receive. Examples for cardiac care are door-to-balloon-times in patients with a ST-segment elevation myocardial infarction and medication prescription according to the guidelines [idelines , 11. Theidelines . Anotheridelines . In hearidelines . In caseoutcome indicators. Examples of these are overall mortality rate, hospital readmission rate, functional health status and patient satisfaction. Outcome measurement is considered the most important measurement of quality of care but has to be acquired per patient and is therefore relatively time-consuming and expensive. In 2013, the Court of Audit (Algemene Rekenkamer) concluded that the quality of most indicator sets is limited and that only 7 % of the indicators collected by hospitals were outcome indicators [Quality of care is most effectively measured by clinical outcome measures, referring to the effect of the provided care on the health status of patients: dicators .National quality measurements are initiatives from government, supervision institutions, insurance companies and patient organisations. From the perspective of the individual hospital and/or cardiology department these initiatives can be judged to be external requests for accountability.Dutch Healthcare Inspectorate  has an important task, as described in Article 36 of the Healthcare Insurance Act, to verify if hospitals meet the minimum level of quality according to general healthcare acts and the professional standards as defined by the different medical specialists [The cialists . Verificcialists . The Safaccreditation programs to prove and objectify a certain level of quality of care as well as maintenance of quality of care to outsiders. The Netherlands Institute for Accreditation in Healthcare  aims to assure and improve Dutch healthcare by using an international accreditation program in which amongst others the VMS indicators are embedded. Some hospitals in the Netherlands use the international accreditation program, such as the Joint Commission International. Besides quantitative quality indicators, the accreditation systems comprise explicit quality policies and quality instruments, such as incident reporting and audits.Hospitals use external health insurance companies play a central role, positioned between patients and caregivers, with a shared responsibility to ensure good quality and cost-effective care. For the first time it became possible for the insurance companies to selectively contract. Additional to the responsibility in limiting the rising healthcare costs, insurance companies are required to analyse and interpret quality of care provided by caregivers. Article 14 of the Healthcare Insurance Act, and the general directorial based on this, states that insurance companies share the responsibility for efficient and timely healthcare of good quality, based on professional standards defined by the scientific professional organisations and healthcare providers. The explanatory memorandum of the act states that more information on outcome of caregivers will be available in the future [Dutch Healthcare Authority , with its task of overseeing the regulated healthcare market, is positive about the increased attention to quality of care in contracting during recent years [As described in the introduction, the Dutch healthcare system changed in 2006, aiming to reduce rising healthcare costs while improving quality of care. In order to achieve this, the Dutch government introduced a regulated healthcare market. Two new important acts were introduced: the Healthcare Insurance Act (Zorgverzekeringswet) and the Act of Regulation of Healthcare (Wet Marktordening Gezondheidszorg) , 16. In e future . Currente future , 19. Thent years .When focussing on cardiology in the Netherlands, there are three large national registries: (1) the National Cardiovascular Data Registry (NCDR), (2) the Supervisory Committee for Heart Interventions in the Netherlands  and (3) Meetbaar Beter. These registries are all initiated by the healthcare professionals involved and funded by the participating hospitals. From the perspective of the hospital and cardiology department, these initiatives can be regarded as internal quality initiatives, primarily meant to improve the internal quality of the individual healthcare provider. Increasingly, on request of the government, Healthcare Inspectorate, insurance companies and patient organisations, these registers are used for external accountability as well. The NCDR was initiated by the Netherlands Society of Cardiology  and organised in steering committees to develop different databases for every area in cardiology . FurtherThe first initiatives to register the quality of cardiac care on a national basis were started in Sweden and the United States. Currently, the Swedish registry SWEDEHEART collects data from all 74 hospitals in Sweden. In the United States, the American College of Cardiology (ACC) initiated the National Cardiovascular Data Registry (NCDR®CathPCI), which contains information on 12 million patients from 1577 participating centres . EnglandSince registration is a time-consuming process, it is important to ascertain whether the used quality indicators actually provide the desired effect of improving quality of care. Chatterjee et al. have described three mechanisms by which registrations can help to improve patient outcomes .reporting about quality of care in cardiology itself can lead to an incentive for hospital leaders and clinicians for improvement. In order to achieve this, it is important that results can be shared safely. Studies show that by paying attention internally to quality of care, improvement in outcomes of healthcare can be observed, which is called the Hawthorne effect [First of all, e effect .Public reporting can also be a powerful incentive for clinicians and hospital leaders to improve. Besides, transparency increases confidence of patients in the healthcare system. However, public reporting of quality indicators in the United States also demonstrated some disadvantages. First of all, some studies comparing reporting states and non-reporting states show no differences in outcome [www.kiesbeter.nl [ outcome . A furth outcome . A regis outcome . Public  outcome . Althoug outcome . To imprbeter.nl .Pay-for-performance is the newest quality improvement mechanism, which is gaining attention from healthcare leaders and healthcare insurance companies as a strategy for maximising quality while controlling costs. Pay-for-performance implies a shift in paying for quality healthcare instead of volume of care, which can be a strong stimulus to improve quality [ quality , 37.As addressed before, the results of any measurement must be relevant for the different stakeholders in healthcare. In the current use and development of quality indicators it is also important to take into account that indicators are scientifically acceptable. The indicators should therefore be reliable and valid .Reliable means that the indicator provides the same result on repeated measures and that the dataset is as complete as possible with uniform datasets which are collected in a uniform way. Also the Dutch Federation of University Medical Centres  points out in their report on a central vision on registration of care the value of a uniform standardised dataset. They aim to develop a uniform structure of elementary data elements and the use of a unified medical language based on international standards [tandards . The usetandards .Validity means that the indicator measures what it is intended to measure. This requires a good methodological quality, taking into account potential differences in case-mix and random variation. A common remark heard by doctors is that they worry about case-mix correction and that a negative outcome compared with others can be explained by the more difficult patient population served. A good case-mix correction applied in crude data could change the compared clinical outcome and is important to avoid unintended consequences [equences , 41, 42.On a national level, the current registries have to establish a unified collaboration and define useful indicators. NCDR, Meetbaar Beter and BHN are currently formalising this. It is intended that as of January 2016 NCDR and Meetbaar Beter will collaborate on the PCI database. On a regional level, hospitals should work together to acquire and exchange follow-up data, which requires commitment by the hospital’s board of directors in measuring quality of care on a local level. Possibly this can be achieved by appointing a board member on quality of care, as proposed by the Dutch government. Secondly, feasibility is of major importance. Currently, hospitals and their departments deliver between 600 and 1000 quality indicators to external parties each year. Since possibilities for automatic computation are still limited in most hospitals, this task is extremely time consuming. This leaves little time to use these externally reported quality indicators for internal improvement programs. Indicators should be easy to register in daily practice and ideally automatically obtainable. For this, integration of hospital electronic patient file systems with the national registries is essential. To ensure a long-term and reliable registry, solid funding is crucial. However, next to this national funding, sufficient funding on a departmental level is vital, especially if implantation is expected to become mandatory. Finally, it has to be decided what level of transparency is useful to improve the quality of care.The Dutch Minister of Healthcare has declared the year 2015 to be the year of transparency with the aim of improving healthcare by transparent reporting of quality of care. Furthermore, with the introduction of the regulated healthcare market, the position and role of the healthcare insurance companies provide an increasing focus on measuring quality of care. Initial thoughts are that quality indicators are connected with a lot of work without appreciating the benefits. Knowledge on and active participation in improving quality of care and quality measurements will be essential for cardiologists in daily clinical care. Active participation also offers major possibilities to design the most optimal quality measurement system and to take the lead in improving quality of care.None.Martin J. Schalij is a member of the Board of the National Cardiovascular Data Registry.Bas A.J.M. de Mol is a member of the Board of Directors of Meetbaar Beter.Giovanni Amoroso is a member of the Advisory Board of Meetbaar Beter.Victor A.W.M. Umans is a member of the Board of Governors of the NCDR and Meetbaar Beter.


Zika virus, which was first discovered in 1947, has become a global threat to human health as it is rapidly spreading through Latin America, the Caribbean, the US and Asia, after causing a large outbreak in the Northeast region of Brazil in 2015. There is ample evidence to support that Zika virus is associated with neurological complications such as microcephaly. The review aims to provide an overview on the complex issues involved in the emergence of Zika virus’s neurological disorders and to discuss possible explanations of Zika virus introduction and dissemination in Brazil. We also suggest national and global strategies to adequately respond to the Zika virus emergence.We provide an analytical evaluation of the main issues related to the Zika outbreak in Brazil, based on available scientific literature, including government documents, and on epidemiological information from national surveillance databases.Aedes aegypti might be the contributing factors for such an outbreak in Brazil. The Zika virus emergence emphasized the importance of cross-disciplinary perspective. Besides the scientific-based vector control strategies, it is important to understand the nature of the evolutionary processes involved in the viral evolution in complex ecosystems and to have social and anthropological knowledge on the conditions related to the spread of the disease in order to properly respond to the spread of the Zika virus.The studies on the clinical manifestations of the Zika virus infection coupled with the epidemiological surveillance information in Brazil have provided significant evidence that the Zika virus is associated with neurological disorders such as microcephaly and Guillain-Barré syndrome. Based on phylogenetic and molecular analysis, the hypothesis regarding the introduction of Zika virus in the country is that it took place following international events in 2013 and 2014, when many foreign visitors could have brought Zika virus into Brazil. The immunologically naïve status of populations in the Americas, previous infection with dengue virus, and the increased activity of The experiences of Brazil have demonstrated the significance of multi-disciplinary approach in response to new and resurgent arboviral diseases and provided important lessons that could be applied to other developing countries. Zika virus was first discovered in Uganda in 1947, and the first human case was documented in 1952 . The EmeThis paper will examine the complex issues involved in the emergence of Zika virus and discuss hypotheses regarding its introduction and dissemination in Brazil. Additionally, the paper also aims to provide insights into the eco-social determinants of Zika virus emergence and ways of integrating diverse conceptual frameworks into a transdisciplinary perspective. We hope that the lessons learned from the Brazilian experience can provide valuable insights for dealing with the emergence of new infectious diseases in other developing countries.Flavivirus genus and is mainly transmitted through the bite of infected Aedes mosquitoes (https://commons.wikimedia.org/wiki/File:Aedes_aegypti_feeding.jpg), which are also vectors for chikungunya, dengue, and yellow fever [Zika virus is an arbovirus in the ow fever .The symptoms of Zika virus infection are mild, similar to those of dengue, including fever, rash, joint pain, muscle pain and/or conjuntivitis and in most cases hospitalization is not required . HoweverTwo lineages of the Zika virus exist: the African lineage and the Asian lineage . The virSevere fetal birth defects such as microcephaly have been found in infants born to women infected with Zika virus, according to PAHO guidelines and National Surveillance Protocol in Brazil ,13. The Subsequently, several scientific studies have been conducted regarding Zika virus infection-related neurological disorders in newborns . In one Additionally, an increasing number of Zika virus infection-related cases of Guillain-Barré syndrome have been observed in Brazil. Although significant under-reporting may be expected to take place because Guillain-Barré syndrome is not a notifiable disease, information from Brazilian hospitals indicates an increase of 29.8% in hospitalizations from 2014 to 2015, from 1,439 to 1,868 cases; of note, some hospitals, such as Antonio Pedro Hospital in Rio de Janeiro, have reported an unusual increase in the number of cases .Aedes albopictus mosquitoes that are widespread in Latin and Central America, the US, and other regions not yet affected by Zika virus [Culex, a tropical domestic mosquito widespread in Brazil, might be able to transmit Zika virus since some arboviral infections are transmitted by several species of Culex [The pathogenesis and the mechanisms by which the Zika virus exerts its potentially severe effects on the brain of newborns and adults are still unknown. In Brazil, complete information regarding the number of pregnant women infected by Zika virus who gave birth to babies with microcephaly is lacking due to significant under-reporting and limited access to health care in the poorest regions. Although studies have suggested that Zika virus infection in the first trimester of pregnancy is related to more severe cases of microcephaly in newborns, a recent groundbreaking study in Brazil has found cases of Zika virus-associated severe microcephaly in all stages of gestation, including cases in the second and third trimester of pregnancy . We do nka virus . Furtherof Culex . This poAdditionally, other routes of transmission in addition to mosquito bites should be further studied. It is very likely that Zika virus can be spread through blood transfusions, and suspected cases in Brazil are under investigation. Sexual transmission has been confirmed by the US CDC as a route of transmission, although we do not know the transmission rate ,22. AlthAedes mosquitoes tend to concentrate. In 2014, the World Cup could have introduced Zika virus to Brazil, since many foreigners gathered in stadiums located in multiple states in Brazil. Finally, teams of rowers from French Polynesia, where a Zika virus outbreak occurred in 2013 and 2014, attended a canoeing championship in Rio de Janeiro in 2014. Concerns have been raised that the Olympic Games may lead to the introduction of new viruses into the country and to the possible global dissemination of Zika virus and other infectious diseases, despite significant governmental efforts to minimize these risks.A recent phylogenetic and molecular analysis by Brazilian researchers with international collaboration showed a single introduction of Zika virus into the Americas, estimated between May and December 2013 which indicates that the virus had been circulating in Brazil earlier than the first Zika virus infection case reported in 2015 ,25. ThisAedes aegypti mosquito activity. Additionally, it is important to note that during the large outbreak in Brazil, as in French Polynesia, the symptoms of Zika virus were reported in the context of a concurrent dengue epidemic [Aedes mosquitoes, produce more serious symptoms, such as higher fever and worse pain.Several explanations have been proposed regarding why the Zika virus emerged and caused an outbreak in Brazil. One possible explanation is the immunologically naive status of populations in the Americas compared to the populations of African and Asian countries where Zika virus has been circulating for decades and widespread immunity most likely exists against the virus ,25. A seepidemic . It is aWolbachia bacteria as a method of biologically controlling Aedes mosquitoes [For several political and institutional reasons, related to the decentralization of responsibilities in the National Health System and the elimination of federal structures in charge of vector control, such as the Superintendency of the Public Campaigns of Brazil - SUCAM in 1990, routine vector control has not been treated as a high priority in Brazil, although successful efforts have been made in some states and municipalities. In this context, emergency strategies are now under evaluation. In order to deal with Zika virus infection, several novel vector control strategies have been recently proposed and are now under the scrutiny of the scientific community and policy makers. One strategy is to modify the genes of mosquitoes to produce faulty offspring and reduce the quantity of larvae. This strategy has already been approved by the National Biosafety Commission in Brazil and applied by a British company, Oxitec, in some Brazilian cities. Another strategy is the sterile insect technology developed by the United Nations International Atomic Energy Agency, in which laboratory-bred male mosquitoes are exposed to nuclear radiation in order to make their sperm sterile before being released into the wild to mate with female mosquitoes. In this way, the mosquito population could be reduced in a few months. Another promising strategy to control Zika virus transmission by mosquitoes is using squitoes . NeverthThe Zika virus outbreak in Brazil revealed the need to further develop two important areas of knowledge in controlling and managing this arbovirus. The first crucial area of knowledge is the ecosystem. Having a comprehensive ecosystem-focused perspective is crucial in addressing vector-borne diseases with complex dynamic cycles involving vertebrates and blood-feeding vectors, such as mosquitoes and ticks. The importance of an ecological perspective is often missed in public health and epidemiological surveillance, and the absence of this perspective might explain previous failures in dealing with unexpected pandemics. The complex conditions affecting the evolution, introduction, mutations, variations, and adaptations of arboviruses in new ecological niches should be understood from this perspective -30. In pSocial and anthropological issues are another important area. Although genetic, immunological, and environmental conditions are important, understanding the social, economic, and anthropological aspects of the vulnerable population is also necessary because a pathogen requires a receptive population in order to cause disease. The specific social issues contributing to the Zika virus outbreak include rapid urbanization in conditions of extreme poverty, leading to intense deforestation that favors the contact of populations with unknown vectors and pathogens, as well as the intensification of international travel and population mobility. In addition, social vulnerabilities to new disease are not only a consequence of socioeconomic conditions, but also of the social behaviors related to risk and disease perceptions. It is therefore important to understand cultural and behavioral barriers when dealing with the emergence of new diseases. The importance of such barriers is demonstrated, for example, by the vulnerability of web users in Brazil to an erroneous rumor disseminated online that attributed Zika virus infection-related disease in newborns to vaccinations in pregnant women. Such barriers are also reflected by the social leniency of policy makers and the population overall regarding vector control measures, despite the availability of widespread information about this issue. Some studies have examined why access to information is not sufficient to change perceptions and behaviors. These studies have indicated that understanding the emotional component of attitudes is a crucial factor that could bring about effective access to behavior-changing information, and that an adequate understanding of emotions is required in the dissemination of new information ,32. ThesOther social and organizational issues in Brazil should be addressed in response to the Zika virus. Concerning health policy, the overall quality of National Health System services should be improved to deal with outbreaks of Zika virus. Although Brazil has a well-established universal health care system, it has been severely underfunded and undermined by the rapid increase of low-quality private health plans. Additionally, despite the existence of a well-established epidemiological surveillance system in Brazil, surveillance programs should be strengthened and refined in order to improve the quality of indicators and the ability to respond to unexpected occurrences of new and resurgent diseases.Aedes mosquitoes and to Zika as well as dengue and chikungunya, the poorest tend to be more vulnerable, and nearly 94% of Zika virus-related microcephaly cases have been reported in the economically deprived northeast region of Brazil. The majority of the Brazilian population lives in poor areas without adequate housing and sanitation, meaning that policies for better housing, sanitation, and garbage collection should be urgently implemented.Another issue is social policy concerning poverty and inequality. Although nearly everyone in Brazil is now exposed to The specific nature of the disease caused by Zika virus also highlights certain ethical issues. Abortion in Brazil is illegal; therefore, when effective diagnostic kits for Zika virus infection are developed, Brazilian society will have to come to a consensus regarding what to do when a pregnant woman tests positive for Zika infection. Women’s movements and organizations advocating for reproductive rights may be expected to play a crucial role in this process.Aedes in their houses as a response to the Zika virus outbreak, this campaign has not been effective because it has not been able to address transmission outside the home, which is conditioned by the urban and environmental determinants of transmission. Novel Zika virus control methods that incorporate environmental, urbanization, social, sanitation, and vector control policies with broader perspectives are urgently needed.Moreover, environmental policies are important in light of the dramatic global environmental and climate changes related to accelerated deforestation, urbanization, and global warming; these changes affect Brazilian ecosystems and have favored the proliferation of vectors and the emergence of new infectious diseases. Although the Brazilian government has put in place an extensive national campaign to mobilize the population to avoid the proliferation of Innovations and technological development policies focused on the development of new products are a major aspect of dealing with the Zika virus outbreak in Brazil. Currently, Brazilian institutions, despite very limited resources for research and development, are working on developing new and innovative diagnostic tools for the Zika virus, and it is expected that a new diagnostic tool produced by Bio-Manguinhos/Fiocruz will be available soon, after registration with the Federal Government Agency. This Bio-Manguinhos product is an ‘on-the-spot’ rapid test kit for measuring immunoglobulin M and immunoglobulin G.The experiences of Brazil with Zika virus underscore the conclusion that the conceptual approach to this new disease should shift from a traditional tropical neglected disease framework to an emerging and resurgent neglected disease perspective. Emerging and resurgent neglected diseases such as Zika virus are no longer confined to tropical regions and the most economically disadvantaged areas of the globe, but threaten other countries, including developed nations such as the US and European countries. Vector-borne viral diseases therefore deserve more public health attention, and an effective eco-social approach is needed in order to anticipate risks and provide interventions before the emergence and global spread of new and resurgent diseases. The experiences of Brazil have demonstrated that a cross-disciplinary approach supporting a social ecosystem health perspective  is cruci


The mortality rates of older people changes with the seasons. However, it has not been properly investigated whether the seasons affect medical care expenditure (MCE) and institutionalization. Seasonal variation in MCE is plausible, as MCE rises exponentially before death. It is therefore important to investigate the impact of the seasons on MCE both mediated and unmediated by mortality.Data on mortality, MCE and institutionalization from people aged 65 and older in a region in the Netherlands from July 2007 through 2010 were retrieved from a regional health care insurer and were linked with data from the Netherlands Institute for Social Research, and Statistics Netherlands . The Seasonal and Trend decomposition using Loess (STL) method was used to divide mortality rates, MCE, and institutionalization rates into a long-term trend, seasonal variation, and remaining variation. For every season we calculated the 95% confidence interval compared to the long-term trend using Welch’s t-test.The mortality rates of older people differ significantly between the seasons, and are 21% higher in the winter compared to the summer. MCE rises with 13% from the summer to the winter; this seasonal difference is higher for the non-deceased than for the deceased group (14% vs. 6%). Seasonal variation in mortality is more pronounced in men and people in residential care. Seasonal variation in MCE is more pronounced in women. Institutionalization rates are significantly higher in the winter, but the other seasons show no significant impact.Seasonal changes affect mortality and the level of MCE of older people; institutionalization rates peak in the winter. Seasonal variation in MCE exists independently from patterns in mortality. Seasonal variation in mortality is similar for both institutionalized and community-dwelling elderly. Policy-makers, epidemiologists and health economists are urged to acknowledge and include the impact of the seasons in future policy and research. Developed countries are faced with ageing populations and increasing health care expenses. Investigating the determinants of health care expenditure in the older population is therefore of high importance. Many epidemiological studies show that there is seasonal variation in mortality –16, but It has been found that mortality rates in the older population rise during winter time in Europe –10, 16, Here, we study the effect of the seasons on MCE and institutionalization . We aim to answer two research questions: (1) is there seasonal variation in mortality rates, medical care expenditure (MCE), and institutionalization rates (admission rates to care and nursing homes) in Dutch people aged 65 years or older?; and (2) does seasonal variation in mortality rates, MCE and/or institutionalization rates differ between subgroups, based on gender, age, vital status (close to death or not), and residential status ? We use the ‘STL decomposition method’ to detect a possible seasonal variation in the different measures. This method divides the data into a long-term trend, seasonal variation around the long-term trend, and ‘remaining’ variation. For the second research question we divide the study population into different subgroups.Health care in the Netherlands can be separated into two main sectors: medical care and long-term care. Medical care refers to consultations, medication and treatment from general practitioners, medical specialists, dentists, pharmacists, and therapists (such as physiotherapists and psychotherapists). Some forms of instrumental aid and transportation are also provided through the medical care sector. In the studied time period, health care providers bill health care insurers in the form of diagnosis related groups. Medical care is legally arranged through the Health Insurance Act (HIA).care offices. After an indication is set, the care office appoints a health care provider for a client, or distributes a personal budget. The health care insurer who has the highest share of clients in a region acts as the care office for that region.Long-term care in the Netherlands is legally arranged through the Exceptional Medical Expenses Act (EMEA). Entitled to care through the EMEA are people who cannot provide in their basic care needs independently due to a physical, psychogeriatric or psychiatric ailment, or a mental, physical or sensorial handicap. Before someone may receive long-term care through the EMEA, the Center for Indication Setting has to evaluate the client’s health status and issue an official indication. When an indication is set for a client, the actual provision of long-term care is arranged by so-called st 2007, residential care is indicated in terms of Care Weight Packages (CWPs). CWPs are pre-defined bundles of care, consisting of different types of long-term care on different levels, complemented with residence. From July 2007 through December 2010, residential care was categorized into ten CWPs: the first four relate to different types of residential care in care homes, the second four to nursing homes, the 9th to rehabilitation, and the 10th to palliative care.Indications for residential care are defined in type and level (hours per week). Since July 1Centraal Bureau van de Statistiek) for data collection. After consulting the IRB of Statistics Netherlands, a single transfer of data from the health insurer to Statistics Netherlands was undertaken over a secure line. A formal waiver was received by the IRB of Statistics Netherlands. After the data transfer, the Statistics Netherlands first removed any personal data. The leading author could then only access the de-identified data in a secured room of Statistics Netherlands. The authors had no access to identifying information. Any output destined for publication was first scrutinized by the IRB of Statistics Netherlands, so no output could be traced back to individuals. No data are publicly available. Data collection and analysis was in full accordance with privacy legislation and protocol.After consulting the internal review board (IRB) of the regional health insurer, data on health care expenditure were retrieved from a health insurer. A formal waiver of IRB approval was received from Statistics Netherlands  study was started in 2011. For this study, data on health care expenses of 61,495 people aged 65 and older in a period of 42 months were retrieved from a regional Dutch health insurance company (Zorg & Zekerheid) and matched with data on socio-economic characteristics from Statistics Netherlands. Data were collected using the following steps:With the aim to perform multiple studies on the association between the life situation of older people and their health care expenses, the Sociaal Cultureel Planbureau).After consulting the IRB  of the regional health insurance company, data on MCE were retrieved from the management information system of the health insurance company. Data were collected for the period July 2007 through 2010 for all persons who lived in the regions where the health care insurer acted as the long-term care office, and who reached the age of 65 before 2011. Addresses were linked with data on socio-economic status by postal code, provided by the Netherlands Institute for Social Research , an information system which offers an oversight of all the coded messages that are sent between organizations active within the confounds of the EMEA. ECR messages designating the start and end of long-term care provision were used to determine whether a client was institutionalized. Institutionalization rate was defined as the admission rate to care and nursing homes.After consulting the IRB of Statistics Netherlands a single transfer of data from the health insurer to Statistics Netherlands was done over a secure line. CBS staff merged the data using citizen service numbers and dismissed any personal data afterwards. The authors could then only access the de-identified data in a secured room of Statistics Netherlands. The authors had no access to identifying information. Any output destined for publication was first scrutinized by the IRB of Statistics Netherlands, so no output could be traced back to individuals. Data collection and analysis was in full accordance with privacy legislation and protocol. Socio-demographic variables collected at Statistics Netherlands were: age, gender, marital status, and time of death.The total study population of the LHCOA study  was used to investigate the association between the seasons and mortality, medical care expenditure (MCE) and institutionalization rate. If an association between seasonal change and mortality as well as MCE is found, it will be unclear whether the association with MCE is mediated by mortality in combination with the high costs of dying, or whether there is a direct association between seasonal changes and MCE. Therefore, the total study population was divided into two groups: subjects who died before 2012 , and those that survived until 2012 . If an association between seasonal changes and MCE exists in the survivor group, there is evidence for a direct association, unmediated by mortality rates and the costs of dying.Besides splitting up the study population into a deceased and non-deceased group, we also separated subgroups on the basis of age, gender, and residential status. We divided the population in community-dwellers and institutionalized subjects to further investigate the link between mortality and outside temperature. Institutionalized subjects were admitted in a care home or nursing home and were therefore predominantly or even exclusively exposed to a constant inside temperature. If there is also seasonal variation in mortality for the institutionalized, it is plausible that seasonal variation is caused by other factors than temperature alone.st and ends on March 20th. Therefore, winter data were defined as January, February and March. Spring, summer and autumn were defined using the subsequent three monthly periods.Seasons represent three-monthly periods. In the Netherlands, the winter season officially starts on December 21The Seasonal and Trend decomposition using Loess (STL) method was used to analyse seasonal variation in mortality risk, MCE, and institutionalization rate. The STL method decomposes longitudinal data into a long-term trend, seasonal variation, and remaining variation that does not stem from the long-term trend or from seasonal variation . The lonThe long-term trend is portrayed with a dotted red line, and the seasonal cycles around the long-term trend are shown with a solid black line. There is a strong long-term trend in institutionalization rate (panel C) between autumn 2007 and autumn 2011. The number of institutionalizations per 10,000 persons for every season rises from 46 in the summer of 2007 to 75 in the winter of 2009. Hereafter, the number slowly decreases towards 62 institutionalizations per 10,000 persons in the autumn of 2010.The average number of deaths , panel APanel B of The average number of institutionalizations was 65 per 10,000 persons in the study period. Only the institutionalization rate in the winter differs significantly from the long-term trend, when, on average, 6 more older people are institutionalized per 10,000 population. Consequently, there is a rise of 9% in institutionalizations in the winter compared the long-term average, and, since the institutionalization rate in the summer equals the long-term average, it is also 9% higher when comparing the winter to the summer . The autumn is characterized by the lowest number of institutionalizations.In There is greater seasonal variation in the mortality of men than that of women: the male mortality rate is 26% higher in the winter than in the summer, and this difference is 16% for women. In contrast, seasonal changes in MCE are more prevalent for women than for men: MCE is 16% higher in the winter than in the summer for women, and this difference is 10% for men. There is not much difference between the two age groups concerning seasonal variation in mortality rates, MCE and institutionalization rates. However, seasonal variations are slightly more concentrated in a winter peak for the older patients, and more dispersed throughout the seasons for younger patients.There is seasonal variation in mortality rates for both community-dwelling and institutionalized subjects. For community-dwellers mortality rates differ significantly from the long-term trend in all the seasons. The average number of deaths per 10,000 persons was 67 in the summer and 81 in the winter, meaning the number of deaths are 21% higher in the winter compared to the summer. With 27%, this difference between the winter and summer is higher for those who were institutionalized. For them, mortality rates differ significantly from the long-term trend in the winter and summer only.Institutionalization rates are consistently lowest in the autumn and highest in the winter, regardless of which subgroup is considered. The size of the relative differences between the autumn and the winter are also similar across subgroups: the lowest difference is 13%, found in males and those aged 80 years and older, while the highest difference is 17%, found in those aged younger than 80 years.We find that older people die more in the winter and autumn than in the spring and summer. Furthermore, their average level of MCE is considerably higher in the winter than in the spring and summer, and their risk of institutionalization peaks in the winter. Seasonal variation is stronger for men than women, but rather similar between age groups, deceased and non-deceased subjects, and institutionalized and community-dwelling elderly.Previous studies already showed that mortality in the older population is associated with the seasons –16, but Different biological pathways could underlie the influence of ambient temperature on older peoples’ health. For example, it has been found that colder temperatures are associated with increased blood pressure , 30, higBesides ambient temperature, there are many different season-dependent factors that potentially affect population health. First, it is possible that flu underlies seasonal variation in mortality and MCE, as prevalence rates of flu are higher in the winter, and institutionalized people are also—or even more—susceptible to flu compared to those in the community setting . Second,A higher prevalence of flu in the winter, as well as reduced hours of sunlight, may explain why older people in residential care also show seasonal variation in their mortality rates. Our analysis shows that men suffer more from seasonal changes than women, which stands in contrast to other findings , 8, 15. There are different explanations for the winter peak in institutionalizations. First, it is possible that climate conditions drive up the demand for long-term care. In this case, an exacerbation of chronic illnesses in the winter could stimulate elderly patients or their family to choose for more intensive long-term care. Second, it is possible that higher mortality rates in the winter drive up the supply of long-term care. In other words, a higher number of deaths results in a higher number of vacancies, and, consequently, a higher rate of institutionalizations if care and nursing homes are functioning at full capacity. Third, although small changes in long-term care policy took place from July 2007 through 2010 –some specific types of home care were abolished—it is implausible that these changes caused a peak in institutionalizations in the beginning of each year.The existence of seasonal variation in MCE, both close to death as well as independent from impending death, and institutionalization is a novel finding. For the purpose of our analysis, we were able to analyse data on a large study population, which could be separated into several subpopulations, and we used an advanced statistical method to disentangle seasonal variation from a long-term trend and other variation. However, the time period over which we could perform our analysis was rather short . Because, in addition, the data pertained to monthly or quarterly averages, we could not assess the proportional impact of flu, snow and ice, air pollution, sunlight, ambient temperatures, or other climate conditions on mortality, MCE and institutionalization. Another issue pertains to the representativeness of the study population. The study population consists of clients from one health insurer within specific regions of the Netherlands. Although the study population is quite comparable to the Dutch population aged 65 and older in terms of gender and marital status, the number of people aged 80 and older in the study population was relatively low (20% vs. 26.5%) . We coulWe performed this study for three reasons: (1) to make policy-makers aware of the impact the seasons can have on the health of older people (if any), as well as the collective health care budget; (2) to show epidemiologists and health economists if and how much the seasons affect MCE and institutionalization rates; and (3) to find out if specific patients groups are more at risk during certain seasons—in this case policy-makers and clinicians will know which patient groups will most likely benefit from targeted interventions.If the findings from our analysis of the older population in this region of the Netherlands are translated to the entire older Dutch population in 2012 –with a size of ±2.7 million—they would imply that there were 6,880 more deaths amongst older people in the Netherlands in the autumn and winter than in the spring and summer . In addiFurthermore, seasonal variation in mortality rates and medical care expenditure could warrant policy changes that could benefit older people and/or decrease the expenditure levels. The finding that institutionalized elderly have a more pronounced seasonal variation in mortality, show that these people may benefit from programmes targeting health care workers’ vaccination or hygiene, improving sunlight exposure or vitamin D status, or promoting better climate control in residential care facilities. To prevent increased levels of MCE or deaths of community-dwellers in the colder seasons, it is of primary importance that we understand which climate conditions impact their health, and through which biological pathways.Further investigations into seasonal changes in health, MCE and mortality should preferably use daily data over a long period in time, and include many different variables, such as ambient temperature, flu prevalence, sunlight hours, air pollution, atmospheric pressure, and humidity. Furthermore, including data on the types of illness or causes of death could disclose which biological pathways are mainly associated with seasonal changes in health and expenditure.Seasonal changes affect the mortality risk and level of medical care expenditure of older people; both outcomes are highest in the winter and lowest in the summer. Institutionalization rates peak in the winter. Seasonal variation is stronger for men than women, but similar between age groups. Changes in outside temperature cannot solely explain the seasonal variation in mortality because seasonal variation in mortality is similar for institutionalized and community-dwelling elderly. Also, seasonal variation in mortality cannot solely explain the variation in medical care expenditure, because the seasonal variation in medical care expenditure is present in the deceased and non-deceased population. Policy-makers, epidemiologists and health economists are urged to acknowledge and include the impact of the seasons in future policy and research. In a time where many countries are faced with population ageing, it is imperative that we gain insight into the causes of seasonal-dependent health deterioration as well as the best clinical means and policy measures to improve the health of older people.


P > 0.05), cervical spine ROM, and a reduction of spinal pain. The conclusion is that there is a significant association between TMD treatment and reduction of cervical spine pain, as far as improvement of cervical spine mobility.Temporomandibular dysfunction (TMD) is considered to be associated with imbalance of the whole body. This study aimed to evaluate the influence of TMD therapy on cervical spine range of movement (ROM) and reduction of spinal pain. The study group consisted of 60 patients with TMD, cervical spine pain, and limited cervical spine range of movements. Subjects were interviewed by a questionnaire about symptoms of TMD and neck pain and had also masticatory motor system physically examined (according to RDC-TMD) and analysed by JMA ultrasound device. The cervical spine motion was analysed using an MCS device. Subjects were randomly admitted to two groups, treated and control. Patients from the treated group were treated with an occlusal splint. Patients from control group were ordered to self-control parafunctional habits. Subsequent examinations were planned in both groups 3 weeks and 3 months after treatment was introduced. The results of tests performed 3 months after the beginning of occlusal splint therapy showed a significant improvement in TMJ function ( Recent years have seen a significant increase in the number of patients suffering from temporomandibular disorders (TMD) . AccordiThe issue of relationships between temporomandibular disorders and body posture is still a source of speculations. The knowledge about connections between distant body districts has to be proven by appropriate diagnostic procedures and instruments.TMD are musculoskeletal disorders needing a multidisciplinary effort to manage with other professionals  .Because of the variety of TMD symptoms, many patients had a history of multiple treatments and medications and were treated previously by laryngologists, neurologists, or physiotherapist, but the therapy did not bring the expected, long lasting results. According to currently prevailing theories, temporomandibular dysfunction is considered to be associated with imbalance of the whole body .In addition, the body as a whole operates on the principle of compensation, when it comes to disturbances in the upper quarter, such as increased muscle tension; this will lead to compensatory changes within the muscle tension in the spinal region so as to force the correct position/posture. These adaptive changes occur at all levels, within tolerance of the body , 6.When the body capacity to compensate for the pathological changes progressing in given areas is exceeded, however, imbalance sets in and pathological symptoms will appear. Each individual, obviously, has a unique compensation limit beyond which such symptoms are triggered off.It was pointed out by many authors that pain in the upper quarter and masticatory motor system may be caused by cervical spine disorders  and vice versa –9.It could be explained by specific functional and morphological connections between the cervical and temporomandibular regions.The sample was comprised of 60 individual  and was divided into two groups with randomization. Study and control groups both consisted of 30 people with TMD, cervical spine pain, and limited cervical spine range of movements (ROM). Subjects were directed from Cooperating Orthopaedic Service.Groups were not different regarding age and gender.Patients from both groups met the criteria for inclusion and exclusion of studies .Patients from both groups were recruited from cooperating clinics and previously diagnosed by an orthopaedist who excluded morphological and degenerative changes of cervical spine. Cervical spine pain was diagnosed by an orthopaedist according to the Neck Pain Task Force recommendations .Each patient had to have had cervical spine pain for at least 12 months in multiple episodes at a frequency of at least once a week. Patients were included in the study if having pain in the area between occiput and C7.Subjects gave written consent to participate in the study. The study was approved by the Ethics Committee of the Medical University of Silesia (number KNW/0022/KB1/6/I/10 from 16.03.2010).Each patient was examined three times. At the 3-week and 3-month evaluations, symptoms of TMD and cervical spine pain and mobility were studied.medical history and physical examination, based on a survey card (according to RDC/TMD);analysis of pain, using the visual analogue scale (VAS) and the cervical Oswestry scale for the cervical spine;TMJ functional evaluation by JMA device;cervical spine motion evaluation with the MCS device.In order to describe individual TMD symptoms, the entire sample filled out a questionnaire according to research diagnostic criteria for TMD, the translated Polish version (RDC/TMD axis I). The questionnaire focuses on symptoms specifically in the jaw-face, neck, shoulder girdle, intensity of spinal pain, and any other complaints of TMD and spinal origin. Presence of symptoms was marked according to duration, frequency, and intensity. The survey card was completed by each patient 3 times during three consecutive examinations which enabled a comparison of symptoms between groups according to treatment provided in treated group.The examination included the following:On a questionnaire, patients indicated the intensity of spinal pain experienced at the time of examination on a 100 mm visual analogue scale (VAS). Additionally, subjects described symptoms of pain and reduced mobility of cervical spine by filling in the cervical Oswestry scale.Clinical examination was performed according to RDC/TMD guidelines, too.Previously trained examiner assessed face symmetry, dentition, and occlusion, as far as “upper quarter” muscle tenderness to palpation with an emphasis on the masticatory muscles, trapezius muscles, suprahyoid muscles, infrahyoid muscles, sternocleidomastoid muscles, and neck muscles in the region of the linea nuchae. Each time the muscle tension was examined by the same examiner.Mandibular motion was recorded using jaw motion analyzer (JMA) from Zebris, (GmBbH) and the software provided (WinJaw) . The devThe subjects were provided with an explanation as to the objective of the axiographic examination and its course as well as what types of mandibular movements should be made and how. For each examination, it was necessary to make a paraocclusal clutch mounted on the vestibular surface of the lower teeth and fitted with an electronic sensor. The tool was made of light-cured Multitray (Espe).The study was based on the performance of patients' movements: opening and closing of the mandible, lateral movements, protrusion, and retrusion. To avoid bias, all subjects performed each trials three times. For each movement, the baseline position was the mandibular rest position. It seems that the rest position should be the starting point when assessing the motor function of the stomatognathic system using instrumental techniques .The advantages of this system are the ease of use and a positional accuracy of about 100 micrometers. Software allowed creating data report, which consists of graphic diagrams of TMJ function .Afterwards, the MCS  ultrasonic-based device was used to collect external kinematic data of the cervical spine movements. Patients with a neutral (comfortably seated) position performed maximal head movements: flexion, extension, rotation to the right and left side, and lateral flexion movements. Each movement was repeated three times in order to minimise measurement errors. The system was calibrated before each measurement. Data were monitored in a real time .Thanks to the repeatable measurements, values were found describing the cervical spine ROMs, presented in the form of relevant graphs.After the subjects' examination, data containing information about the quality and range of movement in both the TMJ and cervical spine were stored on a personal computer.After the first examination, each patient selected for the treated  group was supplied with an occlusal splint. Every patient suffered from TMD of muscular origin (RDC/TMD axis I); therefore, subjects were supplied with an occlusal splint SVED . SVED is a removable, flat-plane appliance which makes contact only with the anterior teeth in the opposing arch . It diseThe SVED appliance is used in case of hyperactivity of masticatory muscles, without the occlusal reason of TMD . It is uAccording to many researchers, there is no ideal way to handle the problem of control treatment, especially in splint studies. The use of a placebo control group can balance the nonspecific effects in the treatment group and allow for independent assessment of the real treatment effect . In our P < 0.05 was assumed to be significant while the test probability of P < 0.0001 was highly significant.The statistical analysis of the results was performed using the statistical package STATISTICA 9.0 (StatSoft). The test probability of 60 subjects were examined: 30 belonged to the treated group and 30 to the control group. Patients were randomly admitted to groups. The characteristics of age and gender for both groups are shown in All patients were simultaneously assessed by the same examiner.Referring to TMD research diagnostic criteria, in patients from both treated and control groups myofascial pain (I) or disc displacement with reduction  was diagnosed.After a three-month therapy with an occlusal splint considerable improvements of TMJ function were found in the experimental group, with 78% of the subjects reporting no DDR symptoms or acoustic phenomena like clicks during mandible movements; the abduction path of the mandible was symmetrical, and there was no pain during the movements .Most interestingly, however, there were changes on the condyle path in the TMJ during the measurements made with a JMA. Deviations within the condylar path which had been noticeable in the first examination (such as lack of symmetry between the length of the path in the right and left TMJ) became reduced in 28 subjects as a result of the treatment, and during the third measurement, the graphs of the condylar paths were asymmetrical on both sides in as few as four subjects. In 24 subjects, there were considerable improvements, which also improved the TMJ function.In the control group, no changes in the TMJ function were observed in the clinical examination or instrumental check with a JMA in successive examinations.Muscle tension was examined by palpation by the same examiner. In all subjects, upper quarter muscle tenderness  was diagnosed during three consecutive examinations. The presence of muscle pain and tenderness during palpation was registered in both experimental and control groups.During the third examination, the muscle tension of the subjects in the experimental group lowered considerably and they reported lack of pain in the examination by palpation. Out of the 27 subjects in whom intensified tension of the examined muscles had been found, 22 reported no complaints during the third examination. No significant changes were found in the control group.The whole group showed cervical spine pain. Cervical spine pain according to VAS scale in a treated group significantly improved during three-month therapy .During treatment, cervical spine pain diminished and after 3 weeks it occurred in 39% of subjects and after 3 months pain was only in 8% subjects from treated group (2 subjects).P < 0.0001).The difference between treated and control groups was statistically significant ; that is, there were more subjects in the experimental group with the result conforming to the norm.For the anteflexion movement, the improvement of the results was highly significant (P = 0.0082); that is, there were more subjects in the experimental group with the result conforming to the norm.Likewise, for the retroflexion movement, the results were improved by a highly significant factor (P > 0.05) changes were found; that is, there was no ROM improvement in the cervical spine towards the values in the norm.In the control group, no significant (The results of improving the mobility and reduction of cervical spine pain influenced the cervical Oswestry scale score. The average score on the first examination in a treated group was 9.22 points and during therapy, after 3 months, the average score changed to 3.71.The results obtained have confirmed a correlation between the pathologies and the positive impact of treatment within the motor aspect of the stomatognathic system on the alleviation of spine pain, even in subjects experiencing such pain for many years.It is important to understand the complex interrelations between the stomatognathic system and pain and dysfunctions in other areas of the body in order to be able to treat patients more efficiently and effectively at the initial stage, when painful symptoms appear and when curing them is possible as well as much swifter and more efficient. To be able to make successful therapeutic interventions, dental surgeons should cooperate in an interdisciplinary fashion with neurologists, orthopaedists, or laryngologists. They all should also take such interdependencies into account in their diagnostic work with their own patients.Scientists often note the importance of a holistic approach to therapy. There are many voices in favor of this approach that symptoms of the disorder are usually not isolated and the dysfunction of one region of the body also applies to other regions –20.Although the etiology of cervical spine pain very often remains unexplained, medical specialists in many cases report the comorbidity of dysfunctions in the stomatognathic system and the pain syndrome in the cervical spine . NumerouIn case of TMD, there are often large discrepancies between therapists concerning type of occlusal splint most appropriate to use. Many types of splints can be distinguished, for example, stabilization splint, repositioning splint, relaxation splint, or splints only for protecting oral tissues. SVED splint, which is a typical relaxing appliance, was used because of its influence on jaw muscles. No studies about different types of splints used in patients with both TMD and spinal pain were found .Our studies as well as the clinical followup suggest that TMD is very frequently present along with pain in the cervical spine. The key aspect of the studies described here is the considerable ROM improvement in the cervical spine and the elimination of cervical spine pain felt there by the subjects in the experimental group. Taking into account the results of our study, it seems obvious that interdisciplinary cooperation between orthopedist, laryngologist, neurologist, and dentist is necessary and essential.