Big data analytics offers promise in many business sectors, and health care is looking at big data to provide answers to many age-related issues, particularly dementia and chronic disease management.The purpose of this review was to summarize the challenges faced by big data analytics and the opportunities that big data opens in health care.Challenges and Opportunities, respectively. We rank-ordered and analyzed the themes based on the frequency of occurrence.A total of 3 searches were performed for publications between January 1, 2010 and January 1, 2016 , and an assessment was made on content germane to big data in health care. From the results of the searches in research databases and Google Scholar (N=28), the authors summarized content and identified 9 and 14 themes under the categories The top challenges were issues of data structure, security, data standardization, storage and transfers, and managerial skills such as data governance. The top opportunities revealed were quality improvement, population management and health, early detection of disease, data quality, structure, and accessibility, improved decision making, and cost reduction.Big data analytics has the potential for positive impact and global implications; however, it must overcome some legitimate obstacles. Big data analytics offers promise in many business sectors, and health care is looking at big data to provide answers to many age-related issues, particularly dementia and chronic disease management. This systematic review explores the depth of big data analytics since 2010 and identifies both challenges and opportunities associated with big data in health care. The review follows the standard set by Preferred Reporting Items for Systematic Reviews and Meta-analysis (2009) [Big data is commonly defined through the 4 Vs: volume , velocity , variety , and veracity . The first 3 Vs are found in most literature ,3, and tAs of 2012, about 2.5 exabytes of data are created each day; Walmart can collect up to 2.5 petabytes of customer-related data per hour [There are several large sources for big data in health care: genomics, EHR, medical monitoring devices, wearable video devices, and health-related mobile phone apps. Approximately 483 studies on genomics are registered with the US Department of Health and Human Services; these studies are being conducted in 9 countries, and they all use portions of the data from the Human Genome Project . The EHRThe decrease in the cost of storage has enabled an exponential distribution of data collection, but the ability to analyze this quantity of data is the center of gravity for “big data” in health care. In the United States, financial incentives offered for the “meaningful use” of health information technology has spurred growth in the adoption of the EHR and other enabling health-related technology since 2009.Health information systems show great potential in improving the efficiency in the delivery of care, a reduction in overall costs to the health care system, as well as a marked increase in patient outcomes . The US With the implementation of this legislation as well as the technologies associated with it, it is imperative to effectively organize and process the ever-increasing quantity of data that is digitally collected and stored within health care organizations. Other industries such as astronomy, retail, search engines, and politics have developed advanced data-handling capabilities to convert data into knowledge. Health care needs to follow their lead so that decisions regarding organizational objectives and goals can be met ,11,12. TThe purpose of this systematic review is to objectively review articles and studies published in academic journals in order to compile a list of challenges and opportunities faced by big data analytics in health care in the United States. Particular emphasis was paid to age-related applications of big data.Articles and studies were eligible for analysis if they were published between 2010 and 2015, published in academic journals, and published in English. The researchers chose a range from 2010 to 2015 for two reasons: HITECH was passed in 2009, and it appeared that a blossom of research and other articles seemed to occur in 2010. We focused on academic journals for their peer-review quality and to decrease the chance of selecting something about big data published from a noncredible source.A combination of key terms from Medical Subject Headings (MeSH) and Boolean operators were combined and used in 2 common research databases, CINAHL and PubMed, and combined with a general search from Google Scholar see  in JanuaThese terms were chosen not only because they are the focus of the review, but also because they were identified in the initial research into the definition of big data.The following search string was used in all 3 searches:  OR ). This search string was used in CINAHL, PubMed (MEDLINE), and Google Scholar. In the 2 research databases, our team was able to restrict the search to academic journals (including other systematic reviews). MEDLINE was excluded in CINAHL because it was already captured in PubMed. Google Scholar creates difficulty for searches because of its severe limit of filters typically associated with academic research. The initial 13,935 results were limited by restricting dates to the last 5 years, limiting results to academic journals and MEDLINE, and in Google Scholar by restricting the keyword search to titles. The result from the filters ended with 121 articles to review.Through group research and a series of consensus meetings, researchers were trained to identify articles germane to this review and to recommend elimination of all others. A shared spreadsheet was used by the research team to parse through the list of articles. Researchers read all articles in their entirety. A total of 97 articles were eliminated due to various exclusion criteria , and 4 additional articles were identified from the references of the 24 that remained. The group of reviewers made these rejections or additional recommendations through a series of consensus meetings where we met to discuss their recommendations and consensus was reached through discussion. A total of 28 articles remained in the final review.Each article was reviewed by at least two authors to identify the relevant points. All reviewers used a spreadsheet template to summarize their key observations from each article. One team member combined the spreadsheets into one and shared it once again. Reviewers held one more consensus meeting to discuss their findings. From this meeting, trends were identified, and from those trends, inferences were made.From the list of observations, reviewers were able to identify some common threads that emerged as challenges and opportunities in health care that permeated multiple articles. Separate tables were created to group the threads, and from each of these tables, common themes were identified. These common themes only emerged when reviewers combined their observations. These themes were tabulated and counted for additional analysis.As depicted in Multiple reviewers read each article in its entirety. Articles were included or excluded based on the criteria illustrated in A study catalog number was assigned to each article to simplify the analysis. Researchers summarized the main points of each article for further analysis.Through the combination of observations, reviewers identified common threads  and themes from each thread. Themes were organized into affinity diagrams  and 2, cNine themes emerged under the category of challenges: data structure, security, data standardization, data storage and transfers, managerial issues such as governance and ownership, lack of skill of data analysts, inaccuracies in data, regulatory compliance, and real-time analytics. Examples for each theme are provided in The 4 Vs appear in multiple places under the Challenges category. Volume and variety are seen by name under the theme of Data structure. Variety is also implied in the same theme, but listed as Incompatible formats, as well as Raw and unstructured datasets. Variety can also be inferred from the theme of Data standardization, listed as Limited interoperability. Velocity is seen in the theme Real-time analytics. Veracity is seen under the theme of Data Standardization, but listed as Data acquisition and cleansing, Terminology, and Language barriers. It is also inferred in the theme Inaccuracies listed as Inconsistencies and Lack of precision.Issues related to data structure were addressed in the majority of the papers reviewed for this study. It is essential that the key functions of data processing are supported by the applications of big data . Big datResearch data within the health care sector is more heterogeneous than the research data produced within other research fields ,5,12. DaThere are considerable privacy concerns regarding the use of big data analytics, specifically in health care given the enactment of Health Insurance Portability and Accountability Act (HIPAA) legislation . Data thAlthough the EHRs share data within the same organization, intra-organizational, EHR platforms are fragmented, at best. Data is stored in formats that are not compatible with all applications and technologies ,22. ThisLimited interoperability poses a large challenge for big data, as data is rarely standardized ,13,16,22Data generation is inexpensive compared with the storage and transfer of the same. Once data is generated, the costs associated with securing and storing them remain high . Costs aData governance will need to move up on the priority list of organizations, and it should be treated as a primary asset instead of a by-product of the business . Data owIt is important that health care workers are also kept up to date with the use of constantly changing technology, techniques, and a constantly moving standard of care ,24. Due Self-reported data is extensively used in health care, and so it is crucial that the data collected in this manner be consistent . KeepingHealth care organizations should be aware of the various legal issues that can surface in the process of managing high volume of sensitive information. Organizations implementing big data analytics as a part of their information systems will have to comply with a significant amount of standards and regulatory compliance issues specific to health care . Only 4%One of the key requirements in health care is to be able to utilize big data in real time. Real time is defined by enabling the use of applications such as cloud computing to view said data in real time. The use of these technologies leads to issues of security and privacy within patient information . Only 4%Fourteen themes emerged under the category of opportunities: improve quality of care, managing population health, early detection of diseases, data quality, structure, and accessibility, improve decision making, cost reduction, patient-centric care, enhances personalized medicine, globalization, fraud detection, and health-threat detection. Examples of each theme are listed in Despite the challenges that big data needs to overcome, the advanced analytics that are promised through big data offer tremendous opportunities for most stakeholders in the health care industry . More than 64% of the articles analyzed focused on quality improvement and more than 60% on managing population health and early detection of diseases through big data analytics. If even some of the opportunities of big data are realized, they can radically change patient outcomes and the way decisions are made by providers, and help solve some macro-level issues related to health care within countries such as the United States .Big data has the potential and ability to improve the quality and efficiency of care ,23,29-31Quality of care will also be improved by reducing waste of information, which will reduce inefficiencies ,26. ThisThe management of population health and the early detection of diseases were topics that the authors thought would have highly similar results after the analysis. Although there was a large overlap between the 2 themes, there was also specific variation between them. So, the researchers chose to keep them separate. The theme of managing population health focused on special populations rather than public health.Big data analytics define populations at a finer level of granularity than has ever been previously achieved ,14,15,33Big data allows for the early detection of diseases, which aids in clinical objectives related to achieving improved treatments and higher patient outcomes ,15,22,25Literature suggests that big data enables rapid capture of data and the conversion of primary, raw and unstructured data into meaningful information ,17,31,34Big data enables appropriate use of evidence-based medicine and helps health care providers make more informed decisions ,13,15,22Decision-making process can be highly optimized by the availability of accurate and up-to-date information, as decision making is influenced by the generation of new practices and treatment guidelines within clinical research. Allowing big data to influence decision making will allow for a faster and simpler process. This is done by either supporting or replacing human decision making. About 39% of the literature mentioned this opportunity.The literature suggests that the decrease in cost of the elements of computing, such as storage and processing, leads to a decrease in the cost of data-intensive tasks ,13. ThisIncreasing the use of technology is slowly changing the direction of the health care sector from disease-centric care toward patient-centric care . Big datWith the use of big data, the objectives of personalized medicine can be translated into clinical practice ,25,30. ABig data will actively help in disseminating the knowledge acquired from the data collected ,22,30. BOne of the most significant benefits offered by big data is that it is instrumental in detecting fraud in an efficient and effective manner ,23. For Big data offers opportunity for improving capabilities of threat detection quickly and more accurately. This can be especially beneficial for government use . Big datOpportunities most often mentioned or discussed were improve quality of care , managing population health , early detection of diseases , data quality structure and accessibility , improve decision making , cost reductions , patient-centric health care , enhancing personalized medicine , and globalization . The other two opportunities each comprised less than 15% of the observations.Although the integration of big data is well underway in industries such as finance and advertising, it has not yet fully assimilated into health care. Challenges and opportunities were made quite clear in the articles analyzed in this review. Three of the 4 Vs  were consistently adhered to. The fourth V, veracity, was found, but rarely listed by name. A big limitation in this review is the low number of articles used in the analysis. If we were to do this over again, we would query another database to see whether additional articles were available for analysis.Selection bias seems to exist in any study. Our control for selection bias was the initial research up front to agree on a definitive definition of the concept of big data, and our consensus meetings to discuss findings. The consensus meetings offered great value to the process because they enabled the group to hear the focus of an individual and either provide feedback to confirm the focus or agree that the unique focus was warranted for all the articles in the review.Another bias that we discuss regularly is publication bias. Journals tend to publish results that are statistically significant, which inherently limits the publication of research that may not reach that level. Our control for publication bias was to include Google Scholar in our search. Our intent was to identify material in lesser-known journals that might not be indexed in PubMed (MEDLINE) or CINAHL.Big data and the use of advanced analytics have the potential to advance the way in which providers leverage technology to make informed clinical decisions. However, the vast amounts of information generated annually within health care must be organized and compartmentalized to enable universal accessibility and transparency between health care organizations.Our systematic literature review revealed both challenges and opportunities that big data offers to the health care industry. The literature mentioned the challenges of data structure and security in at least 50% of the articles reviewed. The literature also mentioned the opportunities of increased quality, better management of population health, early detection of disease, and data quality structure and accessibility in at least 50% of the articles reviewed. These findings identify foci for future research.


Bioengineering & Translational Medicine was launched in 2016 with the goal to highlight the scientific and technological issues relevant to the translational challenges of bioengineering science and technologies. Clinical translation of promising biological technologies can have a transformative impact on human health. Several advances in bioengineering have already had a huge impact in the diagnosis and treatment of human diseases. However, with rapid development of new technologies coming down the innovation pipeline, it is critical to develop streamlined pathways for their eventual translation to the clinic. The journal has been met with significant excitement by the scientific community.Bioengineering and Translational Medicine. Specifically, a new scientific meeting, Translational Medicine and Bioengineering Conference, was launched to further highlight the significance of this topic. The conference was organized on November 12 and 13, 2016 in San Francisco, CA , just ahead of AIChE's annual meeting. It brought together scientists, bioengineers, leaders from industry, and various stakeholders as part of a single‐track conference format at the interface of innovative biological technologies and clinical translation.Last year saw another milestone for AIChE and SBE in the field of Professors Ravi Kane and Mark Prausnitz from Georgia Tech were the inaugural co‐chairs of the conference, and along with individual session co‐chairs, organized an exciting program that brought forth cutting‐edge translational bioengineering technologies in biopharmaceuticals, gene and drug delivery, immunoengineering, biomanufacturing, and stem cells and regenerative medicine in technical sessions dedicated to each of these topics. Each session had a strong mix of invited speakers as well as contributed platform presentations. The program also included a panel discussion on entrepreneurship in which entrepreneurs from academia, industrial leaders, and technology transfer specialists shared invaluable thoughts and experiences in the path traveled from the lab bench to the clinic. The conference provided a unique platform for bioengineers to present innovative advances at different stages of the translational spectrum.BioTM features contributions from some of the participants in this conference as well as other scientists in the field. Prof. Christopher Jewell (U. Maryland) and coworkers review the latest advances in immunomodulatory biomaterials for applications in regenerative medicine and tissue engineering.This special issue of Bioengineering and Translational Medicine.We invite you to read the excellent array of review and research articles in this issue of


Aims. To establish a logistic regression (LR) prediction model for hepatotoxicity of Chinese herbal medicines (HMs) based on traditional Chinese medicine (TCM) theory and to provide a statistical basis for predicting hepatotoxicity of HMs. Methods. The correlations of hepatotoxic and nonhepatotoxic Chinese HMs with four properties, five flavors, and channel tropism were analyzed with chi-square test for two-way unordered categorical data. LR prediction model was established and the accuracy of the prediction by this model was evaluated. Results. The hepatotoxic and nonhepatotoxic Chinese HMs were related with four properties (p < 0.05), and the coefficient was 0.178 (p < 0.05); also they were related with five flavors (p < 0.05), and the coefficient was 0.145 (p < 0.05); they were not related with channel tropism (p > 0.05). There were totally 12 variables from four properties and five flavors for the LR. Four variables, warm and neutral of the four properties and pungent and salty of five flavors, were selected to establish the LR prediction model, with the cutoff value being 0.204. Conclusions. Warm and neutral of the four properties and pungent and salty of five flavors were the variables to affect the hepatotoxicity. Based on such results, the established LR prediction model had some predictive power for hepatotoxicity of Chinese HMs. Chinese herbal medicines (HMs) have been worldwide applied , and the Yao Xin, the innate nature of Chinese HMs on which Chinese HMs depend to exert or generate the effect. Yao Xin includes five aspects: four properties, five flavors, channel tropism, ascending and descending and floating and sinking, and toxicity )  .The data were put into the prediction model to get the prediction probability. When the cutoff value for the prediction probability was 0.204, in the 431 hepatotoxic Chinese HMs, 184 nonhepatotoxic Chinese HMs were misjudged as hepatotoxic one and, in 107 hepatotoxic Chinese HMs, 19 hepatotoxic were misjudged as nonhepatotoxic Chinese HMs. The overall accuracy rate was 50.558% .This research aims to establish an LR prediction model for hepatotoxicity of Chinese HMs based on TCM theory and to provide a statistical basis for predicting hepatotoxicity of HMs.The correlation between the independent variables  and the dependent variable (hepatotoxicity and nonhepatotoxicity of Chinese HMs) was evaluated with chi-square test for two-way unordered categorical data, and the result showed that hepatotoxic and nonhepatotoxic Chinese HMs had no correlation with the channel tropism but had correlation with four properties and five flavors. Unconditional LR was applied to screen the influential factors from the two categories of variables, totally 12 variables. The influential factors include warm and neutral from four properties and pungent and salty from five flavors. Pungent is the risk factor while salty, warm, and neutral are the protective factors for hepatotoxicity of Chinese HMs.Hepatotoxic and nonhepatotoxic Chinese HMs have no obvious difference in the distribution on channel tropism. The so-called hepatotoxic Chinese HMs by biomedicine actually have multiple channel tropism, and the so-called nonhepatotoxic Chinese HMs have multiple channel tropism, too. This might be due to the fact that the organs in biomedicine do not correspond with the organs in TCM . For exaIt is generally held that the volatile oil, glycosides, and alkaloids are the main material basis of pungent HMs . ResearcAccording to the TCM theory, salty flavor has the function to soften the hard mass and cause purgation. Modern pharmacological research has shown that inorganic salts and iodine are the main components of salty Chinese HMs , and theTCM holds that four properties are the summarization of the body reactions due to the action by medicine. Chinese HMs with the function to promote body to become warm or hot are the warm or hot Chinese HMs (hot is stronger than warm); otherwise, the Chinese HMs are cold or cool. The neutral is the one neither hot nor cold. In this study, the hepatotoxic or nonhepatotoxic Chinese HMs of hot properties are less than those of cold, cool, warm, and neutral properties, which might be the possible reason that hot property did not show correlation with hepatotoxicity of Chinese HMs according to our statistical analysis. táo rén (Semen Persicae) with neutral properties has the function to promote or suppress the cyclic AMP-dependent protein kinase (PKA) cAMP/PKA signal pathway in the experimental rats with blood stasis of cold or warm patterns [β-adrenergic receptor/cAMP/PKA axis protects against the oxidant-mediated cell injury [Research has shown that, in the experimental rats with cold patterns, Chinese HMs with warm and hot properties could promote the metabolism of glucose and lipid and protein synthesis in the mitochondria, therefore to increase the energy metabolism in the mitochondria . Anotherpatterns . Also otl injury , 29. Besl injury , 31. Soml injury . Some rel injury . TherefoIn the analysis on the LR prediction model of hepatotoxicity of Chinese HMs, we have established that, in the 431 nonhepatotoxic Chinese HMs, 184 were misjudged as hepatotoxic; in the 107 hepatotoxic Chinese HMs, 19 were misjudged as nonhepatotoxic. The misjudgment rate was 49.44%. The possible reasons are as follows: the inclusion criterion for the hepatotoxicity is so broad that the included variables from the four properties and five flavors show weak correlation with the hepatotoxic Chinese HMs.Research has also shown that the hepatotoxicity could be further classified. For example, HMs with the cold property show an intensive effect in liver hepatitis, HMs with the hot property show a stronger effect in liver cirrhosis, and both of them manifest effects in hepatocellular carcinoma . TherefoIn the analysis on the misjudgment of this LR prediction model for hepatotoxicity, it is shown that the ratio for nonhepatotoxic Chinese HMs being misjudged as hepatotoxic is 43.38%, and the ratio for hepatotoxic Chinese HMs being misjudged as nonhepatotoxic is 17.75%. Therefore, it could be concluded that the judgment for hepatotoxicity of Chinese HMs is stricter than that for nonhepatotoxicity of Chinese HMs by using this prediction model. If this model is applied to the development of new drugs from Chinese HMs, it will be more likely to avoid the risk of hepatotoxicity and to ensure the safety of Chinese HMs. Besides, researches have shown that various HMs which are traditionally considered “nontoxic” are gradually found to have potential hepatotoxicity [In the future, with the development of the research of hepatotoxicity of Chinese HMs, there will be more and more data available for the establishment of the prediction model, and the predictive power of this logistic regression prediction model for hepatotoxicity will be increased correspondingly.In this research, four properties, five flavors, and channel tropism, 24 variables from 3 categories, were analyzed for their correlations with the hepatotoxicity of Chinese HMs. There were 12 variables from four properties and five flavors to be input for LR and to establish an LR prediction model. This research employs a new method by combing TCM theory with modern statistics. By combining TCM theory with modern research on hepatotoxicity, this research provides a prediction model for hepatotoxicity of Chinese HMs based on statistics. The method employed in this research is promising for predicting hepatotoxicity of Chinese HMs and could provide some references for avoiding hepatotoxicity in the development of new drugs from Chinese HMs. The combination of generality and vagueness of TCM theory and accuracy of modern science could be a new method for combing biomedicine with TCM.


Japan has the largest percentage of elderly people in the world. In 2012 the government implemented a community-based integrated care system which provides seamless community healthcare resources for elderly people with chronic diseases and disabilities.This paper describes the challenges of establishing a community-based integrated care system in 1974 in Mitsugi, a rural town of Japan. This system has influenced the government and become the model for the nationwide system.In the 1970s, Mitsugi’s aging population was growing faster than Japan’s, but elder care was fragmented among a variety of service sections. A community-based integrated care system evolved because of the small but aging population size and the initiative of some local leaders of medical care and politics. After the system took effect, the proportion of bedridden people and medical care costs for the elderly dropped in Mitsugi while it continued to rise everywhere else in Japan. Mitsugi’s community-based integrated care system is now shaping national policy.Mitsugi is in the vanguard of Japan’s community-based integrated care system. The case showed the community-based integrated care system can diffuse from rural to urban areas. Japan’s elderly population is growing. The percentage of people more than 60 years old is 32.3% and the average age is 45.9 years old, the highest in the world \3The government of Japan has introduced a nationwide community-based integrated care system. The purpose of this system is to care for elderly people with chronic disease or disabilities in a comprehensive and integrated manner, while containing social security costs.The community-based integrated care system, to the letter, integrates a community’s health-care resources, through the coordination not only of hospital outpatient and inpatient sections but also of welfare facilities, home-visit care services, and even mutual support activities among neighborhoods Figure  56]. Am6. Am56].The community-based integrated care system originated in 1974 in a rural town, Mitsugi, located in a mountainous area of Hiroshima prefecture. Mitsugi Hospital, the town and prefecture governments cooperated to create Japan’s first community-based integrated care system. After it became successful, Mitsugi’s system was used as a model for nationwide integrated care. This paper explains the establishment and outcomes of Japan’s first community-based integrated care system in the rural town. The history of Mitsugi could inform policy making in other countries with aging populations.2  with agriculture as its principal industry in 1970s [Mitsugi was a rural town of 8800 inhabitants, population density 106/kmMitsugi General Hospital provided only acute care in the 1960s, but later added long-term care and preventive services  in Mitsugi were originally employed by the municipal government. But the mayor helped Dr. Yamaguchi to have them employed by the hospital instead.However, many residents initially resisted Dr. Yamaguchi because they were not accustomed to the innovative service-providing system. In addition, many health professionals, including doctors, were more comfortable with the sectionalism and unwilling to adjust to the integrated system. Dr. Yamaguchi has served for 30 years as a surgeon and the hospital head in Mitsugi, which gave his support for integrated care more persuasive power. He also had strong political and financial support from the governor and the mayor. He met face to face with representatives of residents and health professionals who opposed his proposal, and finally won them over. Then he built the system which spread through the town.Community-based integrated care in Mitsugi town has achieved three results.The first and most notable was the reduction in the number of bedridden people. Mitsugi town had a larger proportion of bedridden population than Hiroshima prefecture until 1983, but ten years after the implementation of the community-based integrated care system the figure had fallen and stabilized at one percent  could have been strengthened with the formation of volunteer organizations as a part of the community-based integrated care system. Periodic health promotion classes for residents sponsored by the hospital and the volunteers in the Hospital Complex might have reinforced the bonds among local residents, building social capital and spreading health awareness. The stronger connection and awareness might have led to the increase in the number of people undergoing medical checkups . When mo13141516All Japanese citizens have been covered by the social health insurance since 1961 so that they can receive affordable medical care. In addition, a mandatory long-term care insurance system was implemented in 2000, because the number of elderly people who needed long-term care swelled as the population aged . ThroughAfter establishing the economic framework, the Japanese government opened Community-based Integrated Care Centers in every district  of Japan since 2005, when the government revised the Long-term Care Insurance Act . The Cen19A research team of the community-based integrated care system was appointed by the Ministry of Health, Labour and Welfare in 2003. The head of the Mitsugi General Hospital, Dr. Yamaguchi, reiterated the significance of the system in the Diet and to the advisory board of the national government. Finally, the system created in Mitsugi town became the basis of national policy in 2012. In the policy, the framework of the care system was referred to Mitsugi’s, but the details were left to the discretion of each municipal government because of differences in scale, social resources, history and culture. For example, not each community needs a hospital-centered model like Mitsugi Hospital Complex. The government hopes that the system will be in place nationwide by 2025 when Japan’s population of older people is expected to reach its peak .Rural areas could be the vanguard of solutions to Japan’s aging problem, because the rural population is aging faster than the cities. Hence, the effort in these rural areas should be noted to by the national governments which have to deal with aging citizens.Japan’s most important healthcare policies have traditionally originated in cities and spread to rural areas. For example, the first policyholders of universal health insurance were urban municipalities and corporations, so the rural municipalities and the rest of the country followed suit. However, the community-based integrated care system showed the opposite pattern: the influence spread from the rural area to the central city and finally nationwide. In other words, Mitsugi has proven that a small town that met the needs of its aging residents could be a national model. The problem of an aging population is serious in developed countries and soon will be among developing countries . In suchThere are four possible reasons for Mitsugi’s foresight in building a community-based integrated care system.Mitsugi town had a more rapidly aging population than the rest of Japan, and therefore required a more urgent solution. The number of bedridden elderly people also became a problem in Mitsugi sooner than elsewhere. Without these problems, there would have been no need for a solution.In addition, towns such as Mitsugi have fewer hospitals, welfare facilities and preventive organizations than large cities do. Since there is usually only one of each of these facilities in a rural town, it is relatively easy to coordinate their services. Residents of cities with many medical and welfare institutions, have many options. It is therefore difficult for them to integrate medical, welfare and long-term care services.A third reason is that the budget for the construction of welfare facilities came from Hiroshima prefecture . This suLastly, Mitsugi enjoyed strong and innovative leadership. Dr. Yamaguchi, appointed head of Mitsugi General Hospital in 1966, noticed the increase of bedridden patients caused by inadequate long-term care at home or the discontinuation of rehabilitation after discharge from the hospital. His observations moved him to construct the system. He started by moving part of the public administration into the Mitsugi Hospital Complex and instructed medical staff to bring medical, nursing, long-term care and rehabilitation services to patients in their homes. Some residents and staff members objected to these new initiatives. However with the support and encouragement of the mayor, the objections were overcome .Therefore, talented leaders, imminent problems, a simple service structure that was characteristic to rural areas and political support from the prefectural and/or the national government appeared to make this success possible. A strong leader was imperative to unite the stakeholders.The community-based integrated care system now has three tasks.Above all, the system should be tailored to each community. Although the community-based integrated care system became national policy in 2012, the system has not yet been established nationwide. Special care must be taken in cities where there are chaotically distributed hospitals and institutions that are difficult to coordinate. Large cities have more health care institutions and professionals than rural towns like Mitsugi do. Unlike those in Mitsugi, health institutions in an urban area are managed by many corporations. Thus multi-institution and multi-occupation collaborations are more complicated in urban than in rural areas. It is also important to keep in mind that not all communities have an energetic and visionary leader like Dr. Yamaguchi. Thus political leadership of municipal governments is needed to implement the integrated care system in a community, particularly in urban communities.It is also essential to enlist the participation of residents. Residents are more than recipients of care; they are a fundamental element of the system. They can identify elderly neighbours who need medical or long-term care services, support them and introduce them to the system.Finally, the system needs to be economically sustainable. The community-based integrated care system is expected to contain rising medical and long-term care costs. Although this effect was obvious in Mitsugi, it is not known that this will be the case on a nationwide scale. It is possible that the proper allocation of resources to each municipality would be a key point of economic sustainability.Japan’s community-based integrated care system was born in the rural town of Mitsugi. The system has slowed the growth of healthcare costs and decreased the proportion of bedridden elderly. Now the system has become nationwide policy and is spreading rapidly. The solution to problems of an aging society may originate in rural areas where the population is older and resources are limited, as happened in Mitsugi. Application of the rural system to urban places, however, does have some limitations, so the system should be tailored to the characteristics of each community.Bedridden: confined to bed and with a need for constant care as a result of conditions such as strokeCare house: a facility which offers the minimal lifestyle support services such as supplying meals and common bathrooms for the independent elderly, but who are nervous about living aloneCare manager: a professional who draw up care services plan and contacts service providers to meet the needs of people who need long-term care or other servicesComprehensive Health and Welfare Facilities: the facilities in Mitsugi consisting of the special nursing home, the rehabilitation centre, the geriatric health service facility, the care house and the group home for elderly people with dementiaGeriatric health service facility: an intermediary facility between hospitals and homes and nursing homes, which provides medical, rehabilitation, nursing, and daily care services such as bathing, meals, and toileting to enable patients to go back homeGroup home for elderly people with dementia: a facility in which dementia patients live together and receive care and supports with a homelike atmosphere. The capacity of a group home is 5–9 residentsHome-based long-term care service: long-term care workers, visiting patients’ homes to assist with meals, toileting and bathingHome-visit care services: the services which professional staffs provide at patients’ home, such as home-based long-term care, visiting nurse, visiting physician and visiting physical or occupational therapists serviceOffice of Collaboration for Comprehensive Community Medical and Other Care Services: the office in a hospital which liaises with other hospitals and their associated facilities so that patients can move smoothly between them.Public health nurses: nurses who work for prevention services such as a health checkup and management of vaccinationRecovery stage rehabilitation ward: a ward where the rehabilitation services are provided for patients who have finished acute treatment but are not ready to go homeRehabilitation centre: a facility which provides rehabilitation care services for people who need to recover their function before returning homeSocial worker: a professional who provides advice and aid about welfare for people with physical or psychological disabilitiesSpecial nursing home: a facility which provides long-term care services to help bathing, meals, and toileting for the elderly who require long-term careVisiting nurse service: nurses visit patients’ house to provide nursing careVisiting physical or occupational therapists service: physical or occupational therapists visit patients’ house to provide rehabilitation servicesVisiting physician service: doctors visit patients’ house to provide medical services


Regular physical activity has a positive effect on physical health, well-being, and life satisfaction of older adults. However, engaging in regular physical activity can be challenging for the elderly population because of reduced mobility, low motivation, or lack of the proper infrastructures in their communities.The objective of this paper was to study the feasibility of home-based online group training—under different group cohesion settings—and its effects on adherence and well-being among Russian older adults. We focused particularly on the technology usability and usage and on the adherence to the training . As a secondary objective, we also explored the effects of the technology-supported intervention on subjective well-being and loneliness.Two pilot trials were carried out exploring two different group cohesion settings (weak cohesion and strong cohesion) in the period from 2015 to 2016 in Tomsk, Russian Federation. A total of 44 older adults (59-83 years) participated in the two pilots and followed a strength and balance training program (Otago) for 8 weeks with the help of a tablet-based virtual gym app. Participants in each pilot were assigned to an interaction condition, representing the online group exercising, and an individual condition, representing a home-based individual training. Both conditions featured persuasion strategies but differed in the ability to socialize and train together.P=.03), whereas in the high cohesion, such association was not found. Overall improvement in the satisfaction with life score was observed between pre and post measures , but no decrease in loneliness.Both interaction and individual groups reported a high usability of the technology. Trainees showed a high level of technology acceptance and, particularly, a high score in intention to future use . Private texting (short service message [SMS]) was used more than public texting, and the strong cohesion condition resulted in more messages per user. Joint participations to training sessions (copresence) were higher for the social group with higher cohesion. The overall adherence to the training was 74% (SD 27%). Higher levels of social support at baseline were associated with higher adherence in the low cohesion condition (F1,18=5.23, Online group exercising was proven feasible among healthy independently living older adults in Russia. The pilots suggest that a physical training performed in a virtual environment positively affect the life satisfaction of the trainees, but it does not provide support for a decrease in loneliness. High cohesion groups are preferable for group exercising, especially to mitigate effects of low social support on adherence. Further research in motivating group interactions in training settings is needed. Regular physical activity is a key factor to a successful aging, contributing to positive outcomes in health and well-being in later life -4. It caEngaging in regular physical activity can be challenging. Older adults might suffer from reduced mobility, low self-efficacy, lack the proper infrastructures in their communities, or simply find it difficult to leave home and participate in physical activities on a regular basis ,8. For tIntervention programs to promote physical activity have shown to be effective in increasing and maintaining physical activity . In partHowever, despite the body of literature on the topic, little attention has been paid on populations living under difficult environmental conditions and undergoing complex social changes, such as the Siberian community. Seasonal fluctuation has been found to determine the level of physical and social activities of older adults  leading The above observations point to the need for solutions that can help older adults living under the above conditions to keep physically and socially active. Technology-supported interventions have been shown in the past to be successful in this goal .cohesiveness (frequency of contact and group dynamics) ) compared with the pretest measures (mean 21.34 [SD 5.8]).Eight participants did not answer to one or more questions of the SWLS and thus, have been excluded by this analysis. On the subset of participants without missing answers, SWLS score was analyzed with a repeated measure ANOVA with time (pretest vs posttest) as within-subject factor, and group  and study (Tomsk1 vs Tomsk2) as between-subject factors. Only the main effect of time was significant . Participants reported a lower level of loneliness in the Tomsk1 study (mean 4.77 [SD 1.7]) compared with the Tomsk2 study (mean 4 [SD 1]).The same analysis was performed on R-UCLA Loneliness Scale. Eight participants were excluded from the analysis because of missing values in the pretest or posttest questionnaires. Only the main effect of study showed a tendency toward significance (Participants’ rating on the usability of the app shows that the group exercise app (assigned to the interaction group) has a high usability and that the added complexity in relation to the more traditional home-based version  did not significantly affect its usability.When asked in detail, participants reported the training feature as very usable, whereas the messaging as usable but with a lower score (1 point lower), possibly because of the typing. The intention to use the app in the future was also very high, which along with the analysis of the actual usage, points to the feasibility of using the online group-exercising tool for training in a social context. These results are in line with a previous usability study and usage behavior analysis done on the Gymcentral tool .As in our previous study analyzing online interactions in a training context among Italian older adults , we expeThe results of copresence show us that participants from the interaction group in Tomsk1 (strong cohesion group) participated in significantly more training sessions with the company of others compared with the meetings by chance in the individual group. We have seen the same effect in our previous study  featurinWe have observed a higher adherence for the groups with high cohesion, and in particular, under the group-exercising treatment . However, the ANCOVA showed neither a significant main effect for group or for study, nor interaction between study and group. This suggests that the added group exercising feature did not account for a significant difference in persistence rate compared with the individual training with persuasion features .In our previous study with Italian older adults , we obseThese results contribute to the ongoing discussion on the differences between individual and group training . This observation is in lines with the literature highlighting the social support structure as an important determinant of adherence ,8. InterEnjoyment of physical activity is described as determinant of physical activity ,8 and isImplementing group exercising can be challenging, especially in heterogeneous populations. Individual differences among older adults can lead to motivational issues and problems in tailoring the training . In addiIn our previous study with Italian older adults , we obseSeasonal fluctuation has been found to determine the level of physical and social activities of older adults , especiaAlthough our studies were set in spring and summer periods, we did experiment the effects of the seasonal fluctuation but at recruitment and for quite the opposite reasons. June to September is gardening season, and independent living older adults usually engage in this activity, spending most of the period in their summer houses (Dacha). This influenced the availability of participants in our study as it created obstacles for some candidates that showed initial interest in participating . After this experience, the second study was moved to earlier spring months (April-June) to increase the pool of potential candidates. However, we did not see a significant difference in the program adherence that could be explained by these two different seasons. Further studies are needed, especially to understand the effects of the extreme winter season.Recent history, along with current social, political, and economical factors have impacted negatively in life satisfaction and happiness of older adults in the Russian Federation . Thus, dIn investigating the impact of physical training, we have seen an overall improvement in the SWLS score for all participants, regardless of the version of the tool used. This is consistent with our previous study with Italian older adults , where wParticipants did not observe any decrease in the loneliness score as a result of the training, not even those in the online group exercise condition. This is contrary to our expectations, given the social context provided by the group-exercising and the social interaction features. In Trento, Italy , we did The lifespan gap between males and females in the Siberian region is one of the biggest in the world: life expectancy at birth for men is 64.7 years, whereas for women it is 76.3 years . These dThe amount of participants in the Tomsk2 study was twice bigger than in the first Tomsk1 study, 40 and 20 participants, respectively.The difference in the group size between the two studies is because of (1) the complexity of the study design and (2) the difficulty in finding participants of older age willing to participate, given the specific social characteristics of the region (older adults living in Siberia are not used to participate in studies). Therefore, we were able to involve only 20 participants for the study Tomsk 1. The following year, as we built better contacts with various retirement organizations and local organizations became more familiar with the project, we were able to involve 40 people in the study (Tomsk 2).Group cohesion was defined as a property of the pool of candidates: participants acquainted with each other and engaging in joint activities. This property was maintained during randomization by ensuring that pairs of friends would end up in the same groups. While being a solid definition, the fact that cohesion was not qualitatively measured should be noted as a limitation.There is a lack of translations of international standardized measure in Russia. Therefore, except the SWLS , no translation was available for the measures used in the study. These measures were translated and adapted to Russian language and culture by our research group by using the standard translation or bask-translation procedure. During this procedure, we ensured to reach semantic, idiomatic, and conceptual equivalence between the original English and final Russian versions.Although, without a validation study, we cannot be completely sure that these instruments fully fit the socioeconomic characteristics of Siberia, we believe that the standard procedure adopted to translate these instruments provided reliable results. This should be considered as the limitation of the study.Two questions were excluded from the SUS because in the pretest of the prefinal version of the scale (during the translation or back-translation procedure), older adults found it difficult to understand them (“I found the various functions in this system were well integrated” and “I thought there was too much inconsistency in this system”). Therefore, whereas in the original scale the total SUS score ranged from 0 to 100, in our study it ranged from 0 to 80. This is a limitation of our study and could make it difficult to interpret the usability results. However, it is worth noting that no usability scale suitable for older adults existed in Russian language, and our study provides the first adaptation for this culture. Future studies should investigate the validity of this short version of the SUS.The results point to the feasibility and effectiveness of technology-supported physical interventions, and in particular, of online group exercising among Siberian older adults. High cohesion groups are preferable for group exercising, especially to mitigate effects of low social support on adherence. Cultural differences might explain the preference of private messages over public ones. Results in terms of subjective well-being are promising, but enabling interaction has proved not to be enough to observe a decrease in loneliness. Thus, further research is needed to understand how to better enable community-building interactions.


A change in the pharmaceutical environment has occurred from previously only needing to convince regulators of a product's safety and efficacy to obtain marketing authorisation to now needing to satisfy the value perceptions of other stakeholders, including payers, to attain market access for products. There is thus the need to understand the concept of market access that may be defined as ‘the process that ensures the development and commercial availability of pharmaceutical products with appropriate value propositions, leading to their prescribing and to successful uptake decisions by payers and patients, with the ultimate goal of achieving profitability and best patient outcomes’. The aim of this research therefore was to explore the understanding of market access among various stakeholders and how their understanding of this concept could improve patient access to pharmaceutical products.A literature review was conducted on MEDLINE by using the term ‘market access’ to find articles with explicit definitions of market access for pharmaceutical products; non-peer–reviewed and other grey literature sources were also examined. A paper-based interview survey was also conducted in three different settings. The respondents were asked about what factors they think contribute to the successful development of pharmaceutical products, as well as their definition of market access for these medicines.The peer-reviewed literature review did not reveal appropriate comprehensive definitions for market access, although several definitions were proposed from the non-peer–reviewed literature. These definitions ranged from basic to detailed. The survey of 110 respondents revealed differing levels of understanding of market access. Factors considered to influence successful market access, as described by the respondents, included unmet need/burden of disease (68.2%), clinical efficacy (47.3%), comparator choice (36.4%), safety profile (36.4%), and price (35.5%).The concept of market access is still poorly understood, and the definition varies depending on the stakeholders’ perspectives. For cost-effective products to be developed and made accessible to patients, there is a need for wider understanding of market access and the value perspectives of the various stakeholders. There is also a need to determine whether and how involved payers should be in the development of pharmaceutical products. It is widely accepted that activities during research and development, sales, and marketing have been the main drivers of commercial success for pharmaceutical companies. These activities typically involved submitting data on efficacy, safety, and tolerability to the regulatory agencies; and once approved, marketing the drug to the appropriate physicians and pharmacists. Access to the market therefore involved a small set of stakeholders . In addiPrevious reports suggested that one of the factors contributing to successful product development was government support for academic research and development . The colRecently, research seems to suggest that the ‘one size fits all’ method of drug development, as used to create blockbusters, is on the decline. Instead, personalised medicine is the new way forward; hence, the need for a broader definition of market access . The aimthe process that ensures the development and commercial availability of pharmaceutical products with appropriate value propositions, leading to their prescribing and to successful uptake decisions by payers and patients with the ultimate goal of achieving profitability and best patient outcomes  develop a robust definition for market access and 2) determine how market access could influence what factors lead to the successful development of pharmaceutical products.Journal of Market Access and Health Policy was conducted. The references sections of all the articles identified for inclusion were also searched for additional references.A search of the peer-reviewed literature was conducted on MEDLINE by using the term ‘market access’. Articles had to include an explicit definition of pharmaceutical market access. The search criteria included English language, humans, and publication dates between 1 January 2000 and 1 January 2015. This time frame was chosen to coincide with commencement of the widespread use of health technology assessments. Titles and abstracts were initially screened for relevant articles, and then the full text was reviewed for historical and contemporary definitions of market access. Internet searches, using the Google search engine, of grey literature were also conducted to identify non-peer–reviewed definitions of market access. Furthermore, a specific search of the A paper-based, qualitative, and structured questionnaire see  was deveAt a health industry conference setting (ISPOR 2014), two researchers randomly approached attendees, briefly introduced themselves, outlined the purpose of the survey, and then asked them if they would be willing to anonymously respond to the questionnaire. Some of the attendees were approached based on their status as well-known, highly respected key opinion leaders and for their influence in their respective fields. The researchers then asked the questions, recording the responses on the question sheet. In the educational setting, the respondents completed the questionnaire on their own after attending a session on market access; in the pharmaceutical setting, respondents were approached after internal meetings and asked to complete the survey.List five factors that you believe would influence the development of a successful pharmaceutical product elicited 17 response categories .Journal of Market Access and Health Policy, yielding 45 articles in total for analysis.In total, 110 articles were identified from the literature review: 55 of these articles were excluded based on not meeting the inclusion criteria and 22 of these articles were excluded based on a full-text review. In addition, 10 articles were obtained from the Google search and two from After a full-text review, only four of the articles included a definition of market access , 6–8 Ta. Most ofIn total, 110 respondents answered the questionnaire: 48 at the conference, 45 at the educational course, and 17 at the pharmaceutical company. Of the respondents, 76 (69%) were pharmaceutical industry experts, 13 (12%) were pharmaceutical consultants, 11 (10%) were academics, 8 (7%) were policy makers or health technology assessors, and 2 (2%) were healthcare professionals.Q2. List five factors that you believe would influence the development of a successful pharmaceutical product?Across all professions, the top five factors believed to influence development of a successful pharmaceutical product were as follows: unmet need/burden of disease, clinical efficacy, comparators, safety, and price . The resQ7. What is your definition of market access regarding pharmaceutical products?It would be so difficult to define ‘market access’ in pharmaceutical products: considering the implication products may have on the wider healthcare market, understanding the impact the changing healthcare market will have on the product, and preparing a positive healthcare environment which suggests uptake of the product. Examples of appropriate market access definitions can also be found in Respondents offered a wide range of definitions of market access regarding pharmaceutical products , each wiOdeyemi  proposedStakeholders. The percentage of respondents who included the stakeholders in their definition of market access is shown in Product availability, affordability, and acceptability (packaging/posology/patient friendly) for patients as primary end users’. and Make treatments available for those who really need them for as long as they need them or benefit from them despite the patient ability to pay for it and make patients aware of those treatments’ availability in order to seek them/use them.The capability of an organisation to understand and anticipate payer needs and deliver value to this customer group, and also as Gaining access on the market. A product will have good market access if it: has the best recommendations, is included on formularies, has no price barriers.With payers seeing their influence increase, especially being depicted as the gatekeepers to drug access, respondents named them as the next most important stakeholders. Their role in market access was mentioned in different ways, such as Optimis[ing] access of a drug along the development life-cycle with the appropriate target product profile , developing early access propositions with health economic evaluation.Several respondents also recognised the importance of pharmaceutical companies in their definition, with one respondent defining market access as [A] connection of three parties: patient, industry, physician. and Patients are diagnosed/treated in fastest time by [the] appropriate drug/treatment. Most of the respondents indirectly mentioned physicians by saying drugs being prescribed possibly with the belief that only physicians can prescribe drugs, so negated to specifically mention them.Physicians are often found at the penultimate stage to drug use by patients, and market access was loosely described as Varies. [It] should be everything that is done to get the product to be prescribed (regulatory etc.), whereas another said The discipline governing all matters that can eventually impact a products’ access to a market. In the pharmaceutical sector, this notably entails regulatory/licensing matters, rules governing the setting of a product's price and possibly funding/reimbursement.The role of regulators in market access was appreciated by the lowest number of respondents. Perhaps this low number is because some still see their role just as providing regulatory approval or marketing authorisation that later leads to market access. However, Eichler et al. suggest that in the future, a two-stage process between the licensing and reimbursing decisions will occur . First, Obtain[ing] the commercialisation of a product and [The] process where manufacturers seek reimbursement to launch a product onto the market.How respondents perceived the importance of pharmaceutical and patient outcomes when defining market access is shown in Define high value product to patient[s] in need and improve their health and [Market Access] can be defined as the uptake of the product by patients that need it, and paid by the insurance/social security, providing efficacy/effectiveness where other products are unable to.Patient outcomes mostly include the improvement of health-related quality of life, for example, the improvement of health outcomes such as the reduction in severity of symptoms or an improvement in the method of administration of the treatment. Market access was defined as Try[ing] to have knowledge of [the] economic environment, and regulations around drugs to All the phases that lead to effective marketing of a product. More detail was found in another definition, [Market access is a way to] optimise access of a drug along the development life-cycle with the appropriate target product profile , [and] develop[ing] early access propositions with health economic evaluation.The life-cycle position in which respondents deemed market access activities to most take place are shown in [A] process of launching and commercialisation, getting approval and reimbursement and Understand[ing] the value of drugs and communicat[ing] this to payers and patients, not only in terms of efficacy, but also budget impact and cost effectiveness, after market authorisation.Odeyemi  also adv[A] process where manufacturers seek reimbursement to launch a product onto the market and Does not stop with launch of product. [It] depends on successful uptake of drug afterwards, positive recommendation, reimbursement actually available on market. Although not specifically mentioning post-launch, it is indirectly suggested in the responses.Odeyemi  finally All aspects of [the] process to secure use and reimbursement of a new product, and a more thorough definition from a pharmaceutical industry expert as All actions that will help a pharmaceutical product to be accessible on the market. The market concerns all stakeholders who have an influence inside and outside of the sponsor of the drugs. On one side: regulatory, clinical development, medical, commercial, health economics and outcomes research, market access, [while] on the other: payers, health authorities, patient associations, etc.In general, only 2 (2%) of 110 respondents alluded to all 10 variables in their definition: a respondent from academia vaguely defined market access is The way to enter the market smoothly and to be accepted by the market. Two respondents did not answer the question at all. Most respondents gave between four and six variables: 17 (16%) gave four such as Analysis of structures and organisation/processes and implementation of services that make the medicine available to patients. and It may be the process to ensure that all the patients who are likely to respond to the drug can get the drug with the appropriate price; 15 (14%) gave five variables, for example, Process to detect the gaps or the factors which determine the pharmaceutical products use. Developing a strategy and giving a solution to patients for having better access to drugs and Collaboration among payer, pharmaceutical companies, and physicians to make products available in a good environment to patients and 17 (16%) gave six variables, including Getting the right drug to the right patient at the right priceand A drug that is approved needs to be made available to the patients who need it. Market access is dealing with all activities required to reduce barriers to access .Ten respondents (9%) failed to mention any variables in their response, such as Understand the value of drugs and communicate this to payers and patients, not only in terms of efficacy, but also budget impact and cost effectiveness, after market authorisation. and Moment of discussion between stakeholders  aiming to find real value of a product, making sensible uptake decisions.None of the respondents gave nine variables, although two (2%) did give eight variables: Academics mostly defined market access as involving payer, pharmaceutical industry, and patient stakeholders, almost equally taking into account pharmaceutical industry and patient outcomes (64% and 55%), and taking place mostly during the post-launch (91%) and peri-launch (73%) phases .Pharmaceutical consultants also defined market access as involving pharmaceutical industry (77%), payer (69%), and patient stakeholders (54%), equally incorporating pharmaceutical industry and patient outcomes (both 38%), and mostly occurring in the post-launch (77%) phase .Although being too few to draw comparable conclusions, healthcare professionals defined market access as including all stakeholders, with a focus on pharmaceutical outcomes, and with activities around market access occurring during the post-launch phase . PharmacPolicy maker/health technology assessors mostly defined market access as incorporating payers (75%), patients (63%), and pharmaceutical industry (50%) stakeholders, with twice as many respondents saying pharmaceutical outcomes than patient outcomes (50% vs. 25%) were important, and happening during the post-launch (38%) phase .To achieve regulatory approval, pharmaceutical companies need to demonstrate that a product is safe, effective, and meets quality standards. However, to ensure successful market access, they also need to demonstrate the product's value during pricing and reimbursement negotiations.From the literature review, market access was loosely described as the process to ensure that all appropriate patients who would benefit get rapid and maintained access to the drug, at an affordable price. Although there were a handful of meaningful definitions, none completely took into account all the various stakeholders, outcomes, and phases in the product life-cycle.Market access is not only about satisfying payers as stakeholders (through negotiating price discounts) but also about satisfying patients (through the appropriate selection of the most suitable patients for treatment) . The cleUnmet medical need/burden of disease was considered to be the most important factor influencing the development of a successful product: the higher the need for a treatment in a certain disease area, the more likely it should be successful. Surprisingly, research and development was not deemed as important, despite the obvious need for it to inform manufacturers’ decision makers about the development of the new treatment. Early dialogue ought to have been higher up the list too, because it would enable manufacturers to focus more on the aspect of the new treatment that would be of interest to the differing stakeholders. It was unusual that good trial design was rated low compared to clinical efficacy, comparators, and safety because these factors are all joint considerations.Because the majority of respondents were pharmaceutical industry experts, the level of congruence with the total population is expected. For academics, the expectation was that research and development would be the most frequently named factor; although this outcome was not the case, it was among the top five.Not surprisingly, 63% of policy makers are interested in early dialogue, because it would be beneficial to all stakeholders involved in health technology assessments. What is interesting is that twice as many respondents said price was important compared with cost effectiveness (50% vs. 25%). One would have thought that these two factors would be closely linked. Perhaps the respondents imagine that outright price has more of an effect on decision makers than cost effectiveness. This could be due to price generally being fixed as an input in economic evaluations (and therefore not flexible to change), whereas other factors can alter the cost effectiveness of a medicine .The survey revealed that market access involves patients and payers as stakeholders, with a view of satisfying both patient outcomes  and pharmaceutical outcomes  after the pharmaceutical product has been launched.In terms of the stakeholders involved in market access, regulators being seen as the least important stakeholders would, in the past, not have been surprising. But currently, regulators and payers are perceived as having overlapping influence on market access, so it would have been expected that respondents named these two more equally. Although it is understood that patients are the most important stakeholder, surprisingly their outcomes  are almost as important as those of the pharmaceutical industry (profits). At minimum, the difference in outcome importance should have mirrored the difference in stakeholder importance. Finally, for the life-cycle position, as with stakeholders, this would not have been a surprise in the past, but considering a change in attitude about what factors lead to the commercial success of a product, it would be expected that successful market access also depends on activities in the pre- and peri-launch phases of the life-cycle.The common themes in the most appropriate definitions are that communication among all stakeholders is very important and that all should benefit , for example, the pharmaceutical industry may attain the right price for treatment, patients may have minimal barriers to accessing the best treatments, and payers may be charged an acceptable price for the treatments. However, the majority of responses neglected to mention when during the product life-cycle the communication should take place. It is not only important to know which stakeholders with which to communicate but also to know when to communicate with them to optimise the product development cycle.As can be seen in a sample of the responses, there is a wide discrepancy in different respondents’ understanding of market access. Several descriptions were very basic and generic, with no mention of elements specific to the pharmaceutical industry, whereas others were very detailed. The difference in the levels of detail provided by respondents also helps to emphasise that even within the same professional environment, some experts have a better grasp of market access than others.A common understanding of what is meant by market access is essential to the development and accessibility of medicines and devices that will benefit patients.The literature review focused on articles published starting in 2000; however, none of the reviewed articles referred to any published work before 2000, so it is unlikely that any relevant information regarding a definition was overlooked. A possible limitation could be that only articles published in English were sought; however, a relevant non-English language article could reasonably be expected to be referenced in an English article.The survey was answered by a small number of respondents, so no statistical inferences could be made about the findings. More participants, especially representing patients and regulators, from wider professional backgrounds would provide more meaningful results. The survey made use of open-ended questions to capture as much detail as possible from respondents. These responses were then coded to aid analysis. It is possible that some of the details in the responses could not be codified and were therefore lost. This type of omission could be lessened if there were validated codes. Also, in the international conference setting, respondents were approached and asked to take part without prior warning, and several people declined to take part. As was seen in some of their responses, it is possible that respondents did not have enough time to thoroughly consider their answers to the questions, for example, the importance of good trial design was rated low compared to clinical efficacy, comparators, and safety, which all contribute to good trial design. If the survey were administered to more prepared respondents, it is possible that more people would have responded and more insight could have been obtained.The concept of market access is still poorly understood, and the definition varies depending on the stakeholders’ perspectives. The survey described here revealed that a good awareness of unmet need/burden of disease, clinical efficacy, choice of comparators, safety, and price were the most important factors influencing the development of a successful pharmaceutical product. For cost-effective products to be developed and made accessible to patients, there is a need for wider understanding of market access and the value perspectives of the various stakeholders.the process that ensures the development and commercial availability of pharmaceutical products with appropriate value propositions, leading to their prescribing and to successful uptake decisions by payers and patients, with the ultimate goal of achieving profitability and best patient outcomes.As proposed, a multi-perspective definition of market access is Thus, research is underway to determine whether and how involved payers and other stakeholders should be in the development of pharmaceutical products. This new research should not only define the stakeholders but also elucidate how they should be involved in the different stages of product development.Click here for additional data file.


Eczema is a chronic atopic disease that is highly prevalent among children worldwide. Identification of factors that may contribute to childhood eczema is needed in order to develop strategies in its prevention. Over the past decade, accumulating evidence has suggested a potential correlation between the experience of stress by mothers and the risk of eczema development in their child. The present review attempts to provide an overview of the studies that contribute data on this correlation. The literature search was conducted using five databases, resulting in the inclusion of eleven studies in the review. The findings of these studies were summarized narratively. Further, an appraisal of the reporting quality of the included studies was conducted using a twelve-item checklist adapted from the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) checklist. Overall, the included studies showed that a positive correlation exists between the experience of stress among mothers and eczema risk of their child. The findings highlight the importance of the implementation of stress reduction programs for pregnant women and those in their postpartum period within communities in order to enable these individuals to relieve stress effectively. Eczema, or atopic dermatitis, is a common chronic disease characterized by the inflammation of the skin. It is estimated to have affected 40 million individuals worldwide , and itsStress is normally induced by a stimulus of a stressor which may include traumatic life events, and undesirable home or work environments, which would lead to the activation of the hypothalamic pituitary adrenal (HPA) axis and cortisol production, and potentially increased risk of postpartum depression . Indeed,Previously, a systematic review on the association between the experience of maternal stress during pregnancy and childhood eczema had been published by Andersson et al. in 2016 . NeverthA comprehensive literature search was conducted in September 2017. Five databases were used during the literature search, including PubMed, OVID MEDLINE (since 1946), EMBASE, PsycINFO (since 1806) and CINAHL. The combination of keywords used for the literature search is shown as follows: “eczema” or “atopic dermatitis” and “maternal stress” or “prenatal stress” or “psychological stress” or “psychosocial stress” or “anxiety” or “prenatal depression” or “postpartum depression” or “postpartum blue”.Included studies in the review are required to be original research articles that report observational cohort studies on the association between the following two parameters: the experience of any forms of stressors by mothers which leads to maternal stress and the odds of their infants developing eczema or atopic dermatitis during childhood. Studies that report cross-sectional, prospective and retrospective cohort studies, including those involving secondary data analysis, were included. Studies that do not report the association mentioned above were excluded. Moreover, studies that are not published in English were also excluded. All relevant and eligible studies that were published before September 2017 were included in this review.Using the search strategy described above, one author first selected the relevant and eligible studies to be included in the review by screening the titles and abstracts of the extracted studies. The inclusion of the extracted studies was then verified by four other authors. The full-text articles of the abstracts that match the eligibility criteria were then examined to confirm the eligibility of these articles to be included in the review.Data extraction was performed by one author after the finalization of the inclusion of studies for the review. Verification of the extracted data was then performed by four other authors in order to ensure the accuracy of the extracted data to be presented in the review. Extracted data include study settings, study design, cohort size, the stress factor investigated the confounding factors involved in the included studies, and the odds ratios (OR) or relative risk (RR) of the aforementioned association. A total of three items of disagreements occurred after the verification of the extracted data by the authors, and they were resolved by discussion between the authors in order to reach a consensus.p values.Owing to the heterogeneity of the stress factors involved, a meta-analysis on the extracted data was not feasible. Therefore, the findings of the included studies were presented in a narrative and tabular form. If applicable, both the adjusted and unadjusted OR or RR reported in the included studies were presented. Further, the significance of the aforementioned association reported in the studies was presented in the form of The reporting quality of the observational studies included in the review was assessed using twelve selected items adopted from the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) checklist for cohort studies . This asIn total, 1221 publications were identified through the literature search using the search strategy described above. Of these 1221 publications, 583 were duplicates and were therefore excluded. A further 385 publications were removed as they are either not original articles or those that are not published in English. The abstracts of the remaining 253 publications were then screened to extract the relevant articles that report observational cohort studies examining the association between eczema or atopic dermatitis and maternal stress. With the further exclusion of 242 articles which do not meet these criteria, 11 studies were included in the review. The full-text of these 11 studies were then examined to ensure that they meet the eligibility criteria of the review. The PRISMA flow diagram showing the different stages of the study selection process is presented in The ratings of the quality of the studies in reporting observational studies are presented in Moreover, upon inspection of the methodology of the data collection reported, we found that most of the included studies utilized a self-report approach for data collection. For the methodology in the ascertainment of childhood eczema, all of the included studies primarily utilized data obtained from parental self-report. Likewise, the included studies involve the use of questionnaires to collect data on maternal stress exposure among the study participants, although some of these studies ,17,18,19n = 8, 73%) are prospective cohort studies, with a longitudinal design [The characteristics of the included studies are listed in l design ,19,21,22l design  or crossl design ,23. Two l design ,20 involParticipants in the included studies are generally previously pregnant women with at least one child. The sample size utilized in these studies ranges between 242 and 32,271 mother-child pairs. The average sample size is 6474 mother-child pairs.The included studies have involved the investigation of the association between a variety of stress factors experienced by mothers and eczema or atopic dermatitis risk among their child. These stress factors include perceived stress and psychological distress at pre-conception , prenatan = 8, 73%) were able to demonstrate that the association is significant. The reported adjusted ORs/RRs range from 0.6 to 4.2, although most of the studies reported an adjusted ORs that range between 1.0 and 1.5, suggesting that maternal stress factors demonstrate a weakly positive correlation with childhood eczema risk.A summary of the findings of the included studies on the association between various maternal stress factors and childhood eczema risk is presented in Four studies ,14,17,18Four studies ,16,17,18Fairly consistent results were obtained from the three studies ,17,20 thTwo studies, published by Hartwig et al.  and de MOther stress factors that were investigated by the included studies of this review include perceived stress , psycholNotably, three studies ,20,21 haIt has previously been well established that maternal stress would exhibit detrimental effects on infants, such as developmental defects and impaired behavioral development ,25. HoweThe findings of the present review demonstrate that a variety of stress factors experienced by mothers would generally lead to an increased risk of their child developing eczema, and eight of the included studies showed that such increase was statistically significant. These stress factors include prenatal depression, postpartum depression, prenatal anxiety, maternal stress during pregnancy, prenatal adverse life events, job strain during pregnancy, prenatal distress and perceived stress. Nevertheless, heterogeneity of the findings does exist among the included studies. Notably, contradictory results were reported by studies that investigated the association between depression and childhood eczema risk ,14,17,18Although being speculative, it is possible that the utilization of individuals of various ethnic groups among the studies could have contributed to the discrepancies, as it was cited that individuals in different racial groups, albeit in the same country, appear to exhibit variations in the tendency of allergy development . In the p = 0.05), such association was determined to be insignificant when the strict definition of atopic dermatitis was used . In light of the potential of the utilization of various methodologies for the measurement of outcomes and that of subjects of various ethnic groups among the studies in yielding heterogeneous findings, caution should be exercised in the interpretation of the findings of the review. Nevertheless, the included studies have in general shown that maternal stress appears to show a positive association with childhood eczema risk. To confirm this, further studies need to be conducted, involving subjects with different ethnic groups, to examine the aforementioned association using universal methodologies in assessing the occurrence of eczema and stress measurement.Nevertheless, we cannot rule out the possibility that the heterogeneity of the methodologies utilized in examining the association mentioned above could also play a part in the discrepancies. First, various included studies have identified different sets of confounding factors that may affect the measured outcomes, and the reported ORs that have been adjusted for were based on these identified sets of confounding factors. As the confounding factors accounted for were different between the studies, this could potentially lead to variations in the statistically-determined ORs among the studies, which in turn leads to variations in the extent of the significance of the positive association determined by the different studies. Second, the methodology used for the ascertainment of eczema was different between the studies. Notably, in the Braig et al. study , the autOne further point of note is that the current number of studies that examine the association between the experience of maternal stress factors at the pre-conception stage and the postpartum period and childhood eczema risk is too small. Therefore, although our review points towards a generally increased eczema risk among children whose mothers have experienced maternal stress during their pregnancy, it is difficult to draw a conclusion on whether the experience of stress by mothers at pre-conception or postpartum stages would increase childhood eczema risk. Further studies examining the association between the experience of stress at these two stages and childhood eczema risk are warranted to address this issue.Owing to the high prevalence of childhood eczema worldwide, the effective prevention of the disease among the young children is of paramount importance. With the findings showing that maternal stress would generally exhibit a positive correlation with childhood eczema risk, strategies should be taken to ensure that exposure to stressful conditions by mothers should be kept to a minimum, both during their pregnancy and postpartum period. For example, education of pregnant women on stress reduction should be enhanced. Health talks should be regularly held for pregnant women in communities, disseminating knowledge on the effective strategies to relieve stress and deal with adverse life events, such as regular exercises. The importance of seeking social support and professional help immediately when signs of anxiety and depression appear during pregnancy and postpartum period should also be widely disseminated among pregnant women. Further, as job strain during pregnancy was found to be a factor that increases the risk of childhood eczema, pregnant women should also be encouraged to take the mandatory paid maternity leave during the period of pregnancy. Pregnant women should also refrain themselves from working overtime for higher wages, as long working hours were previously suggested to be causal to anxiety and depression . All theThe present review has some limitations that need to be acknowledged. First, as mentioned above, the differences in the ethnic groups of the subjects and the methodology in the ascertainment of childhood eczema among the included studies of this review could have contributed to the heterogeneity of the review findings, resulting in the difficulties in drawing firm conclusions on the association between the experience of maternal stress and childhood eczema risk. Second, all of the included studies utilized a self-report approach, largely in the form of a questionnaire, in the determination of stress exposure among mothers and/or ascertainment of eczema development in their child. The obtained data using this subjective approach of data collection would therefore be prone to recall bias, limiting the reliability of the findings. Future studies should consider the use of objective measurement strategies in the assessment of these outcome measures, as suggested by Andersson et al. . For exaOver the past years, an increasing number of studies have addressed the question on whether the experience of stress by mothers during their pregnancy would detrimentally affect their children by increasing their risk in developing eczema, an atopic disease that is highly prevalent among children worldwide. The findings of the included studies in the present review generally point towards a higher risk of children to develop eczema during childhood if their mothers are subjected to a variety of stress factors, particularly during pregnancy. These findings therefore suggest the importance for pregnant women to avoid exposure to stressful conditions. This in turn highlights the need for the provision of education for pregnant women on the strategies of stress reduction during their maternity leave, and these women should be encouraged to take part in stress reduction programs that are recommended to be made available in local communities. Nevertheless, inconsistencies in the findings among the included studies were evident, potentially due to the heterogeneity in the ethnic origin of study participants and methodology utilized in outcome measurement among the studies. In light of this, further research is required to confirm the aforementioned association, preferably with the use of objective measures in stress level measurement and physician-diagnosed eczema for the ascertainment of eczema development, in order to contribute more data for a more reliable conclusion on the positive correlation between maternal stress and childhood eczema.