Drug information service is a dedicated and specialized service provided by pharmacists to enhance knowledge of medicines use, promote rational prescribing among prescribers, and reduce medication errors. Saudi Arabia has a National Drug and Poison Information Center (NDPIC) responsible for answering drug queries. There is a lack of literature that reports the current scenario of drug information services in the country, especially the Eastern Province. This study reported the current status of drug information services being provided among tertiary care hospitals of the Eastern Province of Saudi Arabia. All hospitals provided drug information services. The qualification of personnel was mostly bachelor’s level (46.2%) and without proper training (54.8%). The most common queries received in a day were related to drug alternatives, dosage, and administration, as well as the availability of drugs. Physicians were the main users of the service. The most common health resources employed for the service was Lexi-Comp (76.9%) and Micromedex (69.2%). The use of Saudi National Formulary was not reported by any hospital, which highlights a potential research gap to address i.e., to investigate the lack of use of SNF by practitioners. Drug information service is a specialized service provided by pharmacists to enhance drug knowledge, empower rational prescribing, and reduce medication errors . This seSaudi Arabia has a National Drug and Poison Information Center (NDPIC) responsible for answering drug queries. The center has a total of 31 hospitals with established drug information centers. It is distributed in the following manner: the Central region has 11 established drug information centers, while there are nine in the Eastern region, three in the South, five centers in the West and two drug information centers in the Northwestern region of the country . The couThis descriptive study, which was five months in duration (January 2017 to May 2017), was conducted in five cities including Dammam, Dhahran, Al Hufuf, Khobar, and Qateef, located in the Eastern Province of Saudi Arabia. The study incorporated tertiary care hospitals across five cities of the Eastern Province of Saudi Arabia i.e., seven hospitals in Dammam (53.8%), two hospitals (15.4%) each in Dhahran and Al Hufuf, and one hospital each (7.7%) in Khobar and the city of Qateef. This amounted to a total of 13 healthcare facilities to assess drug information services. The data source or target population was the pharmacy department of the hospital, particularly the head of the pharmacy department or pharmacy manager. The study used a structured, closed-ended survey questionnaire to assess the service parameters, which was exclusively developed by reviewing the literature. The survey questionnaire contained a total of 10 questions. It included questions related to the demographic information of the drug information personnel, quality assessment information such as mode of delivery, frequency of information sought, type of drug information sought, and the persons seeking such information, lag time, etc., as well as the use of resources to obtain such information. Prior permission was sought from the hospitals before the commencement of the study. The survey was conducted among the hospital pharmacy managers by dropping off the questionnaire and collecting it again at their time of choosing. The study was noninvasive in nature and the participants were briefed about the objectives before completing the questionnaire. The study was exempted from review, however, a letter addressed to the concerned hospital was produced on request.N = 10, 76.9%) while some were in the private sector . All hospitals  confirmed that they provide drug information services. Moreover, almost half of the hospitals  had a dedicated drug information office followed by a third proportion  that provided the service through a clinical pharmacy department. One hospital utilized an on-duty pharmacist and another hospital reported that anyone, whether pharmacist, pharmacy manager, or a technician present on the telephone line in the pharmacy department provided the service.Most of the hospitals were in the public sector  and Doctor of Pharmacy (Pharm.D) , followed by few hospitals  which declined to mention the qualification of the staff responsible for the service. One hospital had a pharmacist with Master’s qualification. Additionally, almost half of the hospitals  had previously trained staff for the said purpose followed by a third  that did not mention the details, and almost a quarter  that did not have such training. The mode of inquiry was mainly direct access and via telephone , followed by emails  and direct access alone . One hospital provided drug information service by telephone only and another by all modes.Furthermore, the qualification of the personnel was mostly bachelor’s level i.e., Bachelors in Pharmacy (B.Pharm)  of the service was also sought from the hospitals. In this context, we found out that the majority of the hospitals provided immediate response to the drug information queries received, but only half of them kept a record for quality assurance purposes. The response was mostly verbal. Moreover, only two hospitals assimilated that information to produce newsletters. This hospital focused on continuous education programs for the patients as well as healthcare professionals. The data pertaining to the quality of service is tabulated in N = 10, 76.9%) and Micromedex . The data is presented in With regard to the resources used for answering queries, we found that most of the hospitals used Lexi-Comp’s Drug Information Handbook , pregnancy and lactation issues, as well as drug interactions were sought occasionally. Information regarding the toxicological parameters of drugs was rarely sought. The summary of these results is tabulated in The frequency of queries received per day from allied healthcare professionals and patients was also documented. Most commonly, the queries were received from physicians and pharmacists followed by nurses. The drug information service sometimes received queries from patients and interns. The summary of these results is presented in Our study revealed that drug information service is now provided in all major tertiary care hospitals across five cities in the Eastern Province. Though all hospitals provide the service, most of the pharmacists providing the information had bachelor’s qualification and only half of them had specialized training. This is not in accordance with the standards normally assumed for the service. While all pharmacists can provide drug information to consumers and healthcare professionals to some extent, the quality of the service is believed to improve if the pharmacist has had formal training or supervision of a drug information specialist . This wiOur study also found that most of the queries were received from physicians. Studies conducted in other parts of the world also observed physicians being the most common enquirers of drug information ,11. The Since the common resources used did not contain information about the local availability and alternatives available in Saudi Arabia, perhaps a better solution to this problem may be the use of the Saudi National Formulary (SNF), as it can serve as a better alternative to other resources in such situations. The Saudi National Formulary contains drug information tailored for use in the country with related information . HoweverOverall, it is believed that the drug information service may be improved by an upgrade of personnel i.e., pharmacists with higher qualification, training in drug information service, and appropriate experience should be hired, followed by updating the Saudi National Formulary (SNF) and establishing a mechanism for medication error identification and reporting.Drug information service was provided in all major healthcare settings. Pharmacists working as a drug information specialist mostly held a bachelor’s degree in pharmacy, with most of them not having any specialized training in the domain. This issue needs to be addressed for the future as it may be considered as a shortcoming and may require upgradation. Physicians benefitted the most from the drug information service, however, their queries were mostly related to the logistical constraints of drug availability and alternatives. Overall, the service is adequate. The use of the Saudi National Formulary was not reported by any hospital, which highlights a potential research gap to address i.e., to investigate the decreased use of the SNF by practitioners. This study will help understand the potential areas for improvement of the service and the ways in which drug information service in the country can contribute to positive patient outcomes.


Tobacco companies use a host of strategies to undermine public health efforts directed to reduce and eliminate smoking. The success, failure and trends in domestic litigation used by tobacco companies to undermine tobacco control are not well understood, with commentators often assuming disputes are trade related or international in nature. We analyse domestic legal disputes involving tobacco companies and public health actors in high-income countries across the last decade to ascertain the types of action and the success or failure of cases, develop effective responses.WorldLii, a publicly available online law repository, was used to identify domestic court cases involving tobacco companies from 2004 to 2014, while outcome data from LexisNexis and Westlaw databases were used to identify appeals and trace case history.We identified six domestic cases in the UK, Australia and Canada, noting that the tobacco industry won only one of six cases; a win later usurped by legislative reform and a further court case. Nevertheless, we found cases involve significant resource costs for governments, often progressing across multiple jurisdictional levels.We suggest that, in light of our results, while litigation takes up significant time and incurs legal costs for health ministries, policymakers must robustly fend off suggestions that litigation wastes taxpayers' money, pointing to the good prospects of winning such legal battles. In some cases, they even write the legislation.13 Where legislation is passed that challenges their interests, they seek legal remedies to prevent, or at the very least delay, the implementation or continued application of these laws.14One reason for this slow progress is because tobacco companies aggressively seek to thwart these public health efforts; tactics which the parties to the FCTC now consider its greatest barrier to implementation.16 there has been less attention to its actions in domestic courts. Here we explore the industry's use of litigation from 2004 to 2014 in high-income countries that have ratified the FCTC, including an evaluation of types of claims pursued and an account of their success or failure.Although actions brought by Big Tobacco under investor-state dispute mechanisms and arbitration frameworks have been discussed extensively,17 a free-to-use, non-commercial, independent legal database. Unlike other databases compiled by not-for-profits that are often issue focused and therefore subject to selection bias, WorldLii integrates over 270 databases from 48 legal jurisdictions and is used by lawyers in both developed and developing settings for routine legal research. It is the largest, most jurisdictionally diverse database of domestic case law text available to legal researchers, although it does not index cases or provide details of case history. Therefore, we matched the cases WorldLii identified to LexisNexis18 and Westlaw,19 both online legal research databases available via paid subscription, which index and track the history of cases, providing any updates. In concert, these databases enabled us to evaluate the cause of action, type of law applied, and whether and how tobacco companies achieved their objectives through litigation.To identify litigation strategies of major tobacco companies in domestic contexts, we searched WorldLii,Our search first applied the terms ‘tobacco’ and ‘public health’ to the WorldLii case law database, which automatically excluded statute, regulation and international law documents. This yielded 459 results, of which the case names indicated irrelevance, especially cases of individuals charged with tobacco consumption related offences. We manually excluded results if they did not (i) involve a tobacco industry party opposing a public health action; (ii) involve a decision that was purely procedural; and (iii) took place in a non-FCTC jurisdiction. We consolidated daily hearings, original hearing and appellate judgments, leaving a total of six judgments for review.ratio decidendi . A narrative synthesis approach was used to evaluate the data, given that the qualitative nature of the findings did not permit a meta-analytic approach.In determining the subsequent history of these judgments, we used LexisNexis and Westlaw to identify whether a case had been appealed, and if so, whether it was upheld or overturned, fully or in part. These databases also allowed us to determine whether the parties were involved in a related, but separate, case. The following information was extracted for each case: (i) the case name and reference; (ii) the jurisdiction; (iii) the cause of action; (iv) the question/s of law; (v) whether the decision was in favour of or against the tobacco industry; and (vi) the All six cases meeting the inclusion criteria relied on Public Law, considering Constitutional or Human Rights Law. These cases took place in the UK, Australia and Canada. We review each in turn.The UK has no written constitution, so legal claims have proceeded under the legal and political bases that form the UK Constitution, including European Law. Cases have considered whether primary or secondary legislation is compatible with European law, as well as the legislation on devolution to Scotland.British American Tobacco UK Ltd & Ors, R (on the application of) v Secretary of State for Health [2004] EWHC 2493 (Admin) UK, the tobacco industry challenged the legality of England's Tobacco Advertising and Promotion  Regulations 2004. The case took place in the High Court, involving a single bench judicial review. Tobacco parties claimed that the tobacco advertising regulations were not proportionate. European Law on proportionality requires that the measure is in pursuit of a legitimate aim; the measure be suitable to achieve the aim; the measure be necessary to achieve the aim and the measure be reasonable.21 In this case, it invoked several questions: are the Regulations disproportionate to the aim of promoting health because they allow only so limited an amount of advertisement at point of sale as to impair the ‘very essence’ of commercial free speech? Are the Regulations disproportionate because they amount to ‘too blunt an instrument’ to meet the perceived objective? And, therefore, do the Regulations infringe the laws of the European Union? Is there adequate evidence to show that the Secretary of State properly assessed for himself whether less severe regulations would be sufficient for his purposes?In the case The Court drew on several matters of EU Law, including decisions of national courts and the European Court of Justice. The Court found against the tobacco parties on the basis that the proportionality test was indeed satisfied. His Honour Justice McCombe accepted that the Health Minister had assessed for himself whether less severe regulations would not have satisfied the legislative purpose, and therefore, that the Minister had fulfilled the test.Sinclair Collis Ltd, R (on the application of) v Secretary of State for Health & Ors [2011] EWCA Civ 437, involved judicial review of compatibility of primary and secondary legislation with EU Law. The Court was asked whether to impugn sections 22 and 23 of the Health Act 2009 and the Protection from Tobacco  Regulations 2010 on the basis that they violated the principle of proportionality. On this occasion, the Court found, in a 2-1 judgment, that the public health justification was proportionate and therefore against the tobacco industry party Sinclair Collis Ltd, the largest provider of tobacco dispensing solutions in the UK. The ban was deemed justifiable by reference to the wide margin of appreciation that the principle afforded to the Government. Lady Justice Arden stated ‘… in the context of public health protection, European Union law without doubt permits a low level of intensity of review with respect to the acts of the national legislature’ [173]. However, Lord Justice Laws dissented, considering the prohibition to be disproportionate, identifying a less restrictive alternative that might have been used.Another UK case, Collis v The Lord Advocate [2012] ScotCS CSIH_80, wherein tobacco parties claimed Section 9 of the Tobacco and Primary Medical Services (Scotland) Act 2010 was incompatible with EU law on free movement of goods. The plaintiff, a wholly owned subsidiary of Imperial Tobacco, asked whether it was within the powers of the Scottish Parliament to prohibit the sales of tobacco from vending machines, asking whether restrictions were proportionate in terms of European Law. The Court found against the tobacco industry, finding that the measure was not disproportionate in Convention terms, as the prohibition struck a balance between the public interest in maintaining good public health and the petitioners' private economic interest in its use of vending machines and therefore was valid according to European Law.Scottish courts heard Imperial Tobacco Ltd v The Lord Advocate (Scotland) [2012] UKSC 61 UK, the tobacco industry relied on another area of UK Constitutional Law, seeking to contest the compatibility of the Tobacco and Primary Medical Services (Scotland) Act 2010 with Scottish devolution legislation. The case involved a challenge to both sections 1 and 9 of the Act as being outside the legislative competence of the Scottish Parliament. The Court again found against the industry, concluding the Act was well within the competence of the Scottish Parliament.In JT International SA v Commonwealth of Australia [2012] HCA 43. This case considered whether Section 15 of the Tobacco Plain Packaging Act 2011 (Cth) resulted in an acquisition of any property of the plaintiffs otherwise than on just terms in violation of Section 51(xxxi) of the Constitution. The High Court found there had been no ‘acquisition’ of ‘property’, and therefore, that the Commonwealth succeeded on this point. Importantly, the plaintiffs were ordered to pay the Commonwealth's costs in this case.The tobacco industry also failed in Canada  v. JTI-Macdonald Corp., [2007] 2 S.C.R. 610, 2007 SCC 30, the Court unanimously upheld new federal advertising restrictions in their entirety. However, this case stood in stark contrast to RJR-MacDonald Inc v Attorney General of Canada [1995] ICHRL 51, a decision over a decade earlier in which the tobacco industry also relied on human rights law to argue that the similar provisions in the Tobacco Products Control Act, S.C. 1988 infringed the right to freedom of expression. In this earlier case, the industry party argued that the Canadian Charter of Rights and Freedoms was infringed by the legislation's banning of certain advertising and requiring unattributable health warnings, as such an infringement was not justifiable. In this case, the Courts struck down some provisions of the Act, thereby favouring the industry, finding that while the legislation validly enacted these provisions it did indeed violate the right to freedom of expression. Thus, sections 4–6 and 8–9 were unjustified and therefore inoperable.The result was similar in Canada. In The Canadian Parliament responded by enacting new restrictions on tobacco advertising. The new Act was similar to its predecessor, but addressed the issues raised in the earlier case. However, the tobacco industry promptly challenged it on the same grounds. In the 2007 case, the Court unanimously upheld the new federal advertising restrictions in their entirety. There were some crucial differences between these cases. In 2007, unlike 1995, the Attorney General produced voluminous evidence on the harm caused by tobacco and the role of advertising in youth initiation. Chief Justice McLachlin noted that this evidence was a significant factor in reaching her judgment, but also that this did not relieve the government of its obligation to justify the measures. She concluded, along with the majority, that the provisions were to be upheld. The result was, in effect, to overturn the tobacco industry's 1995 victory, but not to overturn the previous case.Increasing legislation to tackle the health effects of tobacco has led the industry to challenge its legality. We documented six domestic cases meeting our inclusion criteria spanning 2004–14, identifying how the dominant cause of action has been founded in Public Law, specifically Constitutional and Human Rights Law, rather than International or Private Law on trade.While we did not focus on mapping full case histories, including procedural hearings, we note that legal disputes could result in multiple procedural and pre-trial hearings, as well as appeals across multiple jurisdictional levels in federal states like Canada and Australia. In almost all cases, the action centred on testing the compatibility of laws and regulations with documents that are either constitutions or have similar primacy over primary and secondary legislation. This is unsurprising as findings of incompatibility with primary legislation can relatively easily be addressed by amending legislation, whereas it is much more difficult to amend constitutions and the like.22 This literature critiques the expansion of such dispute mechanisms on the basis that they take place in secret, rather than in open national courts, with decisions made by individuals who need not be legally trained. The relevant decision-making bodies are not constrained by precedent, and while they must not do anything that is clearly illegal, they do not reach decisions primarily on the basis of legislation or jurisprudence. This means that they are, prima facie, less likely to respect the safeguards for public health contained within much legislation and that outcomes are far less certain.16 The backgrounds of those involved may also lead them to frame disputes primarily as trade matters, with little understanding of what a health framing might look like.Commentators often focus on tobacco companies' use of private and international law to prevent or delay implementation of public health reforms. Much of the existing literature documents Big Tobacco's use of Investor-state dispute settlement (ISDS) and arbitration mechanisms.23 The negotiations are being conducted largely in secret, and there are serious concerns that they will increase the scope for industries producing harmful products to challenge governments seeking to reduce consumption of their products, or as the industries will frame it, appropriating their property rights, whether to trade-marked images or future revenue streams.24 The prospect for simultaneous domestic and international action by tobacco parties is therefore increasing.The existing literature focuses on bilateral and multilateral trade agreements currently being negotiated that will increase the opportunities for ISDS and other arbitration processes.25 Alongside domestic litigation, such developments mark significant issues for government, however on the domestic front victory public health provisions usually prevail. Governments must be prepared to fend off accusations that costly litigation wastes taxpayers' money by pointing to the good prospects of success.It is crucial that governments be aware that the litigation, arbitration and public relation strategies adopted by industry are intertwined. The new generation of regional trade agreements, such as Transatlantic Trade and Investment Partnership (TTIP) and the proposed Trans-Pacific Partnership (TPP), pose significant implications for tobacco litigation, and the potential to increase costs around defending public health measures generally.Our review also shows that governments must draw on expertise of those in diverse areas of law, not just trade law and arbitration, who are involved in policymaking as well as dispute processes. What is clear is that those governments regulating to reduce non-communicable diseases must expect to face simultaneous disputes in national and international fora, but that with the right expertise and effective use of the evidence, such disputes can be won.26 The threat of litigation is likely to weigh heavily on governments of small, poorly resourced countries that will struggle to prepare a defence against a well-resourced transnational corporation. However, this review should encourage such governments to ignore industry threats, drawing on the persuasive precedent of these existing disputes in common law countries.Our results show that the tobacco industry rarely succeeds, with only one victory in 1995, undone by later law reform in Canada. Such results raise the question of why the industry engages in such litigation. One possibility is that it values the threat of litigation. Litigation is extremely complex and costly, in time and resources, for governments involved.9 and its 2001 predecessor.27 Litigation has the additional advantage of diverting the attention of the few tobacco control experts in a country. Yet there are risks in litigation for the industry. First, it is also costly for it, consuming time and money. Although the transnational tobacco companies have access to resources far in excess of health ministries, these resources are not unlimited and they must calculate how best to deploy them. Second, there is the danger that they may be forced to reveal information they would rather conceal during the process of disclosure, as happened when an advisor to the tobacco industry sued for libel in a Swiss court.8 Third, although now much less of a problem than in the past when the industry was still able to portray itself as being socially responsible, there is the danger of reputational risk, as happened in the notorious McLibel case where McDonalds won in the court of law but lost heavily in the court of public opinion.28A second possibility is that litigation is a means to delay the implementation of legislation. In this respect, it would simply be a continuation of other tactics used by the industry, such as those employed to slow the passage of the European Union's 2014 Tobacco Products DirectiveThe use of Public Law is likely to continue, if not expand. Regulating tobacco products reveals a tension within the ever-growing field of human rights between the public interest and rights to private property and corporate freedom of expression. Such a conflict requires the courts to consider and weigh these rights; a point made most obviously in the UK cases where the test of proportionality is applied. Both at a philosophical level, where such a debate reveals the tension between human rights and neo-liberal ideology, and at a practical level, where corporations take on democratically elected governments, the issue of how far governments can or must go to protect the public interest sits central. It is therefore crucial that governments continue to defend public health action in these disputes to set precedent that is persuasive in other national level courts. This impact of fending off these disputes is no longer just nationally significant, but internationally relevant.www.tobaccocontrollaws.org are cultivated and therefore subject to selection bias in routine searching and reporting.The nature of legal databases precluded undertaking a fully systematic review or quantitatively assessing successes and failures on a global scale. In using WorldLii, we only search jurisdictions covered by the database, which was selected because of its ability to be used freely by those in both developed and developing settings. The database is not fully comprehensive, but as yet no legal database covers every legal jurisdiction across the world. Other databases maintained by issues-based not-for-profits like We also limited our study to jurisdictions that have ratified the FCTC. This decision was a practical one, as not only did WorldLii cover these jurisdictions, but we also knew these countries had made formal commitments and would be the most likely sites of reform. This leaves other countries, including the USA with its many jurisdictions, as ripe sites for future research on the use of public law.Wellcome Trust Investigator Award and also funded by EU HRES-313590. A.B.G.'s contribution to this work was supported by Grant Number RO1CA160695 from the US National Cancer Institute. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute or the National Institutes of Health.D.S. is funded by a


The sharp increase of the aging population has raised the pressure on the current limited medical resources in China. To better allocate resources, a more accurate prediction on medical service demand is very urgently needed. This study aims to improve the prediction on medical services demand in China. To achieve this aim, the study combines Taylor Approximation into the Grey Markov Chain model, and develops a new model named Taylor-Markov Chain GM  ). The new model has been tested by adopting the historical data, which includes the medical service on treatment of diabetes, heart disease, and cerebrovascular disease from 1997 to 2015 in China. The model provides a predication on medical service demand of these three types of disease up to 2022. The results reveal an enormous growth of urban medical service demand in the future. The findings provide practical implications for the Health Administrative Department to allocate medical resources, and help hospitals to manage investments on medical facilities. The population aged 65 and over has increased almost twice as fast as the younger population in the past two decades . This shTo predict individual medical services demand, an early study by Grossman  applied Among the recent studies, a Markov Chain (MC) model has been widely adopted. For example, Teresa (2012) and Akita (2016) applied the MC model to calculate the transition probability of patients in treatment ,22. UjjwThe GM  prediction model was created by Deng (1989), who is the founder of Grey system theory . Many stThere are three major limitations in applying these methods. First, the traditional regression analysis requires a large database to guarantee prediction accuracy. Second, applying the MC model requires the calculation of disease transition probability. Disease transaction features vary across different disease categories and patients. The probability matrix of disease transaction is different from one patient to another. Third, the traditional Grey GM  model is hardly able to provide accurate predication regarding random vibration and high noise. Medical service demand is highly influenced by disease spectrum, living environment, and national health policy. Historic data of medical service demand is limited.This study aims to address the above limitations in the current medical demand prediction literature by developing a new model which is based on the traditional GM  model and combines the MC model and Taylor Approximation algorithm. The traditional GM  model is used to predict the medical services demand. Then the MC model improved by the Taylor Approximation algorithm is implied to estimate the transferring state of the residual sequence in the GM  model to improve the prediction accuracy. The remainder of the paper is structured as follows: The improved T-MCGM  model is made up of three methods, including GM , Markov Chain, and Taylor Approximation. The purpose of GM  is to predict the medical service demand of specific diseases by adopting historic data. That of Markov Chain is to revise the absolute error in GM  by estimating the transferring state of residual sequence. These two methods combined with Taylor Approximation can effectively search the optimal upper and lower bound parameters for transferring the state of the residual sequence.The traditional Grey GM  model is developed as the following procedure:If we assume the original data series is Moreover, the next mean generation sequence is:Based on the above the data series, it can develop the whitenization differential equation in the GM  model as the following:In addition, the difference equation in GM  is:In Equations (1) and (2), Therefore, it can develop Grey Prediction equation, which is:Prediction of medical service is highly influenced by random influences, such as a disease’s morbidity and seasonal factors. Thus, the traditional GM  model has difficulty in predicting accurate medical service demand with original data series. In order to improve the current prediction of medical services demand, the following section applies the Markov Chain model to improve the GM  model, which is able to predict the transferring of the residual sequence in the GM  model. The improved model can resolve the randomness and volatility of services demand, and have a more accurate prediction on medical services demands.In practice, assuming the actual medical services demands are known, the series of absolute error is obtained between the actual demands and prediction, and it is a non-stationary random series in the Markov chain. In practice, medical service demands are different because of different types of diseases. Thus, this random series can be divided into different statuses, with In addition, and there are the low bound and upper bound of state in residual, which are calculated as:m. If we assume that Therefore, the Markov state transaction matrix consisted of If we assume In Equation (10), ectively .The new prediction model is based on the traditional MC model, and applies Taylor approximation, to develop the Grey MC prediction model.In order to develop the Grey MC prediction model, it has to transfer the Grey number. This transaction is named the whitening transformation of the Grey number. In our study, we can whiten this Grey number by following Equation (12):In this equation, Based on Equation (13), if we can confirm vectors Step 1:  InitializationSet the number of iterations as K.Set the initial whitening coefficient as:Set the objective function vector as:Set the approximate function vector as:Set approximate parameter as:Step 2:  Calculate the approximate function vector In Equation (20), and:Step 3:  Set the evaluation function as:If we assume a tolerable error ε, at the point which the evaluation function iteration terminates and enters step 4.Step 4:  Iterate the approximate parameter:Let:It can achieve Equation (25).Lastly, we need to increase the number of iterations (K = K + 1), and repeat the step 2. When The T-MCGM  model we developed is unique in three main aspects. First, it has the advantage of creating the prediction without requiring large databases or sample sizes. Second, the Markov Chain model requires the object to be stationary, while the object of T-MCGM  can be non-stationary. Third, T-MCGM  is able to revise the volatility and noise in the prediction. Thus, it has a better performance than ARMA and BP in terms of predicated accuracy. To better verify the effectiveness of T-MCGM , the following section applies it with empirical data, and compares the results with other prediction models.We used the database of China Health Statistic Yearbook, and obtain the medical services demand of diabetes DD), heart disease (HD) and cerebrovascular disease (CD). These three types of disease are very common in the aging population in China, and they have features that include high incidence rate, multiple causes, and other random factors. Therefore, these diseases can be used as an ideal case to test the improved Grey MC model. Hospitalizing rate within two-weeks is selected as the indicators. The data of hospitalizing rate within two-weeks from 2006 to 2015 are listed in Based on After the model completes the iterations, it can achieve the optimization of the vectors Based on In order to test the feasibility of T-MCGM  model, our study selects other three models which include auto regressive moving average (ARMA), back propagation neural network (BP), and GM  to compare with T-MCGM . The test focuses on two criteria, including absolute mean percentage error (MAPE) and root mean square error (RMSE), to compare the four models’ performance in these criteria. The result of the comparison is presented in As shown in By applying the T-MCGM  model in urban areas of China, we have noticed that there will be an increase of the demand of medical services from 2016 to 2022. Regarding the types of disease discussed above, some suggestions are provided to be considered in further medical resource allocation.The demand for medical services in diabetes and cerebrovascular disease has faster increasing rates than heart disease. This can be explained as individuals older than 65 are the main patients of the first two. Different diseases require different medical resources. For example, the patients with chronic disease need plenty of drug resources and nursing staff, while patients with serious acute disease need surgical treatment. Therefore, medical service prediction should consider the different types of disease.There is a larger fitting error in the demand fitting curve in 2010–2011. This may be caused by the New Medical Reform Policy which has been practiced since 2009. The scope of urban medical insurance is expanding and the proportion of reimbursement is increasing. The demand of medical services for chronic disease is stimulated. The prediction models based on GM  are weak, as without considering policy-driving factors, the demand increase of the prediction for medical services presents the hysteresis characteristics.The individual living standards and individual health awareness have increased in many developing countries in recent years. Therefore, the T-MCGM  model for medical services prediction can be applied to these countries for releasing their limited medical resources, such as India and Brazil. It is especially able to contribute a more accurate medical demand prediction in these countries, and provide adequate resources for medical service provision.The prediction of the demand of medical services for specific diseases has practical implications for the medical and health authorities, hospitals, medical colleges, and drug manufacturers. Different diseases require different medical resources. For example, the patients with chronic disease need plenty of drug resources and nursing staff, while patients with serious acute disease need surgical treatment and beds in hospitals. In this paper, the forecasting results from 2016 to 2022 can promote health service organizations to allocate limited medical resources, including doctors, nurses, pharmacists, and other human resources and drug resources. However, due to the limited access to the administration data on medical resources allocation, the practice of optimizing limited medical resources has not been discussed from a technical perspective in this paper. This aspect needs to be simulated and studied in further research.Generally, T-MCGM  overcomes the shortage of omitting the driving factors in the GM  model, and also weakens the volatility and noisiness of data by combining the Markov chain. Regarding this advantage, T-MCGM  has presented good adaptability for poor data and small samples. With using the same group of historical data of medical service demands, the model has a better prediction than the ARMA and BP models. In terms of the volatility and noisy of databases in medical service demands, the T-MCGM  model is more suitable for predicting the demands of patients.However, the development of T-MCGM  requires combining the three different models, which are based on a large amount of calculation and time consumption. Thus, it is not easy to carry out for solving urgent predictions of medical service demands and allocations of health resources in reality. Further research includes considering the prediction on rural areas in China, and focusing on comparing the difference between urban areas and rural areas in medical services demand. In this regard, the further research aims to contribute more allocating schemes for urban and rural areas.The T-MCGM  model represents a feasible and efficient method for predicting the trend of annual medical services demand for various diseases in China. The prediction results can be used by the national health administration to allocate limited medical resources, and for develop hospitals and other health organizations to develop proactive service plans.


To model population health impacts of dietary changes associated with the redevelopment of the UK food-based dietary guidelines (the ‘Eatwell Guide’).Using multi-state lifetable methods, we modelled the impact of dietary changes on cardiovascular disease, diabetes and cancers over the lifetime of the current UK population. From this model, we determined change in life expectancy and disability-adjusted life years (DALYs) that could be averted.Changing the average diet to that recommended in the new Eatwell Guide, without increasing total energy intake, could increase average life expectancy by 5.4 months  for men and 4.0 months (3.4 to 4.6) for women; and avert 17.9 million (17.6 to 18.2) DALYs over the lifetime of the current population. A large proportion of the health benefits are from prevention of type 2 diabetes, with 440,000  new cases prevented in men and 340,000  new cases prevented in women, over the next ten years. Prevention of cardiovascular diseases and colorectal cancer is also large. However, if the diet recommended in the new Eatwell Guide is achieved with an accompanying increase in energy intake (and thus an increase in body mass index), around half the potential improvements in population health will not be realised.The dietary changes required to meet recommendations in the Eatwell Guide, which include eating more fruits and vegetables and less red and processed meats and dairy products, are large. However, the potential population health benefits are substantial. Dietary carbohydrates are an important source of energy to support our day-to-day activities. But there is growing concern that an increasing consumption of carbohydrates in the form of free sugars, together with a decreasing consumption of higher fibre carbohydrates, is contributing to weight gain and poor health outcomes, including type 2 diabetes, cardiovascular disease and cancer .Free sugars include sugars added to foods and beverages before consumption, and naturally occurring sugars such as those in honey, syrups and fruit juices, but do not include sugars incorporated within intact fruits and vegetables or sugars naturally present in milk . Foods hIn the United Kingdom (UK), until recently the Government provided healthy eating advice in the form of the eatwell plate, which illustrated the different types of foods that we should eat, and the appropriate proportions required to achieve a healthy diet. Following a review of the latest evidence on carbohydrates and health, the Scientific Advisory Committee on Nutrition (SACN) advised the Government to reduce the recommended average intake of free sugars to no more than 5% of dietary energy intake and increase the recommended average intake of fibre to 30 grams per day . This inIn an optimisation modelling analysis , we founWe modelled the impact of dietary changes on health of the UK population for two dietary scenarios: (1) if everyone changed from the current UK average diet to a diet that meets dietary recommendations that were in place before the SACN report of 2015 (the ‘old recommendations’ scenario); and (2) if everyone changed from the current UK average diet to a diet that meets dietary recommendations used for the new Eatwell Guide . Both seIn a previous paper we have described how we used optimisation to identify the diet for each scenario that is minimally changed from the current UK diet, but meets recommended intakes of nutrients and foods, and does not lead to an increase in total energy . For thiWe used a multi-state lifetable model, PRIMEtime , to simuPRIMEtime simulates the current population over time until everyone has died, taking account of changes in incidence, prevalence and mortality of lifestyle risk factor-related diseases. Changes in diet have an impact on disease, either directly  or via intermediate variables . Our modelling of these relationships was based on evidence of significant effects in meta-analyses of epidemiological studies that had examined associations between diet and disease. The diseases influenced by changes in intake of foods  and nutrients (e.g. fibre and sodium) include coronary heart disease (CHD), stroke, type 2 diabetes and cancer of the breast, colorectum, lung, and stomach. Changes in energy intake (which affect body mass) additionally influence risk of cirrhosis and cancers of the pancreas, kidney and liver. The risk factors and diseases included in the PRIMEtime modelling of the dietary scenarios, and data sources used in the analyses, are shown in To calculate the impact of dietary changes on disease incidence, we first calculated the effects of dietary changes on intermediate variables. This included calculation of changes in:systolic blood pressure from changes in salt intake, using effect estimates from meta-analysis of salt reduction randomised trials total serum cholesterol from changes in fats  and dietary cholesterol, using effect estimates from meta-analysis of metabolic ward studies of solid food diets in healthy volunteers ;total serum cholesterol from changes in free sugars, using effect estimates from meta-analysis of trials of free sugar reduction ; andbody mass index from changes in total energy intake, using energy balance equations  and measWe then quantified the impact of each dietary or metabolic risk on disease, using the population impact fraction (PIF) equation to determine the change in probability of disease incidence, based on change in prevalence of the risk factor and relative risk or the disease:x) is the current prevalence distribution of a risk factor;p(x) is the prevalence distribution of the risk factor after the diet is changed;p′(x) is the distribution function for the relative risk of disease; andRR that had been adjusted for energy. Where a disease was influenced by more than one dietary or metabolic risk factor, we calculated the combined impact multiplicatively, adjusting for risk-disease pathways that are not independent using mediation factors estimated in the Global Burden of Disease study , and selTo determine the impact of dietary changes on population health measures, we ran the PRIMEtime model both with and without dietary changes. The baseline scenario reflected ‘business-as-usual’, where current trends in incidence and case fatality from diseases  are assumed to continue into the future. The scenarios simulated the effect of dietary changes on disease, over-and-above current trends. From the difference between the baseline and simulations, we determined the impact on population life expectancy and on number of disability-adjusted life years (DALYs) that would be averted. DALYs are a summary measure of health that reflects impact on both morbidity and mortality from disease. They are calculated in the PRIMEtime model from the number of years of life that are lived by the population, adjusted for time spent in ill-health (i.e. with ‘disability’ from diseases). The disability adjustment is determined from disease disability weights measured in the Global Burden of Disease study .In addition to the health impact, we also estimated the contribution of the dietary risk factors to the overall health gain, by eliminating each risk factor causal pathway in turn. For each scenario, we estimated the impact of each risk factor from the increase or decrease in total DALYs when the risk factor is eliminated.We determined uncertainty  for our main outcome measures  using Monte Carlo analysis. A table of the uncertainty around modelling input parameters, as well as further information about the design of the PRIMEtime model and sources of epidemiological data, can be found in There are substantial health benefits to be gained if UK adults can change to a diet that meets recommended levels of foods and nutrients without increasing total energy intake . ChanginIf everyone followed the old dietary recommendations, average life expectancy of the population would increase by 2.3 (2.0 to 2.6) months for men and 1.6 (1.3 to 1.8) months for women, but average improvements in life expectancy would be greater if everyone followed the dietary recommendations in the Eatwell Guide, increasing by 5.4 (4.7 to 6.2) months for men and 4.0 (3.4 to 4.6) months for women . The potWithout a constraint on energy intake the potential health gains from changing to a diet that meets either old recommendations or recommendations in the new Eatwell Guide, are much smaller. There would be 52% fewer DALYs averted for men and 57% fewer DALYs averted for women, under both dietary recommendation scenarios. Potential improvements in life expectancy are around 40% lower for a diet that meets old recommendations, and around 50% lower for a diet that meets recommendations in the new Eatwell Guide, when energy intake is allowed to increase.When the total energy of the diet is prevented from increasing, a large proportion of the health benefits are from prevention of type 2 diabetes . AchieviWithout any constraints on energy in the diet optimisation, energy intake increases by 13% when the diet is optimised to meet the old recommendations and increases by 16% when the diet is optimised to meet the recommendations in the Eatwell Guide. In our modelling, this leads to an increase in BMI and related diseases, including diabetes, cardiovascular disease, cirrhosis and a range of cancers. While these effects are countered by beneficial effects from increases in intake of fruits, vegetables and fibre, and a reduction in intake of unhealthy fats, red and processed meats, the net effect would be an increase in future cases of diabetes for men and women with a diet that meets old recommendations and for women (but not men) with a diet that meets recommendations in the Eatwell Guide. There would also be an increase in cases of cirrhosis and cancers of the pancreas, kidney and liver, due to the rise in BMI levels.When total energy of the diet is not allowed to increase, the majority of health gain is from reductions in red and processed meats, and increases in fibre, fruts and vegetables, with changes in other dietary risks  having only a minor impact. When total energy of the diet is allowed to increase, the changes in red and processed meats, fibre and fuits and vegetables are still responsible for the majority of health gain, but there is also a substantial health loss associated with the increase in energy intake.Although the only differences between the Old recommendations and Eatwell Guide scenarios are the stricter free sugar and fibre constraints in the optimisation model, only around 25% of the added health gains are actually mediated by the free sugar (2%) and fibre (23%) risk factors in the health model, when energy is constrained. Without any constraint on energy, around 50% of the added health gains are mediated by the free sugar (5%) and fibre (45%) risk factors. The remaining proportion of the health gain is primarily mediated by the fruit and vegetable and red and processed meat risk factors. The changes in consumption of fruits and vegetables and red and processed meats come about because of the shift in consumption patterns produced by stricter sugar and fibre guidelines. As can be seen in The potential benefits to population health from the updates to dietary recommendations in the Eatwell Guide are substantial. The strengthening of sugar and fibre recommendations more than doubles the health that could potentially be gained if everyone were to follow dietary recommendations without increasing energy intake. It is important that people are encouraged to improve diet quality, by shifting between food groups , without increasing overall energy intake of the diet, which can have substantial impact on obesity and related diseases, lessening the improvements in health. The results show how big changes in fruit and vegetables and meat consumption that are recommended in the Eatwell Guide could translate into big improvements in health when compared to average consumption levels in the current UK diet.If average energy intake of the diet does not increase, the population health benefits from prevention of type 2 diabetes are particularly large. As in many countries, the prevalence of type 2 diabetes in the UK has been increasing , and treAlthough SACN has published energy recommendations, these were not applied by Scarborough et al  in derivFor modelling health outcomes in this paper, the optimisation modelling was re-run without the constraint on energy, to illustrate the potential magnitude of effect on BMI and related diseases if energy intake was allowed to vary freely. We found that without the energy constraint, average adult energy intake increased by 16% to meet the dietary recommendation in the new Eatwell Guide. In our modelling, this led to an increase in BMI (assuming no increase in energy expenditure) and a loss of health from BMI-related diseases. However, an increase in physical activity could potentially counter these health losses.It should also be noted that the derivation of the modelled diets by Scarborough et al  used basThe model simulates what would happen to the health of the current population if everyone was to change to a healthier diet. It takes current trends in the incidence and case fatality of the dietary-related diseases into account, and disease risks have been selected and adjusted to avoid double-counting of health effects from dietary changes. There are, however, still ambiguities in the causal pathways between diet and disease outcomes in the epidemiological literature. Ideally, all of the relative risk parameters that have been included in the PRIMEtime model would be mutually adjusted for each other, but this is not possible when using parameters sourced from published systematic reviews. Similarly, all of the relative risk parameters included in PRIMEtime have been taken from meta-analyses of prospective cohort studies. Although these observational studies have been adjusted for potentially confounding factors  it is not possible to remove the possibility of residual confounding either due to missing explanatory variables, or poorly measured explanatory variables.In addition, there is uncertainty in model parameters, such as future trends in diseases and current measurements of diet, that we have not included. There is also uncertainty in the structural decisions we have made in the model design. In using a proportional multi-state lifetable model of diseases, for example, we assume that the disease processes are independent. While we do address links between diabetes prevalence and cardiovascular disease outcomes, where we have good evidence of risks, it is likely that there are other interdependencies that we do not capture (e.g. a slight increase in risk of cancers in those with cardiovascular disease). It is very likely therefore that there is greater uncertainty in our results than we have been able to quantify in the modelling.The recent analyses of disease burden in the UK  and EnglThis difference in outcomes relating to sodium is most likely due to a difference in the optimal intake of salt that is modelled in the two studies. The old dietary recommendation for average salt intake in England is ≤6g/day of salt, and this has not changed with the new Eatwell Guide. After more than a decade of intervention to lower salt consumption in the UK, the average salt intake, as measured from dietary intake in the NDNS , is relaDespite the differences in outcomes around sodium, the implications of our dietary modelling and the burden of disease analyses are broadly similar. However, there is an important difference in the way that the counterfactual diet has been determined. In the burden of disease studies, the counterfactual diet is an ‘ideal’ in which everyone achieves the theoretical minimum risk exposure level . In our population health modelling analyses, however, the counterfactual diet that is input to the model has been derived using optimisation, which identifies a diet that is minimally changed from current food and drink consumption, but meets recommended levels of intake for nutrients  and foods . In some cases, these UK recommendations are different to targets used in other analyses . Unlike the burden of disease study, the optimisation analyses can identify a diet that meets recommendations, and this diet may include changes in average consumption of foods that are currently within UK recommended ranges (e.g. red and processed meats) or for which there are no current recommendations (e.g. dairy products). The optimisation does not, however, take people’s preferences into account, such as the propensity to eat certain foods together  or likelihood of substituting one food for another (e.g. regular milk for low fat milk).To achieve the health gains that we have modelled, the UK population would need to increase consumption of fruits and vegetables, carbohydrate-based foods, fish and legumes, while reducing consumption of red, processed and white meats, dairy products and foods high in fat and sugar. Our previous study found that the impact on total food and drink costs for the individual would on average be insignificant, actually reducing slightly from 2016£6.02  to £5.99 (£5.93 to £6.05). However there would be economic implications for the meat and dairy industries due to reduced demand for their products. While agriculture adds just 0.7% to GDP in the UK , meat anFrom a global perspective, there may be benefits from reduced farming of animals for food production. Animal-based products generally contribute more to greenhouse gas (GHG) emissions than plant-based products , 36 and Under the Climate Change Act 2008, the UK Government has committed to achieving an 80% reduction from 1990 levels of GHG emissions by 2050 . While tIn addition, while we have shown that population health could improve substantially by adhering to the dietary recommendations in the Eatwell Guide, further research is needed to identify interventions that will help people change their dietary choices. Research in countries such as Australia , 43 and S1 File(PDF)Click here for additional data file.


Biclustering techniques are capable of simultaneously clustering rows and columns of a data matrix. These techniques became very popular for the analysis of gene expression data, since a gene can take part of multiple biological pathways which in turn can be active only under specific experimental conditions. Several biclustering algorithms have been developed in the past recent years. In order to provide guidance regarding their choice, a few comparative studies were conducted and reported in the literature. In these studies, however, the performances of the methods were evaluated through external measures that have more recently been shown to have undesirable properties. Furthermore, they considered a limited number of algorithms and datasets.We conducted a broader comparative study involving seventeen algorithms, which were run on three synthetic data collections and two real data collections with a more representative number of datasets. For the experiments with synthetic data, five different experimental scenarios were studied: different levels of noise, different numbers of implanted biclusters, different levels of symmetric bicluster overlap, different levels of asymmetric bicluster overlap and different bicluster sizes, for which the results were assessed with more suitable external measures. For the experiments with real datasets, the results were assessed by gene set enrichment and clustering accuracy.We observed that each algorithm achieved satisfactory results in part of the biclustering tasks in which they were investigated. The choice of the best algorithm for some application thus depends on the task at hand and the types of patterns that one wants to detect. Gene expression data are generated from experiments with high-throughput technologies, such as microarrays  and RNA-Data clustering techniques became very popular tools for gene expression data analysis , being uIn order to overcome the aforementioned limitations, it becomes necessary the application of techniques capable of identifying subsets of genes with similar behaviors under subsets of experimental conditions. Such techniques should also allow a gene or experimental condition to take part of one or more clusters. From this perspective, the main objective is to simultaneously cluster rows and columns of a data matrix in order to find homogeneous submatrices , which cIn , the firIn face of the increasing number of biclustering algorithms available in the literature, comparative studies were carried out and reported in –17. ThesThe authors in  comparedApart from the use of limited collections of algorithms and/or datasets, a potentially critical issue with the previous comparative studies in –17 conceIn summary, in this work we aim to improve on the existing studies by: (a) comparing a larger number (17) of biclustering algorithms widely referenced in the literature; (b) compiling larger synthetic and real data collections with a total of 4080 and 62 datasets, respectively, that allow biclustering analysis in biological scenarios; and (c) evaluating and comparing the algorithms in different scenarios, using the compiled collections of synthetic and real data, in the first case evaluating the results with more suitable external measures recommended in , and in We chose seventeen algorithms for this study. They are the ones compared in –17 and oCheng and Church’s Algorithm (CCA)  is divided into twelve equally spaced intervals, and each expression value of the dataset is transformed into a discrete level between zero and eleven, where each level corresponds to an interval. Values below −3.0 belong to the first level and values above 3.0 belong to the last level. Finally, for each level cialized  because tg and tc, to prune genes and experimental conditions out of the bicluster being formed. For the experiments with the first synthetic data collection, the values suggested by  with steps of 0.5.ISA has two parameters, ested by  were tooested by , which cThe biclusterings found on synthetic data were evaluated through the CE  and CSI p-value after the Benjamini and Hochberg multiple test correction 17] consip-values as shown in the pairwise comparison. Plaid also performed well in such a comparison, with the advantage of obtaining 100% of biclusters containing GO terms. With KEGG, OPSM and Plaid stood out from the remaining algorithms. Both presented between 40 and 65% of enriched biclusters and were the top ones in the pairwise comparison. Thus, the Plaid algorithm can be an interesting alternative for gene clustering tasks, since it performed well both in GO and in KEGG evaluations.On real data we performed two different experiments. In the first one, we evaluated the quality of the groups of genes contained in each bicluster produced by each algorithm in 27 different datasets by performing enrichment analyses using GO and KEGG. With GO, LAS, OPSM and SAMBA were shown to be interesting alternatives because, although they did not recover the highest fractions of biclusters enriched with some GO term, they found the biclusters with best Finally, in the second experiment with real data, we evaluated the cancer sample clustering accuracy of the algorithms on 35 datasets. During the analysis of the solutions, it was evident that MSSRCC and Spectral were superior when compared to the remaining biclustering techniques in general.


Informing plays a prominent role in attracting medical tourists. The enjoyment of proper medical information systems is one of the most important tools for the attraction of medical tourists. Iran’s ability in designing and implementing information networks has remained largely unknown. The current study aimed to explore information needs for designing a medical tourism website.This qualitative study was conducted in 2015 for designing Hospital Medical-Tourism Website (HMTW). A purposive sampling method was used and data were gathered using a semi-structured questionnaire. Totally, 12 faculty members and experts in the field of medical tourism were interviewed. Data were analyzed using the MAXQDA10 software.Totally 41 sub-themes and 10 themes were identified. The themes included the introduction of hospital, general guide for patients, tourism information, information related to physicians in hospital, costs, treatment follow-up, online hospital appointment scheduling in website, statistics and news of hospital medical tourism, photo gallery and contacts. Among the themes, the participants highly emphasized four themes including costs (100%), tourism information (91.6%), information related to physicians in hospital, (83.3%) and treatment follow-up (83.3%).This profitable industry can be developed through considering information requirements for hospital medical tourism website. Nowadays, tourism industry is one of the most important economic activities. In recent decades, we have witnessed the increasing growth of the global tourism market . Such a Medical tourism is an organized trip from the individual’s living environment to another place to maintain, improve and recover the individual’s physical and mental health . This tyMedical tourism included a wide range of medical care from oral care to cosmetic surgical procedures . All conIran, given its advantages regarding medical tourism, such as low cost, high quality of health services, competent physicians and abundant natural attractions, has decided to take these advantages . TherefoThe lack of recording and statistics system mentioned as well as the lack of information and its retrieval as the main obstacles to the development of the dentistry tourism . Some prThe authorities have not taken adequate actions to introduce the power of medical tourism and to design and utilize information networks , and IraThis study was conducted to provide a minimum set of data required for designing hospital medical tourism website, in 2015 with using the purposive sampling. Samples were selected based on research goals,  purposefContent analysis method is a proper method for obtaining reliable and valid data from text data . That inFurthermore, the conventional approach was utilized in this study as a content analysis approach . First, Data analysis was performed using the MAXQDA10 software. To ensure the principle of data immersion, the interviews were listened several times and then were transcribed. To ensure the accuracy in the interpretation of the findings and data credibility, enough time was allocated to each interview; agreement on codes and checking the transcribed interviews were done by the researchers (Peer check), and participants verification (Member check) was also used.Interviews were conducted in a quiet environment and in terms of the time, interviewees agreed it. Interviews were recorded after obtaining respondent’s consent. To ensure that the researchers had same perceptions of participants’ statements, the transcribed interviews were given to them for verification. In addition, the individuals participating in the study were assured that all information would remain confidential until the end of the study. When analyzing the data, instead of mentioning the personal characteristics of participants, a code was given to each questionnaire. Finally, data were categorized and analyzed and information for the medical tourism website was identified.Low ability in the field of the application of information and communication technology;Low ability regarding the status of facilities;Weakness in coordination and communication between organizations related to health tourism ;The lack of scientific and targeted planning for attracting medical tourists;The weakness in the use of modern advertising;The lack of staff fluent in international language in the majority of hospitals;Low medical standards in some hospitals;The lack of attention to and weakness in the introduction of the country’s abilities in order to attract medical tourists , 25, 26.There are shortages and problems in the field of medical tourism in Iran, including:The interviews about HMTW should include 10 main themes and several sub-themes, HMTW information needs are provided in All respondents believed that cost is a key part of the information and can be effective in attracting health tourists.In this regard, one of the participants, “By evidence and documentation, we must prove to individuals and users that our hospitals are cheaper and the quality of services is higher than other hospitals in the region and competing countries in the region, so preparing a list of hospital costs compared with the prices of hospitals in other countries is needed, of course, this information should be continuously updated” (Participant No. 11).Most of the participants (91.6%), believed that the tourist information is one of information needs for designing HMTW. For example, “Appropriate and worthy introduction of tourism attractions is as important as having them to benefit from these attractions, and because these sites are available to everyone and these attractions should be presented well (Participant 3).“For example, there may be a prominent physician and many people choose the hospital due to the physician, because one of the main reasons for referring to a hospital is a specific doctor in that hospital. Moreover, having physicians’ information can be useful for patients in terms of the degree of specialization of that physician ” (Participant 1). In this regard, 83.3% of participants agreed and regarded this information to be important.“Patients should ensure that they will not be left after treatment and hospital take their responsibility. In addition, patients’ treatment follow-up removes the need the physical presence of patients and their families in the hospital where they received services, and patients by referring to the website, can find out what to do after the treatment, for example, how to sit and walk after some treatment procedures may be important” (Participant 5). 83.3% of the respondents believed that treatment follow-up should be considered in the design of medical tourism website.Introducing the hospital, general guide for patients, statistics and news of hospital medical tourism, photo gallery, contacts and online hospital appointment scheduling in website were other factors recommended by participants to be considered in designing medical tourism website. In addition, most of the participants in the study evaluated costs item as the most important item on the website while they evaluated the online appointment-scheduling item as the least important item for foreign medical tourists.The most important general characteristics considered when designing a website for medical tourism are the ability to translate contents in different languages including the language of target countries , proper graphics, structural stability, loading speed, and updating website content. Overall, the purpose of the participants is to respect the principle of user-friendly in designing and using the website.Many studies about medical tourism in the world have emphasized the importance of medical information systems in the development and growth of this industry –30. TherThe countries in the region, including UAE, Saudi Arabia, and Turkey have a more advanced position than Iran. From the results of previous studies , 13, infWebsites are the most important means of medical information. The existence of HMTW will greatly help the development of medical tourism , 13. MosAccording to The part related to information on physicians in hospital, is other important sectors in the medical tourism website that may have significant impact on the patients’ decision to choose a hospital as their destination. The access to information such as physicians’ degree has effect on patients’ decision regarding selecting hospital . Given tOne of the most important sectors of medical tourism website is tourism information that by proper presenting it, many tourists can be attracted. In Canada, medical tourism companies on their websites and social networks such twitter, youtube, and Facebook have attempted to attract tourists by introducing tourism attractions and medical services at the international level . ResultsIn designing and using medical tourism website, hospital appointment scheduling arrangements should be considered for visitors. Centers providing services use online appointment scheduling to manage the access to service provision, because the online appointment scheduling system reduces waiting time effectively and therefore, increases patient satisfaction with the center providing services . Long waOn the HMTW, methods of contact such as telephone fax and e-mail should be provided to clients, because in the medical tourism industry communication must be available 24 h a day, 7 d a week . TherefoItems including the introduction of hospital, statistics as well as general guide for patients should be considered in designing the HMTW. In designing HMTW, issues such as the ability to convert to various languages such as languages of target countries, proper graphics, structural stability, loading speed, updating and the content of the website should be considered. Given that, Universities of Medical Sciences in the country have not had successful performance in designing, maintaining and using websites , therefoDesigning proper medical tourism websites for hospitals is a good opportunity to attract health tourists for the country. Websites in a virtual space act as a gateway that people can easily select their destination with high quality, low price and proper services. Therefore, authorities make the necessary decisions to apply hospital medical tourism websites.Ethical issues  have been completely observed by the authors.


Cancer radiation therapy with charged particle beams, called particle therapy, is a new therapeutic treatment presenting major advantages when compared to conventional radiotherapy. Because ions have specific ballistic properties and a higher biological effectiveness, they are superior to x-rays. Numerous medical centres are starting in the world using mostly protons but also carbon ions as medical beams. Several investigations are attempting to reduce the cost/benefit ratio and enlarge the range of therapeutic indications. A major limitation of particle therapy is the presence of low but significant damage induced in healthy tissues located at the entrance of the ion track prior to reaching the tumour. It is thus a major challenge to improve the targeting of the tumours, concentrating radiation effects in the malignance. A novel strategy, based on the addition of nanoparticles targeting the tumour, was suggested over a decade ago to improve the performance of conventional photon therapy. Recently, similar developments have emerged for particle therapy and the amount of research is now exploding. In this paper, we review the experimental results, as well as theoretical and simulation studies that shed light in the promising outcomes of this strategy and in the underpinning mechanisms. Several experiments provide consistent evidence of significant enhancement of ion radiation effects in the presence of nanoparticles. In view of implementing this strategy for cancer treatment, simulation studies have begun to establish the rationale and the specificity of this effect. In addition, these studies will help to outline a list of possible mechanisms and to predict the impact of ion beams and nanoparticle characteristics. Many questions remain unsolved, but the findings of these first studies are encouraging and open new challenges. After summarizing the main results in the field, we propose a roadmap to pursue future research with the aim to strengthen the potential interplay between particle therapy and nanomedicine. Conventional radiotherapy is applied in 50% of cancer treatments. Based on the properties of high-energy photons to traverse the entire body, this non-invasive method is used to treat deeply seated tumours. However, as the interaction of photons is not tissue specific, severe side effects or even secondary cancers may be induced when healthy tissues are damaged. It is thus a major challenge to develop new strategies and improve the tumour selectivity of radiation effects.The enrichment of tumours with high-Z compounds has been proposed as a new strategy to improve the effects of radiation as due to the amplification of primary (electronic) processes. To avoid confusion with radiosensitizing drugs, those compounds that make cells more sensitive to radiation, such as DNA repair inhibitors, oxygen transporters [see for instance , the use of highly penetrating photons remains critical for the treatment of tumours located in close vicinity of sensitive organs  and the treatment of paediatric cases, where damage of surrounding tissues can have severe consequences. The latter are mainly related to the geometry of the irradiation  and to the young age of the patients, which emphasizes later risk effects . The second is the recent pencil beam active scanning mode, where a beamlet of a few mm is scanned, spot by spot, on the tumour, modulating the energy for each depth slice  platinum complexes activated by different ion radiations , (ii) gold NPs combined with proton radiation and (iii) platinum NPs and gadolinium-based nanoagents (AGuiX) combined with carbon radiation. In the second section, the recent modelling and simulation studies dedicated to radio-enhancement induced by ion radiation are collected together with a summary of the known results and the remaining open questions to be faced.−1) are used as ionizing radiation  used as radio-enhancers (presented below). Given that nanosize bio-damage is the most lethal for living cells, the amplification of these types of damage is a major challenge of the strategy. Hence, DNA plasmids have been used as nano-bioprobes to detect and quantify the induction of nanosize bio-damage. The study of Usami et al.  demonstrLater, the same group observed that the effects of medical carbon ions  and iron ions  may also be used to improve treatment  to amplify the effects of carbon ions was shown in vitro , are not suitable for clinical transfer.As an alternative, nanotechnologies open new perspectives to target tumours. The effect of nanoparticles, combined with particle radiation, has been probed with high-energy protons and medical carbon ions (see below).The effectiveness of high-Z nanoparticles to improve the performance of proton radiation was first demonstrated by Kim et al. . They obThe efficiency of gold to enhance the effects of proton radiation was confirmed in vitro by Polf et al. . This grJeynes et al.  found thRecent molecular scale experiments performed with platinum and gadolinium nanoparticles, activated by 150 MeV protons, highlighted the amplification of nanosize bio-damage . These theranostic agent have unique multimodal properties, including improvement of MRI contrast and enhancement of radiation effects  is very rare. Thus, the dose enhancement effect occurring in the case of an ion traversal should be weighted by this very low probability to occur (≈10−3 to 10−4). In total, this would lead to a noticeably reduced overall dose enhancement effect. This study has shown a larger effect of gold and platinum, as compared to other high-Z materials, in acting as dose enhancers. More importantly, it demonstrated that, for proton radiation, a significant dose enhancement effect can be observed, mostly due to Auger electrons and consecutive cascades. However, this process is not sufficient to justify any overall macroscopic effect such as those observed in several experiments.In the case of ion beam irradiation, an enhancement of radiation effects was observed in the presence of nanoparticles either at the molecular (DNA damage), in vitro (cell killing) and in vivo (mouse tumour regression) levels, as discussed in the previous section and listed in Table The amplification effect of ion radiation by high-Z NPs may be explained by other mechanisms, such as modification of the radiation chemistry pathways and enhancement of radical mediated component of radiation damage, as suggested with X-rays , as has been demonstrated for the RBE  may be significant. The OER with ion beams shows a strong peculiarity, decreasing with high LET . The nanoagents of the future will have various designs  has been initiated (Bolsa Ferruz et al. The association of particle therapy and nanomedicine is a new era. Its evolution depends on the capacity of the different communities to share their expertise in developing competitive nanoagents and predictive models. In this context, a collaborative European research programme entitled Marie Curie ITN “ARGENT” (


Editorial on the Research TopicChildren and Companion Animals: Psychosocial, Medical, and Neurobiological ImplicationsThis Research Topic presents experiences with companion animals provided to children in varied settings. Methods include monitoring of the ongoing interaction of children with companion animals, or conducting interviews or surveys, as well as experimental interventions where changes occurring with the presence of the animal are assessed. Children in Austria, Germany, Jamaica, Japan, and the United Kingdom, as well as a minority from the United States, are represented in these studies.Nakajima contrasts two approaches: incorporating animals into school curricula or employing them in interventions to facilitate specific learning. Animal-rearing is a Japanese educational tradition, specified by the Japanese government in the course of study for formal elementary education. Matsuda , experienced the most bites.Having a dog at home presents some level of risk of dog bites to children. Guérin et al. argue for the importance of offering choices to children with autism who may benefit from contact with animals, even those who are profoundly affected and non-verbal. They propose developing electronic presentations of active animals so the autistic child can witness the animal and its behavior, and reveal their level of interest in a particular animal.For children diagnosed with Autism Spectrum Disorder, interest is growing in the possible use and value of assistance dogs , throughHart et al. to explore the extent to which cats are compatible pets with these children. The cats exhibited affectionate behavior and very low levels of aggression with the children. The children were very attracted to the cats, pointing to the value of selecting well-socialized cats for autistic children.Families having both a companion cat and an autistic child 3–12 years of age participated in a study by A broad range of topics on children and pets remains unexplored, including cross-cultural ways of dealing with children’s specific challenges such as autism . PositivAll authors listed have made substantial, direct, and intellectual contributions to the work and approved it for publication.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.The handling Editor declared a shared affiliation, though no other collaboration, with one of the authors LH.