Home-based palliative care is a recognised model of health service provision globally, but is just emerging in Nigeria. The aim of this study isto review the spectrum of adult cancer patients involved in home-based palliative care, the services provided, outcome and benefits.Records of all adult cancer patients seen on home-based palliative care between March 2009 and January 2013 by the hospice and palliative care unit, University College Hospital (UCH), Ibadan were reviewed. Their biographical data, days on programme, diagnosis, stage of disease, major complaint, pain score, other symptoms, services offered, number of home visits, follow-up, and outcomes were extracted, reviewed, and analysed. The data were analysed using SPSS version 16.0.Sixty patients were enrolled during the study period: there were 20 (33.3%) males and 40 (66.7%) females out of a total of 787 patients. All of them reside within catchment area of the hospice. Breast and prostate cancer constitute 21.7% each, gastrointestinal 16.7%, liver 11.7%, and cervical cancer 10.0%. Homes were visited 1–23 times per person. Days on programme ranged from 9–1207 days (average: 286 days). Pain was reported by 52 (86.7%) with scores of 7 to10 in 26 (50.0%). Only eight (13.3%) were pain-free. Services offered included pain and other symptom control, counselling and training for carers at home, provision of funds and comfort packs, bereavement services. The cost of services was heavily subsidised by the Centre for Palliative Care, Nigeria (CPCN), a non-governmental organisation and UCH. Although all patients are now deceased, the compassionate care received at a subsidised cost was highly valued, as shown from the appreciative comments of relations and carers.Home-based palliative care provided at low cost was beneficial to patients and their families. More can be achieved through the training of more health professionals, increased funding, and increased public awareness of the services. The World Health Organisation (WHO) defines home care as the provision of health services by formal and informal caregivers in the home in order to promote, restore, and maintain a person’s maximum level of comfort, function, and health including care towards a dignified death. Home care services can be classified into preventive, promotive, therapeutic, rehabilitative, long-term maintenance, and palliative care categories. The strength of this approach is the dignity and privacy it gives to the patient and their families to be cared for in the comfort of the patient’s home, giving psychological, social, and spiritual support. Bereavement support is also an essential component of palliative care .Home-based care was conceived as a means of alleviating the strain on overburdened and under-resourced hospitals whilst providing better and more holistic care to patients living with life-limiting illnesses such as cancer and human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS). Groups of home-based carers, often drawn from religious groups, would visit patients in their communities, providing them with palliative and spiritual care, and educate the patients’ families in how to care for people living with HIV/AIDS.Home-based care was meant to be a support mechanism for the hospital system and people living with HIV/AIDS (PLWA) and their families; a way to empower communities to respond to the impact of HIV/AIDS themselves by supporting them through the process. Home-based care however is now a recognised model of service provision for palliative care globally. Formal provision of home-based palliative care services for patients with chronic illnesses was started in Ibadan,Oyo State in 2006 by volunteering members of the CPCN, a non- governmental not for profit organisation. The UCH, a federal government tertiary hospital, in collaboration with the CPCN group established a hospice and palliative care unit in the hospital in 2007 to provide inpatient, daycare, home-based care services, and bereavement support. Patients enrolled for home-based care reside within the catchment area of the hospice, defined to be within a 30 km radius of the hospice location in Ibadan. This ensures that patients can be seen during working hours and maximises limited available manpower and financial resources. The unit also provides training for health professionals and carers. This is the first of such units in Nigeria. The UCH palliative care programme provides inpatient care, outpatient care at the hospice, daycare for adults and children living with life-limiting illnesses, including but not limited to those with cancer.The aim of this paper is to discuss the spectrum of adult cancer patients seen by the unit and services offered to them in their homes from March 2009 to January 2013.All patients referred to the hospice and palliative care unit were fully enrolled and consent was obtained for home-based palliative care from the patients and their main carers. The first visit was undertaken in the company of a carer or relation accompanying the palliative care team of doctor and nurse from the unit.Records of 787 adult patients who had been enrolled for palliative care were reviewed to extract data on the patients with life-limiting illnesses who gave consent for home-based palliative care. Their biographical data, days on programme, diagnosis, stage of disease, major complaints, pain scores, other symptoms, services offered, number of home visits, follow-up, and outcome were extracted and reviewed. Pain was assessed using the Numerical Rating Scale (NRS): 0 = No pain,10 = Worst possible pain. The days on programme were obtained from the day of referral to the palliative care unit to the day of demise of the patient. The data were analysed using SPSS version 16.0.A total of 60 adult cancer patients were enrolled for home-based care during the study period: there were 20 (33.3%) males and 40 (66.7%) females out of a total of 787 patients enrolled for palliative care in the period under review. The other 727 patients were not on home-based care for reasons such as: living outside the catchment area of the hospice or not giving consent for home-based care. However they received palliative care rendered to them either on the hospital wards as inpatients or in the hospice as outpatients and were followed up while on the wards and also via telephone. The age of patients ranged from19–98 years. The age distribution is as shown in All the patients had advanced stages of cancer: with 3 (5%) patients at stage II, 7 (11.7%) at stage III, and 50 patients (83.3%) T stage IV. The cancer diagnosis of these patients is shown in Homes were visited 1–23 times per person, an average of once per week and apart from symptom control, comfort packs (consisting of items such as food and toiletries) were given as a form of support. These items were provided through the CPCN—a not for profit organisation—or from individual donations to the unit. Days on programme ranged from 9–1207 days (average: 286 days).Pain was the major complaint in most patients. Out of the 60 enrolled patients, 52 (86.3%) had complaints of pain from multiple sites including primary and metastatic cancer sites and the scores on the NRS are as shown in Patients complained of other symptoms such as cough, weight loss, weakness, pedal oedema, inability to sleep and fatigue for which they were managed appropriately by the team.Other services offered at patients’ homes included psychosocial counselling and training of carers on wound dressing, drug administration, safe patient handling, and care. Some funds were provided for indigent patients as well as the comfort packs. Physiotherapy services were provided for some of the patients by the physiotherapist in the palliative care team when required. Apart from visits, patients were also followed up via telephone calls and bereavement support was also offered after death.Although all patients were dead by the end of the review, their families were appreciative of the palliative care provided at subsidised cost, as reflected in their comments shown in Cancer remains one of the leading causes of death in developing countries. It has been reported that 650,000 people of an estimated 965 million are diagnosed with cancer yearly and that the lifetime risk of a woman dying from cancer in Africa is two times higher than in developed countries .In this study, breast cancer was the commonest in women (21.7%) while prostate cancer was the leading cancer (21.7%) in men. This correlates with a previous review in Nigeria . ProstatHome-based care has been practised informally by religious groups and individuals over the years with very little or no documentation. It however, remains an integral form of service provision for palliative care all over the world. The documented successes and benefits of these programmes include: enhancing the quality of life, easing the pressure on the few health facilities; alleviation of families’ lack of essentials; stigma reduction, and high levels of behaviour change.et al showed that 60–70% of patients with cancer present late in Nigeria. Many of the patients attribute their cancer as caused by spiritual forces. As many cancer patients die even after receiving conventional western medical treatment, other cancer patients become discouraged from seeking western medicine, and therefore resort to complementary and alternative medicine (CAM) treatments, prayers, or faith to obtain healing [Formal provision of home-based care in Nigeria is a relatively new concept and though it is still evolving, it has improved since 2007 when the UCH unit was established. As in the report by Parkins [ healing , 6.Homes were visited between 1–23 times per person. This was usually determined by the clinical state of the patient at referral and the receptiveness of the family towards receiving the team. As part of the advocacy and getting patients families involved, a member of the family is asked to lead the team to the home of the patient for the first home visit. The costs of the visits are heavily subsidised by CPCN through fund raising to cover provision of funds and materials for the comfort packs, functional vehicle, and driver for transportation. Services are also rendered by volunteer members of CPCN who are mostly health professionals with palliative care skills. Comfort packs were given to indigent patients to reduce the cost of care and unnecessary suffering. The content of such packs is tailored to the possible needs of patients in a given locality and include pain medications, food items, toiletries, adult diapers, and sterile wound dressing materials to meet the basic needs of the patient. The continued provision of these comfort packs however would require both international and local funding from charitable organisations and individuals.The University College Hospital (UCH), provides paid medical and non-medical staffs: doctors, nurses, administrative staffs who run the hospice. The latter constitutes the larger expense. Subsidisation of costs also includes lower consultation fees charged at the hospice and palliative care unit (about 50% less) than in the other hospital clinics and lower costs for oral morphine which is prepared from powder from the hospital pharmacy (about 75% less than imported liquid morphine). These efforts assist most of the patients who are very indigent to even have access to home-based care at the end of life.All patients with life limiting illnesses referred to the unit and evaluated as requiring palliative care were enrolled on the programme. There are no criteria that limit the enrolment of patients on the programme, e.g., six months or less to likely death, as practised in some developed countries. An interdisciplinary team approach, focused on the patient and family, with care provided by a team consisting of a physician, nurse, social worker, and other trained health professionals were employed for the home-based care.Although the average number of days on programme was 286 days, there were patients who were referred on the day they died and not much could be achieved because of the constraints of time and the disposition of the family at such a sensitive time. This further reinforces the need for health education for people to present early at hospitals and for health professionals to involve the palliative care team early and not wait until the end.Pain was the most distressing complaint and the major reason for patient referral to the unit. The numerical rating scale 0–10 was used in scoring pain. Patients both educated and uneducated found it easy to understand and their caregivers too. It was used to assess pain at initial contact and also to rate pain at subsequent visits. Although most patients reported moderate to severe pain on enrolment, relief of distressing pain was achieved in the majority of patients. Liquid oral morphine prepared at low cost at the UCH pharmacy was the only strong opioid analgesic available in the country. Stocking, supply, and distribution of opioid medications to facilities where they are needed is done by the federal government. The challenges previously encountered on opioid availability and accessibility are now being resolved through the collaboration of the government and the Global Access to Pain Relief Initiative . Other sEmotional and spiritual support was also offered for psychosocial issues by members of the team. Issues around financial support, care for the family, job security and dependence on family with resultant loss of income are often discussed with patients and their families since healthcare in Nigeria is mostly catered for through ‘out of pocket’ expenses. The involvement of trained chaplains, Imams, or other religious leaders in home-based care would provide a more comprehensive and holistic service for Nigerian patients who are very religious.By integrating palliative care into curative care practices earlier in the disease trajectory, chronically ill patients nearing the end of life report improved satisfaction with care and demonstrate less acute care use resulting in lower costs of care. In addition, patients enrolled in the palliative care programme were more likely to die at home than in comparison to group patients . Home-baThus, patients who wish to die at home should have affordable home palliative care with bereavement support , 12.The needs addressed through the home-based care are multifaceted and many more patients with life-limiting illnesses would benefit if this is made available in their communities .There are challenges which include the reluctance of some patients to receive home-based care, which is possibly because of the secretive nature of the African setting and the fear of stigmatisation. There is also insufficient funding for the provision of these services. Another limitation is the inadequate number of health professionals trained in palliative care, it being an emerging specialty in Nigeria. There is also the need for trained informal caregivers to provide and support the provision of home-based care in the community. The CPCN and other stakeholders are involved in advocacy for inclusion of palliative care including the home-based care model in the national health care system.Most of the families who received care had come to see the palliative care team as an extended part of their families and sometimes they even discuss and request support on funeral plans and legal issues which are normally reserved for family members only. In general, families were appreciative of the subsidised home-based palliative care services provided. This reduced the burden of taking patients to and fro from the hospital and the purchase of oral morphine and other pain medications at higher cost. One of the patient’s family had this to say: ‘we really appreciate the palliative care team for the several visits to our home to see our father, their words of advice and encouragement, the regular phone calls to know how he is doing. We appreciate their efforts’. A patient (Mr A) also had this to say: ‘I thank the palliative care team because they have really shown themselves to be caring indeed. In fact, I have been able to get relief of my pain as chronic as it was before I met them. I am relieved with the way they have constructed my pain relief plan’.This study was a retrospective notes-based study and efforts are currently being made to institute a prospective study using standardised tools and outcome measures.This study reviews an innovative model of home-based palliative care services offered to adult cancer patients and the first of such in Nigeria. It highlights the importance of such a service in reducing expenses, community involvement, and the use of volunteers in end of life care. While so much is being done to improve the quality of life of these patients, more can be achieved through the training of more health professionals including aspects of effective pain management, increased funding, and increased public awareness on the availability of these services.


The Mectizan Donation Program (MDP) was established in 1987 to oversee Merck’s donation of Mectizan  for the control of onchocerciasis (river blindness) worldwide [P0rior to the donation of Mectizan, vector control was the only strategy used to control the disease. The World Health Organization’s Onchocerciasis Control Program (OCP) led the effort for 25 years, which resulted in very low endemicity in some West African countries. When Mectizan was donated, the implementation of mass drug administration (MDA) emerged as the primary strategy to control and eliminate onchocerciasis. The success of MDA led to the concept that drugs for other neglected tropical diseases (NTDS) could be distributed using the same strategy.When MDP began, there was no distribution mechanism to reach the entire population at risk for onchocerciasis, particularly those living in remote, rural areas with poor health infrastructures. Merck approached a number of United Nations and international development agencies to request help distributing the drug, but because of lack of an established model, none came forward to facilitate distribution of the drug . DetermiThe Onchocerciasis Control Programme (OCP) in West Africa began coordinating Mectizan distribution in some of the highly endemic areas for onchocercal blindness, while non-governmental development organizations (NGDOs) worked with Ministries of Health to cover the remaining areas of Africa. As mapping activities expanded, showing the real extent of the disease, it was clear that NGDOs and Ministries of Health did not have the resources to scale up as required. As a result, the Ministries and NGDOs, together with support from WHO and World Bank, created the African Program for Onchocerciasis Control (APOC) to coordinate distribution efforts throughout Africa.Mectizan for onchocerciasis is donated to Ministries of Health, mostly through NGDOs, and distributed by country programs and NGDO partners primarily through the Community Directed Treatment with ivermectin (CDTi) strategy, which was developed as a sustainable and cost-effective method to deliver Mectizan by the WHO Special Programme for Research and Training in Tropical Diseases (TDR) and APOC . APOC adIn addition to drug donations, MDP also provides technical and often additional financial resources to address specific problems encountered on the ground. The new CDTi strategy, distributing drugs at the community level, created some significant challenges see . MechaniThere were challenges to implementing mass distribution of a drug with dosage based on weight. At the community level, weighing each patient to calculate the dosage was costly and cumbersome. Procuring and maintaining accurate scales was an issue, and they did not work well on uneven and dusty surfaces. Following a study in Nigeria, it was determined that height could be used as a surrogate for weight to determine the dosage . CommuniThe early packaging and tablet size of Mectizan (6 mg tablet) also created problems. First, the drug was packaged in foil strips of six tablets each that were cumbersome to open by community distributors in the field administering the drug to hundreds of people at a time. Second, the 6 mg tablet size presented a problem when it was necessary to split tablets to administer the correct dose. The NGDOs brought these problems to Merck’s attention and Merck reformulated the drug into a 3 mg tablet size packaged in bottles of 500 instead of the foil strips.Merck further adapted to problems identified in the field by analyzing the drug’s stability, which resulted in extension of the shelf life from two to three years to prevent wastage and the need for disposal in areas where safe drug disposal was limited .In 1998, Merck expanded the donation of Mectizan to include the elimination of lymphatic filariasis (LF) in countries co-endemic with onchocerciasis. The rapid scale up of treatments for LF required a significant increase in Mectizan production, which has been sustained since the expansion, although sufficient geographic coverage for LF elimination in Africa remains problematic.Loa loa microfilarial loads. Loiasis is endemic in Central Africa and therefore presents a safety challenge because of the potential for neurologic SAEs, the cause for which remains to be fully elucidated [In areas where loiasis is co-endemic with onchocerciasis and/or lymphatic filariasis, serious adverse events (SAEs) following treatment with Mectizan can occur in subjects with high ucidated . MDP, MEucidated . FurtherBy the end of 2012, the distribution of Mectizan had ceased in almost all endemic foci in the Americas. Colombia was the first country worldwide to receive verification of elimination of transmission by WHO [There is increasing evidence that elimination can also be achieved in Africa with changes to the current control strategies in some areas, such as multiple yearly treatments and improved geographic and therapeutic coverage ,14. A nuDrug forecasting needs to be much more accurately assessed to ensure that Merck’s manufacturing capacity is in sync with the demand. Now that Mectizan for onchocerciasis is available to almost all communities that need it, the average number of tablets needed each year is well known. However, some areas will increase the frequency of treatment from once to twice yearly as new strategies develop, and some hypoendemic communities will require treatment. Projections for scaling up Mectizan and albendazole distribution for LF elimination are also well estimated; however, implementation of the scale up in many countries has been slow to progress.The success of Mectizan for onchocerciasis control and elimination can be attributed to the partnerships that have developed as a result of the donation. APOC has played a critical role in the distribution of Mectizan for onchocerciasis control and is now shifting its focus towards elimination. It will also focus on greater coordination with other health interventions for NTDs, beginning with improving the linkages between onchocerciasis and lymphatic filariasis and the necessary support to health services at the local and national levels. A number of African countries have worked with APOC and WHO AFRO to develop national master plans for NTD control. As APOC transforms into a new entity  at the beginning of 2016, new strategies will be developed for the elimination of these two diseases and for improved coordination of interventions for other NTDs. While this is a positive step forward, there will be new challenges, given competing obligations, priorities, and limited resources of health systems.PENDA will urgently need to acquire the necessary financial and human resources to expand its role to further integrate interventions for multiple diseases that share similar strategies and target populations. Rapid scale up before 2016 is vital if elimination targets are to be met. The need for accurate forecasting and reporting will be essential during this time to avoid under- or, more likely, over-estimation of drug needs in each country. Over-estimation may result in excess inventory in storage-limited situations, causing a high risk of drug expiration, and in potential problems with manufacturing capacity.Operational research needs are assessed by partners on an ongoing basis. Challenges remain to develop the most effective use of Mectizan to achieve elimination of both diseases in areas co-endemic for onchocerciasis, LF, and loiasis. Questions around the integration of interventions for NTD control need to be resolved. More research is needed to answer questions on the most efficient way to map diseases, identify priority treatment areas, coordinate MDA and other delivery systems, and monitor for safety ,16.There have been many lessons learned during more than 25 years of Mectizan donation. MDP initiated the use of mass drug administration as a major strategy to control and eliminate river blindness. Donations from Merck have made the elimination of onchocerciasis a realistic goal for low-income endemic countries. Since the inception of the program, river blindness has been virtually eliminated in the Americas. The commitment of Merck remains firmly in place, and by 2025, there is hope that the donation will have achieved much more than was ever expected 25 years ago.


On two sunny days in Rome in November 2014, more than 200 people with an interest in core outcome sets (COS) from around the world gathered at The Pontificia Università Lateranense for the fourth meeting of the COMET Initiative. They came from 14 countries: Austria, Canada, Denmark, France, Germany, Ireland, Italy, Netherlands, Poland, Portugal, Romania, Switzerland, UK and USA. The programme was introduced by Liz Gargon (COMET Project Coordinator) and a summary of the coming days was provided by the chair of the COMET Management Group (Paula Williamson). Paula also presented the COMET strategic plan and provided a general update and progress report since the last meeting in Manchester in June 2013. Over the two days, the invited plenary talks were complemented by three workshops, 52 posters (50% more than the number at the 2013 meeting) and four contributed presentations.th November, Roberto D’Amico (University of Modena) talked about the need for core outcome sets to improve evidence synthesis, and Silvio Garattini (IRCCS-Istituto di Ricerche farmacologiche Mario Negri) followed him by discussing the use of surrogate and composite endpoints. He underlined the differences between core sets and these end points and explained how the latter did not always examine the outcomes most important to patients. This became a prominent theme throughout the meeting and was the focus of a dedicated session on 20th November focussing on patient engagement and involvement in COS development. A patient representative (Rosemary Humphreys – HOME Initiative) emphasised why core outcome sets are so important to patients, highlighting how patients looking for information on their conditions on the internet and elsewhere are confronted not only by the challenges of finding reliable information but, when they do, they might find themselves looking at trials that did not compare the same outcomes. She also stressed how doctors might know about the condition, while patients know about the impact. We also heard about the potential challenges of public involvement from the perspective of a COS developer . Iain spoke about the practical, but essential, aspects of arranging face to face meetings and ensuring comprehensive involvement from all sections of a patient group or society, including ‘hard to reach’ groups. Heather Bagley, COMET Patient and Public Involvement (PPI) coordinator, concluded this session with a presentation on ‘Involving people and the COMET PPI strategy’, which outlines COMET’s public involvement objectives and initial plans for public involvement activities. This report is available at http://www.comet-initiative.org/resources/publicinvolvement.On 19In a session designed to turn the generalities of developing COS, into the specifics of individual projects, we also heard from three COS developers  about the methods used and their experiences of developing COS. Discussion included the importance of defining the scope of the COS from the outset and thinking about implementation early on in the process. This provided the foundation for later sessions, including one on COS development methodology . We also learned more about the relevance of COS to systematic reviews, in particular Cochrane Reviews. Holger Schünemann (McMaster University) highlighted the links to the GRADE summary of findings tables, suggesting that COS can help reviewers decide on the important outcomes to present in their tables. Valerie Smith (Trinity College Dublin) presented a survey of outcomes in Cochrane Reviews, emphasising that consistency of reporting of outcomes across and between Cochrane Review groups is a challenge and that Cochrane needs to play its part by using COS in their reviews to help overcome this. The example of pain as an outcome that cuts across many of these Groups was explored further by David Tovey (Cochrane Library) and Peter Tugwell (University of Ottawa). It was clear that there is much to be done to help standardise the outcomes across and between Cochrane Groups, and COS might be a great starting point for this.The final session focussed on the links between COS, COMET and other groups, such as the European Medicines Agency (Irmgard Eichler) and National Institutes of Health (Jerry Sheehan), and showed the potential role for COS in the development of regulatory guidelines. Sean Tunis  reported on the first COMET network meeting in North America, held earlier in the year, where many organisations including FDA, AHRQ, NIH and PCORI came together to learn about the importance and relevance of COS, and to think more about the role that each of these organisations may play. Payers were highlighted as being stakeholders that had not been mentioned much through the meeting but were another group that might have an important role to play in the development and implementation of COS, due to the rising costs of healthcare and the pressures on them to spend money efficiently. Sean described how he will use COS and refer to COMET in guidance papers developed by the Green Park Collaborative. Perhaps the most importance message from this session was that we need to find ways to collaborate and add value to the work of these other organisations. This was exemplified by Khalid Khan (Barts and The London School of Medicine and Dentistry) who described the CoRe Outcomes in WomeN's health (CROWN) Initiative, a consortium of women’s health journals aiming to promote core outcome sets in all areas of the specialty, which now has around 70 different journals signed up and committed to the initiative.COMET IV provided a unique opportunity for stakeholders from different environments to share their ideas and progress, and engage in discussion and debate. Participants shared their challenges, needs, solutions and resolutions. The meeting brought together key scientists and consumers responsible for developing and implementing COS, including trialists, systematic reviewers, health service users, clinical teams, journal editors, trial funders, policy makers, trials registries and regulators. There was resounding support for the COMET Initiative and unanimous agreement that COS have a vital role to play in the future of clinical trials and health research. Since COMET IV, we have already had follow up contact with people and groups from the meeting. One example is the European Commission Initiative in Breast Cancer (ECIBC), and we hope that our days in Rome will be the catalyst for much successful and productive collaboration in the future. It was clear from the enthusiasm and dedication shown throughout COMET IV that there is a continued commitment to COS development and application.http://www.comet-initiative.org/events/FourthCometMeetingThe slides from COMET IV presentations can be viewed at:


The manipulation of glass ampoules involves risk of particle contamination of parenteral medication, and the use of filter needles has often been recommended in order to reduce the number of particles in these solutions. This study aims to develop a theory-based intervention to increase nurse intention to use filter needles according to clinical guideline recommendations produced by a large university medical centre in Quebec (Canada). Using the Intervention Mapping framework, we first identified the psychosocial determinants of nurse intention to use filter needles according to these recommendations. Second, we developed and implemented an intervention targeting nurses from five care units in order to increase their intention to adhere to recommendations on the use of filter needles. We also assessed nurse satisfaction with the intervention. In total, 270 nurses received the intervention and 169 completed the posttest questionnaire. The two determinants of intention, that is, attitude and perceived behavioral control, were significantly higher after the intervention, but only perceived behavioral control remained a predictor of intention. In general, nurses were highly satisfied with the intervention. This study provides support for the use of Intervention Mapping to develop, implement, and evaluate theory-based interventions in order to improve healthcare professional adherence to clinical recommendations. Due to the properties of glass, glass ampoules are often used in the process of parenteral administration of medication. In fact, glass ampoules possess good chemical resistance; they are also impermeable and easy to clean and administer and can be sterilized and vacuumed. Moreover, glass ampoules allow for storage of photosensitive substances and the accurate measurement of medication . HoweverFilter needles can reduce or eliminate particles in medication administered parenterally , 4, 9. TIn a context where nurses are largely responsible for the preparation and handling of parenteral medication in hospital settings , 18–20, Ajzen's theory of planned behavior (TPB) , 23 is cIn the first phase of this research project, conducted in a multisite university medical centre in the province of Quebec, Canada, we used the TPB to understand the determinants of nurse intention to follow recommendations on the use of filter needles in their practice. The results of this first phase are presented in another publication . Based oThe Intervention Mapping (IM) framework was used to guide all the steps related to this intervention.IM is a framework elaborated by Bartholomew et al.  that proThe two first steps of the IM framework were achieved through a collaborative project between the university hospital nursing directorate and a research team. Step 1, needs assessment, was based on a comprehensive assessment of the health problem, the program goals, and the desired changes in behavior. In the context of the release of new clinical practice guidelines regarding the use of filter needles in the organization, the nursing directorate identified a potential problem regarding nurse adherence to these guidelines, as it was seen as a key condition for the optimal use of filter needles. Due to the higher cost of the needles, their use was limited to specific circumstances, such as in the case of parenteral injection in newborns and children . In collFor step 2, the behavior change objective was to improve nurse adherence to recommendations regarding the use of filter needles in their practice. The identification of behavioral determinants related to the change objective was achieved through a questionnaire survey among nurses from eight care units of the university medical centre. This survey identified attitude and perceived behavioral control, as well as three specific beliefs related to these constructs, as the main determinants of nurse intention to follow recommendations regarding the use of filter needles. The detailed results are presented elsewhere . Thus, tThe third step of the IM framework consisted in the identification of strategies based on behavioral change theories. These change strategies were selected jointly by the nurse in charge of implementing guidelines on the use of filter needles (JC) and a researcher (MPG), using brainstorming and consulting the literature on behavior change strategies , 32. We The fourth step of IM is the program production. This was again done jointly by JC and MPG, with input from the nursing directorate (BM), and included the creation of the program theme, its scope and sequence, and the list of needed materials. We designed the documents to guide the realization of the intervention by reviewing available materials and creating new ones if needed. For instance, a poster was designed based on a previous message about the “rights” of injection see . We maden = 270).With respect to step 5 of the IM framework, program implementation was scheduled during the fall of 2013. All chief nurses from the target units were contacted beforehand and informed about the intervention. Two nurse trainers performed the intervention in five pediatric units of the university medical centre . In total, 36 sessions of 15 minutes in length were completed with the nurses working in these units between November 25 and 29, 2014 . SubseqAfter the intervention, posters were displayed in the area dedicated to the preparation of medication of each unit, informing about the potential risks related to particles from glass ampoules in medication and the six steps of a secure preparation: right patient, right medication, right dosing, right moment, right route of administration, and right needle see .The sixth step of IM is the program evaluation. We used a before-after design with one group. Due to practical constraints, it was not possible to use a control group since the intervention units were not comparable to other care units in the hospital.n = 364) of eight care units (five pediatric units and three adult intensive care units) in order to identify the primary determinants of nurse intention to follow recommendations related to the use of filter needles. The questionnaire was developed following experts' recommendations for the development of psychosocial questionnaires [In the first part of the project, self-administered questionnaires were distributed to all nurses .The postintervention questionnaire was developed based on results from the first phase of the study and pretested by four nurses who were not from the intervention units. It was distributed to all nurses from the five pediatric care units who participated in the intervention, just after its completion. As recommendations on the use of needles were limited to vulnerable groups, such as neonates and children, the intervention only concerned these five units. The postintervention questionnaire included two sections. The first section presented questions about the psychosocial determinants identified during the first phase of the study (six questions measuring attitude and three questions measuring PBC). Nurse intention to follow recommendations regarding the use of filter needles was assessed by a single item. The second section of the questionnaire assessed participants' satisfaction with the intervention based on six questions developed specifically for this study. All questions were assessed on a 7-point Likert scale. See Supplementary File 1 in Supplementary Material available online at Finally, the assistant head nurses of the various units were questioned about the use of filter needles one month after the intervention to learn if there were changes observed since the intervention. t-tests and Wilcoxon rank tests on all items and constructs to detect differences before and after the intervention. To test the theoretical model, we used a logistic regression in order to learn if attitude and PBC constructs had a significant influence on intention. We dichotomized the intention by classifying it in two categories: high intention  and moderate intention (intention below 7). Due to the very high postintervention intention score, the categories were unbalanced . Nurse satisfaction with the intervention was analyzed by conducting a descriptive analysis of the six items measuring it in the questionnaire. All statistical analyses were done using SAS 9.3 [We conducted SAS 9.3 .Ethical approval was requested from the ethical committee of the university health centre. The committee concluded that approval was not necessary because the project was part of a quality improvement initiative. This study still adhered to the usual ethical considerations of informed consent, voluntary participation, and confidentiality.For the preintervention survey, 254 questionnaires were completed and returned on a possibility of 364 nurses working on the five pediatric units. Twelve questionnaires were excluded, resulting in 242 questionnaires included, for an effective response rate of 66.5%. For the postintervention questionnaire, 169 of the 270 nurses who received the intervention completed the questionnaire, for an effective response rate of 62.6%.  t-test. However, both tests indicated that all variables were significantly higher after the intervention, as shown in Since the theoretical constructs did not follow a normal distribution, the Wilcoxon rank test was deemed more appropriate than theP = 0.0032). The final logistic regression model explained 32.5% (Nagelkerke R2) of the variance in the intention score. The area under the ROC curve, which represents a measure of the correctness of the classification that would result from the regression model, was 0.74, which is considered as fair [A logistic regression model was used in order to learn whether the constructs targeted in the intervention (attitude and PBC) had a significant influence on intention. In the final regression model, only PBC remained as a predictor of intention, with an odds ratio of 3.60  and confirmed that the items measured a single factor with an eigenvalue of 4.80.The satisfaction questionnaire was developed in-house and comprised five specific items regarding the intervention and a global satisfaction item. We also computed the Cronbach alpha and performed a confirmatory factor analysis in order to verify the internal consistency of the items related to satisfaction from the postintervention questionnaire. These analyses showed good internal consistency  or 7  to the six questions related to satisfaction in the questionnaire  in order to achieve this goal.Nurse intention was already high in the preintervention questionnaire (mean of 6.69 on 7) and increased slightly after the intervention (mean of 6.94). This finding is important because, despite a high baseline value, it shows that the intervention could still improve nurse intention to follow clinical guideline recommendations. The same holds for the two theoretical constructs from the TPB that were targeted by the intervention. Both direct determinants of intention, that is, attitude and perceived behavioral control, significantly improved following the intervention. Moreover, all items measuring the beliefs associated with these constructs were significantly higher after the intervention. Of particular interest is the fact that the specific behavioral beliefs that were targeted by the intervention, namely, reason and enjoyment, showed a significant increase of 0.46 and 0.95, respectively. The control belief that was targeted by the intervention, ease of use, also showed an increase of 0.32 after the intervention.PBC was the only construct that predicted nurse intention to follow recommendations related to the use of filter needles in their practice after the intervention, while attitude was not significant any longer. This could be due to the high intention scores among respondents, which left very limited variance to be explained. As PBC was the stronger determinant of intention prior to the intervention, this construct remained the only predictor in the postintervention regression.This finding supports the fact that showing nurses how easy using filter needles can be increases the chances to improve their adherence to recommendations related to their use. Many studies have reported PBC as a prominent predictor of healthcare professional intention to follow clinical recommendations. Among them, the Kortteisto et al. study on physician intention to use guidelines , the FoyIt is worth noting that the vast majority of nurses seemed very satisfied with the intervention. As we were not aware of any tools available in French to assess nurse satisfaction with a behavior change intervention, we developed our own tool. We hope that this simple six-item questionnaire can be used for evaluating participants' satisfaction with other similar interventions.Although it was not possible to assess nurse behavior in this study due to resource constraints, we did an informal follow-up with the assistant chief nurses of all five units that received the intervention. Apart from a problem regarding the availability of filter needles in one unit during the week following the intervention, all assistant chief nurses said that nurses were very keen to follow recommendations regarding the use of filter needles in parenteral injections. Nurses mentioned that they had no choice but to use filter needles because they were now aware, based on scientific evidence, of the potential harms to patients associated with the injection of glass particles.There are several limitations to consider in this study. First, care units that participated in this study come from a single multisite university medical centre in the province of Quebec (Canada). Although the results may be different in other settings and may consequently be difficult to generalize, we believe that it is possible to follow the approach for targeting similar behaviors in other settings of care since the study applies the Intervention Mapping framework , a strucClinical recommendation adoption and adherence among healthcare professionals is a continuous challenge. This study, based on the Intervention Mapping framework and the theory of planned behavior, allowed for the development, implementation, and evaluation of a theory-based intervention among pediatric care nurses in order to improve their intention to follow clinical recommendations regarding their use of filter needles. Based on the results, we believe that the intervention did improve the intention of these nurses to use filter needles according to recommendations in their practice. In light of this study, theory-based interventions may be a potential solution to improve adherence of healthcare professionals to clinical recommendations.Postintervention questionnaire (translated from French).


Since the 1960s and the therapeutic use of hematopoietic stem cells of bone marrow origin, there has been an increasing interest in the study of undifferentiated progenitors that have the ability to proliferate and differentiate into various tissues. Stem cells (SC) with different potency can be isolated and characterised. Despite the promise of embryonic stem cells, in many cases, adult or even fetal stem cells provide a more interesting approach for clinical applications. It is undeniable that mesenchymal stem cells (MSC) from bone marrow, adipose tissue, or Wharton's Jelly are of potential interest for clinical applications in regenerative medicine because they are easily available without ethical problems for their uses. During the last 10 years, these multipotent cells have generated considerable interest and have particularly been shown to escape to allogeneic immune response and be capable of immunomodulatory activity. These properties may be of a great interest for regenerative medicine. Different clinical applications are under study . This review focuses mainly on tissue and organ regeneration using SC and in particular MSC. The concept of regenerative medicine is an emerging multidisciplinary field to revolutionize the way “The history of SC began in the mid nineteenth century with the discovery that some cells could generate other cells. In the beginning of the 20th century, SC were discovered when it was found that the bone marrow contained hematopoietic SC and stromal cells , 2. The In 1998, cells from the inner cell mass of early embryos were isolated as the first embryonic stem cell lines , 7. Late in vitro from bone marrow but also from other tissues of mesodermal origin: fetal or neonatal tissues , adipose tissue, joint synovium, dental pulp, and so forth [Multipotent SC, self-renewing, and adherent MSC, represent a small fraction of the marrow stroma –21. Thesso forth –30. MSC so forth . They caso forth –36. Receso forth –42. in vitro culture [ in vitro population doublings but was affected by the age of the donors [ in vitro differentiation and tissue regeneration in vivo decrease with age and according to the donor pathology [MSC do not have a defined profile of surface antigen expression but there are available markers to identify them. They are mainly characterized by the expression of different antigens, CD105, CD73, CD90, Stro-1, CD49a, CD29, and CD166. On the other hand, MSC do not express antigens CD34 and CD45 (specific of the cells of hematopoietic origin), glycophorin (specific of blood cells), antigens of differentiation of the various leucocyte populations , and HLA-DR –46. The  culture , the rese donors . Recent athology . They geathology . Bone maathology –59. in vitro reprogramming of an adult cell after addition of selected transcription factors. The major advance in this field was performed in 2006 with the possibility of a direct reprogramming of somatic cells into pluripotent cells starting from fibroblasts [Oct 3-4 and Sox gene family are determinant regulators for the induction process). In the course of the reprogramming, an extinction of the characteristic genes of the fibroblast, a reexpression of embryonic genes (SSEA 1 and 4), and activation of telomerase are observed. However, the efficiency of the technique is low. It is likewise necessary to underline that the IPS are exposed to a significant risk of malignant transformation due to the presence of the oncogene c-Myc used in the reprogramming. The present interest of this type of lines and its nonembryonic origin is the possibility of establishing specific lines of deficient patients for clinical research. The IPS are thus a tool for the study of the mechanisms of cell differentiation and genetic diseases and also for pharmacological screening [IPS result in the acquisition of a novel state followed by theroblasts , 9. Genecreening .https://www.clinicaltrials.gov/).The majority of medicine specialities and different applications can benefit in the next decade from the progress in regenerative medicine: most are at experimental stages, with the exception of bone marrow transplantation. Cell therapy covers very large potentials in many clinical fields in cancer and in regenerative medicine –63, and Nevertheless, before SC therapeutics can be applied in the clinic, more research is necessary to understand their behaviour upon transplantation as well as the mechanisms of their interaction with the diseased microenvironment. Many authors underlined that regenerative medicine is likely to transform in the future the way we practice medicine, using pharmacological or surgical procedures. The mechanism of action of SC is still being determined. The general consensus today suggests that the most probable mechanism may be through the release of cytokines and other growth-promoting factors.How to differentiate SC to the desired cell phenotype and which biological and environmental parameters are important during culture for differentiation?What are the best suitable cells: which precursors or differentiated cells?What are the possible immunological barriers when allogenic cells are used?What are the best biomarkers to identify pluripotent/multipotent/precursors cells?What is the role of the microenvironment ? What are the bioreactive molecules such as cytokines or growth factors that can support the formation of the desired tissue?Are there potential karyotype changes during cell culture?The translation from laboratory to clinics by using good laboratory practice (GPL) could impact on cell properties? in vivo?Which are the best methods to trace cellsBefore clinical applications, many challenges are to be solved .How to dThe severity degree of the pathology has to be considered.What type of grafting is planned for the patients?The site of grafting should be defined.What is the benefit for the patient?What is the clinical evaluation method to investigate the functionality of the graft?Possible side effects.It is important to note that clinical applications of biotherapies are strongly controlled in Western countries. Harvesting cells or tissues of human origin can only be performed in health centers accredited by Public Authorities . The European Regulating Authorities are also very strict about the nature of the clinical trials and about the choice of the patients. Before grafting, different points must be precised.Cancer SC has been for long a concept of hematology, particularly in acute myeloid leukaemia. However, more recently, research studies have described the concept of tumor initiating cells in solid tumors –72. The  ex vivo manipulations of grafts were developed to eliminate tumoral cells or T lymphocytes. By 1984, new sources of HSC have been highlighted in the peripheral and placental blood [Using chemical agents or specific monoclonal antibodies,al blood , 78. Thaal blood . Since 1al blood –82. in vitro, can be proposed for anticancer applications [The use of cytotoxic T cells or NK cells, isolated and amplifiedications –87. The ications , 89, andSeveral clinical trials have been proposed (34 in the beginning of 2014). The main applications are MSC and graft failure, graft versus host disease, and treatment of myelodysplasia , 91. ThiRegenerative medicine, based on the graft of tissue native cells  or SC able to differentiate into somatic cells, holds great promise if clinical hurdles can be overcome, particularly their possible tumorigenic property. This was highlighted in a case report involving a child who received fetal neural SC as a treatment for a neurodegenerative disease, but who later unfortunately developed multifocal glioneuronal tumor from transplanted neural stem cells . Many stThe regeneration of damaged tissues or organs implies the existence of cells able to proliferate, differentiate, and give a functional contribution to the regenerative processes. Among the possible middle-term therapeutic applications, cardiac insufficiency, atherosclerosis, osteoarticular diseases, diabetes, and liver diseases can be considered.https://www.clinicaltrials.gov/” (mainly in USA (25%), Europe (30%), and Asia (40%)), with most of them using MSC.In regenerative medicine, four important issues have to be taken into account: (1) the choice of the reparative cells that can form a functional tissue; (2) if necessary, the choice of appropriate scaffolds for transplantation; (3) the role of bioreactive molecules, such as cytokines and growth factors that support the formation of the desired tissue; (4) grafting and safety studies (GMP compliance). More than 3,000 clinical trials are indexed in “Every year in France, 10,000 new cases of serious cardiac insufficiency are detected. Heart transplants remain the only treatment for the most advanced stages but the shortage of donors and complications of immunosuppression restrict the indications. Surgical remodeling of the left ventricle only deals with the particular anatomical forms and recent negative results have led to a review of the indications. Mechanical ventricular assistance remains a temporary solution for those waiting for a transplant. There is thus a need for new treatment solutions. Xenotransplantation is not progressing since the immunological challenges are considerable and there are major safety considerations. Gene therapy and IPS are still in their infancy , 101 andToday more than 40 clinical trials are listed with a majority of bone marrow, Wharton's jelly and adipose stem cells –113. His Osiris Therapeutics completed a human trial using allogeneic SC for the treatment for heart disease. An intravenous drip was used to deliver of the shelf MSC to patients that had recently suffered a heart attack. No deaths occurred, and the treatment is now widely thought as safe [The treatment of myocardial infarction (MI), however, is subject to a significant constraint: the immediate availability of cells. The intracoronary injection of stem cells prepared starting from a withdrawal of bone marrow did not lead to significant improvements (3% maximum of the ejection fraction of the left ventricle). In the same manner, the intravenous injection of MSC does not give significant results. In the case of heart failure, the cell therapy turns out to be no efficient and it seems difficult today to envisage a regenerative therapy. At the end of 2007, the US based stem cell company as safe .Today there is no regulatory approved cell treatment for myocardial infarction, but research and clinical studies offer the hope for successful cell therapy in the next decades.Lower limb ischemia causes a decreased blood flow in the lower leg with intense pain and swelling . RecentlHarvest Technologies Corp.  presented some positive results from a 30-patient clinical trial of a stem cell-based treatment of critical limb ischemia (CLI). Clinical evaluation of the patients with thromboangiitis obliterans disease conducted for 12 weeks showed that the treatment had significant clinical effect. The most important finding was that more than 85% of patients were able to save their legs. Other major endpoints also showed significant improvement including quality of life assessment and individual perception of pain; there was 100% reduction in the use of pain medications. Limb perfusion, as measured by TcPO2, also showed statistically significant improvement. Thirty-three percent of the patients had serious ulcers and 90% of these showed 90% or better wound closure in 26 weeks. There were no adverse events associated with the treatment. Pluristem Therapeutics Inc.  began a Phase I clinical trial with a placenta-derived SC product for the treatment of CLI . The different trials (12 patients) generally evaluated the safety of the product in patients with CLI.In 2009Cerebral infarct is a process, in which brain damage increases with time. Therefore the time when treatment is started is critical. At present, the only effective treatment (tissue plasminogen activator) has to be administrated very soon after the stroke . In animActually, IPS cells should be ideally generated without using viral vectors and without teratoma formation for being suitable for clinical use. But today the main clinical trials in topic use autologous bone marrow MSC –124. GERON Company [The classical notion of a renewal of adult neuronal cells is today questioned, but the therapeutic applications still remain uncertain. The spinal cord repair is currently the purpose of a great deal of work after injury , 126  is a neurodegenerative disease characterised by a progressive muscle weakness that can result in paralysis and death. The multicausality of neuron death poses a considerable problem to the development of new therapeutic strategies, including cell therapy. Numerous hypotheses have been developed about the origin of ALS, but it seems that the immune system may be involved. Cell transplantation approaches in ALS remain to generate a neuroprotective environment for degenerating motor neurons by transplantation of nonneuronal cells, rather than to replace lost motor neurons. Among the cell therapy approaches tested in motor neuron disease animal models, systemic injection of human cord blood mononuclear cells has proven to reproducibly increase the life span of SOD1G93A mice, a model of familial ALS, even if only few transplanted cells were found in the damaged areas. Bigini et al. showed that human cord blood (mononuclear cells) significantly enhanced symptoms progression and prolonged survival in SOD1G93A mice and were localized in the lateral ventricles, even 4 months after administration . HoweverThe prevalence of osteoarthritis and degenerative joint disease will increase in the near future, driving the market for SC therapies for joints and cartilage . In factCartilage is a mesenchymal tissue composed of one cell-type (chondrocytes), extracellular matrix (ECM), and water. Chondrocytes represent only 1-2% of cartilage volume. The cartilage ECM is composed of collagen fibers (mainly type II collagen) supporting glycoproteins and proteoglycans which have a protein core associated with glycosaminoglycan molecules such as hyaluronic acid (HA) and chondroitin sulfate. The tissue fluid, mainly water, contributes to the particular mechanical properties of cartilage and provides nutrition and exchange with synovial fluid and with extracellular fluid or other adjacent tissues. Hyaline cartilage functions with minimal friction. It demonstrates an excellent ability to provide and adaptation to compression and distributes loads on the surface of the joint , 141. In vitro preparation of functionally developed biocartilage substitutes is an attractive concept for future clinical treatments of cartilage injuries and degeneration. Today a FDA approved cellular-based therapy for cartilage defects uses chondrocytes [ ex vivo to obtain a large number of cells for transplantation. Autologous expanded chondrocytes have a low risk of immune rejection but they have a tendency to dedifferentiate (loss of phenotype) in vitro. In other words, the influence of mechanical forces on cell function in vitro has been demonstrated for engineering cartilage and bones [Because of the limited self-healing capacity of cartilage, repair of articular defects caused by degenerative joint diseases or traumatic injuries represents an open challenge and current therapies for cartilage repair are inadequate for restoring form and function –144. In drocytes . In thisnd bones . In cartnd bones –149.Many clinical studies performed have demonstrated the therapeutic potentials of MSC from bone marrow or adipocytes –153. WhaWhile MSC therapy is promising, the incomplete understanding of their biological characteristics and function limits today the utilization of MSC in clinical application . Role of epidermidis are spread along the basement membrane. The main clinical trials [In mammals, cell renewal on the external surface of the skin is ensured by the keratinocytes of the basement layer which divide actively and are differentiated into cells of the stratum corneum. That activity implies the existence of SC. Unlike the SC of hair follicles confined in a niche, the SC of thel trials  are mainl trials , 162.The cell graft appears to be an alternative to the medical treatments for pancreas diseases. The first attempt of cell therapy by grafting of islets of Langerhans was published more than ten years ago –167. OthIn response to a variety of chronic injuries such as hepatitis, alcohol or drug abuse, metabolic diseases, autoimmune attack of hepatocytes or the bile duct epithelium, and congenital abnormalities, liver fibrosis occurs and finally leads to hepatic cirrhosis and liver failure. Liver transplantation is the accepted treatment option for this end-stage liver diseases and acute liver failure resulting in irreversible liver dysfunction. However, it is limited by the shortage of donor organs. Moreover, it is difficult to accept such a heavy surgical treatment for some patients because of the shortage of donor organs. In fact, correction of hepatocyte functional deficiency is the prime goal of liver transplantation. There is growing evidence in support of cell therapy. As an alternative to liver transplantation, some authors tried to use hepatocytes to treat patients with liver diseases instead of liver transplantation. However, the obstacle against their clinical applications is the requirement of large number of hepatocytes that are not available from patients themselves and as well as from other donors either. Thus, it is necessary to search for a novel source of cells. SC therapy has been accepted as one of the new approaches to recolonize liver. Several studies reported the hepatocyte differentiation potential of embryonic, fetal, or adult MSC but also IPS –187. in vitro. These cells which include MSC derived from bone marrow, umbilical cord, adipose tissue, and placenta are used in 32 trials mainly for cirrhosis  [As the liver contains three different cell types, which are organized in three-dimensional structures, growth and regeneration processes are highly complex. Therefore the idea of using one-type of SC leading to these three types of cells to repair liver is acceptable. Various populations of SC are under investigation in terms of their regenerative capabilities. Recently, studies showed that extrahepatic adult MSC of different origins have demonstrated their ability to express a hepatocyte-like phenotype after being differentiatedntation) –191. in vitro from bladder cells cultivated on a collagen and polyglycol acid matrix [The group of Atala in USA performed urethra transplant in young patients, preparedd matrix .Recently, the SC therapy for erectile dysfunction has been investigated. Transplantation of SC (adipose-derived stem cells or bone marrow stem cells…) was performed by intracavernous injection , 194. MoThe main potential applications are postprostatectomy and postradiotherapy, diabetes associated erectile dysfunction, and Peyronie's disease . Human cThe different ophthalmologic treatments with SC (mainly bone marrow) are related to retina diseases, macular degeneration, glaucoma, and hereditary dystrophy –199.In vivo production of red blood cells (RBC) can be of a great practical interest. Recently, RBC preparation has been possible in vitro based on CD34+ stem cells [em cells , 201. Them cells . Anotherem cells . Differeem cells .The relevance of research into the creation of reconstructed organs is justified by the lack of organs available for transplantation and the growing needs for an ageing population. On a technical level, the development of these reconstructed organs involves two complementary stages: decellularization of the target organ with a need to maintain the structural integrity of the extracellular matrix and recellularization of the matrix with stem cells or resident cells , 206.Whole organ engineering like liver, kidneys, heart, or lung is particularly difficult because of the structural complexity and heterogeneity of organ and cell types. But new ways of researches are currently focused on the matrix to support recellularization and a promising approach is the direct use of extracellular matrix of the whole organ. Thus rodent, porcine, and rhesus monkey organs have been decellularized to obtain a scaffold with preserved extracellular matrix and vascular network.Decellularization can be achieved through an intra-arterial infusion of a solution containing the detergent Triton X-100 and ammonium hydroxide. This method causes all the cellular elements to disappear, leaving elements of the extracellular matrix and the vascular system. Other methods of decellularization have also been used, employing other chemicals, enzymes, or physical ways (ultrasounds) , 208. in vivo. Fetal cells conserve their ability to proliferate and are easily differentiated without running the risk of induction of teratomas in vivo. These obstacles could be removed in future by using nuclear transfer techniques from the patient's somatic cells (IPS). Finally, the stem or progenitor cells present in most organs are another source of cells that could be used for in vitro organogenesis. But, they often remain difficult to define, isolate, and grow in culture.Several types of cell can be considered for recellularization purposes: SC  or the patient's autologous cells. SC probably represent the ideal source of material due to their ability to proliferate. Their use appears to be limited, nevertheless, by their allogenic nature, which could possibly trigger an immune response and consequent rejection, in addition to the risk with ESC of the formation of teratomasFurthermore, the type and number of cells to be used for recellularization vary depending on the organ to be reconstructed. Apparently, specific cells of the organ to be reconstructed are indispensable. Other types of cell, such as endothelial cells and fibroblasts, are also needed, since they promote the functional cell phenotype and contribute to the structural organization of tissue. The matrix of the vascular system of the organ to be reconstructed needs to be reendothelialized so as to orientate the blood flow and prevent thrombosis. in vitro and ex vivo can take several weeks until they have completely developed in the matrix. For seeding the use of an extracorporeal pulsating or continuous infusion system (bioreactor) is indispensable for providing the cells with an oxygen supply and keeping the infusate at a constant temperature [Currently, growing organsperature , 210. ThEncouraging work has recently shown the feasibility of creating bioorgans for the reconstruction of heart, lungs, liver, and kidneys. Clinical applications still remain a distant prospect, however.Heart construction could be an alternate option for the treatment of cardiac insufficiency in the future. It is based on the use of an extra-cellular matrix coming from an animal's heart and seeded with cells likely to reconstruct a normal cardiac function. Though the decellularization techniques now seem to be under control, the issues posed by the selection of the cells capable of generating the various components of cardiac tissue are not settled yet. In addition, the recolonization of the matrix does not only depend on the phenotype of cells that are used but also impacted by the nature of biochemical signals emitted. The complexity of those problems results in the full replacement of the heart with a biomaterial substitutes to standard transplanting is one prospect . HoweverThe decellularization of animal hearts  has been performed by D. Taylor through the infusion of chemical detergents. This study shows that the integrity of the matrix  can be maintained as well as the permeability of the vascular tree and the competence of the heart valves . in situ in the three main cell types . The problem of obtaining cardiogenic cells is also more complex since they not only need intrinsically contractile properties, but they must also be capable of coupling and modulating their frequency in response to neurohumoral or pharmacological stimuli. The plasticity of adult somatic cells is limited; however, it does not allow them to differentiate into cardiomyocytes. This property is only possessed by pluripotent cells, capable of acquiring a cardiac phenotype under the influence of the appropriate signal inducers. Such pluripotent cells could be human embryonic stem cells (hESC) whose allogenic character poses the problem of rejection (to say nothing of the ethics debate) or autologous, adult somatic SC rendered pluripotent through reprogramming (IPS). Regardless of the origin of such pluripotent cells, however, their clinical use implies an in vitro differentiation stage and then a selection process so that only the cardiogenic progenitors would be used. More recently, a direct conversion of the adult cells (fibroblasts) into cardiomyocytes has been proposed, again passing through the pluripotent cell stage. This approach still seems to be remote for clinical applications [Recellularization is more difficult due to the diversity of the cell populations that need to be reconstituted. Three ways to achieve this goal can be considered. (i) Use of a single population of pluripotent cells is capable of giving rise to all types of heart cells through the effect of environmental signals . (ii) Use of adult cells already differentiated for target lineages. The obtaining of fibroblasts and vascular cells can be achieved, especially as they can be taken from a future “recipient” of the reconstituted organ, as has been successfully demonstrated in the creation of implantable blood vessels. (iii) The third intermediate strategy consists of using a single population of progenitor cells at the mesodermic stage that would be liable, depending on the signals produced by the host tissue, to achieve differentiationications .An important challenge is the transfer of cells into the matrix to recolonized . While cIn summary, by the complete replacement of a human heart by another heart constituted from a matrix of animal origin and seeded by cells capable of providing the organ with effective, mechanical activity remains a remote prospect and is unlikely to become a reality within the next 10 to 20 years. in situ, suitable for the cell amplification, and being with suitable size of pores for the cell communication which is necessary for the formation of the functional tissue. Under microscope, the pore size needs to be at least 50 μm which is necessary for the vascularization of the patch and assure the MSC metabolism. The biological materials have more advantages than artificial materials because the integration of the cells is optimal for the construction of the cardiac SC patch. As the MSC derived from Wharton's jelly are easy to collect, the umbilical artery can be collected at the same time. The natural matrix of the umbilical artery possesses the essential property for the construction of a biocompatible cardiac patch.Another strategy for cardiac repair is the preparation of cardiac patch , 216. ThAbout fifty million people throughout the world are living with chronic respiratory failure at a terminal stage. The only treatment for this disease that seriously reduces life expectancy is, in selected cases, lung transplantation, but the results still are poor.A tracheobronchial graft remains a challenge –221. Res in vitro mimic stromal mesenchymal cells. The role of these cells in tissue repair has been demonstrated in animal models. Recently it was described that resident, multipotent pulmonary SC are capable of self-renewal as well as clonogenicity. The phenotype and functional characteristics of these new cells have been specified in vitro and in vivo.Pulmonary regeneration using SC is more complex . In factThe lung also contains resident specific MSC that have been described and characterised –226. TheFinally, numerous studies performed on animals have shown a beneficial role played by exogenous MSC produced by bone marrow. The effects observed in lesional pulmonary edema, sepsis, pulmonary hypertension, and even idiopathic pulmonary fibrosis have resulted in clinical applications that are currently being assessed –231. The in vitro physiological studies also showed that the ventilatory capacities and gas exchanges had also been maintained. An in vivo implantation of the bioartificial lung produced spontaneous ventilation for six hours. After this, pulmonary edema occurred. Several research routes, such as improvement in differentiation and maturation of the injected cells, a longer incubation period in the bioreactor and optimization of postoperative ventilation have been proposed.With respect to the creation of a bioartificial lung,recent works on the subject have been realized with decellularized rat lung in order to obtain a supporting matrix . EpithelRecently, others authors also decellularized a rat lung using chemical treatment, retaining only the framework matrix of the lung. This decellularized lung was then placed in a bioreactor that was used to mime the physiological conditions (negative pressure and pulsatile vascular perfusion). Epithelial cells from new-born rats were injected through the trachea and endothelial cells were injected into the vascular system. After four to eight days of incubation, this biolung was grafted on to a rat . The comThe decellularization of lungs was then reproduced on the lungs of pigs, nonhuman primates, and even humans –235. EmbThis initial research opens up a promising route for developing a functional bioartificial lung, with the prospect of application to humans within 15 to 20 years . However via the portal vein [Recent researches have shown that it was possible to use decellularized liver treated by detergents as scaffold, which keeps the entire network of blood vessels and the ECM . The inttal vein . This meBesides decellularized whole organ scaffold, the choice of cells selected to repopulate a decellularized liver scaffold is critical to the function of bioengineered liver. At present, potential cell sources are hepatocyte and MSC. SC, such as liver stem cells, ESC, IPSCs, and MSC, are a promising alternative for primary hepatocytes. Recent studies have shown that MSC originated from extrahepatic tissues can differentiate into endoderm cell-lines as hepatocytes. Several methods have successfully differentiated MSC into hepatocytes, such as stimulation MSC by cytokines as growth factors direct and indirect coculture of MSC with hepatocytes, or promotion of MSC differentiation in a three-dimensional matrix. In some cases, differentiation of MSC into hepatocytes can also be an alternative approach for whole organ transplantation in treatment of acute and chronic liver diseases . Moreove via intermediate ages, with the aim of optimizing decellularization techniques and recellularization in vitro [The kidney is certainly one of the most difficult organs to reconstruct due to its tissue complexity and the heterogeneous nature of the cells from which it is constituted. There is relatively few researches on kidney autoconstruction, though experiments performed on rats, pigs, and monkeys . The firin vitro , 250. ThAs with other organs, the research into the construction of a kidney raises numerous questions about the preparation of a matrix and the sources of the cells used for recellularization. Biological matrices have proved their superiority over the synthetic matrices sometimes used in tissue engineering. In the case of the kidney, the most frequently employed matrices are allogenic, even though xenogeneic matrices can be considered, although they might be subject to specific immunological and regulatory issues.In summary, a large number of questions and problems remain to be solved before a kidney can be prepared or constructed from ECM. Furthermore, none of the “self-constructed” organs in animals has proved to be capable of performing the vital function in the recipient for longer than a few hours. In the case of the kidney, no transplant has yet been reported even though it is the main challenge for research. The objective remains plausible, however, even if clinical applications appear to be very remote, certainly not before 15 to 20 years.Even if initially MSC were proposed for cell therapy based on their differentiation potential, the lack of correlation between functional improvement and cell engraftment or differentiation at the site of injury has led to the proposal that MSC exert their effects not through their differentiation potential but through their secreted product , 252. ThThe results from most investigations show that MSC-conditioned medium or its components mediate some biological functions of MSC. Several studies have reported that MSC-derived exosomes have functions similar to those of MSC, such as repairing tissue damage, suppressing inflammatory responses, modulating the immune system, or even decreasing cancer cells proliferation –264. in vivo allogeneic administration, and may provide an alternative therapy for various diseases.Together these studies provided pivotal support for the paracrine hypothesis such that MSC therapy is increasingly rationalized on MSC secretion rather than its differentiation potential. However, the mechanisms are still not fully understood and the results remain controversial. Compared with cells, exosomes are more stable and reservable, have no risk of aneuploidy, a lower possibility of immune rejection followingThe regeneration of tissues and organs and the use of SC for clinical uses are and will remain a challenge for the development of cell therapy and tissue engineering. Fetal and adult SC and in particular MSC provide exciting therapeutic tools of regenerative medicine. However basic research should be developed to better understand the biological process and molecular mechanism of SC differentiation, as well as the role of the mechanical signals.increase of the yield of preparation of the differentiated stem cells and study of the heterogeneous character of the preparations;possibility to have a standardized and reproducible product (preparation of controlled batches);technical problems regarding the definition of scaffolds, cells used, long-term stability, and culture medium. In particular, the impact of the biomaterial used remains to be defined;grafting (biotissue can be introduced via direct cell implantation (cell therapy), biotissue transplantation, or gene therapy);risk of teratogenic effect and of immune reaction ;religious and legal issues with respect to the different country regulations.Several challenges should be overcome:Current knowledge allows optimism for the future but definitive answers can only be given after long-term randomized and controlled clinical trials.


The number of individuals traveling abroad is increasing annually. The rising popularity of medical travel and the absence of clear minimum quality requirements in this area urgently call for the development of international standards to ensure good practice and patient safety. The aim of this study is to identify the key domains in medical travel where quality standards should be established. Drawing from the evidence-based OECD framework and an extensive literature review, this study proposes three critical areas for consideration: minimum standards of health-care facilities and third-party agencies, financial responsibility, and patient centeredness. Several cultural challenges have been introduced that may pose a barrier to development of the guidelines and should be taken into consideration. Establishing international quality standards in medical travel enhances benefits to patients and providers, which is an urgent necessity given the rapid growth in this industry. Medical travel is defined as the crossing of national borders with the purpose of receiving treatment that has been determined as essential to maintaining quality of life by a health professional, but may not need to be performed urgently . MedicalAlthough some individual countries offer definitions for standards of quality health care, there appears to be no universal definition for international quality standards . BroadlyDespite the absence of a universal definition, several guidelines exist regarding quality in the health-care context on clinical, national, and international levels. The Institute of Medicine  and theThere are, however, a number of limitations regarding the applicability of these existing guidelines within a medical travel context, particularly when it comes to global medical standards. Currently, the international guidelines are not reinforced by legislation; and therefore, health-care providers are not required to facilitate these standards in practice. The guidelines also do not provide comprehensive instructions on how to implement, monitor, or supervise the standards. Additionally, the OECD guidelines do not consider individuals who travel abroad for medically necessary care. Incorporating medical travel into the OECD guidelines will ensure a more comprehensive perspective of quality of medical care, taking into account the key motivations of medical travelers.Quality of care, cost, and access are among the key driving factors that influence a patient’s decision to travel for obtaining medical care –12. In aThis paper offers a potential approach to establishing international quality standards for the rapidly expanding industry of medical travel. This approach addresses the challenges and issues, identified by conducting a scoping of the available literature considered most important in the design and implementation of frameworks for these standards. A two-step process is proposed to establish international quality standards in medical travel.Given that the OECD framework already incorporates the domains of quality, cost, and access, there is a stable base for the development of international quality standards for medical travel. Subsequently, the OECD framework should be adapted to incorporate specific medical travel considerations . It has been suggested that the development standards should be naturally linked to the WHO as the pre-eminent global health policy institution . Howevervia a non-governmental body [such as the International Organization for Standardization (ISO)]. This offers considerable oversight toward maintenance of guidelines and standards. The selected organization should ensure that medical travelers receive care of appropriate quality, independent of where they are traveling. As this article focuses on establishing the standards in the first place, it is beyond its scope to detail all relevant considerations, though the establishment of the standards alone would provide medical travelers with an explicit statement of good practice, which covers a variety of potential risks and creates an opportunity for such access to expand responsibly.Second, the application of the standards could eventually benefit from independent review The main domains that need to be incorporated within an international quality framework for medical travel include minimum standards of care and resources, insurance and cost considerations, and maintaining a patient-centered approach across cultural boundaries. These domains were identified as the most salient based on scoping the existing literature that discusses quality challenges in the context of medical travel.As quality is one of the key factors on which patients base their treatment decisions, it is vital to ensure that health-care facilities operating on an international medical market meet a minimum quality standard to inform potential patients about their medical care options.In contextualizing any minimum standard, a geographical location should be considered. As the OECD proposes that quality standards should be partly subject to countries’ differences , the couIndependent, external peer review is necessary to ensure that a particular health-care facility meets the minimum quality standards , 18. WitTo resolve this discrepancy, organizations providing international accreditation should be liable to a higher authority that would oversee the peer-review process of health-care facilities. The International Society for Quality in Health Care (ISQua) possesses the resources to take up this role . HoweverFurthermore, the cost of peer-reviewing services must be considered. While accreditation may be relatively affordable in developed countries, facilities grounded in low-level income areas may find it more difficult to engage with the accreditation process due to limited financial resources .Apart from health-care facilities, third-party agencies that mediate the process of receiving care abroad have a substantial impact on quality standards within the medical travel industry . Given tSerious consideration should be given to insurance and costs in medical travel , includiMost definitions of quality in health-care services refer to patient centeredness, a concept of care where the overall well-being of the patient is prioritized . This inTransparency refers to making accurate and useful information about performance and outcomes available to staff, patients, the public, and regulators . A transFurther challenges in the development of the standards revolve around linguistic and religious differences. Communication is likely to be impeded when doctor and patient do not speak the same native language, which may contribute to adverse events and medical errors –29. A stAnother significant barrier to establishing international quality standards lies in the area of religious and spiritual differences. These differences – capable of changing the course of treatment completely  – may noThis paper outlines a potential approach to and consideration of factors in establishing international quality standards of care in medical travel. The OECD framework together with the key domains addressed in this paper provides policymakers with the resources to establish quality standards in medical travel. From the economic perspective, OECD may be best placed to take a leading role in developing these, having presented one of the initial calls for medical travel in the efforts to control health costs. However, to ensure the appropriate benefits for health and health services, organizations such as the WHO and other health policy bodies should be involved. As developing the standards is only the first step to their successful implementation, a wide range of stakeholders including international medical associations, insurance groups, and independent non-governmental organizations will be subsequently required to take collaborative action to support the development and further adherence to the standards. For medical travel to be assured as safe, cost-effective, and accessible for individuals in need, such standards must be in place and carried out in practice.KR designed the study. OK, BK, CM, AS, and EH conducted the literature review and identified three main domains to be considered for the development of international quality standards in medical travel. OK, BK, CM, AS, and CD wrote the manuscript. KR and SH supervised the project and edited the manuscript.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 reviewers (NM and MM) and handling Editor declared their shared affiliation, and the handling Editor states that the process nevertheless met the standards of a fair and objective review.