Healthcare systems are overloaded and changing. In response to growing demands on the healthcare systems, new models of healthcare delivery are emerging. Community paramedicine is a novel approach in which paramedics use their knowledge and skills beyond emergency health response to contribute to preventative and rehabilitative health. In our systematic review, we aimed to identify evidence of the community paramedicine role in care delivery for elderly patients, with an additional focus on palliative care, and the possible impact of this role on the wider healthcare system.A systematic review of peer-reviewed literature from MEDLINE, Embase, CINAHL, and Web of Sciences was undertaken to identify relevant full-text articles in English published until October 3, 2019. Additional inclusion criteria were studies focussing on extended care paramedics or community paramedics caring for elderly patients. Case studies were excluded. All papers were screened by at least two authors and underwent a quality assessment, using the Joanna Briggs Institute appraisal checklists for cross sectional, qualitative, cohort, and randomised controlled trial studies to assess the methodological quality of the articles. A process of narrative synthesis was used to summarise the data.Ten studies, across 13 articles, provided clear evidence that Community Paramedic programs had a positive impact on the health of patients and on the wider healthcare system. The role of a Community Paramedic was often a combination of four aspects: assessment, referral, education and communication. Limited evidence was available on the involvement of Community Paramedics in palliative and end-of-life care and in care delivery in residential aged care facilities. Observed challenges were a lack of additional training, and the need for proper integration and understanding of their role in the healthcare system.The use of community paramedics in care delivery could be beneficial to both patients’ health and the wider healthcare system. They already play a promising role in improving the care of our elderly population. With consistent adherence to the training curriculum and effective integration within the wider healthcare system, community paramedics have the potential to take on specialised roles in residential aged care facilities and palliative and end-of-life care.The online version contains supplementary material available at 10.1186/s12913-020-06037-0. In response to growing demands on the healthcare systems, new models of healthcare delivery are emerging –4. The hIt has been well established that the world’s population is ageing . ElderlyElderly adults residing in RACFs are a complex and vulnerable population, with high levels of frailty, functional impairment, and comorbidities including cognitive impairment . The numElderly adults, including RACF residents, comprise a considerable percentage of all emergency department presentations and hospital admissions –16. ResiGiven the identified negative impact of hospitalisation on the elderly population, it has been suggested that ways to prevent ED presentation for non-urgent conditions, which might be better managed at place of residence, be explored , 21. SevIn light of this, CPN could potentially be further evolved to become an additional resource for RACFs through the provision of more specialised care, especially in palliative and end-of-life situations. The rapid expansion of paramedic practice has left the profession with developing professional and clinical boundaries, and current frameworks may no longer be consistent with actual practice or the expectations of healthcare consumers. Exploring new and emerging models of healthcare that align paramedicine with the changing landscape is essential to guide the advancement of this profession . In thisWhat role does CPN currently have in healthcare delivery for elderly adults?What is the impact that this healthcare delivery by CPs could have on patient health and the wider healthcare system?Is there evidence to support CPN involvement in healthcare delivery in RACFs and PEOL care?We addressed the following research questions:A systematic review of the literature was conducted using the PRISMA reporting guidelines . BecauseThe aim was to identify evidence for the role that community paramedicine could have in the care delivery for elderly people. MEDLINE, Embase, CINAHL, and Web of Sciences were searched to identify all relevant full-text articles in English published until October 3, 2019. The search terms covered the following areas, using MeSH terms and text words: (1) emergency medical services, including ambulance and paramedic; (2) palliative and end-of-life care; (3) aged care, including nursing homes and health services for the aged; and (4) terms related to community paramedicine. The search strategy is available in a supplementary file  appraisal checklists for cross sectional, qualitative, cohort, and randomised controlled trial studies were used to assess the methodological quality of the articles .The authors looked for strengths and weaknesses in each article by answering ‘Yes’, ‘No’, ‘Unclear’, or ‘Not Applicable’ to each question. For this quality assessment, a numerical value of one was attached to each ‘Yes’ answer, and the ‘Not Applicable’ answers were not included. The number of ‘Yes’ answers was then divided by the total number of applicable questions of the checklist. Studies with a score of 70% or more were considered to be at low risk of bias –35. As tOne author (JV) extracted the data in line with a piloted form looking at study characteristics and main findings. The first round of data extraction summarised the study characteristics, these included year, country, patient population, role or task of the paramedic, and the paramedic’s extra training. The second round focussed on study participants, aim of the study and the main findings.JV undertook the first round of identifying emerging themes. Each paper was viewed through the prism of the role of CP and a process of narrative synthesis was used to summarise the current state of knowledge and understanding , identifIn an iterative process, two other authors  independently reviewed the data and adjusted the summarised themes by expanding or merging themes and subheadings. Finally, all authors reached an agreement on the main themes.The literature search identified exactly 1700 records Fig. .Fig. 1PA total of ten studies, which were reported across 13 articles Table , were inIn regard to the care delivery for elderly adults, all studies, with the exception of one , describMost studies reported on assessment as part of the role of the CP , 47–50. The next most commonly identified aspect of the paramedics’ role was referral. Based on the identification of high-risk patients, CPs would ensure targeted referral to community resources, community services, or to specific primary healthcare workers , 49, 51.Within the studies focussing on preventative risk assessment, education was another important preventative tool –45, 47. The last aspect of the role of a CP was communication. This was generally described as regular communication of the patient’s health information with their family physician , 44, 47.The observation that the role of the paramedic varied across the studies might be related to the lack of additional training that were reported throughout the studies reviewed Table . TraininOur second research question aimed to investigate how a CP working in care delivery for elderly patients might have impact on both the patient’s health and the wider healthcare system. The findings for each study can be found in Table Several studies reported improved patient health outcomes –48, 50. Patient satisfaction was reported as being high , 47, 48.The majority of studies saw a reduction in emergency calls, transport to ED, ED visits, or hospitalisation , 47, 50.As CPN is a new shift in the way this workforce is used, integration was seen as a challenge in some studies , 50, 52.Communication between the CPs and other services could be improved according to some studies , 50. It Our systematic review found limited high-quality evidence to support CPN involvement in the care delivery in RACFs and PEOL care specifically, although there was high quality evidence for the role of CPN in care of elderly patients. Jensen et al. reported on a paramedic involvement in EOL in a long-term care facility . The parTwo other studies were conducted in senior subsidized housing buildings with residents aged 55 and over , 44, 47.In this systematic review we aimed to identify evidence of the CP role in care delivery for elderly patients, with an additional focus on palliative care, and the impact that this new role might have on the wider healthcare system. All studies included fulfilled the JBI critical appraisal criteria, with most scoring high on the criteria. In terms of care delivery for elderly adults, the role of a CP was often a combination of four aspects: assessment, referral, education and communication. Additional training in the studies varied considerably, and there was no evidence of the international curriculum for CPN being used . The stuThe role of the CP varied across the studies, which is not surprising given that the concept is still evolving. This might also be linked to the finding that the training varied across the studies, and that the studies showed no evidence of using the international curriculum as a guide to additional training for CPN . An addiAlthough the issue of how education and training might impact on outcomes was not one of our primary aims, it would be of interest if the identified programs were to be more widely implemented. Most of the included studies were from the US or Canada, which explains that the entry-to-practice education on death and dying for paramedics was lacking, as well as the reliance on short courses to upskill participants. In contrast, in Australia and the UK paramedics are educated in universities alongside other health professionals, with all health professional programs sharing content. In Australia it has been identified that paramedic education in the area of death and dying  could be enhanced .“A community paramedic is defined as a paramedic who has completed a formal and recognized educational program and has demonstrated competence in the provision of health education, clinical assessment and monitoring, point-of-care diagnostics, and treatment modalities within or beyond the role of traditional emergency care and transport.” (p.13) They add to this that the goal of any CPN program should be to “promote the patient’s access to the right care, delivered by the right provider, at the right time, resulting in the best outcomes and the most effective and efficient use of resources. The foundation of any program will be dependent on stable and sustainable partnerships among numerous community-based agencies, teams and organizations.” (p.10) [Paramedicine as a profession has a unique position in the community and healthcare system. Paramedics have high autonomy in their work and they have a role in establishing or maintaining the trust from the community . These c” (p.10) . TherefoAs mentioned earlier, there is a universal shift in the way the healthcare workforce is utilised, due to shortfalls in workforce supply or distribution. The workforce has diversified with for example specialised roles for nurses and other health professionals, of which CPN is an example. De Bont et al. categorised the development of new extended roles into two groups: (i) specialised roles which occupy a narrowly defined area of expertise, (ii) generic roles, which have a broader scope and cover a larger part of the care pathway. They concluded that the extended roles develop new ways of health service provision that suit healthcare organisations, encouraging and shaping organisation-oriented healthcare delivery .A challenge to the integration of CPN programs is that the extended scope of practice may be classified as both a specialised and a generic role. As the CPs, especially in the care delivery for elderly adults, receive specific additional geriatric, risk assessment, or PEOL training, the role has developed according to the increasing complex needs of the elderly population. However, the CP also takes on a role of health advocate, educator, and point of reference between community health services, physicians, and hospitals, covering a larger part of the care pathway. The profession continues to be seen by other healthcare professionals as being exclusively as an emergency health profession. Moreover, good integration within the healthcare system is key to ensuring the long-term sustainability of any CPN program.Our review found limited evidence for the involvement of CPs in the care delivery in RACFs and PEOL care. However, two studies were conducted in subsidized building for seniors, where the CPs had weekly sessions during which they checked for health risks and provided health promotion and education to residents , 44, 47.In PEOL care, many different healthcare professionals are involved, resulting sometimes in fragmented care. Another issue is the large discrepancy in numbers between those who wish to die at home and those that actually do so. A recent report on the sustainability of community PEOL care services, found that workforce shortages, along with pain medication and symptom management are key aspects that need to be addressed if patients’ wishes in regard to place of care and place of death are to be addressed . CPN couThe role CPN could have in RACFs and PEOL warrants further research, as the role could be a promising initiative to improve the health and specialised care for the older community.This review provides evidence to show that CPN involvement in the care delivery of elderly adults is increasing with positive results both for the population and the healthcare system. Based on the limited evidence available, this review has found that CPs could potentially provide the specialised care needed in these areas, whilst simultaneously reducing the pressure on hospitals and other healthcare providers.Since CPN is a developing concept, there is limited high-quality evidence available. Out of the potential 25 studies, only 13 satisfied the JBI critical appraisal criteria. However, the majority of the 13 studies included in this review scored highly on the JBI critical appraisal benchmark.Another limitation of this review is that it could be argued that it is challenging to compare outcomes, due the variation in CP training across the studies. Nevertheless, the quality of each study was high, and the outcomes were consistently positive. This, in turn, facilitated the identification of overarching themes.We see the results of the different studies as a strength. The shift to utilising CPs is promising on a number of levels, from patient health to the wider healthcare system. Our review is one of the few to summarise the evidence available in the evolving practice of CPs.The healthcare system is often overloaded and ever changing. With workforce issues, rather than focussing on more healthcare workers, there is a growing international trend to develop new models of healthcare delivery to address the demand. With an ageing population, the demand on care delivery for elderly adults is inevitably increasing. The use of CPs in the care delivery could be beneficial to both patients’ health and the wider healthcare system. CPs already play a promising role in improving the care of our elderly population. With consistent adherence to the training curriculum and effective integration within the wider healthcare system, CPs have the potential to take on specialised roles in RACFs and PEOL care.Additional file 1. Database Search Strategy – Overview of applied search strategy across the databases.Additional file 2. JBI Critical appraisal – Overview of critical appraisal results of the 25 studies.


Purpose of review: The aim of this study is to assess the most significant Perinatal Palliative Care (PnPC) development projects in the literature and summarize the shared key principles.Recent findings: PnPC is a new concept in neonatal intensive care approach. Advancements in perinatal diagnostics and medical technology have changed the landscape of the perinatal world. The threshold of viability continues to decrease, and diagnostic information is available earlier in pregnancy and more rapidly at the bedside; overall outcomes continue to improve. This rapid technological improvement brings ethical debates on the quality of life of patients with life-limiting and life-threatening conditions and the need to involve the family in the decision-making process, according to their wishes and cultural beliefs. Although the Perinatal Hospice concept was developed in the 1980s in the US, the first recommendations on how to develop a PnPC pathway were published in the early 2000s. We considered the most relevant position statements or guidelines on PnPC published in the last two decades. Some of them were more pertinent to pediatrics but still useful for the fundamental concepts and PnPC project's development.Summary: Health care providers and institutions are encouraged to develop PnPC programs, which have the goal of maximizing the quality of life of infants with non-curable conditions. These may generally include the following: a formal prenatal consultation; development of a coordinated birth plan between obstetrician, newborn care, and family; access to other neonatal and pediatric specialties, as needed; comfort palliative care during the prenatal, birth, and postnatal periods; and psychosocial and spiritual support for families, siblings, and staff. The goal of the program is to ensure that infants who are expected to survive only hours, days, or months do not suffer unnecessary pain and discomfort in a family-oriented environment in which parents are allowed to stay with their infant all the time with a grade of involvement based on their wishes and expectations .A dedicated multi-disciplinary team that is comprehensive of all the specialists involved in the perinatal care path should continually reassess all the needs  of the newborn and his family while trying to give timely and concrete answers to each of them. This is in accordance with the recent ACOG Committee Opinion #786 entitled Perinatal Palliative Care that is also endorsed by the American Academy of Pediatrics , 3.Perinatal Palliative Care integrates the clinical care of the infant starting from the diagnosis of a life-limiting conditionor from a decision to withholding or withdrawn life support. This also offers an advanced care plan when the transition from intensive care to comfort care is proposed because the best interest of the infants is not prolonging life , 3.Thereafter PnPC may start before birth and continue through comfort palliative care and end-of-life care. After death, there is bereavement care in a continuum of activities to support infant and parents based on their wishes, values, preferences, and spiritual needs. Counseling, debriefing, and emotional support for the staff should also be part of the care path .In all of these steps, it is possible to share an integrated care plan and bundles between the professionals involved to make the process more effective always with respect for the unique individuality of the infants and its family. This study summarizes the development of a PnPC program via a narrative review of the evidence on perinatal management in the world's most industrialized countries.While not adhering to strict PRISMA standards, this review utilized a thorough review of Embase, PubMed, and Google Scholar and the National Bioethics Committed websites via a combination of the following search strings: practice guidelines; AND perinatal palliative care; AND limit of viability. No language restrictions were applied. All potentially relevant titles and abstracts were retrieved and assessed for eligibility.We retrieved 34 full text articles from electronic databases and six from National Bioethics Committed websites. We excluded 10 articles as no pertinent with the review. Six papers manually searched were included.The application of palliative care concept to the newborn was described for the first time in the United States in 1982 . Brian CIn 2007, the core standards for Pediatric Palliative Care in Europe were published: IMPaCCT International meeting for Palliative Care in children. Those standards referred to pediatric populations and could also be validated for PnPC in the major points. However, PnPC is a pathway dedicated to fetus and newborns with life-limiting or life-threatening conditions, and thus this standard should be integrated with prenatal consultation and birth plans as well as decision-making on extreme prematurity and the perinatal hospice  published a Policy Statement on Pediatric Palliative Care and Hospice Commitments, Guidelines, and Recommendations. This team considered children with life-threatening and life-shortening conditions, and they summarized 12 recommendations that should be respected when developing a PnPC program. Briefly, the transversal standards for pediatric palliative care (PPC) include the availability of a dedicated interdisciplinary team that should have sufficient expertise to address all the basic needs of the child and his family . The PPC team should provide collaborative integrated multimodal care in relation to the regional pediatrics hospices while maintaining a core level of competency. The PPC team should be consulted frequently if there is a child with life-limiting condition to provide the best and most prompt care possible and should provide communication and decision support, family support, sibling support, and health care professional support. PPC should be a core part of medical school, residency, fellowship, and continuing education curricula. The PPC team should support and engage in research, and the program should have a quality improvement agenda. PPC teams should address ethical issues and engage in relationships with the hospital's ethics committee. The PPC program may have full financial support .The AAP , EuropeaGuidelines have identified three types of patients for whom PnPC may be anticipated and offered in the newborn period: (a) those born at the threshold of viability; (b) those with birth anomalies that may threaten vital functions, and (c) those for whom intensive care has been appropriately applied but developed an incurable disease , 6.Most guidelines suggest a multidisciplinary approach involving an interdisciplinary team who can address all the needs of the child and family. It is important to develop an action plan via a multidisciplinary project group with the steps needed to put guidelines into practice at the local level. This may differ from setting to setting. Basically, an effective perinatal palliative care team may include obstetricians, neonatologists, health care providers with expertise in pediatric palliative care, nurses, social workers, mental health professionals, religious counselors, and experts on the child's disease , 11, 14.Advanced technology can suggest precociously if the fetus is carrying a life-limiting condition. The diagnosis can be made early in pregnancy with invasive or non-invasive prenatal investigations . The condition may also be suspected and confirmed at birth.In such cases, antenatal counseling should occur with a multidisciplinary team including at least the gynecologist, the neonatologist, the palliative care team when available, and the consultant with expertise in the child's disease , 11, 14.A death that is anticipated before birth affords the family the opportunity to work with the health-care team to develop both a birth plan that specifies their desires for how they want the birth to evolve and a palliative care plan. The family's participation in making these plans helps to provide them with a sense of control, and the plan honors their choices for their baby. This is worthwhile in creating a therapeutic alliance for ongoing care. This individualized proposal for delivery and neonatal care could be reviewed during the following consultations until birth. When the birth occurs, the plan should be followed regardless of which health professionals are present at the time , 15.In 2016, the National Institute for Health and Care Excellence (NICE) published guidelines on end-of-life care for infants, children, and young people with the life-limiting conditions: planning and management  or those newborns that cannot improve despite massive medical treatment . In such cases, guidelines suggest creating a trusting relationship between family and team. The family should be included into the decision-making process without overwhelming them; this can shift the intensive care approach to a palliative one. These transitions may include discontinuation of mechanical ventilator support, artificial circulatory support, and/or artificial nutrition and hydration , 9.Newborns can survive less than a few hours or much depending on the disease. If the diagnosis was made prenatally, then the parents are aware of the child's condition and have a birth plan. The PnPC may be applied in the delivery room. PnPC is generally offered by the neonatologist to guarantee comfort, maintain temperature, and prevent respiratory distress to the newborn , 15. Parwww.perinatalhospice.org) reported 226 perinatal hospices in the USA and 57 international programs. Perinatal hospice is a family-centered, safe, and quiet place where all of the care is focused on the quality of life of the baby and honoring parent values and wishes; in the case of discharge to home, the focus is on the education of the family on the management of the newborn . Such care includes pain and symptom management, prenatal palliative care consultations, end-of-life care, communication and conflict resolution, collaboration in the care of the medically complex infant, and discharge to hospice where available , 14, 16. newborn .In 2014 Alexandra Mancini et al. “Practical guidance for the management of palliative care on neonatal units” on behalf of the Royal College of Pediatrics and Child Health . HoweverPalliative care has two fundamental concepts: withholding and withdrawing treatment , 27. WhiThis approach is applicable in high resource countries. In a retrospective multicentric study performed in Latin-American NICUs showed a completely different approach in end of life decision making. Withdrawing the support was no existent and usually the baby died with full life support. Preterm babies <27 gestational weeks were not admitted to the NICUs .The European Standards of Care for Newborn Infant Health by EFCNI were published in 2018 and were meant as a benchmark for the development of standards in each individual country . They arThe National Association of Neonatal Nurses (NNAN) published a position statement on palliative and end-of-life care for newborn and infants in 2015 focusing on transport of infant when a redirection of care is chosen as well as nutrition and hydration and on nurse education .integrative model” and the “consultative model”  in which brain death is demonstrated , 38. In The strength of our study is that it provides an overview of the most significant aspects of PnPC and aims to provide key principles to create or implement a PnPC program. We recognize some limitation. We did not perform a systematic review but only a narrative review of the most relevant evidence on PnPC in literature and we did not include internal or unpublished guidelines of PnPC that many hospitals might have.Advancements in perinatal diagnostics and medical technology have changed the landscape of the perinatal world. The threshold of viability continues to decrease, and diagnostic information is available earlier in pregnancy and more rapidly at the bedside. The overall outcomes continue to improve. This rapid technological improvement also brings ethical debates on the quality of life of these patients and the need to involve the family in the decision-making process.Many professional organizations and scientific societies in industrialized countries promulgate management guidelines for these infants and newborns with poor prognosis pathologies, but the management of these patients, as well as their survival, is very heterogeneous. Survival depends on various factors including social, religious beliefs, law restrictions, and national ethics opinions .In the last two decades, the principles and best practices in a PnPC program were mostly defined along with an overarching palliative care paradigm. However, the literature suggests that there are still many challenging aspects surrounding the implementation of PnPC. These are still lacking in many places were perinatal care are delivered. In our opinion, this is due to several reasons.First, the key principles of PnPC include advancing care planning, symptom management, and psychosocial support for families and NICU staff even in the neonatal period. Help with the decision-making process and how to manage conflicts and bereavement care are quite definitely defined , 15, 41.Second, the outcomes of a “standardized” program and quality improvement initiatives are inconsistently reported. This may due to difficulties in measuring the quality of care/improvement in this setting.Third, the fact that the PnPC is strongly focused on end-of life care limits the use of PnPC encouraging the misconception that palliative care should be reserved for only end-of-life situations. Rather, it should be considered a comprehensive and coordinated model of care—a curative treatment for fetus/neonates with life-limiting or life-threatening conditions with the goal the quality of life of the infant and family according to their wishes and values.It is essential to give evidence of rigorous PnPC implementation process as well as evaluation of a wide range of outcome data. Only in this way we can give evidence for successful implementation of PnPC, which is still very low.The PnPC and its benefits have been endorsed by many institutions and scientific societies , 12, 16;The continuity of the incurability pathway should be advised because in some situations the infants may survive months and need a different allocation of care. It is also essential that the link between regional pediatric hospice and territorial (primary) care be clear . During PnPC is a new concept in neonatal intensive care approach. Withholding or withdrawing the intensive care does not mean stopping treatments. Rather, it means redirecting active treatment to a different approach , 32. PnPPnPC is a new field of newborn care. It aims to ameliorate the health status of children with life-limiting conditions. Creating a PnPC program is mandatory to guide physicians and parents through this difficult journey.PL conceptualized and designed the review and drafted the initial manuscript. MC drafted the final version of the manuscript. FB aided in designing the manuscript and contributed to the content. FR reviewed the literature. All authors contributed to the article and approved the submitted version.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.


In recent years, various studies have followed in the literature on the therapeutic effects of mesenchymal stem cells (MSC) on damage in retinal cells. The evidence that MSCs exert their regenerative and damage reduction effect in a paracrine way, through the release of soluble factors and exosomes, is now consolidated. Exosomes are microvesicles formed by a double layer of phospholipid membrane and carry proteins and RNA, through which they play a therapeutic role on target cells. Scientific research has recently focused on the use of exosomes derived from MSC in various models of retinal damage in vitro and in vivo as they, compared to MSCs, have similar functions and at the same time have different advantages such as greater stability and handling, a lower chance of immunological rejection and no risk of malignant transformation. The purpose of this review is to summarize current knowledge on the therapeutic use of exosomes derived from MSCs in retinal damage and to stimulate new clinical perspectives regarding their use. Retinal damage is a consequence of many acute and chronic ocular diseases. It is represented by a morphological and functional alteration of the retinal nerve cells and results in a visual impairment, most of the time irreversible . CurrentMesenchymal stem cells (MSCs) have received much attention from the scientific community, because they have been shown to have a neuroprotective, anti-inflammatory, immunosuppressive, and apoptosis reduction action against neuronal cells , 3. In aOver the past 20 years, several studies have investigated the therapeutic efficacy of MSCs in the treatment of retinal defects and degenerations in both in vitro and in vivo models, obtaining encouraging results on their use –19. The In cases of retinal defects, the MSCs would lead not only to a better result from the anatomical point of view, with a faster repair of the retinal defect, but also to a better result from the structural and functional point of view, inducing the regeneration of photoreceptors, bipolar cells, and RPE cells –23. The In a previous experimental study conducted on rats by our group, it was shown how human MSCs are able to survive, migrate and integrate into the damaged retinal layers after intravitreal injection. After grafting in the vitreous body, the marked MSCs are in fact localizable in the ganglion cell layer already 1 week after surgery in cases of retinal injury induced by ischemia, unlike the controls with healthy retina  26]; so; so26]; The survival of MSCs was quite high only in the intravitreal implant, unlike those per via trans/subscleral. Through the intravitreal injection, cell growth and development are in fact much more favoured. The implanted MSCs occurred in clusters of cells arranged in a row or as single cells. In our study, there was never an immune response.At the retinal level, the best integration is obtained if the MSCs transplant is performed in conditions of immaturity or ischemic, dystrophic, or mechanical tissue damage. In these conditions, in fact, the interruption of the internal limiting membrane or of the blood-retinal barrier favours the establishment, proliferation, differentiation, and reparative effect of MSCs.The limitations of this study are that human MSCs were injected into the rat retina, and therefore, their biological effect may have been influenced as recognized as nonself. Another limitation is the poor diffusion of MSCs through biological barriers: soluble factors or exosomes derived from MSCs, compared to MSCs themselves, manage to cross the blood-retinal barrier much more easily, which in inflammatory processes is more permeable. Exosomes, in particular, thanks to their small size, manage to spread well through barriers and can be genetically modified to ensure a better therapeutic effect , 28.Analysing the mechanism of action of MSCs, recent studies have in fact highlighted how they do not act by direct differentiation but in a paracrine way, through the secretion of soluble factors and exosomes .In particular, MSCs can express a wide variety of factors that could repair and protect damaged retinal cells such as NGF, CNTF, BDNF, NTF, bFGF, and IGF1, through mechanisms widely described in literature , 29–33.In recent years, attention has focused on exosomes, which would seem to be the real mediators of the biological effect of MSCs on target cells. The purpose of this review is to summarize current knowledge on the therapeutic use of exosomes derived from MSCs in retinal damage and to stimulate new clinical perspectives regarding their use.Exosomes are microvesicles with a double layer of phospholipidic membrane which are secreted by all cell types and which were first described over 30 years ago , 35. TheThe most common way to isolate exosomes is centrifugation at 100,000 g for at least 2 hours and the suitable temperature for their storage is -20° C, thanks to which their size remains constant even for a long period , 41.Exosomes are essentially composed of lipids, proteins, and RNA. Due to their endosomal nature, all exosomes contain membrane proteins dedicated to cell transport and fusion , transmembrane proteins , and phospholipases. These proteins are detected through flow cytometric analysis, western blotting, and ELISA and allow the identification of exosomes . ExosomeA recent study by Zhao et al. has shown that an abundant quantity of exosomes is contained in the vitreous . In factMSCs produce exosomes like all other cells, but with some differences. First, MSCs have been shown to produce more exosomes than other cells . It was Furthermore, it has been shown that in the exosomes derived from MSCs there is the 20S proteasome, which is responsible for the degradation of intracellular proteins damaged by oxidative damage and therefore contributes to the cytoprotective action of these exosomes . This prThe use of MSC exosomes also allows to switch from cell-based therapy to cell-free therapy, with the advantages that this entails . In factSeveral studies have also confirmed that exosomes derived from MSCs have beneficial effects comparable to those of MSCs thanks to their content of miRNA and proteins –61. A reCurrently, MSC exosomes have been successfully applied in several studies on cardiovascular disease , 65, kidAt retinal level, it has been seen that exosomes derived from MSC possess all the advantages of MSC in limiting the extent of damage, in reducing apoptosis, in limiting inflammation, and in promoting cell survival; at the same time, they do not involve a risk of allogeneic and xenogenic immunological rejection, of malignant transformation or obstruction of the small blood vessels –57, likeFor the treatment of retinal damage, in particular, the exosomes derived from MSC are easier than the MSC themselves for administration by intravitreal injections for the lower risk of vitreal opacity, of vitreoretinal proliferations, and long-term pathological differentiation.In his study, Yu et al. investigate the efficacy of MSC-derived exosomes in case of retinal damage, induced on mice with laser krypton spots, both in vivo and in vitro . The resMead et al. demonstrated that bone marrow-derived MSC exosomes (BMSC) allow for a significant neuroprotective and neurogenic effect in an optic nerve injury model in rats . After 2μm and long-standing (>6 months) 20 or 50 μg of MSC-derived exosomes were injected into the macular hole region at the end of a regular pars plana vitrectomy (PPV). The study shows that four out of five patients experienced macular hole closure and that three out of five had satisfactory improvement in BCVA. The work therefore concludes that the intravitreal injection of exosomes derived from MSC at the end of a regular PPV could improve the anatomical and functional outcomes in cases of macular holes refractory to a first surgery or in large and long-standing ones.In the study of Zhang et al., MSC-derived exosomes have been used successfully in the treatment of refractory and large macular holes . Five paα, a cytokine that allows to intensify the inflammatory response and cell death by apoptosis following retinal damage [α also allows an increase in autophagy, a mechanism that plays a key role in the reduction of apoptosis and in the increase in the survival of the photoreceptors, as indicated by previous studies [The exosomes derived from MSC have also been studied for the treatment of retinal detachment. Ma et al. in his work investigate the therapeutic effects that exosomes derived from MSC bring in a retinal detachment model induced in rats, by injecting 1% of hyaluronic acid at the subretinal level . The resl damage –82. The  studies .MSCs are currently used clinically in a wide variety of diseases, and it is now clear that they exert most of their biological effects in a paracrine way, through the secretion of soluble factors and exosomes. In recent years, many studies have followed that have investigated the use of exosomes derived from MSC in various pathologies in vivo and in vitro models, and it has been shown that they have a therapeutic effect in myocardial damage from ischemia/reperfusion, in kidney damage, and in immunological and neurological pathologies. Even in cases of retinal cell damage, the exosomes derived from MSC were found to have a neuroprotective effect, limiting the extent of the damage and promoting cell survival. Their use has been successfully studied in many diseases of the retina, including cases of retinal cell degeneration , cases oThe treatment of pathologies and retinal damage with exosomes derived from MSC typically takes place through intravitreal injection, a mode that allows direct action of exosomes on the cells of the retina and which avoids possible adverse effects towards other organs. Compared to MSCs, exosomes, in addition to being easier to manage and maintain, are also safer since they do not cause a risk of vitreous opacity, long-term pathological differentiation, and vitreoretinal proliferations. In clinical trials carried out with the use of MSC, in fact, there have been three cases of severe bilateral vision loss after the intravitreal injection of stem cells derived from autologous adipose tissue . FurtherMathew et al. in his work indicate that the intravitreal injection of exosomes also allows a more homogeneous uptake by the cells of the retina . This isRecently, exosomes have started to be thought of as possible vectors for targeted cell therapies. In fact, there is the possibility of generating exosomes engineered with specific surface proteins to reach certain target cells and with a content of specific miRNA filaments to fulfill certain biological functions. In addition, the accumulated evidence suggests that it is possible to modify and improve the secretion profile of exosomes by genetically manipulating the cells that produce them , 84. HowThe microenvironment is also important. In a previous study published by our group, we observed that the presence of the supernatant derived from the culture of retinal pigment epithelial cells, belonging to the ARPE-19 cell line , allows it is important to underline that exosomes also seem to play an important role as diagnostic markers for intraocular tumour diseases. Ragusa et al. in his study show that in cases of uveal melanoma, there are changes in the vitreous body and exosomes contained in it compared to healthy controls . In partThe translational role that MSCs can play in regenerative medicine is very interesting. Indeed, by interacting with 3D printed biomaterials, MSCs are induced to differentiate towards specific cell lines and can induce a modulation of cellular and cytokine pathways, resulting in a new and promising therapeutic strategy –87. The The new challenge of cell therapy will be to act on quiescent retinal stem cells. They are stem cells that have been discovered in the pars plana, pars plicata, and retinal periphery and are in a quiescent state. There is 1 stem cell for every 500 cells, and the human eye contains about 10.000. Retinal stem cells are kept inert by an inhibitory factor, which is still under study and whose inactivation could lead to the reactivation of the stem cells themselves . In the The administration of exosomes could also have important repercussions at the level of brain circuits and neuronal plasticity, in particular in diseases such as maculopathy  and glauThanks to their characteristics, the administration of exosomes can bring about advantages in the therapeutic and biological-cellular rehabilitation possibilities of maculopathy  and glauIn these two pathologies, the damage to the retinal ganglion cells is different, as it is limited in maculopathy while it is widespread in glaucoma; despite these differences, they represent two excellent models for the study of biological rehabilitation induced by exosomes.One of the potential therapeutic strategies proposed to prevent the loss of retinal photoreceptors has been the administration of growth factors (such as bFGF or GDNF) through devices. This strategy did not achieve the desired effects and led to teratogenic and neoplastic changes. The potential of exosomes is to have a retina-protective effect by stimulating the preexisting cells of the microenvironment to produce growth factors, thus implementing an intrinsic biological modulation .The current evidence suggests that a project for a “unified biological-clinical-surgical specialist ophthalmological centre” is indispensable, avoiding fragmentation and dispersion .exosomes are a cell-free therapy and offer significant therapeutic benefits: they are easy to isolate, manage and store and do not involve a risk of immunological rejection, malignant transformation or vitreoretinal proliferationexosomes derived from MSC are excellent vectors for drugs or genes, making them an excellent potential resource for gene therapy and cell therapyexosomes in the context of regenerative ophthalmology lead to superior results compared to cell grafting, even if autologousthe route of administration of choice for exosome inoculation for vitreoretinal pathologies is intravitreal injection via pars planathe absence to date of truly effective and decisive therapies for degenerative neuroretinal diseases, the number of which is expected to triple in the next 20 years due to the progressive lengthening of the average lifeexosomes favour the activation of quiescent stem cells at the intraocular level and in particular at the chorioretinal level, stimulating the activation of an intrinsic biological rehabilitationthe use of instrumental exams such as angio-OCT and functional-RMN could document the activation of a biological rehabilitation and shorten the transition times from animal to human experimentsIn conclusion, research on exosomes must be strengthened and developed in the light of the following evidence:Currently, the correct dosages, times, and methods of treatment remain unknown. In addition to investigating the above aspects, further studies are needed to observe the long-term effects of therapy with MSC-derived exosomes and to clarify the mechanisms by which they act on retinal cells.


Dear Editor We had just started our shift at the emergency department that day, when a highly agitated pale middle-aged woman was brought to the emergency department by the emergency medical service (EMS). Behind her were 5 of her family members, 3 were her children and the other 2 were her sister and her brother in law. She was immediately transferred to the cardiopulmonary resuscitation (CPR) room and cardiac and respiratory monitoring were provided, central venous access was established , and fluid infusion was performed. During the time these services were provided, a history was taken from her relatives.The patient’s children were the ones who provided the history: apparently, their father had died 20 days before due to COVID-19. Dealing with his death was difficult for them, especially for their mother, due to the strong emotional bond with the father. The whole family had decided to commit suicide by consuming rice tablet . On the day we met them, the mother takes an unknown number of aluminum phosphide tablets without the children knowing and then drinks instant coffee on the balcony, after which she develops symptoms and is brought to the emergency department. After a little while, the mother develops cardiorespiratory arrest in CPR, she is intubated and resuscitation is performed and her cardiac rhythm returns for 1 hour, but then develops arrest again and her heart stops beating despite cardiac resuscitation. Giving the news of her death and informing the anxious relatives waiting behind the closed doors is done with difficulty, they can be heard crying, moaning and shouting and sometimes cursing the healthcare staff.During the second CPR, the hospital’s social worker is informed and consultation is received, especially regarding the patient’s children, and subsequently the social emergency gets involved. A few minutes later, the social worker goes to the patient’s family, explains the patient’s condition, and says that there isn’t much hope for her to return and provides consultations regarding psychological support of the family members and dangers threatening the children and emphasizes the need for involvement of the social emergency. A short while after that, the mother’s death is announced.The social worker informs the eldest and calmest family member that each of the children should be supported by a number of family members and should not be alone at home. In addition, social emergency gets involved and sends a group of experts to take necessary measures.From this point on, the information we will report about the patient and her family was provided by the elder daughter of the patient who is 30 years old : In the midst of the tumultuous situation and mourning and consultation with the family members, the 32-year-old son of the patient , who had been very psychologically disturbed and cursed the healthcare staff after the death of his mother, leaves the emergency department for a phone call. He seemingly calls the seller of the deadly tablet and leaves the emergency department without notice. Others had thought that he is mourning somewhere in the courtyard of the hospital.She said that her brother had left the hospital immediately after the phone call when others were receiving consultations in the hospital. After buying the tablet, he goes to his father’s grave, takes the tablet and dies there. The family members called him when they noticed that he is missing and since he did not answer, they called the police. The police found his dead body beside his father’s grave 3 hours later and informed the family. He was transferred to a hospital, which was in vain.The younger sister who is 22 years old (master of genetics), was admitted to a mental hospital and received electroconvulsive therapy (ECT) twice during her admission. However, the older sister seems to be mournful but coping with this mental crisis.We would like to emphasize that this family was sufficiently wealthy and highly educated from a socio-economic point of view.The recent coronavirus epidemic had serious social and mental effects on the people of China, especially those who were quarantined and could not have face to face communications and express traditional social behaviors . AnxietyNumerous studies have reported the negative psychological effects of COVID-19 including symptoms of stress due to trauma, disorientation and confusion, and anger in those involved in stressful situations. The long duration of quarantine, being afraid of getting sick, disappointment, exhaustion, storing insufficient food, incomplete information, financial problems, and stigma have been identified as stressors in the COVID-19 epidemic . Therefore, for improvement of psychological wellbeing in Iran, people should receive psychological services and be informed of ways to access these services through various sources including social media, phone, online services, or in person.Groups of people who might need psychological services should be identified and categorized for establishment of the connection. For instance:Patients with COVID-19 (with mild to severe symptoms), patients whose COVID-19 test has become positive, families, friends and colleagues of the patients, all healthcare workers, researchers who study COVID-19 in laboratories, people living in regions with high risk of COVID-19, those taking care of elderly family members in their house, mothers, especially those who have 8 – 10-year-old children, pregnant women, child laborers and people who do not receive much attention, all people in any profession, patients with special mental diseases (such as obsessive compulsive disorder and mysophobia) and psychological patients who should consume medication .It seems that psychological traumas due to COVID-19 are more dangerous than the pathogenic nature of the virus. This bitter clinical experience was a tragedy similar to thousands of similar incidents that might only attract the attention of a few or be neglected due to unawareness. The necessity of providing psychological support for survivors of COVID-19 patients is not less than using effective drugs for patients with COVID-19, both are lifesaving. Therefore, providing vigorous psychological support for families of these patients and not abandoning them in the face of a peculiar sorrow caused by an invisible enemy through employing social workers and social emergency teams, and establishing psychological and psychiatric consultation groups are strongly recommended and can reduce future mental disorders and suicides. The physicians are recommended to play a role by identifying these traumas, using the suggested methods, and asking for consultation and social aid for the patients’ survivors and following up on their psychological wellbeing.


On 21 March 2020, Zimbabwe’s Health Minister in a press conference announced that the first case of COVID-19 from a patient who had recently travelled from England had been recorded. This marked the beginning of rising cases of infections that reached 4893 on 12 August, 2020 and 122 deaths during the same period. Although the country has also had a significant number of recoveries totalling to 1544 as of 12 August, 2020, it is the management of the pandemic in general that is raising concern among citizens and observers alike. Already, the country was facing a series of economic and political challenges as it attempted to recover from the 2017 unanticipated coup that removed the late former president Mugabe from power after decades of his rule, followed by a disputed election that resulted into a post-election violence. Similarly, the country was yet to recuperate from the EU-US led economic sanctions on the country as well as mediocre economic policies that caused rapid depreciation and shortage of the local currency.coup d’etat. The president, the 1st vice president, minister of foreign affairs, lands minister (recently died of COVID-19), the defence minister and other executive members are all former high-ranking military officers. It is expected their experiences and training in the army would be of significant importance during the war against COVID-19. However, as the government tries to respond to the pandemic, sectors such as health, economy, education, and social services which had already been weakened by previous unrelated crises continue to show signs of vulnerability and further disruption as a result of the COVID-19 pandemic. The impact of government policies to try and curb the spread of COVID-19 have also impacted the informal sector, which provides employment to many citizens, public transport, mining, education, and agriculture [Zimbabwe continues to be led by individuals with military background since the 2017 This paper seeks to examine the response by the government of Zimbabwe in dealing with the COVID 19 pandemic. It argues that the training and strategies several executive members acquired from the military could be used in combating the spread of invisible enemy (Coronavirus). However, a combination of poor policies, ineffective government actions and counterproductive measures threaten to cause more harm to the Zimbabweans than the pandemic. The paper begins by providing an epistemology of the disease in Zimbabwe, then looks at how the government has responded to the pandemic. It then examines the challenges emerging from the negative impacts of the disease and the government policies on the citizens. The authors conclude with a set of policy recommendations.Over three decades of economic crisis, characterised by hyper-inflation, unemployment, and corruption, overall public service delivery in Zimbabwe including the health sector has been adversely affected. Even before the outbreak of COVID-19 in Zimbabwe, the health sector was shaky, understaffed and underfinanced . As of 2The experience Zimbabweans are going through during the pandemic is difficult one  Bulawayo (3), Mashonaland West (6), Mashonaland 8) Manicaland 7) Masvingo (6), Matebeleland South (6) Matebeleland North (7) Mashonaland Central (6) and Midlands (9) [ Masvingo Manicalath place of countries with most cases in the world [The health sector crisis is just one of many threats Zimbabweans are facing during the pandemic. Two other critical issues facing the country include police brutality and food insecurity. The latter refers to the dangerous efforts people are taking to access food even if it means crossing the border. For example, there has been sustained border crossing activities from Zimbabwe to Musina, a northern town in the Limpopo province of South Africa. People are crossing the border on foot without proper immigration documents . What ishe world .The second critical issue during the pandemic is the level of impunity and police brutality in the country. The arrest of journalist Hopewell Chin’ono, and politician Jacob Ngarivhume, who had gone public to condemn corruption particularly at the Ministry of Health marked the beginning of a planned nationwide protest against corruption on 31 July 2020 . The govThe third challenge Zimbabweans are facing during this time is corruption. Corruption situation in Zimbabwe has worsened during COVID-19 pandemic. Corruption has been manifested through the lack of accountability in the use and distribution of COVID-19 funding, equipment, misreporting of donations, awarding of procurement contracts of personal protective equipment (PPEs) and medicine without following the proper procurement channel. For instance, the Minister of Health and Child Care Dr Obadiah Moyo was fired and is currently facing prosecution for awarding procurement contracts for PPEs and medicine worth US$60 million at inflated price . Dr MoyoThe fourth concern has been whether the Zimbabwean government is able to conduct sufficient number of tests. There are just few diseases that have pushed governments to encourage mass testing in this century. Apart from HIV/Aids, Cancer and TB the other disease that has led to calls for mass testing, COVID-19 is the latest in this category. The importance of testing cannot be emphasised enough as information on the number of positive cases will not only help in policy formulation, but also contact tracing and putting potential patients under surveillance. Fears of possible cases going undetected in Zimbabwe is high as the government had only managed to test 369 people in the first 40 days after the first patient was confirmed . This reOn 19 March 2020, the president of Zimbabwe, Emmerson Dambudzo Mnangagwa through the Statutory Instrument 76 of 2020 on Civil Protection  declared COVID-19 as a national disaster. The government established a National COVID-19 Response Taskforce headed by the second Vice President Kembo Mohadi. This taskforce consists of representatives from different ministries and is further divided into subcommittees that are tasked to monitor the pandemic situation and coordinate the response to the crisis. It was also tasked with mobilising financial resources locally and internationally to cushion the country from the negative impacts of the pandemic.On 30 March 2020, the first 21-day national lockdown was announced by the president. The terms of this lockdown included the suspension of all non-essential activities, compulsory wearing of face masks for the essentials workers and the frontline workers to wear personal protective equipment (PPEs). Statutory Instrument 83 of 2020 on Public Health   Order, 2020 gave detailed information on rules and regulations during lockdowns. The statutory instrument prohibited all forms of gatherings and restricted the movement of the public except those providing essential services. Essential services that included hospital services, state security services, emergency services such as fire brigade and ambulance services, water and electricity services, sanitary service, money transfer and exchange services, and service providers of communication were allowed to continue to operate during the pandemic.The government established isolation centres in all 10 provinces of the country. The government ordered the closure of its borders to reduce the number of imported cases. The government closed all airports except for 3 international airports. Zimbabweans in other countries were allowed to return and it was made compulsory for them to isolate themselves for 14 days upon their return. The government allowed the movement of humanitarian workers and aid into the country. Schools were also closed, and students were asked to return to their homes until further notice.The government allowed the usage of foreign currency (at interbank rate or ruling rate) when paying for goods and services. Recipients of remittance were allowed to withdraw money using payment agencies such as Mukuru and Western Union. This measure increased food securities in households who had access to foreign currency. However, 90 percent of Zimbabweans had no access to foreign currency as they lived paycheck to paycheck. The Statutory Instrument 87 of 2020 on Customs and Excise (Tariff) reduced the duty of fuel with the aim of enabling the essential service providers to have access to affordable fuel. The providers of transport services gained access to affordable fuel for the provision of transport to the essential workers. Statutory Instrument 88 on Customs and Excise  (Amendment) Regulation 101 detailed the Zimbabwe Revenue Authority (ZIMRA) may refund duty on essential goods imported for fighting COVID-19. These goods included medical supplies such as gloves, masks, and food supplies.Since the outbreak of COVID-19 pandemic in Zimbabwe on 20 March 2020, Many Zimbabweans have suffered a double tragedy. The Zimbabwean government is led by people with military background who can be described as men of strategies. However, the way the Zimbabwean government is handling the COVID-19 response has fallen short of the expected impact on a team of former high-ranking military officials with training on strategy could do. This has left the citizens with immense uncertainty and hopelessness forcing some to call for protests, an act that can badly expose thousands more to the disease. But their desperate efforts to demonstrate against the government amid a global pandemic shows that majority of the citizens are left with limited options to turn to. The country’s economy was already devastated by a combination of international sanctions, poor governance, and economic policies as well as deep rooted corruption. The biggest challenge at this time is the fate of the citizens who have been left to seek solutions by themselves as they battle the disease, the police, and a collapsing economy. The Zimbabwean government is failing to strategize on how to reduce the spread of COVID-19 virus without inflicting more pain on its citizens who are already suffering from socio -economic constraints. However, not all is lost, there is still an opportunity for the government, the people, and other stakeholders to unite and form a formidable force that can overcome the negative impacts of the pandemic and lead to a healthy post -COVID 19 recovery. Below are some recommendations:Transparency: Although the government of Zimbabwe has not been one of the most transparent entities, extraordinary times call for extraordinary action and this pandemic is one of such instances. The government can make available information on the number of cases, where and when the tests were taken, resources allocated to combat the disease and how they have been utilised, challenges facing the government in its responses and changing measures being implemented to keep up with the changing trends and emerging information about the disease. The government should also make public procurement processes, donations being received, efforts to make vaccine available when it is approved as well as how the government intends to cushion the citizens from the short- and long-term impacts of the disease.Effective and efficient response: while the government has been implementing other globally popular approaches such as lock-downs, encouraging citizens to sanitize and keeping social distancing, there are issues that are particularly unique to Zimbabwe that requires the government to craft policies and adopt measure that will offer more practical solutions to the people. For example, given the already struggling economic situation in the country, the government can reach out to other development partners to help it provide face masks which are critical to reducing the spread of the disease yet very elusive especially for low-income earners [ earners . The govShow leadership in addressing the growing grievances: Amid the pandemic, the government is having to deal with growing opposition from political, professional and community organisations over different concerns. For example, the strikes called by health practitioners demanding better pay and improved working environment comes at a critical time when the government needs more personnel in dealing with the pandemic. In addressing the grievances by frontline workers, the government needs to show leadership and not its coercive powers given that some of the concerns raised by these health workers are genuine and have a bearing on whether the country can overcome the challenges of the disease. Similarly, the on -going mass action called by activists demanding accountability could have been subverted should the government responded proactively to allegations of corruption especially with COVID-19 resources.Medical cost: there is no doubt that one of the main concerns among Zimbabweans is whether they are able to afford the medical cost for testing and treating of COVID-19. This requires serious government attention as the issue of cost for treatment is also associated with the question of accessibility and availability of sufficient medical practitioners to provide treatment to the people. To solve this problem, the government will be required to adopt a multi -dimensional approach. For example, a robust public-private partnership initiative or a memorandum of understanding where private entities can collaborate with the government or exercise social corporate responsibility and pool recourse to help subsidise the cost of treatment or testing for the citizens. Insurance companies, both public and private can include COVID-19 treatment in their most basic premium.Re-evaluate the existing strategies periodically: While this pandemic has put many governments to test over their ability to effectively respond to public health crises, most governments seem to be trapped with few response strategies which clearly appear to be ineffective in most countries. From measuring temperatures, to claims of contact tracing, and from alleged mass testing to availability of facilities, these strategies may have worked elsewhere but their implementation in developing countries does not appear to be working. For example, contact tracing requires the use of sophisticated technology, adequate personnel, appropriate intelligence to effectively implement. Similarly, mass testing requires sufficient kits, personnel, and standby facilities where those infected can be quarantined. So far, the Zimbabwean government which claims to be using the above strategies has not proved that it has sufficient capacity to adopt these measures. Therefore, the government can re-evaluate some of these approaches and replace them with cheaper, effective, and easily adaptable approaches.Bring others on board: Zimbabwe’s governance structure is one that can be considered to be highly centralised. This kind of governance structure has increasingly become less popular especially in the wake of emerging public administration reform measures that brought about principles such as New Public Management and Good Governance. The two approaches emphasize decentralisation not just of functions but also decision making. The current pandemic offers a unique opportunity to adopt similar measures that will see increased involvement of different actors at the national, regional and the local levels. Apart from a recommended increase in inter-governmental relations, the central and local authorities can work closely irrespective of their political affiliations to curb the spread of the disease. Local response units can be established to work closely with National COVID-19 Response Taskforce based in the capital city of Harare. These local units are able to communicate valuable information about the realities on the ground ranging from preparedness in terms of health facilities, compliance to government guidelines and other emerging issues that can hinder the effectiveness of government response. The local units will act as a source of valuable information that can be used in the formulation, readjustment and monitoring of policies and government efforts to combat the disease.The COVID-19 pandemic has undoubtedly disrupted different spheres of human society. In some societies, the disease continues to inflict more pain as government response measures are doing little to cushion the citizens from the pre-existing and newly emerging challenges. One such country is Zimbabwe, which amid the pandemic, the cost of living has spiked, mass protests have resulted into dangerous confrontations between the citizens and security forces, and growing uncertainty due to lack of medical insurance, increased unemployment, and declining incomes. However, not all is lost, an intelligently designed response measure, sober and responsive leadership and collaboration between the government, the citizens and the private sector could go a long way in bringing a new experience during and after the pandemic.


To effectively impact the significant population burden of injury, we completed a situational assessment of injury prevention practice within a provincial public health system to identify system-wide priorities for capacity-building to advance injury prevention in public health.n = 20) and focus groups (n = 19). Participants included a cross-section of injury prevention practitioners and leadership from public health units reflecting different population sizes and geographic characteristics, in addition to public health researchers and experts from academia, public health and not-for-profit organizations. Thematic analysis was used to code all of the data by one reviewer, followed by a second independent reviewer who coded a random selection of interview notes. Major codes and sub codes were identified and final themes were decided through iterations of coding comparisons and categorization. Once data were analysed, we confirmed the findings with the field, in addition to participating in a prioritization exercise to surface the top three needs for support.A descriptive qualitative study was used to collect data on the current practice, challenges and needs of support for injury prevention. Data was collected through semi-structured interviews (Major themes that were identified from the data included: current public health practice challenges; capacity and resource constraints, and; injury as a low priority area. Overall, injury prevention is a broad, complex topic that competes with other areas of public health. Best practices are challenged by system-wide factors related to resources, direction, coordination, collaboration, and emerging injury public health issues. Injury is a reportedly under prioritized and under resourced public health area of practice. Practitioners believe that increasing access to data and evidence, and improving collaboration and networking is required to promote best practice.The results of this study suggest that there are several system level needs to support best practice in public health injury prevention in Ontario including reducing research to practice gaps and supporting opportunities for collaboration. Our research contributes to the literature of the complexity of public health practice, and presents several mechanisms of support to increase capacity at a system level to improve injury prevention practice, and eventually lessen the population burden of injury. Injury represents the leading cause of morbidity and mortality for Canadians ages 1–34 years .In the province of Ontario, Canada there are 35 locally governed public health units serving a combined population of 14.4 million . LeeThe themes that were identified from the data related to the current public health practice challenges of injury prevention, capacity and resource constraints, and injury prevention as a low priority area in public health practice. There are considerable gaps in the availability, access, and knowledge of emerging issues in injury prevention research at a practitioner level, in addition to the need for greater connection between research and practice. Injury prevention practitioners’ ranked increasing access to data and evidence, and improving collaboration and networking as priority needs to influence their practice.These findings are not surprising given the existing literature that describes the need for increased capacity to fulfil the requirements of public health roles generally, , 19–21 aThe first prioritized item described the need for evidence of effective interventions for public health practice. Leeman et al. 2017) describes two concepts related to the difficulty in implementing evidence-based interventions: complexity and uncertainty  describe. In thisIn interventions with a high level of complexity, implementation exists within a context of an increased number of, diversity within, and interdependence of stakeholders, organizations, and system-level support . Data frParticipants highlighted the need for external support to provide evidence summaries, either in the form of literature reviews, rapid reviews, or systematic reviews. Practitioners reported lack of time and capacity to conduct evidence syntheses themselves, given a context of resource constraints and leadership to guide the process. In this case, increasing collaboration with researchers and public health units on areas of specific need for evidence and then providing this information would have a significant impact in the work of public health. In the collaboration process, efforts should be placed in better understanding the type of knowledge product needed, as large-scale systematic reviews of interventions are often not required to make decisions for a program of public health. Literature in this area suggests that using a hierarchical approach, where the use of evidence is strategic, maximizes the impact of injury prevention efforts . It is sThe second prioritized need described the value in increasing access to local data and systematic use of both population level and programmatic indicators. Data is used to develop locally driven, prevention plans that meet the requirements outlined in the OPHS . The admFinally, this study highlighted a need for improved and on-going collaboration and networking with research and other public health units. The public health unit staff, particularly at the level of front line practitioners, discussed the importance of collaboration and networking equally to the need for access to local data and evidence. This is supported by literature, , 31 as wThere are several strengths to this work. To our knowledge, this is the first situational assessment of injury practice across the Ontario public health system. Only through fulsome understanding of the context of practice can needed supports to improve population level outcomes be identified. Data collection and analysis were performed concurrently, allowing the addition of new codes as well as creating space for reflection during the data collection process. Our sample size was relatively large, enhancing the reliability  within our data. Our sampling methodology identified the best people to talk to and created opportunities to develop relationships with public health unit staff and stakeholders as well as to develop mechanisms for prolonged engagement with the field of injury prevention. The semi-structured nature of the questions asked during the interviews and focus groups allowed the process to be guided by what the participants considered important. Finally, the iterative process to our methods allowed simultaneous reflection of the literature and the collection and analyses of the data.There are limitations to this study. First, we were unable to capture every perspective of injury prevention practice across the province. Therefore, it is possible that certain views are not represented in these data and could have further informed both the analyses and prioritization of action. In addition the results of this study may not necessarily be generalizable to other provinces in Canada. Given the nature of our data collection processes, we did not include evidence of participant views on each theme. This may undermine the validity of the data as well as provide a less rich description of the phenomenon of study; however, we had a relatively large sample size, met theoretical saturation and implemented a process of data verification with our participant’s throughout the process of both data collection and analyses. These methods increase the trustworthiness and interpretation of data as presented. Another limitation is of the qualitative descriptive approach itself. This approach stays close to the data and does not abstract far as to generate a theory . Our aimThe results of this study suggest there are several challenges in injury prevention and opportunities for system-level solutions to support practice in Ontario. We assessed current injury prevention practice, the existing challenges, gaps and needs, and proposed system-level solutions. This includes increasing universal access to local data, providing synthesized evidence across the public health approach, developing applied public health research projects, and creating opportunities for provincial collaboration and networking for and with communities of practice. These efforts can increase the success of injury prevention programming at a local level by reducing the duplication of efforts and by increasing practitioner capacity. Leeman et al. 2017), Hanson et al. (2012) as well as Mitchell and Ryder (2020) describe the need to readdress the public health approach to prevention to include reviewing the necessary inputs to local practice to create effective and sustainable prevention programming , Hanson , 34. HanAdditional file 1: Table S1. Key informant and focus group interview guides.Additional file 2: Table 2. Consolidated criteria for reporting qualitative studies (COREQ) checklist1.


Cygnus cygnus) on the Asadokoro tidal flat, Hiranai town, Aomori Prefecture, Japan, were recorded by elementary school students for more than 50 years between 1956 and 2010. The Asadokoro tidal flat, which lies along the coast of Mutsu Bay, has been designated a National Special Natural Monument, known as “The swans of Kominato and their migration grounds.” This long history of observation unfortunately came to an end with the closure of the elementary school in 2012. If analyzed together with data on environmental factors, such as temperature changes or the effects of avian influenza, this dataset could provide a potentially valuable source of information, and consequently, future secondary use of the data is anticipated.The arrival and departure dates and the daily maximum populations of migrating swans ( In each of the years from 1956 to 2010, observations and recording of swan populations were carried out almost daily at Asadokoro tidal flat . Each yeCygnus cygnus and the tundra swan C. columbianus. Nevertheless, the results of a recent survey conducted by the Hiranai Society for Swan Protection have indicated that most of the swans observed in this area are whooper swans .Observations were conducted twice daily, at approximately 8:00 am before the start of classes and at approximately 3:00 pm after classes had finished. From 2002 until the final year of observations in 2010, the timing of the morning survey was changed to approximately 10:00 am, coinciding with the morning break. Observations during each survey period were conducted for approximately 20 min. Of the two daily counts, the one yielding the largest number of individuals was taken as the population number for that particular day. Given that swans differ considerably from other migratory birds that fly to this area with respect to size and color, it is assumed that the elementary school students are unlikely to have confused the swans with other species. However, it is conceivable that they may not have been able to distinguish between the whooper swan Although the survey was conducted for the final time in the fiscal year 2010, the data for that year were excluded from the dataset presented herein, owing to the lack of certain population data. In March 2012, Asadokoro Elementary School closed down, and the monitoring of swans that had continued for more than 50 years ended. To date, there has been no resumption of similar monitoring.Not applicable.Masaki Ogata: Resources, Writing - Original Draft; Takeshi Mitsuya: Resources, Data Curation; Yoshiyuki Tanaka: Data Curation, Funding acquisition, Writing - Review & Editing.The authors declare that they have no competing financial interests or personal relationships that influenced or could be perceived to have influenced the work reported in this article.


Expanded access is the use of investigational drugs (IDs) outside of clinical trials. Generally it is performed in patients with serious and life-threatening diseases who cannot be treated satisfactorily with authorized drugs. Legal regulations of expanded access to IDs have been introduced among others in the USA, the European Union (EU), Canada and Australia. In addition, in the USA an alternative to expanded access is treatment under the Right-to-Try law. However, the treatment use of IDs is inherently associated with a number of ethically relevant problems.The objective of this article is to present a coherent framework made up of eight requirements which have to be met for any treatment use of an ID to be ethical. These include a justified need for the use of an ID, no threat to clinical development of the ID, adequate scientific evidence to support the treatment, patient’s benefit as the primary goal of the use of an ID, informed decision of a patient, fair access of patients to IDs, independent review, as well as the dissemination of treatment results.While this framework is essentially consistent with the legal regulations of expanded access of the USA, the EU, Canada and Australia, it is substantially wider in scope because it addresses some important issues that are not covered by the regulations. Overall, the framework that we developed minimizes the risks and threats, and maximizes potential benefits to each of the four key stakeholders involved in the treatment use of IDs including patients, doctors, drug manufacturers, and society at large. Expanded access, also termed compassionate use, special access, early access or preapproval access, is the use of investigational drugs (IDs) outside of clinical trials . The curWhile the treatment use of IDs is legally permissible in many countries, it is inherently associated with several ethically relevant problems. Generally, it involves four main stakeholders—patients, doctors, drug manufacturers, and society at large. Each of those parties has its interests and priorities which in some cases may be in conflict. For instance, too frequent use of IDs might pose a threat to the progress of clinical trials, which are essential for the introduction of new drugs to clinical practice . TherefoSome of the important ethically relevant problems associated with the treatment use of IDs have not been addressed by the current regulatory systems –18. For When designing our framework we considered the current legal regulations of expanded access of the USA , the EU Justified need for the use of an investigational drugTreatment with IDs with uncertain safety profile is associated with substantial risks to patients, often without a guarantee for cure. Moreover, widespread use of those drugs would be at odds with the fundamental principles of the current regulatory systems whose primary objective is to ensure that only safe and effective drugs are used in therapy [The framework is made up of eight main requirements. These include the following: (1) A justified need for the use of an ID; (2) No threat to clinical development of the ID; (3) Adequate scientific evidence to support the treatment; (4) Patient’s benefit as the primary goal of the treatment; (5) Informed decision of a patient; (6) Fair access of patients to IDs; (7) Independent review; as well as (8) The dissemination of treatment results. Each of these requirements is discussed along with its ethical relevance. therapy . It coul therapy ). OveralIn general, two main conditions have to be met to consider the treatment use of an ID. Firstly, those drugs should be used only in serious or life-threatening diseases , 13. ExpThere are different situations in which no authorized treatment can be satisfactorily used. For instance, in some orphan diseases there is no authorized treatment at all . In othe2.No threat to clinical development of the investigational drug Randomized controlled trials are the gold standard of studies to evaluate the safety and efficacy of IDs [Expanded access principles were originally developed with a view to enabling treatment use of IDs in a limited number of patients who meet the main criteria, especially have a serious or life-threatening disease that cannot be treated satisfactorily with approved drugs, and are not eligible for enrollment in a clinical trial. However, over recent years different initiatives have been undertaken to provide access to IDs to a larger number of patients . These iy of IDs . They ary of IDs . If a lay of IDs . SecondlOverall the treatment use of IDs should be considered only in patients who for any reason cannot participate in clinical trials , 13. Thi3.Adequate scientific evidence to support the treatment To be ethical, the treatment use of IDs must be based on adequate scientific evidence. Otherwise, the patient is exposed to substantial risks without reasonable chance for cure. Based on the available data about the safety and efficacy of an ID as well as the patient’s condition, potential benefits and risks of the treatment can be estimated. Two key problems that need to be considered in this context include the likelihood and importance of potential benefits and whether the condition and prognosis of the patient justifies taking the risks associated with the treatment. However, one of the most difficult questions regarding the use of IDs is what level of evidence can be considered sufficient to start the treatment? In principle, firm conclusions about the safety and efficacy of drugs can be drawn following the completion of large Phase 3 trials; earlier phases yield only preliminary data about the effects of IDs [The current clinical trial enrollment criteria are in some cases quite restrictive. Consequently, only a small percentage of patients who exhausted all authorized treatment options may be eligible for participation in trials . For alls of IDs . Decisios of IDs . Howevers of IDs , 32.The requirement presented in this section is important also because performing the treatment based on adequate evidence, along with informed consent of the patient  are the primary safeguards to shield the doctor in case of eventual litigation.There are many studies reporting on successful use of IDs in different diseases –35. On t4.Patient’s benefit as the primary goal of the treatment Over the last years the sharp distinction between clinical care and biomedical research has become increasingly blurred [With regard to the safety of IDs, according to the data collected by the FDA, serious adverse events resulting in a clinical hold on an investigational new drug (IND) development program occur extremely rarely in expanded access programs . Thus, i blurred , 39. A p blurred , 40. Sys blurred .The primary objective of an expanded access program should always be the treatment of patients. When the data about the effects of IDs are collected in those programs, protocols should be designed as to maximize the direct benefits for actual patients; the collection of data should be a secondary objective. Moreover, in principle, expanded access programs are dedicated to patients ineligible for enrollment in clinical trials. Studies whose primary objectives include the evaluation of the safety and/or efficacy of IDs should not be classified as expanded access programs, but as clinical trials .5.Informed decision of a patient The treatment use of IDs poses high risk of adverse events compared with most treatments employed in standard clinical care. Furthermore, patients with serious or life-threatening diseases who have exhausted all authorized treatments are considered particularly vulnerable in that they are very likely to overestimate potential benefits and underestimate risks associated with the use of new drugs which may give them the last chance for cure [Concerns have been also expressed that some doctors could try to exploit treatment with IDs as a pretext of ‘pioneering’ novel therapies without paying sufficient attention to patients’ actual needs . While tfor cure . TherefoSome authors have rightly risen a problem of the capacity of vulnerable patients for making rational, informed decisions regarding treatment with IDs . HoweverThe main decision-making model that has been employed in the treatment use of IDs is informed consent. It is one of the main requirements for both expanded access and treatment under the Right-to-Try law in the USA , 11. Infvs palliative care [6.Fair access to investigational drugs Treatment with IDs is not a part of standard medical care. The access to those drugs is very limited in view of applicable legal regulations and the production of only small quantities of IDs intended primarily for the needs of clinical trials. Of particular concern is a possibility that access to IDs might be easier for some individuals  at the cost of others. In order to prevent such abuses, every care should be taken to ensure fair access of patients to those drugs. In fact, ensuring fairness is considered one of the key ethical requirements of expanded access [We also believe that patients who have exhausted all authorized treatments may benefit from shared decision-making (SDM). SDM is a process involving a doctor and a patient which aims to reach a mutual treatment decision based on the best available medical evidence and a patient’s preferences and values. Over the last decade the importance of SDM has substantially increased and it is currently considered the cornerstone of patient-centered care . SDM hasive care . It apped access . OverallWhile some pharmaceutical companies have provided patients with access to their IDs for a long time, there are no industry-wide best practices regarding patient selection. A reasonable practice is to select patients based on medical criteria considering the overriding principles of nonmaleficence and beneficence . This meThe second important problem related to fairness in the access of patients to IDs is the cost of the treatment. Generally, the policies for charging patients for the treatment use of IDs vary by country. For instance, in the USA, in single patient expanded access, the sponsor can charge patients for the use of IDs, but can recover only the costs directly associated with making the drug available to the patient including the ID’s production cost . HoweverAnother important issue is the availability of information about programs providing access to IDs outside of clinical trials. Unequal access to that information will limit fairness, as some patients may not be aware of the existence of novel treatments. A major step towards an increase in transparency of expanded access programs was the introduction in the USA of the 21st Century Cures Act, which mandated drug manufacturers to public posting of key data about their programs . Of grea7.Independent review Each request for the use of an ID should be reviewed for two reasons: 1) such treatment is not a part of standard medical care and its potential benefits and risks may be hard to evaluate by a doctor [An important factor that can limit fairness in patients’ access to investigational treatments is that some doctors may be simply unaware of a possibility to use such treatments in their patients . While ta doctor ; 2) the a doctor . Thus, tThe review of expanded access requests must be performed in accordance with applicable laws. In some countries, including the USA, Canada and Australia, expanded access is overseen by drug regulatory agencies . In the 8.Dissemination of treatment results Both in the USA and the EU legal regulations were introduced to mandate making public the results of clinical trials [Unlike expanded access, treatment under the Right-to-try law does not require any institutional oversight . Howeverl trials , 66. By l trials . For insl trials , 69. Howl trials , 70. Whil trials . Howeverl trials .The treatment use of IDs has become a very complex enterprise involving an interplay of sometimes conflicting interests and priorities of different stakeholders, especially patients, doctors, drug manufacturers and society at large. It is also associated with a number of ethically relevant problems. IDs can be used both in single individuals and groups of patients. Particularly difficult to design and run are large, often international, expanded access programs which can involve thousands of patients . HoweverThe framework is coherent in that all eight conditions have to be met for the treatment use of an ID to be ethical. However, the requirements presented in this article are not strict procedural guidelines or regulations. They are fairly general in nature and have to be adjusted to applicable legal regulations. For instance, in some countries, especially the USA, Australia, and Italy, expanded access requests have to be reviewed not only by a relevant regulatory agency, but also by an IRB; in other countries, there is no such requirement . AnotherWe are aware of a fact that our framework may not provide a simple and unequivocal answer to every clinical dilemma that can emerge in treatment use of IDs. For instance, in some cases potential benefits of different stakeholders involved in treatment use of IDs can be mutually incompatible. We believe that in such cases the fundamental principles of medical ethics should apply, especially the principle of nonmaleficence. The overriding value should always be the patient’s safety.The considerations contained in this article may be helpful for those involved in the design, review and conduct of programs involving the treatment use of IDs. For instance, IRB members could refer to the considerations presented in this article when performing review of expanded access requests. Moreover, our framework can be used by doctors who consider investigational treatments in their patients.