Neurological biomarkers are particularly valuable to clinicians as they can be used for diagnosis, prognosis, or response to treatment. This field of neurology has evolved considerably in recent years with the improvement of analytical methods, allowing the detection of biomarkers not only in cerebrospinal fluid (CSF) but also in less invasive fluids like blood. These advances greatly facilitate the repeated quantification of biomarkers, including at asymptomatic stages of the disease. Among the various informative biomarkers of neurological disorders, neurofilaments (NfL) have proven to be of particular interest in many contexts, such as neurodegenerative diseases, traumatic brain injury, multiple sclerosis, stroke, and cancer. Here we discuss these different pathologies and the potential value of NfL assay in the management of these patients, both for diagnosis and prognosis. We also describe the added value of NfL compared to other biomarkers currently used to monitor the diseases described in this review. Neurofilaments (Nf) belong to the family of intermediate filaments and their localization is exclusively neuronal. Nf differ from other types of intermediate filaments by the complexity of their structure and the composition of their subunits. Three subunits of Nf can be identified (and differentiated on SDS gel according to their molecular weight): NfH , NfM , and NfL  during neuronal damage, the measurement of NfL in these biological fluids as potential biomarkers of axonal damage, axonal loss and neuronal death raises many hopes in terms of diagnosis and prognosis .®  SimoaTM device, and the third one is an immunoassay, based on a microfluidic approach, which can be implemented on the EllaTM device from the Protein Simple® company. These three approaches use the same detection antibodies. A fourth approach, based on electro-chemiluminescence, can be implemented on the Mesoscale Discovery (MSD) devices . However, the cut-offs for NfL measurement remain to be homogenized, or even defined, depending on the method, the clinical contexts and the physiological parameters influencing the concentrations such as age, body mass index or renal function , the second one is based on Simoa (single molecule array) technology and is implemented on the Quanterixtion see . The objAlzheimer’s disease (AD) is the most prevalent cognitive neurodegenerative disease with approximately 900,000 people affected in France and more than 225,000 new cases per year . As for almost all neurodegenerative diseases, NfL is increased in blood and CSF of AD patients  of AD patients remains more moderate than in most other neurodegenerative diseases , the measurement of NfL could be of interest in the differential diagnosis with other primary progressive aphasias and, more generally, with frontotemporal lobar degeneration (FTLD), where NfL levels are higher  comparing Braak 0_II vs. Thal 4–5 and Braak V–VI subjects  is the second most common neurodegenerative disease in France (after AD) and the first leading cause of motor disorders. In France, 150,000 people are affected and 25,000 new cases are diagnosed every year . Interestingly, NfL levels do not seem to increase in the CSF of PD patients and several publications have reported similar levels to those of healthy controls  also have significant elevated levels of NfL in CSF compared to healthy and PD patients, they have lower levels than PSP, MSA, and CBD patients  is a heterogeneous group of neurodegenerative diseases characterized by behavioral disorders and deficits in executive and language functions. It is the third most common cause of neurocognitive impairment after AD and LBD. In clinical practice, the challenge is to differentiate FTD patients with various primary psychiatric disorders (PPD), because of the overlap of some behavioral symptoms with FTD. To date, there is no validated biomarker to distinguish PPD from FTD but NfL, as a non-specific biomarker of neuronal death, appears to be promising to fill this gap in diagnosis.post-mortem pathology analysis and 14 of them described this marker for an FTD population including also familial forms  in FTD groups compared to PPD and control groups , with a sensitivity of 79% and specificity of 89%  to discriminate patients from controls  and at 73% in patients whose NfL level was lower than 1,989 pg/ml , increased serum NfL has been described during the conversion phase corresponding to the onset of symptoms , the most common form of prion disease, is responsible for extremely rapid cognitive decline. Its diagnosis is based on clinical criteria, EEG and the detection of the 14.3.3 protein in the CSF. Alternatively, a very large increase in t-tau concentration, with a high t-tau/p-tau ratio are strong arguments for the diagnosis. Recently, studies have shown the interest of NfL measurement in CSF  protein becomes abnormal and toxic to the neurons of the striatum when the number of CAG repeats is greater than 35. Mean concentrations of NfL in plasma at baseline were significantly higher in HTT mutation carriers than in controls  and the difference increased from one disease stage to the next, thus correlating with the severity of symptoms  is a neurodegenerative disease of central and peripheral motor neurons, resulting in rapidly progressive amyotrophy and a greatly reduced life expectancy. Diagnosis can be challenging due to the heterogeneity of clinical presentations and the criterion of evolutivity. Therefore, it is common for patients initially identified as having ALS to have their diagnosis reconsidered as a slowly evolving motor neuron disease. In recent years, the NfL assay has emerged as a promising biomarker for the diagnosis and prognosis of ALS.Published studies first focused on the determination of NfL in CSF  or plasma (n = 49).Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS), which can cause significant physical and cognitive disability and is responsible for a significant deterioration in quality of life. It is the most common neurological disease affecting young adults, three women for one man, with onset occurring mainly between the ages of 20 and 40. It is a multifactorial disease linked to genetic susceptibility factors in association with environmental risk factors and epigenetic factors leading to immune dysfunction , thus suggesting sNfL might serve as a biomarker from very early stages of MS  score. This elevation is also predictive of the occurrence of relapses and progression of brain atrophy in the short term . This indicates that longitudinal sNfL changes rather than absolute sNfL values at a given time point might be indicative of disease activity and treatment stratification ] are currently being studied to discriminate RRMS from SPMS patients Selner, . HoweverTM platform for the determination of blood NfL in this context  and in people considered stable with no evidence of disease activity  is a major public health problem (more than 500 per day in France). About 80% of cases of TBI are classified as mild head injury . The morbidity associated with head trauma is considerable. Nearly 50% of victims have residual disabilities that may include progressive neurodegeneration, cognitive impairment, and dementia. Head injuries must be carefully diagnosed to foresee, anticipate, and treat the medical and/or social after-effects they cause. Blood and CSF biomarkers of neurodegeneration, particularly NfL, could help in the diagnosis and prognosis assessment.The number of publications regarding the interest of NfL in TBI is growing rapidly (391 articles in PubMed as of 01/06/2022). An increase in NfL levels in the CSF and blood is found during TBI, reflecting the axonal damage suffered  recently confirmed that NfL levels at 48 h were an independent risk factor for cognitive sequelae within 3 months after stroke , to the cerebral or medullary localization of metastases of an extra-cerebral cancer , to a carcinomatous meningitis  or to autoimmune reactions triggered . The treatment of these cancers is also responsible for neurological complications, and this neurotoxicity is in most cases dose-dependent. Neurological damage may affect the central nervous system (CNS), the peripheral nervous system (PNS) or both simultaneously. Early diagnosis of these disorders can often reduce symptoms and prevent permanent neurological deficits. Imaging tests such as MRI or electromyography (EMG) are used to identify these disorders, but there are no blood biomarkers  that can be useful for the diagnosis of these pathologies. Moreover, the currently available markers do not allow the evaluation of lesion progression and response to treatment. Various studies have explored the use of NfL in these indications.Primary CNS tumors and brain metastases are major causes of morbidity and mortality. The earlier the diagnosis, the better the management of the patients and the survival rates, which are anyway low in these cases. Several publications have thus focused on the use of NfL as a diagnostic and prognostic blood marker. High blood levels of NfL in brain metastases  early, even before the diagnosis of brain metastases . The increase in treatment lines and the development of new therapeutic modalities increase the risk of neurotoxicity. It can be challenging to make the diagnosis, but it is essential to get it done as soon as possible. Several studies have shown that the concentration of NfL correlates with the development and severity of toxicity resulting from various treatments. Thus, patients treated with paclitaxel, known to induce peripheral neurological manifestations, show an increase in blood NfL concentration 4 weeks after chemotherapy (compared to controls), resulting in an 86% sensitivity and 87% specificity , 1 week after treatment. In the case of post-immunotherapy autoimmune encephalitis, blood and CSF NfL rises and this result might be useful for tolerance monitoring  in cancer patients aged 51–60 years may predict the presence of brain metastases  are proteins selectively expressed in the cytoskeleton of neurons, the increase of which is a marker of neuronal damage. NfLs are highly specific to neurons but increase in many clinical settings and other candidates for neurological damage are currently under development. Indeed, neuronal damage is common and can be observed both during neurodegenerative diseases  but also in other neurological contexts . In this review, we have provided an overview of these different contexts, showing that the determination of NfL in biological fluids has a wide range of potential uses, sometimes for differential diagnosis, but more often for prognosis or monitoring of the therapeutic response of many neurological diseases . We discThe NfL assay may be particularly relevant for the diagnosis of ALS or PD dementia for example. It would also be useful for the differential diagnosis between FTD and psychiatric disorders, between different Parkinsonian syndromes, or between Alzheimer’s disease and Prion disease, for which the levels of circulating NfL are very different. It is important to note that the level of NfL is a good marker of severity: its level is indeed correlated with a poor prognosis in many neurodegenerative diseases  and predicts the cognitive decline following repeated head trauma and stroke. The signs and symptoms on which the clinical diagnosis is based sometimes appear late in the course of the disease compared to the time of onset; the dynamics of blood NfL in the preclinical phases of neurological diseases and the possibility of detecting blood levels of NfL in an ultrasensitive manner could be used to identify diseases at an earlier stage. Finally, NfL can also be used to monitor the response to therapies and the neurotoxicity that such treatments may cause.Nonetheless, it is important to keep in mind that NfL is a marker of neuroaxonal destruction independent of the mechanism causing the neuronal damage. The specific diagnosis will require consideration of a great deal of information, including the patient’s history, physical examination, imaging, and other laboratory tests. It seems essential to define reference ranges of normality for this biomarker, depending on the biological sample considered (CSF or blood), the analytical test performed, age and BMI for each medical indication in order to correctly interpret NfL results according to the context. Indeed, many factors other than the primary neurological disease, including age, BMI, cardiovascular risk factors, unrecognized head injury, etc., may be confounding factors that influence blood NfL and should therefore be taken into account when evaluating this biomarker in patients.The homogenization of the thresholds of this biomarker according to the assay methods would allow a rapid development of its use in clinical routine for an optimized management of the patients. The extent of its use means that NfL could soon become a must for the clinical activity of the neurologist .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.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Cultural competence development in the formative process of healthcare professionals is crucial for the provision of culturally appropriate health care. This educational issue is highly relevant in the growing multicultural composition of southern Chile. The objective of this study was to examine how the healthcare professions curricula at the Universidad de La Frontera, in La Araucanía Region, prepares future professionals to respond to patients' cultural needs.A sequential transformative mixed methods design composed of two phases was carried out. Phase 1 reviewed all printed material and documentation to explore content that developed cross-cultural skills and competencies in the curricula. In Phase 2 semi-structured interviews were conducted with academics with responsibilities for the development of the curriculum in each career, to detect how academics envisage the incorporation of cultural competence in the curricula.Regarding curricular contents, findings indicated that the healthcare professions curricula at The Universidad de La Frontera have similar approaches to the inclusion of CCT in subjects’ syllabuses, with inclusion of the different CCT, particularly in the Dental and Medical curricula. However, this coverage showed significant variations in the undergraduate healthcare curricula. The analysis revealed that themes around the Ethics and human values for professional practice; the Psychosocial and cultural determinants of health; the Relationship health-family-community, and to a lesser extent, the Clinician-patient relationship were well covered in the courses. On the other hand, Inequalities in health was the theme with the least contact time in all three courses.Academics called for a better organisation of the inclusion of CCT in the curricula. They also highlighted the challenges of maintaining the dominant paradigm underlying healthcare models, practices, and orientations within the academic staff and health discipline.Curricula contents findings indicate that the healthcare professions curricula at Universidad de La Frontera have similar approaches to the inclusion of CCT in subjects’ syllabuses. However, its depth of coverage allows for improvements. The systematization of CCT and teaching–learning methodologies in healthcare professions curricula is necessary to develop formative processes that allow future professionals to be aware of and respectful with patients’ cultural characteristics and needs.The online version contains supplementary material available at 10.1186/s12909-022-03743-7. Cultural competence (CC) in health care is defined as "a process in which the health care provider continually strives to achieve the ability to work effectively within the cultural context of a patient." This includes five key interdependent elements: cultural awareness, cultural knowledge, cultural ability, cultural encounters, and cultural desire  CampinhaMore recently, the concept of cultural safety has been introduced. Cultural safety is defined as ‘the ongoing critical reflection of health practitioner knowledge, skills, attitudes, practising behaviours and power differentials in delivering care that is safe, accessible and responsive healthcare free from racism' , 8. CultCultural competence and safety are considered as a continuous process consisting of five constructs , 6. ThesThe model of cultural competence and safety focuses on the process by which healthcare professionals develop cultural awareness, knowledge and skills that lead to changing attitudes, valuing diversity, and understanding their own cultural biases. Therefore, this process requires providers to be truly culturally competent, with prior cultural encounters, and to possess cultural awareness, knowledge, and skills that enable effective cross-cultural communication , 2, 6. TIn addition, the model emphasizes that the healthcare encounter should include effective cross-cultural communication. This process is based primarily on the cultural desire that requires providers to be truly culturally competent, in addition to having had cultural encounters and possessing cultural awareness, knowledge, and skills , 6, 9.The interaction between healthcare professionals and patients in the context of a clinical encounter could be explained using the interactive model . AccordiChile, like most present-day countries, has culturally diverse societies composed of numerous cultural groups such as First Nation people, recent immigrants , previous immigrants , who coexist within a culture more predominantly influenced by Spanish colonialism.It is estimated that the foreign-born population in Chile increased by a 12.4% between 2018 and 2020 . The majMany immigrants and indigenous people retain native languages and traditions, generating not only ethnic or linguistic diversity, but also cultural differences . Each cuTranscultural skills have been regarded as crucial for healthcare professionals who work in inter or multicultural scenarios. Cultural and linguistic mismatches between healthcare professionals and patients have been highlighted as one important source of difficulty in conducting proper medical care , 14. In Although CC is a process, its acquisition and development must begin during the education of the health professional , 15. WitTo achieve CC, it is essential that healthcare profession students, receive training that promotes the knowledge necessary to understand culturally influenced health behaviours, as well as acquiring the ability to communicate effectively with patients from cultures other than them –18.The aim of this study was to examine how the healthcare professions curriculum  at The Universidad de La Frontera, Temuco, Chile, prepares future professionals for efficient and safe management of patients' cultural diversity needs. More specifically, the study will: a) gain information about the content and development of cross-cultural skills and competencies; and b) describe how the academics involved in the planning and organizing of the curriculum of these programs envisage the incorporation of cultural competence into the study plan.This study will provide information for the development of strategies to improve healthcare profession students’ capacity for intercultural communications. This information will also contribute to better relationships between healthcare professionals and their patients. In turn, this will translate into better treatment outcomes, and patient satisfaction. Methodological strategies for cross-cultural education would respond to the educational needs detected by the study to expand cultural competencies among students of Medicine, Dentistry and Nursing at The Universidad de La Frontera.To achieve the objectives of this study, the project adopted a sequential transformative mixed methods design composed of two phases , as showThis phase’s objective was to obtain information about the curricula contents for the development of cross-cultural skills and competencies that prepare future healthcare professionals for the appropriate management of patients with diverse cultural backgrounds. To achieve this phase’s objective, a systematic documents review was conducted in order to examine how cross-cultural education has been incorporated into the curricula of three healthcare courses: Dentistry (6 Years), Medicine (7 Years), and Nursing (5 Years).Psychosocial and cultural determinants of healthConcepts of cultural diversityBeliefs, behaviours and expectations related to health and illnessInequalities in healthThe clinician-patient relationshipIndigenous people concepts of health and diseaseThe analysis was conducted to analyse the subject syllabuses from each of the three courses. Within each course, subject syllabuses were collected and analysed considering the representation of cultural competence related themes (CCT). The evaluation of the presence of transcultural content in subjects’ syllabuses was based on six pre-determined themes , 20, folInductive coding was also carried out to determine whether there were any additional CCT themes that were not considered in prior research that were relevant to this study.The initial analysis was presented to the other researchers, who audited the analysis, reaching stability in the findings. Codes were created and patterns were found in course syllabuses indicating that other themes regarding CC were present. The analysis was presented to the other researchers, who discussed it in light of existing literature. Key CC concepts and themes are described in Supplemental Table Consistent syllabuses are those in which the approach to elements that allow the development of CCT in various sections of the subjects’ syllabus is observed, demonstrating coherence between competencies, learning outcomes, contents, methodologies, and bibliography.Intermediate syllabuses contain elements that allow the development of CCT in some sections of the subject’s syllabus, however, there is no internal coherence of these elements in the subject program.Emerging syllabuses are those in which the presence of elements that allow the development of CCT is observed, however, these are not observed in all sections of the syllabus, and do not follow a solid organization.Not observed correspond to those in which none of the CCT were found.All themes were analysed in relation to how deeply established and developed they were in the syllabuses, aspect which will be referred to as depth of coverage. Four categories of syllabus were identified:Sixty-one academics from the subjects assessed in Phase 1 were invited to take part in individual face-to-face interviews. For some of the subjects, academics were in teaching teams, so they nominated one of them to represent the team to provide an account of their methodological approach to the subject. In other cases, one academic was in charge of more than one subject. For this reason, in Medicine, a professor who was in charge of four subjects in that course took part  for the management of content and cross-cultural skills in the identified subjects.Challenges and barriers faced in teaching cross-cultural content and skills.These interviews were aimed at obtaining further information, and clarification of the information collected. Three general themes were explored in the interviews:Prior to the interviews, the researcher provided potential participants with a copy of the Plain Language Statement, verbally clarified the aims of the study, and explained the interview and analysis process, data security, and the individual’s right to withdraw. Those who volunteered to participate were requested to provide verbal consent to participate and to send a signed consent to the interviewer via e-mail. All interviews were video and audio recorded and transcribed for further analysis. Additionally, the interviewer scribed general notes of the responses throughout the interview. Notes and transcriptions were reviewed by the researcher conducting the interviews, the project leader, and another member of the research team to ensure accuracy and consistency. Transcripts were eliminated of any identifying information. Pseudonyms were assigned to each participant and used in transcripts and reports.This phase adopted a content analysis method, following Grounded Theory’s inductive coding techniques (yet not following a Grounded Theory Design) . InterviThe scheme was validated by iteration with the data. However, it was not possible to reach theoretical saturation due to the number of interviews conducted. The content analysis was performed using the ATLAS.ti 8.4 software.A systematic documentary review was carried out on the three selected healthcare professional programs. The documents analysed corresponded to the University’s Professional Training Policy, the course study plans, and 144 subject syllabuses . Five elective subjects were not included in this analysis: two in Dentistry and three in Nursing.Relationship health-family-community: It refers to the role of family and community in the prevention of illness, and the understanding of how family and community culture interfere in healthcare prevention and treatment.Ethics and human values for professional practice: It refers to the ethical practices that healthcare professionals should incorporate into their professional activities, such as respectful attitudes toward their patients’ cultural background and practices.Intercultural communication: The abilities, skills, and knowledge that allow the healthcare professional to effectively interact with patients from different cultural backgrounds.CCT included 6 predetermined themes and 3 themes that emerged from the inductive analysis. Emergent themes identified were:Tables In the case of Dentistry, Ethics and human values for professional practice; Psychosocial and cultural determinants of health; and the Clinician-patient relationship were the most common themes in the subjects’ syllabuses. The theme Inequalities in health was not observed in the Dental syllabuses. Table In the case of Nursing, Relationship health-family-community; Ethics and human values for professional practice; Psychosocial and cultural determinants of health and Clinician-patient relationship were the most common themes of the syllabuses. The themes Beliefs, behaviours and expectations related to Health and illness and Inequalities in health were not observed in any of the subjects’ syllabuses of the nursing course. Table In the case of Medicine, themes Ethics and human values for professional practice; Psychosocial and cultural determinants of health, and Relationship health-family-community were the most found in the syllabuses analysed in the medical courses. Table Seven academic staff consented to participate in this phase of the study. They reported their opinions on the three main topics, as illustrated in Fig. Academics agreed on two aspects of this topic: a) the critical need for including CCT in the healthcare professions curricula and, b) the need to address these topics more explicitly in subjects, through specific teaching–learning activities. These activities were mainly related to of the need to incorporate alternative conceptions of healthcare provided by local indigenous and immigrant cultures to offer more assertive treatments to patients. Additionally, academics observed a growing multicultural representation in their daily professional practices in both urban and rural healthcare centres.Although the academics agreed that the incorporation of CCT needed more explicit consideration, they identified a set of teaching–learning methodologies they have included in their subjects for the management of content and CC and safety skills. Figure In relation to resources, academics reported the use of specialized literature, webinars, and intercultural communication manuals. They relied mainly on the use of specialized literature as a basis for their classes. This literature included specialized references on varied cultural practices of local cultures, as well as immigrant cultures. Specialized literature also included references regarding different theoretical perspectives on cultural related themes.Webinars have been widely used during the COVID-19 pandemic as a resource that allows students to have access to first-hand contact with specialists located in different jurisdictions. Intercultural communication manuals and resources have been designed by academics and are specific to the local context in relation to immigration ..Strategies mentioned by the academics in relation to the development of transcultural themes were some types of research methods, such as ethnography, case-studies, and problem-based learning, in which students must analyse clinical scenarios and patients from a transcultural perspective. Furthermore, they also reported some types of practice-oriented strategies, such as Roper’s model , observaActivities mentioned by the academics were: the use of role plays; open showcases about intercultural topics; workshops; group work; writing essays; class debates and discussions; the elaboration of scientific posters; and group reflections on intercultural topics. These activities were related to the materials provided by the lecturer in each subject.Academics reported two main assessment strategies: tests associated with conceptual and theoretical knowledge about transcultural topics; and the use of rubrics associated with some of these activities, whenever they constituted an evaluation activity. Academics reported that the use of rubrics allowed them to assess whether students had achieved and were able to demonstrate specific competencies related to transcultural communication.Challenges and barriers encountered by participants when teaching cross-cultural content and skills were a) the maintenance of a disciplinary orientation of healthcare professions programs; and b) the traditional discarding of minority cultures’ knowledge and practices related to healthcare. In regard to the maintenance of a disciplinary orientation of healthcare professional programs, academics reported that traditional teaching approaches based on disciplinary knowledge were more valued than approaches based on the development of competencies, in this case transcultural competence. This resulted in students and newly graduated health professionals reproducing those judgements. The change of teaching styles and judgements was considered one of the main challenges to the implementation of innovated curricula and teaching strategies.Academics also identified some resistance to change in their academic colleagues, which they attributed to personal world views and value systems, as well as to the perceived expectations from their profession and the traditional lack of appreciation of local indigenous cultures. Participants agreed that although these cultural perspectives are becoming more acknowledged in the undergraduate curricula, particularly in recent years, there is still a wide range of subjects which do not include them. Academics commented that the inclusion of CCT has been an extremely controversial topic during curricular reviews. For example, academics commented on the polarization of the staff between those academics with a disciplinary focus, and those with a more integrative view of the patients’ needs.Experiences of culturally oriented intervention programs in rural health centres were reported as a way to demonstrate the importance attributed to the inclusion of these themes, not only in the curricula, but also as part of new study lines among academics.There is an increased recognition of the importance and understanding that cultural competence and safety is a learned process. Consequently, a systematic documents review was conducted to examine how cross-cultural education has been incorporated into the curricula of three healthcare courses . This study also reviewed the cultural challenges faced when implementing a culturally safe healthcare curricula and the academics perception of the coverage of cultural aspects in the curriculum of healthcare courses. The literature indicates that compared to medicine and nursing, information on cross-cultural dental education is relatively limited , 24–30.Ethics and human values for professional practice; the Psychosocial and cultural determinants of health; the Relationship health-family-community, and to a lesser extent, the Clinician-patient relationship were well covered in the courses.Regarding curricular contents, findings indicated that the healthcare professions curricula reviewed at The Universidad de La Frontera, have similar approaches to the inclusion of CCT in subjects’ syllabuses, with inclusion of the different CCT, particularly in the Dental and Medical curricula. However, this coverage showed significant variations in the undergraduate healthcare curricula. The analysis revealed that themes around the On the other hand, areas which were poorly covered included Beliefs, behaviours and expectations related to health and illness; and Indigenous people concepts of health and disease. In particular, the Inequalities in health theme, was covered marginally in the Medical curriculum only. Similar cultural safety content (shortage and coverage) has been noted elsewhere , 20, 31.Evidence from the interviews with academics supported these conclusions. Academics called for a better organisation of the inclusion of CCT in the curricula. That is, an improved organization of themes within subjects in relation to how they are included in their different aspects . Although academics described various teaching–learning methodologies used for the teaching of CCT, they also recognized that there is an urgent need to include these CCT related methodologies in a more explicit and consistent manner in the curricula.Academics also highlighted the challenges generated by the maintenance of a disciplinary orientation within the academic staff and health discipline, which focuses on a biomedical model of healthcare, and a lack of appreciation and knowledge of traditional model of healthcare practices of indigenous cultures and of other minority groups within the national healthcare system. These findings echoed those of Farías-Cancino et. al . who higAs such, it is possible that the current approach towards CCT in healthcare professions training might lead to an incomplete or biased understandings of the type of relation professionals should establish with their patients. These might become less patient-centred, less positive, and prone to poor communication and cultural discrimination .Although this study provided valuable insights into the cultural competence training of healthcare profession students, it is not without limitations. The most obvious limitation was the fact that the data were restricted to only one institution, the only state university in La Araucanía Region, which might result in conclusions that are not applicable to all Chilean healthcare professions curricula. Additionally, the study relied on self-reported data from motivated academic, and there is the probability of social desirability bias. However, considering these limitations, we believe that the current approach was adequate, particularly given the exploratory nature of the study.Thus, this inquiry is only in its initial stages. Notwithstanding, information from this study is significant because it is the first Chilean study to document the extent in which CC content is covered, and to compare how those contents are covered in the undergraduate curricula of healthcare professions. The high proportion of First Nation people living in the Region where this university is located, highlights the importance of health professionals having the appropriate cultural competences to provide a cultural safe practice.Furthermore, present findings become even more relevant due to the growing interest and need to include CC content in healthcare professions curricula. In fact, the United Nations has recognized culture as a causal agent of sustainability and integrated it into the SDG goals . This neA better perception of cultural competencies and intercultural safety in the dental, medical, and nursing curricula provides an understanding of their success in addressing the need for cultural competence and safety. Being aware of the current characteristics of healthcare professions study programs provides opportunities to make relevant modifications in order to improve formative processes, and subsequently, local multicultural healthcare scenarios. This will then provide the opportunity to modify the curricula of these courses to improve educational outcomes and in this way respond to the educational needs for the development of intercultural strategies and competencies. Moreover, the study will allow for the establishment of baselines for future comparisons within the same cohorts of students.Healthcare professionals play an important role in addressing patients’ overall health and well-being, and need to constantly reflect on their skills, expertise, and experience to best support a multicultural patient base. The systematic inclusion of Cultural Competencies related themes and teaching–learning methodologies in healthcare profession curricula is necessary to develop formative processes that allow future professionals to be aware of patients’ cultural characteristics and needs. It is essential that health professionals are able to provide culturally safe healthcare. It is hoped that this study further contributes to creating culturally safe environments and therefore the elimination of cultural and culturally based inequalities in health.Additional file 1: Supplemental Table 1. Key Concepts and contents of cultural competence and transcultural contents.Additional file 2: Supplemental Table 2. Distribution of academic staff invited to participate in the in-depth interview and participants by course.


Temporal bone dissection plays an important role in the training of surgeons; however, they are difficult to obtain.To develop a synthetic replica of the temporal bone for dissection training.Experimental.An acrylic synthetic resin replica was obtained from a human temporal bone. For the evaluation of the method, we selected five ear surgeons to dissect the model in a laboratory of experimental surgery. A questionnaire was filled, assessing external appearance, the simulation of procedures  and their final conclusion.The evaluation indicated satisfaction in using the model (80%), being more evident concerning the dissection of the mastoid segment of the facial nerve and translabyrinthine access to the internal auditory canal. The placement of a ventilation tube was reasonable for 60% and satisfactory for 40% of them. Mastoidectomy was satisfactory for 60% and fully satisfactory for 40%.Dissection in this simulator does not replace otologic training in cadaveric temporal bones. However, given the increasing difficulty in obtaining the latter, the development of new teaching tools should be encouraged to continuously improve surgeons. The use of cadavers for medical education and training started in 500 B.C. and its history evolved hand-in-hand with the development we have today in Medicine. For many years, this practice was prohibited because of religious and ethical issues; however, it was after the renascence that Leonardo da Vinci, Michelangelo and Andreas Vesalius consolidated human anatomy and dissection methodsStudy with cadavers is fundamental in schools of medicine, nursing, physical therapy and other health-care disciplines. Training of surgical techniques in cadavers also plays an important role in the education and enhancement of surgeons. The current Brazilian legislation, by means of law # 8,501 from November 30 of 1992, establishes that only those cadavers which remain unclaimed for 30 days can be used for research and educational purposesTraining in temporal bone dissection laboratories is already routinely carried out for the learning of surgical anatomy and to train otolaryngologists, in accordance with the theories from Fitts and Posner for the training of motor skillsThus, if on the one hand we have the legislative and the difficulty in obtaining cadavers representing a major limitation, on the other we have the need to develop new teaching approaches such as simulators and training in virtual environments.The goal of this project was to develop a replica of the temporal bone, with proper anatomical reliance in order to train dissection in the laboratory.The project was analyzed and approved by the Ethics in Research Committee, through protocol # 054/09.As primary model we used a left side temporal bone we acquired from the Coroner's Office of the city of São Paulo, through an official request # 18/2008.After properly cleaning the specimen, we did a broad mastoidectomy in order to identify the sigmoid sinus, mastoid tegmen, vertical portion of the facial nerve and lateral semi-circular canal. After drilling the posterior wall of the auditory meatus we removed the tympanic membrane and ossicular chain. Figure 1HUsing molding, high fidelity silicone and thermocuring acrylic (Reg. ANVISA 10234680006) we built three modules  for later assemblage. The tympanic membrane was built from vegetable parchment paper. We stress that the technique used to build the mastoid complex was changed in order to obtain a porous material, similar to the pneumatization of the temporal bone region.  and 3Fig–Blue: sigmoid sinus–Red: mastoid tegmen–Yellow: mastoid portion of the facial nerve and internal acoustic meatusBefore assembling the three modules we painted some of the structures with acrylic paint, namely: –Blue: sIn order to evaluate the simulator we selected five experienced ear surgeons skilled in experimental dissection to study the models and later fill out the questionnaire, taking into account the external appearance, the simulation of procedures  and their final conclusion. The aforementioned procedures were done in an experimental surgery lab, with the equipment routinely used to dissect temporal bones.The opinions of the surgeons are listed on the following table. Each mark (*) represents the opinion of each surgeon. Table 1IdBefore 1992 there were no laws regulating the use of cadavers for educational purposes. Different problems were faced by medical schools in attempting to find bodies from indigentsLaw # 8.501 from November 30, 1992 rules the conditions of cadaver destination for education and research. The cadavers which are unidentified and unclaimed after thirty days can then be sent to educational institutions. Should the cadaver be identified; however, without information from relatives or legal guardians, local authorities should publish the information in the main newspapers of the city during at least ten days, as a public service. Bodies suspected of unnatural or criminal cause of death cannot be used. Moreover, the law establishes that for recognition purposes, the authority or institution in charge shall keep the following information regarding the deceased: general characteristics, photos, fingerprints and identification - should there be anyNonetheless, knowing that the cadaver is only donated after thirty days and that often times it is not put into formaldehyde before 72 hours post-mortem, the degeneration process makes its use impossible6. Moreover, we have seen the spread of medical and other health care disciplines schools, which increases even further the demand for cadavers.These factors, associated with the constant pressure for better results have led educators and researchers to develop new tools to train surgeonsFitts and Posner's theory shows that learning is aninternal human process, and it depends on practice and it tends to be permanent. Such process happens in three stages - cognitive, associative and autonomous - in which, as the individual progresses on his/her training, better are the outcomes achieved, its consistency and less number of mistakes, together with an increase in the person's capacity to identify and correct problemsTraining in simulators, as well as conventional dissection, can separate the acquisition of skills from medical practiceThe present study aims at showing that this simulator enables temporal bone dissection training in conventional labs, for it bears proper anatomical reliance and provides a realistic feeling during surgery. Nonetheless, some problems have been raised, such as tympanic membrane stiffness, the greater resin density when compared to the temporal bone and the lack of a facial nerve, since in this simulator the nerve was only painted there. Despite these criticisms, which will serve to enhance the simulator, dissection was deemed satisfactory by the surgeons who evaluated it.Dissection in this otologic simulator does not replace the actual dissection of temporal bones from cadavers; nonetheless, it is a promising alternative for the practical teaching of otologic surgery. With the growing difficulty in obtaining natural temporal bones, we must develop new teaching tools for the continuous improvement of surgeons.


Moringa oleifera grows well in different parts of Africa, including Ghana, and throughout the world as it can tolerate moderate cold and severe drought. Dubbed as the “Miracle Tree,” Moringa has a number of nutritional, pharmaceutical, and cosmetic applications. It is also used as a cure for diabetes and various forms of cancer. Another promising use of this plant is the production of biodiesel. However, such application demands vast cultivation areas and this can lead to competition with the cultivation of crops for food, forestry, and environmental protection. Furthermore, it requires suitable cultivation schedules that favor the growth of pods containing oil-rich seeds. The present work investigates the availability of land for Moringa cultivation in Ghana to increase the energy production from the plant. The study reports on an overview of the soil, water, and climatic conditions that favor Moringa oleifera cultivation and oil production, the conversion of Moringa oleifera oil to biodiesel, and the performance of Moringa oleifera biodiesel versus mineral diesel as well as the commercial enhancement of the Moringa product. Global population growth has increased the energy consumption chain, available energy demands, and resource production. The world population and available energy production crops are exceeding their carrying capacity . The immNevertheless, to successfully produce sustainable and readily available energy crops for green energy production, Achten et al.  noted thMoringa oleifera cultivation as bioenergy crop types and proper management practices would help protect the environment and sustainable development of Moringa oleifera bioenergy  as  as 51] a 1% w/w) .Acid-catalyzed transesterification is not as popular as base-catalyzed. This is due to the slow rate of reaction and the high methanol to oil ratio required. Acid catalysts are also characterized by low activities with high temperatures during transesterification . The lonA report by Takase et al.  using soEnzymatic transesterification using lipase catalyst is becoming more attractive as a result of the easy product separation, less wastewater, easy glycerol recovery, and absence of side reactions. Lipases are generally known to act better on long-chain fatty acids than short-chains. Biocatalysts are more expensive and their regeneration and reusability are limited by longer operation time . The reaCandida Antarctica immobilized on acrylic resin) for biodiesel have indicated the process as promising [Studies on lipase-catalyzed transesterification using Novozym , an exhaust gas line, performance and emissions measuring equipment, a fuel conditioning system and heat exchanger, and a by-pass line. Two gasoline filters were installed adjacent to the fuel tank so that if one filter becomes clogged, the fuel supply could be cleaned without halting the engine [Moringa oleifera biodiesel after it has warmed. A by-pass valve was installed in the exhaust gas line before the heat exchanger to maintain the temperature of the Moringa oleifera oil within a range of 80–90°C. Following that, the diesel and Moringa oleifera biodiesel's performance on the engine was evaluated for a variety of physical, chemical, and thermal characteristics . And as Moringa oleifera biodiesel had a low sulfur concentration, it produced less SOx.Moringa oleifera biodiesel had a calorific value of about 90%. The NOx emissions were also influenced by the fuel's nitrogen concentration (formation of fuel NOx).The presence of oxygen in fuel increases combustion characteristics and emissions while decreasing the fuel's calorific value. When compared with mineral diesel, Moringa oleifera in Ghana, it is evident that the cultivation of Moringa oleifera and its subsequent use for biodiesel as a nonedible resource will help increase energy and food security. Moringa and its value change can contribute to sustainable development goals in Ghana since the plants can be grown on wastelands to reclaim them, may not compete with food crops for limited lands, are relatively cheap, available, and offers similar or even higher fuel yields, and properties as mineral diesel. Also, Moringa oleifera development can be used to curb the high unemployment rate through job creation, increased income of the Ghanian populace, diversifying, and enhancing the quality of the environment (pollution reduction). Replacement of fossil fuels with biodiesel from Moringa oleifera and other nonedible resources production will also offer the youth and children the opportunity to engage in productive businesses and enhance their standard of living. It can therefore be deduced from the study that Moringa oleifera is a multipurpose nonedible resource in Ghana and its commercialization can result in Ghana's economic improvement.Energy is said to be a key factor in Ghana's development and provides vital services that improve the quality of life of its people. Meanwhile, the resources for energy production and use have resulted in major concerns on the environment (from the use of resources and pollution point of view) , 62. The


The rationale behind this review is the potential of developing a single score tool for meat quality evaluation based on visual and sensorial assessments of fresh meat. Based on the known sensory wheel concept, the first step was to create quality wheels capturing most common intrinsic and extrinsic quality cues of pork and beef outlined in the latest scientific papers. This resulted in identifying meat color, sensory characteristics and fat content as the most important intrinsic quality cues of fresh beef and pork. Furthermore, the highest number of studies showed the importance of price, certification logos and brand for beef quality evaluation. According to recent articles, price, breed, animal welfare and a veterinary certificate are the most important extrinsic attributes for pork consumers. The second step was to develop a single-score tool named the “Meat quality index”. It has been developed in line with published approaches of different total quality index concepts used in the food sector, providing insights into its application in the meat sector. As a result, this review proposes a unique approach in using quality index application, through the consumer’s preferences aspect of fresh meat. The production of meat according to the technical product specifications helps producers to meet consumers’ demands for the most common quality characteristics of meat, which generally encompass microbiological attributes, chemical attributes  and sensory attributes , as well as other attributes . However, the evolution of the consumer’s perception, expectations and needs places additional quality criteria for meat producers that they need to fulfill . Taking In recent years, consumers developed demanding requirements in terms of meat quality, which are linked with their preferences affected by many diverse factors. By analyzing these factors, meat producers can properly react in order to offer diversified meat products to consumers. Therefore, the first challenge is to identify quality cues currently used by consumers to evaluate meat. These quality cues are usually divided into intrinsic and extrinsic characteristics . The keySome authors have studied the relative importance of meat quality attributes from a consumer’s perspective, by comparing these attributes, like in the case of beef, by analyzing their interrelationships, the influence of cues on expected quality and the correlation between extrinsic and intrinsic quality cues ,3,4,5,6.Sensory science has developed a sensory wheel to visually depict different sensations that can possibly be associated with a food product during consumption . In thatWhen it comes to quality indexes, this approach can be found in the food sector mainly in papers analyzing nutrition  and different types of quality indexes related to the evaluation of food quality. One of the first food quality indexes was developed with the aim to make a model that could enable overall description of food quality . The indThe main objective of this paper was to consider the potentials for developing QWs based on recent scientific papers related to intrinsic and extrinsic quality attributes of beef and pork meat that pave the way for creating a unique total quality index (QI). A literature review has been performed to identify the main intrinsic and extrinsic characteristics associated with beef and pork meat. To perform this task, the following criteria were applied: range of years (2018–2021); type of articles (research and review); type of journals (only with impact factor); search engine (Google Scholar); keywords used  .At this phase, the authors explored how many papers studied beef quality using the concepts of intrinsic and extrinsic characteristics. The second step was to place the consumer preference context. The final phase was to exclude papers that were not relevant for this review. The final selection revealed 41 studies that suggested different intrinsic and extrinsic cues. The intrinsic characteristics of beef quality are presented in The assessment of consumer responses on beef attributes was predominantly obtained by the use of a five-point Likert scale. The second consumer’s preference method frequently used was the first-choice experiment, which encourages consumers to select among different product profiles (choice scenario). Many authors use standards to present the levels for attributes in their experiment’s designs. Thus, the use of a standard was included in the summary of consumer’s preference-methods. However, in the sample of articles used in this study, the Australian meat standard was predominantly used . On the Choice-based methods have been noted as the most practical methods for evaluating extrinsic beef quality. These characteristics also became subjects of ranking or scaling methods, mostly in cases of evaluating their importance by consumers . ConcernThe same approach was applied for analyzing “intrinsic and extrinsic quality characteristics of pork consumer preference“ .The most dominant instrumental method for evaluating pork intrinsic characteristics related to color was the use of a colorimeter or computer vision system . When itIt was revealed that the choice-based methods were more frequently used to measure the importance of extrinsic attributes of pork quality .Basic intrinsic attributes of beef are meat color, fat content and cut , but othMeat color correlates with myoglobin content, but it also is closely related to intramuscular fat content and pH . FurtherIt was mentioned that odor, tenderness, juiciness, flavor and overall liking were most frequently analyzed through sensory testing of fresh meat. Sensory evaluation serves the meat industry and scientists to quantify the tenderness of meat from actual consumer feedback . The nutFat content is noted as one of the main factors when determining meat suitability . From a In this study, meat color, sensory characteristics and fat content were represented as the most important cues of fresh meat quality, both for beef and pork, since they were examined in the highest number of analyzed papers .It has been generally accepted that a certain degree of marbling has a positive effect on the juiciness, tenderness, palatability and flavor of meat . FurtherThe size of a primal cut  depends mostly on the size of an animal. All possible beef cuts are defined and described in the Institutional Meat Purchase Specifications and Handbook of Australian Meat 7th Edition ,38. AlthGenerally, the term drip loss can be defined as the fluid, mainly consisting of water and proteins. The amount of drip or drip loss is usually experimentally measured through the water-holding capacity (WHC) and determined in duplicate on 50 g fresh samples taken at 24 h post-mortem and placed in a special container (meat juice collector). A poor water-holding capacity is unwanted, as it means weight loss. However, the amount of drip of a meat cut depends on the conditions under which it is determined .The time postmortem and the duration of measurement;Geometry of the piece;Temperature during the measurement;Type of package;The sample’s position within the package.These conditions are:From the consumer’s point of view, this attribute is directly related to product appearance. According to previous literature, consumers’ choices were mostly based on three appearance characteristics: color, drip loss and fat content .Meat texture is a multi-parameter attribute that is closely correlated with a sensory evaluation of tenderness. It is possible to improve the beef’s tenderness (texture) by considering factors such as the animal breed and feeding system and post mortem factors, such as carcass refrigeration after slaughter, hot carcass hanging, ageing time and culinary methods ,43. The The process of evaluating overall quality of fresh meat consists evaluations of both, intrinsic and extrinsic quality cues. Extrinsic quality cues represent information related to the product, its promotion, storage conditions, price, package, etc. The main role of these cues is to influence the consumer’s first impression. The meat brand name is often a synonym for a traceable, guaranteed and authentic product. Although, in the past, fresh meat was mainly unbranded and purchased in butcher shops, nowadays meat producers try to differentiate their products on the basis of branding, especially when brand is connected with products of specific geographical origins and nutritional characteristics. Hence, the brand name is common to the “value added” group of attributes that increase the value of product . As the When it comes to label, it presents an important source of information about quality for consumers concerned about safety and nutrition/health. However, Indonesian consumers preferred not to buy beef with an unclear Halal label in spite of its freshness and red color . FurtherAs the color of fresh meat is highly influenced by package, this extrinsic quality cue was defined as important . In addiFrom the farmers’ point of view, the choice of animal breed depends on the geographical area, a history of breeding a specific domestic breed originating in the territory and the type of production (extensive or intensive). However, consumers often link extensive production with traditional breeds, organic meat and free-range livestock production. According to the study by López-Pedrouso et al. , the strConsumers often associate animal welfare with natural, green, organic and eco-friendly animal production process. The production of free-range and sow stall-free pork leads to organic pork that increases consumers’ willingness to pay . FurtherOne of the most frequently studied attributes was the price of meat. This is a very important extrinsic quality cue, as its increase can reduce meat consumption and increase the availability of meat alternatives. It was found that price strongly influences the purchasing decision . FurtherWhen it comes to experience attributes such as cooking ease, culinary skills and ways of shopping, their impact on the consumers’ purchasing decision were ranked as intermediate . FurtherSome future trends lead to situations where a known seller or place of purchasing will not be as significant as other quality cues such as the price or food safety certification (traceability system) . In thatThe sensory wheel construction techniques were used as a basis for creating suitable QWs to complement the quality evaluation at the point of meat purchase. The concept of creating these tools is similar to the scientific conversion from the sensory lexicon to the sensory wheel. This approach provides an attractive way to convey cues for product differentiation to its potential consumers. Basically, attributes in QWs serve as a checklist against which the attributes of products in front of consumers are compared. A summary of the quality cues provided in the literature review was used for formation of the QWs. The cues that were defined by consumers as the most important were included in beef and pork QWs .The quality wheels are dual-purpose tools intended to prevent the lack of communication between meat consumers and producers and help them to clearly understand the quality of meat. As the sensory wheel could be used as the basis of flavor description, the quality wheel could be used as the basis of the description of all of a product’s characteristics. Hence, these two types of wheels function in a similar way. For example, beef flavor wheels guide panelists through more and more precise describing words for flavor, texture and aroma in a direction from the middle to the edge of the wheel. It helps panelists to accurately discover which aroma they feel. Consequently, with a more comprehensive understanding of meat quality, producers can identify directions on how to improve it, while consumers can make better purchase choices.The principle of using the quality wheel is similar, it helps consumers and producers to find out which quality cues interact with each other. For instance, if consumers seek experienced juiciness, then fat marbling is an important cue for consumers, so they need to consider the type of meat cut. The short loin cuts, such as T-Bone, tenderloin and striploin, and cuts between the 5th and 13th rib are the most preferable cuts where marbling may occur ,62. TherQ) represents the square root of the sum of squared individual meat quality indexes.n presents the individual attribute from a possible range from n = 1 to N attributes, where N presents the total number of attributes studied.As any modification of the production system  may affect meat quality and the shelf life of the final product, particular quality and safety evaluations need to be done. In those cases, quality parameters that are under examination could be parameters suitable for future quality index construction. In general, two main questions arise when developing quality indexes. The first is related to the methodology of calculating specific quality attributes, and the second is how to develop an overall single score based on all individual attributes. Based on the work of Finotti et al. , individThe nearer to the target value the parameter is, the better the quality is;The smaller the characteristic’s value is, the better the quality is;The higher the characteristic’s value is, the better the quality is.When calculating individual quality indexes, there are three potential rules:One approach in developing an overall meat quality index is to identify key quality attributes .However, for easier understanding of how these rules correspond to meat quality evaluation, the categorization of the rules is outlined in It can be noticed that some extrinsic characteristics cannot be used directly in the QI formula but can be used as factors. In that context, the remaining characteristics that are not presented in these tables but in wheels can be involved in making appropriate environments for using the QI, such as different brands, sellers, animal welfare programs, breeds, feeding systems, processing technologies and so on and can be used to differentiate samples. Furthermore, the type of package, storage temperature and level of hygiene can be used as determinants that can influence the quality of a product during storage time .One of the first examples of linking price with the QI is in the study by Finotti et al. . When itThis review outlines the importance of understanding intrinsic and extrinsic meat quality cues and the potential of using meat quality wheels. It has been elaborated why quality wheels may be useful tools for both consumers and meat producers in finding the optimal number of quality characteristics that are considered at the point of meat purchase. According to previous literature, meat color, sensory characteristics and fat content have been shown as the most important intrinsic quality cues of fresh beef and pork from the consumer’s point of view, where odor, tenderness, juiciness, flavor and overall liking, respectively, were the most frequently examined. On the other side, when it comes to extrinsic quality cues, price, certification logos and brand name were noted as the most important for evaluating beef quality. Furthermore, price, breed, animal welfare and a veterinary certificate were noted as main determinants of pork quality. As an outcome, this review has identified approaches in evaluating individual quality characteristics and metrics for developing an overall meat quality index. The lack of some characteristics in previous literature, such as experience attributes for the extrinsic quality of beef and credence attributes for the intrinsic quality of pork, is a limitation of this study, and this aspect may represent a theme for further research. Future research should focus on validating the proposed meat quality index for both beef and pork meat employing consumer research. The proposed QI formula does not pretend to be the unique practical answer to the need for evaluating quality in the meat industry, but seeks to show a way through which the base of the quality evaluation can be established. The main feature of this index is its flexibility, because it can be adapted to every choice of the quality parameters presented in this study. Hence, both intrinsic and extrinsic characteristics are applicable for this type of quality index. For the purpose of a validation process in future research, we have proposed quality parameters, how to group them and the mathematical index in terms of the chosen parameters.


Acute and chronic pain are very disturbing conditions for the patient, with numerous implications on the short- and long-term outcome of patients . While aThis is why guidelines, drugs and medical interventions have been proposed to treat acute and chronic pain , 4. WhilThe incidence of chronic pain is generally high. It was reported that in Europe, for example, more than 20% of population suffer from moderate to severe chronic pain, with huge medical and social costs and great impact on patients’ life , 6. TherThis is why, in the last years, considerable efforts have been done to implement guidelines for treatment of acute and chronic pain in which central concept is the multimodal pain treatment ,10. In tDespite the availability of multimodal therapy and numerous medical interventions in pain management, opioids still play a major role in acute and chronic pain treatment. In the last near 40 years since opioids were introduced for pain therapy, these drugs remain the mainstay for moderate/severe pain treatment. In this context, in the last 30 years an exponential increase in the amount of opioids used for acute and especially for chronic pain was registered around the world, especially in US and the trend remains constant in the last 6 years including in Europe , 16, 17.This raised the question if is pain better treated or is illicit prescription of opioids increased? Statistics in the last 20-30 years show that both of these issues are valid. In the last years, it has been reported that pain is better recognized, reported and treated, especially in cancer patients and palliative care ,15 leadiOn the other hand, an over prescription and illicit consumption has been registered especially in US , 13, 14.Taking in consideration this global picture, the next questions are if Europe is also in an opioid crisis and where is Romania in this context? The arguments for raising the first question include the increase in opioid use in Europe in the last 20 years and a relatively increased number of death due to illicit opioid use insome European countries, while in other countries this number decreased or was stable along the last years . Recent Where are we in Romania? Data published so far show that in Romania the opioid consumption is low as compared with other European countries or in a classification of all countries , 14. HowConsidering these data, similar to other Eastern European or American countries, the question is if Romanian patients suffer from less pain or pain is undertreated and what action needs to be taken . Of courThis will lead to indicating the best action to be taken to have a balance between an adequate acute and chronic pain treatment and the risk of over prescription and illicit consumption of opioids.Finally, similar to other countries, many gaps in pain treatment still remain in our country . These i


Difficulty in transportation to access skilled providers has been cited repeatedly as a major barrier to utilization of emergency obstetric care in Nigeria.The objective of this paper is to describe the design, implementation, and outcomes of a mobile phone technology aimed at rapidly reaching rural Nigerian women who experience pregnancy complications with emergency transportation and access to providers.The project was implemented in 20 communities in two predominantly rural Local Government Areas (LGAs) of Edo State, in southern Nigeria, as part of a larger implementation project aimed at improving the access of rural women to skilled pregnancy care. The digital health innovation named Text4Life, allowed women to send a brief message from their mobile phone to a server linked to Primary Health Care (PHC) facilities and to access pre-registered transport owners. Pregnant women were registered and taught to text short messages to a server from their mobile phones or those of a friend or relative when they experience complications.Over 18 months, 56 women out of 1620 registered women (3.5%) texted the server requesting emergency transportation. Of this number, 51 were successfully transported to the PHC facilities, 46 were successfully treated at the PHC, and five were referred to higher-level care facilities. No maternal deaths occurred during the period, while four perinatal deaths were recorded.We conclude that a rapid short message sent from a mobile phone to a central server and connected to transport providers and health facility managers is effective in increasing the access of pregnant women to skilled emergency obstetric services in rural Nigeria. Maternal mortality is a major public health challenge in developing countries, with a higher proportion of the burden among pregnant women living in rural communities. The World Health Organization (WHO) reports that 94% of the world’s 295,000 maternal deaths occur in low and lower-middle-income countries. Sub-Saharan Africa contributes 66% of these deaths . NigeriaA significant proportion of the Nigerian maternal deaths occur in rural communities and are linked to limited access to health services, weak health infrastructure, and adverse socio-cultural factors –6. The 2The Federal Ministry of Health (FMOH) and all major health policy agencies in Nigeria have recognized increased access to skilled obstetric care, especially in rural areas, as critical to reducing the high rate of maternal mortality. Although the Nigerian government acknowledges the critical role of primary health care in improving women’s access to skilled pregnancy care, especially in rural areas, the implementation and use of this model of care has been poor throughout the country , 9.In 2017, we initiated formative, intervention, and implementation research to identify innovations and evidence for improving women’s access to skilled pregnancy care in Primary Health Centres (PHCs) in rural Nigeria. In the formative research, we identified difficulty with transportation as a major barrier to the use of existing PHCs by pregnant women , 11. ThrMaternal and child health initiatives across sub-Saharan Africa are embracing the use of electronic or mobile technology to improve access to and use of skilled obstetric care, particularly in marginalised and vulnerable populations. These initiatives have proven to be effective in improving women’s use of health facilities, in enhancing two-way communication between healthcare workers and pregnant women, and in increasing pregnant women’s self-efficacy through the provision of relevant health information –14.Working in collaboration with women, community leaders, and policymakers and using community-based participatory research methods, we designed an intervention, Text4Life, which coordinates women with providers, transport, and supports triage of cases by the PHCs. The interventions were implemented for nearly 24 months, with impressive results, and with no recorded maternal mortality in the rural communities . The objThis paper is drawn from a larger separate sample pretest-posttest quasi-experimental research conducted in rural Edo State, Nigeria between July 2017 and March 2020, and the post-project activities. The general aim of the larger research was to increase rural women’s access to skilled pregnancy care in primary healthcare centres.The project was implemented in 20 randomly selected rural communities in two Local Government Areas (LGAs) of Edo State in Nigeria. Edo State is one of the 36 Federal states in Nigeria, with a population of over 4 million people, the majority of whom live in rural areas . Edo StaThe study was set in Etsako East and Esan South East LGAs, two predominantly rural LGAs located in the northern part of Edo State, both bordering the southern part of the River Niger as it enters the Atlantic Ocean. We chose Okpekpe in Etsako EastLGA and Ewatto in Esan South East LGA, two wards comprising 31 villages and hamlets, from which 20 were randomly selected for the project. Both wards have two PHCs each for four PHCs covering the villages and hamlets.These communities were chosen because of their rural locations and the fact that PHCs are the only available sources of healthcare. There are no secondary or tertiary health care facilities in the immediate proximity although transfers can be made to secondary or tertiary facilities in other locations which are between 20 and 173 km.The sample size for the larger implementation research comprised 1408 ever married women at baseline and 1411 at endline who were randomly selected from households. The detailed description of the design, the selection of the study communities, sample size determination at the baseline and endline, and the intervention activities which included Rapidsms (Text4Life) have been described elsewhere . HoweverThe formative research included qualitative needs assessment to identify gaps and challenges. Women reported that the major challenges related to care were transportation difficulties and access to skilled providers, among others . We thenNext, we worked with the local leaders to identify and appoint members of WDCs, with a chairperson for the two project sites and to develop and manage the application functions. The WDC is an initiative recommended by Nigeria’s Federal Ministry of Health to build community linkages and partnerships for the management of PHCs across the country . Based oText4Life was built upon an open-source framework for basic short message services, data collection, and communication platforms written in Python and Django programming language . It was Textit receive messages from women and automatically sends dual replies to the phones of the WDC chairpersons and PHC workers. The device included a reversed billing method that triggers an alert message at no cost. We worked with the WDCs to identify reliable taxi owners in the communities who agreed to participate in the fully explained project. The technology included a web-user interface created for the project by Textit. This interface is a visual platform for interactive messaging. The account gives access to aggregated and disaggregated data for the team and enables the tracking of individual history of patients and reports. The password-protected web interface provides an overview of the system’s outputs, including individual messages sent out, reports, statistics, and administrative data.The automated messages were designed to reply with customized messages  that are then relayed to the sender, healthcare providers, and a WDC Chairman. This conversation workflow ran on an electronic communication device, looking out for SMS keywords and sending appropriate responses. Additionally, it can act on data from messages using Textit integrations and an application programming interface (API). It sends bulk SMS messages, managing them in an email-like inbox, sending automated messages, building bots for social networks, and keeping track of users in a simple customer relationship management (CRM) software.In addition, each Textit® interaction is defined by a systematic workflow, which defines how the user of the application will progress through the flow. Textit® creates a logic flow routine to route users based on their responses. At any point in the flow, one can trigger an action, such as sending personalized short messages, emails, or calling through an external software intermediary such as the API, which can speed response time. Group messages are sent to pregnant women, the health workers, and WDC chairmen on a regular basis to provide health information and platform updates.Each interaction creates a record associated with each user. The records are transferred into MS Excel representing data for all registered pregnant women. The user interface connects data across user groups for each project site, thereby serving as a tracker for the number of women registered and the inputs and outputs over the system. The system was designed to provide access to PHCs for pregnant women in case of an emergency. Text4life is accessed by pregnant women through registration with the WDC and the payment of a small fee - Naira 4000  which could be paid in instalments. It enables the use of all facilities including antenatal, delivery, and postnatal care as well as the transportation at no cost. This was a part of a community health fund created as one of the intervention activities for the larger project .Women were recruited and registered, with records of contact details including their telephone numbers and those of their next of kin and neighbours. If a pregnant woman were in distress, she would trigger an alert system by sending a keyword to a dedicated registered phone number configured to the central server. The pregnant woman receives automated feedback from the server for her to wait while an action is being taken. Simultaneously, a dual SMS is relayed through a web-designed interface to the phone number of the WDC Chairman in the ward, and the health care provider at the PHC. Additionally, the pregnant woman’s information is displayed on the message relayed to the WDC and PHC, which prompts them to take immediate action. The WDC then calls the transport owner to pick up the woman in distress, while the healthcare providers prepare to receive the woman in the PHC see Fig. .Fig. 1SuThe WDC Chairs oversee the project in their communities and report directly to the community leaders for timely decisions. The WDC educates community members about the need for antenatal clinics through village meetings. They also arrange the transport system, including referrals and transport to higher-level health facilities as needed. The WDC managed the community health fund, from which the cost of transportation and delivery care were paid.To build capacity among community stakeholders to manage the system, a series of capacity-building workshops were organised. This consisted of four two-day workshops for the WDCs, PHC providers, and pregnant women (and their spouses or caregivers) in the two project sites (two per site) and two workshops for the health providers in the PHCs. During the workshops, trainers described the system and demonstrated the use of the Text4Life app. The education included explanation of the possible complications of pregnancy for which women would require immediate transfer. They were also taught the specific ways to send messages in English and interpret replies from the central server. Health providers were taught to prepare to receive women and the specific actions to be taken to respond to emergencies, including referrals to specific secondary care hospitals within the vicinity of the PHCs (with contact details) to which women with severe complications could be referred. On completion of the training, mobile phones were distributed to the healthcare workers in the PHCs and the WDC members. Each phone number was registered with all network providers in the communities.The second training series was training of female volunteers in each community. These volunteers were selected based on literacy and ability to triage emergencies using the SMS system. Further trainings were conducted at each PHC.Each participant and interaction are automatically uploaded to the server and transformed into variables. Additional variables were added to each record to denote outcomes of interactions and the pregnancy. Records were checked against WDC and PHC records to track the number of referrals to higher-level health facilities and the outcomes of treatment in the referral facilities.Data were exported to Microsoft excel and analysed to review descriptive information about the number of women who registered in the project, number who reported complications using Text4Life, used the transport, treated in the PHCs or referred. The number of maternal and perinatal deaths was calculated.The use of the device began in June 2019 and has continued since. The results presented here are for the period June 1, 2019, to December 31, 2020, spanning approximately 18 months of implementation.As shown in Table Of those reporting complications to the platform, 51 (91.1%) were transported by registered taxis to the PHCs. The common complications reported included bleeding, preterm labour, severe lower abdominal pain, and severe back pain among others. The reasons for five women not being transported included “taxi not available (on other duties) at the time” (4), while one woman delivered at home before the taxi arrived.Among the 51 women transported to the PHCs, 46 were successfully treated, while five were referred and transferred by the same taxi to a referral hospital.No maternal deaths were recorded among the women registered under the platform during the period, although four perinatal deaths occurred. Among the perinatal deaths, one was a macerated stillbirth in a woman who had foetal death in utero; two were stillbirths following labour at a secondary care hospital, while the remaining death was an early neonatal death due to preterm delivery.This study described the implementation of a mobile phone app designed to rapidly reach rural pregnant women who experience complications with emergency transportation and access to providers. The results indicate that the intervention is feasible, especially when applied with the active participation of community members and transport services. Difficulty with transportation has featured repeatedly as one of the major challenges that limit women’s use of skilled pregnancy care especially in rural settings , 19–21. We had also earlier reported the results of the post-intervention compared to the pre-intervention survey which showed a near elimination of transportation difficulty and provider unavailability as a cited barrier to the use of PHCs in the communities after the introduction of the text4life model . The resThe use of technology in health has gained much attention in recent times . With thIn Nigeria, while the use of electronic communication for registration of birth has been reported , there hSeveral factors account for the success of this study. The first and the most important is the involvement and engagement of community stakeholders in the design and implementation of Text4Life. Well-selected WDC members that report periodically to community chiefs was critical to the project’s success as it ensured a high level of commitment to the project. This engagement process helped to build trust and accountability, which contributed to the project’s success. We believe that this approach will stimulate the sustainability of the project as key members of the community gained knowledge from the training and skills they received during the project implementation. Second, the project received garnered support from multi-stakeholders as described elsewhere , while tThis Text4Life app is different from other models. For example, in contrast to a project in Rwanda , our proTo the best of our knowledge, this is one of the most comprehensive eHealth technology innovation for increasing access to emergency skilled obstetrics care ever undertaken in the African region. The involvement of local community leaders ensured the project effectiveness and would likely promote its sustainability over time. The additional information provided on risks and methods of management of pregnancy during the project delivery also helped to expand the benefits of the project to include women’s agency and knowledge to use maternity services provided by skilled providers.Despite these laudable outcomes, limitations of concern include the fact that only 56 women out of the 1620 registered pregnant women (3.5%) used the Text4life platform for emergency transportation. This may be because the use of the platform was recommended for women who lived far away from the PHCs and who had no immediate transport at the time they experienced a complication. Our record indicates that among women requesting transportation through the Text4Life platform, a large proportion (> 90%) were moved to the PHCs with emergency transport. Among those not reached with transport, this was due to late arrival or non-availability of the taxis at the time the request was made. This implies that a system involving the use of multiple and alternative methods of transport and that includes a response from the transport owners regarding their availability at the time of the request would have to be considered.In addition, the study is limited by its restricted scope given that only two wards in two LGAs were included in the sample. A research design based on a larger sample size involving several sites in different parts of the country would be necessary to identify the challenges and bottlenecks that need to be overcome for scaling the innovation throughout Nigeria’s health care system. This may perhaps include a more systematic randomised or quasi-experimental research designed in the format of implementation research to provide information on the appropriate context for the delivery of the intervention in the country.In conclusion, this study demonstrates the potential of a rapid short message sent from a mobile phone to a central server and connected to transport providers and health facility managers to increase the access of pregnant women to skilled emergency obstetric services in rural Nigeria. Further study with a larger sample of women and covering wider population segments will be needed to firmly establish this approach as effective for reducing transportation delay as a cause of the high rate of maternal mortality in Nigeria.