Telemedicine has emerged as a tool for overcoming the challenges of healthcare systems and is likely to become increasingly viable, since information and communication technologies have become more sophisticated and user-friendly. We aimed to identify all Cochrane systematic reviews (CSRs) on telemedicine within healthcare and to summarize the current evidence regarding its use. Review of CSRs, developed at the Discipline of Emergency and Evidence-Based Medicine, Escola Paulista de Medicina, Universidade Federal de São Paulo. We searched for studies that compared use of telemedicine with conventional treatment or management of diseases within healthcare. Diagnostic telemedicine studies or studies using automatic text, voice-text or even self-managed care were excluded. The main characteristics and the certainty of evidence were synthetized and critically discussed by all authors. We included 10 CSRs that investigated a broad range of diseases. There is still insufficient evidence to determine what types of telemedicine interventions are effective, for which patients and in which settings, and whether such interventions can be used as a replacement for the standard treatment. Harm relating to telemedicine technologies needs to be better investigated and addressed. Telemedicine might be an excellent way to facilitate access to treatment, monitoring and dissemination of important clinical knowledge. However, given the recognition of systematic reviews as the best evidence resource available for decision-making, further randomized controlled trials with stricter methods are necessary to reduce the uncertainties in evidence-based use of telemedicine. Telemedicine is the use of information and communication technologies to provide healthcare services, especially when distance is a critical factor in accessing the healthcare provider.Although telemedicine is not a novel activity, it has over the past few years emerged as an alternative tool for addressing the challenges of universal healthcare systems, such as expansion of access to specialized healthcare services in regions that lack these resources.Telemedicine provides a virtual environment that enables remote interaction between healthcare professionals and their patients, and among healthcare professionals themselves. This particular characteristic, which goes beyond conventional standards, changes paradigms and has ethical and legal implications in each country where it is used, especially in relation to the confidentiality of patients’ data.In the United States, it has been estimated that more than a quarter of consultations are undertaken through telephone calls.The territorial extent of Brazil is huge, with thousands of isolated, difficult-to-access places and unequal distribution of good-quality medical resources. These characteristics put the right to universal, comprehensive and equitable healthcare services at risk and indicate that there is great potential for expansion of telemedicine in this country.The aim of this study was to identify all Cochrane systematic reviews (CSRs) on telemedicine within healthcare and to summarize the current evidence regarding its use.Review of Cochrane systematic reviews (SRs).Discipline of Urgency and Evidence-Based Medicine, Escola Paulista de Medicina (EPM), Universidade Federal de São Paulo (UNIFESP), Brazil.We considered the latest versions of the published Cochrane SRs. We did not include any protocols or any SRs that had been withdrawn from the Cochrane Database of Systematic Reviews.We considered all patients who made use of any category of telehealth intervention, without any restriction relating to type of intervention or the age or sex of the participants.We considered any category of telemedicine intervention for treatment or management of diseases within healthcare. We excluded studies that assessed the effect of telemedicine for diagnostic purposes or studies that used automatic text or voice-text or even self-managed care.We considered any outcomes that had been assessed and reported by the authors of the SRs included.We conducted an unrestricted systematic search within the Cochrane Database of Systematic Reviews (via Wiley) on February 26, 2019. The search strategy is presented in The selection phase consisted of reading of all the abstracts retrieved, by three researchers independently , to check their eligibility in relation to the inclusion criteria. Any disagreement was resolved through reaching a consensus among these three authors or by consulting a fourth author (CDQF).,Out of the 326 reviews that had been included in the primary analysis, we selected 10 SRs (published between 2011 and 2016) containing data on 53 randomized controlled trials (RCTs) with 6,836 participants, which had assessed the effectiveness and safety of telemedicine within healthcare. These SRs addressed the effects of telemedicine regarding heart-failure patients (n = 1),2 = 0%; low quality of evidence). In relation to exacerbations requiring hospitalization, there was uncertainty regarding the benefit or harm, compared with the standard monitoring procedure .This review2 = 54%; low quality of evidence). Adverse events, whether serious or non-serious, were not reported in any of the studies included in this review. Small benefits regarding quality of life were observed, although the studies were unblinded. Some benefits regarding lung function were reported, but the effects were uncertain due to possible attrition bias.Overall, the evidence relating to asthma control was very weak due to the inconsistency of outcomes. The patients in the telemedicine groups scored better in the Asthma Quality of Life Questionnaire than did those who were monitored using standard protocols . Moreover, the cluster study showed that there were positive effects in the face-to-face check-up groups .The effect of exacerbation events that needed emergency department visits favored the face-to-face check-up groups, but this was uncertain due to the small number of events . However, neither the RCTs  nor the cluster implementation study  showed any statistically significant benefits, compared with face-to-face check-ups, regarding exacerbations that required hospital admission.The authors of this review reported that there were no differences relating to the scores obtained in the Asthma Control Questionnaire between the remote and face-to-face groups . There were no differences between the two groups regarding asthma-related quality of life, as determined through the Asthma Quality of Life Questionnaire .The results relating to unscheduled healthcare visits were imprecise with few events and, therefore, it was impossible to draw a conclusion. Lung function assessed by means of forced expiratory volume in the first second (FEV1) was only reported in one study. The authors of this reviewAll the available evidence was based on small RCTs. Outcomes relating to lung function, asthma control and exacerbations requiring oral corticosteroids were only reported in one study. The evidence was downgraded by the SR authors to moderate quality regarding asthma-related quality of life and asthma control because of the lack of blinding of the participants and outcome assessments. The evidence regarding the lung function was downgraded because of imprecision relating to the small sample size. The data on the other outcomes were of low quality due to the wide CIs, small number of events and risk of bias.https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD011715.pub2/full.For further details, the full content of this review can be accessed through: This reviewTotal number of exacerbations was only analyzed in one RCT, with borderline statistical significance (P = 0.06). In another trial, it was reported that the mean number of exacerbations per month was significantly higher among the controls than in the telehealthcare group . The number of days that were free from exacerbation after one year was higher in the intervention group (30%) than in the control group (5%).Quality of life was assessed through scores from the validated St George Respiratory Questionnaire (SGRQ), and improvement of quality of life showed slight clinical significance with very wide confidence intervals . The patients who received telehealthcare were much less likely to attend the emergency department than were the individuals in the control group , and the number of patients with one or more hospital admissions was lower in the telehealthcare group . There was no difference in mortality rate between the groups . There were no differences between the groups regarding lung function or patient satisfaction. The authors of this review encouraged support for telehealthcare, even though the evidence came from very heterogeneous studies.https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD007718.pub2/full.For further details, the full content of this review can be accessed through: This review=telerehabilit%7Cwithdrawn%7Ctelerehabilitationhttps://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD011019.pub2/full?highlightAbstract.For further details, the full content of this review can be accessed through: This reviewThe telerehabilitation interventions included physical activity and educational, behavioral and symptom management programs. The duration of the interventions ranged from one to six months (median of 12 weeks). The main outcomes evaluated were the following: functional activities; improvement in symptoms or impairments ; quality of life; and psychosocial outcomes.No quantitative analysis could be conducted in this review,Multiple sclerosis is a complex condition and the range of telerehabilitation interventions and their prescription requirements can vary from person to person and are difficult to standardize. Factors such as the patients’ functional abilities, personal characteristics and comorbidities and the characteristics of the healthcare system may influence patients’ outcomes. The interaction of these factors with rehabilitation strategies and their impact on patients’ outcomes is still little understood. However, because the multiple sclerosis population is young and has high rates of internet use, these patients are likely to be receptive to telerehabilitation.In addition to the limited number of studies in this review and the high heterogeneity among these studies, methodological weaknesses were identified in them .https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD010508.pub2/full?highlightAbstract=telerehabilit%7Cwithdrawn%7Ctelerehabilitation.For further details, the full content of this review can be accessed through: Ten RCTs (n = 933) were included in this review.The telerehabilitation interventions included use of telephones, videoconferencing hardware and software, desktop videophones, in-home messaging devices, video recordings, emails, online chat programs and online resource rooms. The intervention approaches included upper limb training, lower limb and mobility retraining, case management and caregiver support. Several outcomes were evaluated, such as physical function, independence in activities of daily living, quality of life and participant satisfaction.Pooled data from 661 participants did not show any statistically significant results regarding independence in activities of daily living when a case management intervention was evaluated . No statistically significant results regarding upper limb function  were observed when computer software was used to remotely retrain upper limb function.Insufficient evidence was found to draw any conclusions regarding the effects of the intervention on mobility, health-related quality of life or participant satisfaction with the intervention. No adverse events were reported within the studies.Overall, telerehabilitation offers great potential as an intervention to be used in addition to current therapies or as a therapy for patients with difficulty in accessing places where face-to-face rehabilitation can be provided. However, it is still important to investigate whether there are any differences in the same therapy between delivery face-to-face and delivery via telecommunication.https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD010255.pub2/full?highlightAbstract=telerehabilit%7Cwithdrawn%7Ctelerehabilitation.For further details, the full content of this review can be accessed through: The aim of this reviewThe results from the review showed that the lengths of hospital stay were similar in the telemedicine group  and the control group . The quality of the evidence was very low due to the small sample size and imprecision of the effect estimates.The participants formed a very specific group: families living within the urban area, with good internet access, who were competent in English and had higher economic status than other possible candidates. There was a withdrawal rate of 20% within the control group, since these newborns were transferred back to level-2 nurseries. The data regarding family satisfaction and other outcomes were insufficient for conducting proper analysis.Thus, so far, there is not enough evidence to promote use of telemedicine to support parents or caregivers of newborns receiving intensive care as an effective procedure. However, this study dates back to the year 2000 and many technological resources have been developed since then. For this reason, we cannot rule out the idea that application of telemedicine to this kind of population now could have a different outcome.https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD006818.pub2/epdf/full.For further details, the full content of this review can be accessed through: The aim of this reviewThe main findings were that there were no differences between the intervention and control groups regarding adherence to antiretroviral medication, with low quality of evidence , or regarding depressive symptoms, also with low quality of evidence . In relation to all other information , there was insufficient data to provide meta-analyses.https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD009189.pub2/full.For further details, the full content of this review can be accessed through: This reviewThe main findings from this review regarding non-invasive telemonitoring were that it gave rise to reductions in the all-cause mortality rates ; and reductions in heart failure-related hospitalizations . Structured telephone support also reduced all-cause mortality  and had a positive impact regarding reduction of hospitalizations caused by heart failure . All of these outcomes were graded as presenting moderate quality of evidence.This review did not show any difference regarding reduction of the risk of all-cause hospitalizations, , with very low quality of evidence. The outcomes of length of stay, quality of life related to the health condition, cost effectiveness and treatment adherence were not described consistently, which hindered development of a meta-analysis. The funnel plot analyses demonstrated that there was strong evidence of publication bias.https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD007228.pub3/full.For further details, the full content of this review can be accessed through: This reviewThe severity of headache pain was reduced through remote psychological treatments . For mixed pain conditions, i.e. musculoskeletal pain or abdominal pain with recurrence, there was a beneficial effect regarding reduction of pain intensity post-treatment .At follow-up, however, no statistical difference in headache conditions was achieved . This was also observed regarding the outcome of depression, when analyzed in the same headache groups . For headache and mixed conditions, there were no beneficial effects from the therapies included as interventions in this review . No data were available in relation to any other outcomes, or in relation to adverse events.The authors of this review did not use GRADE  in the assessment of risk of bias because of the lack of information in the studies included. However, they classified most of the studies as presenting “low risk” or “unclear risk” of bias.https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD011118.pub2/full.For further details, the full content of this review can be accessed through: The use of telemedicine is likely to become increasingly viable as information and communication technologies within healthcare become more sophisticated and user friendly. The driving force behind this is the need for an alternative to face-to-face interventions that enables service delivery in the natural environment, i.e. in patients’ homes.,,For pulmonary care, telemedicine has become an important alternative to the standard care. Chronic obstructive pulmonary disease (COPD) is the third leading cause of death worldwide.Telerehabilitation is an emerging method that extends rehabilitative care beyond the hospital, using telecommunication technology at home or in the community.We also performed a broad search in the Medline database via PubMed on March 12, 2019, in order to find other reviews. The PubMed search strategy is provided in ,In general, the Cochrane reviews had broader searches and identified greater numbers of randomized trials than were described in other reviewsFurthermore, although the purpose of telemedicine is to reduce costs and overcome some barriers such as availability of transportation, hospital costs and ability to make visits to healthcare professionals, no Cochrane reviews have identified any trials on its cost-effectiveness. Establishment of telemedicine services can be expensive due to the costs of equipment, training and ongoing technical support. Therefore, it is important to determine whether, once telemedicine services have been established, they should be used as an alternative or as a supplement to the conventional therapy that is delivered face-to-face.It is also relevant to note that the use of technology to facilitate communication may, on the other hand, lead to miscommunication. For example, healthcare professionals may make errors relating to their assessments of patients, or these patients may misunderstand the advice or instructions provided by the healthcare professional. Therefore, not only the benefits, but also the harm associated with telemedicine needs to be addressed.Overall, there is still insufficient evidence regarding what types of telemedicine interventions are effective, and for which patients in which setting. Here, we can also highlight the lack of robust, methodologically strong studies evaluating the effectiveness of the different technologies relating to telemedicine interventions. Researchers should ensure that trials are adequately powered, developed with high methodological quality and reported in compliance with the Consolidated Standards of Reporting Trials (CONSORT) guidelines.In the data universe of the Cochrane Library, we found 10 Cochrane systematic reviews relating to the use of telemedicine within healthcare. The quality of the evidence reported was too low to support or refute the use of this technology within clinical practice as an effective intervention for replacement of standard treatment. The best evidence available was of moderate quality, relating to the effectiveness of telemedicine among patients with heart failure, for reducing the risks of heart failure-related hospitalization and all-cause mortality.Given the growing interest in telemedicine and the recognition of the Cochrane Library as the best evidence resource available for decision-making, further RCTs with stricter methods are necessary in order to address many structured clinical questions and inform better systematic reviews. Such RCTs will be able to evaluate the efficacy, effectiveness, efficiency and safety of telemedicine. In this manner, the uncertainties regarding the therapeutic, managerial, ethical and economic aspects of evidence-based telemedicine could be reduced. Moreover, telemedicine may be an excellent way to facilitate access to treatment and monitoring and to disseminate important clinical knowledge among healthcare professionals.


Karipidis et al.   database (ODEB) .To perform our assessment, the Karipidis review was critiqued and classified into different categories as summarised in Tables Examination of the Karipidis 5G health review reveals many errors in classification and analysis. Some are minor, and although indicating a lack of diligence, they have no substantial implications for the outcomes identified in the papers reviewed. Of much greater concern are the number of misstatements, misclassifications, and exclusions of important findings from sound research.The Karipidis review is at best a superficial analysis of a restricted set of available publications investigating exposures to radio frequencies in the >6 GHz range. No attempt has been made to understand or reconcile differing study outcomes. Karipidis has simply restated the results for specific endpoints, showing papers that have demonstrated statistically significant effects and those that have not. Divergent findings have been used to suggest ‘inconsistency’ as a problem, thereby diminishing the importance of biological effect findings. In contrast, our assessment  providesA literature search identified a significant number of relevant papers  were missing from the Karipidis collection. These papers cover all major themes presented by Karipidis and more, with the majority showing statistically significant effects. By restricting the paper selection criteria, the balance of evidence can be skewed. A lack of transparency regarding papers found and ultimately discarded by Karipidis means that selection bias cannot be excluded.Also missing from the Karipidis review is an analysis of potential publication and funding biases, which would allow the reader to assess how such influences affect study outcomes. This is often very obvious. For example, on a related topic, Carpenter  found thThe biased selections and assessments that have been uncovered in the Karipidis review create an unbalanced view of the science, and skew the final conclusion towards uncertainty. In contrast, when appraising all relevant findings, the evidence found in our review points to risks not fully considered by the International Commission on Non-Ionizing Radiation Protection (ICNIRP) or the Australian Radiation Protection and Nuclear Safety Agency (ARPANSA) in their respective RF guidelines and RF standards. These guidelines do not reflect the current state of scientific knowledge and are based on acute heating protection only , which iOther important works have been omitted from the Karipidis review. Epidemiological studies suggest that RF exposures from other technologies such as radar are associated with an increased risk of hemolymphatic cancers , and expOther researchers  agree thFinally, the Karipidis review lacks representation of many species, including plants, amphibians, birds, domestic animals and most importantly, insects. Therefore, readers are provided with little to no understanding of how MMWs impact these important ecological entities. This is a significant gap.The above critique of the Karipidis review raises a number of ‘red-flags’. These require clarification and clear justification before telecommunications companies are given carte blanche to begin rolling out novel modulated signals to which biological systems have never been exposed.Karipidis has conducted an investigation resulting in the exclusion of important findings, while also overemphasising quality deficiencies and inconsistencies in the data, thereby suggesting confirmation bias. Di Ciaula  argues tIn this regard, Gee’s discussion  of risk In our opinion, the Karipidis review provides insufficient evidence of safety, which is being used by Industry  as justiThe Karipidis review seemingly equates risk management with the need to confirm evidence of harm. The point at which harm becomes a public issue is far too late, given the size of the population being exposed without formal consent. We consider that risks to humans and the environment identified in past epidemiological studies , as wellWe find the Karipidis review to be both inadequate and incomplete, sending the wrong messages regarding safety assessment and public health.


Living guideline methods are evolving. The aim of this study was to determine how frequently searches for new evidence should be undertaken for the Australian Living Stroke Guidelines.Members of the Living Stroke Guidelines Development Group were invited to complete an online survey. Participants nominated one or more recommendation topics from the Living Stroke Guidelines with which they had been involved and answered questions about that topic, assessing whether it met criteria for living evidence synthesis, and how frequently searches for new evidence should be undertaken and why. For each topic we also determined how many studies had been assessed and included, and whether recommendations had been changed.Fifty-seven assessments were received from 33 respondents, covering half of the 88 guideline topic areas. Nearly all assessments  were that the continual updating process should be maintained. Only three assessments (5%) deemed that searches should be conducted monthly; 3-monthly , 6-monthly  and yearly  searches were far more frequently recommended. Rarely  were topics deemed to meet all three criteria for living review. The vast majority of assessments  deemed the topic a priority for decision-making. Nearly half indicated that there was uncertainty in the available evidence or that new evidence was likely to be available soon.Since 2017, all but four of the assessed topic areas have had additional studies included in the evidence summary. For eight topics, there have been changes in recommendations, and revisions are underway for an additional six topics.Clinical importance was the most common reason given for why continual evidence surveillance should be undertaken. Workload for reviewers was a concern, particularly for topics where there is a steady flow of publication of small trials.Our study found that participants felt that the vast majority of topics assessed in the Living Stroke Guidelines should be continually updated. However, only a fifth of topic areas were assessed as conclusively meeting all three criteria for living review, and the definition of “continual” differed widely. This work has informed decisions about search frequency for the Living Stroke Guidelines and form the basis of further research on methods for frequent updating of guidelines. Living guidelines are guidelines which are continually kept up to date as new evidence emerges, with frequent searches for and incorporation of new research . ImportaThe topic is an important priority for health decision-making; perhaps due to large numbers of people affected, substantial potential impact of the decision on health outcomes, or known variation in practice.There is uncertainty in the existing evidence; for example, the certainty of the evidence is not high , or therThere is likely to be emerging evidence that will impact on the conclusions of the evidence synthesis, potentially leading to changes in recommendations; areas where new trials have been recorded in trials registries or where there is an ongoing, high rate of trial publication .The criteria to determine when a living, continual mode of updating is appropriate for a particular clinical topic area include the following:An additional consideration is whether there are adequate resources to conduct and screen the searches and update the evidence summaries.Living guideline methods are in early development, and pilot projects are underway globally to produce living guidelines in areas including COVID-19, diabetes, arthritis and maternal health –7. EstabOne area of ongoing methods development in living guidelines is establishing the frequency with which recommendations need to be updated. Decisions about frequency have important implications for the resources required to conduct the searches, assess the impact of any new studies and incorporate new evidence. For other types of living syntheses, such as living systematic reviews, monthly searches are recommended .The optimal frequency is likely to vary between topics depending on the urgency or importance of the issue and how rapidly the evidence base is evolving, as well as pragmatic issues like resourcing. For example, the Australian guidelines for the clinical care of people with COVID-19 are updated weekly; however, other living guidelines have been updated much less frequently, with searches undertaken monthly or quarterly , 7, 9. AAs part of the process of reflecting on the methods used in the Living Stroke Guidelines, we undertook a survey of the Living Stroke Guidelines Development Group members to ascertain their views about the clinical topics they had been involved in for the Living Stroke Guidelines. To inform methods for the Living Stroke Guidelines, and also living guidelines methods more broadly, we aimed to explore whether Living Stroke Guidelines Development Group members felt these clinical topics met the three living evidence synthesis criteria , and howThe Living Stroke Guidelines consist of eight chapters addressing 88 topic areas, for which nearly 300 recommendations are made . Each toXM. The survey was open for a 3-week period and asked participants to nominate one or more clinical topics from the Living Stroke Guidelines with which they had been involved and then to answer a series of questions about each topic area  an anonymous online survey, and (2) evidence surveillance records for the living guidelines . Clinical experts who are contributing to developing and maintaining the Living Stroke Guidelines were invited by email to participate in an anonymous, online survey conducted using Qualtrics an anonyParticipants could elect to answer these questions for up to five topic areas they had been involved in. The survey included one additional free-text question not linked to any topic area: “What else should we consider in thinking about frequency of updating the Stroke Guidelines?”Simple descriptive statistical analysis of the quantitative data was undertaken using Microsoft Excel. Qualitative data were imported into NVivo 12 and analysed using crafted codes which were then collapsed into key themes. Qualitative data were analysed by one author (TT) who is experienced in mixed-methods research and was involved in the initial development of the guideline methods, but who had no prior contact with the participants or involvement in the day-to-day operation of the guideline program.To determine whether and how new research had influenced guideline recommendations in the period being examined, for each of the topic areas nominated by the participants, we reviewed our records to establish whether additional relevant research evidence had been identified by our evidence surveillance and incorporated into the guidelines since the guideline update in 2017 (prior to introduction of living methods), and whether the recommendation had changed during that time period.Ethics approval was granted by the Monash University Human Research Ethics Committee (Project Number 26354). All participants provided informed consent.Box 1 Survey question for each topic areaShould this topic area be continually updated, i.e. “living”? (Yes/No/Maybe)*Is this topic a priority for decision-making? (Yes/No)*Is there uncertainty in the currently available evidence for this topic? (Yes/No/Varies for specific interventions/outcomes)*Is it likely that new evidence which may impact the guideline recommendations for this topic will become available soon? (Yes/No/Unsure)How often do you think evidence for this topic should be searched for, reviewed and updated? Are there other considerations which might influence how often this topic should be updated? (Free text)*These three questions are the criteria for appropriateness for living evidence synthesis approaches .One hundred and two clinical experts in the Guidelines Group were invited to participate, and 33 participants contributed to this analysis .We received a total of 57 assessments, covering 44 unique topic areas , maybe , no ].The eight topics reported as not, or only potentially, needing to be continually updated are provided in Table Ten assessments, of nine topics, were that topics met all three criteria for living review (identified by ^ in Table Forty-five assessments (79%) indicated the topic was a priority for decision-making. Three topics were assessed by two participants, and there was disagreement between assessors as to whether they were a priority for decision-making.Twenty-eight assessments (49%) reported uncertainty in the available evidence; for 21 (37%), this varied with specific interventions or outcomes, and for eight (14%), there was not felt to be uncertainty.There was a similar pattern for likely future availability of evidence, with 26 (46%) assessments that new evidence was likely, 24 (42%) unsure and seven (12%) that new evidence was unlikely to be available soon.For suggested frequency of updating, three assessments (5%) deemed this should be monthly, 14 (25%) every 3 months, 13 (23%) every 6 months, 17 (30%) yearly, four (7%) when a new update of a high-quality systematic review is published, and six (11%) other, with a variety of suggestions made, mostly linked to publication of large trials.Data on results of searches and impact on guideline recommendations are provided in Table importance of the topic area was the most common reason given for why continual evidence surveillance should be undertaken. Topic areas across the scope of the guideline were described as “critical” [ID 29], “the most important topic” [ID 38] or “very important topic” [ID 35].The it would be good to get consumer input into these questions as well as the stroke team. We do not always fully appreciate what topics are important in recovery beyond the main medical and functional considerations” [ID 35].Respondents also highlighted the need to ensure that consumers were consulted in the process of assessing the importance of topic areas, noting that “likelihood that new evidence would change the recommendation was also felt to be an important determinant of how often new evidence should be incorporated. Respondents noted that for some topic areas, including every new trial led to “lots of work for little relative change to recommendations” [ID 14], and that for these topics, updating “more than yearly is not worth the resources” [ID 38].The Workload for reviewers was frequently mentioned as a concern, particularly for topics where there is a large number of reviews of smaller trials. Recommendations on how to best manage this varied though, with some participants suggesting less frequent review, and others that frequent, smaller amounts of review work were more manageable.[This recommendation] is likely to continue to be based on a large number of reviews of smaller trials. The time taken to go through this it makes sense to keep it to an annual review. [ID 38]There is an overwhelming amount of evidence continually being produced for this topic. Because of this I think regular review of the evidence will make the workload more manageable. [ID 4]Availability of new evidence was highlighted as a key reason to update recommendations, and particularly publication of new, large randomized controlled trials. This was felt to be particularly important if the existing evidence base was mostly indirect evidence  or only addressed the practice of some clinical groups (e.g. physiotherapy but not nursing).searching and evidence surveillance were raised. One was a suggestion that only “critical topics [that] are constantly under research (e.g. thrombolysis) be continually updated; and that, for other topics, a prompt system be set up to ask the guideline group members, perhaps on a quarterly basis, whether a recommendation need be updated” [ID 29]. The second was that the team consider “setting restrictions on the types of new papers that will pass initial screening ” [ID 17].Two other issues related to communication were also requested, particularly to clarify the role of the working groups and to share “upcoming evidence” [ID 33] to be presented at conferences or news of recently registered trials, which might lead to relevant results in the future.Improvements to Our study invited participants to assess the extent to which a continual model of updating was appropriate for the 88 topics covered by the Australian Living Stroke Guidelines. For the 44 topics assessed by the participants, the vast majority were deemed appropriate for continual updating. While limited by the topics for which responses we received, this data provides initial support of the decision to make the entire guideline, rather than selected recommendations, living. However, a key finding was the understanding of what would constitute “continual” update differed widely among the survey participants. Even when restricted to the topics which participants assessed as needing to be continually updated, the majority of assessments were that the evidence should be updated either six-monthly (25%) or yearly (29%)—a monthly search frequency was deemed necessary for only 6% of topic areas assessed. The qualitative data suggest that the assessment of updating frequency is likely to have been influenced by the perceived workload required to review the literature. Interestingly, there was a difference of opinion over whether less frequent but larger rounds of updating were likely to be more manageable than more frequent, smaller rounds of updating. These findings that appropriate frequency of updating is likely to vary with topic, align with those found by researchers working with standard guideline methods .uncertainty of existing evidence and likelihood of new evidence criteria, with almost half giving equivocal responses for both questions. The central role of priority for decision-making as a criterion is strengthened by the similar results found in qualitative data. This raises the question of whether the assessment of appropriateness of living evidence synthesis might be improved if it was made jointly by teams with both the clinical expertise to assess priority for decision-making and the methodological skills to assess uncertainty and likely future flow of evidence. Alternatively, it might be that the priority for decision-making criterion should be more heavily weighted in the assessment of appropriateness of living evidence approaches.While most topics were assessed as needing continual updating, only nine topics conclusively met all three criteria for living review. The priority for decision-making criterion was met by more than three quarters of topic assessments; participants were less definite in their responses to the questions about the The data from our evidence surveillance show that while new potentially relevant evidence was found for almost all of the topic areas assessed, in only a minority of cases did this new evidence lead to changes to recommendations. At the time of publication, new or updated recommendations were made to 16/44 topics included in this survey. Six of the remaining topics not coved by responses have been changed. This suggests that new evidence most frequently serves to bolster rather than challenge the results of existing evidence syntheses. The addition of new evidence which does not change the direction of recommendations appears to improve the perceived credibility and trustworthiness of the guidelines from end users’ perspectives . An evalAs a pioneering project, the Living Stroke Guidelines are leading the way in exploring methodological issues for living guidelines. It will be valuable to compare experiences across the other living guidelines projects to determine variation in guideline topic and development approaches. It will also be useful to consider how methods developments in other areas of living evidence synthesis might or might not apply to living guidelines. For example, while the guidance for Cochrane living systematic reviews sets an expectation of monthly evidence searches , an evalThe development of living guideline methods is in its infancy. This study provides useful insights into the perceptions of clinicians and guideline development group members on how decisions about frequency of updating living recommendations could or should be made. While there was only a reasonably small number of respondents (33), this represents a third of the 102 clinicians involved in the guidelines, and assessments were made of half of the topics covered by the guidelines. Topics not covered in responses to the survey included more acute medical areas, and fewer topics (6/44) had changes to the recommendations compared with those included in survey responses (16/33). It is unclear if this would significantly alter the current study outcomes. The study is also limited by our, largely pragmatic, decision to have assessments made at the level of the guideline topic rather than the specific question or recommendation. This means our data are not granular enough to identify variations within a topic in updating requirements; however, as an early investigation of this important topic, we feel it nevertheless makes a useful contribution. None of the participants expressed any concerns that their responses might not apply to the whole topic area.The results of this study were used to refine methods for the Living Stroke Guidelines, with evidence surveillance continuing monthly but with input from clinical experts sorted every 6 months to confirm potential inclusion and impact. This reflects the clear opinion of the vast majority of responses that surveillance methods should continue for all topics, but that the frequency of clinical expert input is less than initially tested. However, evidence with a clear impact on existing recommendations, as judged by a central project team, will be fast-tracked for clinical expert input. Future work in this area should build on research undertaken to investigate definitions and methods for frequent updating of guidelines using traditional guideline development models  and the In this survey, members of the Living Stroke Guidelines Development Group considered that the majority of topic areas should be continually updated, or “living”, and that the definition of “continual” might include options in which searches for new evidence are undertaken on a 3- or 6-monthly basis, or less frequently for some recommendations. This research provides important insights into the application, and need for further development, of methods from a pioneering living guideline project.


Integrative Medicine is a terminus not well-defined. Most probably, when asking an integrative physician, you will get the answer that it is the combination of academic and complementary/alternative medicine—the best from two worlds.This clearly is a misconception due to two reasons. First of all, it introduces two more ill-defined terms: complementary and alternative, which are often defined in a way that boundaries are floating as we will see later on. Second, a suggestive notion is hidden in the harmless word “combination”.In this context, in the discourse on Integrative Medicine another word is used: pluralism. It refers to a combination of evidence-based diagnostic and therapeutic methods and of methods that are considered helpful by a group of experts, so-called empirical medicine. By this, most proponents of Integrative Medicine open the door for methods which are not based on evidence but on tradition, or as, for example, anthroposophist call it “singuläres Kausalerkennen” (singular recognition of causes). The contrast to evidence-based in this case often is named “cognition-based”. This is tempting for physicians as it restores the white coats—“I know what is good for the patient”. Moreover, groups of experts with the same “re-cognition” may unite in expert associations which for lay people including politicians, judges and journalists are hard to distinguish from science-based associations. Moreover, in case one points to the importance of evidence to put treatment decisions on a sound weighing of benefits and harms, one immediately will be pushed into the corner of the bad guys as one allegedly withheld patients natural methods.The argument heard most often is that these “soft” methods (another not helpful term) at least don’t do harm. This most obviously is quite wrong as also soft methods (for example herbs or teas) may have side effects or interactions. Moreover, even in case of a placebo effect as with homeopathic globules, harm may be done by inducing false beliefs. These beliefs may in case of a cancer disease lead to a delay of treatment. Furthermore, these methods also do cost money either to the patient him/herself or to the society. The argument that homeopathy or acupuncture is less costly than many evidence-based treatments is not valid as in case of a serious disease the evidence-based treatment is still needed.At first glance, there might be a place for placebo treatment for many ailments which are not life-threatening and normally underly self-healing as a common cold or headache. Many physicians and ethicists would consent. But is it really ethically justifiable that the trust of patients in the physician is deceived?There is another argument, often cited for alternative medicine: the patients are asking for it. Yes, patients often ask for globules, consult acupuncturists or healers. However, when talking to those patients, you will never hear them telling that they purposefully choose methods with no more efficacy than placebo. No patient with cancer who takes globules does this with the notion to simply rely on self-healing.Let us get back to the wording of complementary and alternative medicine—abbreviation CAM. Most often, they are defined like this.Alternative medicine is any method which is used instead of a treatment recommended based on scientific evidence. In contrast, complementary medicine is used in addition.Does this definition help? I do not believe so. If this were the case, one method may be alternative in one patient and complementary in another. Moreover, at least in oncology with multimodal treatment strategies: is “alternative” the case of a breast cancer patient who denies any treatment from operation to chemo- or radiotherapy to endocrine therapy? Or is it sufficient to be “alternative” that a patient after operation, chemo- and radiotherapy and 3 years of tamoxifen decides to use Cimicifuga instead of an aromatase inhibitor?Alternative medicine is any use of non-evidence-based method instead of or along with evidence-based treatment without even considering risks from side effects or interactions.In contrast, complementary medicine comprises additional, complementing methods which are evidence-based, are matched to the main evidence-based cancer treatment and for which the risk profile is well-known and considered in a benefit-risk assessment for the individual patient. Complementary medicine has different origins such as naturopathy, phytotherapy, mind–body-techniques. The aim of complementary medicine is to reduce side effects of cancer treatments, improve well-being and quality of life.Therefore, what is the difference to supportive medicine and/or psycho-oncology? I am not sure, whether there is a strict distinction Yet, the unique quality of complementary medicine is that it is the answer to the patients’ question “What can I do by myself?”. In fact, this question is a strong offer from cancer patients to us physicians. And we might answer with an invitation: “I appreciate very much, that you are reflecting on this important issue.” And from this on, we might start communicating on what cancer is, how cancer develops and how modern treatments work. We might explain side effects and supportive treatments, we might involve a psycho-oncologist and we might start training our patients to be self-efficacious in using ginger tea against nausea (without forgetting to take anti-emetics) or choosing between honey, sage, peppermint or chamomilla against mucositis, doing a relaxation exercise or mindfulness practice or just have a walk with the dog or go playing with the grandchildren .Therefore, in case you now think that all this is nice stuff in comprehensive cancer centres with a department on integrative oncology—no, simply keep in mind that the most natural methods we all have access to are eating and being physically active. Thankfully, these are the fields of complementary medicine with the best evidence and any physician or nurse should not only know this but should also talk on it with every patient.Last and most important: what is Integrative Medicine? We just have described it: take the best from the world of evidence: evidence-based treatments, add evidence-based supportive medicine, evidence-based psycho-oncology, evidence-based nutrition and sports as well as evidence-based complementary medicine, communicate at your best and as often as possible with the patient and his next-ones. Remember that you are the human person that is the patient’s guide in a most unsettled time of his/her life. Last but not least, you are also the guide for those at the end of their patient journey who think about stopping treatment that provides more harm than benefit. In this case—and please start it in just time: palliative care improves survival and quality of life. Remember: the victory march of homeopathy was not due to any evidence of efficacy but to being less harmful than the traditional methods of bloodletting and others.


Despite the number of available methods to predict prognosis in patients with heart failure, prognosis remains poor, likely because of marked patient heterogeneity and varied heart failure etiologies. Thus, identification of novel prognostic indicators to stratify risk in patients with heart failure is of paramount importance. The spleen is emerging as a potential novel prognostic indicator for heart failure. In this article, we provide an overview of the current prognostic tools used for heart failure. We then introduce the spleen as a potential novel prognostic indicator, before outlining the structure and function of the spleen and introducing the concept of the cardiosplenic axis. This is followed by a focused discussion on the function of the spleen in the immune response and in hemodynamics, as well as a review of what is known about the usefulness of the spleen as an indicator of heart failure. Expert insight into the most effective spleen-related measurement indices for the prognostication of patients with heart failure is provided, and suggestions on how these could be measured in clinical practice are considered. In future, studies in humans will be required to draw definitive links between specific splenic measurements and different heart failure manifestations, as well as to determine whether splenic prognostic measurements differ between heart failure classes and etiologies. These contributions will provide a step forward in our understanding of the usefulness of the spleen as a prognostic predictor in heart failure. Cardiovascular diseases contribute to an estimated 17.9 million deaths each year . An estiThere is substantial heterogeneity in the clinical progression of patients with heart failure because of marked patient heterogeneity –8 and vaThere are a number of traditional and established predictors of prognosis in heart failure; however, many have their shortcomings. Raphael et al.  emphasizOther factors have also been investigated as prognostic determinants in patients with heart failure. A lower resting cardiac power output has been demonstrated as a prognostic factor in patients with advanced disease after adjusting for certain variables, including age, sex, left ventricular ejection fraction (LVEF), and mean arterial pressure . MoreoveAlthough the spleen has received limited research attention thus far, it is emerging as a potential prognostic indicator in patients with heart failure based on new evidence that highlights crosstalk between the heart and spleen, termed the “cardiosplenic axis” , 21–23. This review will describe the structure and function of the spleen and discuss the concept of the cardiosplenic axis. This will be followed by a focused discussion on the function of the spleen in the immune response and in hemodynamics, as well as a review of what is known about the usefulness of the spleen as an indicator of cardiovascular disease and heart failure. Expert insight into the most effective spleen-related measurement indices for the prognostication of patients with heart failure will be provided, and suggestions on how these could be measured in clinical practice will be considered. In this review, we aim to collate current knowledge to provide insight into how this area of research could be carried forward for potential application in the clinic.3, weighs ~ 120 g, and is highly vascularized, storing 20–30% of total blood volume [The spleen performs a number of functions that are facilitated by its structural components. The spleen varies in size between individuals, but it is typically ~ 10 × 6 × 3 cmd volume . Larger-d volume , 26. AltFunctionally, the red pulp plays a role in immunity that is distinct from that of the white pulp . LeukocyThe relationship between the spleen and heart was first identified by Rein et al. in 1949 , who shoSince these initial observations, the spleen has been further shown to influence the function of the heart, providing further evidence of the cardiosplenic axis. A key observation is that splenic contraction and volume reduction counteract tissue hypoperfusion. Splenic contraction is mediated by sympathetic control and is intended to compensate for systemic oxygen demand. This is associated with various states, such as hypovolemic shock , 36, sepAcute myocardial infarction is one example of a cardiovascular event that increases sympathetic nervous system activity, which mobilizes progenitor cells from the bone marrow, in turn boosting monocyte production in the spleen . Beta-adFurther links between the spleen and the heart have also been noted. For example, positive inotropy has been reported in isolated cardiac preparations when exposed to splenic extracts . Moreove.The spleen is an important reservoir for the deployment of leukocytes to tissue sites of injury and inflammation , 47. In In mice, the cancer therapeutic doxorubicin disrupted immunometabolic pathways, triggered by persistent inflammation in the spleen and heart . SpecifiLike the spleen, the myocardium has its own resident macrophages; however, unlike spleen-derived macrophages, cardiac macrophages are minimally inflammatory and promote angiogenesis and tissue repair . During It is important to note that the role of macrophages in fibrosis is not well understood owing to conflicting evidence. The conflicting observations may be due to differences in gene expression between different macrophage populations. For example, Haider et al.  showed tIn addition to its function in immunity, the spleen also plays a role in hemodynamics. A previous study has shown that splenic size increases in patients with advanced heart failure after left ventricular assist device (LVAD) implantation . AnotherFujinami et al.  observedA recent study has shown that splenic volume is correlated with right arterial pressure and pulmonary capillary wedge pressure . Moreove2 may be hemoglobin concentration [The most widely known function of the spleen is to provide macrophages that remove old or damaged erythrocytes and platelets from the circulation for subsequent degradation. Erythrocyte-derived hemoglobin is degraded into heme and globin, and iron molecules within the heme are subsequently recycled for the synthesis of de novo hemoglobin molecules. The spleen also stores erythrocytes. Hypoxia and exercise separately trigger spleen contraction, resulting in the release of stored erythrocytes . A studyntration . Anemia ntration –71 have In this paper, we have reviewed the available evidence on the cardiosplenic axis and the splenic manifestations that have been observed in heart failure to date. However, it is important that a consensus be reached on how these parameters can be measured clinically and how they may be useful to examine heart failure prognosis.Of note, it is necessary to identify novel biomarkers to predict prognosis in patients with heart failure, for whom predicting risk is often challenging, and to provide a personalized strategy with precision medicine to improve outcomes.The cardiosplenic axis represents a reservoir of immunological and hemodynamic processes that play a central pathophysiological role in heart failure. Therefore, it is our opinion that the spleen may be a useful tool to predict prognosis in patients with heart failure. At the macroscopic level, the size, volume, stiffness, and function of the spleen should be considered. At the microscopic level, there is a need to explore and develop molecular and cellular markers that are specific to the spleen, particularly those that can be evaluated by simple practical analyses, such as blood tests. Some of these factors are outlined in more detail below.There is no established method to clinically assess spleen function in patients with heart failure at present; however, we speculate that certain immune cell types, such as proinflammatory C–C chemokine receptor 2 (CCR2)-positive macrophages, CD4 + T helper  cells, regulatory T cells, and CD8 + T cells, might be useful to predict heart failure prognosis. As explained by Prabhu , cardiacFurthermore, when considering which factors might be most useful for prognostic prediction in patients with heart failure, Halade et al.  showed tAs described earlier, in patients with advanced heart failure, splenic size increases after LVAD implantation, and a significant negative correlation has been observed between splenic volume and systemic vascular resistance , which iIn terms of imaging approaches to assess spleen size and volume, computed tomography of the spleen could be used to monitor at-risk patients, although this method is relatively expensive and uses ionizing radiation. Ultrasound can also be used to measure spleen size, is more widely available than computed tomography, and does not use radiation, thus avoiding any potential damage from repeated measurements . DopplerA summary of the future perspectives and directions that should be taken to address the current knowledge gaps is shown in Table First, it has been hypothesized that all organs possess endocrine function and may therefore contribute to whole-body homeostasis . For exaSecond, much of the existing evidence demonstrating the role of the spleen in heart failure is from animal studies; thus, further studies should be conducted in humans to clarify the relevance of the cardiosplenic axis and to identify potentially useful spleen-related prognostic predictors for heart failure.Third, the physiological mechanisms of the role of the spleen in heart failure remain unclear, and the relationships between physiological indices and cellular and molecular markers specific to the spleen have not yet been clarified. Further knowledge in this area would be useful for the potential application of the spleen as a tool for prognostic prediction in heart failure.Fourth, it has been emphasized that heart failure varies in etiology and pathology and can be highly variable; hence, splenic involvement may depend on the cause of heart failure. Therefore, its assessment may only be relevant for specific subpopulations of patients. If the cardiosplenic axis is demonstrated to play a definitive role in heart failure in humans, research to identify subpopulations of patients in whom the spleen may be a useful prognostic tool will be a valuable step toward precision medicine.Finally, it has been established that prognostic models for heart failure are more effective than individual clinical variables alone . Thus, iIn this study, we reviewed evidence of the interplay between the heart and spleen, termed the cardiosplenic axis, in cardiovascular disease and heart failure. The spleen forms a major part of the immune system, and evidence suggests a role for the spleen in immune cell mobilization as a mediator of inflammation and cardiac remodeling. Other evidence suggests a relationship between splenic size and systemic blood volume regulation and hemodynamics. Most studies have been conducted in animals; thus, future studies in humans should aid our understanding of the importance of the cardiosplenic axis and drawing of definitive links between specific splenic measurements and different heart failure manifestations, including hemodynamic changes, inflammation, fibrosis, and remodeling. It should also be determined whether splenic measurements have variable importance between different heart failure classes and etiologies. These contributions will represent a step forward in understanding the usefulness of the spleen as a prognostic predictor in heart failure.


Presence is a therapeutic skill that has a healing effect not only on the mental healthcare user but also the nurse. There was a need to explore nurses’ perceptions on factors that limit presence, especially in a public psychiatric hospital in a rural province such as North West, South Africa, where there are limited resources and nurses need to rely heavily on their therapeutic use of self.To report on nurses’ perceptions of factors limiting presence when working in a public psychiatric hospital.A qualitative descriptive inquiry was applied, with purposive sampling. Semistructured individual interviews were held with 10 nurses. Thematic data analysis was applied.Intrapersonal factors that were found to limit presence arose from the view that mental healthcare users (MHUs) are difficult to engage with; the tendency to view ‘good care’ primarily as physical care with limited insight into presence was also recognised. Interpersonal and transpersonal factors related to difficulties in communicating with MHUs and in the work environment.Addressing factors that limit presence were found to require courage, the overcoming of interpersonal distance and a transformational process.This article contributes important insights that can be used by nurse leaders to promote the practice of presence to improve the quality of psychiatric nursing care in developing contexts, such as a rural province in South Africa. Taking into consideration that the practice of presence is a healing experience for both the mental healthcare user (MHU) and the nurse – characterised by fully and holistically being there for the other, attentiveness, comfort, doing for and competent performance of nursing procedures  nurses and professional nurses who were registered with the South African Nursing Council. Perceptions were defined for this study as ‘views’, ‘understanding’ and ‘opinions’ . Permission was obtained from the North West Department of Health and from the management of the psychiatric hospital where the research took place. This approach ensured that the psychiatric hospital’s management and the participants were involved as collaborative partners. Voluntary, written informed consent was obtained from participants after a recruitment process through which fair selection was ensured. All research team members signed confidentiality agreements. The social value of this research is that the results, conclusions and recommendations add to the body of knowledge in psychiatric nursing and provide information on factors that hinder nurses working in a public psychiatric hospital to practise presence, in order that such factors can be addressed.n = 8) participated.The demographic information of the sample  is as foThree themes and five related subthemes emerged, as indicated in This theme relates to the intrapersonal dimension of presence, namely the participants’ view of MHUs. Participants perceived MHUs as being difficult to engage with because they demonstrate aggressive, impulsive, uncooperative and manipulative behaviours and have limited understanding. Further, the participants perceived MHUs as being dangerous, and the participants felt unsafe around them. They maintained that MHUs need constant supervision. One of the participants felt they are expected to advocate for the MHUs, and when they are not appreciated for this advocacy role but rather blamed by the MHU and their families, their practice of presence is limited.The following quotes support this finding:‘They can be naughty, aggressive. I mean aggressive patient with aggressive behaviour as we know mental healthcare users may experience hallucinations, delusions and they can be aggressive without knowing that they are aggressive towards a person.’ ‘Psychiatric patient they want twenty-four-seven observation. All the time because sometime you must make sure you are observing them, they are like small children from school, those that are school you have to say do this, do this always.’ ‘And remember I am the one who is supposed to be the advocate of the patient. If you are not appreciated, that also will put down the morale and then it limits the presence.’ Three subthemes emerged. These themes relate to the interpersonal and transpersonal aspects of presence, specifically factors that limit knowing the MHUs and their needs.The psychiatric nurse obtains information about the mental healthcare users from different sources: Participants interpreted this question to be related to the assessment of the MHUs. They shared that they obtained information mainly from consulting patient files, having discussions with family members and members of the multidisciplinary team. To a lesser extent, they asked the MHUs themselves.The following quotes support this finding:‘Collateral information from the family.’ ‘Proper history from the person and maybe they are unable to, you know, to articulate or to tell their problem, or alternatively their relatives.’ Perceptions of factors preventing nurses from knowing mental healthcare users: Participants felt that MHUs withhold information or provide incorrect information. Language barriers, inadequate history taking and a lack of time to provide individual attention were also seen as limiting factors.The following quotes illustrate this finding:‘The patient is not open enough, so she does not want to disclose.’ ‘Because you will not reach all of them, you will not be able to interview all the patients that are there to know them.’ Perceptions on factors impeding nurses from knowing the needs of mental healthcare users: Participants perceived shortages of staff and communication difficulties as major limitations. Participants elaborated that staff shortages made it challenging to know MHUs’ needs. Frequent re-admissions take up much of the nurses’ time and limit nurses’ interaction with patients in the ward.‘When patients are not able to talk their problems, we wouldn’t know about their needs are because patients won’t tell or say anything.’ ‘Because sometimes, they can be in the situation that is not right. Then by the time that you see that he is right after that then you call and ask him what is happening, and he will tell you this and that is happening according to the questions that you that you be asking him. Because you can’t talk to somebody when she/he is confused, they don’t listen to you.’ ‘Even the shortage of staff can make us not being able to know all the patients. Er, because you will not reach all of them, you will not be able to interview all the patients that are there to know them.’ A third theme was identified, and two subthemes emerged. The first subtheme resembles specific interpersonal and transpersonal factors limiting presence, namely factors limiting the provision of good care. The second subtheme implied specific intrapersonal factors that limit presence, namely perceptions on what nurses need to provide good care to MHUs.Perceptions on factors preventing the nurse from providing good care: Participants perceived that ‘good care’ is care that is provided round the clock and that provides for the basic needs of MHUs. However, poor infrastructure and limited resources were reported to limit the nurses in their ability to provide for the basic needs of MHUs. This made the participants feel that they are not providing good physical care to the MHUs. In this regard, they experienced that members of the management team did not provide adequate support and they consequently felt demotivated and, as a result, demonstrated a relatively low level of performance.‘Good care also it involves like for example, we have been trying for a very long time to be assisted teeth brushes, razors to cut their hair when we are sitting for grooming, we need all these things like during weekend we make them beautiful and then cut their hair and so on and so on, they are not there.’ ‘We are giving care, we are taking care of mentally, physically, and psychiatrically maybe there is a shortage, there is no hot water.’ ‘You know there is one thing I realised, we got managers who stay in the offices, they don’t know what is happening in the wards. They just stay in the offices, they don’t even know if you can ask him/her about the patients that are admitted in the wards, he/she cannot tell you, they don’t know anything because they just stay in the office.’ Perceptions on what nurses need to provide good care to mental healthcare users: Participants perceived a safe environment, protective clothing and adequate security as their most important needs to provide good care. They further expressed the need for a good remuneration package and substantial support from management. They viewed their physical health and mental strengths as imperative in providing good care. They further expressed the need for debriefing and counselling, as well as the need for empowerment through training.The description is supported by the following quotes:‘Provide clothes, provide hot water to the patients, give us protective clothing here. We work with our clothes, when I get here I have to take this shirt off and wear something that can protect me here in the hospital, nothing you don’t get it nowhere. … The security is not enough.’ ‘Mm, me my needs is to further my studies so that I can know how to handle these psych patients.’ ‘We need the recognition; we need to be recognised in terms of the skills in terms of you as a human being.’ ‘I think good managers laugh, one that encourages. … I think that (when the managers) see you doing something that is good they don’t encourage you to keep on doing it, because they keep quiet.’ The results describe the perceptions of nurses working at a public psychiatric hospital, revealing factors limiting presence. Three themes with five related subthemes emerged. The first theme represents a particular intrapersonal factor that limits presence, namely the perceptions of participants of MHUs as being difficult to engage with. The second theme with three subthemes revealed specific interpersonal and transpersonal factors that limit presence, namely factors limiting knowing the MHUs and their needs. The final theme with two subthemes is about good care and also contains interpersonal and transpersonal, as well as intrapersonal, factors that limit presence. Specific interpersonal and transpersonal factors limiting presence include the view that good care entails mostly basic, physical care. It also entailed views on factors that limited them to provide good care, namely limited infrastructure and poor resources and a lack of support from management. Perceptions on what nurses needed to be able to provide good care to MHUs pointed towards intrapersonal factors that limit presence and included the need for safety and security, a solid remuneration package, support and training.The discussion of the key findings follows the structure of intrapersonal, interpersonal and transpersonal factors that limit presence.From the findings, it can be concluded that an intrapersonal factor that limits presence is the perception of MHUs as being difficult to engage with. Vincze, Fredriksson and Wiklund Gustin :149 alsohow nurses apply themselves as an available resource; for example, this includes listening actively to the concerns of the patient to identify the needs of the patient (Petriprin Another possible intrapersonal factor that limits presence is view of the participants that good care mostly entails physical care, the availability of infrastructure and physical resources. The participants did not emphasise a connection with and a deep understanding of MHUs’ experiences as part of ‘good care’. As explained in Peplau’s nursing theory (Petriprin Furthermore, interpersonal and transpersonal factors that limit the presence of caregivers relate to difficulties in communicating with MHUs and difficulties in the work environment. Literature confirms that communication barriers exist in mental healthcare (Gudde, Olso & Whittington Regarding the work environment, it is evident that the study participants highlighted the need for external help from management and additional resources to improve care; they further emphasised that management was not focused on building the relevant skills of carers. South African and international literature confirm that the lack of resources, large amounts of work and frequent admissions in public psychiatric hospitals can indeed increase workload, burnout, frustration, anxiety and a sense of not being cared for (Sobekwa & Arunachallam The strength of the study is that the results revealed intrapersonal, interpersonal and transpersonal factors that limit presence, contributing to the body of knowledge in this field of nursing. The article provides important insights that nurse leaders in resource-poor settings can use to address factors that limit presence.This study is limited to the views of nurses working at a public psychiatric hospital in the North West province of South Africa. However, the comparison of the findings of this research with existing literature, the thick description of the research process and the resulting discussion and recommendations for nursing open opportunities for wider application.Nurses working in psychiatric hospitals need to be encouraged, supported and empowered to negotiate meeting their own intrapersonal needs while providing good care through presence. This is necessary for providing for the needs of MHUs and should be achieved through supportive communication and building a trusting relationship with them. The intrapersonal, interpersonal and transpersonal dimensions of presence should be acknowledged and used as a framework to prepare nurses to practise presence. In the intrapersonal dimension, nurses should be encouraged to use their strengths, such as advocating for MHUs and involving the patients’ relatives. They should be made aware of the value of a presence approach in providing good care to MHUs, as well as overcoming barriers in connecting with and attuning to the needs of MHUs.Self-care and self-awareness programmes should be made available to nurses so that they can resolve their own inner needs, do introspection and reflect on their perception of ‘good care’ and MHUs as human beings. Regarding the interpersonal and transpersonal dimensions, training programmes on providing nursing care through presence should be offered, and nurses should be guided in the therapeutic use of the self and in building trusting relationships to connect with and attune to MHUs and gain an understanding of their needs. Nurses should be guided in using their strengths and presence to build relationships with their supervisors and managers so that management is aware of staff needs. Nurses should further learn to negotiate for their workplace-related needs to be met, including needs for safety and an improved working environment.Nurses should be acknowledged for their efforts to do the best they can to provide nursing care in difficult work circumstances. This can be done through relational management, where management builds relationships with nurses and obtains an understanding of nurses’ perceptions and needs. This acknowledgement can also be given through initiatives such as team-building meetings and meetings to convey appreciation and acknowledgement. Management can support nurses to find meaning in their work despite their circumstances, to be resourceful in creating a better environment for themselves and to communicate with management effectively to make their needs known. Further research should focus on MHUs’ views and needs regarding presence and good care, as well as the perceptions of management teams at psychiatric hospitals on presence, good care and factors limiting presence.The purpose of this study was to explore and describe the perceptions of nurses working in a public psychiatric hospital in the North West province of South Africa regarding factors that limit presence. The results of the study shine a light on the intrapersonal, interpersonal and transpersonal factors that limit presence. Nurses’ perception of who MHUs are; a one-sided focus on physical care as ‘good care’; limited communication between the nurse and the MHU; the need for improved infrastructure and resources; a more supportive work environment; and the need for training, including training on presence, are factors that limit presence. These findings inform the direction that needs to be taken to eliminate the factors that limit presence, in order that the practice of presence can be enhanced. Presence has a healing effect and can improve the quality of care to MHUs.


Global technological progress has generated alternatives for psychological assistance, both for the evaluation and for the treatment of different emotional disorders. Evidence suggests that Internet-based treatments are effective for the treatment of anxiety and depression disorders. However, in Latin America online treatments are still scarce compared to developed countries and have similar problems as developed countries, such as high dropout rate. One possible solution to help decrease the dropout rate is to design and develop online interventions based on the needs and characteristics of the users. The user-centered design (UCD) is a fundamental concept to develop successful online interventions. The objective of this article is to provide a perspective overview on how UCD could improve the impact of self-applied psychological interventions in low- or middle-income countries in Latin America; however this proposal can also be applied in low- and middle-income countries in other regions of the world. The literature on UCD has demonstrated its efficacy when properly applied in online interventions; however, it is not common to see how this methodology has been applied in research in online interventions, and regarding Latin America, this is even more scarce with a very limited number of articles implementing the principles of UCD. Before the Coronavirus SARS-CoV-2 COVID-19) pandemic, the prevalence of anxiety and depressive disorders worldwide were already a matter of concern for international governments. According to the WHO, an approximate estimate of 322 million people suffered from depression and 264 million from anxiety disorders, with an increase of 18.4 and 14.9% respectively from 2005 to 2015 9 pandemi, and alcHowever, a vast majority of individuals in low- and middle-income countries do not receive psychological treatment for mental health disorders, mostly because it is not perceived as necessary. This could be related to a lack of health literacy, and mostly due to lack of infrastructure available to offer psychological treatment to the population . AccordiGlobal technological progress has generated alternatives for psychological assistance, both for the evaluation and for the treatment of different emotional disorders. Evidence suggests that Internet-based treatments are effective for the treatment of anxiety and depression disorders –14. LikeFrom the framework of Evidence-Based Psychotherapy, on the one hand, it is recommended to rigorously analyze the available scientific evidence to measure the efficacy of an intervention, that is, the therapeutic changes produced in controlled clinical trials. On the other hand, to measure effectiveness, it is suggested to investigate the generalization of the results of the intervention to the particular and cultural context of the target population; this is known as Evidence-Based Practice (EBP) and involves the integration of research knowledge with the clinical experience of the therapist and the characteristics, opinions, preferences, interests, values, context, and culture of the patient/user . Thus, iRegarding the efficacy of technological-based psychological interventions, specifically self-applied interventions, they have a series of challenges that involve the interaction of a great variety of factors at different systemic levels . Howeveradherence as the extent to which individuals experience the content of internet intervention, and dropout describes an individual who fails to complete the research trial protocol associated with an internet intervention, and thus does not complete the trial assessments  is a fundamental concept to develop successful online interventions and decrease the drop-out rates. According to Abras et al. , “UCD isWhen planning the design process, it is fundamental to talk about one of the most used design processes, the Double Diamond .The double diamond design process illustrates how the design process goes from thinking and possibilities abroad as possible to situations that are reduced and are specially focused on different objectives .The double diamond phases are detailed in: 1) Discover, where the start of a project is a period of discovery, gathering inspiration and insights, identifying user needs and developing initial ideas, 2) Define, the second quarter represents the definition phase, in which designers try to make sense of all the possibilities identified in the Discover phase, 3) Develop, the third quarter marks a period of development where solutions are created, prototyped, tested, and iterated. This process of trial and error helps designers to improve and refine their ideas and 4) Deliver, the final quarter of the double diamond model is the Deliver phase, where the resulting product or service is finalized and launched. The key activities and objectives during this stage are the following: final testing, approval and launch, targets, evaluation, and feedback loops  (p7). ThRegarding Latin America, the UCD is not commonly mentioned or indicated in online interventions, with only few exceptions such as Antelo et al. , where tInCharge Health. The study of UCD and attrition reduction is also being applied in other contexts such as web-Based Psychological Intervention for Patients with Myocardial Infarction with Non-obstructive Coronary Arteries, where the researchers designed a UCD web-based psychological 9-step program focusing on stress, worry, and valued action for persons with such health conditions, and among the several objectives of this tool was also to reduce the attrition of the participants on this intervention (There are several developments of digital mental health tools that are user-centered for several purposes. For example, the low-intensity intervention for Syrian refugees , part ofrvention .On the other hand, there are currently studies trying to implement interventions based on HCD in low-resource communities ; howeverThe objective of this article was to provide a perspective overview on how user-centered design could improve the impact of self-applied psychological interventions in low- or middle-income countries in Latin America, however this proposal can also be applied in low- and middle-income countries in other regions of the world.The literature is still being gathered, but there are excellent examples of how UCD can be implemented in online interventions , 34–43. This manuscript has certain limitations that should be considered. For example, the literature on UCD has demonstrated its efficacy when properly applied in online interventions, however it is not common to see how this methodology has been applied in research in online interventions, and regarding Latin America this is even more scarce with a very limited number of articles implementing the principles of UCD and to the best of the knowledge of the authors, none clearly stating to be implementing the double diamond model. More research needs to be conducted to provide evidence-based treatments to the population of Latin America and the Caribbean.In this regard, this article shows a perspective based on the review of the existing literature, it is suggested for future studies to carry out a meta-analysis on the effectiveness of the interventions and their relationship with the design centered on the user experience in the context of Latin America.The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding author/s.All authors listed have made a substantial, direct, and intellectual contribution to the work and approved it for publication.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.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.


The Middle East respiratory syndrome coronavirus (MERS-CoV) is a zoonotic pathogen that can transmit from dromedary camels to humans, causing severe pneumonia, with a 35% mortality rate. Vaccine candidates have been developed and tested in mice, camels, and humans. Previously, we developed a vaccine based on the modified vaccinia virus Ankara (MVA) viral vector, encoding a full-length spike protein of MERS-CoV, MVA-MERS. Here, we report the immunogenicity of high-dose MVA-MERS in prime–boost vaccinations in mice and camels. Methods: Three groups of mice were immunised with MVA wild-type (MVA-wt) and MVA-MERS (MVA-wt/MVA-MERS), MVA-MERS/MVA-wt, or MVA-MERS/MVA-MERS. Camels were immunised with two doses of PBS, MVA-wt, or MVA-MERS. Antibody (Ab) responses were evaluated using ELISA and MERS pseudovirus neutralisation assays. Results: Two high doses of MVA-MERS induced strong Ab responses in both mice and camels, including neutralising antibodies. Anti-MVA Ab responses did not affect the immune responses to the vaccine antigen (MERS-CoV spike). Conclusions: MVA-MERS vaccine, administered in a homologous prime–boost regimen, induced high levels of neutralising anti-MERS-CoV antibodies in mice and camels. This could be considered for further development and evaluation as a dromedary vaccine to reduce MERS-CoV transmission to humans.  Plasmodium Falciparum, hepatitis C virus, Ebola virus (EBOV), severe acute respiratory syndrome coronavirus (SARS-CoV), the Middle East respiratory syndrome coronavirus (MERS-CoV), and recently SARS-CoV-2 [Modified vaccinia virus Ankara (MVA) is a non-replicating poxvirus that has been used as a viral vector for vaccines against cancer and infectious diseases ,2. MVA-bRS-CoV-2 . These vRS-CoV-2 . MVA hasRS-CoV-2 ,6. In adRS-CoV-2 ,16,17,18+ and CD8+ T lymphocytes via MHC-I and MHC-II activation pathways. These pathways are induced by antigen-presenting cells, including dendritic cells (DCs). DCs are either infected by MVA or engulf proteins from MVA-infected cells. Above all, MVA is a strong stimulator of innate immune responses via the activation of TLR9 and TLR2-TLR6, MDA-5, and NALP3 inflammasome that leads to the expression of type I IFN [+ T cells to the site of inoculation , which is an advantage over the use of the parental-replicating vaccinia virus (VACV) [MVA infects a wide range of mammalian cells but does not replicate, leading to the activation of CD4pe I IFN ,20,21. Ms (VACV) ,23. Thers (VACV) . Previously, MVA has been utilised to develop vaccines against the Middle East respiratory syndrome coronavirus (MERS-CoV) and tested in mice, camels, and humans ,29,30,317 pfu (plaque forming unit) of MVA-MERS vaccine intramuscularly, as compared to 1 × 106 in the previous study. In addition, this study allowed for evaluating the effect of anti-MVA vector immunity in the mouse model.Previously, we have reported the immunogenicity of an MVA-based vaccine for MERS-CoV (MVA-MERS) . The vac9 pfu.Second, we evaluated high-dose MVA-MERS immunisation in dromedary camels. Previously, another MVA-based MERS vaccine was tested in dromedary camels and showed that a simultaneous intramuscular and internasal immunisation, both administered as prime and then as boost, lead to high anti-MERS and anti-MVA antibody titres following that stringent regimen. Given the difficult practicality of applying this approach for camel vaccination in the field for approved vaccines, our study evaluated only intramuscular immunisation, administered in a prime–boost regimen with a high dose of 1 × 10This study represents an investigation of increasing the doses of MVA-MERS vaccines, compared with those reported in previous studies, in experimental mice and camels and investigates vaccine anti-vector immunity in the mouse model.7 pfu of MVA; the mice were immunised in prime–boost regimens at Day 0 and Day 28 as follows: Group 1: MVA wild-type (MVA-wt) prime and MVA-MERS boost (MVA-wt/MVA-MERS); Group 2: MVA-MERS/MVA-wt; and Group 3: MVA-MERS/MVA-MERS. In the camel study, 3 groups of female dromedary camels, aged 15 to 18 months were intramuscularly (i.m.) immunised in the upper leg  with a total of 1 × 109 pfu of MVA; the camels were immunised in prime–boost regimens at Day 0 and Day 28 as follows: Group 1 (n = 2): PBS/PBS, Group 2 (n = 2): MVA-wt/MVA-wt; Group 3 (n = 4): MVA-MERS/MVA-MERS (MVA-MERS vaccine was constructed with the full-length spike protein from isolate (GenBank: KJ650098.1), the transgene had an upstream tPA sequence and was driven by the poxviral promoter F11, produced by The Jenner Institute, the University of Oxford as previously described . In the MVA-MERS .For immunisation, mice were briefly anaesthetised, using vaporised IsoFloH. Camels were physically constrained, kept in special pens, and monitored throughout the study as previously described . Serum sEndpoint titres of serum antibodies were determined using an in-house indirect ELISA as previously described . Briefly+ cells were subtracted from the cellular frequencies of the tested restimulated samples. IFN-γ secreting splenocytes were reported as the average of spot forming cells (SFCs) per million splenocytes for each sample.Mouse splenocytes were harvested for analysis with IFN-γ ELISpot as previously described , using r50 neutralisation titres were calculated for each serum sample using the GraphPad Prism software.MERS pseudotyped viral particles (MERSpp) were produced in HEK293T cells and titrated using Huh7.5 cells, as previously described ,45. In bAll raw data were reading signals collected from ELISA microplate readers for antibody responses; an ELISpot counter for mouse ex vivo IFN-γ ELISpot assays; or a luminometer for luciferase lights as readouts of the MERSpp neutralisation assay. Data were collected in a Microsoft Excel spreadsheet and were placed and analysed using the GraphPad Prism software, Version 9.3.1.  This software was used to perform all statistical analyses.Serum samples from three groups of mice, namely Group 1: MVA-wt/MVA-MERS; Group 2: MVA-MERS/ MVA-wt; and Group 3: MVA-MERS/MVA-MERS, were evaluated at 0, 28, and 56 d.p.i for humoral immune responses. Strong anti-MERS spike antibody (Ab) responses were induced at 28 d.p.i., post-prime, in Groups 2 and 3. The level of Abs was enhanced after the boost (56 d.p.i) in Group 3. In Group 2, in which mice were primed with MVA-MERS and boosted with MVA-wt, no significant change in the level of Ab responses was observed. However, comparing Groups 1 to 3, primed with MVA-wt and MVA-MERS, respectively, and boosted both with MVA-MERS, the anti-MERS-CoV spike Ab responses increased in both groups. Although using MVA with the same antigen (spike protein) for prime–boost enhanced the antigen-specific Ab responses (Group 3), priming with MVA-wt and boosting with MVA-MERS in Group 1 showed a high increase in S-specific Ab responses A. ComparOn Day 56 post-immunisation, the IFN-γ-producing T cells, as measured by spleen ex vivo ELISpot, showed strong responses in the MVA-MERS prime–boost regimen (Group 3). There was an insignificant increase in the IFN-γ T-cell responses in Group 2, compared with Group 1, but this is likely due to the timing of giving MVA-MERS; it was administered at 28 d.p.i for Group 1 and at 0 d.p.i for Group 2. This means there was a one-month difference in assessing the T-cell immune responses in Groups 1 and 2 D. NonethThree groups of MERS-seropositive young camels were immunised in homologous prime–boost regimens, namely Group 1: PBS; Group 2: MVA-wt; and Group 3: MVA-MERS. Serum and nasal swab samples were evaluated at 0, 28, and 56 d.p.i for humoral immune responses. High levels of anti-MERS spike antibody (Ab) responses were observed at 0 d.p.i (pre-immunisation), indicating the level of MERS-CoV seroprevalence in camels. At 28 d.p.i, there was no difference between immunised groups. However, following the boost, at 56 d.p.i, the MVA-MERS vaccine induced higher levels of the anti-MERS-CoV spike Abs A. The neSera from vaccinated mice and camels were utilised to evaluate antibody responses to the vaccine vector, MVA. Regardless of the vaccine-encoded antigen, anti-MVA antibody responses to two doses of MVA were similar in all the groups of either mice or camels A,B. See In this study, an MVA-based vaccine for MERS-CoV, incorporating a full-length spike antigen was tested in a mouse model and in dromedary camels. The vaccine induced high levels of binding and neutralising Abs against the spike, with strong T-cell-mediated immune responses in mice, and high levels of binding antibodies in camels. In mice, the homologous prime–boost vaccination regimen provides evidence that MVA is an efficient viral vector for priming and boosting. The use of MVA-based vaccine in prime–boost immunisation has been shown to be sub-optimal, compared with the use of heterologous prime–boost regimens in which, for example, priming with ChAdOx1-based vaccine and boosting with MVA encoding the same vaccine induced higher neutralising Abs in mouse models . This leOur study attempted to address these concerns and reported that anti-MVA Ab responses post-prime were similar to post-boost levels, in both types of animals. This indicates that anti-MVA-induced immune responses at prime did not affect the anti-MERS-CoV spike Ab level, which was boosted to a higher level. MVA-MERS in mice that had MVA-wt induced high levels of anti-spike Ab responses, which indicates that MVA has a strong effect in priming immune responses in animals that already had anti-MVA antibodies. In homologous vaccination regimens of MVA vaccines, the increases in anti-antigen Ab levels are usually lower post-boost than post-prime, which is supported by the current data and previous reports. Most dromedary camels in Saudi Arabia and part of Middle Eastern and African countries are MERS-CoV-seropositive ,51,52,53The MERS-CoV S protein has been the focus for most MERS-CoV vaccine candidates published to date. Several vaccine candidates based on full-length or truncated S protein including virally-vectored, DNA-based, nanoparticle-based or protein-based subunit vaccines have been developed and investigated in experimental animal models and humans by several groups including our group ,61,62,63This study has some limitations, including its lack of a challenge model to evaluate the efficacy of the vaccine. All camels were seropositive for MVA, which requires further analysis. Since these were juvenile camels, it is unlikely that they were exposed to a poxvirus such as camelpox, but they may have maternal anti-poxvirus from exposed mother camels. Since MVA has around 200 proteins, it is also possible that these camels have some Abs for other pathogens that were cross-reactive. Further experiments are required to set up an MVA (or poxvirus)-specific ELISA rather than a whole-virus ELISA.In the lack of a high number of infections in humans, a MERS vaccine in humans may not be properly developed or evaluated. Therefore, MERS-CoV vaccines for camels are believed to serve as a one-health intervention where a vaccine for camels could reduce the virus circulation in camels in endemic countries such as Saudi Arabia, leading to a reduction in spill-over infections to humans. This study builds on the growing evidence that camel MERS vaccination could be achieved using an MVA viral vector. An MVA-based MERS vaccine was administered to mice and induced strong neutralising Abs and T-cell responses. The vaccine induced strong neutralising Abs in juvenile camels. This vaccine can be further developed to evaluate its durable immunogenicity and efficacy as a one-health vaccine for MERS-CoV.