Following the disease outbreak in the western district of Kagadi on 20A household survey using a semi-structured questionnaire was conducted in 399 households in the two sub counties of Bwikara and Ruteete, Kagadi district. A focus group discussion with members of the community was conducted as well as key informant interviews with at-risk individuals.Descriptive and inferential analysis was performed using STATA version 13 . Comparative analysis of the data from the two sub counties was also performed using cross tabulations in STATA, between each independent variable and the subcounty variable. The descriptive and comparative statistics used were minimum, mean and maximum values, standard deviations, frequencies, percentages, chi square values and t-statistics. A chi-square test was then employed on each tabulation, to determine whether there was an association between the two categorical variables or not. The test was set at an alpha level of 0.05, and where the p-value was less than or equal to the alpha value, we concluded that the 2 variables were associated.Although majority of the respondents believed in the existence of the disease, only 12.8% had knowledge of prevention measures against CCHF. 67.2% of the respondents reported regular interaction with ticks during routine farm operations and they employed tick control measures on their farms. Although the respondents believe the disease is fatal, almost all of them (99%) would welcome a CCHF survivor back into the community. 95.2% of the respondents actively attended to animals but only 25.8% participated in slaughtering animals.Qualitatively, the technical informants had knowledge about CCHF but non technical informants hardly knew about the disease. Limited funding appropriated for local governments, as well as limited engagement in One health activities were some of the barriers highlighted towards the infection prevention and control activities.Most of the focus group discussion participants knew about the disease, but lacked knowledge on its transmission and prevention. Limited access to personal protective equipment and high exposure to tick-prevalent areas when slaughtering and grazing animals respectively, were the major challenges highlighted.Knowledge on CCHF among majority of the respondents was poor. There is a need for educational programs to increase awareness of CCHF in communities. This awareness should be done by both the community leaders and technical people to ensure the community receives enough knowledge on how to prevent and control the disease. To ensure effectiveness of these programs a One health approach should be adopted to implement prevention and control strategies. Crimean Congo hemorrhagic fever causes widespread outbreaks in areas where the principal tick vector is found. In Uganda, several outbreaks have been reported in recent years and this is attributed to silent circulation of the causative agent in ticks and animals which later spills to humans. Unfortunately, there is no vaccine for the disease and the only available treatment option is primarily supportive. Data to inform design of interventions that can prevent the emergence and spread of the disease in high-risk areas is limited. We, therefore, decided to investigate, knowledge, attitudes, practices and risk of the disease in Kagadi district where an outbreak was confirmed in 2020. We found low levels of knowledge on how to prevent the disease although most people in this area participated in activities that put them at a risk of contracting the disease. Funding to support prevention and control of the disease in communities is limited. Additionally, there was poor multi-disciplinary coordination during response to the disease outbreak. This study, therefore, recommends an educational program to sensitize communities on the disease using a multi-disciplinary approach where all related sectors are involved in prevention and control activities. Orthonairovirus of the Nairoviridae family [Crimean Congo hemorrhagic fever (CCHF) is a zoonotic tick-borne viral infection, geographically widespread with many cases occurring in sub-Saharan Africa. It is caused by Crimean Congo hemorrhagic fever virus, RNA e family ixodid tick or crushing an infected tick with bare skin. In Uganda, ixodid ticks, including the Hyalomma ticks , have been reported [This disease is transmitted by a bite from an infected reported  TransmisHyalomma tick populations. There is no vaccine for the disease and the available therapeutic interventions are restricted to treating symptoms.Although CCHF affects animals, they don’t show any clinical signs. However, about 20% of humans infected with the virus exhibit clinically fatal illness . In humaBeyond the detected cases, the knowledge, attitudes, and practices of at-risk individuals in the areas reporting the CCHF outbreaks are not well understood. Thus, data to inform public health interventions in the affected communities is limited. Although a limited number of “knowledge, attitudes and practices” (KAP) studies have been conducted in Asia, there are no published CCHF studies in Africa and Uganda specifically, although the disease continues to pose a significant public health threat to the region.This “knowledge, attitudes and practices” (KAP)/ risk study aimed at providing baseline data for further assessments and help in strengthening the behavioral and communication interventions on the response of CCHF and other related emerging infections. This study identified knowledge gaps and at-risk behaviors related to CCHF.Specifically, this study set out to:Determine the level of knowledge, attitudes, and awareness on CCHF in Kagadi district.Identify risks for transmission of CCHF in Kagadi district.Determine the current practices for prevention and control of CCHF in Kagadi district.This study was undertaken as part of the Arboviral infection study (AFI) approved by the ethics review committee at the College of Veterinary Medicine, Animal Resources and Biosecurity of Makerere University, Kampala, Uganda (Reference Number: SVARREC/20/20l8) and by the Uganda National Council for Science and Technology (Reference Number: HS 2485). Informed written consent was obtained from all study participants before they were enrolled into the study.. It is bordered by Ntoroko district to the west, Hoima to the north, Kibaale to the east and Kyenjojo to the south. The district is estimated to have a population of 459,700 people and 69% of the inhabitants live in rural communities where the main economic activity is farming [This study was conducted in Bwikara and Ruteete sub counties in Kagadi district st January 2020. He had developed fever on 7th January 2020 and self-medicated for malaria without any response. There was no history of contact with meat. The fever progressed into generalized body weakness, abdominal pain and two weeks later, he started vomiting and urinating blood as well as bleeding from the nose. He was then rushed to Kagadi hospital, put under isolation and UVRI was informed. Fortunately, the patient was treated, and he recovered.This district was selected for this study because of the CCHF outbreak that occurred in 2020 . It was This study employed a cross-sectional design (between July and December 2021) to collect information from stakeholders along the livestock value chain in Kagadi district. A semi-structured questionnaire was designed by the researchers and used to collect data from farmers within the sub counties of Bwikara and Ruteete. Key informant interviews were conducted to collect data from a policy maker (district production officer), veterinarians , a laboratory worker, a slaughterhouse worker, a retail meat trader, and a cattle trader.Additionally, a focus group discussion (FGD) was conducted in July 2021 with participants from Ruteete and Bwikara sub counties. The FGD consisted of 8 participants from the 2 sub counties, and it collected data on knowledge practices, attitudes as well as risks for Crimean Congo hemorrhagic fever emergence and spread.In this study, the population consisted of all livestock keeping households in Kagadi district. The sample size was calculated based on an alpha of 0.05 and beta of 0.2 using the formula N = (z2 × s 2)/d2, where the z value is 1.96 at a confidence interval of 0.95%, s shows the standard deviation equal to 0.05, and d represents the extent of accuracy considered as 0.06. The obtained sample size was 267 farms. However, a total of 399 households were recruited to cater for any errors in data collected since the study was conducted during the pandemic when training of research assistants was prohibited and there was a number of challenges anticipated during the data collection exercise. A questionnaire tool uploaded onto ODK software was used to collect data from livestock farmers.Regarding attitudes, 90.2% of the respondents believed in the existence of CCHF; and similarly, 99.0% would welcome a CCHF survivor back into the community. Risk perception among respondents towards CCHF was 20.8%, and 52.9% of the respondents would have an interaction with a CCHF survivor.67.2% of the respondents had had an interaction with ticks during the course of their work. 75.2% of the respondents reported having bushes around their farms. Respondents that reported to be drinking raw milk and eating raw meat were very few, at 1% and 0.5% respectively. The results are presented in Six respondents were interviewed in the key informant interviews (KII). One focus group discussion was conducted, and it involved eight participants , the researcher and a research assistant who took notes and recorded the discussion. Consent was obtained to take recordings and photos of participants.The respondents in the KII were the area veterinarians of Ruteete and Bwikara sub counties, a cattle trader, a slaughterhouse worker, a laboratory technician at Kagadi hospital, the district production officer (DPO) and a retail meat seller while the FGD participants were farmers.Results from the focus group discussion and key informant interviews were combined and transcribed to generate transcripts that were manually coded into key themes from which several key sub-themes were identified. Through thematic content analysis, codes were manually grouped to form three categories, which emerged into key themes namely, knowledge, attitudes, and awareness as theme 1, practices for prevention and control as theme 2 and epidemiological risk factors as theme 3. These themes represented majority of the responses and were presented as texts and narrations. This is presented in The laboratory technician, veterinarians and the DPO knew about the disease, its signs, and symptoms as well as its mode of transmission. The signs and symptoms mentioned were fever, vomiting and bleeding from the mouth and nose. These respondents also highlighted that CCHF is closely related to Ebola virus disease (EVD).The DPO and the laboratory technician were part of the taskforce that was set up to control the disease in the 2020 outbreak. However, the area veterinarians were not involved in the prevention and control activities during the outbreak.The DPO informed the interviewer that there is a disaster preparedness commitment at the district to help in management in disease outbreaks. He highlighted that radio sensitizations are always done in the event of disease outbreaks to inform the public and provide guidelines on how to prevent and control the disease. However, there is a problem of delayed release of funds for these activities. He also mentioned that the district veterinary office is facilitated to conduct regular radio sensitizations to raise awareness about emerging diseases, but this is not done. The slaughterhouse worker, retail meat seller and cattle trader had never heard about the disease.The laboratory technician, veterinarians and DPO knew about practices for prevention and control of CCHF. The laboratory technician highlighted the following practices for prevention and control of the disease at the hospital setting, wearing personal protective equipment (PPE) for health care workers when handling CCHF-suspected cases and CCHF laboratory samples and proper burial of deceased victims. He also indicated that hospital staff are always sensitized and trained on how to handle suspect cases.The veterinarians indicated that wearing PPE  while performing routine activities like meat inspection, disease diagnosis, pregnancy diagnosis could help to prevent the spread of the virus from animals to humans. However, they highlighted that there are limited resources to buy these consumables, therefore, they rarely use them. They also highlighted that they often sensitize slaughterhouse workers and retail meat sellers about the dangers of zoonotic diseases and how they can prevent them. However, farmers and cattle traders are not trained about zoonotic diseases because this isn’t a priority area for veterinary extension and no funds are allocated for that.The DPO indicated that prevention and control of emerging infections like CCHF isn’t a priority area for the district. However, in case of an outbreak, there is an emergency fund that is released from the central government to help in disease prevention and control activities. These resources are always limited and therefore, the health sector is prioritized neglecting other important sectors like the environment and veterinary sectors. He also mentioned that one of the major causes of underfunding of CCHF and related diseases is political involvement in the decision making where politically oriented activities are prioritized over prevention and control of emerging diseases. Additionally, periodic surveillance of common diseases is done in the district, however, there is no budget for emerging zoonotic diseases like CCHF. He also mentioned that due to the relatedness of CCHF to Ebola virus disease, the authorities recommend standard operating procedures of Ebola virus disease to manage the outbreak.There is a common practice of wearing gumboots and overalls among retail meat sellers and abattoir workers, but this is not meant for prevention and control of zoonotic diseases, rather it is for ensuring cleanliness and avoiding injury. They also mentioned that wearing gloves while handling meat would repel potential customers because they would assume that the meat is not safe for human consumption.All the participants acknowledged that they are at risk of getting infected with the virus since they are always in close contact with ticks and animals.Participants who control ticks (3 FGD participants) spray their animals with acaricides monthly but other animals including pigs, sheep and goats are not sprayed with acaricides. One of the participants said,Goats only suffer from internal parasites.” “This study was aimed at assessing knowledge, attitude, and practices regarding CCHF Kagadi district, located in southwestern Uganda. This is the first study of its kind in Uganda and Africa; it was conducted in the sub counties of Bwikara (where an outbreak was reported) and Ruteete which was randomly selected.Overall, participants from both sub counties were found to be at high risk for CCHF exposure as most were engaged in animal husbandry activities which increase the risk to CCHF in communities. More specifically, ticks were found to be a common high-risk exposure in the two sub counties as participants reported getting in contact with them during routine activities like grazing animals. This finding is supported by studies by Sharifian et al and GreiMost participants had heard of CCHF before the investigation, which translated into a high knowledge score regarding CCHF.This is in line with findings of Greiner et al which inAlthough the majority of the participants perceived CCHF to be a fatal disease, study findings revealed that prevention measures were not practiced. This is line with findings of Safieyan et al  who repoThis could be attributed to poor knowledge and attitudes towards the disease. Majority of the participants were farmers with low levels of education, which could have contributed to low knowledge levels. A similar finding was reported by Yilmaz et al, therebyMore than a quarter of the participants reported that they slaughter animals at homes without any protective wear like gloves. Additionally, the majority of the respondents reported that their homes are surrounded by bushes, and tick control on the farms is poor. This increases the risk of exposure to the disease. This finding is in line with a study by Ziapour et al  who highStudies on other zoonoses in Uganda, that is, Marbug and Ebola have highlighted that stigma is one of the biggest issues among survivors in communities after the outbreaks . HoweverThis study was carried out amidst the COVID19 pandemic, and this had implications on implementation of the study. Initially, the study was designed to conduct two focus group discussions (FGDs), one in each of the sub counties. However, this was not possible because of the fear of the disease. Mobilization of participants was hard due to reluctance to attend gatherings although the district authorities had allowed the study to conduct the FGDs as long as the number of participants in each group wouldn’t exceed 10. We, therefore, decided to conduct one FGD with participants from both sub counties.Additionally, the researchers had planned to interview three abattoir workers, two policy makers, two veterinarians, three cattle traders and two healthcare workers. However, it was difficult to recruit all these people because of the risk of contracting COVID19 through in-person interactions. The researcher decided to interview one participant from each of these key informant groups (except the veterinarians). The researchers tried to improvise and do phone interviews, but they decided to abandon this method because most of the respondents contacted didn’t answer their phones when called, and those who picked were either occupied with personal tasks or had network challenges. The research team had no prior training on how to conduct phone interviews, and this might have contributed to the failure of this method.This study employed a cross-sectional design, and thus only collected data to generate informative results. The researchers acknowledge that interventional and promotional studies should have been conducted to improve weak practices of participants in the study area.Our study reports low levels of knowledge and awareness on CCHF. There are significant inconsistencies in disease prevention practices among individuals at risk and this highlights a gap in prevention and control of CCHF. A study by Flusin et al  recommenIn addition to sensitization campaigns on media, awareness campaigns on zoonotic diseases like CCHF can also be integrated into the agriculture extension service program where extensionists who are always in contact with at-risk populations can always sensitize farmers, cattle traders, and abattoir workers on good practices for prevention of CCHF and related diseases. Unfortunately, important actors in prevention and control of CCHF like veterinarians were sidelined during the awareness campaigns conducted after the outbreak, and there is no multidisciplinary coordination at administrative level. Therefore, there is a need to adopt and strengthen a muti-disciplinary approach at all levels in the management of CCHF. This kind of approach is relevant to other communities designing and implementing strategies aimed at prevention and control of CCHF and other emerging and re-emerging zoonotic diseases.S1 Questionnaire(PDF)Click here for additional data file.


Although inadequate research support for intensivists can be one major reason of the poor research productivity, no study has investigated the current research environment in critical care medicine in Asia. The objective of this study was to describe Asian academia in critical care from the research environment perspective. We conducted a cross-sectional questionnaire survey targeting all physician members of the Societies of Intensive/Critical Care Medicine in Japan, South Korea, and Singapore. We collected the characteristics of the participants and their affiliated institutions and the research environment. The outcome was the number of peer-reviewed publications. Multivariable logistic regression analyses examined the association between the outcome and the following five research environmental factors . Four hundred ninety responded  to the survey between June 2019 and January 2020. Fifty-five percent worked for a university-affiliated hospital, while 35% worked for a community hospital. Twenty-four percent had secured time for research within their full-time work hours. The multivariable logistic model found that a secured time for the research activities , practicing at a university-affiliated hospital , having clinical experience of 10 years or longer , and working in South Korea  were significantly associated with higher research productivity. Intensivists in the three countries had limited support for their research work. Dedicated time for research was positively associated with the number of research publications. The advancement of clinical medicine in Asian countries has led to an improvement in mortality among patients requiring intensive care –4. HowevThere are many potential challenges to conducting high-quality studies and trials in critical care medicine due to high disease acuity and severity and heterogeneity of disease etiology of the patients, and poor resource availability, particularly in intensive care units (ICUs) in community hospitals –12. It hTo our knowledge, there is no study about the current research environment in critical care medicine in Asia. We conducted a cross-sectional survey targeting intensivists in Japan, South Korea, and Singapore. The objectives of this survey were to describe the current status of the research environment in the three countries and explore the differences between the countries, which can be applied for future building or improvement of the research program.This study was a cross-sectional questionnaire survey in Japan, South Korea, and Singapore between July 2019 and January 2020.We included all the physician members of the Japanese Society of Intensive Care Medicine (JSICM), the Korean Society of Critical Care Medicine (KSCCM) as of June 2019, and the Society of Intensive Care Medicine (SICM) in Singapore as of November 2019.The questionnaire included four domains:1) Characteristics of intensivists including their sub-specialty, experience of the research activity, and postdoctoral education(s).2) Details of the work environment to conduct research.3) Financial support environment such as grant funding opportunity.4) Ethics committees and their activity.We first performed face validation and content validation when creating the original questionnaire in Japanese. In the face validation, we asked all the co-investigators as content experts to evaluate whether the questionnaire measured what we intended to measure. In the content validity, we invited three critical care content experts (other than the co-investigators) from the pediatric and adult field, who individually assessed whether the questionnaire content accurately assessed all fundamental aspects of the topic. We asked them to fill out a sensibility-testing tool  and a taWe then translated the original Japanese version to Korean, in which the principal investigators (YK and AK) used a computer-based translation tool to prepare a draft version of the translated questionnaire and a co-investigator (SN) added grammatical corrections to it; then, a co-investigator (JHJ), who was fluent in both Japanese and Korean languages, validated it accordingly. We also translated the original Japanese version to English (AK and YK), in which JP performed final validation independently. We did not use backward translations for both languages considering that the questionnaire consisted only of closed questions without any open-ended or qualitative questions.We collected responses using REDCap electronic data capture tools hosted at the University of Alberta , 17. We p-value of < 0.05 was considered statistically significant. All statistical analyses will be conducted with EZR , a graphical user interface for R . The ethics committee of Kameda Medical Center and the Clinical Trial Group committee of JSICM approved this study .Descriptive data were expressed with frequencies (%). The denominator of each variable was the number of respondents answering each question. Each continuous variable's distribution is described by medians and interquartile ranges (IQRs). Mann-Whitney U test, Chi-Square test, and Fisher's exact test were used to compare the continuous and nominal variables, respectively. The Kruskal-Wallis test was used to compare continuous variables among more than two groups. We did not impute the missing data. We compared the findings of physician and ICU demographics by countries of the respondents and types of hospitals they work for, i.e., university-affiliated hospitals vs. community hospitals. We also explored the factors which could be associated with the number of peer-review papers in English by applying multivariable logistic regressions adjusted with the following five research environmental factors . Since we could assume that the intensivists working for a university-affiliated hospital were more likely to have secured time for research activities and availability of research supporting staff, we examined the models with interaction terms for the following two factors . A two-sided Compared with the respondents working for university-affiliated hospitals, the respondents working for community hospitals had less secured time for research activities (14.2 vs. 30.4%), less competitive and non-competitive research funds , less research support personnel (21.3 vs. 42.4%), and less frequency of research ethics committee .Almost all the respondents in South Korea had at least one original publication in any language. A higher proportion of South Korean respondents had more than 20 or more than ten original English language publications than the respondents in Japan or Singapore .p = 0.002) compared to the respondents without. The adjusted OR was 2.61 in the respondents practicing at a university-affiliated hospital  compared to the others. The adjusted OR was 11.2 when having clinical experience of 10 years or longer , compared to those with clinical experience of <10 years. When comparing the cohorts by countries, the odds ratio was significantly higher for the Korean cohort  compared to it in Japan. The models including an interaction term did not present significant evidence of interactions. When we looked at the respondents who worked for a university-affiliated hospital with secured time for research activities and the research supporting staff in their hospital, the odds to have more than ten English publications was 2.4  compared to those without all the three factors.This study is the first report describing the current status of the research environment for intensivists in the three Asian countries. There were some differences in the baseline characteristics of the respondents between the three countries, such as type of hospital/ICU they worked for and years of clinical experience. However, we found a commonality such that a large proportion of the intensivists lacked secured time for the research activities, research supporting personnel, and research funding in their hospital. Also, there were substantial differences in the secured time for the research and research supporting staff in the hospital among the three countries.Our results were consistent with previous studies evaluating challenges for critical care research. A scoping review in lower-middle income settings identified limited funding/investment, inadequate access to mentors/training, and limited research/statistical support staff as barriers in critical care research in lower-middle income countries . An inteBased on our results, one way to overcome the barriers can be to build a collaborative environment between academics and non-academics such as mentoring or sharing research resources. Our study suggests that this is particularly important for the intensivists working for a community hospital supposed to have limited research support or resources, shown in prior literature , 15, 21.Building a financial support system for the researchers in community hospitals should be another essential aspect of promoting research. For example, in Japan and South Korea, competitive government-based research funds ask applicants to belong to an academic institution, which has been a significant challenge for the researchers working in non-academic institutions . BesidesThe limited resources of critical care practice in Asia could also contribute to its poor research productivity. A lack of organizational and human resources for ICUs is a major problem worldwide . Of noteIn this study, we found that the intensivists in Korea had more peer-reviewed publications and better research supporting infrastructure than those in the other two countries. This result may be because a higher proportion of Korean respondents worked for academia. Although this survey was emailed to all the KSCCM members, most Korean respondents worked for university-affiliated hospitals. It may come from a selection bias, which means those who are not interested in research activities did not respond to the survey. This trend was a little stronger in South Korea because responding to the survey was promoted to the board of committee members of the KSCCM.Ethical issues can be a challenge for critical care research given the urgency of patient condition and the difficulty of obtaining informed consent from the patient . ApplyinLastly, to further boost critical care science, it is essential to train new intensivists to pursue research. Providing a roadmap in the research career will attract them and alleviate worries for their future job security. A survey conducted in the United States reported that most clinical trainees felt that spending time and research activity efforts would not necessarily lead to their job security or even a better job , 29. It There are limitations to this study:Due to the nature of cross-sectional research, a thorough causal inference could not be made in this study's findings.A selection bias could have occurred. For instance, intensivists interested in research activities might have responded more to this survey. Besides, because most KSCCM members worked for university-affiliated hospitals, working for South Korea and working for a university-affiliated hospital can be confounding.The overall response rate was low. The denominators used for the rate calculation in the Japanese cohort included specific proportions of physicians who were not actively practicing in intensive care such as anesthesiology or emergency medicine. We applied a rigorous methodology in the development and administration stage of this survey to minimize the biases.In conclusion, intensivists in the three high-income Asian countries had limited research supporting environment and infrastructure with some variations among the countries. It is necessary to build a collaborative environment between academia and non-academia and across countries to share the experience and resources, and to present various roadmaps to new intensive care researchers.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by the Ethics Committee of Kameda Medical Center. Written informed consent for participation was not required for this study in accordance with the national legislation and the institutional requirements.YK conceptualized and designed the study, built a survey database, conducted data collection and cleaned the data, carried out analyses, drafted the initial article, revised the initial article, and approved the final article as submitted. AK conceptualized and designed the study, drafted the initial article, revised the initial article, and approved the final article as submitted. NS, TK, and HY conducted a pre-testing, contributed in designing the survey, revised the initial article, and approved the final article as submitted. NS, JP, and JJ played a role in leading and organizing survey distribution in each country, contributed in designing the survey, revised the initial article, and approved the final article as submitted. All authors approved the final article as submitted and agree to be accountable for all aspects of the work.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.


Total knee arthroplasty (TKA) is the gold standard for treating advanced knee osteoarthritis. Among the postoperative complications of TKA are true patella infera (TPI) and pseudo patella infera (PPI), which should be differentiated since TPI exhibits significantly worse clinical outcomes. Multiple radiological patella height indices (PHI) exist; some were modified or originally designed for knees with implanted endoprostheses. However, there is no consensus on measuring and comparing patella height. Due to the lack of established, simple, reliable, and reproducible concepts for assessing patella height for arthroplasty, measuring patella height and the change of patella height by or after TKA have been challenging tasks for clinicians and researchers. This is a review of the current literature on methods for measuring patella height, with special attention to the ability to differentiate between the TPI and PPI after TKA. All literature on the topic was retrieved, and references from relevant articles were investigated until the end of April 2022. The position of the patella is one of the most significant components for optimal knee joint function, and anomalies in patella height can impact knee function . Two disIn recent years, patella height has become a significant concern in assessing knee problems and planning therapy, particularly following knee arthroplasty, since the number of TKAs performed every day has increased dramatically , 5. PateSeveral approaches have been reported for estimating patella height in normal knees and after the implantation of a knee endoprosthesis –15. ThesPatella height measurement is crucial in assessing knee conditions and can help with treatment planning . Both TPPatella height is an important factor for the biomechanics of the whole knee, which is true for native knees and knee arthroplasty.Patella height plays a role in patellofemoral instability. Patella alta contributes to instability because the patella will engage with the femoral trochlea only at higher degrees of knee flexion.Patella infera can lead to limited flexion of the knee, to higher retropatellar pressures, and it can also affect active knee extension. It often leads to anterior knee pain.True patella infera can develop by scarring after surgery even in the second postoperative year, but not later than 24 months postoperatively , 20, 21.With the osteotomy of the tibial tuberosity, a standard surgical procedure has been developed to directly influence patella height by distalisation or proximalisation of the tibial tubercle (bony insertion of the patella tendon).In the year 1938, Blumensaat firstly introduced a method for measuring the height of the patella on radiographs . Since tStrict lateral radiographs should be used for measuring the patella height. Further, many indices are dependent on the knee flexion angle.In Lyon, several works have been performed leading to the CD index, which can be used on lateral radiography or MRI. The CD index is rather independent of the knee flexion angle and can be used throughout a range of 10° to 80° of knee flexion , 12.From MRI studies, it is known that the distance between the tibial plateau and the insertion of the patella tendon at the tibial tuberosity is rather constant, about 29 mm. A patella tendon length of more than 52 mm was considered patella alta.Until 2022, no broadly accepted method or concept that has the common consensus of orthopedic surgeons and radiologists for measuring and assessing patella height in native knees and in arthroplasty.Some indices are femoral referenced, meaning they refer to the femoro-tibial joint line in the extended knee , e.g., dCD index, mBP index. Some indices are tibial referenced (indirect assessment), e.g., IS index, mIS index, mCD index. The original CD and BP indices directly reference the joint line.When the point of reference is tibial and not on the joint line but further distal, the value of the index is not altered, although a PPI might have been created by joint line elevation via insert exchange to a thicker one. Indirect measures with tibial reference like ISI, mISI, and mCDI remained unchanged. They measured true patella height (length of patella tendon) but could not detect PPI. The dCDI and the mBPI were able to correctly demonstrate the creation of PPI , Table 1With a continuous increase in the number of TKA, determining the optimal method for measuring patella height after TKA has become paramount to optimizing the management postoperatively. In current daily practice, different imaging techniques and methods for measuring patella height are used –14. AlthIdeally, a method or concept of patella height measuring allows us to identify the amount of PPI and TPI contributing to patella infera, especially in the postoperative setting. The IS and MIS indices that use the anterior tuberosity of the tibia as a landmark are only able to detect the TPI, while the PPI will not be detected. Therefore, this mandated the use of additional methods of measurement, including BP or CD indices, to detect the PPI. Thus, surgeons recommended that in order to be able to distinguish between TPI and PPI, a combination of methods should be used , 23, 24.In a study on 92 primary TKAs, Konrads et al. evaluated the patella height and its correlation with clinical outcome. They demonstrated that patella height could be accurately assessed using the ISI and the CDI preoperatively, with the utilization of the ISI and the dCDI postoperatively . AlternaIn another study by Xu et al., which included 256 patients who received primary TKA, it was demonstrated that while both the IS and MIS indices are adequate for evaluating patella height, the use of the MIS index postoperatively may be a preferable choice . In addiIn a recent study, a new approach for evaluating patella height and the position of the joint line before and after total knee arthroplasty was reported, which included the use of axis-patella, joint axis-patella indices, and the joint line height . This meThere are several factors to consider when measuring the patella height, but the reproducibility and accuracy of the ratios used are one of the most crucial aspects. The IS index demonstrated excellent reliability and has the best reliability of all the ratios, whereas the MIS index demonstrated moderate to excellent reliability, still being among the most reliable patella height indices , 25–27. Clinical factors such as the knee flexion angle and quadriceps action are the key factors to consider when evaluating patella height ratios since they might have an impact on the accuracy of the assessment . FurtherWhen deciding on a standard concept to analyze patella height in daily practice routine and science, a point of major importance is that the concept should be easy to measure in a reasonable time, and the chosen indices can be used preoperatively and postoperatively without and with implanted implants like partial or total arthroplasty of the knee. The CD index is accepted to be independent of the amount of knee flexion or extension. It can be used with native lateral radiography or MRI of the knee.Overall, the concept described and illustrated in The IS and MIS ratios do not change in cases of proximalization of the joint line following total knee replacement surgery; on the other hand, the BP and CD ratios show a change in the position of the patella articular surface in reference to the joint line, indicating the presence of a PPI . The IS Our present work has some limitations. Firstly, the narrative review design may be subjective and biased; however, to minimize publication bias, we conducted a literature search for current and historical publications, and every attempt was made to ensure that all relevant studies were included and discussed. Secondly, we did not consider non-English language studies. Thirdly, due to limited research, the optimal method to measure the patella height is not yet established. In the future, further investigations are needed to test the measurement method and validate it in greater depth.Finally, after reviewing the literature on this controversial subject and the currently available methods of measurements, the solution to detect the pseudo and true patella infera postoperatively with the highest accuracy is using the right combination of indices. In our opinion, the combination of Insall-Salvati and Caton-Deschamps or Blackburne-Peel preoperatively and the combination of Insall-Salvati and derived Caton-Deschamps or modified Blackburne-Peel postoperatively is the best concept.It is critical to establish a gold-standard protocol that will enable surgeons to precisely identify surgical indications and will also allow us to compare clinical studies. In the absence of a comparison scale, the dilemma of choosing an ideal patella height ratio remains unanswered. However, the most important factor in measuring the patella height is using a combination of methods to avoid misdiagnosing the patient. Therefore, the concept proposed in the present instructional review seems sufficient and easy to use in daily practice and science.


An Internet-based system for testing and analyzing psychological and physiological responses during creative learning was developed using virtual instruments based on microcomputer interfaces and network communication technologies. The system can be used to study and evaluate innovative learning processes and performance at the psychological and physiological levels. This paper presents the design, implementation, and application of the system. Creative learning is becoming increasingly important in contextual education and twenty first century skills; creativity is one of the skills that keep individuals abreast of current, rapidly evolving technologies and functions as one of the priority skills.The existing literature shows that the effect of stress on creative learning performance is an inverted U-shaped (curved) relationship. This suggests that a certain level of stress helps learners maintain focus on creative learning tasks through arousal. A review of previous research on the relationship between stress and creativity confirms the existence of negative, positive, and curvilinear relationships between the two. Cognitive, affective, and behavioral engagement are important processes for creativity , and modThere has been consistent research on the effect of stress on creative learning task performance, but previous studies have not reached a majority consensus on this relationship. Some studies insist that stress has a positive effect on creative learning task performance; however, others even suggest opposite results or even a curvilinear relationship , 1990. SAn alternative account of the relationship between stressors and creativity has been proposed by some researchers , namely,Stress in creative learning can be measured both psychologically and physically. Psychological assessment of stress responses can be measured and assessed in terms of perceptual, behavioral, and physical responses. The assessment of perceived responses to stressors involves subjective estimates and perceptions. Self-reported questionnaires have been the most commonly used tool to measure stress . For a lStress induces changes in autonomic physiological function . GSR is Many attempts have been made to detect human psychological and physiological states by employing various physiological sensors . Brain wAccording to modern cognitive psychology and psychophysiology, by observing and measuring various physiological responses of learners during creative learning, information on emotional responses, attentional changes, and cognitive processing during creative learning can be captured and used as objective evidence for creative learning research. GSR is a variation of skin electrical resistance. It is determined by passing a weak current through the skin and measuring the change in current or by measuring the current generated by the body itself. GSR has been reported to be associated with emotion, attention and stress . The relThis paper focuses on the design of the system, its hardware and software and their respective implementations.The system mainly consists of three parts: creative learning environment subsystem, physiological signal acquisition and processing subsystem, and synchronous recording subsystem, which can be arranged according to the requirements of creative learning activities carried out and the conditions of the laboratory, as shown in This subsystem is the main creative learning environment, including all kinds of hardware and software needed to carry out creative learning activities. The learning environment should support students whether they are working in small groups, pairs, or individually. High tables, low tables, round, and square tables—a variety is preferable. Anything hung in the classroom should be meaningful and support learning. Each space in the Creative Learning Environment sub-system should be carefully designed and organized to create a creative learning environment in which students can engage in creative learning and complete creative learning tasks.Learners wear electrical skin sensors on their fingers , and the location to store the physiological signals of the Client end and the Server end, finally achieving the distributed remote collecting of the physiological signals via network.The module is used to re-display the stored physiological signal recording files to analyze waves of physiological signals afterward, in combination with the synchronously recorded video contents. User can modify the displaying speed to fast re-display, slow re-display, or normally re-display .t-testing, F-testing, A-S plane analysis, (A-f-S)-t plane analysis, Principal Component Analysis (PCA) and Clustering Analysis, Frequency-chart Analysis.The module mainly provides various means to analyze and process physiological signals, including wave correcting, wave compressing, average and square difference, The module is integrated with the above five modules to generate analysis reports in various formats such as Word or Excel and to store the analyzed results such as waves or tables in different formats or directly print the resulted various graphs, tables, and/or waves or to store each object on the screen in different graphic formats according to user’s requirements.The module is also integrated with the above modules, and required helps are available anytime.The following section will introduce the implementation process of the software by illustrating the server end of the module for distributed physiological signal collection.The properly collection of physiological signals is the prerequisite to conduct the application study of physiological indexes and determines the subsequent analysis of these signals, therefore, the proper collection of physiological signals is the key to the system. The integration of virtual instruments with network technology to form the distributed networked the virtual instrument system is one direction of the virtual instrument system development. There are mainly two basic models to create Internet-based distributed remote virtual intelligent testing system: C/S model and B/S model. This system mainly adopts C/S model to achieve Internet-based distributed remote collecting and monitoring of physiological signals.The distributed physiological signal collecting and monitoring in the system is mainly for the remote computer to collect and monitor physiological signals at the server end via the network. The client end defines parameters for the server end to remotely collect physiological signals which can be stored in the server end or the local client end, or it simply monitors the waves of physiological signals being collected at the server end.Implementation of the ProgramingThe system adopts DataSocket of LabVIEW to achieve the Internet-based distributed remote collection of the physiological signals.DataSocket (DS) provides a single interface which can be used by various programing languages and multiple types of data communication. There are two functions in LabVIEW to receive and distribute data: DataSocket Read and DataSocket Write. The program to distribute data automatically transforms user’s data into byte flow transferring on the network via DataSocket Write, while the data-receiving program reverts the byte flow into its original data type via DataSocket Read.① The Program Design for the Server EndDS function adopts DSTP (DataSocket Transfer Protocol) developed by NI to communicate with DS server. In order to start the remote collection of physiological signals, it’s necessary to first determine the address of DS server, such as dstp://192.168.7.89/daqset, where daqset is data label used to determine the address of specific data item on DS server. In practical application, the address at the server end must be identical with the address where the Client needs to access so as to establish connection to achieve the remote collection and monitoring of physiological signals.When the communication between the collecting program at the server end and DS server is established, the Client can begin to define the parameters for physiological signal collection at the server end. At this point the Client sends data to the Server via the function of DataSocket Write, while the server captures the data for parameter setting from the Client via the function of DataSocket Read.② The Program Chart for the Server EndIt has been shown that stress negatively affects creativity by reducing the demand for cognitive resources that are not available for creative thinking, and that people adopt simpler cognitive strategies that may undermine creativity . Some thThe original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding author.The individual(s) provided their written informed consent for the publication of any identifiable images or data presented in this article.The author confirms being the sole contributor of this work and has approved it for publication.The author declares 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.


Epidemiological studies involving large samples usually face financial and operational challenges.To describe the planning and execution of ADHERE Brazil, an epidemiological study on 1,105 kidney transplant patients, and report on how the study was structured, difficulties faced and solutions found.Cross-sectional multicenter study in 20 Brazilian kidney transplantation centers.Actions developed in each phase of implementation were described, with emphasis on innovations used within the logistics of this study, aimed at estimating the prevalence of nonadherence to treatment.Coordination of activities was divided into four areas: general, regulatory, data collection and statistics. Weekly meetings were held for action planning. The general coordination team was in charge of project elaboration, choice of participating centers, definition of publication policy and monitoring other coordination teams. The regulatory team provided support to centers for submitting the project to ethics committees. The data collection team prepared a manual on the electronic collection system, scheduled web meetings and was available to respond to queries. It also monitored the data quality and reported any inadequacies found. Communication with the centers was through monthly reports via e-mail and distribution of exclusive material. The statistical team acted in all phases of the study, especially in creating the data analysis plan and data bank, generation of randomization lists and data extraction.Through these logistics, we collected high-quality data and built a local research infrastructure for further studies. We present supporting alternatives for conducting similar studies.http://clinicaltrials.gov/ on October 10, 2013; NCT02066935. It results in better survival, better quality of life and lower costs.2 Nonadherence to immunosuppressive drugs that are necessary to avoid graft rejection is associated with an increased risk of acute rejection episodes, graft dysfunction, lower graft survival and higher healthcare costs.2Nonadherence to treatment of chronic diseases is one of the main determinants of long-term complications.3 However, this country has a large geographical size and great cultural, social and economic diversity, which translates into large variation in transplantation activity across the country, when normalized according to population size.4 Evaluation of and addressing nonadherence after KT is crucial to achieve the best results. However, Brazilian studies are scarce, limited to small samples, and are therefore not representative of the general population.12Over recent years, Brazil has reached the second highest position in the world, in terms of the absolute number of KTs performed in the world’s largest public transplantation system.8 Then, we estimated the prevalence of and identified factors associated with nonadherence to immunosuppressives after KT in a single center in the city of Juiz de Fora, Minas Gerais.10 Discussion on the need for a multicenter study that could better portray Brazilian epidemiology arose when these results were presented in national conferences in 2011. Over a period of two years, these discussions continued and led to planning of a project among Brazilian national researchers in collaboration with a world-reference research center that had already started a similar study on heart transplantation (Building Research Initiative Group: Chronic Illness Management and Adherence in Transplantation - BRIGHT study).13 Consequently, the ADHERE Brazil study was designed as a multicenter cross-sectional study with the following objectives: to estimate the prevalence of nonadherence to immunosuppressives and other aspects of nonpharmacological treatment; to evaluate multilevel factors associated with nonadherence to treatment; and to benchmark the participating centers, bring the subject up for discussion and disseminate data to support future actions towards reducing these behaviors.14Studies on adherence to immunosuppressives after KT by our group began in 2009. In the initial project, we performed a cross-cultural adaptation and validation study of a self-report instrument for diagnosing nonadherence to immunosuppressives.16However, conducting such a large study, comprising twenty kidney transplantation centers and an ideal sample size of 1,139 patients, presented several challenges. This was an epidemiological study, and therefore without interventions, but which needed adequate infrastructure, in order to follow regulatory policies, and needed funding similar to that required in clinical research. For example, the study required a study coordination room, a meeting room and a specific area for archives and staff training.17 Indeed, in our project we faced some difficulties, but feasible solutions were found that translated into a path towards positive results. Considering that these challenges may be experienced in similar research proposals, a report presenting a detailed list of actions may help other researchers succeed.A multicenter study can be divided into four phases: 1) Planning; 2) Project development; 3) Study implementation; and 4) Dissemination. Some detailed reports on each of these phases exist, but the actions developed and the project management may vary according to the project and local characteristics.Thus, our objective was to present the stages followed by the researchers responsible for conception of the ADHERE Brazil study; show how the development of the study was planned and implemented; and describe the difficulties found and solutions applied. Ultimately, reliable results could be obtained regarding the diagnosis of nonadherence to treatment and associated factors. We therefore present a description of the actions taken, especially in the project implementation phase, with emphasis on the innovative and adaptive processes employed.http://clinicaltrials.gov/ on October 10, 2013; NCT02066935).This was a cross-sectional and descriptive study on the procedures undertaken for execution and management of the ADHERE Brazil multicenter study  under the number NCT02066935 and on the Open Science Framework scientific dissemination platform (https://osf.io/dpr2j/).The initial idea for the project arose in 2011. It was then designed over a two-year period. A group of co-investigators, whom we called the ADHERE Brazil study consortium, was then consolidated. The project was registered at the Research Department of the Federal University of Juiz de Fora, the institution to which the principal investigator was attached; and on the Clinical Trials website . Invitations were sent out in May 2013, and the final composition of the participating centers was completed in May 2016. A total of 22 centers were invited because two of the initially invited centers subsequently refused to participate. The new invitations were made using the same criteria and characteristics as for the original centers. Among the 20 centers that ultimately participated in the ADHERE Brazil study, 38.2% showed low activity (< 50 transplantations/year), 36% were moderately active (50-150 transplantations/year) and 25.8% were highly active (> 150 transplantations/year). This distribution was similar to what had been reported by the Brazilian Transplant Register5 .20Scientific participation and authorship were defined before the study started and were described and agreed upon in a publication policy statement. The regulatory and fundraising phases began in 2014. The first sets of data were collected in December 2015 and finalized in April 2017. Dissemination of results began in 2015 and is ongoing. By April 2021, 17 presentations had been made in national/regional conferences and five in international events, and two articles had already been published.As mentioned above, we established an early research collaboration with the Leuven Basel Research Group (LBARG). They already had broad experience in international dissemination of knowledge and multicenter studies. The group supported all the phases of our study, through a strengthened partnership and promotion of a better qualified process.To make the project feasible, coordination of actions in four areas was proposed: general, regulatory, data collection and statistics.General coordination was performed by the principal investigator of the study, who was responsible for project elaboration, study consortium formation and sending invitations to the participating transplantation centers. She also participated in all the other phases: regulation, data collection and analysis. In addition, she prepared other reference documents for the study, such as the statements for center participation feasibility and confidentiality, as well as the publication policy of the study.In the center recruitment phase, after the informal invitation had been accepted, the centers received a confidentiality agreement, which addressed the importance of confidentiality of the project content and of the data collected during the study. After signing, the center received the feasibility document, which contained information that would ensure that the participating center had the minimum infrastructure to be able to conduct the study. The center also received the publication policy statement on issues relating to publications generated using ADHERE Brazil study data, authorship and subprojects. Centers were only included in the study after the leading local investigator of each center signed these documents. After the regulatory phase, participation was formalized through a research contract signed by the parties involved.Soon after regulatory approval had been obtained, applications for financial support were sent out. Support was sought from the national governmental funding agency  and from the local state agency ; and also from private companies interested in research relating to transplantation. Unfortunately, the project was not selected for governmental support, but two pharmaceutical companies decided to join the proposal. The operational support provided by a clinical research structure and the virtual and centralized data collection system, together with interest in the potential results, seemed to contribute to the companies’ decision. However, other than financial support, the companies had no role in any of the stages of the project design, data collection, analysis or writing of the manuscripts. The resources enabled personnel payments (regulatory and data collection activities), participation in events, translation/editing and printing services.Weekly meetings were held among the general coordination team and the other coordinators to schedule the following phases of the study: forwarding the participating center projects to the local ethics committees; organizing and training for data collection; checking the ongoing data collection; and performing data analysis. This coordination team was responsible for following up on all the activities necessary for development of the project, with organization and control of the information .thBrazilian Congress on Transplantation 2015 and 17thBrazilian Congress of Nephrology 2016), along with distribution of material containing the visual identity of the study   Weekly meetings mentioned above; 2) Definition of well-established functions among the other coordination teams; 3) Creation of an e-mail address shared by the coordinators; 4) Communication with the centers via Skype or other communication sources such as telephone or e-mail, to answer questions; 5) Monthly newsletters to the centers, which totaled 28 between 2015 and 2020, reporting on study progression; 6) Meetings with members of the participating centers at national conferences to disseminate information about the study proposals (14nd pens) ; 7) ProvInitially, the coordinating center submitted the project to the research ethics committee (REC) of the institution at which that center was located. After approval, which was granted in May 2014, the centers recruited were asked to submit the project to their local RECs. Participation of each center depended on receiving approval from the local REC. Patients were only included after they had signed an informed consent statement (ICS).The first step for the coordinator of the regulatory team was to send all the guidelines for REC submission to the other 19 participating centers and a model of the formal documents to be included in the national REC website (Brazil Platform): research project, ICS model, budget model and schedule model. This guidance greatly facilitated REC submission by the participating centers. However, there were some difficulties, which can be gauged from the time that elapsed between obtaining the first REC approval (September 2014) and obtaining the last one (February 2017), which amounted to 30 months.The main difficulty faced was the lack of familiarity with the Brazil Platform among the participating researchers, with regard to registering researchers, preparing documents to be included and, subsequently, formulating answers to any questions raised by the RECs. For these points, availability and participation of the regulatory team was essential for solving any issues. Another difficulty was the refusal of two RECs to evaluate the project because it was a multicenter study. These cases were then referred to and evaluated by the coordinating center’s REC. This process delayed patient inclusion in these centers. Lastly, after initial approval of the project, two amendments for replacement/inclusion of two new centers had to be submitted to all RECs. The archiving of documents submitted to each local REC and final approvals from them was done by the regulatory team.It was also the responsibility of this coordination group, after the end of data collection, to forward the final report to the coordinating center REC and to send a model to the participating centers, for them to perform the same procedure in local RECs.21This team was also responsible for registering the project on the Clinical Trials website, which ensured transparency with regard to execution and publication of results and avoidance of bias, with ethical support for the participants, since the results generated would promote scientific knowledge.The two-member data collection coordination team oversaw organizing the training of personnel involved in data collection at the participating centers and monitoring and checking data inclusion during collection. The objective of this coordination team was to make available staff who had been trained to operate the data collection system, on the Research Electronic Data Capture (RedCap) platform, and who would be easily accessible to people at the centers, by telephone, e-mail or other communication platforms.14 and on previous studies.13 The RedCap system was used for data collection. This is a safe internet-based software platform that was created at Vanderbilt University, in Nashville, United States, for the purposes of data capture and storage, which could be fed remotely by trained individuals (http://www.project-redcap.org/) at the coordinating and participating centers. The ADHERE Brazil project was created on this platform; thereafter, the data collection questionnaires were included. Each center had remote access to the project to include data and access only their respective data, thereby ensuring anonymity.The interviews and questionnaires used in the ADHERE Brazil study were prepared based on a theoretical frameworkAll the research coordinators of the centers participating in the ADHERE Brazil study were trained to use the RedCap system through a manual that was prepared specifically for this purpose, and through Skype meetings. In addition to training, each center was asked to include a “test patient” in the system before data collection started.Another data collection coordination function was to send randomization lists that had been generated by the statistics coordination team, to the participating centers so that patients could be selected to participate in the study.Lastly, to ensure data quality, the data collection team checked the data weekly, as the patients were inserted into the RedCap system by the participating centers, to detect missing data or possible typing errors. Following this evaluation, reports were generated every week and sent to the centers, requesting them to check and correct inconsistencies if necessary. A one-week deadline was given for checking the data. Thereafter, the data were checked again.One of the biggest challenges of the data collection coordination team was to adjust for missing/inconsistent data from each center. Data collection was only considered finalized after inconsistencies had been checked and corrected. To solve such problems after a report had been sent more than once, telephone contact was made to detect possible process difficulties. Using this strategy, data collection began in December 2015 and was completed in April 2017 , with inclusion of 1,105 patients, which corresponded to 97% of the ideal sample size.The statistical coordination team participated in all study phases, from conception to analysis and dissemination of data.More specifically, it was responsible for the sampling strategy, and for defining the sample size and the criteria for patient distribution in each center. It created the database in the RedCap system and sent access passwords to the 20 participating centers. RedCap access levels differ, depending on the function: the centers only had access to their own information, while the data collection and statistics coordination teams and the principal investigator had broader access. Additionally, the statistical coordination team was responsible for generating randomization lists using computer software to select patients for the study. These lists included information provided by the centers, such as the number of patients scheduled per day in the post-transplantation clinic and the number of patients to be included in each period.Another function of this coordination team was to organize data extraction after data collection through the RedCap system had been completed, thus generating the initial ADHERE Brazil study database. The entire analysis plan was defined by this coordination team in agreement with the researchers’ consortium. It was also responsible for defining and guiding the tests performed and for performing more complex analyses.The ADHERE Brazil study involved data collection from 20 Brazilian KT centers. Active participation by the general, regulatory, data collection, and statistical coordination teams was essential for enabling effective collection and reliable analysis of the information generated. Consequently, these integrated actions enabled inclusion of 97% of the ideal sample size, which was accomplished with high-quality data collection and integration among the coordination teams. The strength of our study that we can highlight is that we were able to accomplish a high-complexity study using low-cost available solutions, thus generating unpublished data with great potential to contribute towards healthcare practice.21 weekly updates with discussion of the problems that arose, together with short and medium-term planning of solutions, aligned project progression and established the actions and functions to be fulfilled.21 This proposal was essential for solving problems in our study, as previously described in health and educational research settings.24 Management skills among health researchers are not fully available because such abilities are not systematically developed during undergraduate courses. Additionally, investigators are frequently involved in other activities such as teaching or healthcare assistance outside of research, and thus have limited time to dispend on further educational and training efforts.25The general coordination team conducted activities in conjunction with the other coordination teams in a harmonious fashion. Based on the basic principles of project management in research,17 all research in Brazil involving human beings has to be evaluated by a REC to ensure respect for and protection of research subjects.21 The role of RECs is to ensure that the principles of research ethics are respected in the study and that the rights of those involved are preserved.21 Although there is clear legislation on regulatory procedures for this type of research, the effectiveness and operational particularities of RECs still vary across Brazil.27 For multicenter studies, which involve multiple REC evaluations, some avoidable inefficiencies have been reported, mainly due to discrepancies in the opinions of these multiple committees.27 This can be demonstrated through the long period of time that was spent on this phase, which was the longest. The regulatory coordination team was created to deal with these issues, and to promote and facilitate regulatory procedures in each center, since the study included some institutions with fully functioning clinical research units and others that had never participated in research. We proposed to have someone with expertise in regulatory processes always available to assist at all levels, from preparation of documents to submission of the project and its amendments to the Brazil Platform website. A similar strategy has been reported by others in multicenter studies.28In line with international standards,23 It is important to emphasize that the quality of the data collected in surveys depends on the adequacy and quality of questionnaires, in order to guarantee validity and reproducibility through clear and simple questions.17 Furthermore, to increase survey quality, it is essential to provide standardized training for data collectors.23 In the ADHERE Brazil study, all professionals who collected data received training for this purpose. Another key feature was simultaneous data collection and storage through a computer platform connected to the internet, which minimized errors, since it allowed for immediate checking for missing or erroneously filled data. These errors could be reported back to the person responsible for data collection, so that prompt corrections could be requested. Systematic and consistent checking of quality during the ongoing data inclusion is a powerful measure for preventing errors and missing data.17 In our study, each local center made adaptations and took appropriate steps to ensure that data were collected in a way that guaranteed satisfactory results.23The data collection phase is essential. Good planning at this stage can prevent possible distortions and interviewer influence on the interviewee, which thus enables methodological and scientific rigor.28 High-quality research is associated with formal early statistical planning.29 Thus, it is essential to have statisticians’ participation at all stages of a research project so that they can significantly contribute not only to data analysis, but also to the choice of method and analysis software, and to presentation and interpretation of results.29 The availability and effective participation of the statistical coordination team at all levels of our study led to attainment of this quality threshold.It is worth mentioning that it is the responsibility of statisticians to plan studies, interpret the data obtained through field research and present the results in a way that facilitates decision-making by researchers.27 This made it difficult to discuss the key points of the proposal from a local perspective. Therefore, we discussed the findings based on the available published reports. We think this aspect of our proposal highlights its originality and relevance.The limitation of this study was the scarcity of articles describing experiences relating to strategies for conducting multicenter epidemiological studies. Especially within the Brazilian scenario, we found reports only about obstacles to the ethics regulatory process.30 and SARS-COV-2 Infection in Kidney Transplant Recipients: a Brazilian Multicenter Study .Since the conceptualization of the ADHERE Brazil study, we have been making efforts to disseminate the proposal and the results. Our proposal was registered on the Clinical Trials and the Open Science Framework websites, and we have presented summaries of our results at international, national and regional meetings. In confirmation of the potential for applicability and reproducibility of our proposal, we have already identified two Brazilian multicenter studies that mirror our methodology: the DGF Brazil Study GroupThe experience acquired in conducting this study led us to conclude that through the project management actions described, it was possible to collect reliable data on adherence to immunosuppressive treatment after KT and to ensure that the ethical principles and safety measures involved in the research and data collection were adopted, since all work processes proposed for conducting the study were strictly followed. In addition, this article presents alternatives for conducting studies of similar nature to the ADHERE Brazil study.


Despite some preliminary studies of the available herbal medicine preparations and their curative effects on COVID-19, experts still fear that unproper use of such homemade medicines could do more harm than good to people relying on unproven alternatives of questionable efficacy. The main purpose of this study was to evaluate the safety of herbal medicines used for respiratory system disorders in the Pasvalys district during the COVID-19 pandemic in Lithuania. An archival source was also studied, looking for possible recipes for the treatment and prevention of respiratory diseases in Lithuanian traditional medicine, emphasizing the safety guidelines. The survey was conducted using the deep interview method. The respondents mentioned 60 species of medicinal plants from 29 different families used for the treatment and prevention of respiratory system disorders . Twenty eight out of 60 plant species were not included in the European Medicines Agency monographs and only 50% of all included species were used as indicated by the European Medicines Agency for respiratory system disorders. The trends in the ethnopharmacological choices of modern consumers and the analysis of archival sources can be a great source of ideas for new herbal-based pharmaceutical preparations for COVID-19 symptoms in Lithuania considering the safety recommendations. Traditional medicine is a set of knowledge, skills, and practices based on the theories, beliefs, and experiences of different cultures used to improve health by preventing and treating physical and mental disorders . Folk meThe traditional knowledge associated with medicinal plants nowadays is gaining importance worldwide, due also to the emergence of the new disease of COVID-19 . In the The COVID-19 pandemic has become the greatest threat to humanity in the 21st century, and its impact on the health and economy is expected to be even more severe for communities located in remote areas ,7. The sViral respiratory infections are some of the most common infections worldwide, with the majority of the world’s population suffering from at least one infection a year . RespiraAccording to the general trend of ethnopharmacological measures used for COVID-19, the most popular are plants that have medicinal properties against influenza and malaria as well as plants with immunomodulatory properties, and plants that have a positive effect on respiratory disorders ,10. MediThe limited availability and accessibility of conventional medicine during COVID-19 have made traditional medicines more appealing due to their wide availability and increased position of safety. Several herbal medicines are believed to alleviate or cure COVID-19 and its symptoms . DespiteResearchers of ethnopharmacology have noted that the global COVID-19 pandemic forced individualization in the home environment, and the collapse of the entire health care system made people turn back to the forgotten knowledge of traditional medicine to have both medicine and food ready at one’s fingertips . Even ifThe main purpose of this study was to evaluate the safety of ethnopharmacology used to treat respiratory tract disorders in the Pasvalys district during the COVID-19 pandemic in Lithuania through the assessment of the compliance of the indications for the use of medicinal plants with European Union herbal monographs. The archival source of E. Šimkūnaitė dated 1925–1947), with recipes of the famous herbalist in Lithuania, which became especially popular during the COVID-19 pandemic, was also evaluated. On one hand, ethnopharmaceuticals may be an excellent alternative to medication, especially during and after COVID-19, but special attention should be paid to safety recommendations. The therapeutic effects of herbal preparations are often underestimated, but the potential for overdose is also underestimated, especially when the nearest health care professional is not readily available. Critical and scientific study of the traditional treatment for COVID-19 may also act as the basis of counternarrative and education in response to the growing body of misinformation surrounding alternative COVID-19 treatment [–1947, wiThe study was conducted in the Pasvalys district located in the northern part of Lithuania, in Panevėžys county, near the Latvian border . This isThe district has no lakes, and there are only a few ponds. Karstic depressions, sinkholes, are characteristic of the Pasvalys district. Forests cover 16.6% of the municipal area, with deciduous forests the most common.Pasvalys is located at the confluence of Lėvuo and Svalia. The name of the town was first mentioned at the end of the 13th century. In 1497, the Grand Duke of Lithuania Alexander donated land to the church started by the priest J. Grotas, and allowed the town to be established. Pasvalys was developed along the main road to Riga, so the town suddenly became a center of merchants and craftsmen . In Pasv2, which makes up 2% of the total area of Lithuania. According to the data provided in 2020, there were 22,816 inhabitants in the Pasvalys district. There are two big towns in the district, Pasvalys and Joniškėlis; seven smaller towns, Daujėnai, Krikliniai, Krinčinas, Vaškai, Pumpėnai, Pušalotas, and Saločiai; and 398 villages [The area of the Pasvalys district is 1289 kmvillages . Most ofThe study was conducted in 2021, from May to October in the Pasvalys district, Lithuania . During To begin with, we aimed to become acquainted with and gather information about the people living in the study area. All participants in the study not only treated and prepared herbal pharmaceutical forms themselves, but also advised and taught how to prepare them to others who sought help. This target group was made up of herbalists, but only one respondent in this group sold prepared pharmaceutical products and accepted money for the consultation of how to overcome health problems with natural remedies and incantations.A qualitative “snowball” method was used to search for respondents, during which the interviewee suggested another person who could share knowledge about the use of natural substances for the treatment and prevention of respiratory diseases. The research method was a structured interview. The respondent was initially introduced to the topic of the study and given the summary information, then an informed consent form to participate in the study was signed. The interview was conducted using a ready-made questionnaire. The questionnaire consisted of 16 questions that included a structured part of the interview. With the help of the questionnaire, the demographic data of the respondents, information about the cultivated and collected medicinal plants, their parts, preparation methods, and indications were collected. The investigators marked the received information in their notes, audio recordings on the Dictaphone were made with the respondent’s consent, and all data were encrypted. Additionally, some respondents were visited for a second time to supplement and clarify the information. The study identified the indications for use by the respondents and compared them with the monographs presented in the European Medicines Agency (EMA) assessment . The purTaxonomic identification, botanical nomenclature, and plant family assignment were performed based on the validated databases of the World Flora Online database  and AngiThe data obtained during the research were compared with the archival source of E. Šimkūnaitė dated 1925–1947), kept at the Museum of the History of Medicine and Pharmacy of the Lithuanian University of Health Sciences, using the method of comparative analysis. Eugenija Šimkūnaitė was a famous pharmacist, herbalist, ethnographer, and habilitated doctor of the biological sciences. The woman devoted her entire life to the study of medicinal plants and folk medicine. This archival source was chosen due to the scientific structure, methodology, and identified plant species, and the increased popularity and availability of E. Šimkūnaitė’s recipes during the COVID-19 pandemic [5–1947, kThe research data are stored at the Museum of the History of Medicine and Pharmacy of the Lithuanian University of Health Sciences.Thirty respondents (28 women and 2 men) participated in the study, and all respondents agreed to provide data on the use of natural substances for respiratory disease treatment and prevention. The percentage of men and women was uneven, because traditionally, knowledge of herbal medicine in Lithuania is transmitted through the women’s line and even nowadays, usually herbalists are women. Most respondents who participated in the structured interview were older adults and the elderly, 23  belonged to the category of 50 years and older.The study focused on the education of the respondents. Most respondents had secondary or special secondary education, 27% each. A significant part of the respondents (26%) had obtained a higher education. This was followed by respondents with higher vocational education (17%). The smallest part (3%) was the category of people with basic education. Most respondents had a secondary or vocational secondary education, those with secondary education did not acquire a specialty, and mostly indicated that they were housewives, and respondents who had a vocational secondary education most often indicated being a technician and an accountant. Respondents with a higher education indicated being a health care professional: nurses, veterinarians, and physiotherapists, but these were a minority. Considering the results of the research, we can state that few people among the respondents worked in health care; however, they all practiced traditional medicine and were basically self-taught.It was very important to prove the authenticity/reliability of the knowledge gathered during the study. The structured interview asked respondents where they had gained the knowledge about traditional medicine, the use of medicinal plants, and how they had learned to treat with the help of natural substances. The results on the sources of information obtained during the study are presented in Almost all respondents mentioned that they had acquired ethnopharmacological knowledge from their parents and grandparents, such answers accounted for as much as 93%. These results indicate that traditional medical knowledge is passed down from generation to generation to preserve knowledge about natural remedies. Most respondents stated that they had treated their children with folk remedies, who in turn now opted for natural treatments for their offspring. Such answers show that people tend to trust traditional medicine and it is not forgotten to this day. Furthermore, a large proportion of respondents cited neighbors and acquaintances as a source of information . Thus, the respondents tended to share and exchange their accumulated knowledge of traditional medicine. Books and magazines as a source of information were cited by 60% of respondents, and 33% mentioned the radio, TV, and the Internet. It is interesting that traditional herbalists mentioned the Internet, TV, and radio in such a high percentage. This may also indicate that the respondents who were practitioners and actively interested in this field used all of the available information tools, and followed the current affairs and latest trends of traditional medicine through the radio, television, and even Internet. Only 23% consulted doctors and pharmacists to improve their knowledge on natural substances. The respondents stated that due to the epidemic situation, they were more likely to see a pharmacist than a doctor because pharmacists were more accessible during the COVID-19 pandemic. A pharmacist was seen by 63.30% of respondents and 23.30% contacted a doctor. Only a small part of the respondents answered that they did not turn to a health professional, and such answers accounted for 13.30% of the total citation frequency. However, when comparing the results of other ethnopharmaceutical research in Lithuania, we observed the opposite, where respondents did not turn to a doctor and/or pharmacist for ethnopharmaceutical knowledge and did not trust health care professionals in this matter . The datThymus vulgaris L. (22 citations), Tilia cordata Mill. (17), Matricaria recutita L. (19), Rubus idaeus L. (14), Tussilago farfara L. (eight citations) and Foeniculum vulgare Mill., Glycyrrhiza glabra L., Salvia officinalis L., Mentha x piperita L., and Calendula officinalis L. (six citations each). These herbs are popular for the treatment of upper respiratory tract diseases as other ethopharmaceutical research in Lithuania has also shown. During the first phase of the pandemic (December 2019–August 2020), the most frequently reported species during the pandemic named by the Lithuanians were Allium sativum L., Allium cepa L., Urtica dioica L., and Tropaeolum majus (L.) Kuntze [Radix glycyrrhizae rhizome [This ethnopharmaceutical study in the Pasvalys district identified 60 species of medicinal plants belonging to 29 families for the treatment and prevention of respiratory diseases. All of the collected data are summarized in detail in ta Mill. , Matrica rhizome .The main indication for use was cough, as shown by the overall study data . From thDifferent parts of the plant  have different active ingredients, which can make one part of the plant toxic and the others beneficial to health. Phytotherapy may use the whole plant or only a part of the plant . The parRubus idaeus L. [The aboveground parts of the plants were most often selected by the study participants and the most popular method of preparation was tea . While mdaeus L. ; in our daeus L. . Importadaeus L. . This isAccording to the research, medicinal plants are prepared as various pharmaceutical forms such as teas (herbs are added to boiling water), decoctions (herbs are boiled), and infusions , poultices (a cloth for poultice is soaked in decoction), and ointments . The preparation methods for the treatment of respiratory diseases and data from the archival sources are compared in According to the data obtained in the Pasvalys district survey, the most popular method of preparation was tea , while in the archival data, the most frequently mentioned preparation method was decoction . In the archival data, teas accounted for only 3% of the total citation frequency, and in this study conducted in the Pasvalys district, decoction was mentioned in 17.9% of all citations. The decoctions were made with water or milk, sweetened with honey, and heated for a few minutes, while the tea was prepared simply by pouring boiling water over the herbs. This tendency to use a simple method of preparation (tea) only proves that medicinal plants were intended for long-term treatment of respiratory diseases, which would not require a more thorough preparation. According to the data of the archival analysis, the more thorough preparation method (decoction) with an increased concentration of active substances was intended for short-term treatment. Comparing the new Pasvalys survey to the historical data, it was observed that the preparation methods of medicinal plants among the modern respondents was poorer, simplified, and less attention was paid to the amounts of raw material, preparation time, and other details. The limited time of use and the exact amount of the herbal raw material were emphasized in the archival material, as was the necessity to consult a physician about its prolonged use .As the global use of herbal medicinal products continues to grow and many more new products are introduced into the market, public health issues and concerns surrounding their safety are also increasingly recognized . Most plDuring interviews in the Pasvalys study, the adverse effects of herbs or herbal preparations were not recorded but were most likely not identified because the respondents underestimated the potential adverse effects of herbal medicine. The results obtained in the study conducted in the Pasvalys district showed that only 32 out of 60 herbal raw materials used by the respondents were described in the EMA monographs . The othArctium lappa L.), which were used to treat cough and tonsillitis, the roots were used to treat tonsillitis, but the EMA recommends using roots for the treatment of the urinary tract, appetite improvement, and seborrheic skin diseases. Horsetail (Equisetum arvense L.) herbal tea was used by the subjects to relieve cough, but in an EMA monograph, horseradish is used to treat urinary tract and superficial wounds. Mint tea and infusions of mint (Mentha x piperita L.) were used by respondents to relieve cough and for inhalations for cough and blocked nose. According to the EMA recommendations, mint leaves are used to treat various digestive disorders . Urtica dioica L. was frequently mentioned by the respondents and its leaves and roots were used to treat asthma and cough. According to the EMA recommendations, the leaves of this medicinal plant are used to relieve joint pain and as a supplement in mild urinary tract disorders, and the roots are used to relieve lower urinary tract symptoms associated with benign prostatic hyperplasia. St. John’s wort (Hypericum perfoliatum L.) was used for sore throat and cough, but according to the EMA recommendations, St. John’s wort should be used to reduce indigestion and relieve anxiety symptoms. Strawberry (Fragaria vesca L.) leaves were used by the respondents to treat cough, and the EMA guidelines use strawberry leaves for mild diarrhea and urinary tract treatment.The most popular and commonly used medicinal plants of which the indications for use did not comply with the EMA recommendations were the seeds, leaves, and flowers of the burdock (Tussilago farfara L.) was mentioned many times by the respondents, and is listed among the most popular medicinal plants in the Pasvalys district, but according to the latest scientific literature, it is quite toxic when used internally. Researchers have found that coltsfoot alkaloids have a hepatotoxic effect on the liver [It is also important to mention that coltsfoot (he liver . Restriche liver . The EMAOcimum sanctum L., Piper nigrum L., Zingiber officinale Roscoe, Cinnamomum verum J. Presl, and Vitis vinifera L. have been used to improve the immunity in COVID-19 patients. Patients with sore throat and cough are advised to carry out steam inhalation with Mentha arvensis L. with Syzigium aromaticum L. powder [Lavandula angustifolia Mill., Melissa officinalis L., and Mentha x piperita L was used to relieve cough.Despite not being approved by regulatory bodies as a definitive guideline in COVID-19 management yet, the application of ethnomedicine has resulted in several herbal medicine candidates that show a promising result regarding its efficacy in managing COVID-19 ,39. In m. powder ,41. AccoSeveral traditional Chinese medicine formulations used after the outbreak of COVID-19 have significant antiviral, anti-inflammatory, and immunomodulatory activity. Based on recent updates, several herbs and isolated phytomolecules have been found to inhibit the SARS-CoV-2 viral infection through different mechanisms .Zingiber officinale, Eucalyptus globulus, Gliricidia sepium, Citrus x limon, and Matricaria recutita. Scientific information has demonstrated their effectiveness in treating these infections [The present study from Western Colombia focuses on the importance of traditional, cultural, and generational history with reference to the use of important and significant medicinal plants to find a strategy to fight the new virus. According to the use during the COVID-19 treatment process, the following species obtained the highest use values within the various mixtures: fections . Some offections ,43.According to the Pasvalys study results, systematized in Thymus vulgaris L., Tilia cordata Mill., Matricaria recutita L., Rubus idaeus L., Tussilago farfara L., Foeniculum vulgare Mill., Glycyrrhiza glabra L., Salvia officinalis L., Mentha x piperita L., and Calendula officinalis L. need further investigation for herbal formulations for the possible treatment of respiratory system disorders as one of the COVID-19 related symptoms. Trends in the ethnopharmacological choices of the modern consumer (Unlike modern medicines, herbs are often claimed to be non-toxic due to their natural origin and long-term use as traditional medicines. However, numerous difficulties can also occur due to the long-term use toxicity, drug–herb interactions, and misidentification of the plant species. The COVID-19 pandemic can be identified as the cause as it has caused difficulties in reaching a physician, leaving pharmacists as the most widely available health care professionals. On the other hand, the question arises as to whether the consultation and the knowledge of the pharmacist were sufficient and met the expectations of patients. Herbalists are not health care professionals, but the use of herbal home-made preparations during the pandemic was raised in all countries. However, it should be assessed whether the measures recommended by herbalists are in line with the evidence-based indications described in the EMA monographs. Although most indications based on the archival source do not agree with the EMA assessment , it may consumer  and the consumer  can be a