Organizing and executing a large clinical trial is a complex process, and often recruitment targets are not met. We describe the organization of the Levodopa in the Early Parkinson’s disease (LEAP) trial and the results of an external assessment of the recruitment process.Several strategies were used to ensure that recruitment for the trial was effective and efficient. We analyzed the patterns in referrals, inclusions, and non-inclusions to investigate whether there were bottlenecks in the referral and inclusion process. For the external assessment of the recruitment process, the QuinteT Recruitment Intervention (QRI-Two) was used retrospectively, focusing on finding possible issues impeding recruitment that are less easily recognized.Recruitment took 57 months, which was 27 months longer than initially expected. 6.8% of the estimated eligible patients in the Netherlands were included. The number of referrals differed widely between participating centers and regions in the Netherlands, with the region of the principal study center having the most referrals. Reasons of exclusion varied across regions, as in some regions more patients already started, wanted to start, or did not want to start with Parkinson medication compared to other regions.Executing a large, investigator-initiated clinical trial on a limited budget still remains possible by focusing on minimizing administrative and organizational procedures. Our study suggests that centers with closer institutional ties to a principal study center tend to have a higher referral rate. The review of the LEAP trial recruitment strategies and data using the QRI-Two suggested that the variations in referrals and reasons of non-inclusion could indicate the presence of issues related to clinical equipoise, patient eligibility, or study presentation. Integrating a recruitment intervention could have explored issues with study presentation and equipoise that might have increased recruitment efficiency.ISRCTN30518857. The registration was initiated on 02/08/2011 and finalized on 25/08/2011. Recruitment started on 17/08/2011, after the initiation of public registration.ISRCTN  Executing a large, investigator-initiated clinical trial on a limited budget still remains possible by focusing on minimizing administrative and organizational procedures.Our study suggests that centers with closer institutional ties to a principal study center tend to have a higher referral rate.A review of the recruitment strategies and data using a QRI-Two indicated that prospectively integrating a recruitment intervention could have provided insights about equipoise, eligibility, and study presentation issues in order to increase recruitment efficiency.Before patient recruitment for a trial can be started, a complex and intensive process has preceded: a sound trial plan has to be designed, and a myriad of practical questions have to be answered concerning patient recruitment, execution of assessments, developing a database, organizing trial and data monitoring, and obtaining funds. Unfortunately, recruitment targets are often not met, resulting in an underpowered trial or an extended recruitment period, with only partially answered or unanswered questions, and a waste of resources. In a Cochrane Review, it was estimated that these problems occur in more than 50% of trials , and a rFor the motor symptoms of Parkinson’s disease (PD), levodopa is the mainstay of therapy because it is very efficacious in relieving symptoms and it is inexpensive . From thIn this paper, we describe the organization of the trial, including strategies to tackle anticipated recruitment and retainment challenges. In addition, the results of an external assessment of the recruitment process are presented.To separate possible disease-modifying effects from the direct symptomatic effect of levodopa, a multi-center, randomized delayed-start, double-blind placebo-controlled trial design was used. Patients with early PD whose functional health did not yet warrant initiation of PD medication were randomized to either 80 weeks of treatment with levodopa/carbidopa or 40 weeks placebo followed by levodopa/carbidopa for 40 weeks. A total of eight study visits were necessary to be able to adequately measure the progression of symptoms. To be able to detect a minimal clinically important difference of 4 points on the Unified Parkinson’s Disease Rating Scale at 80 weeks, 446 patients needed to be included [Planning for the trial took place in the beginning of 2010. To complete recruitment in a reasonable timeframe of a few years, we estimated the number of potentially eligible patients in the Netherlands, as this would indicate how many centers were needed to refer patients for the trial. In December 2009, the population in the Netherlands aged between 55 and 75 numbered 3,541,977 people . The incTo verify whether our estimated inclusion ratio was expected to be realistic, we also examined other relevant studies. As the TEMPO-, ELLDOPA- and ADAGIO-trials all had similar target populations—recruiting patients with early PD in most Western countries, in a randomized RCT using a placebo—these trials could be examined to verify whether the projected inclusion ratios of 19.2 and 22.5% were realistic , 11, 12.The trial infrastructure consisted of five regional main study centers strategically spread throughout the Netherlands, of which one was the principal study center. At each of the five centers, a trained research nurse was stationed. When a neurologist diagnosing PD thought a patient was eligible, the trial was briefly introduced, printed trial information was provided, and permission was asked to send contact information to the principal study center. This information consisted of the date of referral, name of the referring neurologist and center, a filled-in checklist with inclusion and exclusion criteria, and the patient’s name, date of birth, address, and phone number.After the contact information was registered at the principal study center, the research nurse at the patient’s regional main study center was automatically informed by e-mail. Within three working days, the referred patient was contacted by phone to answer possible initial questions of the patient, and an appointment was made to further explain the trial. All procedures—informing the patient, inclusion, randomization, and assessments—were performed by the research nurse at the patient’s local center or home, and supervised by the researcher in the regional main study center. Patients were compensated for travel costs. When an assessment was performed in a local center, it only had a facilitating role in providing an outpatient clinic room, as all necessary equipment was brought by the research nurse. As a result, the time investment for referring neurologists was kept minimal, continuity of research nurses for patients was guaranteed at a high degree, research nurses could focus on the LEAP trial because of the large number of assessments that were scheduled, and personnel costs were low. The referring neurologist remained the treating and main responsible neurologist for the patient during the study.Considerable effort was directed to raising trial awareness before and during the trial. The communication strategies primarily targeted neurologists in all centers that signed the IPS, since these could refer patients for the trial. All communication, management, and administrative tasks were executed by the coordinating research nurse at the principal study center, principal investigator, two PhD students, the research nurses at the regional main study centers, and occasional administrative help from medical students.If it was not possible to plan a presentation, the center was not allowed to refer patients because of an expected lack of commitment.Before starting the trial, the main contact person of a center received a scripted phone call to explain the trial, emphasizing that the results of the trial would have clinical consequences, and that time investment for checking study eligibility and referral was kept to a minimum—having in mind the busy schedule of a general neurologist. Answers to questions were prepared beforehand. Six months before starting recruitment, a kick-off presentation was given to explain the trial in all centers that signed the IPS. During this presentation, it was explained how the trial team thought what would be the least confronting method to introduce the trial by the neurologist—often very soon after diagnosis: first, it was advised to inform the patient that there is a large trial in the Netherlands for patients with early PD investigating when to start with PD medication and that the neurologist thinks the patient could be eligible for the trial. Second, the patient could be asked if they consented that contact information was sent to the principal study center in order for a research nurse to contact the patient and further explain the trial. Furthermore, as the trial team did not budget reimbursements for recruiting neurologists, it was explained how the trial team minimized the time and administrative burden for participating neurologists, and that the main contact person of referring center was included in the LEAP Study Group—and with that in the main article publishing the results of the trial. Finally, a study website (leapamc.nl) was developed by a professional website designer, and accounts at Facebook and Twitter were set up to regularly share trial news. Pocket cards and posters with the inclusion and exclusion criteria and the registration process were handed out for the offices in the outpatient clinics of all referring centers.To reraise awareness and receive feedback concerning the logistics of the trial, the main contact person of all referring centers was called on a regular basis, asking them to keep the trial under the attention of his or her colleagues, how we could further accommodate the neurologists at that center, whether there were any issues in relation to the clinical follow-up of included patients, and to again explain how the trial team thought what would be the best way to introduce the trial.Monthly e-mails were sent targeting all participating neurologists to inform about the trial progress using a dashboard with an overview of the inclusion progress. Each time an important inclusion milestone was met, a newsletter was sent to all referring centers, combined with a large cake, pens, or mugs—all having the LEAP logo clearly visible. Approximately 1 year after the start of enrollment, all centers that actively referred patients were approached for a second presentation to give an update about the trial progress and reraise awareness of the trial. Two times, a presentation was allowed during the yearly congress of the Dutch Movement Disorders Working Group.To bring the trial to the attention of possibly eligible patients with early PD, a presentation was given at a large patient congress early in the course of the trial, and two lay publications explaining the trial were published in the magazine of the Dutch PD patient association. Before initiation of the trial and during the trial, all research nurses were trained at several teambuilding meetings on the study procedures during the contacts leading up to the inclusion of a patient. During these trainings, instructions were given about the best, neutral ways to present trial information to an eligible patient—having in mind that patients were necessarily asked to participate in a trial at an emotionally difficult moment soon after being diagnosed with PD.Safe manufacturing, packaging, labeling, storing, and shipment of trial medication is highly specialized, and time-consuming and administrative demands concerning accountability are equally demanding—even for levodopa, the most commonly used PD-medication for several decades. The trial team contracted ACE Pharmaceuticals and ACE Apothecary  to execute all trial medication-related issues, instead of conventionally contracting the pharmacies of all referring centers or those at the main study centers. Much time and effort were saved for the trial team in this way, and probably made the risk of trial medication-related mistakes smaller. After the digital randomization by a research nurse, an e-mail was automatically generated by the database and sent to ACE Pharmaceuticals and ACE Apothecary. Subsequently, the trial medication was shipped to the patient’s home. This ensured that the principal study center only had one professional partner responsible for all trial medication-related issues.According to the Dutch law, Medical Ethical Committee approval was obtained at the principal study center. As neurologists only referred patients for the trial, the Medical Ethical Committees of just the four other regional main study centers had to approve local execution of the trial; all referring centers were given notice of this mode of conduct with a standard letter.To cover the costs of executing this investigator-initiated trial, a total of about one million Euro was obtained from The Netherlands Organization for Health Research and Development , Stichting Parkinsonfonds, Stichting Parkinson Nederland (both Dutch charitable funding organization for PD research), and Parkinson Vereniging (Dutch patient organization). Trial medication in the first 42 weeks of the trial costed approximately EUR 250,000; a large part of other expenses went to the research nurses’ salaries. Funding for the research nurses in the five main study hospitals was provided on the basis of included patients. Thus, per included patient, there were enough resources for that hospital to perform all measurements. The contract with the pharmaceutical company providing the study medication was on the basis of a fixed contract price. Therefore, no extra funding was needed for the study duration extension.For this goal, a version of the QuinteT Recruitment Intervention was used. A QRI is usually integrated with an RCT from the design stage to optimize recruitment, but a QRI-Two has been designed to be applied to RCTs that are underway by reviewing trial materials (protocol and patient information) alongside recruitment monitoring data . In thisDuring the study, we registered data concerning all referrals and inclusion, which included the following: name and date of birth of the patient, referral date and center, referring neurologist, date of inclusion, when and which trial personnel was employed, when and which actions were undertaken aiming to improve referral or inclusion rate, and reason of non-inclusion.For the QRI-Two review, we analyzed the following. Based on the registered data, we calculated the ratio of referred patients versus possible eligible patients, based on the population at the moment the trial started including patients nationwide in January 2012. To investigate whether there were effects on referral- and inclusion rate of seasons, vacations, sending cakes at inclusion milestones, or the change of a research nurse, we visually inspected graphs showing referral and inclusion rates. Finally, we analyzed variations across centers in reasons why patients were not included. Analyses are descriptive; no statistical tests were done.The prospective recruitment strategies mostly focused on the organizational and logistical issues, which the LEAP trial team anticipated and addressed to complete recruitment to the trial.There were 62 centers that signed the IPS. Seven academic and fifty non-academic centers participated in referring patients for the LEAP trial  in the most populous region Southwest, and high (19.3%) in region Northwest, the region of the principal study center. Both regions are similarly highly urbanized and densely populated , which is 6.8% of the estimated eligible patients. The overall ratio of included versus referred patients was 58.2%, with only the northeast region having a somewhat lower inclusion ratio of 49.5% , including a total of 170 patients—38.1% of the total 446 patients  because before the first contact with the research nurse PD medication was already started—suggesting that there may not have been equipoise for these patients. Other reasons for non-inclusion were clearer, in that the patient could not be reached, already participated in another trial, or because of extended stays outside the Netherlands. However, there were 41.6% excluded for “unknown” reasons, which may reflect poor reporting or “hidden” issues with eligibility/equipoise . A furthThe review of recruitment and monitoring data found some indications of potential issues with eligibility, equipoise, and study presentation. These included variations in the contributions of centers to enrollment even when populations were similar, the reporting of patient preferences for one treatment or another  among 39% of potential participants, and patients not eligible for the trial because they had already been started on medication. The LEAP trial team reported that while the topic of the trial was of great clinical interest, and there was sufficient “community equipoise” to launch the trial, contemporaneous notes and monitoring data indicated that some centers favored treatment with medication and others with delaying medication either when they joined or during recruitment. Together, these are all clues to potential issues with equipoise, eligibility, and managing patient preferences in some centers or among some clinicians .The LEAP trial was a large, successful, investigator-initiated landmark medication trial answering a burning clinical question on a limited budget. It showed that in early Parkinson’s disease, levodopa/carbidopa 100/25 mg TID had no disease-modifying effect over 80 weeks . HoweverThe clinical relevance of the trial and the minimal effort required meant that general neurologists throughout the Netherlands could be enthused to take part, which was reflected in the high number of centers participating in the trial. Because general neurologists usually tend not to participate in trials, we mark their participation and the formation of an informal research network as a key spin-off achievement of the LEAP trial. The LEAP team developed and implemented a large number of strategies to optimize recruitment, including (a) efficiently streamlining trial procedures such as centralizing medication provision and Medical Ethical Committee-approval, (b) raising trial awareness among neurologists, (c) ensuring trial processes were easy to complete and took as little time as possible, (d) supporting centers when they started to recruit with frequent communication and rewards for success, and (e) ensuring participation was easy and as pleasant as possible for patients by liaising with patient groups and having home visits and continuity of nursing staff. The administrative burden was diminished greatly by only having to obtain Medical Ethical Committee approval in the five main study centers, while patients were being referred from 57 centers, and because all trial medication-related tasks were outsourced to one central party. Therefore, the research team in the principal study center could be kept small and focused on trying to improve recruitment and inclusion rate and maintaining an up-to-date trial administration. The combination of all these factors resulted in the low costs for this large trial, including the cost-neutral extension of the trial. Funding for the research nurses was provided per included patient, and as recruitment lagged, research nurses were seldom occupied with the trial on a full-time basis, and also had some other work in their respective hospitals. The contract with the pharmaceutical company that provided the study medication was on the basis of a fixed contract price; therefore, no extra funding was needed for the trial extension.As the referral rate was considerably lower than expected, the extended recruiting period has been partly compensated by the high inclusion ratio of 58.2% of the referred patients. One of the key contributors of the high inclusion ratio may have been the combination of optimal training of research nurses, ample time for face-to-face contact for the patient with mostly the same research nurse, and the convenience that assessments could take place at the location of the patients’ preference . AlthougDespite the fact that the LEAP trial completed its inclusion goal, it took over 2 years longer than expected, even though a large number of centers participated in the study. Reviewing the recruitment data, we noted that a relatively small number (15) of the participating centers referred the majority of patients (70.2%). In contrast, a similar number—13 centers—only referred one patient. The inclusion criteria required that patients had to be referred shortly after being diagnosed with PD—often an emotional moment, which could have influenced the willingness for a patient or neurologist to discuss referral for a study—suggesting the possible involvement of a “hidden challenge” such as equipoise or issues with study presentation in some of the centers. The aimed for inclusion ratio of all estimated eligible patients of about 20% proved to be too ambitious, although prior to the study, we did not possess data to have a more realistic estimation. It is a key priority for future investigator-initiated trials to have better data to estimate recruitment rates .In this context, the steady referral rate of all participating centers throughout the trial is of interest, particularly despite the efforts to improve it—as this also suggests that there may have been other factors at work. Trial teams need to decide whether to focus resources on improving inclusion ratios or referral rate to enable as many eligible patients as possible to consider participation .Furthermore, as a majority of the centers from which the most patients were included were situated in the region of the principal study center, this shows that this is apparently a factor that boosts the willingness to participate in referring patients. The large difference in the ratio of estimated eligible patients versus referred patients of the Northwest and Southwest regions supports this opinion. These centers had interns, residents, or neurologists previously trained at the principal study center, suggesting that these centers could have a higher commitment to the trial. Previous QRIs also suggest such variations might also signal that sites varied in their assessment of eligibility and/or equipoise , 20.In our trial, 39.4% of the not included patients did not participate because of reasons related to the patients’ opinion, possibly leaving room for improvement of the inclusion ratio. The presence of patient preferences distributed across the interventions is often an indicator of underlying difficulties with equipoise that are reflected in the way the trial is presented to patients . FinallySince QRI research has shown that clinicians who are more comfortable with equipoise can present the study more effectively, a QRI integrated prospectively would have investigated the reasons of neurologists to refer patients and the way they and the research nurses presented the trial to patients . WithoutThis study has shown that the LEAP trial—an investigator-initiated medication trial studying a neurodegenerative disease in an early stage—was successful in achieving the aim for sample size. This was achieved on a limited budget by focusing on minimizing administrative and organizational procedures. However, the trial did take 2 years longer than anticipated to complete recruitment. A review of recruitment processes and monitoring data showed that centers with closer institutional ties to a principal study center tended to have a higher referral rate, and variations in referrals and reasons of non-inclusion suggested the presence of “hidden” challenges related to clinical equipoise, patient eligibility, or study presentation. Integrating a recruitment intervention such as a QRI prospectively could have explored the hidden challenges and found solutions that could have increased recruitment efficiency.


Infection is a major cause of pregnancy failure in eutherian mammals. The reproductive pathogens are diverse and can be either viral, bacterial, fungal, or protozoan. There is a direct negative impact on pregnancy and, in the case of farm livestock, sustainability is compromised, leading to significant economic loss. These novel contributions to the latest research in the field of reproductive pathology represent a major breakthrough for the improvement of animal and human health within the “One Health” concept.The contributions were six articles published within the topic totaling more than 103,000 views to date.Montbrau et al. from Spain reported the efficacy of a new commercially available inactivated vaccine against ovine enzootic abortion (OEA) produced by Chlamydia abortus, an intracellular bacterium that causes strong economic losses in the small ruminants industry worldwide. The authors suggest that this vaccine is adequate for the control and prevention of OEA, suggesting further future studies to elucidate the type of cellular protective immune response induced by the vaccine.Santos et al. from Brazil showed a brief, but very current review, on canine brucellosis, an infectious and zoonotic disease caused by Brucella canis. The authors emphasized the importance of completing the serological diagnosis with molecular methods as well as the development of safe vaccines necessary to control canine brucellosis and its associated risk of zoonosis.Decaro from Italy presented an excellent update on HoBi-like Pestivirus, an emerging group of pestiviruses that are detected in cattle and other ruminants in South America, Europe, and Asia, where they cause serious reproductive disorders in these species.Wolf-Jäckel et al. from Denmark, using molecular methods such as polymerase chain reaction (PCR), next-generation sequencing, real-time quantitative 16S rDNA PCR (qPCR) amplicon sequencing, and FISH, found that these molecular methodologies are good alternatives to traditional microbial culturing methods. The authors identified several bacterial and fungal abortifacients from aborted or stillborn bovine fetuses and placentas.Pastor-Fernández et al. reviewed the interactions between placental host-apicomplexan parasites such as Neospora caninum and Toxoplasma gondii, the etiological agents of bovine neosporosis, and sheep and goat toxoplasmosis, respectively. The authors described the interactions and the importance of an alternative to improve the in vitro systems based on caruncular and trophoblast cells. The use of placental explants is widely developed in human research. The authors discussed in vivo, in vitro, and ex vivo placental models that have proven useful to unravel the pathogenic mechanisms and the host immune response responsible for fetal death caused by neosporosis and toxoplasmosis.In Spain, The editors are convinced that you will find in this Research Topic stimulating, and that the information may generate new ideas for research.As a personal experience, it has been a pleasure to work as a co-editor with the journal Frontiers in Veterinary Sciences and I encourage my colleagues to participate in similar actions that can contribute to the transfer of knowledge on reproductive science in the veterinary medicine area.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.


Concerning primary site infection, 54.02% of the participants had the intra-oral cavity within the past 5 years. Muslims had greater odds to experience an OC adverse outcome and death  than the Catholics. Those with no formal education significantly had greater likelihoods to have an OC adverse outcome and death  than those with higher education or university. Those with primary education had greater likelihoods  to have an OC adverse outcome than those with higher or university education. Those with oral hygiene had less risk to have an OC adverse outcome and death  than their counterparts. Using multi-sectorial approaches, including policy makers, clinicians, and researchers from public and private institutions, may be of an added value to promote clinical research on OC for earning knowledge, contributing to combat risk behaviors and improve the population's information and education on OC prevention.Oral cancer (OC) is one of the most common cancers that remain global public health concerns in low- and middle-income countries. The epidemiology of OC in Africa endures uncertain. Earlier reports suggested a relatively low incidence of OC among Africans. Acting on behavioral factors and setting early diagnosis and treatments of OC can tremendously reduce morbidity and mortality related to it. This study determined factors associated with the OC adverse outcome and death in the Rwanda Military Hospital. A cross-sectional study was conducted among 311 medical records of patients who consulted in the Oral and Maxilla Facial Department between January 1, 2007 and December 31, 2019. Associated factors were estimated by use of odds ratios (OR) with their 95% confidence intervals (CI) in bivariate and multivariate logistic regression analyses to estimate predictors of an OC adverse outcome and death. Almost three quarters of the participants were from rural areas ( The epidemiology of oral cancer (OC) indicated that this disease is the 11th common disease worldwide, and two thirds of the cases are from low- and middle-income countries (LMICs) . So, theEvery patient suffering from OC presents different symptoms and levels of pain. Staging and diagnosing the disease are important for tailored and adequate treatment for each patient's specific OC type . The typMoreover, factors like smoking, untreated oral disease, alcohol, and HPV contribute more to the burden of OC in different regions of the world , 15, butIn Sub-Saharan African countries, high prevalence of mortality due to poor knowledge of OC management and other health issues has been debatable . This inA retrospective hospital-based cross-sectional study was designed to estimate the proportion of oral cancer case fatality at Rwanda Military Hospital (RMH) and determine the factors associated with the oral cancer adverse outcome and death among patients seeking healthcare services at the RMH.This study was conducted at the Rwanda Military Hospital (RMH), which is a public health facility situated in Kigali City, Rwanda. This health facility is the only military hospital and one of the five national referral hospitals in Rwanda , 28. TheThis study targeted patients presenting diagnosis of oral cancer at RMH between January 1, 2007 and December 31, 2019. The study included the participants who represented signs and symptoms of oral cancer and visited the Oral Maxilla Facial Surgery department of this hospital. The patients who were diagnosed with OC were provided with healthcare interventions or treatments. The current study was only conducted among the patients who were at the fourth stage and who were under the treatments such as surgery and radiation. The medical records of all the patients with other diagnosis other than OC at the fourth stage were excluded from this study. This department recorded a total of 311 patients with OC as the principal diagnosis at the fourth stage; hence, all the diagnosed patients with OC were exhaustively included in this study.Data were collected by trained health providers for 2 weeks in January 2020. The participants from the study had their health records at the abovementioned department. All the data were extracted from the patient registries from this department. Records of patients with cancer were reviewed to extract clinical information and a demographic profile that were routinely recorded in the department that provide care for patients with OC. Among the patients that were contacted to complete missing information, no patient refused to take a part in in the study. However, for the missing information, the researchers contacted the patients or their guardians to provide more details. These patients were contacted over the phone to collect the missing information about their health status. Missing data and follow-up data were retrieved and updated from the case records. Besides, all discrepancies were appropriately checked and corrected by referring back to the original patients' records. About 5% of data validation was applied by second data entry personnel to assess accuracy of the data. All rates of missing information were reported for each question of the questionnaire. A paper-based checklist was used for data collection. Furthermore, the researcher inputted the data into Microsoft Excel 2010 and then later exported them to STATA version 13.0 for statistical analysis.The main outcome variable was “an oral cancer adverse outcome and death” in which we refer to as a patient experiencing an adverse outcome and death or not. This binary variable was coded as “1 = Yes” and “0 = No.”Independent variables were investigated. Those factors included sociodemographic variables and behavioral characteristics of the patients. Among the sociodemographic variables, type of residence was coded as follows , gender of the patient grouped as , education categorized as , while ages of the patients were grouped into . Furthermore, marital status was coded as  and religion as . Concerning behavior-related factors, the alcohol use was categorized as , smoking or tobacco use as , and oral hygiene as .p < 0.05 were considered.All descriptive and analytical statistical analyses were performed using STATA software version 13. Bivariate logistic analyses were performed to indicate the associations between dependent and independent variables. The significant variables in bivariate analyses were exported into multivariate logistic regression models for determining associated factors of an OC adverse outcome and death. The odds ratios were used to assess associated factors. The 95% confidence intervals and statistical significance levels of The Helsinki declaration regarding the ethical principles for medical research that involve human participants was taken into consideration as recommended , 30. Then = 111, 35.7%) were aged 41–60 years, were males , and were married . Near two thirds of the study participants  were Catholics, and about a half had at least primary school education . Overall, the participants came mostly from Eastern Province  of Rwanda, with a greater proportion of them residing in rural areas . The results also demonstrated that a good proportion of the participants came from middle-income class  who were likely to brush their teeth at least one time daily . Additionally, more than 50% of them never smoked tobacco  even though most of them had ever consumed a certain quantity of alcohol  (Our findings show that the average age was 50.6 years (SD = 20.2). Out of 311 records, the majority  .n = 166, 53.4%) were diagnosed with intra oral cavity within the past 5 years. More patients  accepted OC treatments at our RMH than the few  who refused   died, but the majority survived  .p = 0.011], while those with secondary education were nearly three times more likely to experience an oral cancer adverse outcome and death . Furthermore, the participants with primary education had nearly 2 times more exposed to an OC adverse outcome and death  than those with higher education. Furthermore, the results indicated being Muslims was significantly associated with an OC adverse outcome and death. These results showed that Muslims had almost 9 times the risk to experience the oral cancer adverse outcome and death  than the Catholics , atholics .p < 0.001] when compared to the Catholics. Furthermore, those who had no formal education were almost 3 times more likely to have an oral cancer adverse outcome and death  when compared to those with higher education. Results indicated that those who attended secondary schools had almost 2 times greater risk to develop an OC adverse outcome and death  when compared to those who had higher education or university. The results also showed that those with oral hygiene were less likely to experience the OC adverse outcome and death  , = 0.039] .The purpose of this epidemiological study was to determine the factors associated with the OC adverse outcome and death in the Rwanda Military Hospital (RMH). Although the case fatality was not documented in the other parts of Africa, ~2.9% of the patients with OC who were consulted at the RMH died. This case fatality rate is higher than that reported from Uruguay . Our resAmong these patients, the compromised patients with four-stage OC, the study deducted that factors, such as education, poor oral hygiene, and religion, were significant predictors of the OC adverse outcome and death. Our results are similar to the findings from prior studies , 35. EssEven though the studies in United States identified that the stage of cancer, age, overall health situation, and primary site infected affect the treatment success of oral cancers , 40, 41,Furthermore, the study found that religion plays an important part in determining if individuals are treated or otherwise from oral cancer. Our results revealed that the Muslims were more likely to have greater likelihood of having an OC adverse outcome and death when compared to the Catholics, which controverted the preceding studies that documented no sociodemographic characteristics contribute to a low rate of patients with OC who accept OC treatment initiation or delay . Even thThis study had numerous limitations. The inability of the study to detect factors associated with oral cancer in terms of an anatomical oral cancer site was probably related to retrospective nature of the study and the fact that it relied on secondary information from a number of variables and observations. Besides, the study was limited to the sample that was available but not big enough to allow generalized findings. This suggests further studies with more variables and observations to investigate factors associated with unspecified oral cancer sites among cases recorded at RMH. For the latter; the topic for this study shows that the related data have the most of challenges regarding completeness and consistency in data collection. This handicapped this study to clearly and objectively estimate the prevalence of the oral cancer adverse outcome and death. The registry did not provide complete information on certain vital factors such as HPV and HIV status. This confounded the study and might have affected the true estimate of the oral cancer adverse outcome and death.To conclude, the mortality in this study among the patients diagnosed with OC in the fourth stage of the OC represented an elevated OC adverse outcome and health that seem to be associated with the major factors, such as education, religion, and oral hygiene. Hence, these parameters need to be taken into account for the individualized therapy management of patients with OC, and more efforts are important to bring light on this burning sector of public health. Based on the nature of this study, we recommend to include in the cancer registry an exhaustive list of necessary variables to be able to deeply understand the epidemiology of OC. Additionally, as several previous studies were hospital-based studies and population based-studies are rare, we recommend further epidemiological studies to conduct population-based studies on assessing the burdens of the OC in sub-Saharan countries where this disease remains the public health burden.The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding author.Ethical approval was provided by the Institutional Review Board, Rwanda Military Hospital in the Republic of Rwanda. After obtaining the authorization to conduct the study from the Ministry of Health through the general director of RMH, the permission to use the medical records was requested from the patients or their guardians, using the telephone registered at the hospital. Confidentiality was ensured.HN had substantial contribution to conception, data collection, and statistical analysis. AU supervised the study, contributed to the study conceptualization, and assisted in data analysis. AN assisted in conceptualization and implementation of the data analysis and interpretation of the results and provided the manuscript feedback. AU and AN played the editorial role of the manuscript. EB drafted the manuscript and contributed to the interpretation of the results and data analysis. All the authors read and approved the final manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.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.


Animals are an integral and important part of human life. It is clear that when traveling, tourists often choose places where animals are present. They look for places with wild animals more often. Our article introduces issues concerning the role of farm animals in the creation of agritourism products and the prospects of using animals in agritourism. On the one hand, farm animals are an additional source for people who run agritourism farms and make the stay of tourists in rural areas more attractive. The presence of livestock acts as a magnet, attracting more tourists to these farms and achieving higher returns on agritourism activities. However, among the reasons for the lack of contact with animals in agritourism offerings, farmers indicated: the lack of financial resources and the lack of conditions to provide the animals with adequate maintenance. It is worth introducing farm animals as a tourist attraction in agritourism offerings.Animals are an integral part of human life. Currently, they constitute a relevant factor contributing to the tourist experiences of individuals travelling for tourist purposes. Domestic (farm) animals constitute a tourist attraction, are a source of income for individuals running agritourism farms, and render the tourists’ stay in rural areas more attractive. It is important to maintain the welfare of livestock based on principles of sustainability. The authors conducted research among agritourism providers in Wielkopolska Voivodeship. The aim of the survey was to determine whether agritourism farms keep livestock, what species they are, and whether they are important in building an agritourism product and what the prospects are for using animals in agritourism. A questionnaire was used for the study. The use of a variety of animal species facilitates the maintenance of biodiversity on the farm. Our research shows that 57.3% of the analysed agritourism providers included animals. Additionally, we discovered that the presence of livestock acts as a magnet that draws more tourists towards the individuals running agritourism farms and thus causes them to obtain higher profit from the agritourism business. According to the surveyed individuals, the most influential reason for the absence of livestock on their farms was the lack of financial resources and conditions to provide the animals with proper maintenance. Such findings may prompt the introduction of livestock as a tourist attraction in agritourism in other regions. Animals have been accompanying humans for centuries , constitAnimals are an important and influential element of tourism. For many people, they constitute an integral part of their valued recreational activities . TourismAccording to World Animal Protection, more than half a million wild animals are used as tourist entertainment, yet this number includes only the registered animals in tourist facilities . WildlifNon-consumptive wildlife tourism accounts for 20 to 40% of all international tourism . It is eWildlife tourism provides nature with the opportunity to earn its own right to survive , while tTourism uses various species of animals in different ways. Opportunities to observe or interact with wild animals have been created in numerous tourist destinations that are easily accessible and very popular among many consumers. Such opportunities vary from country to country, with each destination having its own legal and cultural approach to animal welfare. Animals can participate in festivals, be used as street entertainment, or be observed in captivity. They are also frequently associated with the source of income of local communities . TouristThe creation of new tourism products is an ongoing process. One of its primary issues consists of creating them in a way that allows attracting the largest possible number of tourists. Regardless of the geographical region or wildlife, observing, photographing, or having direct contact with wild animals has always been the aim of travels for individuals who value interactions with animals. An example may be trips to Africa organised to observe the so-called “Africa’s big five animals” , gorillaCategories of wild and domestic animals are not fixed and permanent—they are created by humans and contain numerous contradictions . AnimalsChanges in tourists’ tastes may be used to improve standards of animal welfare in the future. Moreover, many Western tourists are inclined to practise “sustainable”, “eco”, and “ethical” tourism .Currently, more attention is focused on the welfare of kept animals. For many modern societies, this is an issue of increasing importance, which dates back to the early British animal protection laws of the 19th century . A propeUnequal power relations, according to which humans control all aspects of animals’ lives;Domestic animals are “everyday” animals, which indicates they are not regarded with the kind of interest that tourists take in strange and exotic animals;There is tension created by a significant number of domestic animals used as a source of food;Due to their controlled existence, domestic animals are perceived as less authentic than wild animals.Research on domestic animals in tourism, including livestock, has received much less attention than studies on wild animals . Four reUndoubtedly, human–animal interactions are extremely important components of the overall experience for humans . AnimalsOne form of tourism in which animals, particularly livestock, are part of a commercial product directed at tourists is agritourism. The literature on the subject does not include works that focus on the use of domestic animals in tourism. Our work helps to fill this gap.Livestock can be a potentially profitable enterprise for small-scale agricultural operations. Livestock can offer a farm new revenue streams as well as increased fertility and weed control. Additionally, this activity can become a tourist attraction and can attract tourists, giving the farm a new function, a tourist function. However, there are new challenges of raising livestock on agritourism farms which are discussed here, including particular considerations related to producing poultry, rabbits, hogs, sheep, goats, bees, and cattle. This study aims to determine whether farm animals—and if so, which species—are kept on agritourism farms, and whether the farm animals affect the attractiveness of the agritourism offering.Agritourism is not a new phenomenon. Busby and Rendle  believe The most important specific features of agritourism distinguishing it from other forms of tourism are the elements that connect the main agricultural and tourist activities, which are the rhythm of life on the farm, the presence of livestock, fresh food, smells, sounds, the proximity of the farming family and villagers, possibility of getting to know family habits, everyday activities of villagers, hospitality, new acquaintances and friendships, culture and customs, tradition and history of villages and the region, folklore, space, contact with nature, freedom of movement, silence, peace, possibility of recreation and sports, etc. ,48,49. UMajewski  emphasis−Observation of the agricultural production process including plant and animal production and food processing, as well as guided tours or private farms (ranches), which are widely offered in different countries;−Actual participation in the process of plant and animal production and processing ;−Animal shows or demonstrations, including cow milking, sheep shearing, angora rabbit shearing, cattle sales, or cowboy rodeos;−Marked trails on the farm;−Direct contact with domestic animals or the nature of farms in different kinds of petting zoos or safaris .Agritourism shows people what is happening on the farm in order to better inform them about daily agricultural practices and activities. Its underlying assumption is that if people see the farm, they will better understand what is happening there and why, which in turn should reduce concerns about animal welfare or production practices . Farm anFarm animals may constitute a valuable agritourism attraction while simultaneously being part of the cultural heritage of rural areas . For manTo be part of the tourism product and a tourist attraction, animals must be provided with adequate welfare which is not necessarily better on small farms compared to large farms. Observing the behaviour of farm animals is the first element in assessing their physical and mental comfort .Freedom to perform natural behaviour, however, is the main issue in the eyes of the general public, so technologies in which the use of enclosures and pastures that should be the basis of nutrition for many species during the growing season play a huge role. These technologies simultaneously ensure a better quality of food raw materials . KeepingAnother method includes using livestock as a raw material for meal preparation. The increasing tendency to seek locally produced food applies particularly to the hospitality and tourism industry, including agritourism, which heavily relies on local identity .Aspects such as humane treatment of animals, the environmental impact of the main supply chain, and the interest of tourists in tasting local food, especially meat, in agritourism is important for many consumers . TouristThe agritourism product is a complex category, and its individual elements perform different functions . LivestoAccording to Sayre and Henderson , animalsAccording to Hurst and Niehm , the marThe study was conducted in 2019, in the form of a telephone interview called CATI (computer assisted telephone interviews), based on questionnaires  preparedThe questionnaire consists of the following parts: part I—questions related to the location of the agritourism farm (3 questions), part II—records and a brief description of agritourism and agricultural activities (8 questions), part III—identification of species kept on the agritourism farm (2 questions), part IV—assessment of the attractiveness of animals kept on an agritourism farm (5 questions). Seven reasons for the lack of animals are identified in the questionnaire. At the end of the questionnaire, the respondents could indicate which species of animals, in their opinion, could make the agritourism offering more attractive.Sample size determination is an important major step in the design of a research study. Its calculation is an essential step in research protocols and is a must to justify the size of research studies in papers, reports, etc. ,72. The study sample consisted of 394 agritourism farms from a total number of 686 farms (as of 2017) located in Wielkopolska Voivodeship. n is sample size, e is permissible error, N is population size, and Zα/2 is value resulting from the confidence interval used; for a 95% confidence level, Zα/2 = 1.96, and P is the estimated proportion in the population . P is the estimated expected proportion in the population covered by the study. As the proportion in the population of operators is unknown, the least favourable assumption was made, namely that P = 50%, because at that P level, the product P(1 − P) reaches the maximum value.The finite population sample size formula was used for calculating the sample size of agritourism farms covered by this study:P = 50%;Confidence level = 95%;Permissible error = 5%;N = 686 (the number of agritourism farms in 2017).It is thus assumed that:The minimum sample size was 246 when the maximum error was 5%. Participation in the study was voluntary and anonymous. When entering the study, it was assumed that if the telephone contact was not possible during the first phone attempt, the next phone attempt would be conducted after one hour. When the second phone attempt was not successful, subsequent phone attempts were made the next day. A total of 394 phone calls were obtained during the survey. All data gleaned were subjected to preliminary analysis, followed by statistical analysis, with the identification of significant differences for two independent samples by the Mann–Whitney U test and the Wald–Wolfowitz runs test. The statistical analysis was performed using the STATISTICA 13.3 program . Three data presentation methods were used to characterise the phenomena examined: tabular, graphical, and descriptive.A total of 365 providers of agritourism agreed to participate in the survey and be interviewed, while 29 refused to participate in the survey. According to the survey, 117 agritourism operators did not run any agritourism business in 2019. The agritourism activity related to hosting tourists on a working farm was carried out by 248 farmers. Only 142 farms out of all the analysed farms kept animals.Given the period of conducting the agritourism business, it was found that the oldest agritourism farm hosted tourists continuously since 1980, while the youngest agritourism farm started hosting guests for on-farm recreation in 2018. It should be noted that more than 1/3 of the surveyed agritourism farms were established in the 20th century. The accommodation base is the most important component of agritourism. All the quarters included in the research provided their agritourists with accommodation in rooms. The number of rooms largely determines the possibility of accommodating a certain number of guests, and the number of beds is also important. The average number of rooms in the researched farms was up to five (80.6%), and the number of beds was 15 (Me = 12). Analysing the data on the number of tourists enjoying leisure in the surveyed agritourism farms, it ranged from 10 to 500 per year.To achieve the research objective, the surveyed agritourism farms were divided into two groups. The first group consisted of providers of agritourism who owned livestock: 142 farms with animals. The second group included agritourism operators who did not own animals: 106 animal-free farms. The study is shows that 57.3% of the analysed agritourism farms in the Wielkopolskie Voivodeship featured animals.When analysing the data concerning agricultural activities carried out in the surveyed farms , statistp < 0.000). There was no statistically significant differentiation (p > 0.05) in the number of rooms and number of beds between the studied groupsOn the other hand, taking into account the share of income from agritourism activity, a statistically significantly higher level was found among operators with animals. Higher income from agritourism activities in facilities with animals resulted from the greater number of tourists using their offering. Their services were used on average by 117 tourists, and the average for operators without animals was 73 tourists. It is worth emphasizing that the average value of the number of tourists turned out to be statistically significant , hens (62.7%), cattle (18.3%), goats (16.9%), sheep (12.7%) and pigs (12.7%) were the most popular animals kept on farms. It should be noted that one in five of the surveyed facilities kept fish in ponds owned by the farm, and one in six of the surveyed facilities kept rabbits. Livestock can become an element of the core of an agritourism product, a basic product, or an extended product . For peoThe choice to keep animals is not accidental since these animals are the key to increasing the tourist attractiveness of the run business. They are the source of meat, excluding horses, which are not eaten in Poland, and they are the source of valued products such as milk, eggs, and fish. The conducted analyses also showed that during the selection of animal species, agritourism operators paid attention to their origin and importance for the conservation of rural heritage. Therefore, they most often chose native breeds of livestock. The respondents who did not keep animals were further asked about the reasons for not keeping animals on the farm . According to almost half (49.1%) of the providers of agritourism, lack of money to keep animals, followed by lack of conditions to keep them (45.3%), is the main reason for not having animals. Interestingly, according to one third of the respondents, the reason for the absence of animals in their agritourism farm is the lack of interest from tourists.First of all, the respondents indicated the reasons that were included in the answer to the questionnaire question; in addition, some of them gave other reasons that were not on the list of answers to the question.One of the reasons for not keeping animals on an agritourism farm was the poor health and age of the farm owners.Respondent 1: “My age and health condition do not allow me to take care of animals”.Many owners indicated that the reason for the lack of animals on the agritourism farm was the lack of time but also the lack of people who would be able to help with the care of animals.Respondent 2: “I don’t have time to work with animals; I miss extra hands to work with animals”.Several respondents indicated that the reason for the lack of keeping animals on an agritourism farm was the lack of appropriate infrastructure, and more specifically of buildings in which these animals can be kept.Respondent 3: “I don’t have suitable buildings for keeping animals”.In contrast to several owners of the surveyed agritourism farms, some indicated that the reason for not keeping animals on their farm was cooperation with other farmers who had animals, and tourists could see them there.Respondent 4: “The animals are at my neighbor’s farm, tourists can see them there”.A few respondents stated that the costs of keeping animals were too high as the reason for not keeping animals on their farm, and their production was described as unprofitable.Respondent 5: “Keeping animals is an additional cost, production is unprofitable.”The above responses from farmers indicate that they are aware of the limitations of keeping animals on the farm and providing them with good conditions and welfare. Perhaps these responses may indicate that if there was more interest from tourists, farmers would overcome the difficulties of not keeping their animals on their farm.The obtained results have practical and important consequences for agritourism owners. Our research shows that farmers consider animals an important element of their agritourism offering. This is confirmed by studies ,74 that The profitability of agritourism is an important factor from the point of view of the development of a tourist activity. The share of income from agritourism activities is important, which shows the development of agritourism as a source of additional income for the farming family . It is vLivestock is an integral part of a sustainable farm . The useKeeping animals can have long-term effects on the environment and can contribute to the preservation of characteristic plant species not found in neighbouring habitats . AnimalsIn addition to providing a variety of food products and clothing products, the animals produce manure, which is a valuable natural fertiliser that enables a steady turnover of organic matter on the farm. Natural fertilisation is part of both sustainable farming and organic farming .Large-scale farms, which also use large-scale animal husbandry, are widely used today . The useCiconia ciconia), and this may, in turn, contribute to increasing the population of the species [The grazing of livestock may affect wild species. It was found that the presence of cows on the pasture significantly influences the feeding efficiency of the white stork . However, when it comes to maintaining local biodiversity and agritourism objectives, keeping exotic animals on farms seems questionable . Exotic The native breeds of livestock, as well as native varieties of crops, are part of the national heritage . The exiTourism needs are evolving, and tourists are looking for a multi-sensory rural experience . The agrIn terms of the appreciation of farm animal welfare, it varies depending on producers and consumers. Consumers often focus on naturalness and its relation to animal welfare, while producers often focus on meeting basic health requirements . AnimalsThe role of farmers should be emphasised; they are a sort of guide playing an important role as facilitators helping tourists to overcome environmental challenges and better understand the animal world .This study makes a significant theoretical contribution to understanding the importance of livestock in building an agritourism product. A large part of the surveyed agritourism suppliers (57.3%) had animals, which are both an immanent feature of the agricultural holding and the agritourism business. In this case, there is a clear relationship related to the size of the land owned, which is important for having adequate space for these animals. Our research has shown that keeping animals in agritourism farms is an attraction for tourists visiting them.Keeping livestock provided an attraction for tourists using the offered services, but it also provided a source of income from the sale of those animals. This is confirmed by the share of agricultural income in total income, which was higher for agritourism operators who owned animals than for those who did not own animals. Plus, it is also confirmed by a higher share of income from agritourism in the group of farms with animals.The surveyed facilities usually keep several species of animals. Their selection is purposeful because these animals are not only key to increasing tourist attractiveness, but they also provide a source of meat, products, and preserves. The biodiversity conservation in agricultural holdings, especially in agritourism farms, should, on the one hand, contribute to the protection and popularisation of husbandry of local animal breeds and varieties of native plants and, on the other hand, make the offering more attractive for guests. This study does not exhaust the problem of keeping animals in agritourism farms. Therefore, it is important that such research is continued in the future, taking into account the opinions of various players in the agritourism market, both farmers and tourists. The survey used a questionnaire to obtain farmers’ opinions on keeping farm animals on agritourism farms. We believe that the research can be extended to include in-depth interviews with farmers running agritourism farms and keeping animals and those who stopped keeping animals completely. This would enable a better understanding of the importance of animals in creating a farm tourism product and the problems that arise for farmers from combining the two businesses.Future research should aim to gain knowledge concerning the preferences of potential agritourists regarding which livestock they would like to encounter during their agritourism trips. In addition, further research is needed among farmers running agritourism activities in various regions of Poland and other European Union countries and the comparison of these results.


In mid-July, 2021, Zhengzhou, the provincial capital of Henan located in east-central China, was hit by record levels of rainfall. A year's worth of heavy rain beat down on the city over just 3 days. The rain washed away cars, swamped low-rise buildings, and swept through the city. Hundreds of people lost their lives in the flood; most of them were drowned.Regional Status Report on Drowning in the Western Pacific, more than 74 000 deaths were attributed to drowning in the region in 2019. The incidence of drowning is disproportionally distributed across the region. More than 90% of drowning fatalities happen in natural bodies of water and even in domestic water storage containers in low-income areas. Among the deaths, children and adolescents living in rural areas are excessively affected.Drowning happens throughout the year, but the increased access to water bodies for leisure activities and more heavy monsoon rainfalls in the warmer season put more people at risk of drowning. As the third leading cause of unintentional injury death globally, drowning kills around 235 000 people each year, and nearly two-thirds of these individuals are from the Asia-Pacific region. In the WHO The full scale of drowning in the Western Pacific region is obscured by many factors, such as poor data collection systems and low public awareness. Some drowning fatalities are never officially recorded or classified due to the remoteness of the incidents, and many non-fatal drownings are not documented as they should be. Additionally, drowning in climate-related extreme weather is not recorded or classified as related to the extreme weather in many countries. Nearly 50% of drowning deaths are not reported in countries most affected by natural disasters. In addition, local people might consider drowning to be a careless accident rather than a problem that can be systematically solved.Evidence-based interventions have confirmed the effectiveness of formal swimming training and putting children under supervision in reducing childhood drowning. Other practical solutions include installing physical barriers to control access to water, training lifeguards, and establishing water safety and rescue teams. Additionally, imposing safe water transport regulations and improving disaster risk management have also been shown to reduce the incidence of drowning. The misconceptions surrounding drowning in many countries in the Western Pacific region is a result of inadequate resources and workforces to roll out drowning prevention strategies. While drowning is a more common issue in some areas of the region, other areas disproportionately benefit from drowning prevention programmes. Populations with the fewest resources are likely to be the least prepared to cope with the environmental threats. Apart from a small number of countries and areas in the Western Pacific region with well developed systems to prevent drowning, most areas of the region—especially those with the more severely affected populations—are still in the early stages of implementing small-scale water safety interventions at the local level.The implementation of drowning prevention strategies is a multisectoral public health issue, which is related to different public health themes, including children's health, disaster risk management, transportation safety, built environment planning, and rural development, requiring the involvement from multiple stakeholders. As seen during the Zhengzhou flood, with the growing adverse effects of global climate change, more people in the region will be exposed to water-related disasters, and the risk of drowning will increase. Actions to prevent drowning need to be accelerated. Countries in the Western Pacific region need to coordinate efforts from different sectors to build up their national water safety plans and to develop and promote drowning prevention systems. These systems should be tailored to specific settings to reduce the avoidable deaths from drowning for the sustainable development of the region.The Lancet Regional Health – Western Pacific