The history of diagnosing hypogonadism and hypotestosteronemia shows us the many steps that were necessary to achieve our current knowledge and the ability to improve these patients’ well-being. Moreover, so far, criteria for diagnosing hypotestosteronemia varies according to the underlying condition, and according to the consensus or guideline adopted. Furthermore, besides the many signs and symptoms, there are several complications associated with low testosterone levels such as osteoporosis, metabolic alterations, as well as cardiovascular disorders. However, data are often conflicting regarding the severity, timing or even the real clinical relevance of these complications, although these studies often lack essential information such as gonadotropin levels or the underlying cause of hypogonadism. The present review focus on the complications of male hypogonadism according to the cause of testosterone deficiency, highlighting the lack of information found in many studies investigating its effects. We thereby stress the necessity to always perform a complete evaluation of the type of hypogonadism (including at least gonadotropins and secondary causes) when investigating the effects of low testosterone levels. In 2.1Other than the alteration of the sexual function, low testosterone levels may lead to several clinical implications.Hypogonadism is a well-established cause of secondary osteoporosis in men. Interestingly, the percentage of hypogonadism found in male osteoporosis has been shown to be around the 15%; however, this finding is not an absolute value and can differ based on the definition of hypogonadism and the population considered –20.Nonetheless, reduced androgen levels are associated with low bone mineral density, increased markers of bone turnover, and increased risk of fracture. In adults, hypogonadism can lead to loss of bone mass, while before puberty it can cause failure to reach bone mass peak –24.. TesMen with androgen deficiency are also characterized by decreased physical energy and motivation, presence of depressed mood and irascibility, sleepiness and decreased attention and memory . If the The relationship between low testosterone and diabesity, defined as the coexistence of obesity and altered glycemia  is bidirectional, although the evidence suggests a stronger effect of diabesity on hypothalamic-pituitary-testicular axis suppression compared with the effect of hypogonadism on promoting diabesity . PotentiEven if in the past an alert emerged concerning cardiovascular risks due to testosterone treatment, these worries have today been questioned, especially when the treatment is performed with medical supervision. The studies that found an association of testosterone treatment with CV events had in fact some major biases, including lack of T measurement during follow-up, treatment inadequacy, comparison with patients treated with phosphodiesterase type 5 inhibitor (which are associated with cardioprotective effects), lack of proper randomizations and broad definition of CV-related events which even included self-reported minor events . On the On the other hand, studies have sustained negative relationship between low serum T levels and increased risk of cardiovascular disease, and both cardiovascular and all-cause mortality , 41. OthThe occurrence of all these complications, and the patient’s overall quality of life, is more pronounced in men with severe or moderate forms of LOH and appear to be less pronounced in patients with low testosterone levels without sexual symptoms .2.2Many of the studies evaluating the complications of hypotestosteronemia, in addition to the different cutoffs used to diagnose hypogonadism, often also fail to investigate the type of hypogonadism, if the clinical outcomes depend solely on testosterone. But how can we be sure that this is really the case? We know that very different condition according to pathogenesis, cause, and comorbidities can produce hypotestosteronemia; so, how can we separate the effects of testosterone and of the underlying condition?2.3As it is widely known KS is the most common X-chromosome related condition  and also a frequent cause of hypogonadism in men, presenting with an incidence among newborns of 1:500 to 1:1000 (AR). Some clinical research studies have found a correlation between AR sensitivity and anthropometric parameters in KS individuals  has been shown to stimulate bone resorption, by binding directly to osteoclasts , 93. It 2.5Circulating endothelial progenitor cells (EPCs) are bone marrow-derived cells required for endothelial repair. Since endothelial dysfunction is known to be the first step of the atherosclerotic process, a low EPC number can be considered as an independent predictor of endothelial damage, future cardiovascular events  and alsoSeveral studies have shown that patients with hypogonadism without other confounding risk factors have a low number of circulating progenitor cells (PCs) and EPCs . When itIt must be noted that all these studies are performed in patients with hypogonadotropic forms with an astounding lack of results concerning primary testosterone deficiencies, leading to a void of knowledge on whether these alterations are actually due to just testosterone levels  or are in part caused by the underlying origin of hypotestosteronemia, such as metabolic conditions (which are known to be related with pro-atherogenic conditions). The only exception is one study done on patients with Klinefelter syndrome (KS), but as already mentioned, this condition must be considered apart from other testicular failures. In this study, KS patients were compared with healthy controls and both groups were further divided according to the presence or absence of cardiovascular risk factors. Based on the results obtained, authors speculated that factors involved in KS, whether hypogonadism, cardiovascular risk factors or other genetically determined factors related to the supernumerary X chromosome might contribute to a reduction in EPCs number and that this could be considered another cardiovascular risk factor contributing to the increased mortality of these subjects . Thus, w3Of a total of 166 articles evaluated in this review, an alarmingly low number of only 74 used the gonadotropin assay in the diagnosis of hypogonadism. Based on what it has been said so far, hypogonadism is not a single disease but a galaxy of distinct conditions that can sometimes be both cause and consequence of low testosterone levels. The lack of consistency not only in the diagnosis of hypogonadism, but also in the information provided by the authors while studying its complications, hinders the understanding of the consequences of testosterone alone and those of the different types of hypogonadism, preventing the understanding necessary for the correct management of each of these diseases. Future studies on hypogonadism should therefore increasingly be directed toward discovering the cause based on the type of hypogonadism, whether it is hypogonadotropic or hypergonadotropic, whenever studying its complications, always assessing gonadotropins and secondary causes.EM, MA, BC, and MB contributed to the conception and first draft of the manuscript. EM, MA, AA, and RB collected clinical data. BC and MB, contributed to the supervision and critical revision of the manuscript. All authors contributed to the article and approved the submitted version.


Toybox is a kindergarten-based intervention program that targets sedentary behavior, snacking and drinking habits, as well as promoting physical activity in an effort to improve healthy energy balance-related behaviors among children attending kindergartens in Malaysia. The pilot of this program was conducted as a randomized controlled trial (RCT) involving 837 children from 22 intervention kindergartens and 26 control kindergartens respectively. This paper outlines the process evaluation of this intervention.We assessed five process indicators: recruitment, retention, dosage, fidelity, and satisfaction for the Toybox program. Data collection was conducted via teachers’ monthly logbooks, post-intervention feedback through questionnaires, and focus group discussions (FGD) with teachers, parents, and children. Data were analyzed using quantitative and qualitative data analysis methods.A total of 1072 children were invited. Out of the 1001 children whose parents consented to join, only 837 completed the program (Retention rate: 88.4%). As high as 91% of the 44 teachers and their assistants engaged positively in one or more of the process evaluation data collection methods. In terms of dosage and fidelity, 76% of parents had received newsletters, tip cards, and posters at the appropriate times. All teachers and their assistants felt satisfied with the intervention program. However, they also mentioned some barriers to its implementation, including the lack of suitable indoor environments to conduct activities and the need to make kangaroo stories more interesting to captivate the children’s attention. As for parents, 88% of them were satisfied with the family-based activities and enjoyed them. They also felt that the materials provided were easy to understand and managed to improve their knowledge. Lastly, the children showed positive behaviors in consuming more water, fruits, and vegetables.The Toybox program was deemed acceptable and feasible to implement by the parents and teachers. However, several factors need to be improved before it can be expanded and embedded as a routine practice across Malaysia. Childhood obesity is a global public health issue. Due to concerns about the morbidity and mortality associated with the high prevalence of obesity, it is now one of the top priorities in the prevention and control of non-communicable diseases (NCDs) . In the Amongst the Southeast Asian countries, Malaysia recorded the highest prevalence of overweight and obesity . Based oInterventions that are instituted during early childhood have been shown to be the best and most effective approach to fostering lifelong healthy behaviors . With thTo the best of our knowledge, the ToyBox Study Malaysia is the first time that the Toybox Study has been implemented outside of Europe. We initiated this intervention program as a feasibility study with the purpose of adapting, translating, and implementing the six-month ToyBox intervention in both urban kindergartens in Peninsular  and rural kindergartens in East Malaysia . Using a two-armed randomised controlled trial (RCT) research design, recruitment was done for both intervention and control groups among communities from different cultures and ethnicities of Malaysia. This project was one of the first national-level intervention studies in Malaysia focusing on children and their parents that involved environment modification and training kindergarten teachers .As recommended by Oakley et al. , processhttp://www.toybox-study.my) was implemented in January 2017 in kindergartens operated under the Community Development Department, Ministry of Rural and Regional Development Malaysia. The kindergartens were catered for underprivileged children from lower-income families either for free or minimal fee. The Toybox program aimed to improve four obesity-related behaviors among children attending kindergartens.The ToyBox Study Malaysia  and health-related outcomes as measured using accelerometer and anthropometer indicators.To identify suitable outcome indicators that can be used in future RCTs based on the pilot RCT trial.The Toybox Study Malaysia can be assessed via an outcome evaluation and a process evaluation. In this study, the specific objectives included:i.Inclusion criteria: 20 to 30 children enrolled per yearii.Exclusion criteria: Kindergarten was involved in other clinical trials or health-based intervention projects.Kindergartens were shortlisted based on the following inclusion and exclusion criteria:Based on the selection criteria above, we obtained a list of the kindergartens in Selangor, Federal Territory of Kuala Lumpur, and Kuching, Sarawak from the supervisors of Early Childhood Education of the Community Development Department, Ministry of Rural and Regional Development Malaysia. The kindergartens in these three localities were then randomly selected based on three blocks . The selected kindergartens were further randomized into intervention and control groups. No dropout of kindergarten occurred after randomization. After that, the study team visited each selected kindergarten to inform the kindergarten teachers about the purpose of the study.i.Inclusion criteria: Children aged between 4 and 7 yearsii.Exclusion criteria: Children with chronic disease, cognitive improvement, or other conditions that limit their participation.In each kindergarten, a universal sampling of the children was done. All children enrolled in the participating kindergartens were automatically recruited in the study based on the following inclusion and exclusion criteria:The children would not know whether they were in the intervention or control group. Once they were identified, the parents/primary caregivers of the children were invited to a briefing on the purpose of the study before they provided written informed consent for study participation. In addition, trained research assistants were also blinded to the group allocation in all data collection, including anthropometric measurement.The intervention of the ToyBox program took place over 24 weeks Table . SimilarActivities conducted under the intervention programs included: (i) Change of environment in the kindergarten ; (ii) Promoting the change of lifestyle on a more regular basis . Teachers also underwent ‘Training of the Teachers’ (TOT) sessions with follow-up to familiarize them with the syllabus that included creative and innovative teachings of the four EBRBs . Newsletters and tip cards were also given to all parents involved. Each intervention kindergarten was provided with a toy box consisting of all tools and materials needed to implement the intervention activities.Children in the control arm group did not have access to ToyBox materials or activities. They continued with their usual activities in the kindergartens.Implementation: the structures, resources, and processes through which the delivery was achieved, as well as the quantity and quality of what was delivered;Mechanisms of impact: how did the intervention activities and the participants’ interactions with them trigger the change;Context: how did external factors influence the delivery and functioning of the interventions in the programIn this study, we undertook a process evaluation alongside the outcome evaluation for the Toybox Study Malaysia. The process evaluations aimed to provide a more detailed understanding of the program to inform stakeholders on policy and practice implications . In the To measure the quality and quantity of the program delivery under the implementation aspect, the evaluation of recruitment, retention, dosage delivered (completeness), and the dosage received (exposure and satisfaction) was performed. The mechanisms of impact were assessed based on fidelity, i.e. whether the intervention was implemented according to plan and what changes needed to be addressed. Under the context aspect, external factors including physical and social factors that affected the implementation of the program were evaluated via FGD with the teachers. Table Based on the standardized protocol of the ToyBox study , recruitBased on the standardized protocol of the ToyBox study , retentiThis component aimed to determine the amount or number of intended units of the intervention or component delivered under the intervention program. The intensity of the actual implementation of the ToyBox Study Malaysia intervention was assessed based on: (i) Number of training sessions for teachers and their assistants; (ii) Implementation/retention of environmental changes in the classroom/ kindergarten; (iii) Implementation/ retention of children’s lifestyle behaviors in the classroom/ kindergarten; (iv) Duration, number, and type of classroom activities implemented; (v) Delivery of materials (newsletters and tip cards) to parents; (vi) Time devoted to the ToyBox Study Malaysia program in each classroom.As stated by Saunder et al. , the dosIn this study, fidelity measured the extent of implementation of the ToyBox Malaysia intervention on the four behaviors  as compared to the initial planning of the implementation time plan. It also assessed the implementation of classroom environmental changes, children’s actual behaviors, classroom activities, and delivery of materials to parents according to the time plan and how these materials were delivered to the parents. In addition, the perceptions and experiences of the teachers, assistants, and parents on the implementation, impact, and sustainability of the intervention were obtained using FGD between November and December 2018 after the completion of the project. A total of nine FGD sessions using semi-structured interview questions were conducted with 23 teachers, 10 assistants, and 18 parents. The sessions were facilitated by two trained research personnel and audio-recorded. Only a summary of the major themes will be presented in this paper as the detailed findings have been published by Lee et al. .Descriptive analysis was conducted and all results were presented using proportions. Thematic data analysis guided by the Framework Approach was adopted for all the FGD data analysis . Data weEthical approval for this study was obtained from the Universiti Malaysia Sarawak Medical Ethics Committee (UNIMAS/NC-21.02/03–02 Jld.2 68) and the Universiti Kebangsaan Malaysia Research Ethics Committee (UKM PPI/111/8/JEP-2017–658). Permission to conduct the study was also obtained from the Community Development Department, Ministry of Rural and Regional Development, Malaysia. Informed consent was obtained from the parents using a form prepared in the Malay language prior to the children’s participation in the study.The recruitment of children aged 4–6 years was carried out from January to March 2017 from 48 kindergartens. A total of 22 and 26 kindergartens participated as the intervention and control groups respectively. A total of 1072 children from three ethnics groups , in Kuala Lumpur and Selangor , Bau, Lundu, Samarahan, and Siburan  were invited. Following that, 1001 children whose parents consented to the study were recruited into the RCT whereby 498 children were randomized to the intervention group and another 503 to the control group. Nevertheless, after the first measurement (T1), only 484 children remained in the intervention group and 463 in the control group. Among the reasons for dropout were absence from the kindergartens despite several attempts to reach them and parental decision to withdraw from the study.At the end of the intervention, a total of 837 children completed the program successfully, giving a retention rate of 88.4% Table .Table 3OPrior to the intervention, a total of eight training sessions that lasted between 1–3 days each were conducted. The training duration varied based on the number of participants from each site. The details of the training are presented in Table Based on the teachers’ monthly logbook over the 6-month intervention period, the implementation/retention of environmental changes and children’s lifestyle behavior achieved an average of 96.7% completeness, with a range of 91–99% for all the elements. The implementation of the program is presented in Table In terms of the number of classroom activities conducted , the proportion of teachers conducting these activities increased from the second month to 100% in the fifth month  and final month (sedentary module repetition). Over 80% of the parents received the printed materials  with the highest number of materials distributed being under the physical activity module in the second month (88%).Based on the teachers’ feedback, 84–100% of them agreed that the guide was easy to read and understand. They also felt that the amount of information in the guide was sufficient and the class activities were easily conducted. All information, content, and activities were in line with the objectives of ToyBox Study Malaysia. In addition, the teachers reported that they enjoyed conducting the activities for the children.The implementation sequence of the four EBRBs, classroom environmental changes, children’s actual behavior, classroom activities according to the materials and time plan, and the delivery of materials  fluctuated between 88% for Month 1 (drinking module), 92% for Month 2 , 84% for Month 3 , 76% for Month 4 (sedentary behavior), 80% for Month 5 , and 76% for Month 6 . Among all the modules, the physical activity module was found to have the highest success rate for conformity.A post-intervention survey using a questionnaire was conducted among all the parents in the intervention group. A total of 451 parents provided feedback. More than 90% of them agreed to some degree that the information in the ToyBox newsletter and tips card was trustworthy and useful. Furthermore, they also undertook some of the suggested activities with their children and enjoyed them.A total of nine FGD sessions that involved 23 teachers, 10 assistants, and 18 parents were conducted. Three main themes emerged from the thematic analysis, i.e. “Under the first theme of “For the physical activity module, the lack of indoor and outdoor space at some kindergartens was the main barrier for the teachers to carry out the activities fully. The participants also commented that the kangaroo stories were too long and boring, thus failing to captivate and retain the children’s attention. As for the data collection process, both teachers and parents commented that the questionnaire was too long. On top of that, the parents felt discouraged when using the accelerometer to capture physical activity data as the equipment required full cooperation from the children and both parents.However, despite all of the abovementioned barriers, the teachers and their assistants complimented the provision of training guides, equipment, and materials that facilitated the implementation of the activities. They commented that instructions in the training guide were clear and easy to carry out, apart from highlighting that the provision of water dispensers and “Quarter-Quarter-Half” plates helped them to incorporate various ToyBox activities into the kindergarten’s syllabus for the teachers to be more creative in their daily routine.Based on the feedback from the parents, the children showed a positive behavioral change as reflected by more frequent water consumption instead of sweetened beverages, as well as increased consumption of fruits and vegetables. They also stated that the children preferred healthier food instead of junk food. They also became less choosy about food choices and more willing to try new food.The teachers and their assistants all expressed an interest in continuing the ToyBox Study Malaysia program if given the necessary support from all parties including the kindergarten authority and ToyBox. They felt strongly that the continuous provision of training and materials would help in the sustainability of the ToyBox program.Based on the findings from this study, the results of the process evaluation provided detailed information on the implementation of the ToyBox Study Malaysia intervention. The areas for improvement serve as an important basis for the enhancement of future obesity intervention programs that target children in the kindergarten setting, especially those from low-income families. Overall, the findings indicated that the intervention was delivered as intended to all participants. More importantly, it was well-received by both the teachers and parents.The retention rate for this study was 85.3%, close to other studies as reported in a systematic review of obesity prevention trials targeting children  whereby In terms of the completeness of the dose delivered, 91–99% of the implementation/retention of environmental changes and children’s lifestyle behavior in the kindergarten were carried out. Teachers and their assistants reported in the FGD that the training modules prepared by the ToyBox team enabled them to complete all the necessary components. In fact, they were very satisfied with the clear instructions in the training manuals that helped them to blend ToyBox materials into their current kindergarten syllabus. This was consistent with the findings from ToyBox Europe teams . HoweverFurthermore, previous studies highlighted the parental influence on the prevention and management of childhood obesity , 20. TheIn addition, the teachers and assistants were happy and satisfied with the training materials. Their attendance at the training session was high. Like primary and secondary schools, kindergartens have also been recognized as an appropriate setting for health promotion activities, especially obesity prevention strategies as these educational institutions represent continual and concentrated access to a group of individuals at a developmentally appropriate age . MoreoveBased on the encouraging feedback from the teachers, assistants, and parents, the ToyBox Study Malaysia intervention program can be viewed as successful. However, the sustainability of the program requires support from all parties. The kindergarten teachers have expressed their interest in continuing the intervention program with the necessary support in terms of knowledge transfer and financial assistance. Without external support, it is difficult to sustain ongoing ToyBox activities, especially in the current kindergartens that are supported by the Ministry of Rural and Regional Development and meant for children aged 4–6 years from very low-income groups.The strength of this study lies in the systematic implementation, monitoring, and evaluation of all the activities based on the original protocol of ToyBox Europe . In addiHowever, there are some limitations to this study. The self-reporting of indicators in the process evaluation may be a disadvantage, particularly as most of the teachers complained that it was confusing to complete the logbook. In addition, there were too many questions to be answered and this could cause response bias among the teachers and parents . Last buBased on the encouraging feedback from the teachers, assistants, and parents, the ToyBox Study Malaysia intervention program appeared to be successful. Despite some challenges, this study showed that the ToyBox program could be completed within the time plan. The use of both quantitative and qualitative research methods in the data collection of this process evaluation strengthened the validity of the results. The findings also indicated various challenges that should be addressed by the stakeholders and operators when designing similar interventions in the future for the promotion of healthy lifestyles.


Research from a range of disciplines highlights the need to adopt a life course perspective that considers earlier life courses to explain outcomes in later life . This includes a more comprehensive assessment of earlier life courses over time and of how they are shaped by societal and political contexts. But quantitative data with detailed information on life courses that allow to address these questions are rare. Or, in case the data are available, the data are rather difficult to handle and appears to be underused. This contribution introduces the harmonized life history data from the gateway to global ageing data platform from two European Surveys, SHARE and ELSA, with data from 30 European countries. Besides providing some details on the collection of life history data in the two surveys, we also describe the way how raw data were rearranged in a user-friendly state sequence format and additionally give some examples based on the resulting data. This illustrates the potential of collected life history data from SHARE and ELSA, clearly going beyond the description of single aspects of the life course. By providing harmonized data of two prominent studies on ageing in Europe in a user-friendly format, the gateway to global ageing data platform provides a unique data source that is easily accessible for research, and permits to study life course and their links to later life in a cross-national perspective. Understanding how individual life courses unfold and how they may influence later life  are central topics of various disciplines involved in ageing research, including sociology, epidemiology and psychology  have yet to reach older ages, or because the richness of prospective data with its information on histories is restricted to the number of waves of data collection (and the life stages covered in the data). Also, data from cohort studies are often not comparable between countries, thus preventing cross-national comparisons. An attempt to overcome these limitations is to supplement the data collection of ongoing cohort studies on ageing by retrospective interviews that additionally collect life history data. In these interviews, participants are asked about their lives before entering the study, for example, entire employment histories the respondent previously had.An increasing number of studies conduct such life history interviews, including two significant studies of ageing in Europe ageing: the English Longitudinal Study of Ageing (ELSA)  to health histories with information on major periods of poor health or disability. This provides remarkable opportunities for comparative life courses research, specifically, for studying previous life courses in a cross-country perspective including the association between life course factors (e.g. patterns of family formation) and various later life outcomes . However, albeit the data are freely available for research purposes, the richness and full potential of the data are still not fully exploited. One important reason may be the difficulty associated with learning multiple surveys, and—specifically in case of life history data—the complex data structure resulting from life history interviews (see below for details). This structure requires extensive data management in each survey to provide information on entire histories, that allow to fully exploit the longitudinal nature of the data.For these reasons, the gateway to global ageing data  was developed as a platform to make data more accessible to researchers and to facilitate cross-country analyses among surveys of ageing, especially those using the Health and Retirement Study (HRS) and its international sibling studies around the globe. One major achievement of the platform, hereby, is to provide harmonized datasets from participating surveys, accompanied by extensive documentations of questionnaires and the provision of all codes to create these harmonized data , and SHARE in 2004, with ongoing waves of data collection in two-year intervals and new respondents  being added subsequently to maintain population representation in both surveys. The two studies rely on nationally representative samples of individuals aged 50 and older (based on probability household samples where respondents and partners are interviewed). This corresponds to a target population of persons born in 1952 or earlier for ELSA and in 1954 or earlier for SHARE . While SHARE started in 12 countries (11 European countries and Israel), new countries joined SHARE in the subsequent years, with 29 participating countries since study onset. For detailed data resource profiles of ELSA, see , and in SHARE between autumn 2008 and summer 2009  . For each of these job spells (or spells when not working), the data contain information on the year when the respective spell started and ended, and variables that specify the spell . The same type of information was collected for accommodation spells or for partnerships. Based on this “spell data format”, though, it is quite complicated for non-experienced researcher to derive simple statistics, for example, to know what the exact employment situation of a person was at age 40. For some respondents, this information may be stored in the second job spell—and for others the information may be given in the provided details for the period when not working between the second and the third job. Technically, this requires extensive data management where the provided spell information of each individual  is used to ascertain a specific state at a given age (based on a defined list of possible states). Further readings with additional information on spell data, its management and analyses can be found elsewhere . As an example, the variable “WORKSTATE25” captures the employment situation at age 25, and the variable “WORKSTATE50” the employment situation at age 50. As a consequence, for each individual who completed a life history interview, this provides information on whole sequences, with information on successive states throughout the life course. Table The first two sequences belong to persons who started to work full-time after full-time education at the age of 19, either in full-time employment (person 1) or as self-employment (person 2), and were both constantly working till entering retirement, with comparatively early retirement of the second person. The remaining examples belong to persons who started working somewhat later after full-time education, and either had a long period of home or family work that was followed by part-time work (person 3), or repeated unemployment interruptions (person 4).Taken together, the state sequence format directly allows to describe the circumstance at a specific age (without need of extensive data management). And this format is also the standard format for sequence analyses Halpin . SequencFull details on the procedures to re-arrange the data and on the derived harmonized states for each of the five histories in the two surveys are available online in the respective codebooks of the two studies . For SHARE, users need to download the raw data from the SHARE Research data centre and run the creation code in Stata that is available on the gateway. All necessary information, sources or links to respective data sources are provided on the gateway. The generated dataset also contains an ID-variable that allow to merge life history data with other datasets of the respective study, for example, with health data from the remaining waves of data collection. Furthermore, the data contain study-specific sampling weights for respondents of the life history interviews (referring to moment of data collection), together with stratum and cluster variables that account for complex survey design.In the following, we give two simple examples of the collected life history data . All figures are based on the latest release of the gateway (based on SHARE version B.3 & ELSA version A.2) and have been produced with Stata. We apply weights to produce appropriate population estimates, and also account for different sample sizes of each country when estimating proportions across countries.Figure The presented harmonized life history data of SHARE and ELSA from the gateway to global ageing data platform provides remarkable opportunities for studying and comparing previous life course across Europe, as well to study their links with later life outcomes. Besides being delivered in a harmonized format , one key feature of the data is that they are delivered in a user-friendly state sequence format that make data more accessible for the research community and allows an in-depth analyses of entire histories. On a conceptual level, this means that the data may facilitate researchers to address one core idea of the life course perspective when studying life course in Europe , ELSA did not ask for this aspect. In case of interest, users may therefore modify and adapt the provided do-files of SHARE to their own purposes. Second, when creating the state sequence data, some decisions are needed, for example, to decide which state is prioritized in the unlikely case that respondents reported both paid employment and a period of not working. For these details, we refer people to the codebook, where respective strategies are clearly described. Third, in the case of health history, the available information  must be considered as rather limited, specifically if researchers are interested in single diseases and the age of diagnoses (e.g. cardiovascular diseases or symptoms of depression). In that case we recommend to use data from core waves where different diseases and their age at onset are assessed, thus allowing to investigate life time prevalence of specific diseases or the age when a disease was diagnosed. Fourth, because of legal regulations, the gateway cannot directly release the harmonized data files on its website, and therefore, needs to refer to other sources. Future users, though, may profit from a gateway data enclave that is in progress, where users will be able to access data from a virtual gateway without need to go through the respective provider of survey data.In conclusion, albeit life history data are increasingly available in ongoing studies on ageing, the extent to which the potential is used is still very restricted. By providing harmonized data of two prominent studies on ageing in Europe in a user-friendly format, we hope this facilitates its use and stimulates research in the field.


Chronic obstructive pulmonary disease (COPD), is a primary public health issue globally and in our country, which continues to increase due to poor awareness of the disease and lack of necessary preventive measures. COPD is the result of a blockage of the air sacs known as alveoli within the lungs; it is a persistent sickness that causes difficulty in breathing, cough, and shortness of breath. COPD is characterized by breathing signs and symptoms and airflow challenge because of anomalies in the airways and alveoli that occurs as the result of significant exposure to harmful particles and gases. The spirometry test (breath measurement test), used for diagnosing COPD, is creating difficulties in reaching hospitals, especially in patients with disabilities or advanced disease and in children. To facilitate the diagnostic treatment and prevent these problems, it is far evaluated that using photoplethysmography (PPG) signal in the diagnosis of COPD disease would be beneficial in order to simplify and speed up the diagnosis process and make it more convenient for monitoring. A PPG signal includes numerous components, including volumetric changes in arterial blood that are related to heart activity, fluctuations in venous blood volume that modify the PPG signal, a direct current (DC) component that shows the optical properties of the tissues, and modest energy changes in the body. PPG has typically received the usage of a pulse oximeter, which illuminates the pores and skin and measures adjustments in mild absorption. PPG occurring with every heart rate is an easy signal to measure. PPG signal is modeled by machine learning to predict COPD.During the studies, the PPG signal was cleaned of noise, and a brand-new PPG signal having three low-frequency bands of the PPG was obtained. Each of the four signals extracted 25 features. An aggregate of 100 features have been extracted. Additionally, weight, height, and age were also used as characteristics. In the feature selection process, we employed the Fisher method. The intention of using this method is to improve performance.This improved PPG prediction models have an accuracy rate of 0.95 performance value for all individuals. Classification algorithms used in feature selection algorithm has contributed to a performance increase.According to the findings, PPG-based COPD prediction models are suitable for usage in practice. Chronic obstructive pulmonary disease (COPD) is characterized by breathing signs and symptoms and airflow challenges because of anomalies in the airways and the alveoli that occurs as a result of significant exposure to harmful particles and gases. COPD is a widespread, preventable, and curable disease . COPD coCOPD is a lung complaint that prevents comfortable and healthy breathing due to the narrowing of the airways. The most common symptoms of COPD, as a progressive chronic disease for which a definitive treatment has not been found yet, are cough with phlegm and shortness of breath. In this disease, which manifests itself in the form of different symptoms depending on its stages, shortness of breath, even with light effort, indicates that the disease has progressed. One of the most important features of the symptoms is cigarette smoke. Both active cigarette smokers and nonsmokers or passive smokers around them are affected.COPD is a progressive disease that develops due to non-microbial inflammation in the airways caused by prolonged exposure to tobacco smoke, noxious gases, and particles. As a result of this inflammation, while the airways are gradually narrowing, irreversible enlargement and destruction of the air sacs  occur in the lung tissue .Because there is insufficient information, approximately COPD, analysis, diagnosis, and treatment are delayed. The specialized doctor makes the diagnosis based on the information collected from the spirometer gadget, which is the approach utilized to diagnose the ailment. These methods are only applied in hospitals and performed by technicians. It is important to monitor the patient’s illness after diagnosis and to monitor the damage the disease has caused to the patient’s body. Early diagnosis and intervention in COPD can stop or slow the progression of the disease. COPD, or chronic obstructive pulmonary disease, is caused by the narrowing of the airways in the lungs that make breathing difficult, and because the disease is often permanent and progressive, diagnosing the disease in its early stages can leave less harm to the patient. Monitoring at regular intervals is very important in terms of the course of the disease. This process can only be performed in hospitals. It is a complicated and time-consuming process .The diagnosis of COPD is made by using the spirometer device. The spirometer should measure forced vital capacity (FVC), and volume exhaled (FEV1) within 1 s of this maneuver and calculated the FEV1/FVC ratio. A medical professional can make a diagnosis by comparing spirometry measurements with reference values determined by age, height, weight, and BMI. When we divide FEV1 by FVC, it is considered to be less than 70% a COPD patient . The difHeart signals convey vital information about the body and illness. Therefore, based on the obtained results, it has been evaluated that it can be used in the diagnosis of COPD. A PPG signal-based COPD diagnostic method is suggested in this study. It is expected that the developed method will also create an infrastructure for the production of portable devices for the diagnosis of the disease and be low in cost.Studies in the literature show that artificial intelligence algorithms can be used in the detection of asthma and COPD . In the In recent years, in the diagnosis of diseases, various types of research areas have been carried out on the usability of some new and helpful classifiers, decision-making software, and tools . One of One of the overall goals of this study is to facilitate the diagnosis of COPD through machine learning, which helps to confirm the diagnosis of COPD. In addition, the improvement of parameters such as diagnosis duration, efficiency, and time are among the objectives . This stThe aim of this study is to diagnose COPD quickly and reliably with artificial intelligence-based PPG signal. In this study, a different and improved model from the literature is proposed. PPG records were collected from patients and healthy individuals for model formation. PPG signals are noise-free and split into sub-frequency bands. Then, features in the time domain are extracted from each frequency band. Feature selection algorithm is used to improve performance and eliminate unnecessary features. With the obtained feature sets, classification was made with the help of machine learning algorithms. The results showed that the diagnosis can be made with a two-second PPG signal.To explain the purpose of the study, the diagram in The data used in the study were obtained from the Sleep Laboratory of Sakarya Hendek State Hospital. The data in question; has been examined and diagnosed by a medical professional according to the criteria for COPD and is classified as either diseased or healthy. In order to carry out the research, permissions were obtained from the ethics committee report numbered 1614662/050.01.04/70 from the Dean of the Faculty of Medicine University from Sakarya and R.T Ministry of Health Republic of Turkey, Turkey Public Hospitals Institution Sakarya Province Public Hospitals Association General Data Secretary, and usage permission numbered 94556916/904/151.5815. A consent form was obtained from all participants. The data used in the study were collected in 2015–2016.Within the scope of the study, the studies have been made on identified patients, six healthy and eight patient, 12 of them male and two female, fourteen people in total. Personal demographic records and COPD registry records are given withinside A digital filter is applied to the PPG signal, and a new PPG signal is obtained, which has a sub-frequency band PPG signal. In an attempt to eliminate noise from the PPG signal, a Chebyshev type II bandpass filter with frequencies ranging from 0.1 to 20 Hz was used, followed by a “Moving Average” filter, and the PPG signal was received without noise . During x shown in formulas represents the signal. These operations are computed using the MATLAB library . While applying the SVMs, the parameter optimization method was used. Using this method improves performance.kNN is a basic machine-learning method that uses the supervised learning approach . AlthougkNN algorithms were proposed in 1967 by The kNN algorithm may be used for both regression and classification; however, it is more commonly utilized for classification tasks . By calcAn ensemble of trees makes predictions by gathering the results from individual decision trees (DT) . ET is aEnsemble methods; It combines the prediction results of multiple base models to produce more robust and generalizable results compared to a single model. The success of these methods is based on two criteria; the learning success of the base learner and their differences from each other. Performance can sometimes drop on models.The Ensemble Tree classifier is a system that was constructed by merging many classification methods to give more consistent and dependable predictions. The system is built with N odd or even classifiers. During classification, the output values produced by each classifier are counted. The decision of the ensemble classifier is determined by the principle of majority vote.In this study, three classifiers were used; ensemble classifier SVMs, kNN, and Ensemble Tree, and the study were prepared in the MATLAB environment.Today, it is seen that organizations are increasingly positioning artificial intelligence instead of operational solutions and rapidly integrating it into their business processes . Hybrid Various performance assessment criteria were utilized to examine the accuracy rates of the suggested systems. Specificity, sensitivity, kappa coefficient, accuracy rates, receiver operating characteristic (ROC), area under the ROC curve (area under a ROC—AUC), and k-fold cross-validation accuracy rate are among them .During the classification of the feature sets, they are divided into (50%) Training and (50%) Test data sets . In the From the training and test results received, the total number of sick patients is 112,184, and healthy ones are 106,815. The best performance results were acquired by using classification algorithms in the processes and combining the hybrid artificial intelligence method with classification algorithms.For the calculation of the performance values, the confusion matrix was created, and the performance parameters were calculated .While interpreting the Kappa value, the ranges in The results acquired within the scope of the study are presented in this section. The goal of this study is to use artificial intelligence with PPG signals to diagnose chronic obstructive pulmonary disease (COPD). For this purpose, the study was organized as follows: Initially, the PPG signals received from individuals (“Data collection”) are divided into three sub-frequency bands . Then, 25 features are extracted to the photoplethysmography signal and in the three sub-frequency bands (“Feature extraction”). In the next step, the diagnosis of individual COPD values was estimated with the help of the feature groups feature selection algorithm (“Feature selection”). Finally, performance assessment criteria were used to evaluate the performances of the proposed models (“Performance assessment criteria”).Within the scope of the study, COPD was estimated by using all the features of PPG and three sub-frequency bands, both separately and together in The COPD prediction model was reconstructed by reducing all feature groups with the help of the Fisher feature selection algorithm –13.The results obtained according to the Performance evaluation criteria used for the Feature selection algorithm in PPG signals are shown in The results obtained according to the Performance evaluation criteria used for the PPG LF feature selection algorithm are shown in The results obtained according to the performance evaluation criteria used for the PPG MF feature selection algorithm are shown in The results obtained according to the performance assessment criteria used for the PPG HF feature selection algorithm are shown in The results obtained according to the performance assessment criteria used for the PPG All feature selection algorithm are shown in Using kNN, SVMs, and Ensemble Tree classification algorithms at each level, the operations are carried out by using optimization at each level. We tried to find the best results using the best performance evaluation criteria. We tried to get the best result for these models by combining the models with the hybrid method.Twenty-five features were chosen when the produced models were analyzed in terms of signal processing effort before utilizing the feature selection technique. To put it another way, the feature selection method has decreased the feature extraction burden by 70%. The findings acquired based on the signal are shown visually in order to assess the outcomes gained in the research in various ways. The training times of the models are about 30 min, excluding the hybrid model, due to the large data set.For the reliability of the study, the leave one out method was applied. The obtained training results are summarized in the The hybrid method is a stable classifier formed by weak classifiers. Although its performance is lower in some cases than singular classifiers, it may be preferred more because it is stable and the variance of the answers is low.The aim of the study is to make the artificial intelligence-based COPD diagnosis quickly and reliably. For this purpose, a different and advanced signal processing and machine learning process from the literature has been developed. More than one model was developed in the study and the comparison of the models is summarized in the results section.With rapidly polluted air, increased pollution, harsh urban life, and consumption of tobacco products such as tobacco, lung disease is one of today’s most significant health problems . It has In a disease where early diagnosis is so important, it has become inevitable to carry out studies for early diagnosis. When we look at the literature, it is seen that the studies on the diagnosis of COPD are generally performed with a stethoscope, demographic information of patients, and spirometers . In the The use of artificial intelligence algorithms as a decision support system in disease diagnosis is increasing day by day . ClassicGenerally, in the literature, it has been seen that in the studies, more than one single classifier such as DT, SVMs, kNN, multilayer feedforward neural network (MLFFNN), Probabilistic neural network (PNN), and artificial boundary networks are preferred during classification processes . EnsemblIn another study for the diagnosis of COPD, with the empirical wavelet transform (EWT) method, kNN, naive Bayes, BayesNet, multilayer perceptron, SVMs, AdaBoost, random subspace, random forest, and J48 algorithm in total nine different types were used and the best performance value for COPD diagnosis was obtained from the classification algorithms in a short time as 5 s . In anotStudies have shown that PPG signals can help identify COPD. Diagnosis of COPD using PPG signals is said to be achieved in real-time in just 15 s . AnotherAll these studies carried out to date contain advantages and disadvantages from each other in terms of different features. This study is an early diagnosis of COPD; in this way, if the treatment process of the patient is started quickly, psychological and physiological difficulties will be minimized.When the model proposed in this study is compared with the literature, the signal processing process includes innovations in terms of machine learning approach. The use of sub-frequency bands in the signal processing process and the hybrid use of artificial intelligence algorithms are the biggest innovations in the study. Differences in these processes directly affected the performance positively.According to the findings of this study, COPD diagnosis might be established by utilizing machine learning with PPG and biological signal processing techniques. It becomes additionally decided that the PPG recording time becomes necessary. With a recording of just 2 s, by using PPG and three sub-frequency signals, three different classification algorithms, combining these models, and using a combined artificial intelligence approach, the exact obtained ratio is 95.31%. These results indicate that the diagnosis of COPD has practical diagnostic methods. The diagnosis of COPD is usually made with a spirometer. However, due to the difficulties of using these devices, different alternatives are needed. The market value of the device is approximately $1,500–$2,500. The proposed model’s rapid diagnosis, reliability, and high accuracy have many advantages because of its technological infrastructure and low cost. The proposed version may be introduced to accessible oxygen saturation gadgets with the usage of easy software. Even with this economic aspect alone, it brings excellent innovation. Therefore, in order to summarize the critical points of the research, it is a system that is (1) easy to use, (2) based on artificial intelligence, (3) has a low economic cost, and (4) makes decisions based on reliable data from biomedical signal measurements. We hope that this research will open new horizons for the diagnosis of COPD.


The finite element method is a widely used numerical method to analyze structures in virtual space. This method can be used in the packaging industry to determine the mechanical properties of corrugated boxes. This study aims to create and validate a numerical model to predict the compression force of corrugated cardboard boxes by considering the influence of different cutout configurations of sidewalls. The types of investigated boxes are the following: the width and height of the boxes are 300 mm in each case and the length dimension of the boxes varied from 200 mm to 600 mm with a 100 mm increment. The cutout rates were 0%, 4%, 16%, 36%, and 64% with respect to the total surface area of sidewalls of the boxes. For the finite element analysis, a homogenized linear elastic orthotropic material model with Hill plasticity was used. The results of linear regressions show very good estimations to the numerical and experimental box compression test (BCT) values in each tested box group. Therefore, the numerical model can give a good prediction for the BCT force values from 0% cutout to 64% cutout rates. The accuracy of the numerical model decreases a little when the cutout rates are high. Based on the results, this paper presents a numerical model that can be used in the packaging design to estimate the compression strength of corrugated cardboard boxes. In logistics, the packaging of products is essential ,2,3,4,5.For the production of corrugated sheets, there are several quality grades of both flat and corrugated sheets, basically classified by their fiber content:Flat sheets can be: kraftliner, which contains only primary pulp fibers; bodyliner (duplex), which contains primary fibers in one part and recycled fibers in the other part; and srenc, which are made by processing mixed waste paper. The papers forming the corrugated layer can be divided into two categories: fluting , which contains primary fibers and is made suitable for retaining the fluting by special chemical treatment; wellenstoff, which is virtually identical to the base material for flat layers; and srenc.The paper material is highly sensitive to moisture and all its strength properties are significantly reduced by high moisture content. High fiber content materials  are less sensitive to moisture than paper materials containing recycled fibers. For this reason, when corrugated board packaging is tested, the type of paper used should always be specified for each layer.For both papers and corrugated sheets made from them, the direction of manufacture should be interpreted. In the paper industry, the direction of manufacture is abbreviated as MD, whereas the direction perpendicular to the manufacture is abbreviated as CD. The mechanical properties  of the paper in the production direction are significantly higher than those of the CD. Similarly, the thickness direction (ZD) that can be interpreted for corrugated sheets is important because it determines the second moment of area of the corrugated sheet under compressive loading ,16,17.In box manufacturing, FEFCO designates each box type by a numerical code, the simplest and most commonly used box variant being the so-called slotted box, designated by the code FEFCO0201 .In logistics, corrugated boxes are stacked for both storage and transport. The determination of the stacking load capacity for corrugated boxes is still a problem for designers .The best-known empirical formula for sizing for stack loading is the McKee equation, which attempts to determine the compressive strength of a corrugated box based on the Edge Crush Test (ECT) of the corrugated sheet . The ECT-Hand holes for carrying ;-Ventilation openings ;-Products requiring cold storage;-Window-like cutouts for reading product identifiers or codes;-Window-like cutouts to reduce the amount of corrugated board used.In practice, it is often necessary to make holes and cutouts of various sizes in the sidewalls of the box for various purposes. These can have several purposes:The effect of sidewall cutouts in reducing the compressive strength of the box has been investigated by several authors, but good estimation for BCT value on various sizes and locations of the cutouts has not yet been published. Experiments and modelling have generally been carried out on specific box types used in practice by the authors, and very often, conflicting data have been obtained ,36.It would be advisable to measure BCT (box compression test) values for each variant under laboratory conditions in a methodical way, by gradually reducing the surface area of the sidewalls, and to develop a FEM parameterization based on this, which represents the measured BCT values with a good approximation. This procedure could also help designers to place a cut of any shape in the actual cut location, and the model could be used to numerically determine the reduction in BCT value.Outer liner: 210 GD2  to measure the strength behavior of different boxes. The BCT setup is shown in Numerical calculations were performed in Abaqus Unified FEA software . Twenty-The proper behavior of the box under load was ensured by defining symmetry boundary conditions in the axis see . The outIn the strength analyses, the linear elastic orthotropic material model was used. Additionally, Hill plasticity was used to differentiate the reference yield strength only in the machine and cross direction . The pacFor each packaging geometry, buckling analysis and main compression calculations were performed, which gives a total of 50 numerical analyses. The 4-node quadrilaterals shell elements without integration, named S4R, were used in all computations . DiffereFor each box sample, the maximum compression force values were determined both with measurement and FEM analysis. These experimental and numerical results are shown in In In In A few deformation shape examples are shown in The authors showed the evaluation of the BCT tests for the sample boxes with large cutout areas  in 40,4,440,41, In In some cases, the deformation shapes are very similar in comparison with the numerical model and the experiment. This can be seen in The results show that the BCT results of the boxes from a low to high cutout rate can be predicted with a high accuracy using this numerical model. The novelty of this paper is to show the ability of FEM analysis to estimate the BCT results of corrugated cardboard boxes with very high cutout rates. In this work, a wide range of the box sizes and the cutout rates were involved, but this range is not comparable with the different type of boxes used in the industry; therefore, all findings apply only to the tested box types. Therefore, a future study should investigate to design and test a box for industry usage with a higher cutout rate.Moreover, the presented numerical model for this study provides a cost-effective and efficient alternative way in comparison to the traditional experimental testing methods, which can be time-consuming and expensive. From a practical point of view, the presented numerical method is accurate enough for the authority of use. By using numerical simulations, the number of physical prototypes needed for testing can be significantly reduced, leading to cost savings in the design and development of corrugated boxes with cutouts. It also has to be mentioned that the numerical model can be used to perform parametric studies, where the effect of different cutout sizes on the BCT values can be evaluated without the need for additional physical testing.Overall, the results of this study demonstrate the potential of using finite element method simulations to accurately predict the BCT values of corrugated boxes with larger cutout areas than what has been shown before. The good estimation for the numerical and experimental results, as well as the low average absolute percentage difference, indicate that the developed model is a reliable tool for predicting the performance of corrugated boxes in real-world applications. Furthermore, this study highlights the importance of considering the effect of cutout area on BCT values, as this can significantly impact the strength and durability of corrugated boxes.This paper presents a numerical simulation and experimental verification method for the investigation of cutout problems of a single-wall corrugated board box. Although the method of choosing samples for the experimental test follows theoretically located and sized cutouts, the numerical result of analysis shows surprising accuracy in load capacity estimating for a corrugated cardboard box, the structure of which is basically made by viscoelastic material. The accuracy of the model decreases how the cutout rate increases from 0% to 64%. The results give new information for engineers to better understand the strength reduction effect of cutout holes such as carrying or ventilation holes.


Background and Objective: Doctors should have full loyalty to their patients, while patients should be able to trust that physicians will act only in their best interests. However, doctors may be faced with situations where they must choose between the patient’s interests and those of a third party. This article presents the results of a study that aimed to identify situations of duality in the decision-making process of medical workers, which can compromise their ethical behavior. Materials and Methods: A cross-sectional study was carried out on a sample of 1070 participants, employed in 120 healthcare facilities in the Republic of Moldova. An online questionnaire was completed anonymously. Descriptive statistics for discrete data were performed by estimating absolute and relative frequencies. To perform the multivariate analysis, the logistic regression was applied. Results: A large number (74.4%) of respondents admitted that they had faced situations of conflicts of interest. Every third respondent (35.3%) had experienced ethical dilemmas when access to expensive treatments should be ensured. Every fourth respondent experienced a conflict between the patient’s interests and those of the institution (26.1%) or the insurance company (23.3%). As age increases, the probability of reporting the dilemma decreases. Physicians reported such dilemmas almost 3 times more often than nurses. A low rate of staff sought support when faced with dilemmas. Half of the respondents (50.6%) preferred to discuss the problem only with a colleague, and 40.1% preferred to find solutions without anyone’s help. There were significant gaps within organizations in terms of the ethical dimension of the decision-making process. Conclusions: Managers should adopt clear institutional policies and tools to identify and prevent situations of dual loyalty. Ethical support should be offered to employees facing such situations. The need to promote an institutional climate based on trust and openness becomes evident. Since its inception, medical practice has been guided by ethical codes that emphasize loyalty to the patient and pursuing the patient’s best interests. Whether it is the Hippocratic Oath in its original version or the various updated versions , or the With this fundamental principle of medicine in mind, patients trust the decisions doctors make from their first meeting, based on the belief that the doctor will act in their best interests .However, in addition to caring for patients, doctors have other obligations, which are not necessarily aimed at the patient’s interests or benefit. First of all, doctors are employees of an institution and are involved in contractual and subordinate relations with their superiors. Moreover, doctors are often faced with other competing interests that directly or indirectly influence the performance of the medical act. These interests include those of other patients, members of the patients’ families, colleagues, hospital administrators, and insurance companies. Thus, putting patients’ interests first sometimes becomes difficult for doctors .Dual loyalty in medicine is a “clinical role conflict between professional duties to a patient and obligations, expressed or implied, to the interests of a third party, such as an employer, insurer, or the state” . Thus, dThe problem of dual loyalty abounds in medicine, and the ethical dilemmas associated with dual loyalty can compromise the ethical behavior of physicians, causing them to participate, knowingly or unknowingly, in the human rights abuses committed by a third party .One area that involves a high risk of dual loyalty is the work of doctors assisting people in state custody (prisoners) . In thisIn order to clarify doctors’ actions with greater certainty, in cases where a violation of someone’s rights and freedoms is alleged, often there are special legal provisions that strictly regulate the doctor’s duty to report the case, thus violating the confidentiality of the patient’s medical information. For example, the legislation of the Republic of Moldova requires the mandatory reporting of gunshot wounds, cold weapon injuries, child abuse, and rape to the police. However, there are many instances where rape victims will ask doctors for assistance but do not wish the police to be informed. This is especially the case when the rape occurs in small a community or rural region where the population knows each other and the victim does not want to be blamed and stigmatized. Thus, the doctor ends up facing a dilemma between moral obligations and medical ethics and the provisions of the law.However, in their daily work, health care professionals face many other situations of dual loyalty, arising from the influence exerted by various third parties on the doctor–patient relationship. Dual loyalty poses particular challenges for health care professionals when subordinating the patient’s interests to those of a third party risks violating the patient’s fundamental rights .Thus, from an ethical standpoint, dual loyalty is loyalty to two separate interests that potentially entails a conflict of interest, i.e., when an individual is involved in two different interests that work against each other. That is, when acting in the personal or organizational interest negatively affects the decisions regarding a third party .The perception of dual loyalty is related to the moral behavior and ethical values that guide an employee, while a conflict of interest signifies action and the implementation of decisions made following dual reflection, which often has legal consequences.In the medical field, a conflict of interest occurs when a doctor or a medical institution, in carrying out their activity, violates the principles of professional or institutional ethics. In doing so, they may also incur legal action arising from pursuing their own interest, or those of a third party, to the detriment of the patient’s interests . The thiAlthough a physician’s conflicts of interest do not always cause direct harm to the patient, they can trigger risk factors in this regard . ConflicThus, the involvement of doctors in activities intended for their own post-graduate training; the education of medical students; or involvement in clinical trials aimed at the discovery of new drugs, treatments or medical devices represents favorable contexts for building relationships with third parties, such as pharmaceutical companies. These relationships fall outside the doctor–patient relationship, sometimes reaching the level of business relationships , generatThe situations described above provide a strong emotional context for the doctors involved, who must make important decisions regarding their professional behavior in the light of dilemmas and conflicts of values. At the same time, decision making in the context of ethical dilemmas in professional activity is a complex process, involving several factors—the doctor’s own visions and beliefs, the circumstances of the work environment, the attitude of the administration, the organizational values and traditions of the medical institution where the doctor works, the doctor’s personal experiences accumulated during their career, etc. To manage ethics in a medical institution, it is important that doctors’ decisions taken in dilemma situations are correct, from the point of view of professional ethics, but also in accordance with the law.Ethics management in institutions is a new discipline within the general management field, which aims to develop and apply tools and mechanisms for monitoring, preventing, and solving ethical problems and conflicts in the institution in order to increase the quality of services and the satisfaction of beneficiaries ,18.Thus, the managerial framework of a medical institution must implement tools and mechanisms to ensure that risk situations of dual loyalty are identified; support and advice are offered when a health care professional faces dual loyalty situations; and moral values are promoted in the decision-making process of employees .A research project entitled “Ethics Management in Healthcare Facilities for Respecting Human Rights in the Provision of Health Services” was carried out in the period 2022–2023 in the Republic of Moldova. This multidimensional evaluation of ethics management in medical institutions focused on 3 distinct aspects: (1) the analysis of the ethical policies and mechanisms adopted by the institution; (2) the evaluation of the ethical behavior of the employees; and (3) the determination of the particular competences of the employees with regard to certain ethical issues. Among the investigated aspects, the phenomenon of dual loyalty was also included, in terms of both its presence in the decision-making process among employees and the institutional context that influences the final decision of the health care professional. Although the scope of the research carried out was much broader, in this article we will only present the aspects related to the phenomenon of dual loyalty and conflicts of interest that have been identified.A cross-sectional study was carried out, which included a sample of 1070 participants (at the margin of error ±3% and the expected frequency at the level of 50%), employed in hospitals and primary care institutions in the Republic of Moldova. Employees of medical institutions in the Republic of Moldova  with at least one year of professional activity were invited to participate in the study.https://forms.gle/qcdxU1Bduy6tDzRn9, accessed on 10 February 2023) and later distributed through the human resources departments of the medical institutions and professional associations, as well as through social networks.Taking into account the sensitivity of the issues addressed and the intention to provide equal opportunities for all potential participants to take part in the study, but also to exclude the influence of the researcher and the medical institution’s administration on the quality of the answers provided, the questionnaire was transposed into a Google Forms format . At the same time, the questionnaire included a separate open question through which the respondents were asked to formulate proposals and suggestions for improving the management of ethics in the institution where they work.When invited to take part in the study, the respondents were assured that their participation would be confidential and that no personal data would be recorded (the completion of the questionnaire was done anonymously). The study was approved by the Research Ethics Committee of the State University of Medicine and Pharmacy “Nicolae Testemițanu” (Decision no. 1 of 16 February 2022).Statistical Analysis of DataDescriptive statistics for discrete data were performed by determining absolute and relative frequencies, completed with 95% confidence intervals (95% CI). Because the dependent variables were dichotomous, to perform the multivariate analysis, logistic regression was applied with the estimation of the B coefficient, the Standard Error (S.E.), the Wald statistic, degrees of freedom (df), the odds ratio , as well as the confidence interval for the odds ratio. The program used for the statistical analysis was IBM SPSS  Statistics (version 26), IBM company .Physicians constituted 64.5% (N = 690) of the total number of respondents, with the other participants being represented by nurses  and non-medical staff employed in medical institutions . The number of specialists in the medical specialties  was close to that of specialists in surgical specialties , followed by the group of family doctors , obstetricians and gynecologists , pediatricians , and other specialties in lower rates. The age for all categories of participants is given in Given that the physicians taking part in the study belonged to one of six possible disciplines  with no hierarchy, we considered this feature a nominal one. This, in turn, generated some problems in the conditions of the multivariate data analysis. As a solution, we performed one hot encoding procedure, transforming this column into another six, with each one representing a separate category with 0, 1 coding.The analysis of the data showed that the participants in the study were frequently faced with situations of dual loyalty that led to conflicts of interest.Every fourth respondent  recognized the existence of a conflict between the economic interests of the institution where they worked and the interests of the patient, confirming that the manager asked them to save institutional resources at the expense of the patient’s necessary treatment. At the same time, every third respondent  faced ethical dilemmas when they had to ensure fair patient access to complex diagnostic investigations and expensive treatments, with 17.1%  facing such dilemmas very often and 18.2%  facing such dilemmas sometimes.Every tenth respondent  admitted that they personally found themselves in situations when they had to promote and protect the interests of the employer  rather than those of their patients.The multivariate analysis for the estimation of indicators associated with ‘Interests of the institution’ can be seen in This model included Age (B = −0.29) and Profession (B = 1.094), completed with the value of Constant (B = −1.597). By interpreting the types of associations, we notice that with the increase of Age by one year, the probability of the respondent reporting the ethical dilemma concerning the interests of the institution where they work decreases by 2.8% . Doctors will report cases of non-compliance on the part of the institution almost 3 times more often than nurses . It is important to mention the relatively narrow confidence intervals and the fact that the described relationships fit within the logic of the research.A group of 83 respondents  admitted that they had faced dual loyalty dilemmas when they had to provide assistance to a terminally ill patient or a very sick homeless person. This dilemma arose for some respondents who had doubts about justifying the waste of resources, effort, and time of medical staff on patients who had no chance of survival or for whom the hospital would not be reimbursed because they did not have medical insurance. These dilemmas were mostly motivated by the limited resources of medical institutions in the Republic of Moldova, but also by the acute lack of medical personnel. It becomes obvious that doctors experience situations in which they must justify the equitable distribution of resources, thereby resulting in ethical dilemmas.The multivariate analysis for the estimation of indicators associated with ‘Unnecessary treatment’ can be seen in The model included Age (B = −0.22) and Profession (B = 1.451) and the field of Pediatrics, completed with the value of Constant (B = −3.968). We observe that doctors will report cases of ‘Unnecessary treatment’ 4.3 times more often than nurses . Respondents from the specialty of Pediatrics reported such cases 4.6 times less often compared with other specialties . The confidence intervals are relatively narrow, and the described relationships fit the logic of the research.The study identified that the decision-making process of the medical staff is also influenced by abusive interference from their superiors, which influences health care professionals to take certain decisions, especially in favor of the interests of the institution instead of those of the patient. It is alarming that more than half of the respondents (68.4%) indicated that they had faced situations of inappropriate influence from their superiors , and 21.8%  mentioned that they encountered such situations often or very often.In the Republic of Moldova, the system of Mandatory Insurance for Medical Assistance is implemented, based on the contributions of employees  and state contributions for groups of vulnerable people who are medically insured by the government . The medical insurance fund is managed by the National Medical Insurance Company (CNAM) which annually contracts each medical institution. Medical services in hospitals are paid per case treated, and primary health care is paid per capita. The Republic of Moldova is a country that faces many economic problems. There is a low level of citizen income, high unemployment, and many people are on the verge of poverty. For this reason, payments to the insurance fund are much lower than the real needs of the health system. The prices provided by the CNAM for the services within the contracts with the medical institutions are very low, barely covering the real costs of medical assistance. For this reason, doctors are always asked by the institutional management to save on prescribing treatments and investigations at the expense of the medical institution.Almost a quarter of the participants  admitted that they had to act in the interests of the insurance company, even if they understood that the conditions imposed did not benefit the patient.The multivariate analysis for the estimation of indicators associated with ‘Interests of the insurance company’ can be seen in The model included Age (B = −0.18) and Profession (B = 1.335), completed with the value of Constant (B = −2.901). We observe that with the increase of Age by one year, the probability of the respondent reporting the ethical dilemma relating to the interests of the insurance company decreases . Physicians reported the ethical dilemma of promoting the insurance company’s interests over the patient’s interests almost 3 times more often than nurses . This phenomenon was particularly reported by family doctors and those in the field of oncology.Dual loyalty can also occur in the context of relationships between medical professionals. Thus, 13.9%  of the participants identified cases when they had to side with a “guild” colleague against the interests of a patient.If they noticed a medical error or unethical behavior on the part of a colleague, only 14.1%  of the respondents stated that they would report the problem; that is, they would notify their superior about it.The vast majority  indicated that they would prefer to talk to the colleague personally, without notifying the superiors, and 12.5%  of the respondents admitted that they would not get involved, considering that it is not their duty to point out someone else’s mistakes.The study identified a large number  of participants who admitted that they faced conflicts of interest in professional relationships, with practically every third respondent  rating such cases as frequent or very frequent.About 18.0%  of the respondents indicated “personal profit” as a characteristic of the climate of the institution where they work, thus emphasizing the predominance of personal financial interests of the respondents.Sixteen respondents  admitted that they had faced situations of dual loyalty and conflict of interest related to being simultaneously employed in a public and a private institution when they had to promote the private institution for their own financial interest.Sixty-nine respondents  indicated that certain pharmaceutical companies offered them very attractive and motivating conditions to give preference to prescribing certain medications from certain manufacturers .The model included the Profession (B = 0.229) and the Family Medicine specialty (B = 654), completed with the value of Constant (B = −6.852). We observe that physicians will more frequently report ethical dilemmas related to pharmaceutical companies than nurses . Such dilemmas were most frequently mentioned by family doctors.Dilemmas and conflicts of interest in professional activity presuppose the need for their correct management within an institution. Once dilemmas are identified, any health care professional should initiate a reporting procedure and seek specialist advice. Our study identified a low rate of health care professionals asking for support when faced with certain ethical dilemmas. Practically half of the respondents  preferred to discuss the identified dilemma only with a close colleague, and 40.1%  of the participants declared that they preferred to find solutions on their own without resorting to someone’s help. Relatively few respondents noted that they would seek the help of other specialists, such as the institution’s lawyer , the ethics committee , or the psychologist .It is alarming that many respondents described the climate of the institution using negative characteristics, such as fear  or indifference , which indicates employees’ low predisposition toward openness and communication with superiors about the problems and dilemmas they face.Moreover, 22.1%  of the participants believed that in the institutions where they worked, insufficient and superficial measures were taken to promote the ethical behavior of employees, while 24.7%  were unable to make an assessment with reference to this topic.Along with the development of contemporary society, there are inherently higher expectations regarding the standard of medical services provided. Political pressure, but also the increasing emergence of patient movements and organizations, promote patient rights to a professional level. Thus, the patient’s complaint and choice have become a priority, influencing the care management policies adopted by institutions, the establishment of transparency, ethical reflection, and legal justification of the actions and decisions taken. As a result, clinicians will increasingly need specific advice on decisions that need to be made in certain cases, both from a legal and a moral perspective ,21.The hospital manager might put the interests of the national health care system and regulatory authorities before the interests of the patient, those of political leaders, employers, or board members, as well as the interests arising from the conditions dictated by the insurance company. Taking into account the fact that a hospital operates depending on the funds at its disposal, there could be situations where the decision to admit a patient or not, as well as the treatments applied, depend on the funds allocated to the institution or the system by which the institution is financed. For example, the most financially “advantaged” patients or patients with better or higher-level insurance may be given preference when the funding system depends on the patients’ ability to pay or on their insurance status . At the About a quarter of the participants in our study indicated the existence of a conflict between the economic interests of the institution in which they worked and the good of the patient, and about a third of the participants faced ethical dilemmas when they had to ensure the fair access of patients to complex diagnostic investigations and expensive treatments. Doctors were three times more likely to face such dilemmas than nurses, most likely due to the fact that doctors are the ones who recommend medical investigations and treatments to patients. The likelihood of facing these dilemmas decreases with age. This fact can be explained by the traditional paternalistic attitude of older doctors, educated in the Soviet period, when the interests of society were promoted over those of the individual—the patient. As employees of the state, physicians were subject to its discipline and directives; they lacked the control over their own work that is essential to a profession . Even thAnother situation, which does not directly concern financial matters, but which emphasizes the priority of the hospital’s interests over the patient’s, is related to the hospital’s reputation. For example, in order to have good quality indicators with a low postoperative 30-day mortality rate, some hospitals in the USA practice prolonged hospitalization and the continuation of treatments that keep the patient alive for more than 30 days postoperatively, without taking into account the patient’s willingness to accept a treatment that unnecessarily prolongs their life ,26.The dependence of the institution on the funds and conditions imposed by the insurance company is another situation that may generate ethical dilemmas and dual loyalty in the behavior of doctors. About a quarter of our study participants said they acted in the insurance company’s best interests, with the likelihood decreasing with age. The probability is higher among doctors compared with nurses, with the most vulnerable specialties being family medicine and oncology.Dual loyalty can also occur when doctors are faced with the dilemma of administering expensive drugs to terminal patients, when their curative potential is questionable, and the hospital will bear high expenses considered unnecessary . In our At the opposite end, there are situations where the doctor has concluded a fee-for-service contract with the medical institution. In such cases, there is the temptation to request more procedures for more money, even when the investigations or procedures requested are not in the patient’s best interests .A concrete example of this is the doctor’s involvement in a private analysis or treatment center and directing patients to this center with the aim of supplementing income, and not necessarily because it is in the best interest of the patient. Instead, this results in a financial gain for the doctor and a potential conflict of interest .Similarly, financial considerations may lead some doctors to approach patients differently when working in both public and private practice, with a tendency to promote or refer patients to private practice for financial gain, a situation reported by a small number of participants in our study.The practices of pharmaceutical companies to offer doctors bonuses for prescribing certain promoted drugs involves the risk of a conflict of interest . In our Drug companies or those producing medical consumables and devices may have a commercial rather than social interest when funding clinical trials . MedicalThe need to support doctors in making decisions in situations of dual loyalty, ethical dilemmas, and conflicts of interest was determined at the end of the last century. In a study of UK hospitals, 59% of respondents indicated that they would prefer this advice to be provided by an ethics committee, while 36% stated they would prefer to seek advice from a qualified clinical ethicist. Initially, there was a lack of opportunity in medical institutions to systematically deal with moral dilemmas associated with medical activity. Gradually, specific methods of ethical analysis were developed to help employees deal with these issues in a more reflective way, through constructive dialogue. Aulisio et al., for example, indicate that ethics consultation helps to identify and analyze the nature of the value conflict or uncertainty and create consensus among the parties involved. The importance of moral reflection on each dilemma or ethical uncertainty is emphasized—not only to develop the professional capacities of the employees, but also to highlight the institutional or organizational problems that lead to the appearance or accentuation of ethical problems .Even if the objectives of the ethical consulting structures in a medical institution seem to be clear, it remains to be determined to what extent these objectives are understood and accepted by key personnel in the institution. Some empirical studies highlight the objectives considered important in practice. For example, the findings of a survey conducted in more than 600 US hospitals show that the following are considered important goals of ethics consultation: protecting patients’ rights (94%), resolving actual or imminent conflicts (77%), actions to improve the quality of care (75%), and increasing patient and family satisfaction (68%) .Dauwerse et al. (2013) proposed four objectives of ethical consultation in hospitals: (1) Encouraging an ethical climate; (2) Promoting an accountable and transparent organization; (3) Increasing professional awareness of the ethical dimension of health care; and (4) Providing good quality assistance .The promotion of ethical values in the institution must be a continuous process and must be monitored by those responsible for the institution’s ethics. Through systematic democratic discussions, employees should be encouraged to talk about the ethical dilemmas they encounter in daily practice. For this, channels and structures must be created to help health workers deal with the moral dilemmas they may encounter and, at the same time, benefit from an increase in job satisfaction. At the same time, the medical institution will achieve better results in terms of patient satisfaction and employee retention .Improving the quality of ethics within medical institutions is becoming a novel process and trend at the international level, which means that the practices in medical institutions are consistent with declared and accepted ethical standards and norms, as well as with the expectations of the institution and the medical team .In a responsible organization, institutional policies must be promoted that also include ethical aspects, especially those that would help managers of a medical institution with decision making when faced with ethical dilemmas. Such dilemmas could include the distribution of funds, types of services provided to certain vulnerable groups of patients, patient selection, etc. Such choices should be based on fair reasoning and dialogue, so that the manager’s decision is made after consultation with employees invited to express their own points of view. Thus, the need for institutional policies regarding the way and procedure to approach ethical issues within the organization, at all levels, becomes evident .Through ethical consultations, practitioners become increasingly aware and better able to recognize ethical aspects in daily practice; they also become aware of the fact that ethical choices are sometimes made without deeper consideration of such choices. Ethical reflection promotes an approach to a situation, for example, by asking oneself: Was I fair enough in my decision? Through ethical consultation, ethical reflection is stimulated, which will directly influence the development of professionalism in a positive way .I personally cannot influence things at the organizational level. Thus, for the administrators of a medical institution, it is important to promote a conducive context that would stimulate the confidence of the staff as well as promoting transparency and ethical dialogue in decision making. This type of communication must be promoted as a continuous, contextual, and situational process, that seeks to answer questions about “what is right” in daily clinical activity. It is imperative that medical institutions work on support for ethics consultation, which can yield multiple benefits, from developing an ethical climate and fostering professionalism to promoting an accountable organization. Ideally, the choice of such goals is the product of discussions between managers and practitioners within the health care institution, including ethicists. In this way, commitment to ethical consulting can be stimulated [Our study determined that sometimes doctors ignore the importance of their own ethical reflection and prefer to execute what has already been decided and documented by others. Consequently, self-responsibility is frequently minimized due to the belief that imulated ,33.This is the first study of this type carried out in the Republic of Moldova. The study was conducted on a large group of participants (doctors and nurses) from all medical institutions in this country. However, the study has a number of limitations that we present below.Completing the online questionnaire did not allow us to keep the representativeness of the participants in the study according to the ratio existing at the country level between specialties, the type of institution, as well as between the proportion of personnel with secondary and higher education. Thus, among the respondents, we determined an increased rate of doctors  and a reduced rate of nurses , which contradicts the distribution of these categories in the target population, where the number of nurses is 2 times higher than the number of doctors. However, these facts may signal the increased sensitivity of doctors to the problem addressed in this study, with the latter having more responsibilities toward patients and the administration.Another limitation may also be the probability of the participants’ formal answer, as they may not be sufficiently honest. Lastly, we appreciate that the models developed by us can be completed and require validation in further studies.Ethical health care is a continuous contextual process, based on concrete experiences and relationships with different stakeholders . Employees of medical institutions are, and always will be, faced with ethical problems and conflicts in their daily work, even if sometimes they are not aware of the moral dimension of their decisions and behavior. The persistence of conflicts of interest, improper influence, uncertainties, and ethical dilemmas in the decision-making process in the practice of medical workers significantly influences their moral status. This creates an internal conflict of values and contradictions, which can affect the behavior and integrity of employees as well as the reputation of the medical institution.The results of our study show that in the medical institutions in the Republic of Moldova there are significant gaps in the organization of the ethical dimension of the institutions where the study participants work, namely, the presence of ethical dilemmas, dual loyalty, and conflicts of interest, the lack of necessary support for ethical decision-making processes, and an unfavorable institutional climate. The need for serious measures to promote an institutional climate based on trust, openness to discussion, and constructive dialogue becomes evident.Thus, managers should adopt institutional policies and clear actions for the implementation of ethical tools to identify, manage, and prevent such situations. The promotion of institutional policies to deal with moral dilemmas, the provision of assistance, and ongoing consultation support for medical workers in the process of making difficult moral decisions must become a priority for current health managers. In the process of organizing the activity of medical institutions, the need to establish and promote a separate field dedicated to these needs is highlighted, namely, that of institutional ethics management.