The disrespect and abuse of women during the process of childbirth is an emergent and global problem and only few studies have investigated this worrying issue. The objective of the present study was to describe the prevalence of disrespect and abuse of women during childbirth in Pelotas City, Brazil, and to investigate the factors involved.This was a cross-sectional population-based study of women delivering members of the 2015 Pelotas birth cohort. Information relating to disrespect and abuse during childbirth was obtained by household interview 3 months after delivery. The information related to verbal and physical abuse, denial of care and invasive and/or inappropriate procedures. Poisson regression was used to evaluate the factors associated with one or more, and two or more, types of disrespectful treatment or abuse.A total of 4275 women took part in a perinatal study. During the three-month follow-up, we interviewed 4087 biological mothers with regards to disrespect and abuse. Approximately 10% of women reported having experienced verbal abuse, 6% denial of care, 6% undesirable or inappropriate procedures and 5% physical abuse. At least one type of disrespect or abuse was reported by 18.3% of mothers ; and at least two types by 5.1% (95% CI: 4.4–5.8). Women relying on the public health sector, and those whose childbirths were via cesarean section with previous labor, had the highest risk, with approximately a three- and two-fold increase in risk, respectively.Our study showed that the occurrence of disrespect and abuse during childbirth was high and mostly associated with payment by the public sector and labor before delivery. The efforts made by civil society, governments and international organizations are not sufficient to restrain institutional violence against women during childbirth. To eradicate this problem, it is essential to 1) implement policies and actions specific for this type of violence and 2) formulate laws to promote the equality of rights between women and men, with particular emphasis on the economic rights of women and the promotion of gender equality in terms of access to jobs and education. Violence against women in health-care institutions is an emergent and global problem. In our study, we describe the prevalence of disrespect and abuse of women during childbirth among women delivering members of the 2015 Pelotas birth cohort, a large population-based study in which 4275 women participated. We also investigated the factors responsible for such disrespect and abuse. Information relating to disrespect and abuse during childbirth was obtained by household interview 3 months after delivery and included verbal and physical abuse, denial of care and invasive and/or inappropriate procedures. Approximately 10% of these women reported having experienced verbal abuse, 6% denial of care, 6% undesirable or inappropriate procedures and 5% physical abuse. At least one type of disrespect or abuse was reported by 18.3% of mothers; and at least two types, by 5.1%. Women relying on the public health sector, and those whose childbirths were via cesarean section with previous labor, presented the highest risk, with approximate three and two-fold increases in risk, respectively. Our study showed that the occurrence of disrespect and abuse during the process of childbirth was high and mostly associated to payment by the public sector and labor before delivery. To eradicate this problem, it is essential to implement policies and actions specific for this type of violence and to promote the equality of rights between women and men, with particular emphasis on women’s economic rights and the promotion of gender equality with respect to access to jobs and education.Access to secure and high-quality sexual and reproductive health services is an essential right for women as these services can make an important contribution towards the reduction of maternal morbidity and mortality rates . In BrazEvery woman has the right to quality healthcare which is dignified, respectful, violence-free and free of discrimination. Abuse, negligence or disrespect during the process of childbirth constitute serious violations of fundamental human rights that are recognized internationally –5. In BrVarious forms of mistreatment and abuse of women during childbirth have been described in the literature, including physical, psychological or verbal abuse, humiliation, discrimination, denial of care and the implementation of contraindicated or improper procedures. These can occur at the level of the relationship between women and their healthcare professionals, or at the level of the healthcare service or system , 8, 9.Studies published during the 1990s were the first to raise attention to the issue of obstetric violence –12. SeveThe objective of the present study, therefore, was to evaluate the incidence of disrespect and abuse of women during the process of childbirth and to investigate factors that might be associated with this practice. Our study was based on a large population of women who gave birth in 2015 in the city of Pelotas, Brazil.The study was based upon the 2015 Pelotas birth cohort , a populWomen delivering in all of the city’s hospitals between January 1st 2015 and December 31st 2015 were recruited and interviewed, and a follow-up home visit was carried out when each baby was 3 months of age plus or minus 7 days. Data were collected through structured questionnaires applied by trained interviewers; detailed methodology can be found in an earlier publication .There are several terminologies relating to violence against women during the process of childbirth, including obstetric violence and mistreatment . In our Socioeconomic and demographic characteristics were collected during the perinatal interview, including mother’s age at delivery , self-reported skin color , marital status (with or without partner), maternal education , family income (measured in Brazilian reais and divided in quintiles), type of payment for childbirth  and type of childbirth . Women who underwent cesarean section and answered “yes” to the question “Did you have regular contractions (at least one every ten minutes) before the cesarean section?” were considered as having gone into labor.Quality control measures included repeating a short version of the perinatal and three-month interview to 10% of the women by means of a telephone call, or through a home visit if the woman could not be contacted by phone.Stata Statistical Software: Release 13. College Station, TX: StataCorp LP) and the database that generated the results of this study can be accessed by contacting the corresponding author. Firstly, descriptive analyses of the characteristics of recruited women were performed and the frequencies of each type of violence, disrespect or abuse were obtained. Poisson regression was then used to conduct crude and adjusted analyses of risk factors. Poisson regression represents a more suitable alternative than logistic regression for this type of analysis because the odds ratios are overestimated in comparison to prevalence ratios, especially when estimates are low [p-values lower than 0.20 in the crude analysis were then included in adjusted analyses, following a hierarchical causal model. Age, skin color, marital status, educational level and income were included as variables in the first level of this analysis. Variables relating to the type of financing used to cover hospitalization for childbirth was included in the second-level analysis while the type of childbirth was included in the third-level analysis. Because poverty and age can be strongly associated with outcome, we decided to retain family income and women’s age in all models, regardless of the p-value in an effort to minimize potential bias.Stata 13 software was used to conduct statistical analyses . All the women provided informed written consent.A total of 4333 women gave birth in the city’s hospitals, of whom 4275 (98.7%) agreed to participate in this study. During the three-month follow-up period, 4110 interviews were conducted (a follow-up rate of 97.2%). Of these, 4087 interviews (95.6%) took place with the biological mothers.Table Table Regarding the associations between the occurrence of at least one type of disrespect or abuse and socioeconomic, demographic, and delivery factors Table , a higheApproximately 18% of women who delivered babies in the city of Pelotas during 2015 were victims of at least one type of disrespectful or abusive treatment during the process of childbirth. This result is similar to the findings of a previous study conducted in Kenya , in whicSome studies have reported disrespectful or abusive treatment during childbirth in Latin America. In Venezuela, a hospital study using a self-applied confidential questionnaire showed that 49.4% of women giving birth reported having experienced some form of inhumane treatment from healthcare professionals . In a suOur present results showed that younger age, family income, type of hospitalization system for childbirth and type of childbirth were associated with the incidence of abuse or disrespect during the process of childbirth.Several studies have been published regarding the relationship between disrespect or abuse during childbirth and a range of associated factors; however, these previous studies yielded inconsistent results. Abuya et al.  found noA study referred to as ‘Birth in Brazil’ (Nascer no Brasil), a nationally representative population-based study in which a total of 15,688 women were interviewed by telephone during the postpartum period, showed a higher chance of verbal, psychological or physical violence among women who went into labor , and a lower chance among those whose childbirth was privately financed  and those who were accompanied by a family member throughout the childbirth process. There was no association between violence and skin color, socioeconomic position, educational level, maternal age or the type of delivery  .In the Brazilian private or supplementary healthcare network, 90% of childbirths occur by means of cesarean section; of these, 78% occur without the pregnant women having gone into labor . ConsideDespite international recommendations suggesting that the proportion of cesarean sections should not exceed 15% , the levThe greater occurrence of violence among women who went into labor, along with the medicalization of childbirth, may be indicative of a lack of training among medical professionals in carrying out vaginal deliveries. In general terms, Brazil has adopted a highly medicalized model for obstetric care, which uses high levels of technology and little participation from the women who receive this care. During the process of childbirth, the doctor is an authority figure who holds knowledge and power, and is the protagonist of the process. In this, the woman in labor acts merely as an assistant who must obey all medical instructions and accept the procedures that are often imposed on her. In this context, disrespect and/or abuse would consist of the abusive use of power when the authority of a doctor, also represented by the team of other professionals that act under his/her orders, is directly or indirectly challenged by “disobedience”, resistance or questioning , 31, 32.Women within the Brazilian civil society have become mobilized to fight for dignified and respectful care during pregnancy and childbirth. The movement referred to as “Delivery through Principles – Women’s Network for Active Maternity” (Parto do Princípio – Mulheres em Rede pela Maternidade Ativa), acts to promote women’s autonomy and defend their sexual and reproductive rights, especially regarding awareness during maternity, and has denounced institutional violence during pregnancy and childbirth care to policy makers . HoweverIn 2014, the magnitude and severity of this issue at a global level led the WHO to publish a statement [One possible limitation of the present study may lie in the under-reporting of disrespectful or abusive treatment, which may have reduced the magnitude of our estimates and diluted the associations observed. To minimize information bias and to avoid embarrassment and the fear of possible retaliation by the hospital or healthcare professionals, information relating to disrespect and abuse during childbirth were obtained during the three-month follow-up period. It is also important to consider the influence of women’s perceptions on their reports. For example, women who had received lower levels of education and were in lower socioeconomic positions may have tended not to notice abuse because they may have considered this to be part of the normal process. On the other hand, women who presented with higher educational levels and, probably, higher levels of information relating to their rights, may have noticed more subtle forms of violence. Another important limitation is the fact that there was no individualized information on which professionals perpetrated the abuse, or whether they were doctors or nurses. Therefore, in our discussion, we considered doctors to be hierarchically superior and responsible for the team and for the decisions made during the process of childbirth.Considering that pregnant women are in a situation of great vulnerability, and that the agents of violence against them are the ones that should be providing comprehensive care, the proportion of women who experience disrespect and abuse during the process of childbirth is absurd and unacceptable. It seems that the subjective “judgment” of permitting professionals to adopt unacceptable behavior is more tolerated in healthcare services, particularly public services. It is therefore fundamental to recognize, within the healthcare model, that obstetric care has become too medicalized and that the ethical background of the professionals involved needs to be reviewed.The occurrence of disrespect and abuse during the process of childbirth in our study was high and mostly associated to payment by the public sector and labor before delivery. The efforts made by civil society, governments and international organizations are not yet sufficient to restrain institutional violence against women in childbearing. To eradicate the problem, it is essential to 1) implement policies and actions specific for this type of violence and 2) formulate laws to promote the equality of rights between women and men, with particular emphasis on women’s economic rights and the promotion of gender equity with respect to access to jobs and education. In this way, it is possible to alter the social norms that strengthen and perpetuate social models that can ultimately lead to a lack of autonomy in women, and exert control over processes which relate to their own bodies and lives, and to the various forms of violence against women .


The Federation of State Boards of Physical Therapy (FSBPT) began the process of implementing the Physical Therapy Compact (PTC) in 2010 with a delegate assembly motion. An interstate compact is an agreement between states to enact legislation and enter into a contract for a specific, limited purpose or to address a particular policy issue. An interstate compact benefits patients, consumers, and licensees by addressing workforce concerns improving licensure portability from state-to-state; facilitating short-term mobility and telehealth consultation for physical therapists. FSBPT formed strategic partnerships with the American Physical Therapy Association (APTA) and Council for State Governments’ (CSG) to develop and implement the PTC. From April 2014-present, FSBPT followed the CSG recommended stages of compact development: Advisory, Drafting, Education, Enactment, and Transition. The enactment phase began once the threshold number of ten states required in legislation passed the compact bill in 2017. FSBPT anticipates the compact will be fully operational and licensees will be able to take advantage of the compact by mid-2018. The Federation of State Boards of Physical Therapy (FSBPT) is a membership organization comprised of the 53 jurisdictional licensing boards regulating physical therapy in the United States. The FSBPT mission is to protect the public by providing service and leadership that promote safe and competent physical therapy practice. At its 2010 Annual Meeting, the FSBPT Delegate Assembly passed a motion to explore the feasibility of establishing a multi-state compact for physical therapy licensure. This motion originated from the acknowledgement that a multi-state licensure compact for physical therapy would increase public protection by positively impacting access to care and facilitating the sharing of disciplinary information. A compact benefits patients, consumers, and licensees by addressing workforce concerns improving licensure portability from state-to-state; facilitating short-term mobility and telehealth consultation for physical therapists.Many organizations are currently having discussions concerning alleviating unnecessary barriers to licensure portability among states. Federal and state governments, the National Governors Association, consumer groups, the American Telemedicine Association, professional associations, and regulatory bodies have all looked into how to expedite the mobility of professionals while still maintaining high standards and protecting the public. The diversity of these groups leads to different end-goals in the improved mobility of health professionals, but overall most groups agree improved portability is one way to address workforce needs and improve the public’s access to health care services.Although there have been numerous changes in the health care practice environment, until the Nurse Licensure Compact was introduced in the late 1990s, there had been little in the way of innovation in the fundamental processes of health professional licensure. Although improvements such as on-line processing and electronic renewals have been implemented, the single-state system of professional licensure remained as the preferred model of regulation in most states. However, in the last 5 years, there has been a lot of interest and momentum in alternative licensing models, including compacts for Physicians , Psychologists , EMS providers , the revision of the Nursing Licensure Compact (eNLC), and of course the Physical Therapy Compact (PTC).An interstate compact is an agreement between states to enact legislation and enter into a contract for a specific, limited purpose or address a particular policy issue. Interstate compacts should not be entered into casually by a state. Compact agreements are unique in their duality as statute and contract. Each state must understand the implications of entering into a contract and must meet the terms required of all compact members.A key component of compacts is the uniformity of legislative language from state to state. To enact a compact, the legislative language be the same from state to state, thus model legislative language is provided to states interested in entering the compact. In order to join the compact in question, the state must pass legislative language that in no way materially changes the compact in order to implement the compact. Any new state interested in joining the compact must have any proposed changes to language of the model legislation reviewed by the Commission attorneys to see if the change(s) qualify as a material difference. If so, the parties involved must understand that the bill as written may not be implemented, even if it has passed the legislature.FSBPT followed the Council for State Governments’ (CSG) recommended steps to develop the PTC: Advisory, Drafting, Education, Enactment, and Transition. A compact regarding healthcare licensure is unique in that the initial interest will most likely be from the Board or professional association rather than originating with a legislator. FSBPT made the decision early on to maintain transparency in all communications regarding the PTC with any interested parties and partner with the American Physical TherapyAssociation (APTA) in the efforts to develop a compact. The buy-in and support of the professional association was critical for a successful educational campaign reaching out to their leadership and membership regarding the PTC. According to CSG, an organization interested in a compact should begin by convening an advisory group of key stakeholders to take a high level look at the key elements and challenges of an interstate compact. The Advisory Group typically meets one or two times, with their work culminating in a set of recommendations as to whether or not to move forward with a compact and what the final compact product should look like. A misconception is that compacts all look alike; in fact the reality is quite the opposite. Compacts can, and should, be tailored to the needs of the profession to which it pertains. If the advisory task force determines a compact is feasible, they are also tasked with determining the high level specifics of how the compact will operate. These high level specifics will be used by the drafting team to make sure the final language remains true to the spirit of the advisory team.The PTC Advisory Task Force met during the months of April–July of 2014. FSBPT cast a wide net when choosing task force members. The rationale was that the broadest representation of key stakeholders representing different interests and geographical areas would yield the best discussions and culminate in a recommendation that would have the best chance of success. The task force was composed of state board members, board administrators, a state senator, physical therapists, lawyers, and professional association ) representatives, with representatives from CSG providing technical assistance. The advisory task force assembled by FSBPT examined the concept of a compact for physical therapy broadly. The task force recommended moving forward with the drafting of the PTC and culminated in suggestions for the final compact product.The next step is to assemble a smaller, more focused group of 5–8 individuals to serve on the Drafting Team. FSBPT chose to retain a core of individuals from the advisory task force and supplemented with qualified individuals to bring an unbiased perspective. The drafting team is responsible to build upon the work of the Advisory Group to create the legislative language of a draft compact. This draft comment should be circulated for wide ranging input and comment from stakeholders in all areas, including the public. After revision, the draft compact would go back to the advisory group for final review and approval. The PTC Drafting Team met January–April 2015, tasked with actually drafting the statutory language of the PTC. CSG again provided technical assistance and support with the drafting of the statutory language. The drafting team crafted the language based on the recommendations of the advisory group, as well as concepts and issues that came up during their own discussions. The PTC draft document was released to a broad audience for a public comment period in May 2015. After receiving comments, the drafting team debated suggested changes and developed the final product on October 6, 2015.The education phase begins immediately following the finalizing of model legislative language. Once the interstate compact is drafted and approved, the states are free to introduce legislation to implement the compact. FSBPT entered into an official partnership with CSG to provide state-by-state technical assistance and education before and during state legislative sessions. Educational efforts will continue after enactment to maximize membership in the PTC. Education of physical therapy licensing boards, licensees, and legislators is paramount to the success of the PTC. The professional association, the Board members, the legislature, and any overarching Boards will need to be educated about the terms and advantages of the compact. Once the PTC language was completed, FSBPT began an enthusiastic campaign to educate the membership regarding the compact. During the same time, APTA began with an educational push of their own, and both organizations worked closely to maintain a consistent message.The enactment phase begins once the threshold number of states required in legislation passes the compact bill. The PTC required ten states to pass compact legislation prior to the compact “going live.” FSBPT staff believed in late 2015, based on the interest communicated by a number of states, that by the conclusion of the 2017 legislative session, the PTC should pass in ten states and be enacted. In 2016 the first four states adopted the PTC: Oregon, Tennessee, Arizona and Missouri. Ten more states followed suit in 2017; The final stage, transition, occurs post-enactment. Although the PTC came into effect in April 2017 when the statute was enacted into law in the tenth member state, the PTC will not be operational for licensees until the Physical Therapy Compact Commission finalizes some standard start-up activities, including the first Commission meetings where the member states meet to discuss development of rules, bylaws, etc., by which the PTC will be governed. Finally, when the compact body is able to run independently, licensees will be able to take advantage of the benefits of the PTC. This is when licensees will begin to work in states other than their home-license state with a Compact Privilege rather than a license. FSBPT anticipates licensees will be able to take advantage of the compact by mid-2018.


Obstetric fistula is a maternal morbidity creating devastating health problems for the women. Continuous and uncontrollable leaking of urine or faeces from vagina can lead to life changing stigmatization for women in third world countries. The underlying factors and consequences of this problem are not yet fully identified and adequately documented in Ethiopia.This study is based on the Ethiopian Demographic and Health Survey data . The survey collected information on a total of 14,070 women who were interviewed face to face on their background characteristics as well as reproductive health issues, out of which 3178 women had complete measurements and were considered in this study. Descriptive and binary logistic regressions techniques were used using demographic, socio-economic, health and environmental related variables as explanatory variables and status of obstetric fistula as a response variable.The results showed that geographical region, place of residence, educational status, age at first birth, age at first marriage, employment status, place of delivery and follow up of antenatal care during pregnancy were significant determinant factors of obstetric fistula in Ethiopia.The study showed that demographic, socio-economic, environmental and health related variables have an import ant effect on determinants of obstetric fistula in Ethiopia. Obstetric fistula is a child birth injury usually caused by unrelieved, prolonged obstructed labor. Obstructed labor can develop during the second stage of labor, when the fetus cannot fit through the birth canal because the pelvis is too small, the baby is too big or if there is a mal presentation. If the woman in labor does not die, the pressure of the baby's head on the mother's pelvis leads to the death of tissue in the birth canal which creates a hole called an obstetric fistula. From this hole, urine or faeces constantly leak. The majority of women also deliver a stillborn baby. Fistula is completely preventable if obstructed labor is diagnosed early and if appropriate timely intervention occurs, which often includes the performance of a caesarean section18. Women suffering from fistula live with chronic urinary and fecal incontinence, the social effects of which include divorce, abandonment and abuse. Many women report feeling ashamed about their condition and therefore alienate themselves from friends and familyWHO has described vaginal fistulas as “the single most dramatic aftermath of neglected childbirth”. Vaginal fistulas are widespread in developing nations, mainly in sub-Saharan African and South Asian countries, where the social culture encourages marriage at a young age, of ten shortly after the girls' first menstrual period between the ages of 9 to 15 Women affected by obstetric fistula are often abandoned by their husbands, stigmatized by the community, physically debilitated and even blamed for their condition. Social isolation and abandonment often lead to low self-esteem, depression and prolonged emotional traumaInformation from various literature shows that obstetric fistula appears to be linked to certain social-economic and cultural factors including young age at marriage, poverty and illiteracy, living in rural areas with lack of emergence obstetric careTesfayeObstetric fistula remains a major public health problem in developing world where unattended obstructed labor is common and maternal mortality is unacceptably high. It is a tragedy in developing world because of illiteracy, poverty, ignorance and lack of health facilitiesMany research findings have documented about the most important immediate clinical causes of obstetric fistula. But in Ethiopia, the underlying factors and consequences of the problem are not yet fully identified and adequately documented. Understanding the epidemiology of obstetric fistula and its determinants helps to design appropriate interventions on the basis of scientific evidences. As a result, this study tries to identify the risk factors asso ciated with determinants of obstetric fistula in Ethiopia using multiple logistic models.The general objective of this study was to examine the determinant factors associated with the prevalence of obstetric fistula in Ethiopia.To assess the effect of socio-economic, demographic, environmental and health related factors associated with the occurrence of obstetric fistula.To determine the prevalence of obstetric fistula in Ethiopia.The data source for this study was the Ethiopian Demographic and Health Survey (EDHS) conducted by central Statistical Agency (CSA) in 2005. It is the second survey conducted in Ethiopia as part of the world wide Demographic and Health Survey Project. The survey was primarily designed to collect data on fertility, family planning, maternal care, infant and child mortality, childhood illnesses, malaria, nutrition, prevalence of female genital cutting, prevalence of obstetric fistula, knowledge of AIDS and other sexually transmitted infections in Ethiopia. The 2005 Ethiopia Demographic and Health Survey was designed to provide estimates for the health and demographic variables of interest for the following domains: Ethiopia as a whole; urban and rural areas (each as a separate domain); and 11 geographic regions (9 regions and 2 city administrations).The 2005 EDHS is a nationally representative survey and of individual women were interviewed face to face on their background characteristics as well as reproductive health issues. The survey was carried out in two stages. In the first stage, 540 clusters  were selected from a list of enumeration areas from the 1994 Population Census. In the second stage, a complete listing of households was carried out in each selected cluster. The 2005 EDHS collected a complete household listing which was prepared for each selected cluster and households. Households were systematically selected from each cluster for participation in the survey. In the survey, women were asked whether they have ever experienced obstetric fistula (OF) in their life. Only 3,178 of them responded about their experience on OF which was be considered in this study.The response variable for the individual is represented by and it measures women's experience of obstetric fistula and it is dichotomized with 1 being experienced and 0 not experienced.Predictor variables are those variables which are presumed to affect or determine a dependent variable. Since based on the reviewed literature, some of the common predictors that are expected to influence determinants of obstetric fistula in Ethiopia were recorded as given below for the purpose of the analysis. In this study possible determinants of obstetric fistula were grouped as demographic, socio-economic, environmental and health related factors.i)Demographic related factorsIn this study the independent variables such as age at first marriage, age at first birth and marital status are expected to demographic risk factors.ii)Socio-Economic related factorsIn this study educational status, employment status and wealth index are included in socio-economic factors.iii)Environmental and health related factorsEnvironmental and health related factors which will be included in this study are region, place of residence, place of delivery, body mass index and frequency of antenatal visits.The purpose of this study was to analyze the impact of women's demographic, socio-economic and environmental and health related factors that determine obstetric fistula in Ethiopia. The analysis was carried out in two parts. In the first part, results of descriptive statistics are presented; in the second part, we identified and examined determinants of obstetric fistula using multiple logistic regression analysis with the help of SPSS software.A total of 3178 women were included in the study from EDHS 2005 sample. The initial population which consisted of 14,070 women all were interviewed face to face on their background characteristics as well as reproductive health issues. Out of which, 3178 women had complete measurements and were considered in this study and others were excluded due to incompleteness of data on the variables which were considered in the analysis. From the sampled data, the prevalence of obstetric fistula was about 18.8% in Ethiopia.The major socio-economic and demographic background characteristics of the respondents are presented in According to Furthermore, Among the socio-economic and demographic determinant factors, age at first marriage, age at first birth, educational status, wealth index and employment status were found to have a significant effect on the incidence of obstetric fistula at 5% levels of significance.The major environmental and health related background characteristics of the respondents are presented in Binary logistic regressions were fitted based on chi-square test result of bivariate analysis. Based on results presented in For categorical data, after a logistic regression model has been fitted, a global test of goodness of fit of the resulting model should be performed. It is necessary to see the appropriateness, adequacy and usefulness of the fitted model. The most commonly used techniques are Likelihood-Ratio test, Hosmer and Lemeshow test, R-Square and the Wald goodness of fit test.The most common assessment of overall model fit in logistic regression is the likelihood Ratio test, which is the chi-square difference between the null model with the constant only and the model containing a set of predictors. Under model summary in Table 4.3, we see that −2Log Likelihood statistics is 2552.525. This statistics show us how much improvement is needed before predictors provide the best possible prediction of the response variable, the smaller the statistics the better the model. The statistics for only intercept model is =. The inclusion of the parameters reduced the statistics by, which is reflected chi-square for omnibus test. The result , shows that the model is adequate, meaning that at least one of the predictors is significantly related to the dependent variable. That is, the null hypothesis is that there is no difference between the model with only a constant and the model with independent variables was rejected. The Hosmer and Lemeshow goodness of fit test divides subjects into deciles based on predicted probabilities, then computes a chi-square from observed and expected frequencies in a 102 table. A non-significant chi-square indicates that there is no difference between the observed and the model predicted values and hence estimates of the model adequately fit the data. Since Logistic regressions were used to analyze the effect of each independent variable on women's status of obstetric fistula, while controlling for the other independent variables. Accordingly region, place of residence, educational status, age at first birth, age at first marriage, employment status, place of delivery and follow up of antenatal care were found to be significant predictors for prevalence of obstetric fistula at 5% level of significance (see Table 4.5). Thus, the estimated model is given by:Where: Predicted probability of obstetric fistula, constant, place of residence of women at level 1, women's region level of educational background of women, age at first marriage of women's at level, age at first birth of women's at level, employment status of women's at level 1, place of delivery of level, follow up of antenatal care of level.Therefore, based on the result of The logistic model showed that the likelihood of having obstetric fistula was significantly significant with geographical regions. Women who were living in Amhara region were 4.646 times more likely to have experience dof obstetric fistula than Addis Ababa region controlling for other variables in the model . Similarly, Women who lived in Oromia region were 4.405 times more likely to have experienced obstetric fistulas than Addis Ababa controlling for other variables in the model . Moreover, women who live in Affar, Somali, SNNP, Gambella and Dire Dawa were more likely to have experienced obstetric fistula than Addis Ababa region. Unlikely the odds of having obstetric fistula among women who live in Tigray, Benshangul gumuz and Harari were not significantly differ from that of women who live in Addis Ababa region. The logistic model showed that women's educational status has a negative effect on the incidence of obstetric fistula. A woman having primary education was 89.3% less likely to have obstetric fistula than women who had no education . Similarly, Women having secondary and higher education were 80% less likely to suffer obstetric fistula than women who had no education controlling for other variables in the model .According to result The logistic model showed that women's employment status is a significant predictor of the incidence of obstetric fistula. Women who were not currently working were 1.328 times more likely to have experienced of obstetric fistula than women who had currently working controlling for other variables in the model . The analysis also showed frequency of antenatal care visits has a statistically significant association with the incidence of obstetric fistula (p<0.001). The odds of women experiencing obstetric fistula among those who had taken antenatal care visits for 7 days and above during pregnancy was 87.1% less likely to occur compared to women who had no antenatal care visit . Similarly, the odds of women experiencing obstetric fistula among those who had taken antenatal care visits for 1–3 days during pregnancy was 79.2% less likely to occur compared to women who had no antenatal care visit controlling for other variables in the model . Furthermore, place of delivery had a significant effect with the incidence of obstetric fistula. Women who delivered from health centers were 80.3% less likely to suffer from obstetric fistula compared to women who delivered from their homes controlling for other variables in the model .The study identified that demographic, socio-economic, environmental and health related variables have an important effect on determinants of obstetric fistula in Ethiopia. The results which are obtained are discussed as follow:The descriptive analysis of this study showed that the prevalence of obstetric fistula in Ethiopia was 18.8%. Based on the result of this study, woman who live in Amhara, Oromia, Gambella, SNNP, Somali, Affar and Diredawa regions were more likely to have experiencing obstetric fistula than women who live in Addis Ababa region.This study found that experiencing of obstetric fistula was significantly associated with age at first birth. Women whose first birth was at an age ranging between 15–19 years were 51.9% less likely to suffer obstetric fistula than women whose first birth was at an age of <15 years. On the same way, women whose first birth was at an age range 25 years and above were 86.9% less likely to suffer obstetric fistula than women whose first birth was at an age range of <15 years. This result is in agreement with MuletaThe finding also showed that place of delivery and follow up of antenatal care were found to be statistically significant with the incidence of obstetric fistula. Women who delivered from a health facility and followed antenatal care for more than one day were less likely to exposed obstetric fistula than those women who delivered from their homes and had no antenatal care visits. This result is in agreement with Roka et al.The result of this study indicated that incidence of obstetric fistula was significantly associated with educational status. Women who had primary education, secondary and higher education were less likely to suffer obstetric fistula than illiterate women. This result is consistent with Roka et al.In this study, place of residence was a major cause problem of obstetric fistula, especially in developing countries like Ethiopia. The study showed that the likelihood of women who reside in rural areas to suffer obstetric fistulas was 5.167 times more than those women who reside in urban areas. Most literature reviewed about this important determinant factor of obstetric fistula, for instance a study done by Wall The model of this study revealed that likelihood of having obstetric fistula among women who had no current employment was 1.328 times more likely to have experience of obstetric fistula than women's who had currently employed. This finding is consistent with a study done in West Pokot by Mabeya Finally, according to the result of this study, multiple logistic regression showed that region, place of residence, educational status, age at first marriage, age at first birth, employment status, place of delivery and follow up of antenatal care were all important factors to determining the incidence of obstetric fistula in Ethiopia.


Herein, we describe the consensus guideline methodology, summarize the evidence-based recommendations we provided to the World Health Organization (WHO) for their consideration in the development of global guidance and present a narrative review of the diagnosis of male infertility as related to the eight prioritized (problem or population (P), intervention (I), comparison (C) and outcome(s) (O) (PICO)) questions. Additionally, we discuss the challenges and research gaps identified during the synthesis of this evidence.The aim of this paper is to present an evidence-based approach for the diagnosis of male infertility as related to the eight prioritized PICO questions.Collating the evidence to support providing recommendations involved a collaborative process as developed by WHO, namely: identification of priority questions and critical outcomes; retrieval of up-to-date evidence and existing guidelines; assessment and synthesis of the evidence; and the formulation of draft recommendations to be used for reaching consensus with a wide range of global stakeholders. For each draft recommendation the quality of the supporting evidence was then graded and assessed for consideration during a WHO consensus.Evidence was synthesized and recommendations were drafted to address the diagnosis of male infertility specifically encompassing the following: What is the prevalence of male infertility and what proportion of infertility is attributable to the male? Is it necessary for all infertile men to undergo a thorough evaluation? What is the clinical (ART/non ART) value of traditional semen parameters? What key male lifestyle factors impact on fertility ? Do supplementary oral antioxidants or herbal therapies significantly influence fertility outcomes for infertile men? What are the evidence-based criteria for genetic screening of infertile men? How does a history of neoplasia and related treatments in the male impact on (his and his partner's) reproductive health and fertility options? And lastly, what is the impact of varicocele on male fertility and does correction of varicocele improve semen parameters and/or fertility?This evidence synthesis analysis has been conducted in a manner to be considered for global applicability for the diagnosis of male infertility. In 2012, the World Health Organization (WHO) held a meeting of experts to scope the field of fertility care in order to develop comprehensive guidelines on infertility. Six Evidence Synthesis Groups (ESG) were established. One group was the WHO ESG on Male Infertility: Diagnosis. Following the initial meeting, key PICO (problem or population (P), intervention (I), comparison (C) and outcome(s) (O)) questions were developed and agreed upon. This included working through the WHO GDG (Guideline Development Group) Committee, as well as through web-based surveys, and through outreach to developing country scholars taking an on-line Geneva Foundation for Medical Education and Research- American Society for Reproductive Medicine- (GFMER-ASRM) WHO evidence-based infertility course. For each PICO question, a systematic analysis of the literature was performed according to the ‘WHO handbook for guideline development’ . A preli- What is the prevalence of male infertility and what proportion of infertility in the couple is attributable to the male?- Is it necessary for all infertile men to undergo a thorough evaluation?- What is the clinical (ART/non ART) value of traditional semen parameters?- What key male lifestyle factors impact on fertility ?- Do supplementary oral antioxidants or herbal therapies significantly influence fertility outcomes for infertile men?- What are the evidence-based criteria for genetic screening of infertile men?- How does a history of neoplasia and related treatments in the male impact on (his and his partner's) reproductive health and fertility options?- What is the impact of varicocele on male fertility and does correction of varicocele improve semen parameters and/or fertility?The following eight topics were pre-determined and identified by WHO, and were later formulated into PICO questions for systematic analysis, as follows:The methodology used to support the provision of the recommendations was outlined by the We qualified the strength of our recommendations (as strong or weak) based upon consideration of the quality of the evidence. These recommendations were then later assessed through the WHO guideline development processes that are based upon other factors including values and preferences of stakeholders, the magnitude of effect, the balance of benefits versus harm, resource used and the feasibility of implementation.Overall, wherever possible, original literature, and data from recently published systematic and Cochrane reviews were used. However, due to the diagnostic nature of the questions, a significant amount of the literature addressing them does not lend itself to high evidence level RCTs. Therefore, in addition, key guidelines and professional committee opinions were examined, in order to assist in developing a broader and more comprehensive evidence base, as well as in the construction of recommendations, and in particular: ASRM—Diagnostic evaluation of the infertile male: a committee opinion (2015) ; AmericaData were presented in summary form and descriptively, in tables or narratively in the evidence reviews for each PICO question. Where appropriate, meta-analyses were conducted. The GRADE framework was applied to the body of evidence for each outcome within each PICO. The WHO then used the worksheets to summarize the volume and quality of the evidence supporting the recommendations as well as to outline the values, preferences and judgements made about the strength of recommendations. The uniqueness of the WHO process was that these balanced worksheets were also to be used to note considerations especially for low- and middle-income countries or settings, and to be able to record the reasons for changes made to the default strength of the recommendations.The principles or best practice guidance need to be consensus-based and are also intended to underscore the importance of respect for reproductive rights and dignity as recipients of care, and the need to maintain high ethical and safety standards in clinical practice. These principles, in addition to the strategies for implementation, monitoring and evaluation, are expected to guide end-users in the process of adapting and implementing any recommendation provided by the WHO to consider for a range of global contexts and settings.The evidence based and detailed analysis, with GRADE tables where possible for each of the prioritized PICO questions, were commissioned by and provided by the first author to the WHO in support of their guideline processes. A WHO assessment of our evidence-based outcomes was then undertaken with many stakeholders who evaluate other factors including values and preferences of stakeholders, the magnitude of effect, and the balance of benefits versus harms, resource use and the feasibility of implementation to better assure global applicability. As required by WHO, following these outcomes, additional independent expert review would be conducted (2016 and early 2017). Once completed, the WHO will be publishing their expert and stakeholder consensus-driven guidelines together with the detailed evidence base  and related products  or associated with the infertility . The rationale for evaluating the male and the extent of that evaluation depends on the goals of the evaluation. Several medical best practice statements  suggest Evaluations of populations of infertile men have identified patients in each of these categories emphasizing the need for evaluation of the male  suggest The question is: Which diagnostic strategy is optimal? A significant number of identified male factors are associated with abnormalities found by semen analysis. However, the aetiology remains to be robustly quantified, especially in light of causes of infertility such as birth defects, acquired forms of infertility, infection, inability to have an erection or ejaculation, various syndromes as well as metabolic and endocrine disorders. Sexual dysfunction may be associated with normal semen parameters but can be identified through a sexual history. Additionally, there are a number of genetic syndromes that predispose or cause male infertility some of which are associated with abnormal semen parameters. An initial evaluation of the male consisting of a reproductive history, a simple PE and semen analysis would potentially identify the majority of these cases, however, these evaluations must also be sensitive to different cultural practices and different regional aetiologies, e.g. HIV, genital tuberculosis (TB) in TB endemic areas, lifestyle, environmental and occupational hazards. Significant medical conditions have been reported in 1.1–6% of men presenting for infertility evaluations and a number of these men have abnormal semen parameters. Importantly, however, there are limited data on the incidence of significant medical conditions that predispose men to infertility. One older data series reported that 0.16% of men had significant medical conditions but normal semen parameters indicating that conditions will be missed by limiting a male assessment to a reproductive history and semen analysis  semen analyses.- A full evaluation by an urologist or other specialist in male reproduction should be carried out if the initial screening evaluation demonstrates an abnormal PE, an abnormal male reproductive or sexual history, or an abnormal semen analysis is found.- Further evaluation of the male partner should also be considered in couples with unexplained infertility and in couples in whom there is a treated female factor and persistent infertility Fig. , Table IIn summary, we strongly recommend based on a moderate quality of evidence that:There are significant areas for future research. For example, what constitutes the most appropriate minimal PE and does this provide significant additional information for male health in general, does performing a PE improve male engagement in diagnosis and treatment, what is the cost-effectiveness of doing a PE on all men attending an infertility clinic instead of doing a PE only after abnormal findings in semen analysis and/or an abnormal reproductive and sexual history, can a globally validated questionnaire/topic list for reproductive and sexual history be used (encompassing low-income settings) to identify individuals at risk for male infertility, and Is the outcome better with earlier diagnosis and is treatment less expensive with earlier diagnosis?Specifically, we posed two clinical questions. This first question was whether the predictive value of semen analysis for reproductive outcome is better using a combination of several parameters compared to a single semen analysis parameter, and the second was whether an evaluation of a single ejaculate versus two ejaculates is sufficient for referral to infertility investigation and treatment.A fundamental challenge in the analysis of the literature is the quality of the laboratory testing which is often performed using sub-optimal methods .The analysis of studies to address this PICO question was limited to those published after 1 January 2000, based on two key assumptions. First, there has been a very slow increase in compliance with WHO recommendations for semen analysis. The fourth edition was published in 1999 and few publications before that bear evidence of significant and clear compliance with the recommended techniques  and 10 studies focussed on single ejaculate parameters as predictors of fertility. Studies identifying a single semen parameter with significant predictive power for fertility are relatively common but the discriminatory power is very often low e.g. expressed as receiver operating characteristic curve/area under the curve (ROC–AUC) close to 0.500 or OR including 1.00 in the 95% CI. In contrast, studies that have investigated multiple parameters, which are more reflective of testicular production/function and maturation, for example With regard to the first question namely, Is the predictive value of semen analysis for reproductive outcome better using a combination of several parameters compared to a single semen analysis parameter? Studies were regarded as eligible if they presented primary data on predictive values [or odds ratios (OR)] concerning multiple or single analysis parameters. Four studies provided data on multiple assessments of parameters , where an ICC close to 1.00 indicates high reliability between a pair of assessments].n = 6482) provided information that could be used to support or reject a recommendation concerning analysis of a single versus two ejaculates  and live birth. Second, a fundamental problem with developing new therapies or diagnostic tests for male infertility is the limited understanding of the formation, maturation and physiological workings of the normal and dysfunctional spermatozoon. There is an urgent requirement to understand these cellular, molecular biochemical and genetic mechanism(s) in order to formulate appropriate diagnostic assays and rational therapy for the male.This is, and is likely to remain, a topical issue. The focus of the analysis was on obesity, smoking and heat exposure.Obesity is a global health problem. It impacts not only cardiovascular diseases but also on many other related health disorders. Obesity may adversely affect male reproduction by endocrinologic, thermal, genetic and sexual mechanisms . As suchn = 31 and 25 for Based on the number of papers able to be included in each meta-analysis paper , but do not follow this up with information about the effect on semen parameters 6/ml, . AdditioNo RCTs were found and almost all of the data were collected retrospectively. Previous studies often suffer from small sample size . Suffice it to say that further work is required to elucidate the effects of heat exposure on male fertility. Ideally, scrotal temperature, semen parameters and a measure of fertility outcomes, such as live births, would have to be measured in prospective cohort studies. Studies must use comparable measures of semen analysis, methods for measuring scrotal temperature and definitions of infertility in order for comparisons to be made. This would allow a systematic review or meta-analysis of the evidence to be carried out.In summary, we strongly recommend, based on a very low quality of evidence, that there is insufficient evidence to conclude that exposure to heat, be it occupational or as a result of clothing or body position, affect semen quality and/or male fertility (Table P = 0.012) and concentration (P = 0.023) after multivariate analysis. Several cross-sectional and case-control studies found differing effects of smoking on semen quality. For example, P = 0.04), whilst Most of the published literature on cigarette (tobacco) smoking and male fertility only looks at the effect of smoking on semen parameters. The quality of the recent evidence linking cigarette smoking to decreased semen quality is moderate, as a systematic review and meta-analysis of 46 cross-sectional studies  smoking on semen quality/male fertility but not all studies report this. However, as smoking has an adverse effect on general health and wellbeing it is recommended that men trying for a pregnancy should abstain from smoking  affecting male infertility is likely to remain a rapidly developing and topical issue. There are a large number of significant areas for future research. Primarily large-scale prospective multi-centre trials encompassing a variety of geographical locations are required to examine the effects of lifestyle  and environmental factors /toxins) on spermatogenesis, semen analysis, male fertility and fertility outcomes, including the health of subsequent offspring.There is a significant body of data to support the concept that oxidative stress plays a key role in sperm dysfunction and male infertility . Two-thirds of the studies showed some improvement in semen parameters and one study reported a positive effect on sperm membrane integrity  reported in well-characterized groups to examine, for example, the effects of dietary supplementation, vitamins and herbal remedies.The determination of whether an infertile male benefits from having a genetic evaluation depends on the aetiology of the reproductive compromise and the severity. A detailed history and comprehensive PE, coupled with adjunctive tests, such as a semen analysis, hormone assays and on occasion testis biopsy, help clarify to which diagnostic category the patient belongs and, as a helpful consequence, assists in determining which genetic studies may be fruitful. For example, if a male has a reproductive history consistent with a known cause of resultant spermatogenic failure, such as chemotherapy, bilateral mumps, orchitis with resultant atrophy or current use of anabolic steroids, and is presently severely oligozoospermic or azoospermic, it can be assumed that these are the proximate reasons for the reduced/absent spermatogenesis and no genetic evaluation needs to be undertaken. The focus of the recommendations was on Karyotype, Y micro deletions and cystic fibrosis (CF) mutation analysis.No Cochrane reviews were identified. The primary evidence was from studies by Karyotype: Men with a sperm count <5 million/ml show a much higher rate of autosomal abnormalities than fertile populations (around 4%) while the highest frequency is found in NOA men (mostly Klinefelter syndrome). Klinefelter syndrome  is the most common of the sex chromosomal aneuploidies. Translocations may be found in a relatively small percentage of men with severe oligozoospermia and azoospermia  or NOA prior to any therapeutic procedure  may occur that partially or completely eliminate the azoospermia factor (AZF)a or the AZFb/c region from the genome, and, consequently, any important ‘spermatogenic necessary’ genes that reside in those intervals. Frequency data compiled by AZFc region in 1/27 men, which varied depending on the Y haplotype. The importance of Y microdeletion testing in the severely oligozoospermic or azoospermic male prior to any therapy (ICSI using ejaculated sperm or TESE) is for prognosis and consideration of PGD. For example, data show that when a complete AZFa, AZFb or AZFb/c microdeletion is present (~1–2% incidence of each in the NOA man) no spermatozoa will be found on TESE. When there is no possibility that sperm will be present, it is unhelpful and hurtful for the male to be operated upon and, in the latter circumstance, for the female partner to have an ovarian stimulation unnecessarily. Men with AZFc microdeletions can produce spermatozoa that are capable of fertilization, embryo development and term pregnancy  or NOA prior to any therapeutic procedure  testing should be performed on all males with severe oligozoospermia (<5 × 10No Cochrane reviews were identified. The primary evidence was from studies by CFTR) gene  The CFTR gene has 27 exons spanning 250 kb of chromosome 7 (7q31) and encodes an mRNA of 6.5 kb and the final protein contains 1480 amino acids. Certain mutations, such as c.1521_1523delCTT (legacy name: F508del), severely impair either quantity or functional quality of the CFTR protein determined by that allele. Other abnormalities, such as the 5 T polymorphism in intron 8 (5 T), only mildly impair quantity or functional quality of the CFTR protein determined by that allele. It is the combination of the two that correlates to the severity of disease expression. If a person is homozygous for c.1521_1523delCTT, for example, s/he will have problematic respiratory and pancreatic disease manifested and diagnosed in childhood. However, if a male has inherited the ‘5 T’ allele and c.1521_1523delCTT on the opposite allele and is therefore a compound heterozygote, pulmonary and pancreatic function may be clinically normal and CBAVD is the only recognizable phenotypic consequence. Bilateral vasal absence, then, is the most sensitive indicator of a biallelic CF gene abnormality as there is differential expressivity and sensitivity to CFTR in different epithelial tissues. In addition, it has been postulated that severity of phenotype may be modified by polymorphisms in unrelated genes such as TGFB1 (transforming growth factor) and EDNRA (endothelin receptor type A)  will also have absence of the vasa and seminal vesicles bilaterally and will, consequently, have a low volume, low pH, and an azoospermic ejaculate. The incidence in males of northern European heritage is 1:2000. An equal frequency of men with low volume, acidic pH, azoospermia will have congenital bilateral absence of the vas deferens (CBAVD) with little respiratory or pancreatic disease, the vast majority of whom will possess mutations/pathogenic abnormalities in both maternal and paternal CF alleles. Whether one presents with respiratory tree (including sinuses) and/or pancreatic disease, simply absence of the vas deferens or somewhere clinically between these phenotypic extremes depends upon exactly which mutations/abnormalities in the alleles are inherited. There are >1985 recognized mutations in the CF transmembrane conductance regulator , 5T and CBAVD .The distribution of CFTR mutations and abnormalities, and these cases may be secondary to a distinct genetic aetiology that affects mesonephric duct development. The phenotypic end-product may be CBAVD and unilateral renal agenesis, as described by CFTR mutations are identified, renal ultrasonography is indicated.In situations of CF or CBAVD, it is always necessary to screen the female partner for CF gene abnormalities so as to have a proper assessment of the risks of any offspring inheriting one of the two paternal mutations and the maternal mutation and presenting with clinical CF or, at the least, CBAVD if male. In addition, the benefit of testing the male with CBAVD helps provide information for his siblings who have a 75% chance of harbouring at least one (or possibly both) of the mutations inherited by the patient from his parents. Finally, patients may have mild CF symptoms such as ‘sinusitis’ or ‘bronchitis’, not previously recognized to be CF-mutation related and which, with a full understanding of their genetic basis, may be therapeutically managed in a different fashion. Not all CBAVD appear to be caused by/associated with CFTR mutation analysis should be offered to all males with CBAVD or CF  in low-income settings be developed, and what is the genetic basis of unilateral absence of the vas associated with unilateral renal agenesis?In a number of aspects this was a very challenging question to address. Although there were several reviews in the area, for example However, on a general level, there is consistency in the recommendations of the major medical societies in Europe and USA: the European Society for Medical Onclology  in order to formulate appropriate diagnostic assays, develop rational therapy for the male, and understand how external factors, such as the environment, negatively or positively influence these processes. Not surprisingly, this is not unique to our discipline. For example, a new strategy to understanding neurodegeneration with a primary focus on the formation and function of the cell is now strongly advocated as absolutely essential to accelerate progress for understanding neurodegenerative disorders  whatever the nature of the compromising event(s) . Moreover, this analysis needs to assess the effects in various geographical locations. In addition to the research themes which accompany each question, we identified other areas that require addressing. For example, what is the impact of age on male fertility? What are the underlying causes related to the male for IVF–ICSI treatment failure? Which gene (or epigenetic) defects in men can predict ART outcomes? What are the most effective educational initiatives towards improving understanding of male infertility? What are the attitudes of men and women  towards the investigation of male fertility? Certainly, in presenting this analysis, a plethora of research questions has been generated.A consistent theme was the focus on the quality of evidence available to support any recommendations. The criteria used can be presented in two, not mutually exclusive, formats: Traditionally, the quality of evidence is represented by using a range of different levels. However, it is clear that a considerable degree of the research related to the diagnosis of male infertility does not easily fit into these categories. The evidence is sometimes observational and not easily amenable to meta-analysis. With respect to the scientific and clinical evaluation of diagnostic methods i.e. methods that measure characteristics of the individuals, RCT are not usually appropriate. Primarily there is no inclusion of a separate group to be used as a control i.e. a group not obtaining the investigated treatment. In the evaluation of a diagnostic method, the control of the diagnostic method can be obtained with another independent method, or from the final clinical outcome. From this point of view, the highest level of evidence cannot easily be obtained through a RCT.Where data/evidence were available the quality of the evidence was often judged to be sub-optimal. One issue was the robustness of studies and thus general applicability. The robustness of the evidence base in reproductive medicine has been discussed . Robust Male infertility is a global and significant health problem. A consistent theme is the requirement for national and international efforts with large-scale, multi-centre studies encompassing different geographical locations. Considerable regional variations in key indices of male reproductive health have been reported  may be feasible in most settings but unfortunately they may not be in some areas without specialized storage facilities.in vitro spermatogenesis to dissecting the workings of the mature spermatozoon. However, progress in this arena is comparatively slow. The robustness of the data is sometimes wanting, and thus the ability to provide the strongest evidence-based guidelines has proven to be a challenge. We provided recommendations based upon the evidence available. However, when looking to the future there is a need to understand why it has happened that the data are limited and not forthcoming, in order to inform the direction of future initiatives and endeavours that could result in more studies that yield robust evidence from men residing in high-, middle- and low-income country settings.There are significant advances in male reproductive health from developments on It is fundamental to know the prevalence of a disease in order to provide resources, estimate impact, make effective health economic arguments, present rational research questions and manage patients. However, there is a paucity of clinical data on the scale of the reproductive health problems and infertility in men on a global level, across all health economies. The best estimates on infertility from demographic health studies use the heterosexual woman, as she self-reports a problem with becoming pregnant, which further assumes a diagnosis of female infertility , or possibly, an assumption of an infertile relationship; and, coupled with an even larger paucity of male diagnosis and management of infertility in low- and middle-income countries, any male infertility prevalence values based upon demographic health reports or from small private clinics are, at best, greatly extrapolated and highly inaccurate  of the potential transmission to the next generation of damaging insults to the male germ line by epigenetic mechanisms (The lack of data in key areas reflects the overall paucity of high quality long-term national and international funding streams to support reproductive medicine, and male infertility in particular. Whilst this has been discussed previously it remains a fundamental block to further progress and a critical issue , 2016b. 2 in the atmosphere (Fundamentally, it is necessary to make more robust arguments to national and international agencies to help drive the research agenda and subsequently place reproductive medicine, with demonstrated impact on couples and individuals, at the vanguard of the funding landscape. The coupling of EDCs and male reproductive health may provide an example. In this field strong scientific, socio-economic healthcare and political arguments have consistently been marshalled to support research into what has been termed an ‘epidemic’ of male reproductive health problems . This tymosphere . We needmosphere , 2017. SSupplementary DataClick here for additional data file.


TM tool. The concept was applied to a total of 105 adult patients at the Centre for Integrated Oncology, Bonn, Germany. In total, 392 recommendations for dose adaptation were made and 320 (81.6%) recommendations were responded to by the oncologists. 98.4% of the recommendations were accepted. The algorithm simplifies the decision and screening process for high-risk patients. Moreover, it provides the possibility to quickly decide which laboratory tests are required and whether a dose adjustment for a particular anticancer drug is needed. The ExcelTM tool provides a recommended individual dose for patients with renal or hepatic dysfunction. The effectiveness of this strategy to reduce toxicity should be investigated in further studies before being adopted for routine use.Most anticancer agents exhibit a narrow therapeutic index, i.e., a small change in plasma concentrations can lead to a less efficacious treatment or an unacceptable degree of toxicity. This study aimed at providing health professionals with a feasible and time-saving tool to adapt the dose of anticancer agents for patients with renal or hepatic dysfunction. A guideline for anticancer agents was developed based on a literature search. An algorithm was generated to enhance the efficiency of the dose adaptation process. Finally, the dosing guideline was converted into an easy-to-use Excel Anticancer agents are characterized by a narrow therapeutic index and large inter-individual pharmacokinetic variability. Therefore a small change in plasma concentration due to organ function impairment may lead to an unacceptable degree of toxicity, interfering with therapeutic outcomes and impeding the success of an anticancer therapy ,2. HenceThe main determining factors for plasma concentrations of drugs in general and anticancer agents in particular are kidney and liver function, since these organs are responsible for drug metabolism and excretion. Renal and hepatic functions decrease as people become older, leading to the fact that the number of patients with renal or hepatic dysfunction increases with the age. Current studies show that more than 60% of all incidents of cancer and 70% of all cancer-related deaths occur in patients with more than 65 years of age . KeepingClinical practice often copes with these challenges to a very low extent. This may be due to a lack of information about the need for dose adjustment in hepatic or renal dysfunction for a large amount of anticancer compounds. It may also be due to the inconsistency of the literature dealing with this issue, since the approval and marketing of new anticancer drugs frequently proceeds with rather limited information on pharmacokinetics alterations in renal or hepatic impairment . DiffereSome researchers, hospitals, and institutions have created guidelines for dose adjustment in organ dysfunction by using a literature search, such as the dosing guidelines for selected anticancer agents in patients with renal or hepatic dysfunction by Lam et al.  or the rTo overcome the aforementioned problems of adequate dosing in tumor patients with organ dysfunction, a practice-based approach is needed. It has to imply a relief of work for the physician in charge and include evidence-based data and recommendations for specific dose adjustment. Furthermore, the approach has to be compatible with a daily routine.In this study, we developed a practicable framework for individual dose adjustment for cancer patients undergoing chemotherapy and experiencing renal or hepatic dysfunction for the Centre of Integrated Oncology (CIO) at the University of Bonn. Based on patient observation and a search of the literature, we designed a feasible approach including an anticancer dose adjustment algorithm and a convenient excel tool, facilitating daily work in the hospital. As distinguished from many other studies covering either renal or hepatic dysfunction, our results include data and recommendations for both organ impairments.Our aim was to provide clinical oncologists and pharmacists with a feasible and timesaving possibility to adapt the dosing of anticancer agents to the individual requirements of patients with renal or hepatic dysfunction in order to maximize the therapeutic outcomes and minimize the toxic effects due to overdosing.TM or the Cancer Centre Ontario Formulary [A literature search was conducted, including clinical trials and reviews investigating the influence of organ dysfunction on the pharmacokinetics and toxicity of anticancer agents and including available reviews and guidelines ,8,9. Morormulary , were chBased on practical experience, an algorithm for dose adaptation in organ dysfunction was developed. The purpose was to enhance the efficiency of the dose adaptation process. Anticancer agents were grouped according to lab data necessary for dose calculation. Furthermore, thresholds for the crucial lab data were identified by reviewing the literature and were integrated into the decision tree. Thus, the rapid identification of the necessary lab data for a specific drug combined with “trigger values” for the queried lab data allowed the rapid identification of high-risk patients in need of dose adjustment of a specific anticancer agent.TM 2007 . An entry mask was created for every anticancer agent included in the guidelines, inquiring into all necessary data for dose calculation. The necessary steps for dose calculation were programmed in the Excel sheet using macros. Renal function is calculated automatically based on the entered demographic and lab data using the equation of Cockcroft and Gault (see guideline application). The calculated or measured values associated with organ function are matched to the guideline for the queried anticancer agent in a further step, and a dose recommendation is provided. A validation of the final tool was done by independent pharmacists.In a final step, an easy-to-use Excel tool was generated from the dose adaptation guideline by using the software Microsoft Office Excelk = 1  or 0.85 .Guideline application was conducted on the medical ward for outpatients in the CIO, University of Bonn, Germany, and included all patients with a prescription of chemotherapy at the CIO from May until December 2009. Demographic data , current laboratory data (serum creatinine (SCr), total bilirubin (T.Bil.), aspartate aminotransferase (AST), alanine aminotransferase (ALT)), and prescribed anticancer agents  were collected from the medical file of each patient by a clinical pharmacist one day before the next therapy cycle using a standard data collection form. Estimations of renal function were made by a calculation of creatinine clearance (CrCl) from SCr using the equation of Cockcroft and Gault :(1)CrClBased on the calculated CrCl, the demographic, laboratory, and therapy information and according to the dose adaptation guideline, an individual dose recommendation for each patient was provided by the pharmacist to the physician in charge. This was carried out in written form. The physician had to decide whether to accept or refuse the dose recommendation and had to respond to it in written form. In the case of a rejection, the physician was asked to give the reason for his decision.Depending on CrCl or lab data for liver function like T.Bil., AST, or ALT, specific dose recommendations were provided, including full dose recommendations, recommendations in per cent, specific recommendations in milligram per square meter, and recommendations to omit the dose. For 45 selected anticancer agents, the dose adjustment guidelines for renal and/or hepatic dysfunction are shown in The final algorithm for renal dysfunction is shown in For practical-use purposes, an easy-to-use Excel tool was developed in a final step based on the dose adaptation guidelines, as shown in The tool was validated by three independent clinical pharmacists from the Institute of Pharmacy, University of Bonn. A total of 46 fictitious cases were used for validation; that is at least one case covering each anticancer agent. The validation was successful, given that the calculated results from the Excel tool conformed to the guideline recommendations for each case. No problems emerged, and all reviewers rated the tool as feasible and easy to use.The dose adaptation guideline was applied to a total of 105 adult patients. Among the 105 patients, 64.8% were male. The median age was 66 years , and 54.3% were elderly patients (≥65 years). Complete patient characteristics are shown in For each prescription, a recommendation was given based on the dose adaptation guideline, if all necessary demographic and lab data  were available. A total of 392 recommendations were made and 320 recommendations (81.6%) were responded to by the physicians. Of the recommendations responded to, a proportion of 98.4% was accepted by the physicians. Only five recommendations were rejected, and the reason for rejection was that the CrCl had only slightly decreased below the guideline limit. In this case, the physician, based on his experience, was of the opinion that the patient could tolerate the full dose.To our knowledge, this is the first time an algorithm that has the potential to facilitate the dose adaptation process in clinical routine has been developed. Unlike other approaches, it covers both renal and hepatic impairment and permits individual dose adaptation recommendations for cancer patients with organ dysfunction in a feasible and timesaving manner. Potential toxicity due to accumulation effects can be prevented in these patients, and, therefore, the tolerability and safety of anticancer treatment can be improved. The development of the easy-to-use Excel tool takes account of the advancing process of implementing electronic devices and software into daily medical care in hospitals. It is applicable for integration into prescription and dispensing software addressing oncologists and clinical pharmacists. The easy-to-handle entry mask and the software-based calculation save time and prevent entry and calculation errors potentially occurring during the demanding every day care process.Nevertheless, like other tools, our tool has some limitations. The calculation and determination of renal and hepatic function is based on clinical lab data. For our algorithm, we relied on the SCr concentration for the calculation of renal function by CrCl using the equation of Cockcroft and Gault. Like other studies, we found that relying only on SCr concentration without using prediction equations to determine the patients with renal impairment would cause a great underestimation of the number of affected patients . CalculaTo determine liver function, we considered the clinical parameters total bilirubin, AST, and ALT. Measuring these parameters is a typical way of assessing liver function in studies and clinical practice, allowing an estimation of liver condition, integrity, and general metabolic function. Especially elevated serum bilirubin concentrations can specifically indicate liver damage and functional loss . What isThe recommendations for dose adaptation emerging from our algorithm are based solely on the aforementioned clinical parameters. They are appropriate only to determinate renal and hepatic function. Every other condition and circumstance justifying dose adaptation, except for organ dysfunction, is not covered by this algorithm. This applies particularly to the occurrence of toxicity during chemotherapy. In this case, the dose has to be reduced with respect to patient safety, regardless of the recommendations given by the dose adaptation guideline. Being aware of this issue, we considered it in the first decision point of the algorithm, which asks for the occurrence of toxicity.To avoid toxicity and assure the therapeutic effect of anticancer agents, therapeutic drug monitoring (TDM) is probably the best alternative ,62. ThisThe risk of under-dosing due to toxicity-associated dose reduction cannot be prevented by our guideline entirely, but, by preventing overdosing due to organ impairment at the beginning of chemotherapy, the risk of toxicity will be decreased. Hence, decreasing the risk of toxicity will also decrease the risk of under-dosing due to toxicity-associated dose reduction. Therefore, under-dosing could be prevented by adapting the dose to the organ function at the beginning of chemotherapy. In case of a toxicity occurrence during therapy, the physician has to consider a dose reduction, regardless of the algorithm.Our research pointed out an approach to transfer scientific evidence to clinical routine and enhance safety in anticancer drug therapy. The question of whether toxicity can be prevented, or at least reduced, by adopting the tool in clinical practice can only be answered in a randomized controlled trial (RCT) including an adequate number of cancer patients with organ dysfunction. The guideline was pretested and applied in a sample of 105 patients in one hospital, but the sample size was too small to generate significant results of efficacy. The developed algorithm and the Excel tool have not been yet assessed in practice. Their feasibility and usability have to be demonstrated by routinely implementing them in a clinical practice setting on oncologic wards by physicians and clinical pharmacists.A dose adaptation guideline for anticancer agents in patients with organ dysfunction was developed, followed by a dosing algorithm and an easy-to-use Excel tool. The algorithm simplifies the decision and screening process for high-risk patients. Moreover, it provides the possibility of quickly deciding which lab parameters are required and whether a dose adjustment for a particular anticancer agent is needed. The Excel tool provides a recommended individual dose. The effectiveness of our method to reduce toxicity should be assessed in a randomized controlled trial.


In organizations, innovation is considered a relevant aspect of success and long-term survival. Organizations recognize that innovation contributes to creating competitive advantages in a more competitive, challenging and changing labor market. The present contribution addresses innovation in organizations in the scenario of Industry 4.0, including technological innovation and psychological innovation. Innovation is a core concept in this framework to face the challenge of globalized and fluid labor market in the 21st century. Reviewing the definition of innovation, the article focuses on innovative work behaviors and the relative measures. This perspective article also suggests new directions in a primary prevention perspective for future research and intervention relative to innovation and innovative work behaviors in the organizational context. In organizations, innovation is considered a relevant aspect of success and long-term survival . OrganizTechnological innovation comprises “new products and processes and significant technological changes of products and processes” . Mentz , p. 12 pPsychological innovation is focused on the characteristics of the innovator,innovative behaviors, and psychological mechanisms that guide innovation . In the In Industry 4.0, innovation is a core concept. Industry 4.0 refers to the trend of increased use of information and automation technologies in the manufacturing environment . TechnolMany advanced countries with economic systems based on the manufacturing industry must compete with emerging markets that have lower production costs . ManufacManufacturing companies need new strategic approaches for holistic human resource management to cope with knowledge and competence challenges related to new technologies and processes of Industry 4.0 .An analysis of the literature also shows that innovation can be facilitated by external social support with regard to the presence of more proximal supportive leaders and organizational support . WithoutThe first definition of innovation in the workplace includes generating creative ideas at the first stage and implementing these ideas at the second stage . SubsequDeepening the construct of innovation, an important distinction regarding the difference between innovation and creativity emerges . RegardiContinuing to deepen the construct of innovation, it is important to consider similar but distinct constructs in the change and innovation literature. For example, these concepts include proactive behaviors , job craIt is also important to distinguish different levels of analysis regarding innovation: individual, team, and organization . AnalysiIn terms of the team level of analysis and its role in facilitating or inhibiting innovation in the workplace, it is important to consider different aspects in terms of antecedents as team input variables and team process variables and in terms of moderating influences on antecedent-criterion relationships . Team inA recent meta-analysis  showed tAccording to an organizational level, innovation is positively associated with management-related factors such as the following: management support and cooperative conflict management ; knowledAlongside these attempts to define innovation, the need to focus on translating innovation in work behaviors of employees emerged . AccordiIn 2000, Janssen underlined three aspects of innovative work behavior: idea generation, idea promotion and idea realization. Until then, the construct of innovative work behavior was considered essentially unidimensional as relative measures. In detail, the innovative work behavior measure  is compoSubsequently, The multidimensionality of the innovative work behavior construct emerged empirically in other scales. The To overcome the limitations of the existing measures, Innovation is a key driver that can guarantee competitive advantages for organizations , but it By presenting some current new instruments and training in this perspective, it is possible, at an individual level, to introduce preventive and new variables in relation to innovative work behaviors, such as acceptance of change  or workpLP and AD conceptualized the work and ideated the structure. LP, OB, and AD analyzed the literature, and all authors wrote the manuscript. Then all authors read and revised the manuscript several times.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.