Monthly Archives: May 2020

Menstrual Restrictions and Its Impact on Empowerment: A Case from Jumla, Nepal

DOI: 10.31038/AWHC.2020323

Abstract

The menstrual blood considered impure, dirty and contaminated in Jumla, a place of research for menstrual restriction and its impact on empowerment where the qualitative method, feminist ethnography employed, through three different methods: history/timeline, participant’s observation and In- Depth Interviews. The restriction during menstruation is very complex, vary from person to person, contradictory position between practice to practice within same person or family. The participant followed 29 types of restrictions related with food, touch and mobility during their menstruation. Because of these restrictions, girls and women deprived from access to food, water, shelter, mobility, hygiene, health, education. As a result, they felt isolated, inferior, disempower, deprivation from participation in school, social activities/celebrations and losing dignity. These situations contributed for compromising rights assured by the constitution of Nepal and considered as violation of human rights. Here, the restrictions during menstruation played a role to construct and shaped the power among girls and boys. As a result, the all aspects of the girls and women’s life affected and eventually they deprived from the empowerment.

Keywords

Menstruation, practice, restriction, women’s dignity, empowerment

Introduction

Globally, depending upon the areas of residence, school’s norms, parental guidance, media etc. few girls and women aware about the menstruation [1] where as many rural, tribal and even educated girls and women do not aware about the menstruation [2]. This kind of experience is very common in Nepali society even school going adolescent girls [3]. Nepalese community considered the menstrual blood as impure, dirty and contaminated that established by religious books, schools and informal institutions. As a result, girls and women are following multiple levels of restrictions during menstruation as common practice in Nepal. Among the development work, media in Nepal and beyond the word Chhaupadi is popular since MDGs (Millennium Development Goals) which as restriction during menstruation. The restriction during menstruation outlawed in Nepal since 2005 and there is law against any forms of discrimination, exploitation, violence during menstruation since 2018 (“Nepal Law Commission – NLC,” n.d.). There are schools of thought regarding the cause of practicing restrictions during menstruation. It has been in practice due to illiteracy, superstition and gender inequality revealed that the concept of impurity and poor menstrual hygiene impacted for Millennium Development Goal (MDG)-two on universal education and MDG -three on gender equality and women empowerment. Likewise, menstruation has multiplier effect for achieving the Sustainable Developmental Goals especially to goal five for gender equality.

Since the 2014, there are few studies started to take place in Nepal and globally that were most focused on hygiene. In Nepal, such studied conducted for the academic purpose as well as NGO’s intervention. Thus, the studies that encompass on consequences due to following the restrictions during menstruation is not available except some opinions in media and activism for instance for 2017, Jyoti Sanghera, a pioneer activist stated that the stigma during menstruation is violation of dignity including violation of several human rights [5]. The menstruation played a crucial role to bring equal position in holding power, participation in decision making at family and workplace [6].

In this connection, this study took place to provide the critical view on impacts of menstruation on empowerment of girls and women with following research questions:

i) What are restrictions practiced during menstruation?

ii) To what extent, the education affects by the menstrual practice?, and

iii) What are the impacts of menstrual restrictions on empowerment?

Methodology

This study employed the qualitative approach where applied postpositivist world view with feminist ethnography for the change at the life of women and society by questioning the policies and demands for social transformation [7]. Chandanath Municipality, Jumla district is the site for data collection due to accessible by bus, cost, time compare to others areas. More importantly, this community has been practicing restrictions during menstruation [8]. In order to avoid the reflexivity, the purpose and process explained with gate keepers. The participants for data collection identified as guided by the gate keepers till the saturation of data. The ethics maintained by securing the approval from National Health Research Council (August 2017) and obtained verbal and written consent. As suggested by the Elana D. Buch & Karen M. Staller, [9] primarily, the three types of methods: history taking/timeline, participants observation and In- Depth Interview employed in order to get rich data around menstrual practices. The interview guide, observational check list used for collection of data. The participants identified through gate keepers as well as snow ball methods specially to find the menstrual girls and women.

Life history/Timeline

The total four menstruating participants between 28-40 years identified. They all represented married and followed Hindu religion. Regards to caste two were from higher caste and the remaining belonged with Dalit and Chhetri respectively. Except one, all participants never ever been to school and three worked at home.

Participatory Observation (non- participant to participatory)

The six menstruating, married participants considered for participatory observation for three days. Out of six, two were never ever been to school, two were belonging with Dalit and rest of them belong with higher caste. And, three were working as health workers, two worked as house wife and one was student.

The place or location, clothing (during menstruation and after), physical gesture and sitting/sleeping, interactions (family and social), physical appearance, personal behaviours/emotions/feelings, key influencers, food/liquid intake, restrictions (private, public), mobility, used and management of sanitary materials, cleanliness observed [10].

Mass observation

Two mass activities; Teej celebration (Annual festival specific for women called red colour festival as well) and Temple observation observed.

In-Depth Interview with Key Informants

The total number of participants was 17 (Female -8, Male-9). All the female ranges from 14 to 80 years of age and have experienced of restrictions during menstruation. Regards to occupation, they belonged with teaching, health service provider, faith healers, journalist and housewife. Except three females, all were married. Regards to education, except one participant, all were educated. In terms of caste, only two participants were belonged with Dalit.

The data and informational triangulation through multimethod approach, probing questions as well as follow up visits during field visits. The field notes, videos, photos used to verify the information. The data started to analysis since the data collection. It was iterative process of collection of data and analysis. The data transcribed, coding, and generate themes. For ensuring the accuracy, the data corroboration with various sources of data. In order to ensure the grounded of data, logical inferences, appropriate themes, justified decisions and methods, credibility and biasness, the research process and analysis reviewed by peers and supervisors time and again as a form of eternal audit.

Results

Restrictions on Touch during Menstruation

Since menarche, participants were avoiding to touch various things by considering the menstrual blood impure. During menstruation, girls and women not eligible to touch places (foundation of house, house, kitchen, temple, toilet), person (male member, faith healers, seniors, priest,), things (tap, river, intercourse, book, cattle, clothes), and plants of vegetables and fruits.

Restrictions to Eat during Menstruation

Menstruators prohibited eating rice, vegetables, fruits, milk products, prasad, meat products, beans, sour foods during menstruation.

Restriction to Work/Mobility/Participation during menstruation

Menstruators restricted in mobility, cannot work inside the house, same road or place as seniors walk/work, around the temple, meetings and cultural celebrations.

Impact on Empowerment

The perceptions, practices and understanding around menstruation have been reflecting the impact on empowerment at individual, organizational and community level and overlapped each other [11]. The feminists considered the empowerment as mutually strengthening and intersecting the sub process where the problems identifying and deconstructing for action and critical reflection 12].

Due to restrictions, there is impact of education and health that overlapping each other and impacted to the lives of girls and women throughout the life. Girls and women do consider the menstruation as matter of shy, stigma, and taboo instead of biological process and pride. Simultaneously, their knowledge, attitudes, and practices pulled down the confidence of girls and women to see them as equal human being as boys or men.

Control of Body of Girls and Women during Menstruation

The imposed restrictions connote the lower status than boys. Those kinds of understanding started to build since age of fivenine years from their mothers, sisters, friends, other relatives and neighbourhood. This brings the `powerfulness’ for boys whereas the `powerlessness’ to the girls. Menstruation appeared as tool to construct the power since childhood. The boys possess the Power Over Decisions and girls resembles the Power over non-decisions according to the power theory [13] McCabe, n.d.).

Before menstruation, girls started to see themselves as humiliation and inferior than boys whereas boys are socializing the opposite direction. In addition, girls lost their dignity and peace of mind since childhood.

The isolation and exclusion from the home and regular activities, for five to seven days in a month has served the status of girls and women due to menstruation. Further, the living status gives the idea of menstrual girls and women are lesser than domestic animals.

Boys, teachers and girls know that the girls have menstruation from her absence of school during menstruation and drop off the class in between. Because menstruation considered as matter of shyness/ stigma/taboo. Such situation further amplifies the state of impurity for menstrual blood. Because of such understanding, girls cannot concentrate on class if they joining during menstruation. They lose their self-esteem, confidence within themselves and lose their dignity in the public. Participants shared that they felt like they are doing any act like crimes thus they felt so guilt while having menstruation and more shame and guilty if anyone knew without letting them directly.

“During my first menstruation, I missed the class for five days. I felt so embarrassed and powerlessness while joining the class next week. I was so flushed to see the faces of teachers and boys in class due to shame and feeling that I committed crime. Because they know automatically if any girl missed the class like this’’.

IDI_Healthworker_Female_5

Due to restrictions, menstruation considered as women’s private business thus girls and women feel humiliated and disempowered. Men never menstruate but they keep learning since about four to nine years old from their sisters, mothers, aunts, relatives and neighbourhood. Almost all of them agreed that they discussed about the menstruation among themselves (secretly). Boys gained the power that they never been menstruating means pure, higher, privileged than the girls. They started to see not only girls are inferior, low status but also started to learn to govern their ideas and body like do this and do not this since childhood to their sisters, friends and others.

As men grow by, their parents, faith healers, seniors are asked to follow the restrictions by limiting themselves because of state of impurity of women. There is a long list of` Do’ this and `Do not’ this regarding to menstruation. As a result, they strongly believed that menstruation is impure state, made by god and men should not contaminate with menstruating girls and women at all. Because men have posses’ superior position by god, men have outstanding power than women. Thus, men see themselves as governor, power holder wherever they are.

Feeling of Inferior

Regardless of caste, class, education and occupation, all female participants felt deeper level of humiliation, inferiority since they menstruate. One of the participants shared her first feeling from menarche was losing myself (aba ma sakiye -IDI_adolesent girl_17). The dehumanization and inferior complexity are deeper and stronger due to compromises the biological needs and social needs such as food, drink, shelter, sleep, security, mobility and isolation from the friends, family, affection, relationship. Participants verified themselves that the menstrual blood and menstruating women is really `impure’, `dirty’. Few close friends were visiting at shelter and often accompanied though they all confirmed that they are real `powerless’ creature in this world because their esteem needs such as self-esteem, achievement, mastery, independence, prestige etc. were heavily scrutinized. Meantime, they also so much confused with the imposed list of restrictions during menarche which were incompatible with learnings what they learned from formal education regards to purification process including cleansing with cow’s dung and urine, spray of golden water. They were depressed with lots of imposition including putting loads of responsibility to women followed by menarche.

Since the first day of menarche, participants experienced surprised, shocked, sad due to ignorance about menstruation, management of blood, the norms or lists of `Do’ and `Do not’ associated with menstruation. Continuously, they felt humiliation, disempower and lower than men. Due to inaccessibility with food, shelter, water, mobility, participation, they equally experienced humiliated, inferior and disempower. The purification process is mandatory and important even during the season of snowing and state of sick. However, all participants thought that the purification process also changed already.

“In the past, we used ash to wash for purity. Now we use soap, surf to wash cloths in river by slapping in stone. I, myself, use the shampoo for washing my hair, use tika on forehead. There are so many instructions for do and do not that make me sad, inferior and frustrated’’.

Timeline/History Talking_Female_3

All participants know that the menstrual girls and women are even not allowed to touch foundation of the house since childhood and often feel inferior to boys and men. Such feeling rises even more after their menarche. They feel themselves less recognized compared to male at family and community. They do not feel that they have any power or authority over the property of the family though they work so hard than boys and men. Participants shared that they often considered themselves as persons with less value. The restriction for not allowing to touch foundation of the house caused them disassociated with their own family and confirmed the feeling of inferior human being in this universe due to impure menstrual blood.

As like the restrictions, not allowing touching the foundation of the house, the restriction for entering into the house resembles the feeling of sad, sorrow, feeling of insecure, low confidence, low status than man. Because of the heavily compromised the biological needs such as food, air, shelter, hygiene, love affection, family etc. which are important for girls and women during menstruation.

Almost all participants including elders shared that they were so frustrated due to not allowing entering into the kitchen. They said that they have to be deprived from the getting food and water when they got hungry and thirsty. They tired up and losing their dignity while requesting and pleasing siblings/children/in laws. Most of the participants simply gave up them to please means they just waited whenever they gave. Few participants just went to bed without having food.

Because of the restriction to avoid touch with men members, girls and women lose their self -esteem, confidence and dignity as well as considered themselves as inferior and low status than men. In addition, participants also deprived from participation in activities related with learning, entertainment, social cohesion and development. Because the men are everywhere at home, school cultural gatherings and meetings at village council.

Due to the supremacy attitude and practice of seniors, the participants had `scared’ `irritating’ feeling towards seniors. They felt embarrassed, humiliation, inferior and often dehumanization’s from the comments passed by the senior. This culture is one of the pushing factors at family and community to engage in voluntary child marriage.

Feeling Isolated

The both deep ignorance and silence and emotional stress including sad, hopelessness, dying soon, crying, feeling isolated pushed participants towards disempowerment during menstruation and rest of the months.

Deprivation from Participation

The joining in a meeting is a form of participation of political process at community. The deprivation as well as the emotional and physical abuses both were double the reverse impact on empowerment. Once, they failed to exercise their rights here, they would fail to claim in municipality political process.

Losing the Dignity

The restriction for not touching the plants of vegetables and fruits promote the condition of deprivation of seasonal nutritious foods which is violation of right to food, right to dignity, right to mobility. Further, these situations created the emotional unwillingness which leads deep psychological trauma. The restriction for not touching the cattle leads disempowerment for girls. Few of them, expressed their anger and frustration against such restriction because they were responsible even during menstruation to cut grass, and graze them but not allow having it. They felt humiliation by considering the low status than the animals.

Restriction to touch toilet during menstruation negatively impacted to learning and health issues e.g. attacked by the wild animals, experienced sexual abuse including rape.

Touch has directly connection with right to dignity and right to participation or mobility or touch of the girls and women during menstruation that is assured by the constitution of Nepal (“Nepal Law Commission – NLC,” n.d.). They also deprived from safety, security, confidentiality, enough water to clean clothes and body etc.

Due to no access with clothes, adequate and nice clothes. These circumstances established the feeling of low status and humiliation among participants.

“I wanted to participate the festival at market with hiding my menstrual blood but I could not participate because my mother scolding that I should not use such new clothes during menstruation. If I were using these clothes during menstruation, I could not use these clothes in any programs for future due to concept of contamination with impure menstruation. The more I remember; I still feel more humiliation and anger though I am against of these naughty cultures’’.

IDI_Health Worker_Female_11

In the beginning, the female participants were spontaneously expressed their believes and practices regarding the reason of restrictions to have milk and milk products. Later, when they discussed deeply about their first feelings and impact, they appeared sad and unhappy. They said that this practice is visible form of discrimination towards girls and women and key reason of being weak. In earlier days of menstruation, they cried, they felt regret as being born girl, they fought with their parents and seniors and even they thought to end their life.

The restriction of not allowing to walk around temple also accelerating the disempowerment among female participants. Because of such practice, girls and women feel underprivileged and disadvantages than men. They feel humiliation, discrimination and anger towards the society, family then themselves due to unable to join in the public activities such as sports, group meetings, celebrations etc.

They had experienced of double victimization due to menstruation and also scolded by the neighbours while they were watching the celebration and meetings from distance. Often the religious or other activities were cancelled due to menstruation where menstrual women got blaming of all lost and reschedule.

“The status of menstruation is the foremost enemy and hateful thing for women. “Sometimes, I pushed myself and tried to join the cultural program but I had to stay and observe things from very distance. Sometimes, the women shouted even observing from distance. They became sad and angry if the menstrual woman is in front them. They believed that they were attacked by god and shaken (Paturne). People even do not allow to plant and gardening in the field at the beginning. The non- menstruating women start and then they allow menstrual women to enter in to field in farm. We are supposed to postpone the religious and cultural activities such as worships, weddings if the women menstruate at the house of hosting’’.

Life History//Timeline_Dalit Women _2

“I do not like to go anywhere because I often feel so weak and lazy and like to lie down.

At bed throughout the period. I often lose my appetite because of discomfort. My culture does not permit me to participate to any marriage ceremony and even religious activities. I am only allowed to go to field for work. Many times, I had to cancel my visits to religious activities with other family members after menstruation’’.

Almost all participants including men said that the menstrual women have rare chances of interactions with older and religious people. They can only interact with limited people such as daughters and female friends. The impact of menstrual restrictions, stigma has hit all aspects of life of girls and women in many ways. Because of restriction, they started to missed out the classes or poor attention on learning and education. Then they started to failing in subjects and eventually stop to go school. Some of them just trapped with early or child marriage because of dismissal of their dream on education and life. It is really complex to understand.

“I am 14 years old now studying at grade ten. It is only 5 minutes walking distance. I do not like to go school for 3-5 days during menstruation. I did marriage just six months before forcefully. My new role as married woman got much workload in the family and caused fail in English. Now, I am bit confused to continue my study or not’’.

Participants Observation__ Adolescent Girl_Dalit _6

Working in the field and collecting firewood or fodder is not a problem at all. But the problem is they have to work in pressure. They have to finish the work within bleeding days otherwise they cannot concentrate these works due to the work at inside the house. This is form of discrimination, violation of human right especially right to dignity, right to freedom, right to choose, right to food etc which is guaranteed by the constitution of Nepal.

Disempowerment due to Deprivation from Learning

Deprivation from learning and quality education, is a serious form of disempowerment. The level of chronic emotional unwillingness, deprivation from quality educational opportunities and trapped early or forced or voluntary marriage of girls, pushed further form of disempowerment.

“The situation was different in the past. In my case, I even, did not send my daughter to school after menstruation. She got marriage and sent to her husband’s house. The same situation applies to some of my relatives as well where daughters have to leave school after menstruation even at present. Now, situation seems changing gradually. Now, I myself prefer to send them to schools though few restrictions still exit in the society.”

IDI_Elder Women_12

The deprivation from touching the source of water supply means deprivation access to water supply. They disempowered from the perspective of health and dignity. The water for drinking and hygiene or clean both the basic need for humans. Participants expressed their frustration from this practice which is unavoidable at all.

‘`I have bitter experience when I got first menstruation in my life. I was not allowed to touch water for 15 days, though I got permission to stay inside my house and eat food without touching other members in the families. I was treated as beggar that made me so frustrated and angry. Even for bathing, I had to go to irrigation canal’’.

IDI_Healthworker_Female_11

Those girls and women who do not follow such restrictions, they have confidence to behave in front of all. Among the participants who represented dalit and Tibetan group, and were working at local hotel said that they never experienced discrimination and nobody asked them to follow restrictions during menstruation. They said they were serving food items to all people including even priests. They said that;

“We belong to dalit and Bhote caste people and work at this hotel for years. We do not make our menstruation period to public and do not follow any restriction as upper caste women follow. We do everything here from cooking food, serving to costumers, cleaning at kitchen, rooms and everywhere’’.

Informal Meeting_Feamle_Lama

During menstruation cycle, women are not allowed to work inside the house due to state of `impurity’ and `dirty’. This is very powerful instruction to dominate the status of girls and women since childhood even before having the menstruation. In Jumla, the kitchen is the primary level of parliamentary where the family members review their daily activities, share the common issues from neighbourhood and plan for next day and future but women in menstruation period have to miss the opportunity to participate among family members. The participants however, were found themselves as victims of social discrimination.

The youth participants said that during their menarche, even the girls from the educated families, were not allowed to go schools due to scare of contaminations. It even applied to those who were not at school. Such restriction not only hampered to their education but to their participation at household activities. The incidence of child marriage connected to menstruation however, was not perceived well. Regarding this, a female local politician said:

`I do not know why the practice of child marriage is rampant in my community. Though the Municipality is organizing various awareness raising activities, there is no impact yet’.

IDI_PoliticalLeader_Female

Discussion

Among 29 different restrictions, few are overlapped and interlinked with each other. These restrictions hit all aspects of the life of girls and women in many ways. As like restrictions, the impact also overlapped and interlinked each other.

There are various ways of defining empowerment, primarily focused on gaining power and used as key concept in almost all discipline [14]. Menstruation has significance role on life of girls and women from womb to tomb and all aspects of the life where they may or may not gain power.

First and foremost, menstruation associated practices constructed the power at an individual level of boy and girl and at institutional. Both girls and boys started to learn the menstruation since young childhood. Without knowing any logic, girls see themselves as like mother who have to work hard, dominated by the men members, powerless due to the state of impurity of menstrual blood. It has similarity with the believe of Rappaport (1987) where the empowerment as process of gaining mastery by people, organizations and Communities, happening at multiple levels [15]. Since childhood menstruating girls and women kept actively engage with their community and an understanding the socio-political dimension around them instead of having observations or self-perceptions regards to menstruation. In this vein, [11] emphasized that that psychological empowerment is more than self-perceptions.

As time passed by, girls started to cope with all consequences brings by menstruation. They do without any questioning, challenging even they do belief in such a deep way where they see logic against restrictions. They see these restrictions as part of culture, order from the god, who make and put everything in order. Consequently, they started to realize that the sexual abuse, domestic violence, rape, intimate partner violence, deprivation from opportunities etc. are all happening because of discrimination against girls and women due to their state of impurity. These are the form of violence but they do not have courage to speak due to deep feeling of powerlessness and hopelessness. Eventually, girls and women converted as victim. In alignment with this, the close tie was revealed between restrictions during menstruation and gender based violence including rape [16]. The state of powerlessness is constructed and learned by menstruating girls and women through the observation, past experience, ongoing practices, behaviour and thinking patterns before, and during the menstruation. Feminist believed that the powerlessness or oppression or deprivation is the outcome of both socio-economic and psychological factors [17]. Further, this study emphasised for understanding the material reality of oppression. In contrary this, powerlessness considered as more than lacking power including inability to cope with emotions, skills, knowledge, lack of self-esteem including lack of external supports [18].

Meantime, boys considered themselves more powerful, superior, privileged at home and community due to the state of purity or no menstruation throughout the life since god’s time. As time passed by, boys started to provoke with all consequences brings by menstruation. They denial to do, arguing even they do belief in such a deep way where they see logic against restrictions. They described these restrictions as part of culture, order from the god, who make and put everything in order. Consequently, they started to realize that the sexual abuse, domestic violence, rape, intimate partner violence, deprivation from opportunities etc. are all happening because of discrimination against girls and women. These are the form of violence but they do remained silence due to deep feeling of powerfulness and state of privileged. Eventually, boys converted as perpetrator.

In this vein, the Garg et al., [19] Johnston-Robledo & Chrisler [20] agreed that the segregation due to impurity and restriction regarding touch, the girls considered themselves inferior, negative feelings towards their body. As Rembeck et al., [21] believed the girls and boys self-esteemed and self-agency built since childhood where the family played a vital role for that and influenced by and from menstrual practice. In this vein, Johnston-Robledo & Chrisler, [20] argued that the lower status of women was determined by menstrual stigma and taboo in the family and community.

AWHC-3-2-310-g001

Figure 1. Menstrual Restrictions construct the power

AWHC-3-2-310-g002

Figure 2. Menstrual Restrictions and its Impact on Empowerment

AWHC-3-2-310-g003

Figure 3. Menstrual Restriction and its impact on empowerment

Menstruating girls and women lose their sense of and motivation to control, skills for decision making and problem solving and critical awareness on socio-political environment as impact of psychological disempowerment. In this vein [11] described as constructs; interpersonal, interactional and behavioural component under the homological framework of psychological empowerment. Additionally, limiting or exclusion due to menstruation also affects women legal rights and freedom of women in public sphere.

The impact of education and health are overlapping here. Girls and women have low self-esteem, feeling of inferior, humiliation, hopelessness, powerlessness because of compromising the needs and rights related with food, water, shelter, environment, education, health and eventually dignity [22]. Dignity is such a right which includes all rights and offers right to all aspects of life of girl, women and any individual. Poor education, poor health is the status of poor human right and status of disempowerment.

Conclusion

Girls and women lose the confidence for living as a dignified human kind due to imposing of varieties of restrictions during menstruation. They used to with this too. In this connection, stakeholders need to carryout the holistic approach to get rid off from the negative impact on the lives of girls and women due to restrictions due to menstruation. Because the above-mentioned figures showed that the impact is not in a single line (liner way). It has multiple connections and overlapping each other’s. The dignity and empowerment during menstruation could bring through combined efforts of different elements such as health, education, water, sanitation.

Limitations

This study confined with qualitative approach and employed in Chandanath Municipality, Jumla.

Conflict of Interest

No any conflict of interest. This has done for the sake of fulfilment of academic requirement as building block of my activism around menstruation.

Funding

There is no any funding for supporting of this study.

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Missing the Menstruation amidst COVID-19

DOI: 10.31038/AWHC.2020322

Background

The entire world was celebrating the New Year eve (December 31, 2019) but China officially informed to World Health Organization (WHO) about the unknown illness that later known as Corona Virus or COVID-19. The novel Corona virus labelled as pandemic by WHO in March 11, 2020 [1]. The impact of pandemic different to men and women and even more deeply and widely affected in the areas where countries are under conflict or post conflict or traditional [2]. In this response the variety of professional are working so hard around the clock where the 70% workforce (among 104 countries) represented by the women workers as a doctors, nurses, social workers, kitchen workers, security personnel and so on [3]. Each crisis situation intensifies the gender inequality and the COVID-19 further intensifies the affect against girls, women and menstruations [4]. This is supported by the idea of women are missing [5].

Roughly, half of this planet is occupied by the women no matter where they are. She could be anywhere but only visible as doctors, nurses or security personnel. Women are everywhere either at COVID-19 laboratory or kitchen of hospital or home or refugee camp or migrant workforce or conflict or anywhere. Indeed, women are everywhere but she is nowhere. The COVID-19 does not cease the menstruation of women regardless of women working in laboratory or patient at ICU or women under lockdown. Globally, the first time in a history that the demand of menstrual products as part of Personal Protection Equipment [6].

More importantly, the stigma, taboo and restrictions during menstruation is practicing across globe with variation on forms and severity. And globally, the menstruation as ignored and side silenced issue in development and human right till now. Furthermore, the dignity during menstruation or dignified menstruation is further unrecognized by the global community [7] . Paudel described the dignified menstruation as `as virtue of human being, each girl, women or menstruators deserved the dignity during menstruation. It is a state of free from any forms of abuse, discrimination, violence associated with menstruation no matter where the menstruator lives. In other words, there should not be difference between 25 and 5 days in a month, throughout the clock of 365 days because of menstruation’ [7].

Objective

The main objective is to assess the space for women amid COVID 19, Pandemic from the perspective of menstruation. The specific objectives are:

Objectives:

I. To understand the impacts of menstruation amidst COVID 19, Pandemic.

II. To examine the global policies and actions towards menstruation around the amid COVID 19 Pandemic, response.

Rational

The Secretary General Antonio Guterres constantly emphasised that the fighting the virus for all of humanity, with the most affected people: women, older person youth, low wages workers, small and medium enterprises, the informal sector and vulnerable groups. In a way, there is no visible need of menstruation and the other way round there is menstruation across all kinds of people.

Once the WHO confirmed the Pandemic for COVID-19, the global community starting from the UNs, governments, NGO and individuals are relentlessly are working for combating with amidst COVID-19 which is happening about a century after. In course of century development and human right discourse, world has been accomplished so many concerns related with women including for menstruation. The varieties of concepts around menstruation were emerged: in 2012, the UNICEF and WHO (Menstrual Health Management), in 2014, the UNSECO and Human Right Council, Water and Sanitation (Menstrual Hygiene Management) and in 2017 Nepal government (Dignified Menstruation). Additionally, the menstrual stigma, taboo, restrictions also discussed as factor for the construction and shape the power starting from childhood and it is a serious cause for provoking the gender-based violence [7].

Methodology

This quick review is under the qualitative, post-positivist world’s view. The data primarily secondary through the internet. The news, policy papers, statements etc. released by the various organizations and available in google during state of lockdown globally. Regards to timeline, it limits between the announcement as pandemic for Corona virus and till April 24, 2020 (total 44 days). However, the primary data also included through various webinar special focuses on menstrual health and hygiene and some observations of live press meets. In a way, the global perspectives assessed as provided by context.

Findings

1. Impacts of menstruation during response amidst COVID 19, Pandemic

Wuhan, an epicenter of The novel Corona virus of China and first city globally, where the front lines female workers were under physical and psychosocial pressure due to stigma and the government did not considered the menstrual products as essential supplies during COVID-19 response [8]. Likewise, the female front-line workers were talking birth controls for avoiding menstruation due to stigma and not supply of menstrual products [9] Jiajia, further shared the impact of menstrual taboo on urinary tract infections that associated with the discussion and supply of menstrual products.

In the same vein, the leading the way organization, WHO, to defeat against novel Corona virus in many ways but missing to acknowledge the needs and urgency of menstruation. It released a document in 18 March 2020 on mental and psychosocial consideration where it displayed message for general population, health workers, team leaders of health facilities, elder adults and people in isolation where the impacts of menstruation (before puberty, puberty, reproductive age, menopause) missed at all [10]. The WHO is also shown inconsistence on what it believes on menstruation (2012) and health’s definition since 1948.

2. Examine the global policies and actions towards menstruation around the amid COVID 19 Pandemic, response

Followed by the WHO’s confirmation of pandemic for novel Corona virus, the global organizations, networks, governments, NGOs, individuals who are working around women’s menstruation, peace, right, empowerment etc. are releasing the petitions, statements through online. This study attempted to examine to what extend these policies or documents reflects the needs and importance of holistic approach of dignified menstruation.

WHO is the leading organization for the COVID-19 responses globally, keeps releasing the resource materials for prevention of novel Corona virus, management of Corona positive patients, promotion of human right through various aspects etc. However, the WHO remained silent at all to response the direct and indirect needs arise from menstruation. Before the COVID-19, WHO recommended for gender transformative policies to address participation, inequalities, gender-based discrimination on pay, employment but not speak how menstruation plays in enabling work spaces [3].

For instance the seven points forwarded by the NGOWG to the security council with the demand for women’s right must be centre for response to COVID-19 [11] . This document is just reiteration of the documents, policies because these points do not visualize the specific actions directly what, where or how? The points number two (Require rights-based and age-, gender-, and disability-sensitive pandemic responses) and the point three (Prevent and respond to gender-based violence) are just coming through decades but not represent the need of menstruation and the role of menstruation in heighten the violence against girls, women and menstruators.

“Point 2: Require rights-based and age-, gender-, and disability sensitive pandemic responses: COVID-19 responses must be grounded in data disaggregated by gender, age, and disability and intersectional analysis that recognizes the gendered impact of the crisis. Point 3: Prevent and respond to gender-based violence: Take necessary measures to prevent, address, and document all forms of gender-based violence, particularly intimate partner violence and other forms of domestic violence’’.

The gender analysis is very common jargon but it does not provide a single clue to intervene the needs associated with menstruation e.g. status of menstruation or choice of menstrual products. Likewise, during COVID-19 response, the girls, women and menstruators are working as frontline workers or at refugee camps or migrant workers or disable or transgender to anyone under the lockdown characterized by quarantines at home or shelter, isolation, travel restrictions, social distancing, and curfews. In this condition, maintaining the stigma, taboo or restrictions is merely impossible thus the chances of increasing violence are high but not recognize at all. In addition, the menstruators are double victimization from the existing the stigma, taboo, restrictions during menstruation and the laws imposed by the governments for COVID-19, Pandemic response.

The almost all organizations and networks included UNs, Asia and Pacific Region; INGOs are primarily recommended for SRHR (Sexual and Reproductive Health Right). SRHR primarily focused on family planning, safe abortion, maternal and child health, adolescent health [12].

The dedicated organizations on menstruation are responding COVID-19 through producing the masks, hand sanitizers. Their surveys were floating over internet and listserv for assessing the supply chain and needs or menstrual products. Few are busy in infographic on importance of hygiene related info and only very few organizations working for promotion of dignified menstruation.

Discussion

The organizations which supposed to stand for dignity, equality, respect have already been working for many decades such as 72 years for Human Right Declaration and WHO (1948), 41 years for Convention on the Elimination of all Forms of Discrimination against Women (1979), 25 years for Beijing Declaration and Platform for Action (1995), 20 years of Security Council Resolution 1325 (2000) but the accounting of women as human being is always missing specially the menstruation. The veil of silence around menstruation play as vicious cycle for sexism and gender equality and 80% of participants of 2015 survey experienced disadvantaged position in society due to menstrual stigma [9].

Focus not for the biological need; menstruation

The entire focus of COVID-19 response fully directed as requirement of men’s protection like Personal Protection Equipment (PPE) and other essentials. It is observed that almost all global or national authorities showed the men members while conducting the press meets and highlighted their needs, demands, and challenges. They seemed so serious for the death and infections from novel Corona virus and focused on medical supplies, equipment and explorations for it. The official relief package also comprised the items except menstrual products. For instance, Government of Nepal relief package for wage labor included 30 Kgs rice, 3 Kgs pulse, 2 Kgs salt, 2 Liters cooking oil, 4 packed soap and 2 Kgs sugar [13]. It is clearly shown that both either ignorance or silence or taboos embedded within the minds of authorities. The menstrual products are not considered as either important logistics or relief packages among authorities or except small or focused organizations. Authorities even ignore to listen the demand of menstrual products and compelled to talking birth control pills [8]. The psychological trauma and hormonal impact on her body is inhuman condition indeed. The oral contraceptives could create the other impacts on her body such as increasing rates of amenorrhea over time, irregular and unscheduled bleeding [14].

Menstruation is nowhere and everywhere under SRHR

The history of sexual and reproductive health is already more than 25 years, fourth international conference on Population and Development in 1994 [15]. Despite having huge scope, it merely talks about the menstruation and its complexity and multifaceted nature on the life of girls, women and society as a whole [12]. The SRHR intervention package clearly showed the ignorance and silence around the need of menstruation (comprehensive sexuality education, counselling on modern contraceptives, Safe motherhood and neonatal health, safe abortion, HIV/STIs, SGBV, Reproductive cancers, infertility and sexual health and well-being). It is concluded that menstruation is very everywhere and menstruation is nowhere. The entire elements of comprehensive SRHR package have indiscernible relationship with menstruation but it is vague to understand the position of menstruation or no observable discussion at all. It is assumed that the ignorance and silence among SRHR actors including WHO even today.

Menstrual Hygiene and products are not demystifying the stigma, rumours and restrictions around menstruation

The menstrual hygiene and products are essential elements of the dignified menstruation which get more attention since 2014. However, the hygiene and products do not guarantee of the dignity of girl, women and menstruators at all. As like China, due to stigma, taboos and restrictions around menstruation, either the demands of menstrual hygiene and products heard or incorporate in to the essential logistics of COVID-19 response or distribute properly to the needy people. For sustained supply of menstrual hygiene and products, incorporate in to the policies and plans, the breaking silence, bursts the myths, rumours and restrictions, is urgent.

The female frontline workers do not represent the women who are vulnerable amid COVID-19

The half of the earth’s population scattered as poor, rural, refugee, migrant worker, women in informal sector, disability, sexual minority, women at isolation, quarantine, conflict and so on. They are living with travel restrictions, limited spacious rooms or tents or quarantine or camps or abusive partners or strange people. The resources for living such as food, toilets, water, soap, hand sanitizers, menstrual products are limited or could be unfilled. It is concluded that the almost all discussion do not account the women who are living except as front liners. They also menstruate about 3000 days in life and about seven years of reproductive life. They also have so many issues with before puberty, puberty and menopause.

Conclusion

Since 2014, menstruation gets more space in both development and non-development sector globally but the dedicated funds or programs yet to planned for achieve the 2030 agenda, `Leave no one behind’. The holistic approach of dignified menstruation could be the tool to address all issues related with menstruation including SRHR, human right and empowerment. Because of talking about dignity during menstruation allow to discuss about the stigmas, taboo, restrictions during menstruation that is supported by the Jiajia Li [9].

Globally the gender-based violence is increasing; 30 in France, 25% Argentina, 35% in Singapore [16]. The menstrual stigma, taboo and restrictions have significant role for the power construction thus the silence of the menstruation is a key underlying cause for increasing gender-based violence.

Recommendation

This COVID-19 is not only the challenge but also the opportunity to understand the complexity and multifaceted nature of menstruation before, during and after the crisis. In the twenty first century, the world has to learn and ready to shift for not only COVID-19 management but also shifting around peace, human right, and empowerment. The global community encourages leaving the blaming and naming around menstruation and having to move forward for the sake of planet as whole.

In specific manner, the following things need to consider in coming days:

• The disaggregated data has to have the menstruation and choice of products.

• The dignified menstruation and gender analysis policies and plan instead of gender analysis in silo. That guarantees the revision of logistic plan or essential supplies for crisis.

• The SRHR elements also need to revise to include the dignified menstruation

• The activities have to plan and implement by endorsing the indicators of dignified menstruations or beyond the infrastructure, hygiene or products.

• Without robust feeling of confidence and dignity, hard to report or fight back against gender-based violence. Thus, mainstreaming of dignified menstruation in to empowerment and human right would be the catalyst tool to prevent and response of the gender-based violence.

Delimitation of the study

This study delimited within 44 days of the emergency of COVID- 19, internet-based desk analysis.

Funding

This is no any funding or any assurance for the study.

References

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  4. Sitepu A and Saminarsih D [2020] COVID-19: Gender lens needed to fight pandemic. The Jakarta Post. [Crossref]
  5. MISSING WOMEN: How to Ensure Beijing+25 Really Leaves No One Behind. (2020) International Rescue Committee. [Crossref]
  6. United Nations. (n.d.). Gender equality in the time of COVID-19. THE DEPARTMENT OF GLOBAL COMMUNICATIONS [Crossref]
  7. Paudel R (2020) Dignified Menstruation in a Global Discourse*An Unseen Topic in Human Rights? – 2020—COVID-19. [Crossref]
  8. Zhou V (2020) Needs of Female Medical Workers Overlooked in Corona Virus Fight, advocate say. [Crossref]
  9. Jiajia Li A (2020) How China’s coronavirus health care workers exposed the taboo on menstruation. South China Morning Post. How China’s coronavirus health care workers exposed the taboo on menstruation.
  10. Mental health and psychosocial considerations during the COVID-19 outbreak (2020) World Health organization. [Crossref]
  11. NGOWG (2020) Why Women’s Rights must be Central to the UN Security Council’s Response to COVID-19. [Crossref]
  12. The COVID-19 Outbreak and Gender: Key Advocacy Points from Asia and the Pacific. (2020) Gender at Humanitarian Action Asia and Pacific Region. [Crossref]
  13. Shrestha PM [2020] Rice, pulses, salt, oil, soap and sugar to be distributed to informal sector workers and destitute. [Crossref]
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  16. Silva I [2020] Coronavirus and gender: Women on frontline need to be included in pandemic response. [Crossref]

From Crisis to a New Routine

DOI: 10.31038/IDT.2020113

Opinion article

Looking back, the days have passed quickly—fifty-five days in the shadow of a threatening and contagious virus, thirty-five days in quarantine, in accordance with the regulations and in case of  infection When a person is asked to stop his/her routine – daily activities — and change habits,  opposition understandably rears its head. While the media repeatedly discusses exit strategies from the COVID-19crisis, the number of victims increases and we have not yet totally succeeded in flattening the curve, I find that for me, it is best to stop, spend time in self-reckoning and in gaining insight. I am primarily motivated by self-accountability in my attempt to understand what is happening and how these scenarios impact my present and my future — as much as is in my control. I hope this article is helpful to others, witnesses to and partners in the same ongoing global crisis. The content that I am presenting was formulated in the spirit of humanistic psychology, inspired by American psychologist and sociologist Abraham Maslow. Maslow presents a hierarchy of needs. In his approach, one can only move from a basic and broad level, to a higher, secondary, and more focused level, when the previous level has been achieved. The reality of  life, as well as the theory’s opponents, show  that the stages may work parallel to the life axis.

According to Maslow’s principles, we have to provide the primary, broad, schematic and conceptual needs, and maintain balance, before we can fulfill the high-level needs of self-actualization. When primary needs are sufficiently fulfilled and the person is not concerned with obtaining food (or money to purchase food), he is free to act in “growth mode” (in contrast with “deficiency mode”). That is to say, simply, if I were hungry and indigent, I probably would not be able to write this text, which I see as a work that supplies second or third order needs. The need for art, beauty and creativity — concepts underlying the principles of humanistic psychology –is not a fundamental need for homeostasis, but rather is driven by an upset equilibrium and creative tension. A person who is full will not continue to eat once he is full (unless he suffers from an eating disorder); however a person who travels the world and enjoys new vistas will continue to explore foreign and interesting places, and will experience tolerable mild tension. I will now focus on two interim levels on the pyramid of needs, level three and four. The third level focuses on belonging, identity and love based on friendship, family, and sexual intimacy. The fourth level focuses on respect and esteem, self-esteem and accomplishment. In my opinion, all of mankind strives to reach the top of the pyramid but attaining the fourth level is crucial for achieving mental health. In order to experience respect and esteem, it is necessary to establish a sense of belonging to the family, the social community and the community of professional colleagues.

The ongoing viral crisis’s profound harmful economic impact has been described and continues to be described in the media, centered around the Passover holiday, 2020. There are holiday expenses which are also felt without crises but heightened and additionally difficult when there is a temporary or ongoing loss of sources of income. The higher socio-economic sectors of the population may not experience real threat nor feel the imbalance of physiological needs. They will not suffer starvation or uncomfortable environmental temperature, for example, but nonetheless will experience a professional threat, in light of the ongoing crisis that meets them in a mature developmental phase, in which professional definitions are a critical part of their self-identity. I have chosen to address this level of vulnerability, as well as offer ways of coping in the given situation. Our day-to-day life with its routine balances our physical and mental needs. The constancy and stability of our schedule make daily lifeand encourages food consumption at set times. Similarly, routine also targets the quantitative balance of household tasks and professional tasks. There are defined times for professional commitments, family, leisure and community. A breach in the routine may upset the balance and manifest in increased consumption of food, compulsive exercise, uncontrolled and addictive television viewing. After a break in the routine, and in striving for homeostasis, we may build a new routine, characterized by variety and optimal balance – if we act as rational adults who can accept a new reality.

Assuming our basic physiological needs are properly addressed, the new challenges during the corona virus outbreak are security in our physical requirements, job security, and a sense of family and community belonging. Respect and appreciation are expressed for example in our being essential workers. If we are absent from the workplace because we are not essential workers or if God forbid, ill with corona, and if our children are mature and independent, and manage distant learning diligently on their own, we may wonder as to our standing and in dispensability. We may feel non-essential. These feelings can be overwhelming in the face of boredom and inactivity, wasted time and an altered sense of time (“I did nothing and it is already noon,” or “How often can one see Orange is the New Black ? ). This becomes even more cumber some and intense if we add self-flagellation, low self-esteem, and guilt feelings. Workers in the same organization may be jealous and frustrated by seemingly arbitrary decisions about their compulsory unpaid vacation or job layoff. They may feel angry, despairing, and helpless in the face of a system perceived as no less destructive than the virus. This may easily lead to feelings of loneliness and depression. We cannot significantly control the situation, but we can take responsibility for our mood and our moral obligation to ourselves and our surroundings to best utilize this unwelcome situation. Here we touch upon the individual’s outlook and stance on life as to the question of “how” as well as his characteristic coping and troubleshooting patterns.

First, good to let the body and mind be in states of exaggeration and overdose and to let go of self-flagellation and self-blame, despite the tendency to do so. Best to skip the feelings of worthlessness and self-abnegation, and allow ourselves to dive into a new world, until we internalize the new, compulsory routine–perhaps we will even succeed to derive pleasure and satisfaction from it. The balance is likely to arrive at some stage if we do not get stuck in a pattern of stern self-judgment. Second, we have a golden opportunity to choose and decide what is worth while to practice during this time and what we wish to strengthen. In being responsible for our morale, we are free to choose strengthening self-care strategies and drop what weakens us. It will be better for us and our surroundings if we choose to be happy and write up a daily gratitude list, than if we list grudges and anger towards a friend who has disappointed us. Instead of being angry, we can make peace. We have an empty space of time that it is worth filling with value-oriented matters.

Third, I will relate to the  opportunity, despite the virus and the quarantine, to partnership and togetherness in the given situation  If we zoom in on our equality, regardless of social status or professional occupation, in the  face of the virus, we can share together the gratitude of all those who remain alive. We can see the obligation of social distancing as a national obligation with an equal burden and moral responsibility—to consecrate life. We can choose to focus on the virus’s lack of discrimination on the basis of gender, religion, or sector, and unite together against a common enemy. Fourth, we should remember and remind our surroundings that we are in an ongoing, but transient situation. The feelings accompanying the situation we have not chosen are also temporary and transient. Feelings are not facts and they, as we have said, are up to us. It will be easier for us to focus on the transience of life despite the overwhelming experiences of challenges and changes that accompany the plague. We can change our thinking if we imagine each day as the last day in quarantine, while simultaneously imagining our return tomorrow to our workplace from which we have physically distanced ourselves, as though it were the last day of the vacation, which necessitated an immediate return, without a gradual adjustment.

Fifth, the coping strategies in the given crisis encourage us as productive and creative human beings. The given days invite action and creativity, originating in human curiosity and the use of our unique skills (cooking, acting, writing). Spontaneous creativity in the spirit of the time aims to cope and solve problems created in an unexpected crisis, fill the paramount need for a pyramid of needs and relate to the individual’s aspirations to express and realize himself/herself. The routine accompanied by cumulative life experience teaches us how to respond to our diverse needs, from our basic physiological needs to our unique human needs of self-actualization. A crisis may upset the balance; however that balance can be restored if we accept the situation without resisting and without self-blame, and if we commit to strengthening our constructive qualities and emotions, utilize the experience of our shared fate and remember that the COVID-19 crisis is transient and will pass. Spontaneous creativity, positive, spirited, flexible action, and our aspiration to adapt and adjust, can turn a crisis into a new routine, along with the new challenges. We will know how to address these challenges and the price they exact in the years to come, based on surveys, case studies and future research.

Social Health Surveillance: A Systematic Review

DOI: 10.31038/PEP.2020112

Abstract

Context: Health service providers increasingly screen for health-related social risks and refer patients to social care resources. However, a national, individual-level social health surveillance system that supports this linkage between medical and social care does not yet exist. Public health surveillance provides the model for a national, individual-level social health surveillance system specifically designed to support the integration of social and medical care in order to address upstream contributors of illness.

Objective: To systematically review the literature describing existing social health surveillance systems in the United States that screen, address, collect, store, analyze, and disseminate social needs or risk factors for the purposes of developing activities that impact population health.

Design: Articles from PubMed, MEDLINE, and Social Intervention Research and Evaluation Network (SIREN) Evidence Library between January 1, 2008 and December 31, 2018 were searched using the Preferred Reporting Items for Systematic Review and Meta-analysis Protocols (PRISMA-P).

Eligibility Criteria: Epidemiological surveillance was used as a model to identify social health surveillance systems, defined as the ongoing collection, storage, analysis, and classification of social determinants of health data essential to the planning, implementation, and evaluation of interventions intended to improve health outcomes.

Study Selection: Thirteen articles met the inclusion and exclusion criteria, representing 9 different social health surveillance systems serving mostly low-income populations in 20 states.

Main Outcome Measures: The social health surveillance systems integrate social and medical care to improve health outcomes.

Results: All 9 social health surveillance systems continuously collected individual-level social determinants of health data from at least 2 of the 17 domains recommended by the Institute of Medicine. A wide variation existed in the social health surveillance systems capabilities.

Discussion: To build a 21st century social health surveillance system, public health leaders should expand epidemiological surveillance in collaboration with the medical and social care systems to include individual level social determinants of health.

Keywords

social determinants of health, social care, social health surveillance

Introduction

The upstream social factors that contribute to illness can overwhelm clinicians practicing in an ill-equipped healthcare system [1, 2]. Innovations increasingly link social care needs, such as food, housing support, and financial assistance, to the healthcare system, [3] which includes physical, mental, dental, and pharmaceutical care. However, a national, individual-level social health surveillance system that supports medical and social care integration does not yet exist. Borrowed from the public health domain, a social health surveillance system can be defined as the ongoing collection, storage, analysis, and classification of social determinants of health (SDH) data essential to the planning, implementation, and evaluation of social care need interventions that are designed to improve health outcomes.

A consensus committee report of the National Academies of Sciences, Engineering, and Medicine (NASEM Committee) appealed for increased attention to individuals’ social context by the United States (U.S.) health service delivery system [1]. The Committee recommended utilizing validated screening instruments, standardizing social risk terms, and facilitating interoperable data systems that enable advanced analytic approaches to population health. However, no best practice exists for social health surveillance systems [4, 5].

In contrast, U.S. epidemiological surveillance systems are sophisticated, robust, and long-standing [6].Public health surveillance is the continuous collection of health information for the evaluation, analysis, and translation of data into knowledge about the health of communities that can enable action [7]. Surveillance of risk factors for non-communicable diseases, such as cancer, heart disease, stroke, diabetes, asthma, and poisonings, has informed public health interventions for over 30 years [1, 6, 8].Public health surveillance systems may be the model for the development of national social health surveillance system. However, existing social health surveillance systems have not yet been described.

A social health surveillance system should consist of three key components: 1) the ability to continuously and systematically collect, store, analyze, address, and classify patient-level social needs and social risk data, 2) the capacity to plan, implement, and evaluate programs or activities that are 3) specifically designed for the purposes to integrate social and medical care to improve health outcomes. That is, effective social health surveillance systems have the capability to link SDH information to health outcomes in order to address upstream contributors of illness–the “causes of the causes” of poor health [9].

Various systematic reviews analyzed other elements of social and medical care integration efforts, including the many different screening instruments available to assess SDH, [10, 11] social care intervention activities in the health care sector, [12-17] types of SDH collected, [18] and the adequacy of electronic health records systems to support social health data collection [19-21]. The purpose of the present study is to gather and synthesize the best available published evidence on current social health surveillance systems.

Methods

This systematic review was guided by the Preferred Reporting Items for Systematic Review and Meta-analysis Protocols (PRISMA-P) guidelines [22]. The research team conducted a search for articles from the following databases: PubMed, MEDLINE, and Social Intervention Research and Evaluation Network (SIREN) Evidence Library. SIREN Evidence Library is an archive of literature run by Center for Health and Community at University of California, San Francisco. PubMed Medical Subject Headings (MeSH) search headings included social determinants of health, mass screening, and population surveillance. Keywords in MEDLINE included “social prescribing,” “social and medical care integration,” “social care needs surveillance,” “social determinants of health surveillance,” “social determinants of health screening,” “socioeconomic status surveillance,” “socioeconomic status screening,” “population surveillance,” “social needs surveillance,” “mass screening,” “social needs screening,” “screening and referral” and combinations of surveillance, screening, and social determinants. In the SIREN Evidence Library, the authors identified articles categorized as “screening research.” The authors also searched citations of articles that met the inclusion criteria.

Table 1. Keywords for database search

MEDLINE Keywords

Social prescribing

Social and medical care integration

Social care needs surveillance

Social determinants of health surveillance

Social determinants of health screening

Socioeconomic status surveillance

Socioeconomic status screening

Population surveillance

Social needs surveillance

Mass screening

Social needs screening

Screening and referral

The search strategy was limited to articles regarding social health surveillance programs based in the U.S. The title and abstract of each article were evaluated for inclusion according to the definition of a social health surveillance system: the ongoing collection, storage, analysis, and classification of SDH data essential to planning, implementation, and evaluation of interventions designed to integrate social and medical care for improve population health.

Two authors (Zachary Pruitt and Ibrahim Akorede) independently reviewed each article included to determine if the study met all inclusion criteria. Search results were imported into EndNote Online. In cases where there was disagreement between authors about study inclusion, consensus was achieved by review of a third researcher (NnadozieEmechebe).

The search yielded 17,598 unique records published in English between January 1, 2008 and December 31, 2018. Of these titles and abstracts, 76 full articles reviewed for eligibility criteria. A final list of 76 studies were selected for inclusion criteria (Table 2). The full review according to the eligibility text review eliminated 63 articles that lacked the required information regarding social health surveillance systems. The final sample contained 13 unique studies that met all inclusion criteria. Articles were excluded for a variety of reasons, as noted in Figure 1 that depicts the PRISMA-P diagram for this study.

PEP-1-1-103-g001

Figure 1. Flowchart of studies included in the Social Health Surveillance Systematic Review

Table 2. Social Health Surveillance Systems.

PEP-1-1-103-t002

Results

Thirteen articles were included in this review, representing 9 different social health surveillance systems. Among articles reviewed in detail, 63 were excluded. Excluded articles only discussed general concepts related to addressing SDH in medical care (24), did not collect SDH data continuously (12), related to systematic reviews of other social and medical care integration topics (6), introduced other studies (5), addressed only the SDH screening mechanisms, (5) included no description of SDH integration with medical care (3), did not address SDH (1), did not discuss how SDH data was stored (1), or other reasons (5).

Existing Social Health Surveillance Systems

The 9 identified social health surveillance systems mostly served low-income populations in 20 states. Each used different screening instruments with collection at varying levels of volume and intensity. A variety of approaches for integrating social care and medical care were present.

Michigan Primary Care Association

The 240 primary care community health clinics (CHCs) of Michigan Primary Care Association conducted SDH screenings.5 SDH data were collected by clinical staff, such as medical assistants, social workers, physicians, front desk staff, and registered nurses. Data were entered into electronic medical record system (EMR) either directly by the health care provider as reported by the patient or through a paper screening instrument that was then scanned into the EMR. The SDH data were used to support state-wide social health intervention programs, such as Michigan’s State Innovation Model (SIM) [23] and Michigan Pathways to Better Health, [24] that were coordinated by community-based “hubs” to facilitate clinical and community resource linkages.

The 2-1-1 System

The 2-1-1 system is a collection of call centers that connects individuals with basic social care needs to social services organizations in their communities [25]. While over 200 programs are administered by different entities across the U.S., only two separate 2-1-1 organizations met the inclusion criteria for social health surveillance systems: Missouri [26-28] and San Diego County [29]. These 2-1-1 systems adapted existing social care referral programs to create linkages between social care organizations and health care systems.

In Missouri, after 2-1-1 call center representatives provided social care referrals, individuals were asked to complete cancer screening. Based on answers to these questions, a computer program identified needs for cancer control services and generated referrals to local cancer prevention services, such as mammography and smoking cessation programs. The Missouri 2-1-1cancer prevention program then followed-up with patients to assess cancer service utilization rates.

The San Diego 2-1-1 system leveraged their already high-functioning social care referral call center to create healthcare navigation programs to help individuals identify social care needs, make and keep needed medical appointments, and removed the barriers to address health-related needs in the community [29].  Another department helped callers obtain access to health-related public assistance programs.

OCHIN

OCHIN centrally manages an Epic-based EMR system used by more than 440 primary care community health centers (CHCs) [30]. Three CHCs in Washington and Oregon were used as pilot sites to collect, review, and integrate social needs with medical care through referrals. SDH data were collected through three different approaches: (1) SDH modules in the EHR available to front desk staff, clinicians, and community health workers, (2) paper surveys entered by patient then coded into EMR system by staff, and (3) a patient portal questionnaire completed by patient before the visit. Based on identified social care needs, community health workers provided social service referrals. The EMR also enabled social care referral summaries to be accessed during subsequent clinical encounters to support follow-up by the care team [30]. In June 2016, the social health surveillance tools were made available to all OCHIN member clinics (97 sites in 18 states), where preliminary evaluations show variation in screening adoption and data collection and medical care integration workflows [31].

Health Leads

Health Leads staffed help desks with college students at urban medical clinics across the U.S [20, 32]. In the Health Leads model, patients’ parents completed a SDH screening survey, providers reviewed screening results and referred patients to Health Leads help desks, and the student “Advocates” utilized the Health Leads database to refer patients and their families to community-based social services. The social needs were captured within the EMR systems and Health Leads’s database, which enabled evaluation of social care interventions on individual or population health.

WellCare’s Social Service Referral Service

Similar to the 2-1-1 system, the non-clinical call center staff of WellCare Health Plan’s social service hotline identified social care needs and referred their Medicare and Medicaid members to social care organizations [33]. The screening results shared with WellCare’s case managers who provided direct assistance to individuals with social and medical care needs [34].

WellRx

Three family medicine clinics in Albuquerque, New Mexico piloted a program in collaboration with University of New Mexico and Medicaid managed care plans to collect SDH data through a paper-based survey instrument [35]. For over 3,000 patients over a 3-month period (later expanded to all patients at 9 primary care locations [31]), clinics stored SDH data in the EMR for access by community health workers who sought to improved patient engagement and create better informed primary care clinicians and staff. The program was also utilized for diabetes control quality improvement project.

The Online Advocate (now HelpSteps.com)

For adolescents and young adults seeking medical care from an urban hospital-based clinic at Children’s Hospital Boston, the Online Advocate (now HelpSteps.com) conducted a web-based screening survey for social risk, such as food insecurity, healthcare access, and interpersonal violence. Based upon identified social care needs, the system—termed “social epidemiology” by the authors—provided referrals to local social service agency to address the identified social risks [36]. The online assessment system acted as a complement to clinical visits in order to improve attention to patients’ social needs [37].

Johns Hopkins Community Health Partnership (J-CHiP)

In 8 primary care outpatient clinics in East Baltimore, Maryland, the Johns Hopkins Community Health Partnership (J-CHiP) community health workers collected SDH data that were combined with care management assessment, demographic, clinical, health history, and other related data to be reviewed during the clinical encounter [38]. J-CHiP interventions sought to reduce provider visit no shows, cost of care, and other utilization indices, such as hospitalizations and emergency department visits.

Social Health Surveillance Attributes

All 9 social health surveillance systems included in this systematic review collected individual-level SDH data continuously. Each of the social health surveillance systems screened for at least 2 of 17 SDH domains recommended by the Institute of Medicine (IOM), but none screened for all IOM-recommended SDH domains.18 None of the 9 identified social health system utilized the same data collection approach, except the 2-1-1 systems in Missouri and San Diego. OCHIN utilized the Protocol for Responding to and Assessing Patients’ Assets, Risks, and Experiences (PRAPARE) assessment tool developed by the National Association of Community Health Centers that integrates with EMR systems, although each pilot site implemented screenings differently [39].

The intensity of public health surveillance systems can be classified as active or passive [40].Correspondingly, active social health surveillance utilizes screening tools to directly identify patient social needs at medical care facilities. A passive social health surveillance system relies on social needs identified and reported by individuals or their caregivers. Among the 9 social health surveillance systems identified in this review, 6 were active (Michigan Primary Care Association, OCHIN, Health Leads, WellRx, The Online Advocate, and J-CHiP) and 3 were passive (WellCare, Missouri 2-1-1, and San Diego 2-1-1).

The passive social health surveillance systems (WellCare and the 2-1-1 Systems) use custom technology platforms to track social services referrals and to store SDH data. The Michigan Primary Care Association, OCHIN, and WellRx stored SDH data in their respective EMR systems. Health Leads in Baltimore stored SDH data both in a database of social service referrals and in the EMR social history. J-CHiP SDH data are stored in a customized care management system. The Online Advocate (HelpSteps.com) survey and referral system stored the SDH data for analysis.

A fundamental component of social health surveillance systems is the ability to analyze these data. Although all 9 social health surveillance systems screened for social care needs for the purposes of integrating social care with medical care practices, our review shows a wide variation in capabilities to plan, implement, evaluate interventions designed to integrate social and medical care. For example, at the Michigan Primary Care Association, the lack of standard screening practices across de-centralized referral “hubs” limited the ability to plan, implement, and evaluate interventions to those SDH domains reliably collected, such as homelessness [5].

Two social health surveillance systems effectively analyzed the relationship between social care interventions and health outcomes and published those results in peer-reviewed literature. The Missouri 2-1-1 System cancer control program successfully planned, implemented, and evaluated their cancer control referral uptake rates [27].The WellCare program published detailed evaluation of the social and medical care integration efforts, including the association of social risk factors to inpatient readmissions41 and the relationship of social care utilization to overall health care spending [33].

For other social health surveillance systems, although capacity for evaluation exists, the results of the influence of social health interventions on medical care outcomes are less clear. For example, Health Leads papers stated that the program could evaluate how resource interventions can impact “individual or population health over time” [20] and “promote greater health equity,” [32] but these results were not yet published. OCHIN [30] and J-CHiP [38] also described capabilities to evaluate the impact of social care interventions on health outcomes, but the results were not published. Other social health surveillance systems relied on health measures collected as a part of the social health surveillance system, such as patients’ perceived ability to manage health needs (San Diego 2-1-1 [29]), diabetes control (WellRx [35]) and self-rated health (The Online Advocate/ HelpSteps.com [37, 42]).

Discussion

Public health surveillance provides the model for a national, individual-level social health surveillance system specifically designed to support the integration of social and medical care.  The public health system obtains large quantities of data from widely-recognized data sources, such as reportable diseases, vital statistics, registries, surveys, and from administrative sources, such ashospital and emergency department discharges data, insurance billing claims, laboratory test results, and poison control hotline data [8, 43]. Critically important, public health transforms this data into actionable information on the health needs and risks of the community served in order to create interventions designed to improve public health [44].The public health system currently conducts national surveys that include SDH, such as Behavioral Risk Factor Surveillance System (BRFSS), to develop community-level representations of social health risk, but community-level data may not enough detail to develop effective interventions seeking to integrate medical and social care systems [45]. When it comes to creating an effective social health surveillance, the tenets of epidemiological surveillance should be upheld but require adaptation.

The NASEM Committee recommended 5 complementary activities needed to strengthen social care integration: awareness, assistance, adjustment, alignment, and advocacy [1]. The 9 existing social health surveillance systems described in this systematic review support these activities directly. First, all 9 social health surveillance systems conduct awareness activities by identifying the social risks. However, the variability in how these SDH data are collected present a challenge to developing a fully-realized national surveillance system. A more effective social health surveillance system would incorporate national data standards for EMRs and other data systems and utilize and interoperable technology infrastructure for sharing between and among organizations [1,18,21].

According to the NASEM Committee, assistance entails connecting individuals to community-based social service assets. Without assistance, the effort to “medicalize” social care needs into medical care rather than investing in upstream community interventions may add to the costs with negligible impacts on health outcomes [46]. Such “collection without connection” negates the benefits of screening for social risk factors and may cause unintended consequences, such as undue burden on providers or distress to patients [47]. All 9 social health surveillance systems provided assistance activities through similar processes – identify a social care need, make social care referral, and follow-up to assess the health-related outcomes. Some organizations assist individuals through a “concierge-based approach” where “navigators” (San Diego 2-1-1 [29]) or “advocates” (Health Leads [20, 32]) assist members with social care needs throughout a defined process.

All social health systems identified in this review altered their clinical approaches to accommodate social health issues, described as adjustment activities by the NASEM Committee [1]. For example, WellCare Health Plans utilized SDH data in their health plan case management processes, [33] the Missouri 2-1-1 System asked additional cancer prevention questions, [26-28] and health care providers at clinics with Health Leads help desks refer patients to students advocates for detailed social service guidance [20, 32].

Finally, according to the NASEM Committee, alignment and advocacy relate to investments and support of the social care services by health systems in their communities, and this systematic review found evidence of alignment and advocacy activities [1].For example, evidence from the WellCare Health Plans SDH data showed that utilization of social services was associated with greater reduction in healthcare costs reinforcing the organization’s commitment to align social care with medical care by issuing microgrants to community-based organizations to support the exchange of additional social care utilization data [33, 48]. Advocacy was demonstrated by the collaboration between the New Mexico Medicaid agency, health plans, and federally qualified health centers to expand the scope of the effort of the WellRx pilot program to address SDH [35].

In public health, active surveillance involves the health department directly conducting research or reaching out to providers and laboratories for data collection, and passive surveillance relies on reporting by clinicians. These public health surveillance components contain social health surveillance analogs. Active social health surveillance utilizes screening tools to directly identify patient social needs at medical care facilities. A passive social health surveillance relies on social needs identified and reported by individuals or their caregivers.

Six of the identified social health surveillance systems use an active approach, which has the advantage of proximate integration of between identification of patients’ priority social care needs and relevant medical issues.4 However, there are drawbacks to active social health surveillance, including the costs to clinicians who may lack the time to address social health risks [1, 49]. In addition, active surveillance may identify social risks but lack the time to obtain social care services. Finally, patients may not be receptive to social needs screening or have general privacy and stigma concerns related to non-clinical social health surveillance systems [50, 52].

A vast majority of public health surveillance systems are passive [53]. Only 3 social health surveillance systems were passive [34, 54]. Social service referral experts free-up clinical resources to conduct their specialized roles [37]. However, privacy and security concerns may be associated with non-clinical sites collecting SDH which may require an increased capacity to comply with privacy and security standards related to the sharing of protected health information [1].

Limitations

Though the search was exhaustive, some social health surveillance systems may not be included. The review includes published studies only so there may be other qualified social health surveillance systems. For example, Kaiser Permanente in California launched Thrive Local by partnering with social care referral system platform called Unite Us to connect social and medical care for patients, but peer-reviewed literature on the program was not yet available [55]. Finally, some social health surveillance systems may have been excluded because some defining aspect, such as identification of health outcomes, may be present in the system but not fully explained the published literature.

In conclusion, the social health surveillance system of the 21st century will utilize a steady stream of SDH data to permit benchmarking, goal setting, coordinated interventions, and description of results of integrating social care and medical care [43]. The 9 social health surveillance systems described in this systematic review fulfill this vision, but further work is needed.

Public Health 3.0 seeks to build on extraordinary public health successes of the 19th and 20th centuries to work across sectors to address SDH to improve population health [56]. Using this new perspective, public health leaders should expand epidemiological surveillance systems into a robust, nation-wide social health surveillance system through a multi-disciplinary collaboration with medicine, public health, social work, and others. To build a 21st century social health surveillance system beyond the programs identified in this review, policymakers should marshal the necessary resources [1, 8]. Without a social health surveillance system that supports the development of effective interventions that address SDH, the downstream clinical encounter will continue to be overwhelmed [1, 9].

Implications for Policy and Practice

  • A social health surveillance system can be defined as the ongoing collection, storage, analysis, and classification of social determinants of health data essential to the planning, implementation, and evaluation of social care need interventions.
  • Each of 9 identified social health surveillance systems implemented different approaches to continuous SDH data collection, but all used the information to integrate social and medical care.
  • The social health surveillance systems were specifically designed for the purposes of addressing social care needs in order to improve health outcomes, such as reducing inpatient readmissions or emergency department visits.

Public health leaders should expand the epidemiological surveillance systems into a robust, nation-wide social health surveillance system through a multi-disciplinary collaboration with medicine, public health, social work, and others.

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Thermal Inactivation of Feline Calicivirus and Herpes Simplex Virus Type 1: Side-by-Side Suspension and Carrier Studies

DOI: 10.31038/IJVB.2020411

Abstract

The efficacy of thermal inactivation for viruses may be studied in solutions (liquid or suspension inactivation) or surfaces (carrier inactivation). Thermal inactivation on surfaces is studied using prototype surfaces (carriers, such as glass or steel). The time kinetics of inactivation and the efficacy of inactivation at different temperatures may differ between surface and suspension heating, although side-by-side studies of suspension vs. carrier inactivation have rarely been performed. Thermal inactivation efficacy depends upon a number of factors, including the matrix in which the virus is suspended or dried on a surface, the specific liquid or surface in which the virus is to be inactivated, the type of virus, the temperature, and the time at temperature. In the present paper, we have evaluated the suspension and carrier inactivation of feline calicivirus (family Caliciviridae) and herpes simplex type 1 (family Herpesviridae). The side-by-side testing design allowed direct comparison of inactivation on carriers (glass and steel) versus inactivation in suspensions (culture medium and newborn calf serum). For both viruses, the time required to inactivate 1 log10 of virus (i.e., the D value) at 65°C was similar (4-7 min) in both carrier and suspension inactivation studies. At lower temperatures (46 and 56°C), the calculated D values were greater for suspension inactivation than for carrier inactivation, and for feline calicivirus than for herpes simplex type 1.

Keywords

Carrier inactivation, D value,Feline calicivirus,Herpes simplex virus type 1, liquid inactivation, Thermal inactivation

Introduction

Thermal (heat) inactivation is an important physical inactivation approach applied for pathogen reduction and has been used for viral inactivation in suspensions and, to a lesser extent, on contaminated surfaces. Pasteurization is an example of thermal inactivation applied to suspensions [1], as is high-temperature, short-time treatment [2]. Steam-in-place and hot water cleaning are examples of thermal inactivation of surfaces [3,4]. Is thermal inactivation in suspension more effective and does it have faster kinetics compared to inactivation on surfaces? Are lipid enveloped viruses such as herpes simplex virus type 1 (HSV-1) more susceptible to thermal inactivation than non-enveloped viruses such as feline calicivirus (FeCV)? For years the prevailing opinions on both of these questions have been in the affirmative. Very few systematic studies have been performed to answer these questions. The question of suspension vs. carrier inactivation by heat has not been addressed in enough side-by-side studies to allow conclusions to be made. While it is generally accepted that the animal parvoviruses (e.g., bovine parvovirus, canine parvovirus) are the most heat-resistant of the viruses [5], the assumption that non-enveloped viruses as a class are more resistant to thermal inactivation than enveloped virus has not been demonstrated unequivocally. The data collected for suspension heat inactivation [5] would seem to argue against this assumption.Thermal inactivation in suspensions is typically a first-order process, meaning that a plot of log10 inactivation is linear with respect to time at temperature [6,7]. Deviations from linearity may occur as a result of experimental error or inactivation of available remaining infectious virus [8]. For a first-order process, a decimal reduction factor (D) can be calculated. The D value is the amount of time required at any given temperature to inactivate 1 log10 of virus. If D values are obtained for at least three different temperatures, a plot of D value vs. temperature may be created [7]. The benefit of such a plot, which has the form of a power curve, is that estimates can be made of D values at non tested temperatures. For thermal inactivation of surfaces, the time kinetics can display non-linearity in plots of inactivation vs. time for the same reasons mentioned above for suspension heating. In addition, it may be more difficult to quench the heat inactivation on surfaces relative to suspensions. In any case, estimates of D values for either suspension or carrier thermal inactivation kinetics can be subject to experimental error. Conclusions regarding kinetics and efficacy should be made keeping this in mind, and the totality of the data should be considered when making conclusions and when estimating extent of inactivation at multiples of D and at non-empirically tested temperatures.

In the present paper, we have evaluated the suspension and carrier thermal inactivation of two model viruses. Feline calicivirus is a surrogate for human norovirus and has therefore received considerable attention in disinfectant efficacy [reviewed in 9] and thermal inactivation efficacy studies [reviewed in 5]. This is a non-enveloped virus in the Caliciviridae family. The second model virus is HSV-1, a member of the Herpesviridae family and an enveloped virus. This is used as surrogate for important animal herpesviruses such as pseudorabies virus and equine herpesvirus [10].

Methods

Viruses

Feline calicivirus (FeCV), strain F9, was propagated in CRFK cells (American Type Culture Collection CCL-94). The virus was diluted in Roswell Park Memorial Institute (RPMI) medium supplemented with 5% newborn calf serum (NCS, source: ThermoFisher Scientific, Waltham, MA) and added to T-75 flasks of the CRFK cells. The flasks were incubated at 36±2°C with 5±1% CO2 for 90 minutes to allow for viral adsorption, after which they were refed with growth medium. Incubation was continued at 36±2°C with 5±1% CO2 until all of the cells exhibited viral cytopathic effect (CPE). The flasks were frozen at -80°C and then thawed at room temperature. The medium from the flasks was collected and clarified by centrifugation at 2,000 rpm for 15 minutes, and the resulting supernatant was aliquoted and stored at -80°C until use. The certified titer of the stock FeCV was determined to be 7.05 log10 tissue culture infective dose50 per mL (TCID 50/mL) in CRFK cells. Herpes simplex type 1 (HSV-1), strain HF, was propagated in Vero cells (American Type Culture Collection CCL-81). The virus was diluted in Roswell Park Memorial Institute (RPMI) supplemented with 5% NCS and added to T-75 flasks of the Vero cells. The flasks were incubated at 36±2°C with 5±1% CO2 for 90 minutes to allow for viral adsorption, after which they were refed the growth medium. Incubation was continued at 36±2°C with 5±1% CO2 until ~80% of the cells exhibited viral CPE. The flasks were frozen at -80°C and then thawed at room temperature. The medium from the flasks was collected and clarified by centrifugation at 2,000 rpm for 15 minutes, and the resulting supernatant was aliquoted and stored at -80°C until use. The certified titer of the stock HSV-1 virus stock was determined to be 7.27 log10 TCID 50/mL in CRFK cells.

Carriers and liquid matrices

Glass carriers consisted of 4-in2 area of a sterile glass Petri dish. Steel carriers consisted of brushed stainless steel discs 1 cm in diameter. The Serum matrix consisted of undiluted NCS,while the Medium matrix consisted of RPMI medium containing 2% NCS for FeCV and HSV-1.

Evaluation of heat inactivation (duplicate replicates)

Virus was spread (Figure 1) onto the glass carriers (0.4 mL virus suspension) or steel carriers (0.05 mL virus suspension) and allowed to dry at room temperature (20–21°C) per ASTM International (ASTM) standard E1053 [11]. For liquid inactivation, 0.2 mL of virus suspension was added to 1.8 mL of NCS or RPMI in glass tubes per ASTM standard E1052 [12]. Carriers containing virus were placed into a hot-air oven (Isotemp™ General Purpose, Fisher Scientific Catalog No. 151030509) set at one of three test temperatures (46°C, 56°C, and 65°C) for 5, 20, or 60 minutes. The relative humidity of the oven was not measured. Glass tubes containing virus/RPMI or virus/NCS solutions prepared as described above were placed into a hot air oven set at one of the test temperatures (46°C, 56°C and 65°C) for 5, 20, or 60, 120, or 180 minutes. The relative humidity of the oven was not measured. Following the heating times, 4 mL of neutralizer (NCS) were added to the virus film on the glass or steel carriers and used to remove the film from the surface with cell scrapers. The liquid heat inactivation conditions were neutralized following heating by addition of 2 mL of cold neutralizer.Post-neutralization samples were serially diluted, and selected dilutions were inoculated onto the proper host cells for each virus (8-wells per dilution in 96-well plates). A virus recovery control (VRC) was included to determine the relative loss in virus infectivity as a result of drying and neutralization. Virus was applied to the carriers (Glass or Steel) or added to liquids (NCS or RPMI) and held at room temperature (20±1°C) for the longest contact time evaluated (60 or 180 minutes). The various 96-well plates were incubated at 36±2°C with 5±1% CO2 for 7–8 days (FeCV and HSV-1). Following incubation, the plates were scored for CPE. The 50% tissue culture infective dose per mL (TCID 50/mL) was calculated using the Spearman-Kärber formula [13]. The titers for the VRC were then compared to titers for the corresponding heat-treated carrier/matrix type to calculate the reduction in infectivity caused by heat treatment [Figure 1].

IJVB-4-1-401-g001

Figure 1. Schematic representation of surface and suspension inactivation methodology (from reference [8]).

Calculation of D and z values and power function analysis

Decimal reduction (D) values were estimated from the most linear portions of the inactivation vs. time curves for the various set temperatures (not shown). The plots included both replicate values for any given temperature and time point, therefore represent an analysis of the pooled replicate data, with a single D value being generated. Rapid deviation from linearity in these plots was noted as complete inactivation of virus occurred rapidly at the higher temperatures. We acknowledge that a certain degree of error is associated with the D value estimation process. Such errors do not detract from the validity of the comparisons to be made between carrier and liquid inactivation results, since comparison of the raw inactivation vs. time results obtained leads to similar conclusions.The z value (°C per log10 change in D) for a given data set was obtained from plots of log10D vs. temperature (not shown), evaluated using the linear regression function of Excel. The z value is obtained as 1/slope (m) from the linear fit equation (Eq. 1):

IJVB-4-1-401-e001

where y = log10D, x = temperature, m = slope, and b = y-axis intercept.

Plots of D vs. temperature were evaluated using the power function of Excel to obtain the line fit equation (Eq. 2): IJVB-4-1-401-e002 (Eq. 2) where y = D, x = temperature, and a and b are constants unique to each line fit equation. This equation allows one to extrapolate the D value at any given inactivation temperature, and can also be rearranged to solve for temperature at any given D value, as shown in (Eq. 3): IJVB-4-1-401-e003 (Eq. 3) allowing one to estimate the inactivation temperature required to achieve a desired D value [7].

Results

Feline calicivirus

The thermal inactivation of FeCV was studied in carrier studies (Glass and Steel), and in suspension studies (RPMI and NCS). This virus is a small, non-enveloped virus that is considered to display medium resistance to physicochemical inactivation [14]. Temperatures of 46, 56, and 65°C were evaluated in two replicate trials each. The mean values from the replicates are displayed in Table 1. The extent of inactivation on carriers was minimal at up to 60 minutes heating time at 46°C. At this temperature, the inactivation achieved in suspension failed to reach even 1 log10. At 56°C, significant (>2 log10) inactivation occurred on carriers by 20 min, but not in suspension heating. In that case, 60 min heating was required. At 65°C, the time kinetics and extent of inactivation at the various times were similar for carrier and suspension inactivation [Table 1].

IJVB-4-1-401-t001

Decimal reduction (D) values were estimated from the initial linear portions of the inactivation vs. time curves at each temperature (Table 2). In the case of the 46°C trials for suspension heating, the D values had to be estimated on the basis of the first-order inactivation vs. time curves for these trials (plots not shown). While not ideal, these estimates allowed comparison between the carrier data and the suspension data, and enabled us to plot the relationship between temperature and D (Figure 2) [Table 2]. The plots in Figure 2 can be interpreted as follows: the resulting power function fit lines may be viewed as surfaces along which any temperature and D value pair is associated with 1 log10 inactivation of the virus [7]. The extrapolation of D to non-empirical temperatures, which may also be done by means of the calculated z values (Table 2), is quite easy and straightforward using the power function coefficients and Eq. 2 (Methods section). Also apparent from examination of Figure 2 is that at lower temperatures (especially 46°C), much longer heating times are required to cause 1 log10 inactivation in suspension, while at 65°C, inactivation is very rapid in both suspension and carrier heating [Figure 2].

IJVB-4-1-401-t002

IJVB-4-1-401-g002

Figure 2. Relationship between D and temperature for FeCV inactivation in suspension (●, NCS; ▲, RPMI) or on surfaces (○, Glass; Δ, Steel).

As FeCV has often been used as a surrogate for human norovirus, a calicivirus of considerable food safety interest, there have been several reports of inactivation of FeCV by suspension heating [15-20]. As these reports included sufficient detail and an experimental design allowing for calculations of D values from at least three different temperatures, it was possible to calculate power function coefficients from each study and therefore to create a plot comparing directly the D vs. temperature relationships (Figure 3). Note that the plot in Figure 3 does not display the temperatures actually tested empirically in the literature studies, rather it displays the D values at 46, 56, and 65°C calculated from the power function coefficients and Eq. 2. The greatest experimental error, and therefore the highest level of variability, is associated with the D values calculated for the lower temperature (46°C). Nevertheless, the plots are qualitatively similar in appearance and each study demonstrates rapid inactivation of FeCV at 65°C [Figure 3].

IJVB-4-1-401-g003

Figure 3. Relationship between D and temperature for FeCV inactivation in suspension. Data from the current study (●, RPMI; ▲, NCS) are compared with FeCV suspension inactivation data from the literature (○, Duizer, et al. [15]; ◊, Buckow, et al. [17]; ×, Bozkurt, et al. [20]; Δ, Bozkurt, et al. [19]; □, Cannon, et al. [16]; ■, Gibson and Schwab [18]). The line in red color represents the overlapping power fit lines for our studies in NCS and RPMI.

Herpes simplex virus type 1

The thermal inactivation of HSV-1 was studied in carrier studies (Glass and Steel) and in suspension studies (RPMI and NCS). This virus is a large enveloped virus that is considered to display medium resistance to physicochemical inactivation [14]. Temperatures of 46, 56, and 65°C were evaluated in two replicate trials each. The mean values from the replicates are displayed in Table 3. Extended time points were used in the study of inactivation in suspension at 46°C to enable estimation of D values at that temperature, as no evidence of first-order kinetics were observed at times less than 60 minutes.The extent of inactivation on surfaces was approximately first-order through 60 min of heating time on carriers at 46°C. At this temperature, the inactivation achieved in suspension failed to reach even 1 log10, and as mentioned above, gave no evidence of linearity of inactivationvs. time though 60 min. At 56°C, significant (>2 log10) inactivation occurred on carriers by 20 min, but inactivation did not occur at this time and temperature in suspension heating. In the case of suspension heating, 60 min was required. At 65°C, the time kinetics and extent of inactivation at the various times were similar for carrier and suspension inactivation [Table 3].

IJVB-4-1-401-t003

Decimal reduction (D) values were estimated from the linear portions of the inactivation vs. time curves at each temperature (Table 4). The D estimates allowed comparison between the carrier data and the suspension data, and enabled us to plot the relationship between temperature and D (Figure 4). As observed with FeCV, the data in Table 4 and the plots in Figure 4 show that at lower temperatures (especially 46°C), much longer heating times are required to cause 1 log10 inactivation in suspension, while at 65°C, inactivation is very rapid in both suspension and carrier heating [Table 4 & Figure 4].

IJVB-4-1-401-t004

IJVB-4-1-401-g004

Figure 4. Relationship between D and temperature for HSV-1 inactivation in suspension (▲, NCS; ●, RPMI) or on surfaces (○, Glass; Δ, Steel).

Herpes simplex virus type 1 is available in most virology laboratories and is often used as surrogate for other herpesviruses. We were able to locate a previous study by Plummer and Lewis [21] that examined the suspension heat inactivation of HSV-1 and another human herpesvirus, cytomegalovirus. As this report included sufficient detail and an experimental design allowing for calculations of D values from at least three different temperatures, it was possible to calculate power function coefficients from each study and therefore to create a plot comparing directly the D vs. temperature relationships (Figure 5). Note that the plot in Figure 5 does not display the temperatures actually tested empirically in Plummer and Lewis [15], rather it displays the D values at 46, 56, and 65°C calculated from the power function coefficients and Eq. 2. The greatest experimental error, and therefore the highest level of variability, is associated with the D values calculated for the lower temperature (46°C). The plots are qualitatively similar in appearance and each study demonstrates rapid inactivation of the herpesviruses at 65°C [Figure 5].

IJVB-4-1-401-g005

Figure 5. Relationship between D and temperature for herpesvirus inactivation in suspension. Data from the current study for HSV-1 (●, RPMI; ▲, NCS) are compared with suspension inactivation data from the literature (×, HSV-1 data from Plummer and Lewis [21]; □, cytomegalovirus data from Plummer and Lewis [21]).

Discussion

Prevailing opinion is that viruses are less susceptible to heating when dried on surfaces than when suspended in solutions, and that dry heat efficacy is related to residual moisture or relative humidity [22-26]. As mentioned previously, there are only relatively few studies [8, 25] that have actually evaluated thermal inactivation on surfaces and in suspension in a side-by-side study design. There are a number of factors that can determine thermal inactivation efficacy, such as presence of an organic load, the specific virus tested, the specific times and temperatures evaluated, and the methodology used for quenching the heating and recovering the infectious virus. A side-by-side study design is useful for eliminating as many confounding factors as possible, thereby enabling a more accurate comparison of inactivation ion surfaces vs. in suspension.Bräuniger et al. [25] examined the inactivation of bovine parvovirus in suspension vs. in the lyophilized state (the authors referred to this as dry heating). Thermal inactivation of a powder of varying moisture content is not exactly the same as the thermal inactivation of virus dried upon a hard surface. The authors reported that the parvovirus was more readily inactivated in suspension than in the lyophilized state with higher residual moisture (2%), while longer heating times were required for inactivation of the virus in lyophilized materials with lower moisture content (1%). In our own studies [8] with poliovirus type 1 and adenovirus type 5, the D values measured at 46°C displayed the greatest difference between the surface and suspension inactivation approaches, with values ranging from 14.0-15.2 minutes (surface) and from 47.4 -64.1 minutes (suspension) for poliovirus. The corresponding values for adenovirus 5 were 18.2-29.2 minutes (surface) and 20.8-38.3 minutes (suspension). At 65°C, the decimal reduction values were more similar (4 to 6 minutes) for the two inactivation approaches. The results with poliovirus and adenovirus [8] suggest that the specific virus under test is a determinant of the steepness of the D vs. temperature curve. This is supported by the results in our present study, where FeCV displayed markedly longer D values at 46°C in suspension inactivation vs. surface inactivation. The differences between D values at 46°C for HSV-1 inactivated on surfaces vs. in suspension were not as striking.

What exactly determines the shape of the D vs. temperature curve? It is apparent from studying the thermal inactivation data for a broad variety of viruses reported by a variety of investigators (reviewed in [5]) that in all cases, the plot of D vs. temperature has the appearance shown in Figures 2-5. Specifically, the data points typically are fit very closely using the power function displayed in Eq. 2). The D vs. temperature relationship is merely a transformation of the log10D vs. temperature relationship which has been used historically in calculating the z value (°C per log10 change in D). It is not surprising, therefore, that deviations from linearity for log10D vs. temperature plotsfrom a given study are associated with poorer power function fits for the D vs. temperature curves generated from the same inactivation results. In either case, it is the experimental error associated with the inactivation (log reduction) measurements and the subsequent error associated with the calculated D values which causes the deviations from expected line fit. The steep portion of the D vs. temperature curve that is observed at the lower temperatures evaluated for a virus is associated with the greatest degree of experimental variability, as shown in Figures 3 and 5. A flattening out of the curve is typically observed at higher temperatures. From a mechanism of inactivation point of view, we have proposed previously [8] that the steep portion of the curve may represent reaching a threshold temperature required for capsid opening. Once this threshold temperature has been reached, relatively small incremental increases in temperature result in dramatic decreases in the time required for 1 log10 inactivation. Differences between surface and suspension heat inactivation of viruses observed at the lower end of the D vs. temperature plot might then correspond to differences in extent or kinetics of heat exchange between the two inactivation approaches.

Conclusion

In the case of thermal inactivation of viruses, the results of suspension inactivation studies should be extrapolated to inactivation of viruses on surfaces with caution. It is not clear which approach represents the worst-case condition, and the more that we study surface vs. suspension heat inactivation in side-by-side studies, the more apparent it is becoming that generalities should not be made. Differences in the specific virus tested, in the presentation of the virus to the heat, in organic matrices which may or may not offer protection to the viruses, and in diffusion of the thermal energy through the liquid or virus film may impact the results. Such differences may favor inactivation in one or the other of the suspension or carrier formats.

References

  1. Pirtle EC, Beran GW (1991) Virus survival in the environment. Rev Sci Tech Off Int Epiz 10: 733-748.(Crossref)
  2. Tomasula PM, Kozemple MF, Konstance RP, Gregg D, Boettcher S, et al. (2007) Thermal inactivation of foot-and-mouth disease virus in milk using high-temperature, short-time pasteurization. J Dairy Sci90: 3202-3211.(Crossref)
  3. Thomas PR, Karriker LA, Ramirez A, Zhang JQ, Ellingson JS, et al. (2015) Evaluation of time and temperature sufficient to inactivate porcine epidemic diarrhea virus in swine feces on metal surfaces. J Swine Health Prod 23: 84-90.
  4. Zentkovich MM, Nelson SW, Stull JW, Nolting JM, Bowman AS (2016) Inactivation of porcine epidemic diarrhea virus using heated water. Vet Anim Sci1-2: 1-3.
  5. Nims RW, Plavsic M (2013) Intra-family and inter-family comparisons for viral susceptibility to heat inactivation. J Microb Biochem Technol5: 136-141.
  6. Quist-Rybachuk GV, Nauwynck HJ, Kalmar ID (2015) Sensitivity of porcine epidemic diarrhea virus (PEDV) to pH and heat treatment in the presence or absence of porcine plasma. Vet Microbiol181: 283-288.(Crossref)
  7. Nims R, Plavsic M (2013) A proposed modeling approach for comparing the heat inactivation susceptibility of viruses. Bioprocess J 12: 25-35.
  8. Zhou SS, Wilde C, Chen Z, Kapes T, Purgill J, et al. (2018) Carrier and liquid heat inactivation of poliovirus and adenovirus. Disinfection. InTech. doi:10.5772/ intechopen.76340
  9. Nims R, Plavsic M (2013) Inactivation of caliciviruses. Pharmaceuticals6: 358-392.(Crossref)
  10. Woźniakowski G, Samorek-Salamonowicz E (2015) Animal herpesviruses and their zoonotic potential for cross-species infection. Ann Agric Environ Med 22: 191-194.(Crossref)
  11. ASTM E1053. Test method to assess virucidal activity of chemicals intended for disinfection of inanimate, nonporous environmental surfaces.
  12. ASTM E1052. Standard test method to assess the activity of microbicides against viruses in suspension.
  13. Finney DJ (1964) Statistical Methods in Biological Assay. (2ndedn), London: Griffen.
  14. United States Pharmacopeia (2016)<1050.1>Design, Evaluation, and Characterization of Viral Clearance Procedures.
  15. Duizer E, Bijkerk P, Rockx B, de Groot A, Twisk F, et al. (2004) Inactivation of caliciviruses. Appl Environ Microbiol 70: 4538-4543.(Crossref)
  16. Cannon JL, Papafragkou E, Park GW, Osborne J, Jaykus L-A, et al. (2006) Surrogates for the study of norovirus stability and inactivation in the environment: A comparison of murine norovirus and feline calicivirus. J Food Prot69: 2761-2765.(Crossref)
  17. Buckow R, Isbarn S, Knorr D, Heinz V, Lehmacher A (2008) Predictive model for inactivation of feline calicivirus, a norovirus surrogate, by heat and high hydrostatic pressure. Appl Environ Microbiol 74: 1030-1038.(Crossref)
  18. Gibson KE, Schwab KJ (2011) Thermal inactivation of human norovirus surrogates. Food Environ Virol3 : 74-77.
  19. Bozkurt H, D’Souza D, Davidson PM (2013) Determination of the thermal inactivation kinetics of the human norovirus surrogates, murine norovirus and feline calicivirus. J Food Prot76: 79-84.(Crossref)
  20. Bozkurt H, D’Souza DH, Davidson PM (2014) A comparison of the thermal inactivation kinetics of human norovirus surrogates and hepatitis A virus in buffered cell culture medium. Food Microbiol4: 212-217.(Crossref)
  21. Plummer G, Lewis B (1965) Thermoinactivation of herpes simplex virus and cytomegalovirus. J Bacteriol 89: 671-674.(Crossref)
  22. McDevitt J, Rudnick S, First M, Spengler J (2010) Role of absolute humidity in the inactivation of influenza viruses on stainless steel surfaces at elevated temperatures. Appl Environ Microbiol76: 3943-3947.(Crossref)
  23. Sauerbrei A, Wutzler P (2009) Testing thermal resistance of viruses. Arch Virol154: 115-119.(Crossref)
  24. Dekker A (1998) Inactivation of foot-and-mouth disease virus by heat, formaldehyde, ethylene oxide and ϒ-irradiation. Vet Rec 143: 168-169. (Crossref)
  25. Bräuniger S, Peters S, Borchers U, Kao M (2000) Further studies on thermal resistance of bovine parvovirus against moist and dry heat. Int J Hyg Environ Health 203: 71-75. (Crossref)
  26. von Rheinbaben F, Wolff MH (2002)Virus Disinfection Manual. (Pg: 1-499) Springer Berlin Heidelberg,Heidelberg, Germany.
  27. Boschetti N, Wyss K, Mischler A, Hostettler T, Kemph C (2003) Stability of minute virus of mice against temperature and sodium hydroxide. Biologicals31: 181-185.(Crossref)

Novel Case of Emergency Room to Operation Theatre for Management of Blunt Chest Wall Injury

DOI: 10.31038/IJOT.2020313

 

We hereby present a novel case of Emergency Room to Operation Theatre for management of Blunt Chest Wall Injury. This is the first case to our knowledge in Australasian literature highlighting the importance of transfer from the Emergency Room to Operative room for early correction of respiratory physiology. A 74-year -old patient was air lifted into our level I trauma centre from a peripheral hospital.This was followingfall from 3-meter height whilst on a ladder. On clinical examination the patientwas able to communicate and maintaining their own airway with oxygen requirement of 15 litres via a non- breather mask to achieve oxygen saturation of 92%.

On examination, there was extensive subcutaneous emphysema and limited movement of the left chest wall on both inspiration and expiration. Prior to being airlifted, a left sided intercostal catheter placed by the peripheral hospital which was swinging with minimal amount of hemoserous drainage. The hemodynamics suggested a pulse rate was 115- sinus rhythm and non -supported blood pressure of 122/80 mm of Hg. Venous blood gas results were as follows- pH 7.16, p CO2 – 70, p O2- 28 and base excess of -5.2.A trauma series scan at the peripheral hospital was suggestive of isolated chest wall injury with anterolateral bi cortical displaced rib fractures and moderate amountof hemopneumothorax (Figure 1A).

IJOT-3-1-304-g001

Figure 1. (A) Computed Tomography of the chest with extensive subcutaneous emphysema and bi cortical displaced rib fractures.
(B): X-Ray chest on presentation.

We organised a repeat chest x-ray (Figure 1B). The x-ray confirmed multi-level rib fractures with associated pneumothorax.Patient was in respiratory failure with a blood carbon dioxide level of 70 and oxygen of 28, thus we decided to procced with surgical stabilisation of rib fractures directly from the emergency department. General anaesthesia was administered via a single lumen tube. Right lateral position with an incision parallel to the lateral border of scapula was undertaken.  Open reduction and internal fixation of rib numbers 3,4,5,6,7 was achieved using Rib Loc (8055 NE Jacobson St., Suite 700 Hillsboro, OR 97124). Ongoing arterial blood gases whilst on theatre table as the stabilisation progressed suggested a fall in CO2 levels to 35. Figure 2 depicts the post- operative x-ray. Patient was extubated the following day and was discharged home on day 5.

IJOT-3-1-304-g002

Figure 2. Post-Operative X-ray chest.

Discussion

This is the first case to our knowledge in Australasian literature highlighting the importance of transfer from the Emergency Room to Operative room for early correction of respiratory physiology. Elderly patients who sustain blunt chest trauma with rib fractures have twice the mortality and thoracic morbidity of younger patients with similar injuries. For each additional rib fracture in the elderly, mortality increases by 19% and the risk of pneumonia by 27% [1]. Literature review suggests in adult patients with flail chest, surgical stabilisation of rib fractures decrease mortality; shorten duration of mechanical ventilation, hospital length of stay, and Intensive Care Unit length of stay; and decrease incidence of pneumonia and need for tracheostomy [2].

The goal at our Level I trauma centre is to attempt stabilisation of the chest wall as soon as hemodynamic stability is established. This case highlights the importance of early surgery to avoid potential morbidity and mortality for adult patients with blunt chest wall injury.

References

  1. Bulger EM,Arneson MA, Charles N. Gregory MJ, Jurkovich (2000) Rib fractures in the elderly. The Journal of Trauma: Injury, Infection, and Critical Care 48: 1040-1047.
  2. Kasotakis, Hasenboehler EA, Streib EW, Patel N,  Patel MB, et al., (2017) Operative fixation of rib fractures after blunt trauma: A practice management guideline from the Eastern Association for the Surgery of Trauma. Journal of Trauma and Acute Care Surgery82: 618-626.

Advanced Nanomaterials for Energy and Environmental Applications

DOI: 10.31038/NAMS.2020316

 

The research areas in the science and engineering have been looking to develop new advance materials for energy technologies, which have the capability of improving life in the world. Globally carbon dioxide emission from fossil fuel combustion increases faster than expected, because of inefficiency in fuel and the weakening of natural carbon sinks.The major source of carbon emissions is the burning fossil fuels and other natural sources. It was observed that nanotechnology able to decrease the need for fossil fuels, thus having a positive impact on global warming. Nanotechnology and its products (or nanomaterials) mostly involve in the applications of renewable energies (such as, solar and hydrogen fuel cells and energy storage device), which result in nearly zero Co2 emissions. Increasing the use and efficiency of renewable/ecofriendly energy resources will overcome the use of burning fossil fuel, and at the same time decreasing the consumption of current fuels is one way to slow down and ultimately stop global warming. The advance development in nanomaterials is still in progress, which can economically absorb the carbon dioxide from the air, capture toxic pollutants from water and degrade solid waste into useful products. Nanomaterials are efficient catalysts and mostly recyclable.

(1) Advance Nanomaterials for Energy Storage applications:

Hydrogen today is enjoying unprecedented state in the world in emerging fields of renewable energy by substitution of fossil fuels (i.e. petroleum, natural gas and coal), which meet most of the world’s energy demand today, are being depleted fast. Combustion products of fossil fuel are creating global problems (global warming, climate change, ozone layer depletion, acid rain, oxygen depletion and pollution), which posing great danger for our environment and eventually for life on our planet. Scientists all over the world agree to replace the existing fossil fuel system with the Hydrogen Energy System. Hydrogen is the fuel of 21st century because of it being light, most abundant, storable, energy-dense, and produces no direct emissions of pollutants or greenhouse gases. Hydrogen energy has potential to solve energy problems of the planet earth giving it a sustainable and safe future, resulting into a clean planet. H2 storage and release is a key challenge which is solved by metal hydrides which can absorb hydrogen in atomic form and release it easily by raising their temperature or pressure. Lots of important advances have been resulted during last one decade for developing nanostructure materials with high volumetric and gravimetric hydrogen capabilities. There is an urgent need to developed low cost, safe and inexpensive nanostructured hydride materials having high hydrogen content and fast desorbing properties at low temperature and pressure. In the present energy scenario, most of hydrogen storage materials have storage capacities not more than 5 wt% which is not satisfactory for practical application as per DOE USA Goal. Many research groups are currently working on hydrogen storage material to get best de/absorption kinetics with ultimate H2 contents. e.g. Mg hydride is a promising hydrogen storage material with reversible hydrogen capacity up to 7.6 wt% for on board applications with fast kinetics, good cycle life and decreased hydrogen desorption temperature. Good hydrogen storage properties are possible by introducing enough catalyst and by ball milling which introduces defects with improved surface properties. Hence lot of research work is needed for improving metal hydrides properties such as hydrogenation, fast charging / discharging rate, fast kinetics, thermal and cyclic behaviour. All over the world serious type of research and development work is going on Hydrogen Energy. Internal combustion engines are being modified for hydrogen fuel. Efficient fuel cells are being developed to convert hydrogen efficiently to electricity. Research and development work on metal hydride refrigeration and air conditioning systems is in advance stages and will be available for commercial applications shortly. Hydrogen fuel subsonic and supersonic transport planes are already in their test runs,In fact hydrogen shows the solution and is capable of the progressive and non-traumatic transition of today’s world energy scenario to feasible, safe, reliable and completely sustainable energy future. Scientists are advocating use of hydrogen for all types of energy applications which was earlier possible only by fossil fuel and they have hoped for the international response to the global climate change. Hence there are enough environmental and public health benefits of direct use of hydrogen energy and justifying for moving ahead, based on what we already know about fossil fuels and their consequences.

(2) Advance Nanomaterials for Solar Cell Applications:

Solar cell materials are the current prospects for clean energy research to offering strong power outputs from low-cost raw materials that are relatively simple to process into working devices. Although the potential of the material (Perovskite based solar cells) is just starting to be understood, it has caught the attention of the world’s leading solar researchers are trying to commercialize it.e.g. organic-inorganic lead halide perovskite solar cells are contenders in the drive to provide a cheap and clean source of energy with electrical power conversion efficiencies of over 29%. The high efficient photovoltaic materials are recognized for optically high absorption characteristics and balanced charge transport properties with long diffusion lengths. Nevertheless, there are lots of puzzles to unravel to understand the fundamental basis of such advance materials. Perovskite solar cells (PSC) are economically viable from a viewpoint of efficiency, however, commercialization is still challenging because of the toxicity of lead, long term stability, and cost-effectiveness. Future research directions will benefit from finding lead-free light-absorbing materials. However, the reported efficiencies are thus far too low to commercialize PSC’s. The cost-effectiveness of the raw materials and the fabrication processes is a significant issue. High throughput fabrication strategies with reproducible materials and processes should be developed. Moreover, mechanical functionalities such as flexibility, stretchable and long term stability properties will lead to making PSC’s more economically viable.

Obesity and Inflammatory Profile: Is Physical Exercise Able to Reverse This Process? A Mini Review

DOI: 10.31038/EDMJ.2020422

Abstract

Obesity represents a public health problem resulting from several factors. The studies highlighted the practice of physical exercise performed regularly, as a strategy to deal with overweight and obesity in different audiences. The present study aims to investigate the mechanisms of obesity advancement, mainly the installation and maintenance of low-grade systemic inflammation resulting from the development of obesity and to export the benefits of regular physical exercise practices for use and disease control. The search for scientific articles in the literature was carried out in the MEDLINE, PubMed, Scielo and Scholar Google databases. Among the articles researched, review studies, observations, clinical trials and consensus positions were considered. The research carried out included the main articles published between 2010 and 2019 and few with a longer publication period due to their relevance. The selected articles present relevant content for understanding the mechanisms by which obesity develops and the role of adipose tissue dysfunction in this process, in addition to studies that discuss the mechanisms by which physical exercise is able to promote the contribution of myocins and try to rebalance the inflammatory profile affected by obesity. It was concluded that muscle contraction resulting from physical exercise can release myocins that help to change the scenario of the inflammatory profile of obese and non – obese individuals, being a non-pharmacological tool in the treatment of obesity and other chronic diseases. The anti-inflammatory role of physical exercise needs to be further investigated.

Keywords

diabetes, Inflammation, Obesity, Overweight, Physical Exercise

Introduction

Obesity is a Chronic Non-Transmissible Disease (CNCD), understood as a multifactorial disorder that assumes the condition of an epidemic, affecting individuals of different age groups and with great prevalence in different countries of the world, having a great relationship with the emergence of several other diseases and high rates of morbidity and mortality [1,2]. The terms overweight and obesity are used to describe an excess of adiposity (or fat) above the ideal for good health. The use of anthropometric indicators, assist in the classification of cutoff points of the Body Mass Index (BMI), being used in the prediction of the weight status [3]. It is possible to point out several factors that can contribute to the development of obesity, among them are diets with positive caloric balance, physical inactivity, reduced basal metabolic rate, genetic and hereditary factors [4]. The interaction of these factors is complex and has been the focus of several studies. The increase in consumption of foods rich in sugars and fat and the decrease in the practice of physical exercises are the main factors related to the development of obesity [5].The impacts that overweight and obesity have on the quality of life of children, adults and the elderly are the targets of several studies. The data found in the literature demonstrate significant reductions in quality of life, psychosocial health, self-esteem, emotional well-being, physical and functional capacities [6, 7]. Current suggestions highlight the practice of regular physical exercise, an important strategy for coping with overweight and obesity, regardless of age. Organizations focused on public health care create guidelines that support these recommendations and provide a reference for professionals who deal directly and indirectly in the prevention, control and fight against obesity [8, 9].

It is known that Adipose Tissue (AT) is an organ with an important role in energy homeostasis, insulin sensitivity, angiogenesis, metabolism, inflammatory responses, immunity, endocrine and neuroendocrine systems [7, 8]. Under conditions of overweight and obesity, it is common for endocrine and functional disorders to occur in adipocytes. In the opposite direction to sedentary lifestyle and obesity, studies have elucidated Physical Exercise (PE) can act to reduce harmful conditions associated with obesity [10]. The present study carried out a systematic review of the literature and aims to assist in understanding the progression of obesity in Brazilian society, the mechanisms involved in AT dysfunction and its low-grade, local or systemic chronic inflammation and physical exercise can modulate such an inflammatory cascade, thus helping to face this condition.

Results

Initially 940 studies were found using the keywords previously mentioned. Initially, the exclusions took into account the relationship between the title of the articles and the proposed theme, leaving 126 articles, which after analyzing the summary and later reading in full, resulted in 52 articles that served as the basis for the production of this research. The other articles were excluded from the research due to their lack of relationship with the proposed theme. Of these, 12 studies investigate the understanding of the progression of obesity in modern society, 23 studies cover the mechanisms involved in the development of obesity and low- grade systemic inflammation and 17 discuss the benefits of PE to combat low- grade systemic inflammation.

Discussion

The rise of obesity

Obesity represents a public health problem with a major impact on the quality of life of affected individuals. Obesity is part of the group of Chronic Non-Communicable Diseases (NCDs), as well as diabetes, cancer, circulatory and cardiorespiratory diseases. Also according to data from the Ministryof Health, NCDs are the main causes of death in the world, corresponding to 63% of deaths in 2008 [11]. Obesity is defined as “an abnormal or excessive accumulation of fat, with possible damage to health” [12] and is related to a large number of disabilities and morbidity and mortality in several countries, in addition to being linked to the development of other pathologies such as resistance insulin, Cardiovascular Disease (CVD), type 2 Diabetes Mellitus (DM) and some types of cancer; being identified as a disease resulting from a conglomerate of factors. [1, 2]. In Brazil, this figure reaches 72% of the causes of death. The presence and maintenance of the condition of overweight and obesity generate great social, financial and family impact for the affected individuals. Treatment for obesity is costly to the public health sectors of various governments around the world. Several authors propose to discuss the real and updated costs of the disease to the public coffers and the Unified Health System (SUS). However, in addition to the values directly attributed to obesity, several other disorders and diseases are associated with the presence of obesity, considerably increasing the costs associated with the disease. According to Bahia, in a survey carried out between 2008 and 2010, the total values for procedures and treatments for overweight and obese people, were around 2.1 billion dollars annually in Brazil [9]. In 2015, a study promoted by the Ministry of Health and the National Supplementary Health Agency, through the Risk and Protection Factors Surveillance System for Chronic Diseases by Telephone Survey [13], carried out in 27 Brazilian cities, found that 52.3% of the adult population is overweight and among them, 17% are classified as obese. The costs to the public health system budget related to obesity and morbid obesity, in 2011, totaled US $ 269.6 million, which corresponded to 1.86% of all Ministry of Health expenses with hospital and outpatient care. in Brazil [14].

It is evident that not only adults and the elderly suffer from this scenario, but also children and adolescents, which makes this an even more important topic to be discussed. Data from the World Health Organization (WHO) indicate that in 2016, almost 2 billion adults over 18 years of age were overweight, among them, more than half a billion were considered obese. As for individuals aged between 5 and 19 years old, the numbers also show a considerable increase, in 1975 only 1% of children and adolescents were classified as obese, whereas in 2016, this percentage increased to 7% worldwide [6,15]. The understanding about obesity has evolved considerably in the last century, as well as the evaluation strategies for verifying the obesity condition itself. Among the possible examples of validated models, it is common to use anthropometric indicators, which help in the classification of the percentage of fat, as well as cut points of the Body Mass Index (BMI), which has been widely used in the prediction of the state of the body weight [3]. BMI classifications vary between results below 18.5, being classified as thin, 18.5 to 24.9, normal BMI and defined overweight when the BMI reaches values between 25.0 to 29.9. The classification of obesity obeys class I with values between 30.0 – 34.9 of BMI; class II obesity, BMI values between 35.0–39.9; and obese class III, with BMI values above 40.0 [16].

Although the Body Mass Index (BMI) can be used to classify obesity in adults, its use in children and adolescents should not be used in isolation. Due to the need to take into account the variation in corpulence during growth, sex and age group [17]. In adults, body constitution should also be taken into account, due to variations in body mass, which can promote misinterpretations of BMI. The normal limit is established by percentile curves of the body mass index. Such values, which were updated in 2000 and are recognized by the World Health Organization [18, 19]. As well as the definition of obesity exposed above, excessive accumulation of fat is usually referred to in the literature as a result of the relationship of several reasons. Tavares, et al. (2010) cites obesity as a multifactorial disease, resulting from the interaction of genetic, metabolic, social, behavioral and cultural factors, in addition to physical inactivity, which is referred to as one of the determining factors for the development and maintenance of the disease. Such notes are reinforced by other authors, such as SAHOO, who discusses the main factors that are commonly associated with theprogression of obesity, among them, diets with positive caloric balance, physical inactivity, reduced basal metabolic rate, genetic and hereditary factors [4, 17]. The interaction of these factors is complex and has been the focus of several studies, however, the increase in the consumption of foods rich in sugars and fats and the decrease in the practice of physical exercises remain among the main factors related by scholars to the greater accumulation of fat and favoring the development and maintenance of obesity [5]. This accumulation comes from the ability to store fat, important for the survival of our species in past ages, however, it has become harmful in the face of the modern lifestyle, with a greater supply of foods rich in fat and lower levels of physical activity [20].

Although there are records of obese individuals who lived thousands of years ago, the disease epidemic in the modern age has become a more relevant public health problem, possibly due to the increasing life expectancy and the rise of NCDs. According to Francisqueti et al., obesity takes on the characteristics of a pandemic, due to the relationship with the emergence of other diseases. For the author, the inflammatory process inherent in the presence of obesity favors the development of cardiovascular diseases and insulin resistance [21]. Formerly it was thought that the function of TA was limited to the storage of fat, however, it is known today that adipocytes have a strong endocrine action. Under conditions of obesity, the secretion of cytokines and proteins is associated with the development of inflammatory processes. This concept is supported by the fact that obese individuals have high circulating levels of inflammation-related products [22] The maintenance of low-grade systemic inflammation in obese individuals is mentioned as one of the determining factors for the onset or development of several diseases, such as those previously mentioned. Resistance to the action of insulin, for example, may occur due to the damage that increased expression of the Tumor Necrosis Factor-alpha (TNF-a) offer the physiological action of insulin [23].

Several studies seek to elucidate the impacts that overweight and obesity cause on the quality of life of affected individuals. The findings available in the literature demonstrate significant reductions in quality of life, psychosocial health, self-esteem, emotional well-being, physical and functional capacities [24-26]. Obesity treatment strategies are very varied, including drug interventions, surgeries, dietaryreeducation, among others. The regular practice of physical exercises has been recognized for years as an important factor for health promotion, however, recent research reinforces the discovery of the ability of physical exercise to promote the secretion of myokines, which contribute to the reduction of the inflammatory profile, being adopted as a non -pharmacological importance for the fight against obesity [22, 23, 27]. Therefore, physical exercise is an important modulator of the immune response. Current suggestions in the literature highlight the practice of physical exercise performed on a regular basis as an important strategy for coping with overweight and obesity in individuals of different age groups. Organizations focused on public health care create guidelines that support these recommendations and offer references for professionals who deal directly and indirectly in the prevention, control and fight against obesity [6, 18, 19, 28]. However, although there are clear recommendations that encourage the practice of Moderate To Vigorous Physical Activity (MVPA) for at least 60 minutes daily [29], it is increasingly common that young people, adults and the elderly do not achieve the amount of daily physical activity recommended. A study carried out using questionnaires showed that 80.3% of adolescents between 13 and 15 years of age, do not reach recommended levels of MVPA worldwide. Phenomenon also observed in individuals of different age groups [30]. Innumerable factors can contribute for young people to practice physical activities or not, among them, socioeconomic, cultural, environmental issues, public policies, available infrastructure, food, relationship with parents and close people, physical self-concept and motor competence, season, body composition, among others. Such variables seem to have a great impact on the adherence of children and adolescents to the recommended practices of physical activity [30-32]. The practice of physical exercise during youth is reflected in adulthood, mainly in the level of physical activity performed, as well as in health and in the probability of developing diseases, such as obesity itself.

In addition to public policies that exhort about the value that the practice of physical activity has primarily on the health and quality of life of the population and that must be vehemently expanded and disseminated. It is extremely important that society fulfills its role as an encourager, support and practitioner, also creating adequate conditions for children, adolescents, adults and the elderly to practice physical activities regularly and comply with the goals suggested by current national and international guidelines [29, 32, 33]. It also contributes to the fight against several dysfunctions and diseases that are associated with a sedentary lifestyle. The appearance and progression of type 2 diabetes mellitus, hypertension, atherosclerosis and non-alcoholic liver steatosis, among other disorders and pathologies, make up the Metabolic Syndrome and are associated with AT dysfunction and sedentary lifestyle [34].

Inflammatory Mechanisms Involved In the Development and Persistence of Obesity

As mentioned above, overweight and obesity are recognized as a serious health risk factor, presenting a direct relationship with the appearance of several diseases, in addition to the premature death of millions of people each year. This phenomenon is recurrent mainly in developed and developing countries, such as the example used in Brazil [16, 22, 35]. It was previously thought that TA was a type of connective tissue with a restricted function of fat storage and mechanical protection for other tissues, however, the scientific literature has advanced in understanding this tissue. It is currently known that TA is an endocrine organ with autocrine and paracrine actions that are important in the regulation of metabolism, in the control of intake, in energy homeostasis, in the storage of fatty acids, among others. In conditions of obesity, TA is directly related to the development of resistance to the action of insulin in peripheral tissues such as skeletal muscle tissue and the liver. This condition favors the onset of Type 2 Diabetes Mélitus. The greater abundance of fatty acids also favors the appearance of heart diseases, especially with the formation of atheromatous plaques, characterized by the accumulation of fat on the wall of vessels and arteries. Several other diseases and some types of cancers are related to the presence of obesity and the disorders related to it [36].

Obesity is a multifactorial disease, and may derive from a conglomerate of conditions. It is common for the progression of the disease to occur as a result of a large supply of calories from the diet combined with a sedentary lifestyle, promoting an increase in the size and quantity of adipocytes [37]. It is believed that during the process of developing obesity, there is compression of the blood vessels that irrigate the adipocytes, by hypertrophied fat cells. It is possible that the anomaly in the function of these vessels impairs the supply of oxygen and other substances for adipose tissue. This process culminates in a cascade of events that lead to a condition called low-grade systemic inflammation [34, 36]. Several mechanisms have been described in the literature as resulting from this anomaly. The affected tissue recruits cells from the immune system, such as m1-type macrophages and neutrophils, which attempt to reestablish homeostasis. The recruited macrophages migrate and infiltrate the AT, resulting in increased local production of pro-inflammatory cytokines, induction of the expression of pro-inflammatory factors and death of adipocytes. This condition of hypoxia of AT increases the expression of the Hypoxia Inducing Factor 1 α (HIF-1α), which is related to the alteration of the expression of several genes, including Monocyte Chemotactic Protein 1 (MCP-1) which promotes increased attraction of macrophages to adipocytes [19, 38, 39].

The infiltration of M1-type macrophages in adipocytes favors tissue inflammation and is associated with altered release of several proteins and adipokines, which are important substances in the regulation of metabolism, immune system responses and in the control of several other organs and systems. Among the products secreted by adipocytes, we can highlight the increased expression of Leptin, which is a hormone with action in the hypothalamus, in addition to several other tissues. Leptinfavors the control of intake and caloric balance, especially after feeding and also in a circadian manner. In conditions of obesity, it is possible that increased leptin secretion occurs, accompanied by dysfunction of its receptors, impairing caloric control and other homeostatic functions regulated by the hormone [39].It is known that fat cells in the condition of obesity and cells of the immune system secrete the Tumor Necrosis Factor – Alpha (TNF-A) cytokine, and the genes that encode it are expressed in subcutaneous and visceral TA. TNF-A is associated with inflammation, apoptosis, cytotoxicity, production of other cytokines and induction of insulin resistance, mainly because it affects hormone receptors and reduces sensitivity to it. In addition to these factors, TNF-A also acts directly in several other processes, such as carbohydrate and lipid homeostasis; inhibition of lipogenesis and stimulation of lipolysis; and also in the formation of atheroma in blood vessel walls [40].

TNF-A promotes increased expression of several types of interleukins, including Interleukin-6 (IL-6) due to its important relationship with the regulation of innate and adaptive immune responses. This interleukin is produced by several immune cells and is increased in obesity. IL-6 is considered a pro-inflammatory factor and appears to inhibit the insulin signaling pathway through the positive regulation of SOCS3 gene expression, which promotes damage by favoring the phosphorylation of the insulin receptor protein (IRS1) preventing its interaction with the beta subunit of the insulin receptor and favoring the onset of Diabetes [41, 42]. In addition, IL-6 stimulates the production of Interferon-Gamma (INF-g), responsible for regulating positively a set of pro-inflammatory factors [43]. According to researcher Isabela Maia de Cruz, IL-6 may favor the increase in the production of C-Reactive Protein (CRP) by the liver. This protein is recognized for its pro-inflammatory function and is also commonly used as an acute phase inflammatory marker for individuals affected by different types of stress, injuries and pathologies, such as obesity itself [44]. CRP is also related to low back pain, especially in obese individuals.

Obese individuals are more likely to suffer from heart disease due to Angiotensinogen, which is synthesized primarily by the liver, but also abundantly by AT. According to LACERDA et al., 2016 [39], Angiotensinogen undergoes action of renin and angiotensin I is converted, which in turn becomes angiotensin II through the Enzyme Angiotensin (ACE). Angiotensin II resulting from the production by obese TA stimulates the production of prostacyclins by adipocytes, which induce the differentiation of pre-adipocytes to functional adipocytes; favors the increase in blood pressure and the production of atheromatous plaques, due to the stimulation of the production of adhesion molecule-1 and macrophage colony stimulating factor in the endothelial wall. Another important disorder occurs with the secretion of the hormone Resistin, which is directly related to insulin resistance in the muscle and liver for inducing the expression of endothelin-1 and thus contributing to endothelial dysfunction. In addition, resistin also favors a significant increase in the expression of VCAM- 1 and MCP-1, which play a decisive role in the formation of the initial atherosclerotic lesion, favoring the appearance of coronary lesions [39, 45]. The high levels of TNF-a and IL-6 have, among other effects, a reduction in the synthesis and secretion of Adiponectin, an important adipokine with several anti- inflammatory and anti-atherogenic actions. It reduces hepatic glucose production and improves insulin sensitivity in the liver and skeletal muscle; decreases serum glucose levels, free fatty acid triglycerides and the concentration of intracellular triglycerides; protective role against insulin resistance; modulates the activation of the transcription factor NF-kB (nuclear factor kappa beta), and the inflammatory response induced by TNF-a [42]. Adiponectin appears to inhibit TNF-a production and vice versa, in TA; therefore, adiponectin can indirectly inhibit the expression of IL-6 and PCR by inhibiting the production of TNF-a. Adiponectin also induces the production of an important anti-inflammatory cytokine, Interleukin-10 (IL-10), and also causes the suppression of phagocytic capacity in macrophages and potentiates apoptosis in monocytes [23].

Although cytokines such as adiponectin and IL-10 play an important role in combating the development of obesity in the low-grade systemic inflammation profile, it is known that pro-inflammatory cytokines contribute to the maintenance of inflammation and favor the expansion of obesity, causing changes in other systems, resulting in reduced satiety and increased demand for food, reduced metabolism and energy expenditure, decreased insulin sensitivity in the liver and skeletal muscle, increased hepatic glucose production and reduced oxidation of free fatty acids (AGL) [34, 46]. In contrast to the state of chronic inflammation of low local or systemic degree promoted by obese AT, it is known that EF plays an important role in combating the pro-inflammatory profile identified in obesity. New studies recognize the role of physical exercise in combating inflammation, according to KRINSKI et al., 2010,physical exercise is an important modulator of the immune response and function. The effects that justify this claim will be better addressed below [27].

Anti-Inflammatory Action Triggered by Physical Exercise

It is established in the scientific literature that the practice of physical exercises is important for the promotion and maintenance of health, due to positive adaptations, which include improvement in the lipid profile, decreased risk of developing obesity, diabetes mellitus 2 and cardiovascular diseases [44]. It is important to emphasize that not only the practice of physical exercises and the adequacy to recommended levels of weekly physical activities are important for health promotion, prevention and coping with various types of diseases, but insufficient physical activity routine is a risk factor important for the development of chronic diseases, especially those treated as Chronic Non-Communicable Diseases (DNCT), which include diabetes, hypertension, cardiovascular diseases and dyslipidemia. The term sedentary lifestyle is used to describe inactive behavior and the practice of activities that do not reach energy expenditure levels above rest levels. According to Meneguci and his collaborators, the effects of physical inactivity on health can be explained due to the fact that low muscle contraction is related to decreased use of glucose by muscles, increased insulin and lipids. These lipids are preferably stored in the AT of the visceral region, which contributes to the cascade of processes that leads to inflammation, as previously mentioned, and contributes to the development of chronic Non-Communicable Diseases (NCDs) [47,48].

A study carried out at UniversidadeEstadualPaulista with Wistar rats initially submitted to a high-fat diet in order to develop obesity in animals, found development of resistance to the action of insulin and an inflammatory profile. After the resistance training protocol, there was an improvement in peripheral sensitivity to the action of insulin and a reduction in the expression of pro- inflammatory cytokines in the soleus muscle of rats exposed to a high-fat diet and resistance training. It is assumed that these changes also occur in several other tissues not evaluated. These findings can be justified by the positive adaptations in the oxidative capacity of the soleus muscle, contributing to the increase in the metabolism of lipids, resulting in a reduction in the transcription factors of pro- inflammatory cytokines and leading to an end to the improvement in insulin sensitivity and the responses of the imune system. The functioning of the immune system, in turn, is dependent on the communication between the nervous, endocrine and immune systems through peptide and neurotransmitter substances. Several studies have shown that the immune function can be modulated by physical exercise. Krinski and his collaborators (2010), explain that the stress caused by physical exercise induces changes in homeostasis control systems, influencing the immunoneuroendocrine axis, in addition to promoting changes in the levels of metabolic substrates [27].

However, the understanding of the relationship between physical exercise and the changes observed in the immune system is based on large studies carried out in the last two decades, until today. Technological advances in the fields of genetics and molecular biology provide analyzes that favor the understanding of the mechanisms involved between the practice of physical exercises and their influence on the immune system [29]. The effects of the practice of physical exercises previously mentioned on the various aspects of health that include the regulation of metabolism, glycemic control and insulin sensitivity, hypertension, immune responses and the fight against low-grade chronic inflammation, among others. They are currently recognized as a consequence of the action of myocins. According to Whitham and Febbraio, (2016), “myokines” are described as cytokines or peptides produced and released into the circulation by skeletal muscle cells due to their contraction. Myokines exert important endocrine or paracrine effects on other cells, tissues or organs. Therefore, it is possible to point out the skeletal muscle as an endocrine organ that communicates with several other systems [47].

As previously discussed in this study, sedentary lifestyle and obesity contribute to the development of several diseases due to the increased secretion of several pro-inflammatory cytokines. In contrast, myokines secreted by muscle cells stimulated by physical exerciseseem to have a protective and antagonistic effect on pro- inflammatory adipokines from adipose cells [49]. Several machines are cataloged in the literature and their effects are widespread on different systems. Some myokines are highlighted due to practical knowledge of their effects on important health markers. Irisine, for example, is a type I membrane protein, secreted by skeletal muscle tissue after physical exercise. There is evidence that relate Irisin to the regulation of blood pressure and reduction of arterial hypertension, participation in mitochondrial biogenesis, darkening of white TA (Just like Meteorin-like 1) and improvement of obesity and glucose homeostasis. However, there may be controversies in understanding the role of irisin in heart disorders [50, 51].

The myokines that are currently best clarified is Interleukin-6. Unlike IL-6 secreted by TA and associated with the development of an inflammatory profile and other disorders, IL-6 secreted by the exercised skeletal muscle plays a different role. It is known that IL-6 as a myocin offers positive implications in several aspects, we can point out its function as an important activator of AMP-activated protein kinase (AMPK) in skeletal muscles, improving glucose uptake and insulin sensitivity; favoring lipolysis and oxidation of fatty acids in skeletal muscle; increased glucose tolerance, through the activation of glucagon as peptide 1 (GLP1) in the intestine, acting indirectly through GLP1 to reduce food intake and body weight [50]. It is possible that IL-6 also acts as an anti -inflammatory and immunoregulatorymyocin, this is due to the inhibition of TNF-a. This assumption starts from the observation of elevated levels of TNF-a in experiments carried out in knockout mice for IL-6. This suggests a negative regulation of TNF-a levels by IL-6. The anti-inflammatory effects of IL-6 are also observed due to the stimulus that this cytokine promotes for the production of other anti-inflammatory cytokines, such as the interleukin-1 receptor antagonist (IL-1ra) and the inhibitory factor of the synthesis of human cytokines IL-10 [49].

In addition to the metabolic effects, many of the myocins act directly within the skeletal muscle itself. Some examples include myostatin, LIF, IL-4, IL-6, IL-7 and IL-15, which, among other functions, regulate muscle hypertrophy and myogenesis. The regular practice of physical exercises, with consequent prolonged maintenance of the increase in circulating levels of IL-6, seems to promote improvement in the central communication of leptin and improvement of nutrient homeostasis, an important factor for the protection against diet-induced obesity and positive calorie balance. In addition, the IL-6 myocin is also related to improving metabolic homeostasis, with reduced insulin resistance promoted by a high-fat diet in mice. There is evidence in the literature that indicates an important improvement in the metabolism of pancreatic β cells and insulin secretion and an improvement in sensitivity to the hormone in several tissues [38, 49, 52]. Another important circulating factor induced in the exercised skeletal muscle is the meteorine-like protein (METRNL), which may be indirectly related to the stimulation of thermogenic genes, through the increase of eosinophils by the action of IL-4 and IL-13. These cytokines, in turn, cause changes in the macrophages in AT, with the adoption of the M2 type phenotype, which increases the expression of thermogenic and anti-inflammatory genes in AT. The increase in circulating METRNL levels is also related to stimulating energy expenditure and improving glucose tolerance [50]. The contraction of skeletal muscle through physical exercise, in addition to promoting increased production and release of several myokines, also modulates immune system responses, through cells such as monocytes, macrophages and neutrophils, in order to repair and remodel the taught muscle tissue. Such disorders promote local and systemic changes, contributing to coping with the inflammatory disorder of obese ED. Several variables imply the amplitude of the observed effects on the secretion of myokines and the production of cells of the immune system, in an acute and chronic way. It is possible to conclude that the different types of stimuli have different effects on the mentioned processes [51].

Several studies relate the sedentary lifestyle to the development of several types of cancers, such as breast cancer. There is strong evidence of myokines produced and released by skeletal muscle stimulated by physical exercise, they have an inhibitory action on the proliferation of cancer cells in breast mammary tissue. This effect has been attributed to oncostatin M, another cytokine related to the IL-6 family. In general, sedentary lifestyle and physical inactivity lead to sarcopenia and the accumulation of visceral fat, resulting in the development of a chronic inflammatory process, which leads to conditions of resistance to the action of insulin, formation of atheroma plaques, neurodegeneration and tumor growth, among other disorders that promote the appearance and progression of several diseases [49].

Conclusion

Obesity presents with a low-grade chronic inflammation resulting from the sustained state of altered immune responses, promoting metabolic complications involved in the disease, such as insulin resistance, and favoring the development of several other diseases. The recommendation to practice physical exercises is supported by studies that satisfactorily demonstrate the benefits of physical exercise to fight obesity, due to the anti- inflammatory effects mediated by changes in the expression of myocins, genes and proteins that influence metabolism and functioning various systems. The benefits of physical exercises prescribed by Physical Educators, are dependent on regularity, however, it is not defined in the literature which values volume, intensity, or even what types of exercises are the most suitable for combating obesity. Therefore, it is necessary for each individual to practice physical exercises according to their own individualities.

Conflict of Interest

We declare that there is no conflict of interest in the development of this research.

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Competitive Pressures and Multiple Births in Infertility Treatment

DOI: 10.31038/AWHC.2020321

Abstract

Background: With the increase in fertility problems and delayed childbearing, demand for infertility treatments has been rising. Today, in vitro fertilization (IVF) is the most successful infertility treatment but it is costly. To meet rising demand for infertility treatment many markets have seen an increased entry of infertility clinics. Concerns have been raised of the effect of high per-treatment cost and rising competitive pressures on the outcomes of infertility treatments. The objective of this study is to examine the relationship between competitive pressures and prices charged by clinics for in vitro fertilization treatments as well as the effect of prices and competition on multiple gestations.
Method: This is a retrospective analysis of 2012-2014 clinic-level data in the United States. This study collects in vitro fertilization prices and combines the price data with the ART Fertility Clinic Success Rates Reports published by the Centersfor Disease Control and Prevention (CDC). The Herfindahl–Hirschman Index (HHI) is a widely-used measure of competition within a market. Regression analysis is used to estimate the relationship between HHI and price variables. The effect of prices and competitive pressures on multiple gestations is estimated.
Results: Multivariate regression results show that competitive pressures do decrease prices charged by IVF clinics (p-value<0.1). IVF refund programs that reimburse couples for multiple failures are more likely to be offered in more concentrated markets (p-value<0.05) and larger clinics (p-value<0.01). Lower prices translate into lower multiple rates for younger women (p-value<0.1). Controlling for prices, competitive pressures decrease multiple rates for younger women (below 35 years of age) but increase multiple rates for older women (above 40 years of age) (p-value<0.1).
Conclusions: Lower IVF prices translate into better quality as measured by the rates of multiples for younger women undergoing infertility treatments. Effect of competitive pressures on quality of care is ambiguous especially after we control for treatment cost. For older women such pressures may lead to more embryo transferred and higher rates of multiples. Further research is needed to identify the relationship between competition and quality of medical care in infertility and other markets.

Keywords

Infertility, in vitro fertilization, competition, econometrics

Background

Infertility and in vitro fertilization

About 11 percent of American women 15–44 years of age have difficulty getting pregnant or carrying a pregnancy to term [1]. Today, over 1.7 percent of all infants born in the United States every year are conceived using assisted reproductive technologies (ART) [1]. To meet this increased demand for ART, the number of infertility clinics in the United States has increased from 263 in 1995 when CDC started collecting ART success rate data to 459 in 2014. Today, in vitro fertilization (IVF) is the most successful infertility treatment but it is invasive and costly. IVF involves ovarian stimulation with prescription drugs with close monitoring by the reproductive endocrinologist to prevent overstimulation, ovarian retrieval (an outpatient surgery), fertilizing an egg with sperm outside of a woman’s body and then implanting it in her womb (another outpatient hospital procedure). Since IVF is a process, rather than a single procedure, costs include medications, laboratory tests, physician fees, hospital charges, anesthesia, and embryology lab fees. A full IVF cycle is priced at over $10,000 and a frozen embryo transfer at over $3,000 [2]. In addition, many couples have to go through several IVF cycles to achieve a live birth. CDC data indicates that only 32.98% of IVF cycles resulted in a live birth. High costs of IVF combined with relative low probability of success lead to more aggressive treatments and poor quality outcomes since patients’ immediate financial interests are best met by maximizing their pregnancy chances on each IVF cycle. Such financial incentives lead to patients transferring more than one embryo so as to limit the number of IVF treatments they undergo despite the health risks and long term costs associated with multiple gestations and births. Although IVF is a medical procedure that treats a medical problem of infertility, most private health insurers exclude it from coverage with only a quarter of insurers covering some infertility benefits [3]. To address costs, some states passed insurance mandates that require employers to cover – or offer to cover- infertility treatments. To date, few Americans have sufficient insurance to cover infertility treatments. While the Affordable Care Act extended insurance coverage to millions of uninsured Americans, IVF is not considered an “essential health benefit” under the Act and most insurers do not cover it outside of states where it is mandated.

Another factor that can address high costs of IVF is competitive pressures that lead to price competition among clinics. However, the effect of competition on IVF outcomes is ambiguous. While deciding on transferring another embryo, patients and clinics face short term benefits (higher probability of success and thus fewer IVF cycles) and long-term costs (higher probability of prematurity, C-section costs, other risks associated with higher risk pregnancy). On one hand, more competitive markets lead to lower prices which may allow patients to transfer fewer embryos per IVF cycle thus reducing multiple births. On the other hand, IVF clinics also compete for patients by advertising higher pregnancy rates and concerns have been raised that competitive pressures may lead clinics to transfer more embryos that may allow clinics to advertise higher success rates. This can lead to more multiple births.
This study examines the relationship between competitive pressures that infertility clinics face and health outcomes. We concentrate on one dimension of health outcomes: multiple gestations per ART birth. High costs of IVF procedure lead couples to transfer more embryos which leads to more multiple births (twins, triplets and high order multiples) per ART birth and thus poor quality health outcomes.

Health care providers in infertility markets compete along two dimensions: prices and quality. Due to lack of insurance coverage, price competition is more important in infertility settings relative to other areas of medical care that are better insured. This study attempts to use unique features of infertility market to distinguish between price and quality impacts of competitive pressures.

Competition and quality of health outcomes

Outside of infertility markets, the relationship between market competition and health care outcomes is ambiguous. While some studies show that hospital competition decreases mortality rates [4-7] others find higher mortality rates in competitive markets [8-9].

Empirical studies on mergers that result in accumulation of market power are similarly inconsistent.  For example, Ho and Hamilton show that mergers increase readmission rates but do not affect mortality rates while Hayford finds that hospital mergers are associated with increased treatment intensity and higher inpatient mortality rates [10,11].

Finally, Mutter, Wong and Goldfarb looked at 12 different dimensions of inpatient quality. They find that the effect of competition is not “unidirectional” with some quality measures showing improvements with greater market competition while others remain the same or even decrease [12].

Infertility treatment markets: The effect of competition

With more IVF clinics entering the market, many hypothesize that under competitive pressures doctors will pursue aggressive treatments so that the IVF clinics can advertise higher success rates. Some industry observers even propose limits on competition [13-15]. Few empirical results that exist however do not support these fears. Steiner measured competition as number of clinics in the area and found that competition did not affect pregnancy rates but decreased high order multiples (triplets and higher) [16]. Hamilton and McManus measured competition with a simple dummy variable (1=monopoly, 0-otherwise). They find that competition does not increase multiple birth rate [17]. Henne and Bundorf (2010) did not find a relationship between the number of competitors an infertility clinic has and embryo transfer decisions [10].

Infertility treatment markets: The effect of insurance mandates

Although previous literature does not exist on the effects of competition on prices of infertility treatments, several studies examined the effect of infertility mandates that make infertility treatments more affordable. Universal insurance mandates are associated with greater utilization of ART and other infertility treatments such as ovulation-inducing drugs and artificial insemination [17,19-21]. Schmidt finds that infertility mandates significantly increase first birth rates for older women [22]. The effect of insurance mandates on multiple gestations is ambiguous. On one hand, infertility mandates in New Jersey and Connecticut had no effecton embryo transfers and the rate of multiples [21]. On the other hand, a growing literature shows that infertility mandates improve outcomes of infertility treatments by decreasing treatment intensity and decreasing probability of multiple gestations per ART birth [17,19, 21]. However, Buckles estimates that state infertility mandates do not significantly affect multiple birth rates, they do increase triplet and higher-order births by 26% [24].

Previous literature on the cost and affordability of ART in the United States is limited but Chambers et al. using international data found that a decrease in a cost of an IVF cycle leads to fewer embryos transferred and higher use of single-embryo transfers. Affordability was measured as net cost of a standard IVF cycle relative to annual disposable income for thirty high and upper middle income countries [25].

Contribution to previous research

This study contributes to previous research on several fronts. First, we collect data on prices charged by IVF clinics to measure the effect of prices on multiple births. We also estimate the effect of the so-called money back programs that some IVF clinics offer. Second, we calculate Herfindahl–Hirschman Index (HHI) to measure market competition which shows more variance across markets in current data due to entry. Having both competition index and price data allows us to separate the effect of competition on prices from the effect of competition on quality. Finally, we are able to measure the effect of state insurance mandates while controlling for prices and competitive pressures.

Methods

Data sources

We use two waves 2012 and 2014of ART Fertility Clinic Success Rates Reports. The data is publicly available by Center of Disease Control and Prevention (CDC). The unit of analysis is a clinic performing ART (no patient level data is available). In this study we use data for non-donor fresh IVF cycles only. Thus, we excluded all cycles where an egg donor was used or frozen embryos were used.

All IVF cycles for each clinic were separated into three age groups since embryo transfer guidelines and IVF success rates vary by maternal age: women below 35 years of age, women between 35 and 40 years of age and women above 40 years of age. We use 2012-2014 ART Fertility Clinic Success Rates Report data to construct the following variables: number of IVF cycles by clinic (this variable captures the volume and the size of each clinic), multiple births by clinic and age group, percent of IVF cycles that underwent PGD (preimplantation genetic diagnosis) to test for genetic abnormalities for each IVF clinic, percent ICSI (intracytoplasmic sperm injection) cycles for each IVF clinic and society for assisted reproductive technologies (SART) membership which requires member compliance with strict embryo transfer guidelines.

Market area characteristics came from publicly available state and MSA-level data. Female labor force participation for years 2012 and 2014 was collected by the Bureau of Labor Statistics (BLS) at the state level. Percentage of educated women variable is based on National Center for Education Statistics report.  This data is collected at the state level and captures percent of women with at least a bachelor’s degree. MSA-level income per capita data came from the US Census Bureau. Data on state infertility mandates was obtained from the American Society for Reproductive Medicine. We also control for state-to-state differences in health care prices. We use annual average cost of living index for the health sector as reported by the Missouri Economic Research and Information Center (2015).

Competition index

We use Herfindahl–Hirschman Index (HHI) to measure market competition. The index is constructed based on total non-donor fresh IVF cycles performed for each clinic. Increases in the Herfindahl index generally indicate a decrease in competition and an increase of market power, whereas decreases indicate the opposite.  The index can vary from zero (perfect competition) to 10000 (Monopoly). We use metropolitan statistical area (MSA) as the relevant market for infertility clinics in our sample.

Price variables

State infertility mandates. Although previous studies used insurance coverage as a main price variable, currently few Americans have sufficient coverage for ART. By 2014fifteen states passed infertility mandates of which only eight states (Connecticut, Louisiana, Hawaii, Illinois, New Jersey, Massachusetts, Maryland, and Rhode Island) require all insurance plans to cover IVF. In addition, Arkansas, Montana and Ohio and West Virginia require some plans (all HMO’s or all non-HMO’s) to cover the costs IVF treatments. We use both definitions of the universal mandate to test the sensitivity of our results. It is important to note that even when insurance coverage is provided, the total value of the benefit may be capped at as low as $15,000 or the minimum number of cycles that must be covered may be as low as one [23].

In our definition of mandated infertility benefits, we do not include states like Texas that only require health insurance plants to offer infertility insurance since employers have the right to refuse such coverage. We also exclude states like California that require coverage of all infertility treatments except IVF.

IVF price measures. We supplement our analysis with price data from a health care price transparency website OkCopay. The price variable includes “one cycle of IVF procedure, using your own eggs, without monitoring” (http://www.okcopay.com/). In this study I used prices that included lab fees but not pharmaceutical prices. The data reflects cash prices, which is the charge before insurance.

In addition, many IVF clinics offer money back programs, (sometimes called IVF refund programs or IVF warranty programs) that allow a fixed fee for a number of IVF attempts and if the treatment is not successful, 80%-100% of money is refunded. Thus, couples that are successful on their first or second attempt most likely overpaid in comparison to traditional fee-for-service IVF.  But, this “overpayment” can be thought of as an “insurance premium” for money back, in the event the treatment is not successful. Data on refunds by clinics was collected from published sources (http://ivfrefund.com/about-ivf-refund.html) and verified with individual clinics. A dummy variable was created; it takes the value of 1 if a clinic offers a refund and zero otherwise.

Price data is only available for the 33.5% of clinics in the CDC sample while data on discounts is available for all 916 clinics in our sample.

Limited price information is an important limitation of this study since one might worry that the clinics that provide data to the transparency websites are systematically different from those that do not in a way that would boas the results. This is especially important since when price variable is included, all regressions are run on this selected sample of 307 clinics. To alleviate this concern we did look at the clinics with price information and did not find them to be different from clinics without price information. Separately we looked at markets where price data is available and markets where price data isnot available and did not find significant differences in market characteristics. These results increase our confidence that lack of data did not bias our empirical results.

Table 1 summarizes descriptive statistics. (Table 1)

Table 1. Descriptive statistics for selected variables

Mean

SD

Minimum

Maximum

Multiples rate for women aged under 35

29.50

17.99

0

100

Multiples rate for women aged 35-39

24.76

19.29

0

100

Multiples rate for women aged 40 and above

14.94

26.26

0

100

HHI

4054.27

3238.41

216.86

10000

Price

13,476.89

3,248.45

5,500

25,850

IVF refund

0.0877

0.283

0

1

Insurance mandate

0.171

0.377

0

1

Cost of living (health)

107.091

17.43

87.3

145.3

Volume (number of cycles)

336.73

570.27

1

7648

% PGD

5.43

10.68

0

100

% ICSI

70.96

19.48

0

100

SART membership

.835

0.370

0

1

Per capita income

49800.49

9074.61

15,200

81,068

Population, thousands

2,695,066

5,021,092

85.56

2.01e+07

% women with at least bachelor’s degree

28.34

4.62

17.4

48.6

Female labor force participation

57.81

3.202

42

69.6

Year = 2014

0.502

0.50

0

1

N
N for Price variable

916
307

Descriptive statistics show that IVF clinics markets vary from unconcentrated (HHI<1500) to monopoly (HHI=10000) although an average clinic is located in a highly concentrated market (mean HHI of 4054). As of 2014, none of the markets can be classified as competitive (HHI< 100). Probability of multiple gestations varied from an average of 14.94% for women over 40 years of age to 29.50% for women under 35 years of age. Average price in our sample was $13,477 with 8.77% of clinics offering IVF refunds.

Empirical analysis

To test the effect of HHI on costs and quality of care, two empirical models are used. First, we estimate the effect of HHI on costs:

AWHC-3-2-305-e001

We use IVF clinic price variable and availability of refunds as our main measures of IVF costs (Costi) for clinic i. Coefficient β1 captures the effect of competition in market m, coefficient β2 captures cost of living (health component), β3 captures the effect of state infertility mandates. In Clinic we control for characteristics of individual IVF clinics such as proportion of ICSI and PGD procedures performed as well as size of the clinic (measured by the volume of the IVF procedures). Variable Marketms is a vector of controls for variables that vary across MSA’s and states that might also affect costs. These include: median family income, population, female labor force participation rate, and percentage of women with at least a bachelor’s degree.  Economic theory predicts that more competitive markets should have lower prices. This relationship holds true in healthcare markets as well. Baker et al. showed that more competition among physician practices is related to lower prices for office visits [26]. Melnick et al. (1992) observed the same relationship in hospital markets: “greater hospital competition leads to lower prices” [27]. Given economic theory and previous empirical literature, we expect higher prices in more concentrated markets (positive β1) and more IVF refunds in more competitive markets (negative β1).

Second model estimates the effect of HHI on multiple gestations. We run the model with and without cost variables to gage the effect of the HHI on price and the effect of the HHI on quality competition. In this study, we concentrate on one important dimension of quality for IVF clinics: the rate of multiple births they produce. Multiple gestations are an important risk factor for preterm birth, with 11% of twins, 36% of triplets, and 67% of quadruplets and higher born very preterm (i.e. less than 32 weeks’ gestation), compared with less than 2% of singletons [28]. Preterm birth leads to increased risk for death, long-term neurological disabilities, and extended time in the hospital [29]. A recent study compared outcomes for women undergoing two IVF pregnancies with singletons and women undergoing one IVF twin pregnancy [30]. The neonatal and maternal outcomes were “dramatically” better for women undergoing two singleton pregnancies. IVF twins had higher rates of preterm births, low birth weight, respiratory complications, sepsis, and jaundice. Women delivering twins had higher rates of preeclampsia, preterm premature rupture of the membranes, and cesarean section. The authors proposed to decrease number of embryos transferred by IVF clinics to minimize the risks associated with multiple pregnancies. In our empirical model we use multiple rates per ART birth by maternal age for each clinic as a measure of quality [30].

AWHC-3-2-305-e002

where the dependent variable measures quality of health outcomes for age cohort a for clinic i. Coefficient β1 captures the effect of market competition, coefficient β2 captures costs of the procedure (prices charged by individual clinics and discounts offered by individual clinics), β3 captures the effect of state infertility mandates.  Although state infertility mandates directly affect IVF costs we treat this policy variable separately.

Although we control for market characteristics at both MSA and the state level, one major concern is that there are likely to be unobservable characteristics that are correlated with both the independent and dependent variables that are driving the estimated coefficients in (2). Therefore, we also take advantage of the panel nature of the data and run (2) with fixed effects to better control for unobservable differences.

Results

IVF costs

We estimate Equation (1) to describe the effect of HHI on IVF prices and refunds offered. Results are presented in table 2. (Table 2)

Table 2. Costs of IVF

 

(1)

(2)

Dependent variable

Price

IVF refund

Estimation method

OLS

Probit

 HHI

 0.0321 (0.0174)*

 0.384 (0.174)**

Mandate

0.0544 (0.0421)

0.186 (0.280)

Cost of living-health

 0.0031 (0.00244)

-0.0122 (0.00759)

West

-0.0226 (0.045)

0.842 (0.287)***

Midwest

-0.112 (0.0498)**

0.251 (0.319)

South

-0.104 (0.0502)**

0.790 (0.287)***

% PGD

0.00248 (0.00129)*

 -0.00869 (0.00759)

% ICSI

0.000919 (0.000748)

0.00472 (0.00441)

SART membership

0.0726 (0.0436)*

 -0.202 (0.227)

Volume

-0.00176 (0.0145)

0.526 (0.0899)***

Per capita income

-0.0764 (0.189)

0.454 (0.637)

Population, thousands

 0.0194 (0.00543)***

 0.103 (0.132)

% women with at least bachelor’s degree

-0.449 (0.154)***

-0.967 (0.713)

Female labor force participation

0.622 (0.419)

 2.011 (1.944)

Year = 2014

0.250 (0.170)

-1.78 (0.197)*

N

 303

 894

R2
F
Chi-squared

0.2196
4.00

84.43

Notes: All continuous variables are in log form; Robust standard errors are in parentheses.* p<.10, ** p<0.05, *** p<0.01

Table 2 shows that more concentrated markets tend to have higher prices, as economic theory predicts. At the same time, IVF refund programs are more likely to be offered in more concentrated markets and in larger clinics. This result is robust to alternative specifications of the model. Health insurance mandates do not significantly affect prices. Other significant variables include regional factors. IVF costs in the northeast are significantly higher relative to Midwest and South. Also, clinics in the South and West are more likely to offer IVF refund relative to Northeast clinics. Prices tend to be higher in more populous areas and lower in areas with more educated women.

Multiple Gestations

The goal of the paper is to examine the effect of determinants of potentially dangerous outcomes from IVF treatments: multiple births. Table 3 presents results of Equation 2 estimates for multiple rates without fixed effects. (Table 3)

Table 3. Multiple births

Dependent variable

 Multiple rate, %

 Age group

<35 year of age

 35-40 years of age

>40 years of age

 HHI

 4.419 (2.51)*

 0.253 (2.73)

-5.72 (2.57)**

Price, thousands

8.68 (4.78)*

0.029 (5.23)

-9.67 (6.79)

IVF refund

-1.93 (4.35)

-1.616 (4.73)

-0.632 (4.15)

Mandate

 3.63 (3.19)

1.18 (3.47)

-1.58 (3.13)

% PGD

 0.0252 (0.101)

-0.206 (0.109)*

0.117 (0.112)

% ICSI

-0.0368 (0.0583)

0.087 (0.067)

0.00438 (0.0608)

SART membership

1.22 (3.35)

1.01 (3.69)

7.17 (3.64)**

Volume

-1.101 (0.993)

 -1.78 (1.09)

1.19 (1.11)

Per capita income

-27.65 (12.59)**

  -14.89 (13.76)

31.02 (11.96)***

Population, thousands

 2.001 (2.009)

  1.59 (2.19)

-5.73 (2.12)***

% women with at least bachelor’s degree

10.39 (14.-5)

-8.78 (15.72)

-26.77 (14.90)*

Female labor force participation

 -38.94 (31.96)

22.36 (35.03)

44.05 (36.13)

West

-3.08 (3.42)

-3.64 (3.73)

-3.14 (3.65)

Midwest

-0.711 (4.53)

-8.57 (4.95)*

-7.01 (4.90)

South

-4.12 (4.01)

-7.62 (4.39)*

2.86 (4.32)

Year = 2014

-15.50 (13.39)

-15.66 (14.54)

22.16 (13.98)

N

294

288

184

R2

 0.217

0.218

0.235

F

2.20***

4.77***

3.65***

Notes: Robust standard errors are in parentheses.* p<.10, ** p<0.05, *** p<0.01; All continuous dependent variables are in the log form

Results in Table 3 show that effect of competition on multiple gestations is ambiguous. On one hand, competition decreases multiples through lower prices and through quality competition for women under 35 years of age. Although price variable is not important for women above 35 years of age, younger women are more sensitive with higher prices leading to more multiples for this age group. Without price variables more concentrated markets result in more multiples. Once we control for cost variables, significance  of  HHI decreases although remains positive and significant at p<0.10. Overall for younger women both price and quality competition is important. For older women (over age of 40) the effect of price and other cost measures is not significant. Thus, for this age group the effect of competition is due to quality competition alone and more concentrated markets actually lead to more multiple gestations. For women between 35 and 40 years of age, regional variables and PGD procedures are more important at determining multiples rates than economic variables.

Table 4 presents equation (2) estimates with individual clinic fixed effects. (Table 4)

Table 4. Multiple births estimates with fixed effects

Dependent variable

 Multiple rate, %

 Age group

<35 year of age

 35-40 years of age

>40 years of age

 HHI

0.304 (0.175)*

 -4.09 (7.72)

-8.84 (4.65)*

Price, thousands

8.57 (4.71)*

8.05 (18.29)

-16.22 (13.70)

IVF refund

-32.37 (11.08)***

9.79 (14.06)

-6.39 (9.35)

Mandate

 4.001 (17.69)

-7.15 (18.47)

-13.22 (14.23)

% PGD

-0.344 (0.584)

0.211 (0.645)

-0.877 0.377)**

% ICSI

-0.168 (0.146)

0.148 (0.163)

0.245 (0.117)*

SART membership

-0.691 (10.48)

1.46 (11.45)

12.79 (9.76)

Volume

-0.172 (2.44)

 -0.857 (2.89)

0.514 (1.83)

Per capita income

-69.79 (39.86)*

  51.91 (42.83)

56.91 (27.98)*

Population, thousands

 -1.03 (5.92)

  -4.46 (6.22)

-9.64 (4.68)*

% women with at least bachelor’s degree

-9.005 (50.95)

-55.62 (53.44)

-83.48 (46.67)*

Female labor force participation

48.58 (135.61)

54.33 (142.47)

215.21 (159.13)

Year = 2014

8.91 (38.04)

14.94 (40.04)

53.09 (30.09)*

N

291

285

184

R2

 0.145

0.076

0.0733

F

2.26***

3.77***

3.76***

Notes: Robust standard errors are in parentheses.* p<.10, ** p<0.05, *** p<0.01; All continuous dependent variables are in the log form

Results in table 4 are consistent with results that were observed without fixed effects. Table 4 shows that IVF refund programs significantly decrease multiple gestations for younger women although do not seem to affect multiple rates for women over 35 years of age.

Table 5 below summarizes how HHI coefficient changes with and without price controls. (Table 5)

Table 5. Effect of competition

Dependent variable

 Multiple rate, %

 Age group

<35 year of age

 35-40 years of age

>40 years of age

HHI coefficient without price, but with clinic characteristics, market and fixed effects controls

0.481 (0.187)***

4.34 (2.48)*

-4.55 (4.86)

 HHI coefficient with price, but with clinic characteristics, market and fixed effects controls (from Table 4)

0.304 (0.175)*

 -4.09 (7.72)

-8.84 (4.65)*

Table 5 finds that the effect of competitive pressures decreases when we control for prices in magnitude but remains significant for women below 35 years of age. For women over 40 years of age coefficient becomes negative and significant. Therefore, competitive pressures may affect quality differently for women of different age groups.

Overall results in tables 4 and 5 show that effect of competition changes with cost controls and may improve health outcomes for younger women but increase multiples for older women.

This study finds that health insurance mandates lead to fewer multiples (results omitted) but once we control for costs of the IVF, health insurance mandates are not statistically significant.

Discussion

Policy implications

The most important economic issues in the US IVF markets are: 1) barriers to access due to high prices and 2) health outcomes. Our empirical analysis confirms the existing consensus that competition lowers prices and lower prices translate into fewer multiples especially for younger women. Once we control for IVF costs, the effect of competition on multiple gestations is ambiguous and depends on the age of the patients.We also found fewer IVF discounts in more competitive markets. Thus, the overall effect of rising competitive pressures on health outcomes is not necessarily negative as previous literature suggests.

On one hand, competition policy is controversial in health care, compared to its use in other markets due to multiple market failures [31]. On the other hand, nothing about the unique features of health care industry suggests that market power is socially beneficial [32]. Despite expressed concerns that under competitive pressures doctors will be hard pressed to compete for patients by allowing more aggressive IVF treatments to boost clinic success rates, empirical results of this study show that this does not always hold true. At least for younger women, competitive pressures lead to fewer multiples by decreasing costs and through quality competition. Also, competitive pressures may be most helpful at improving access and equity when patients are faced with decreasing insurance funding for fertility treatments [33].

Patients searching for IVF clinics are faced with several factors they have to consider: price per cycle, success rate and multiple rate that clinics report. CDC and many IVF clinics make long-term consequences of IVF publicly available and patients are able to make comparisons of clinics by the multiples rates that they produce. This may be an important quality dimension that clinics use to attract prospective patients.

Limitations of the study

To separate the effect of competitive pressures on prices from its effect on quality, this study used the best available price data for IVF clinics to capture the cost of one fresh non-donor cycle of IVF procedure, without monitoring and pharmaceuticals. Unfortunately, this data was not available for all clinics. We did our best to verify and supplement the data but at this IVF prices with hospital and embryology lab charges are not attainable for many US clinics. Thus, low sample size is a problem. Our estimates of the effect of HHI on quality for the entire sample (without controlling for prices) show that competition leads to better quality for women under 40 and is not significant for older women. However, such estimates do not isolate the effect of prices from the effect of quality competition. As price data is becoming more available to consumers, future research is necessary to look at different ways in which competitive pressures affect prices and overall patient welfare.

This study uses only two years of available data. Although looking at a change in HHI over a longer time period may yield better results, price data is not available before 2012. As we accumulate price data to aid patients searching for health care providers, the effect of increasing over time competitive pressures that IVF clinics face can be estimated.

We use MSA as our definition of infertility market area. Since IVF is not an emergency procedure, many couples are able to search outside of their MSA area. Medical tourism allows an increasing number of Americans to cross international borders to obtain health care at a lower price and comparable quality. One may consider the entire world to be the market. In this study we assume that medical tourism is limited and most infertile couples search within their MSA.

Conclusions

This study found that lower IVF prices translate into better health outcomes as measured by the rates of multiples for women undergoing infertility treatments. Further research is needed to identify the relationship between competition and prices as well as competition and health care outcomes. With rising demand for infertility treatments, policy makers must consider the effect of ART funding on prices as well as the effect such funding has on quality and patients’ welfare in ART markets.

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Gastrointestinal Clear Cell Sarcoma Tumour of the Caecum: Case Report and Review Literature

DOI: 10.31038/CST.2020514

Abstract

Background: Clear Cell Sarcoma Gastrointestinal Tumour (CCSGIT) is a rare malignant soft tissue sarcoma which is exceptionally localized in the caecum. Due to its nonspecific symptoms the diagnosis is often late and prognosis is poor. The definitive diagnosis requires a combination of morphological, immunohistochemical and molecular techniques, with positive S100 protein marker and negative for melanocytic markers. Genetic studies show EWSR1 rearrangements in all the cases. Surgical resection is the prior treatment, as neither radiotherapy nor chemotherapy appears to be effective, with average 2-year survival after thediagnosis.

Cases Summary: We present two patients, a 41 year-old male and a 36 years-old female, who presented with acute intestinal pain and obstruction, rectal bleeding and anaemia. Both of them underwent an urgent hemicolectomy. The presence of a S100 positive protein and ESWR1 rearrangements in immunochemical and molecular studies confirmed the CCSGIT diagnosis. Postoperative chemotherapy was administrated in both cases. Both patients required a second surgery: In the first patient the second surgery was required for resection of residual aortomesenteric metastatic nodes, and hepatic metastases on the second patient. Both patients died, 4 and 12 months respectively after surgical treatment.

Conclusion: CCSGIT is a distinctive soft tissue sarcoma with nonspecific gastrointestinal symptoms, late diagnosis and poor prognosis. It mainly affects young adults and the incidence of metastatic disease at the time of diagnosis is high. Its diagnosis is based on the presence of positive S100 protein and EWSR1 gene rearrangements. The Melan A, HMB-45 and C-kit are negatives. Early diagnostic and therapeutic strategies are required to provide the best clinical care leading to long-term survival. These reported cases describe two CCSGITs of primary caecum origin; which can contribute to the development of future targeted therapies as well as offering epidemiological evidence on prevalence and prognosis.

Keywords

Caecum, C-kit, Clear cell sarcoma, EESR1 genetic rearrangements, HMB-45, Malignant gastrointestinal sarcoma, Melan A, surgical treatment, S100 protein

gCore tip: Clear cell sarcoma of gastrointestinal tract is a very rare and infrequent tumour. Classically, it can be confused with other similar tumours such as melanocytic tumours, neuroectodermaltumours and gastrointestinal stromal tumours (GIST). Their immunohistochemical characteristics are based on the presence of a positive S100 protein and negative markers for HMB-45, Melan A and GIST (CD117, DOD-1 and CD34). Other important characteristics for the diagnosis of this tumour are positive EWSR1 gene rearrangements by FISH technique studies. Frequently, the CCSGITs affect children and young adults. They are highly aggressive tumours that commonly reoccur with widespread metastatic nodal and visceral disease, even after treatment. The most frequent intestinal locations are the stomach or small bowel. Colonic location and specifically the caecum is rarely described in the literature. Nowadays the only treatment is surgical resection. However, the prognostic is bad and the overall global survival at 3 years is very low. In the future, it is possible that new targeted therapies would offer a possible better prognostic for patients with this rare sarcoma disease.

Introduction

Clear Cell Sarcoma of Gastrointestinal Tumour (CCSGIT) is a rare malignant neoplasm that originates in the wall of the stomach, small intestine or large bowel. This type of tumour is more frequent in paediatric ages and young adults, and was first described in subcutaneous tissue, tendons and aponeurosis [1-4]. In 1993, Ekfors et al. reported the first case of primary gastrointestinal CCS arising in the duodenum tract4. As of today only about 40 cases have been reported and most of these originated in the stomach and small bowel. Exceptionally, only four cases have been described in primary colon origin [5-8]. In this report we present two cases of CCSGIT originated in the ascendant colon (caecum), with an exceptional clinical occlusive presentation. We carried out a literature review with special emphasis on all diagnostic and therapeutic considerations.

Case Reports

Between 2015 and 2020 two patients, a 36 year-old female and a 41 year-old male, presented clinical signs of intestinal obstruction. Both showed abdominal pain and distension, history of rectal bleeding and anaemia. In both of them the abdominal CT scan revealed the presence of a tumour located in the caecum, with infiltration of surrounding fat and thickening of the adjacent peritoneum (fig 1). The CT also detected multiple suspicious metastatic mesenteric nodes that showed pathological uptake in the PET-CT that confirmed peritumoral nodal spread (fig 2). The colonoscopy identified a neoformative process in the caecum and the biopsy was positive for malignant tumour cells with eosinophillic cytoplasm and eccentric nucleus (rabdoid phenotype). Tumour cells were positive for vimentin, keratin AE1/AE3, EMA and S100 protein and negative for keratin CAM 5.2, Melan A, HMB 45, CD45 and DOG-1. A right hemicolectomy with regional lymphadenectomy was performed and reconstruction of the intestine with an ileocolic anastomosis.

CST-5-1-507-g001

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Definitive histopathological studies showed in both cases a caecum tumour with infiltration of the wall and mucosa ulceration with affection of the muscularispropia layer and the adjacent adipose tissue. The tumour showed extensive vascular and perineural invasion nests with pseudopapillary focal pattern with a predominance of epithelial cells (with fusiform areas) with eosinophilic cytoplasm that clearly rejected the periphery with prominent nucleoli compatible with a clear cell sarcoma (fig 3). Immunohistochemical studies were positive for S100 protein, CD68 and vimentin and weakly for cytokeratin CAM 5.2, LCA8CD45), DOG-1, C-kit, chromogranin, alpha-actin, desmin, HMB-45, Melan A and myeloperoxidase (fig 4). The study of gene rearrangements by FISH technique was positive for EWSR1 gene in both patients and confirming the diagnosis of Clear Cell Sarcoma (CCS) tumour. The first patient underwent adjuvant chemotherapy treatment with 5 cycles of Adriamycin 75mg/m2 with partial response and persistence of metastatic lymph nodes. Finally, resource surgery with extended mesenteric and paraaortic lymphadenectomy was performed. The new pathological study confirmed extensive residual nodal involvement with the same initial diagnosis of CCS. In the second male patient liver metastases were detected in sequential postoperative CTs and a posterior partial hepatic surgical resection was done. Both patients developed important extensive ganglion and diffuse metastatic disease and died eight and twelve months after surgery.

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Discussion

Clear Cell Sarcoma of Gastrointestinal Tract (CCSGIT) is a very infrequent tumour and until 2015 only 40 reports had been published. However only 16 of this reports described tumours that corresponded with the accepted morphological, structural and immunochemical features of a CCSGIT. The most common localization is the small bowel; the stomach and the colon are more rarely affected [1-6]. CCS is more frequent in paediatric and young to middle age adults with reported median age of 40 years (from 17 to 77) [5,6]. There seems to be an equal distribution between the sexes. The most common signs and symptoms are similar to those attributed to gastrointestinal tumours: abdominal pain, intestinal distension or obstruction, gastrointestinal bleeding and anaemia. The unspecific clinical presentation and consequent delayed diagnosis play a key role in the definitive prognosis [5-10].

This rare tumour is a source of diagnostic dilemma as it shows features of melanocytic differentiation. The main diagnosis technique for accurate diagnosis is based on its histology and immunohistochemistry, but these approaches do not distinguish between malignant melanoma and CCSGIT. CCSGIT has a histological appearance that is strikingly similar to metastatic melanoma, and also needs to be differentiated from Gastrointestinal Stromal Tumours (GIST) and poorly differentiated papillary adenocarcinoma. The tumour cells of CCSGIT are predominantly epitheloid with oval or round nuclei and a variable amount of eosinophillic or clear cytoplasm, as observed in our patients, but a case featuring oncocytic cytoplasm has been reported [10]. The nuclei display an irregular nuclear contour. Nucleoli are inconspicuous but occasionally prominent and basophilic. Necrosis and surface ulceration can be seen. Osteoclast-like multinucleated giant cells are a frequent and consistent finding. Metastatic tumours resemble the primary tumour morphological features, including the presence of osteoclast-like multinucleated giant cells. All the metastatic nodes in our patient with the extended lymphadenectomy showed the same histopathology as the primary tumour.

From an immunohistochemical point of view, it is well accepted that CCSGITs are characterized by strong and diffuse staining for the S100 protein. In addition these tumours tend to lack melanocytic specific markers including HMB-45, Melan A, Thyrosinase and macrophtalmic associate transciptor factor (MITF) [8] and they do not express GIST markers (CD117,DOG1 and CD34) [4]. Another important finding is that the EWSR1 gene rearrangements are present in CCSGITs. Antonescu et al team studied three cases of CCSGI and claimed to be the first to describe a recurrent translocation of EWS (22q12) and CREB1(2q32.3) resulting in EWS-CREB1 fusion: they concluded that these cases may present a gastrointestinal neuroectodermaltumour that expresses neuroectodermal markers and a lack of melanocytic differentiation. However, the existence of rare cases of CCSGIT with EWS-ATF-1 gene fusion that also lack melanocytic differentiation supports the theory of a common histogenesis between the two tumours [6, 11]. In our two patients the tumours were positive for S100 protein and expressed some neuroectodermal markers but lacked melanocytic differentiation. The study of gene rearrangements by FISCH technique was positive for EWSR1 gene in both patients.

In terms of treatment, surgical excision is the main therapeutic and curative approach. However, in the majority of the series, more than 30% patients presented metastatic disease at diagnosis. The adjuvant chemotherapy and/or radiotherapy do not contribute therapeutic benefits. The majority of the patients died before 2 years after diagnosis.

Conclusion

In summary, CCSGIT is a rare tissue tumour, which usually affects tendons and aponeurosis of soft tissues. Very few cases reported this tumour in the gastrointestinal tract (CCSGIT). Among them the caecum is an exceptional localisation. CCSGI is considered an aggressive malignant neoplasm with unfavourable prognosis and most patients die within two years from the diagnosis. Clinical manifestations are very unspecific, such as abdominal pain, acute intestinal obstruction, digestive haemorrhage and anaemia, which delay diagnosis and treatment. The definitive diagnosis is based on immunohistochemicqal and genetic techniques. These studies present a positive S1200 protein with negative melanocytic or GIST markers. The EWSR1 rearrangement gene is observed in all cases. In addition, this is an aggressive sarcoma tumour and has poor prognosis. Surgical resection is the only possible curative treatment, specially if indicated early. In all of these cases the discussion of therapeutic strategies in a multidisciplinary sarcoma committee is necessary.

Acknowledgements

We would like to thank the patients for allowing their cases to be reported.

Competing Interests

The authors certify that there is no conflict of interest with any financial organisation regarding the material discussed in this paper.

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