Role of Gatekeepers in Suicide Prevention During COVID-19 Pandemic - Juniper Publishers

 Addiction & Rehabilitation Medicine - Juniper Publishers

Abstract

Keywords: COVID-19; Suicide; Mental health; Psychopathology; Gatekeepers

Abbreviations: WHO: World Health Organization; CNS: Central Nervous System; ACE-2 : Angiotensin-Converting Enzyme 2; CRH: Corticotropin Releasing Hormone; mTOR: Mammalian Target of Rapamycin

Introduction

Suicide is defined as death caused by injuring or harming oneself with intent to die and a suicide attempt is an injury or harm caused to self with intent to die but has not resulted in death [1]. Suicide and suicidal behaviors are influenced by multiple psycho-social and biological factors. Factors such as resilience, good social support are protective against suicide while lack of occupation, financial issues, ill health, poor social support are risk factors of suicide. Prevention of suicide is the need of the hour. Amidst the COVID-19 pandemic is a possible suicide and suicidal behavior increase that is being neglected at community level.

Burden of Suicide

World Health Organization (WHO) statistics show that globally more than 800,000 people die by suicide every year, that is, one death by suicide occurs every 40 seconds. For every completed suicide there are 10-20 suicidal attempts that are reported [2]. About 77% of all suicides occur in low and middle income countries [3]. In India, as per National Crime Records Bureau of India 1.53 lakh people have died by suicide in the year 2020 (vs 1.39 lakh in 2019). The most common form of suicide being death by hanging followed by death by consumption of poisons especially insecticides. Total rate of suicides nationwide is 11.3 [4,5]. Though global statistics collected by WHO shows that the rate of suicides have reduced between 2010 and 2019 in low-middle income countries, statistics from India does not reflect this [6].

Influence of COVID -19 pandemic on suicide and suicidal behavior

Suicide and self-harm behavior are influenced by multiple psychological, social and illness aspects and reflects the severity of the mental health crisis and illness in a given community. COVID-19 infection has impacted the psychological, social and physical health globally and thus self-harm and suicide behavior as well. A study in Nepal has shown that suicide rates were higher during lockdown than immediate post lockdown period and same time period of pre-COVID years. Delay in arrival to hospital, admissions and in hospital deaths due to self-harm were also higher during lockdown [7]. Indian study compiled from news reports and social media showed that more than half of them were tested positive for COVID-19, about one-third was in institute setting and that the most common mode of suicide was by hanging followed by fall from height.

Nearly two-thirds of the patients had contacted a physician within 2 weeks prior to their self-harm. More than 80% of the people who completed suicide did not have pre-existing psychiatric or physical co-morbidities [8]. This may indicate that COVID-19 pandemic and its effect on psychological health and social factors may be an independent risk factors for suicide. Comparing pre-COVID data with the current data shows that depressive illness has increased two to three fold than before. Anxiety and stress levels in the general population have also increased significantly [9-11]. As 90% of people who have completed suicide have a pre-existing psychiatric diagnosis [12], increase in psychiatric illness can lead to increase in suicidal behavior.

Psychosocial factors influencing suicidal behavior during COVID-19 pandemic

Studies have shown that stressors related to COVID-19 infections such as fear of infection, increased vigilance about changes in body and wrongly attributing it to COVID-19 infection, deterioration of physical health due to COVID-19 infection, reduced social support and caregiver ability have impacted the mental health of the people [13]. People who follow COVID-19 related news closely are more prone to develop anxiety as most of the news is distressing and emphasizes the infectivity of the virus and its associated morbidity and mortality. Rumors, fabrications and misinformation on social media also contribute to the rising anxiety levels and exacerbate depressive symptoms [14-16]. Isolation due to lockdowns, work from home and infection can cause loneliness, helplessness and stress. Physical isolation with social and emotional closeness by using social networks and virtual platforms can be a protective factor [17].

Pathogenesis of psychopathology associated with COVID-19 infection

COVID-19 or SARS CoV 2 2019 is well known for its entry through mucosal surfaces and its effect on respiratory system, morbidity and mortality associated with the same. However, lesser-known fact is that SARS Cov-2 infection and associated immune response affects multiple organs and organ systems of the body; one such system being the Central Nervous System (CNS). SARS CoV-2 virus enters the epithelial cells via angiotensin-converting enzyme 2 (ACE-2) receptors. This in turn leads to down-regulation of ACE-2 receptors expression. In animal studies down-regulation of ACE-2 expression has resulted in increased sympathetic activity, reduced tryptophan uptake and production of serotonin; thus, compromising the body’s ability to respond to stress and hence increasing the individual’s susceptibility to depression and anxiety.

ACE-2 receptors in hypothalamus suppress fear responses, anxiety and its related behavior as well as Corticotropin releasing hormone (CRH) which plays an important role in response to physiological stress. ACE-2 receptor down-regulation hampers negative feedback mechanism of glucocorticoids in reducing excessive inflammation. Therefore, in SARS CoV 2 infection an excessive and dynamic inflammation is observed. SARS CoV 2 virus has the ability of infecting all tissue having the ACE-2 receptor including the brain tissue. Hence, direct infection and increased immune response both play a role in pathogenesis of psychiatric illnesses associated with COVID-19 illness. This can be prevented by preformed antibodies occupying the ACE-2 receptors in the brain thus preventing entry of the virus into the neuronal cells. Hence, ACE-2 receptor modulator drugs may have a role in treatment of COVID-19 infection and prevention of psychiatric complications [13].

Though rennin angiotensin aldosterone system plays a role in pathogenesis of stress related depression and anxiety, it is minimal. Bradykinin and mammalian target of rapamycin (mTOR) play a major role in depression and effect of COVID-19 infection on them is not known [13]. Inflammatory mechanisms activated by SARS CoV 2 virus increase inflammatory cytokines such as TNF-A, Interleukin 6 and Interferons in both peripheral and central tissues leading to cell apoptosis. This leads to increased risk of developing mood disorders, anxiety and psychosis. Hence, augmenting anti-depressant or anti-psychotic drugs with immunomodulatory drugs or anti-inflammatory drugs are more beneficial than anti-depressant or anti-psychotic drug treatment alone [13]. Effect of COVID-19 pandemic on pre-existing psychiatric illness and access to mental health care services.

The COVID-19 pandemic, precautionary measures implemented to limit its spread and burden on the health care services due to infection had a major impact on non-pandemic related illnesses and treatment for the same. Restrictions in movement, transport, burden on health care infrastructure made accessing health care services in timely manner difficult globally [18,19]. This has also had an effect on the help seeking attitude and availability of services for people with pre-existing mental illnesses. Re-allocation of all available services in health care services including mental health care professionals to tackle the burden of COVID pandemic may have resulted in lack of timely professional help for people with mental illnesses [20]. As psychiatric facilities were found to be a high risk area of spread of COVID-19 infection, community based or home based treatment through telepsychiatry, psychological support and home delivery of the medications would have been recommended and ideal.

However, due to sudden and unexpected impact of the pandemic mental health services were not equipped to handle this crisis [20]. Study comparing people with pre-existing psychiatric illnesses and those without showed that people with psychiatric illnesses had significantly higher depression, anxiety, stress, PTSD like symptoms, anger, impulsivity and suicidal ideation [21]. Lack of access to mental health care services and medications could have resulted in untreated mental illnesses and above findings. This results in impaired ability of the individuals to cope with stress and in turn cause increase in suicidal ideation and attempts.

Bridging the gap…Gatekeeper?

In India, there exists a huge gap between the requirement of mental health services and the personnel who are trained to provide adequate services. The National Mental Health Survey of 2015-2016 shows that lifetime risk of psychiatric illness is 13.67% and point prevalence was 11.56%. But the available mental health professionals were 0.3 per 100,000 population for psychiatrists, 0.07 per 100,000 population for clinical psychologists and 0.12 for mental health nursing staff [22]. To meet the minimum mental health needs of the population of India there should be 3 psychiatrists per 100,000 populations and for optimum care or in an ideal situation 6 psychiatrists per 100,000 populations. Keeping attrition rate of psychiatrists to 0%, approximately 2700 new psychiatrists need to be trained annually the next 10 years to meet the demands of our country [23].

However, as of 2021-2022 academic year approximately 1200 Post-graduate students are being trained as psychiatrists throughout the country, which is less than half the required numbers [24]. COVID pandemic has also increased the risk factors for suicide thus increasing the need for mental health services in prevention of suicide. Gatekeepers can help in bridging this gap. Gatekeeper refers to people who have primary contact with individuals at risk for suicide, and who can identify such individuals by recognizing suicidal risk factors and refer to a professional. Gatekeeper training refers to training individuals to identify risk factors for suicide among people and refer for appropriate help [25]. Gatekeeper could be teachers, family members, supervisors, religious leaders, faith healers, physicians, police, colleagues and friends. Most of them are however not aware of the signs that people who have risk of suicide exhibit and hence are unable to identify and provide timely health.

Most of the people in the community, especially the youth are hesitant approaching mental health professionals for help for suicide due to stigma attached with suicide and lack of awareness of avenues of help available and fear of being judged. Often times when they approach lay people for help with suicidal ideation, their concerns are trivialized or ignored (probably due to ignorance and their own discomfort regarding suicide) making them hesitant to reach out for help again. Gatekeeper training is a strategy designed to improve early identification of individuals at high risk for suicide and to facilitate timely mental health referrals, responding to the fact that suicidal youth are under-identified and few are using these services.

Identifying people who have contact with population at large and adequate training to recognize and provide first aid for people with risk of suicide before professional help is available becomes important. Educational institutes (like schools, colleges and universities) and workplaces should have a crisis management team who have had gatekeeper training from professionals. Crisis team should include people from the administration and employees who are willing to undergo gatekeeper training and help in suicide prevention.

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Analysis of the Hydrogeological Processes formation Condition in the Baku City Zone and Evaluation of the Subsoil Waters Suitability for Verdures Irrigation for Using - Juniper Publishers

 Annals of Reviews and Research - Juniper Publishers

Abstract

The article is dedicated to the analysis of the hydrogeological process’s formation condition in the Baku city zone and evaluation of the subsoil waters suitability for verdures irrigation. It was determined that a quality of the subsoil waters is suitable for the verdure irrigation in the central, eastern and western parts of the zone, but it is unfit in the northern, north-eastern and south-western parts - local areas of the region. The regionalization of the subsoil waters according to the suitableness degree for irrigation was performed in the Baku city and “A map of the schematic regionalization according to the suitableness degree of the subsoil waters the verdures irrigation in the Baku city” was compiled.

Keywords: Hydrogeological condition; Geological system; Regime; Underground water; Urbanization; Stratigraphic floors; Mineralization; Rocks

Introduction

Lately, a special attention is paid to the renovation and greenery measures realization in Baku and Absheron. That’s why a large usage of the available water-collecting and new water-collecting construction are intended in Baku. An investigation of the hydrogeological process formation legitimaies, research of the watery horizons waterness and various aims, including an evaluation of the subsoil waters quality for verdures watering are a problem actuality. The underground hydrosphere in Baku was adopted as a research object. An aim of the research consists of hydrogeological processes formation condition analysis and an evaluation of the subsoil waters fitness for the verdures watering. The complex research method was used: the materials analysis on geomorphological, tectonic, geological structure and natural condition which set a subsoil water regime; hydrodynamic and hydro chemical methods determining a condition of the hydrogeological processes formation; theoretic methods for a quality assessment of the subsoil waters quality with the purpose of irrigation. There is a great practical importance of the problem that finds its solution in the article. So, definition of the subsoil waters regime forming condition permits to evaluate a modern hydrogeological condition, but the subsoil waters quality assessment gives a chance to fix these waters-use directions.

Analysis and Discussion

An area of the Absheron peninsula is 2000 km2, it is situated in the eastern part of the Azerbaijan Republic. The peninsula was surrounded by the Caspian Sea in the north, east and southern parts, but by the Gobustan foothill plain from west. Gardening and orcharding developed, besides being the largest center of the oil-gas refining and extracting enterprises here. The main living places are Baku, Sum-gait, Khirdalan, Shuvalan, Lokbatan, Sahil, Alat and others. The living points commu-nicate with each over by electricity, railways and automobile roads. Baku a capital of the republic is situated in the Baku bay coast which is one of the natural gulfs in the Caspian Sea. Baku is port city with the international and sandy beaches. It is possible to go aboard ship to the Atlantic and Arctic oceans from here. The sunny shores and sandy beaches are a great importance as a health resort, tourism and rest zone. Azerbaijan is famous with its oil and gas deposits since ancient.

The oil and gas deposits are in the Absheron peninsula, zone of the Caspian Sea, Baku and Absheron archipelagos. The Jeyranbatan reservoir plays a great role in water-supply of the industrial enterprises and population in the Absheron peninsula and irrigation of the sowing areas in the Absheron gardens. Its area is nealy 14 km². The water-source is provided by the Samur-Absheron canal. The subsoil waters in the Baku city spread in all the stratigraphic stage deposits. The subsoil water flow possesses a single circular flow in the sea direction [1]. Presence of Balakhani-Sabunchu-Ramani, Surakhani and Garachukhur-Zig anti-clinals in the eastern part of the city makes a condition for the subsoil water flow form change. The subsoil waters flow spreads in all the directions of these structures as a circular form. The hydro relief inclination is changeable in the city zone. The inclination changes by 0,01-0,1 in the west and east; 0,06-0,01 in the north; 0,014-0,1 in the south. It changes by 0,003-0,08 in Keshla [2].

Some natural and artificial factors participate in the subsoil waters formation in Baku.

The geological-geomorphological factors from the natural ones are considered important in formation and circulation of the subsoil waters. The deposits of the fourth period spread widely in Baku and they are investigated in the different depths. Having a high water-conductivity of these deposits is a great importance in formation of the subsoil waters-supply. So, a water-penetrating coefficient of the water-holding rocks changes by 0,1-25,9m/day [3]. It is known that the zone relief has an important role in creation of the subsoil waters. From this point of view, the ravines, hollows and holds make a good condition for the subsoil waters collection, such relief forms spread widely in Baku. There are stone-quarries of the anthropogenic, old stone, clay and limestones, besides the natural relief forms in the Baku amphitheatre surface, they are filled with water flows: subsoil waters or industrial waste waters in many places. Such quarries are mainly observed in the Alatava area. There are large ancient and modern ravines in the Baku city zone, one of them is in the Yasamal valley consisting of undeveloped and gorges, valleys, the other is strong developed Bibi-Heybat ravine in Patamdar settlement.

The researches show that many parts of the yearly rainfall quantity fall in the autumn-winter period, and this displays itself with the gravitation moisture presence in the aeration zones of the ditches, ravines and other areas with the good micro-relief. The climate factors determine quantity and quality indications of the subsoil waters creating to an important degree. 227 m (on average) atmospheric precipitations, 947-1344 mm evaporation is observed in the zone for a year. An average yearly mineralization degree of the atmospheric precipitations is 102 mg/l. 184,8 kg/hectare salt enter the land surface a year (12,9% of it is NaCl). The water evaporations condensation role isn’t little in the subsoil waters formation. As is known, the condensation waters feed the subsoil waters in the places with the good condition for the water evaporation condensation (in the places with the air’s high relative humidity, little bed depth of subsoil waters, the air temperature change in the large diapason). There is abovementioned suitable condition for the water evaporations condensation in the Baku city.

The research show that the condensation happens over all the density of the aeration zone and subsoil water surface from October to April. The highest value of condensation is observed in the sand, but the less value is in the clay. While rising salinity of the soils and subsoil waters, including humidity shortage, the condensation process intensity gets increased, too. The hydrological factors influence the underground waters discharge. However, a base of this process is the Caspian Sea’s level change (falling and rising). Since 1978 the subsoil waters level has risen 0,4 -1,3m as a result of the sea level rising constantly (2,5m) (according to the hydrogeological observations results per-formed in the regime-observation net). The sea level rising damaged the Republic economy. So, the oilfields, oilwells, pump stations remained under water. All the objects, dwelling and administrative houses’ cellars exposed to the flooding process in connection with the water level rising in the Caspian Sea. An impact of the subsoil waters on feeding of some salty lakes spreading in the peninsula and Baku city isn’t little.

It should be noted that Baku city and Absheron peninsula concern the arid climatic zone, the quick development of the desertification process caused superiority of the artificial factors impact in subsoil waters feeding at present, while the underground waters regime is formed under the climate factors influence [4]. The water from the artificial factors and infiltration from the waters used for the verdures watering possess an important role in subsoil waters feeding. An analysis of the balance table of the subsoil waters in Baku permits to come to such a conclusion that a main role in subsoil waters feeding belongs to the artificial factors. So, 91,4% of the income part from the subsoil water balance is connected with the artificial factors (filtering from 63,2% - water nets; flow from 23,5% - sewerage waters; infiltration from atmospheric irrigative waters); 8,6% is connected with the natural factors (infiltration from atmospheric precipitations and feeding at the expense of condensation waters).

We should note that the rocks of the subsoil water horizon are very watery. During the water-drawing the wells expenditure was registered by 0,2-5,9l/s. The highest waterness is observed in Yasamal. Its reason is explained by the Ganli Lake impact. A special expenditure of the wells is 0,02-0,3l/s∙m. The wells expenditure in the central parts of the city is 0,2-5,0l/s, a special expenditure 0,02-0,3l/s∙m [5]. It was determined that a mineralization degree of the subsoil waters is 1-2g/l in the central part of Baku. Exception the city, west border, all the foreign borders are surrounded by the subsoil waters with 10-20g/l and more mineralization. This is related to the Boyukshor Lake effect. A chemical composition of the waters is Cl-Na, Cl-SO₄-Na-Mg, SO₄-HCO₃-Cl-Na-Ca-Mg. Exception this compostion, all the possible combinations of ions are found. The subsoil waters with the weak mineralization surround a great area of Baku [6].

The area which is surrounded by the verdures in the city zone is 3500 hectares. An ancient primary plant cover:Eldar-pine, olive, plane, fig, apple, quince, cherry, mulberry trees.

The experiment shows that a quality of the irrigated waters for the verdures watering depends on their turbidity, mineralization degree, chemical composition and temperature. So, a temperature of the irrigated waters must be 15-300C; pH index-6,5-8,0; mineralization degree - 1,0-1,5g/l. While a mineralization degree is more than the presented norm the irrigation process should be fulfilled with the measure which prevents a danger of the soil’s salinity (for ex. gypsum must be given into the soil). We should note that exception a mineralization degree of the irrigated waters, their chemical composition must be absolutely taken into account. So, the most harmful salts in the irrigated waters composition are considered soda (Na₂CO₃), NaCl and Na₂SO₄. A quantity of these salts in the soils having a good water con-ductivity shouldn’t pass over the following limit: soda (Na₂CO₃)<0,1%; NaCl<0,2%; Na₂SO₄<0,5% [7]. At the same time the soil solonetz negatively influences the verdures develop-ment. So, hardening of the place which in the plant root is situated in the solonets soils and structure disorder limit the soils fertility, and this is a reason for the plant perishing.

The experiment displays that Na ion absorbed by the soil is mainly a reason for the hardened soil layer formation. The soil has an absorbing and holding ability of various substances which are in contact with the soil (gas, salt, cation and anions). But the absorbed ions aren’t washed by the water, they are kept in the soil. The soil possessing an absorbing ability can absorb Ca, Mg, Na and H ions to a Definity quantity from the soil solution and can be changed with each other to an equivalent number. Taking into account a natural condition good for the soils salinization and solonetzification, i.e. concerning the Baku city zone the arid climate, the irrigated waters quality was evaluated by the zone definition method of the Na-n relative potential adsorption and it was defined that the subsoil waters are fit for irrigation in the central, eastern and western parts of the zone. So, usage of the subsoil waters in the presented areas for irrigation doesn’t create a danger for the soil salinization and solonetzification. Unfitness of the subsoil waters quality in the local areas for irrigation has been investigated in the northern, north-eastern and south-western parts (the soil salinezation and solonetzification is inevitable). So, regionalization was performed according to fitness degree of the subsoil waters for irrigation in the Baku zone and “Schematic regionalization map according to the fitness degree of the subsoil waters for verdures watering in the Baku city” was compiled (Figure 1).

Conclusion

The natural and artificial factors participate in subsoil waters feeding in Baku and a main role belongs to the artificial factors at present while occurring the subsoil waters feeding at the expense of the natural factors for long years. The subsoil waters can be used for watering of the gardens, verdures in the city in future. A quality of the subsoil waters is unfit for irrigation only in the local areas.

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A Crisis and an Opportunity Facing Genetics - Juniper Publishers

 Cell Science & Molecular Biology - Juniper Publishers

Abstract

There are a number of unusual behavioral tendencies amongst humans which appear to challenge the plausibility of a DNA basis. Some of these behaviors show up in the intellectual realm; others show up in the realm of gender orientations; and still others show up in the form of apparent paranormal abilities. Together these challenges - two from the accepted literature and the other from the paranormal literature - will be touched on here. The associated challenges form a concise statement of the excessive expectations placed on DNA. These challenges resonate with the missing heritability crisis and also an associated opportunity to appreciate life’s mysteries.

Introduction

Malaria

In order for biology to make materialist sense DNA has to be able to perform its wide-ranging heritability duties. Some people have questioned the evolutionary inheritance role, in particular whether it is plausible in a physics only sense. In this way some have posited the need for additional input to steer the evolutionary dynamics of DNA [1]. Others have suggested a need for informational fields to steer the output of DNA in order to form living systems, positing that DNA can deliver the requisite ingredients, but that it cannot carry out the requisite organizational tasks [2]. In both of these cases DNA is suggested to need some nonmaterial assistance.

The point of this Mini Review is to focus on the challenges associated with some particular innate human behaviors. There really are a number of extraordinary behavioral tendencies which seriously challenge the feasibility of a DNA basis. The suggested implausibility of such DNA behavioral specifications would be consistent with the larger frustrations encountered in behavioral genetics and more generally in the missing heritability problem. Some extraordinary innate behaviors could then provide their own arguments for DNA’s incomplete inheritance functioning.

Previous work by the author has considered the missing heritability problem, and more particularly behavioral genetics, and suggested that the premodern reincarnation paradigm could help explain some of the DNA deficit [3,4]. A follow up effort then specifically looked at the associated challenge of explaining mental illnesses/difficulties [5].

It will be assumed herein that the reader is familiar with the big expectations associated with DNA (i.e., in particular that we are simply “DNA driven biological machines” [6]) and also the missing heritability problem. This is simply a brief look at some remarkable behaviors and the challenges they pose for biology’s vision, along with a little follow up reflection. For brevity’s sake the referencing here is minimal.

Discussion

Behavioral Challenges

There are a number of accepted behavioral conundrums that are hard to explain within the modern vision of life [3,4]. Whether in the form of prodigies who appear to show up in adult focused and sometimes even learned ways, or in the form of transgender kids who appear to show up with the opposite sex’s agenda and as observed through extensive testing, “trans girls see themselves as girls and trans boys see themselves as boys, suggesting transgender identities are held at lower levels of conscious awareness” [7]. Such behave iors appear to form neglected challenges to biology’s understanding.

One example I have been struck by is the memory capacities associated with hyperthymesia syndrome. A nice presentation of that syndrome is given in a Scientific American article, “Remembrance of All Things Past” [8]. Therein discussions considered about 50 people who were observed in their capacities to effortlessly recall the events of their life in a dated and day-of-the-week fashion. They could also recall significant worldly events that fell on the specified date. One woman, Jill Price, during questioning for example:

correctly recalled that Bing Crosby died at a golf course in Spain on October 14, 1977. When asked how she knew, she replied that when she was 11 years old, she heard the announcement of Crosby’s death over the car radio when her mother was driving her to a soccer game.

Simply the ability to recall the day of the week for a specified date is amazing. Another DNA challenge shows up in the prodigy realm. In previous writing I have described a modern prodigy’s apparently untrained inclination to play the cello and also to compose music.

Here I consider a somewhat more one-of-the-mill prodigy, a Russian pianist named Evgeny “Zhenya” Kissin [9]. Kissin’s mother and father were respectively a piano teacher and an engineer, and they were living what might be characterized as Soviet Jewish Intelligentsia in Moscow. They had initially assumed that Evgeny’s sister, Alla, would follow her mom and play the piano, whilst Evgeny would follow his dad and go into engineering. At eleven months, though, the boy managed to sing an entire Bach fugue after hearing Alla practice it. Thereafter Evgeny pursued singing in response to just about “everything he heard”. This was so relentless that his mother became quite concerned.

Then at twenty-six months Evgeny made his appearance at the piano. He:

sat down at the piano and with one finger picked out some of the tunes he had been singing. The next day he did the same, and on the third day he played with both hands, using all of his fingers. He would listen to LPs and immediately play back the music. “Chopin’s ballades, he would play with those little hands, and Beethoven sonatas, Liszt’s rhapsodies,” [his mom reported]. At three, he began improvising. He especially liked to make musical portraits of people [9].

He liked to quiz the family on his portraits.

Kissin demonstrated exceptional skills very early and this eventually led his reluctant mother to take him to a prominent piano teacher at the famous Gnessin State Musical College in Moscow. There at age 5, that teacher Anna Pavlovna Kantor would later report:

I saw a light in him. Without knowing how to read music or the name of notes, he played everything. I asked him to translate a story into music. I said we were coming into a dark forest, full of wild animals, very scary, and then step by step the sun rises, and the birds start singing. He began in the piano’s lower register, in a dark and dangerous place, and then, lighter and lighter, the birds awaken ing, the first rays of the sun, and finally a delightful, almost ecstatic melody, his hands running along the keys. I didn’t want to teach him. Such imagination can be very fragile [9].

At age 7 Evgeny Kissin began to write down his compositions. He would later state that, “[w]hen I would return from school, I would, without taking my coat off, go to the piano and play”. He then added, “I made my mother understand that that this was just what I needed” [9].

Other remarkable prodigy descriptions are given in Andrew Solomon’s Far From the Tree, as well as Darold Treffert’s [10] Islands of Genius. Of note here is the apparent disconnect in some cases between prodigious child’s focus and their parental background. Also, of note is Treffert’s [10] conclusion that some of these kids seem to know things that they never learned. On that point I introduce the seeming parallel found with some transgender kids who can sometimes demonstrate ambitions that would seem foreign to their own experience. From a New York Times Magazine article [11] a description of a 3-year-old included:

He insisted on wearing gowns even after dress up time ended. He pretended to have long flowing hair and drew pictures of girls with elaborate gowns and flowing tresses. By age 4, he sometimes sobbed when he saw himself in the mirror wearing pants, saying he felt ugly.

A number of these cases are nicely covered in Solomon’s Far from the Tree and they leave you wondering how gender identification along with some associated ambitions are established.

I move now to briefly consider some paranormal behaviors. I do this to further consideration of life’s mysteries as well as for a bit of a protest of science’s prevailing lockout of such phenomena. I introduce this topic via some examples from the late Elizabeth L Mayer’s [12] excellent Extraordinary Knowing: Science, Skepticism, and the Inexplicable Powers of the Human Mind [12]. Her book resulted from her personal paradigm breaking investigations into paranormal abilities following some remarkable experiences involving mediums. Her detour into contacting mediums (her work background was as a prominent psychoanalyst with academic connections) began with her desperation to regain her daughter’s stolen harp. Following a tip from a friend she contacted a man in Arkansas who did work as a dowser. The initial response via phone with the man went as follows:

“Give me a second,” he said. “I’ll let you know if it is still in Oakland.” He paused, then: “Well, it is still there. Send me a street map of Oakland and I’ll locate the harp for you.” Skeptical but what, after all, did I have to lose? I promptly overnighted him a map. Two days later, he called back. “Well I go that harp located,” he said. “It’s in the second house on the right on D— street, just off L—Avenue” [12].

Mayer’s initial response was to find the house (neither street nor the general location were familiar to her) and then try get the police involved. The police, though, said they needed more to follow up with a search warrant. Elizabeth Mayer then decided to place rewards flyers in the two block area surrounding the house which had been identified by the dowser.

Three days later Mayer got a phone call from a stranger in the flyer posted zone claiming to have seen the harp in the possession his next-door neighbor. After a couple of weeks of frustrating phone follow up a meeting was finally arranged in which she could get back her daughter’s prized harp. This experience really rocked Mayer’s “rational” perspective and she concluded it “changes everything”. That conclusion is of course a stretch, but that experience fortified by some subsequent remarkable exchanges with some other mediums that she contacted provided a good introduction to some apparent paranormal abilities. It appears that at least for some individuals under some circumstances they can obtain information in physics challenging ways. As an interesting follow up note, Mayer later in her book adds some more extraordinary information provided by that Arkansas dowser.

In the larger scheme of things such abilities might not be significant, but they certainly suggest that human life can be home to some inexplicable cognitive abilities. In that regard, such abilities might overlap a little with phenomena found in the prodigious intellectual realm. I move along now to consider other phenomena considered by Mayer in Extraordinary Knowing, that involving the apparent ability to view scenes from afar. This phenomena, called remote viewing, conveniently found an almost academic home at Stanford Research Institute (SRI) in Menlo Park, California, not far from Mayer’s residence in the San Francisco area. The work at SRI had occurred through happenstance as an inquiry into a possible grant proposal from a physicist named Harold Puthoff somehow got sidetracked into the hands of a New York based artist named Ingo Swann. That inquiry about a pending proposal into possible “implications of quantum theory for life” somehow found Ingo Swann who in turn made a suggestion that SRI instead consider parapsychological phenomena. Swann mentioned some successful psychic demonstrations that he had been involved with.

Dr. Puthoff prompted in part by curiosity then invited Swann to visit SRI to demonstrate some of his claimed abilities. Thus during a week in June of 1972 Swann visited and the subsequent events as recalled by Puthoff included as follows:

“Prior to Swann’s visit I arranged for access to a well shielded magnetometer used in a quark detection experiment in the Physics Department at Stanford University. During our visit to this laboratory, sprung as a surprise to Swann, [we asked him] to perturb the operation of the magnetometer, located in a vault below the floor of the building and shielded by meatal shielding, and aluminum container, copper shielding and superconducting shield. To the astonishment of Stanford physics professor Dr. Arthur Hebard, whose experiments depended heavily on the magnetometer’s much vaunted imperturbability to outside influence, Swann doubled the rate at which the magnetic field in the magnetometer was decaying. Then in response to Hebard’s disbelieving subsequent request, Swann stopped the field change altogether for a period of roughly forty-five seconds. As if to add insult to injury, he then went on to “remote view” the interior of the apparatus … by drawing a reasonable facsimile of its rather complex (and heretofore unpublished) construction. It was this latter feat that impressed me perhaps better than the former [12]”.

The remote viewing of Ingo Swann sparked quite a bit of interest including ultimately the Central Intelligence Agency. With the latter’s interest as well as some of their funding SRI was able to carry out a series of remote viewing experiments.

The remote viewing work was significant in at least a couple of ways. It turned out to offer not only amazing phenomena (or “anything but ordinary and just blew [the scientist’] minds” [12]) but also some practical results. One remote viewing example was national security inspired and involved a recruit from the ranks of the U.S. Army Intelligence and Security Command, Joe McMoneagle. McMoneagle had been very successful in his military career and from his answers in a series of interviews was judged to have good remote viewing potential. As it turned out McMoneagle in his new intelligence career did indeed turn out “masses of data that were really hot and totally inexplicable by ordinary means” [12].

In one demonstration McMoneagle’s was given some coordinates in the Soviet Union. Those coordinates unbeknownst to McMoneagle was where an enormous building had been built and recently come to the attention of U.S. intelligence officials. McMoneagle’s:

immediate response was that [the coordinates] identified a very cold wasteland with an extremely large industrial looking building that had enormous smokestacks, not far from a sea capped with thick cap of ice. Later we found out the location was Severodvinsk on the White Sea. [12].

After seeing this initial success, the investigators then gave McMoneagle a surveillance photo of the big building and asked him to try to see inside the building. Here is a retrospective excerpt from McMoneagle:

I spent some time relaxing and emptying my mind. Then with my eyes closed, I imagined myself drifting down into the building, passing downwards through its roof. What I found was mind blowing. The building was easily the size of two or three huge shopping centers, all under a single roof …

In giant bays between the walls were what looked like cigars of different sizes, sitting in gigantic racks. … Thick mazes of scaffolding and interlocking steel pipes were everywhere. Within these were what appeared to be two huge cylinders being welded side to side, and I had an overwhelming sense that this was a submarine, a really big one, with two hulls [12].

The US intelligence community’s sense at the time was that the Soviets were building a new type of assault ship in the building. After describing some additional observations, McMoneagle added:

I did a detailed drawing of the submarine, adding dimensions, as well as noting the canted[/slanted] [ballistic missile] tubes, indicating eighteen to twenty in all [12].

Somehow McMoneagle even came up with an accurate January launch date for the submarine. The sub roughly fit Joe’s description, including the presence of twenty canted missile tubes. A look up on the internet offers corroboration on length 574 feet and also provides some insane details like the fact that each of the twenty missiles carried 10 independently targetable nuclear warheads. The name of this Soviet submarine model was Typhoon. A remarkable and seemingly sincere report of “Extraordinary Knowing” which could have had an impact in the foreign policy area.

Elizabeth Mayer goes into a number of the other SRI remote viewing cases and a recent book, An End to Upside Down Thinking, by Mark Gober [13] provides a few more. Gober’s [13] book includes one in which the remote viewer provided details on the kidnappers of Patrica Hurst. These remotely obtained details went from the generic picking out their mugshots and their motivation (political) down to one of the kidnapper’s recent crazy dental procedure involving the removal of his teeth sans anesthesia.

Of additional note here is that Gober’s later book also provided statements from declassified government assessments of SRI’s remote viewing investigations. In one of these documents a science panel consisting of Dr. Donald M. Kerr (Director of Los Alamos National Laboratory), Dr. Fred Zacharaison (physics professor at California Institute of Technology), and W. Ross Adey (Chief of Staff, Research Division, Veterans Administration Hospital) produced a “Principal Findings” document stating (in capital letters) that:

IMPLICATIONS ARE REVOLUTIONARY

MERITS CONTINUED FUNDING IN THE NATIONAL INTEREST

EVIDENCE TOO IMPRESSIVE TO DISMISS AS MERE COINCIDENCE

LACK OF PHYSICAL MODEL DOES NOT PRECLUDE EXISTENCE

INITIATE A FIVE-TO-TEN YEAR PROGRAM

INVOLVE ADDITIONAL LABS [13].

Other declassified assessments were provided in photocopied form. Another supportive conclusion came from the prominent physicist, Freeman Dyson, in the preface of Extraordinary Knowing. In it, Dyson wrote that “ESP is real but belongs to a mental universe that is too fluid and evanescent to fit within the rigid protocols of controlled scientific testing” [12].

Conclusion

Contrary to the contemporary scientific consensus, it really isn’t hard to seriously question scientific materialism. This is particularly true in the area of behavioral tendencies and also endowments. In Darold Treffert’s Islands of Genius he suggests that “[u]ntil we can fully explain the savant, we cannot fully explain ourselves nor comprehend our full capacities” [10]. His logic would seem to apply across quite a bit unusual behavioral phenomena. When coupled with the missing heritability problem I suggest here that argues for a need to reassess the contemporary understanding of ourselves beginning with its presumed genetic basis. One significant development might be expanding scientific horizons to incorporate challenging behaviors, including taboo ones.

For possible basic motivation I am reminded of a fine review of an E. O. Wilson book that I read in Scientific American several years ago. As is not uncommon in such books E. O. Wilson’s forward-looking book conjured up some optimism in its conclusions with regards to humanity’s unfolding sustainability and ecomanagement crises. The reviewer, though, would have none of it. That reviewer concluded humans’ beings will not make significant sacrifices for future people. This reviewer presumably based their conclusion on a materialist evolutionary perspective of humans. Broader investigations of human beings, though, might find reasons for a deeper or dualistic perspective. With such a perspective, in particular one in which a soul tends to reincarnate or return, the logic of life, if you will, could be different. Somewhat consistent with this in Michale Tobias’ man versus nature epic, World War III, the group identified for their encouraging sustainability priorities were the lay Jains.

If the missing heritability problem continues to hold, then that would undercut the modern certainty that underneath it all is simply physics. It is perhaps noteworthy that such a failure would appear to be consistent with the suggestion offered by the Nobel laureate physicist Eugene Wigner [14] about the possibility of a contradiction between the “laws of heredity and of physics” [14].

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Effect of Prolonged GnRH Agonist Therapy Prior to Frozen Embryo Transfer on IVF-ET Outcome in Patients with and without Endometrioma Surgery - Juniper Publishers

 Global Journal of Reproductive Medicine - Juniper Publishers

Abstract

Objective: It remains to be clarified whether prolonged Gonadotrophin-Releasing Hormone agonist (GnRHa) administration before frozen embryo transfer to patients with and without endometrioma resection improves reproductive outcome. This study was designed to investigate freeze-all cycles with subsequent prolonged GnRHa administration in patients with and without endometrioma surgery.

Method: A total of 164 patients with complaints of infertility and diagnosed with endometrioma were included in this case controlled study. Endometrioma resection was performed in 65 out of 164 women and then Controlled Ovarian Stimulation (COS) was performed (Group 1). Fresh embryos were transferred to 40 of 65 patients who underwent endometrioma surgery. Embryos were vitrified in 25 patients and administered leuprolide acetate 3.75 mg for 3 months. The remaining 99 patients were referred directly to the COS without any surgery for endometrioma (Group 2). While fresh-ET was applied to 49 of 99 cases, embryos were frozen in the remaining 50 cases. Subsequently they were administered leuprolide acetate 3.75 mg for 3 months. Primary outcome was Clinical Pregnacy Rates (CPR), Ongoing Pregnancy Rates (OPR), and Live Birth Rates (LBR).

Results: No significant difference was found between the operated and non- operated groups in terms of CPR, OPR and LBR between patients who received fresh-ET. While there was no significant difference in CPR and OPR in operated and non-operated groups who underwent frozen-ET, LBRs were found to be significantly higher in patients who were not operated (p<0.01). Making fresh-ET or frozen-ET in patients who underwent endometrioma surgery did not significantly affect CPR, OPR and LBR. Making frozen-ET in patients who did not undergo surgery significantly increased both CPR (p <0.02) and OPR (p<0.03).

Conclusion: Prolonged use of GnRH agonist treatment before frozen-ET in patients without endometrioma surgery resulted in significantly higher clinical and ongoing pregnancy rates than did patients with endometrioma surgery.

Keywords: Endometrioma; Endometrioma surgery; GnRH agonist; Reproductive outcome

Introduction

The hypothalamic Gonadotropin-Releasing Hormone (GnRH) is a decapeptide that plays an important role in the regulation of reproductive functions. In addition to pituitary expression GnRH/GnRH receptor (GnRHR) system was found to be expressed in extrapituitary regions such as endometrium and ovary [1,2]. GnRHR expressed in granulosa and luteal cells plays a role in follicle development and growth [2]. At the endometrium GnRH/GnRHR has been reported to regulates interaction between the embryo-endometrium in the early stage of implantation [3]. Antiproliferative activity of GnRH/GnRHR system has been suggested to be an effective direct molecular target for GnRH-analog-based therapeutic approaches to treat endometriozis. Continuous administration of GnRH analogs (GnRHa) induces a downregulation of GnRHR and suppresses the release of pituitary gonadotropins. In addition, GnRHa regulates the synthesis and release of peritoneal cytokines and endometrial integrin in endometriosis [4,5].

There is little evidence to support use of medical treatment in women with endometrioma who wish to improve fertility. In line with this, none of the hormonal drugs used in the medical treatment of endometriosis patients cause an increase in spontaneous pregnancy rates [4,6]. On the other hand, long-term GnRHa suppression therapy has been reported to increase IVF-ET outcome during the time it is applied. Really, we have sufficient data to show that GnRHa application has both direct and indirect effects on folliculogenesis and endometrial receptivity in infertile patients with endometriosis. For this reason, prolonged GnRHa administration has started to be widely used either before initiation of controlled ovarian stimulation or before frozen-ET in order to increase the implantation and pregnancy rates in cases with endometriosis. Most of the studies reported that long-term GnRHa treatment performed before IVF-ET or frozen-ET in patients with stage III-IV endometriosis had a positive effect on pregnancy rates. A recent study reported that pregnancy rates increased in patients with endometriosis who received agonist suppression after vitrification [7]. However, there are also studies reporting results that it does not provide any benefit. A recent study reported that long-term GnRHa suppression given before IVF-ET did not cause a significant change in reproductive outcome compared to the untreated group [8].

To date, it remains to be clarified whether prolonged gonadotrophin-releasing hormone agonist administration before frozen embryo transfer to patients with and without endometrioma surgery improves reproductive outcome. When rewieving the literature there is no study comparing patients who underwent endometrioma surgery with patients who did not undergo surgery despite having endometrioma, giving GnRHa treatment before frozen-ET. This retrospective cohort pilot study evaluates freeze-all cycles with subsequent prolonged GnRHa administration in patients with and without endometrioma surgery.

Materials and Methods

164 patients who applied to the Department of Obstetrics and Gynecology & IVF Center, Memorail Kayseri Hospital between 2016 and 2020 with complaints of infertility and were diagnosed with endometrioma were included in the study. The diagnosis of ovarian endometrioma was made as a result of the detection of the following findings with USG (GE, Voluson 730 Pro.). The endometrioma was suspected when a diffuse, regular- margined cyst with a low level internal echo, indicating hemorrhagic cyst, was present for at least 2 cycles, to exclude the nonendometriotic hemorrhagic cyst. Endometrioma patients were divided into two groups according to whether surgical intervention was performed or not. Laparoscopic endometrioma resection was performed in 65 of 164 cases and then controlled ovarian stimulation (COS) was performed (Group 1). The remaining 99 patients were referred directly to the COS without any surgical procedure for endometrioma (Group 2). Fresh embryos were transferred to 40 of 65 patients who underwent endometrioma surgery. In the other 25 patients who underwent endometrioma surgery, all embryos were vitrified in Cryotops as described by previously [9]. Subsequently they were administered a long-lasting preparation of the GnRHa leuprolide acetate (Lucrin Depot®; Abbvie) 3.75 mg every 28 days for 3 months. 99 patients with endometrioma who did not undergo surgery in Group 2 were referred to COS. While fresh-ET was applied to 49 of 99 cases, embryos were frozen in the remaining 50 cases. Subsequently they were administered a longlasting preparation of the GnRHa leuprolide acetate 3.75mg every 28 days for 3 months. Primary outcome was clinical pregnacy rates (CPR), ongoing pregnancy rates (OPR), and live birth rates (LBR).

All participants underwent a routine laboratory and radiological examination to diagnose the underlying factors of infertility. They had normal early follicular Follicle- Stimulating Hormone (FSH), Luteinizing Hormone (LH), Estradiol (E2), Thyroid-Stimulating Hormone (TSH), and Prolactine (PRL) levels, and normal midluteal progesterone levels indicating the presence of ovulation. To have information about over reserve Anti-Mullerian hormone (AMH) levels as well as antral follicle count determined at baseline transvaginal ultrasound examination performed in the early follicular phase. Participants in each group were noted to have a bilateral tubal patency, absence of intrauterine mass forming pathology in uterine cavity documented at Hysterosalpingography (HSG). Two semen analysis was performed in the male partners of the each woman at least 3 weeks&#39; apart and upon 3 to 7 days of abstinence. Because of these detailed examinations, the only detectable cause of infertility was endometrioma in all participants. Participants found to have pathology in semen analysis or HSG were not included in the study. Patients who had received GnRH agonists, progestins or oral contraceptive for treatment of symptomatic endometriosis within 6 months of initiation of their IVF-ET treatment were excluded.

4.1. Statistical analysis

Descriptive statistics were presented as frequency, mean and standart deviation. Shapiro Wilks test was used for evaluation of normality of distribution. Pearson Chi- squared test was used in the analysis of relationships between categorical variables. For the comparison of continous variables, the Students t-test was used with normal distribution. Statistical analyses were performed by using the SPSS 21.0 packages program for Windows. p<.05 was accepted to show statistical significance.

Results

The data including the demographic and IVF-ET results of the cases are shown in Table 1 & 2. No significant difference was found between the two groups in terms of age, duration of infertility and BMI. The number of total oocyte and MII oocyte counts were found to be significantly higher in the non-surgical group compared to the surgical group. While 65 of 164 endometrioma patients were operated, 99 patients did not undergo any surgical procedure. While fresh-ET was applied to 40 of 65 patients who were operated, 25 of them were frozen-Et. While fresh-ET was applied to 49 of 99 patients to be operated, frozen-ET was applied to 50 patients. No significant difference was found between the operated and non- operated groups in terms of CPR, OPR and LBR between patients who received fresh-ET. On the other hand, while there was no significant difference in CPR and OPR in operated and non-operated groups who underwent frozen-ET, live birth rates were found to be significantly higher in patients who were not operated (p<0.01). When we evaluated the cases with subgroup analysis, performing fresh-ET or frozen-ET in patients who underwent endometrioma surgery did not significantly affect CPR, OPR and LBR (Table 1). On the other hand, performing frozen-ET in patients who did not undergo surgery significantly increased both CPR (p<0.02) and OPR (p<0.03). In terms of LBR, a statistically insignificant increase trend was detected (p<0.056). If we divide endometrioma patients into two groups as those who went to surgery and those who did not, regardless of the use of GnRHa, pregnancy rates were found to be similar in both groups following fresh-ET. If we do frozen-ET patients in these groups, CPR and OPR were found to be similar, while LBR was found to be significantly higher in the non-operated group.

Discussion

This retrospective cohort pilot study evaluated the impact of freeze-all cycles with subsequent prolonged GnRHa administration before embryo transfer on reproductive outcome in patients with and without endometrioma resection. In this trial, we found that administration of GnRHa therapy for 3 months before frozen-ET in patients with a history of previous endometrioma surgery resulted in significantly lower clinical and ongoing pregnancy rates compared to endometrioma patients who had not endometrioma surgery. With this study, it has been shown for the first time that performing fresh or frozen ET for patients with a history of endometrioma surgery does not significantly affect CPR, OPR and LBR. However, we do not know whether the similar pregnancy rates in patients who underwent fresh or frozen-ET after endometrioma surgery are a unique feature of the frozen cycle or a feature related to GnRHa suppression or the combined effect of both. In this study, GnRHa suppression was applied to all patients undergoing thaw cycle. In fact, patients who underwent thaw cycles should have been divided into two groups and frozen-ET should be performed only in one group and GnRHa plus frozen-ET should have been performed in one group. In this way, we could say more clearly whether the main effect on pregnancy rates was due to agonist administration or frozen-ET. However, as far as we know from the literature data, although it varies according to etiological factors and age, the reproductive outcome in frozen cycles is higher than fresh cycles. Similarly, it has been reported that GnRHa treatment before IVF-ET or before frozen-ET positively affects pregnancy rates. Surrey et al. showed that prolonged GnRHa therapy prior to initiation of COS in patients with endometriosis resulted in significantly higher ongoing pregnancy rates [4]. In a meta-analysis written by Sallam et al. it was reported that giving GnRHa treatment for 3-6 months before COS significantly increased both clinical pregnancy rates and live birth rates [10].

In our study, patients in surgery group who underwent endometrioma cystectomy received prolonged administration of GnRHa after vitrification of all embryos. Our expectation after this treatment was a significant increase in pregnancy rates. The main support behind this expectation was the studies of Celik et al. in which they reported a significant increase in endometrial receptivity genes after endometrioma surgery [11]. However, despite frozen-ET plus GnRHa treatment in patients with endometrioma surgery, the pregnancy rates were similar to those treated with fresh-ET suggesting that vitrification and long-term suppression are not beneficial in this patient group. When we evaluate our results and literature findings together performing frozen-ET plus GnRHa treatment in patients who underwent IVF-ET after endometrioma surgery does not provide any extra benefit in terms of reproductive outcome compared to fresh cycles.

The second most important result we obtained from this study is that combining freeze all-cyle with long-term GnRha treatment significantly increased both CPR and OPR in the patient without endometrioma surgery compared to fresh cycles. We can explain the possible reasons for the significant increase in pregnancy rates after frozen-ET in the non-surgical group in two ways. The first reason may be due to the gains arising from the nature of frozen cycles. With the help of frozen-ET, we can get rid of the negative effect of estrogen increase due to COS on endometrial receptivity. The second reason for the increase in pregnancy in patients without endometrioma surgery may be long-term GnRHa treatment. There are many studies showing that administration of GnRHa treatment before IVF-ET or before frozen-ET leads to an increase in pregnancy rates [12]. However, there are studies showing that long-term GnRHa treatment is useless. Pre-COS use of GnRHa has been replaced by pre-frozen-ET application due to the possibility of decreasing the number of eggs to be collected. Our results are consistent with the publications reporting that long-term suppressions performed before frozen-ET in patients with endometriosis increase reproductive outcome. Surrey et al. reported that prolonged GnRHa therapy following vitrification of all embryos in patients with endometriosis led to high implantation and ongoing pregnancy rates [7]. However, there are no studies investigating the effect of agonist suppression in patients with and without endometrioma surgery.

While applying GnRHa treatment before frozen-ET was useless in patients who underwent endometrioma surgery, it showed a positive effect on pregnancy rates in patients who did not undergo surgery. We can explain this paradox-like difference as follows. Since pertioneal cytokine and natural killer cell activity will be normalized in the group undergoing endometrioma resection, GnRHa administration may not provide extra benefit in these patients. Since the presence of endometriosis and/or endometrioma is required for the emergence of both the inflammation-blocking and cytokines regulating activities of GnRHa the use of this drug in a disease-free environment may prevent it from showing its normal effect [4,7,13]. On the other hand, in the patients without endometrioma surgery, the presence of endometrioma will trigger abnormal cytokine release and inflammation in the peritoneal microenvironment. Ferrero et al. showed that GnRHa therapy reduces inflammatory proteins in peritoneal fluid proteome of women with endometriosis [13].

Another possible reason for the increased pregnancy rates may be the increase in endometrial receptivity due to the administration of GnRHa. In line with this, Lessey et al. reported that endometrial integrin β3 expression was normalized in patients with superficial endometriosis who received agonist therapy for 3 months or more [5]. As it is known, the production and release of integrins, one of the basic endometrial receptivity molecules, has decreased in patients with endometriosis. In the light of the above data, we can summarize the reasons for the positive effects of long-term GnRHa treatment before frozen-ET on pregnancy rates in non- operated endometrioma cases as follows. GnRHa treatment before frozen-ET might increase the implantation rates by acting through the following mechanisms;

(i) regulates natural killer cell activity as well as cytokines such as interleukin-1 and tumor necrosis factor whose production and secretion are impaired in peritoneal fluids of patients with endometriosis,

(ii) neutralizes the embryotoxic effects of peritoneal fluid,

(iii) increases endometrial cell survival by decreasing apoptosis in endometrial cells,

(iv) enhances endometrial receptivity by increasing endometrial αvβ3 integrin expression,

(v) down-regulates peritoneal fluids inflammatory proteins [4,5,7,10,13].

However, these possible mechanism of actions of GnRHa therapy need to be confirmed with more comprehensive studies.

The retrospective nature and the relative low number of cases are the main limitations of the study. Another limitation is that the absence of the frozen-ET group that is not given GnRHa treatment does not allow us to explain whether the positive results are GnRHa treatment or freezing of embryos or a combined effect. The strengths of our study include the fact that this is the first publication on the subject of use of prolonged GnRHa therapy in women with and without endometrioma surgery after vitrification of all embryos.

Conclusion

Performing endometrioma resection in the period before IVF does not provide any additional benefit to pregnancy rates. On the other hand, women with endometrioma who underwent IVF-ET without endometrioma surgery 3 months of GnRHa treatment before frozen-ET significantly increases CPR and OPR.

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Saving the Suprapubic Tract - Juniper Publishers

 Urology & Nephrology - Juniper Publishers

Abstract

Suprapubic Catheters (SPC) are commonly used for drainage of urine in the frail, elderly patient group worldwide. Losing the suprapubic tract post insertion can occur for numerous reasons, which subject patients for further surgical procedures to regain the suprapubic urine drainage with a higher risk of sustaining complications such as bowel injury. In this article we describe our technique of saving the suprapubic tract in the emergency setting.

Methods: Patients presenting to our hospital with failure to reinsert their SPC over a 6 months period were invited to have their SPC reinserted using our technique. A surgeon and an assistant were present to perform the procedure with the Instruments used including; Ultrasound Scan (USS), guidewire and open-tip urinary catheter.

Result:The procedure was done successfully in the 4 patients presenting with loss of their SPC. Operative time was less than 5 minutes and the procedure were well tolerated with regular analgesia. All patients were satisfied by their procedure and no post-operative complications were observed. Patients were discharged home on the same day and follow-up ensued with their district nurses as normal, with no change in their SPC care plan.

Conclusion: In the presence of the USS and the required instruments, the suprapubic tract can be salvageable in a frail patient group without the need for an emergency or an elective procedure under general anaesthesia. Decreasing the burden on the patient and the operative theatres;

Keywords: Long term catheters, Bladder drainage, Surgical treatment, Palliative, Suprapubic Catheter, Haematuria

Introduction

Long term catheters for bladder drainage is an alternative for urine drainage. Indications include; bladder outlet obstruction in patients with co-morbidities and unable to have definitive surgical treatment, palliative use for elderly frail patients and neurological disorders. Together with long term indwelling urethral catheter, Suprapubic Catheter (SPC) placement is a common method for urine drainage for patients requiring long term catheterisation. The procedure is usually performed under general anaesthesia and can be done under local anaesthesia, especially in the emergency settings. In addition to anaesthetics complications, SPC insertion complications include haematuria, catheter blockage, and recurrent urinary tract infections [1]. Also, one of the not uncommon risks during placing SPC is bowel perforation [2] which can be up to 2.5%, resulting in mortality in 30 days in 1.8% of the cases. This has a higher prevalence among patients with previous lower abdominal surgery [3], mainly due to abdominal wall adhesions, which can be found in up to 59% of patients with previous midline laparotomy scars [4]. After the initial SPC insertion, the first change is usually performed after at least 2 weeks, allowing the suprapubic tract to mature [5] and thereafter SPC changes can be done on a 2-3 monthly basis according to the catheter used. Despite being a routine urological procedure, changing the SPC has risks of its own, such as inadvertent bowel injury [6]. Another complication is failure to reinsert SPC whether during routine change of SPC or after falling out of the catheter. This dictates immediate urological attention, as losing the suprapubic tract would result in the need for another surgical operation for resisting the SPC. This carries the risk of higher chance of visceral injury as the risk of abdominal wall adhesion increases after lower abdominal surgery. In this article we explore the use of Ultrasound Scan (USS) and guidewire to salvage the suprapubic tract.

Methods

In the period between October 2018 to April 2019, 4 patients have been referred to our emergency services with expelled SPC, either during routine change with failure of insertion or spontaneous expulsion of the SPC.

Patients were met promptly in the surgical admission unit by the urology team and rapid assessment took place. Verbal and implied consent were obtained to attempt reinserting their SPC. Instruments used included;

a) Sensor® PTFE-Nitinol guidewire with a hydrophilic tip (Boston Scientific)

b) Open-tip catheter

c) USS machines with a lower frequency abdominal probe (3.5 -6MHz) have greater depth penetration and are more useful for abdominal scanning. The effective width of the US beam is affected by probe construction, depth and focussing and for a 3.5 MHz probe this commonly ranges between 3 to 5 mm.

Technique

a) Implied and verbal consent is sought in a similar manner to inserting a urethral catheter. Antibiotic prophylaxis and analgesia can be administered. Preparation of the operative field using betadine/chlorhexidine is important as usually previous manipulation(s) have been attempted.

b) An aseptic approach to avoid catheter-related urinary tract infections. An aseptic technique includes prepping and covering the puncture site with a large sterile drape, wearing sterile gloves, covering the US probe and cable with a sterile cover/shield and using a sterile conductive medium (USS gel) [7].

c) US scanning of the bladder/supra pubic tract; starting with a transverse lie, just underneath the site of the suprapubic puncture, where the bladder is usually seen partially full and the suprapubic tract is observed. An appreciation of the US probe and beam geometry is essential

d) Ask your assistant to hold the US probe in place and the sensor guidewire is fed through the suprapubic tract to the bladder and is confirmed under direct vision by the USS, you can rock the guidewire in small in and out motions to visualise it and confirm presence in the bladder.

e) Open tip catheter is introduced over the guidewire while assistant keeping the guidewire straight and prevent its expulsion.

f) Urine is drained, guidewire is removed, while catheter is held in place in bladder at the suprapubic tract and the balloon is inflated.

g) Position of the balloon is confirmed with US at the end of the procedure.

Results

In the period between September 2018 to April 2019, 4 patients have been referred to our emergency services with expelled SPC, either during routine change with failure of insertion or spontaneous expulsion of the SPC. Three patients had SPC due to old age and limited mobility and one patient had it for neurological indication. The average Body mass index of the patients was 28.3kg/m2 (range; 22-34 kg/m2). Time interval between removal of SPC and reinsertion varied between 6-12 hours, with an average of 4.5 hours. Patients were met promptly in the surgical admission unit by the urology team and rapid assessment took place, attempting to insert a routine SPC was unsuccessful due to (tight SPC skin opening and inability of advancing SPC to bladder). USS assessment was performed showing full bladder and suprapubic tract patency. Procedure was performed under 5 minutes, provided a surgeon and an assistant were present. Procedure was tolerated by all four patients with no anaesthesia, one patient needed Entonox for pain due to irritation of the neurogenic bladder by the sensor guidewire. Procedure was performed as outlined with all patients having their SPC reinserted, patients were observed for 2-4 hours post-operatively ensuring no post-obstructive diuresis or decompression haematuria and discharged home within the same day. Wounds healed well, and all patients were satisfied with the postoperative appearance of the SP wound. Patients were followed up until there next routine SPC change with no further complications reported.

Discussion

There is double benefit from adopting this technique, first is reducing the cost needed to re-insert the SPC in theatre setting. In their closed loop audit to assess the effectiveness of SPC insertion under local anaesthesia in an outpatient facility, Khan and Abrams demonstrated the huge cost savings they have cut performing the procedure in a simple outpatient facility, which was estimated to a total of £100,000/year per hospital, £790,000/year in their region, and £9,500,000 in the UK [8]. The second benefit is avoiding the formation of another suprapubic tract which has higher chance of visceral injury due to abdominal adhesions from the initial procedure [4], either it was done in an open (Suprapubic cystostomy and SPC insertion) or a closed manner, additionally avoiding the risks of general anaesthesia in the elderly population. In the description of their technique, Susan Willis and Bruce Montgomery, mentioned the utilisation of sensor guidewire and dilators to dilate the tract prior to reinserting the SPC [9]. Our method uses USS to delineate the suprapubic tract prior to cannulation, ensuring the sensor guidewire is following urine in its way to the bladder and not misguided in the abdominal cavity. Also, the real-time imaging use of USS allow visualisation of the guidewire in the bladder confirming the correct placement prior to further manipulation that can lead to loss of the suprapubic tract [10]. Furthermore, the use of ultrasound can then confirm the position of the catheter within the bladder after insertion.

The utilisation of USS greatly benefits this technique. As an imaging modality, it is quick, which is imperative in the recannulation, to avoid closure of the suprapubic tract. Moreover, having a quick scan can hasten the decision as to whether the patient will need to go to the theatres or not and it involves no radiation. This principle is adopted by BAUS based on advice from the National Patient Safety Agency [10]. The benefits are compared to utilising the use of the USS in the insertion of central venous catheters, which has reduced the complications experienced as well as increased the first-time success rate [11]. Suprapubic catheters are often used to improve the quality of life for patients at a late stage of their lives. Therefore, majority of these patients are elderly, frail, or having palliative treatment and often are not good candidates for general anaesthesia. It is imperative for this patient group to have an easy method to reinsert their catheters, without requiring general anaesthesia.

Despite the promising potentials of this technique, limitations were observed. Starting by the duration the suprapubic tract remains salvageable, which is under question and needs further studies to clarify this. Therefore, It is important to mention in the consent process that saving the SP tract is not guaranteed and there may be need to undergo urethral catheterisation and elective formal SPC insertion in theatres, or SPC insertion under general anaesthesia as an emergency in cases of difficult urethral catheterisation in the case of failure. In our limited patient group who presented as an emergency, attempting reinsertion was successful in all the patients, however the difficulty of the technique was noted in patients with high BMI, needing more than one assistant. No correlation was noted between the body habitus and the chances of success, this needs re-examining in a wider patient group. The greater the amount of subcutaneous tissue, the more difficult USS utilisation becomes, leading to attenuation of the sound waves and a poorer image quality. Despite the advantages of performing the technique under local anaesthesia, this will prove disadvantageous to the high-level spinal cord injury patients (above T6) who are susceptible for autonomic dysreflexia, therefore prolonged manipulation by the guidewire and catheter should be avoided. USS might give the inexperienced user a false sense of security and mislead him/her to neglect traditionally taught principles with regard to needle direction. It is key to visualize the needle (or needle tip) constantly during needle advancement [11]. Therefore, appropriate training of the staff involved in the procedure is crucial for optimum usage of the US and to increase the chances of success of the procedure [12]. This is being addressed in the modern era as urologists have been using USS more frequently, especially with prostate biopsies, and BAUS offer ultrasound courses for urologists [13].

Conclusion

Despite having mobile USS and guidewires in most hospitals readily available, this technique is underutilised in the emergency setting leading to the majority of patients to lose their suprapubic tract. This subjects patients to anaesthetics risks and complications of the procedure, in addition to enduring costs of the operative theatre setting. We believe that utilisation of this technique provides a safe rapid alternative for regaining the SPC in an already frail patient population.

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