<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Libido and explain in detail? [/INST] Libido (; colloquial: sex drive) is a persons overall sexual drive or desire for sexual activity. Libido is influenced by biological, psychological, and social factors. Biologically, the sex hormones and associated neurotransmitters that act upon the nucleus accumbens (primarily testosterone and dopamine, respectively) regulate libido in humans. Social factors, such as work and family, and internal psychological factors, such as personality and stress, can affect libido. Libido can also be affected by medical conditions, medications, lifestyle and relationship issues, and age (e.g., puberty). A person who has extremely frequent sexual urges, or a suddenly increased sex drive may be experiencing hypersexuality, while the opposite condition is hyposexuality. In psychoanalytic theory, libido is psychic drive or energy, particularly associated with sexual instinct, but also present in other instinctive desires and drives.A person may have a desire for sex, but not have the opportunity to act on that desire, or may on personal, moral or religious reasons refrain from acting on the urge. Psychologically, a persons urge can be repressed or sublimated. Conversely, a person can engage in sexual activity without an actual desire for it. Multiple factors affect human sex drive, including stress, illness, pregnancy, and others. A 2001 review found that, on average, men have a higher desire for sex than women.Sexual desires are often an important factor in the formation and maintenance of intimate relationships in humans. A lack or loss of sexual desire can adversely affect relationships. Changes in the sexual desires of any partner in a sexual relationship, if sustained and unresolved, may cause problems in the relationship. The infidelity of a partner may be an indication that a partners changing sexual desires can no longer be satisfied within the current relationship. Problems can arise from disparity of sexual desires between partners, or poor communication between partners of sexual needs and preferences.There is no widely accepted measure of what is a healthy level for sex desire. Some people want to have sex every day, or more than once a day; others once a year or not at all. However, a person who lacks a desire for sexual activity for some period of time may be experiencing a hypoactive sexual desire disorder or may be asexual.

Psychological perspectives
Psychoanalysis
Sigmund Freud, who is considered the originator of the modern use of the term, defined libido as "the energy, regarded as a quantitative magnitude... of those instincts which have to do with all that may be comprised under the word love." It is the instinctual energy or force, contained in what Freud called the id, the strictly unconscious structure of the psyche. He also explained that it is analogous to hunger, the will to power, and so on insisting that it is a fundamental instinct that is innate in all humans.Freud developed the idea of a series of developmental phases in which the libido fixates on different erogenous zones—first in the oral stage (exemplified by an infants pleasure in nursing), then in the anal stage (exemplified by a toddlers pleasure in controlling his or her bowels), then in the phallic stage, through a latency stage in which the libido is dormant, to its reemergence at puberty in the genital stage. (Karl Abraham would later add subdivisions in both oral and anal stages.)Freud pointed out that these libidinal drives can conflict with the conventions of civilised behavior, represented in the psyche by the superego. It is this need to conform to society and control the libido that leads to tension and disturbance in the individual, prompting the use of ego defenses to dissipate the psychic energy of these unmet and mostly unconscious needs into other forms. Excessive use of ego defenses results in neurosis. A primary goal of psychoanalysis is to bring the drives of the id into consciousness, allowing them to be met directly and thus reducing the patients reliance on ego defenses.Freud viewed libido as passing through a series of developmental stages within the individual. Failure to adequately adapt to the demands of these different stages could result in libidinal energy becoming dammed up or fixated in these stages, producing certain pathological character traits in adulthood. Thus the psychopathologized individual for Freud was an immature individual, and the goal of psychoanalysis was to bring these fixations to conscious awareness so that the libido energy would be freed up and available for conscious use in some sort of constructive sublimation.

Analytical psychology
According to Swiss psychiatrist Carl Gustav Jung, the libido is identified as the totality of psychic energy, not limited to sexual desire. As Jung states in "The Concept of Libido," "[libido] denotes a desire or impulse which is unchecked by any kind of authority, moral or otherwise. Libido is appetite in its natural state. From the genetic point of view it is bodily needs like hunger, thirst, sleep, and sex, and emotional states or affects, which constitute the essence of libido." The Duality (opposition) creates the energy (or libido) of the psyche, which Jung asserts expresses itself only through symbols: "It is the energy that manifests itself in the life process and is perceived subjectively as striving and desire." (Ellenberger, 697) These symbols may manifest as "fantasy-images" in the process of psychoanalysis which embody the contents of the libido, otherwise lacking in any definite form. Desire, conceived generally as a psychic longing, movement, displacement and structuring, manifests itself in definable forms which are apprehended through analysis.
Defined more narrowly, libido also refers to an individuals urge to engage in sexual activity, and its antonym is the force of destruction termed mortido or destrudo.

Factors that affect libido
Endogenous compounds
Libido is governed primarily by activity in the mesolimbic dopamine pathway (ventral tegmental area and nucleus accumbens). Consequently, dopamine and related trace amines (primarily phenethylamine) that modulate dopamine neurotransmission play a critical role in regulating libido.Other neurotransmitters, neuropeptides, and sex hormones that affect sex drive by modulating activity in or acting upon this pathway include:

Testosterone (directly correlated) – and other androgens
Estrogen (directly correlated) – and related female sex hormones
Progesterone (inversely correlated)
Oxytocin (directly correlated)
Serotonin (inversely correlated)
Norepinephrine (directly correlated)
Acetylcholine

Sex hormone levels and the menstrual cycle
A womans desire for sex is correlated to her menstrual cycle, with many women experiencing a heightened sexual desire in the several days immediately before ovulation, which is her peak fertility period, which normally occurs two days before and until two days after the ovulation. This cycle has been associated with changes in a womans testosterone levels during the menstrual cycle. According to Gabrielle Lichterman, testosterone levels have a direct impact on a womans interest in sex. According to her, testosterone levels rise gradually from about the 24th day of a womans menstrual cycle until ovulation on about the 14th day of the next cycle, and during this period the womans desire for sex increases consistently. The 13th day is generally the day with the highest testosterone levels. In the week following ovulation, the testosterone level is the lowest and as a result women will experience less interest in sex.Also, during the week following ovulation, progesterone levels increase, resulting in a woman experiencing difficulty achieving orgasm. Although the last days of the menstrual cycle are marked by a constant testosterone level, womens libido may get a boost as a result of the thickening of the uterine lining which stimulates nerve endings and makes a woman feel aroused. Also, during these days, estrogen levels decline, resulting in a decrease of natural lubrication.
Although some specialists disagree with this theory, menopause is still considered by the majority a factor that can cause decreased sexual desire in women. The levels of estrogen decrease at menopause and this usually causes a lower interest in sex and vaginal dryness which makes sex painful. However, the levels of testosterone increase at menopause and this may be why some women may experience a contrary effect of an increased libido.

Psychological and social factors
Certain psychological or social factors can reduce the desire for sex. These factors can include lack of privacy or intimacy, stress or fatigue, distraction, or depression. Environmental stress, such as prolonged exposure to elevated sound levels or bright light, can also affect libido. Other causes include experience of sexual abuse, assault, trauma, or neglect, body image issues, and anxiety about engaging in sexual activity.Individuals with PTSD may find themselves with reduced sexual desire. Struggling to find pleasure, as well as having trust issues, many with PTSD experience feelings of vulnerability, rage and anger, and emotional shutdowns, which have been shown to inhibit sexual desire in those with PTSD. Reduced sex drive may also be present in trauma victims due to issues arising in sexual function. For women, it has been found that treatment can improve sexual function, thus helping restore sexual desire. Depression and libido decline often coincide, with reduced sex drive being one of the symptoms of depression. Those with depression often report the decline in libido to be far reaching and more noticeable than other symptoms. In addition, those with depression often are reluctant to report their reduced sex drive, often normalizing it with cultural/social values, or by the failure of the physician to inquire about it.

Physical factors
Physical factors that can affect libido include endocrine issues such as hypothyroidism, the effect of certain prescription medications (for example flutamide), and the attractiveness and biological fitness of ones partner, among various other lifestyle factors.Anemia is a cause of lack of libido in women due to the loss of iron during the period.Smoking, alcohol use disorder, and the use of certain drugs can also lead to a decreased libido. Moreover, specialists suggest that several lifestyle changes such as exercising, quitting smoking, lowering consumption of alcohol or using prescription drugs may help increase ones sexual desire.

Medications
Some people purposefully attempt to decrease their libido through the usage of anaphrodisiacs. Aphrodisiacs, such as dopaminergic psychostimulants, are a class of drugs which can increase libido. On the other hand, a reduced libido is also often iatrogenic and can be caused by many medications, such as hormonal contraception, SSRIs and other antidepressants, antipsychotics, opioids, beta blockers and Isotretinoin.
Isotretinoin and many SSRIs can cause a long-term decrease in libido and other sexual functions, even after users of those drugs have shown improvement in their depression and have stopped usage. Multiple studies have shown that with the exception of bupropion (Wellbutrin), trazodone (Desyrel) and nefazodone (Serzone), antidepressants generally will lead to lowered libido. SSRIs that typically lead to decreased libido are fluoxetine (Prozac), paroxetine (Paxil), fluvoxamine (Luvox), citalopram (Celexa) and sertraline (Zoloft). Some antidepressant users have tried decreasing their dosage in the hopes of maintaining an adequate sex drive. Other users try enrolling in psychotherapy to solve depression-related issues of libido. However, the effectiveness of this therapy is mixed, with many reporting that it had no or little effect on sexual drive.Testosterone is one of the hormones controlling libido in human beings. Emerging research is showing that hormonal contraception methods like oral contraceptive pills (which rely on estrogen and progesterone together) are causing low libido in females by elevating levels of sex hormone-binding globulin (SHBG). SHBG binds to sex hormones, including testosterone, rendering them unavailable. Research is showing that even after ending a hormonal contraceptive method, SHBG levels remain elevated and no reliable data exists to predict when this phenomenon will diminish.Oral contraceptives lower androgen levels in users, and lowered androgen levels generally lead to a decrease in sexual desire. However, usage of oral contraceptives has shown to typically not have a connection with lowered libido in women. Multiple studies have shown that usage of oral contraceptives is associated with either a small increase or decrease in libido, with most users reporting a stable sex drive.

Effects of age
Males reach the peak of their sex drive in their teenage years, while females reach it in their thirties. The surge in testosterone hits the male at puberty resulting in a sudden and extreme sex drive which reaches its peak at age 15–16, then drops slowly over his lifetime. In contrast, a females libido increases slowly during adolescence and peaks in her mid-thirties.
Actual testosterone and estrogen levels that affect a persons sex drive vary considerably.
Some boys and girls will start expressing romantic or sexual interest by age 10–12. The romantic feelings are not necessarily sexual, but are more associated with attraction and desire for another. For boys and girls in their preteen years (ages 11–12), at least 25% report "thinking a lot about sex". By the early teenage years (ages 13–14), however, boys are much more likely to have sexual fantasies than girls. In addition, boys are much more likely to report an interest in sexual intercourse at this age than girls. Masturbation among youth is common, with prevalence among the population generally increasing until the late 20s and early 30s. Boys generally start masturbating earlier, with less than 10% boys masturbating around age 10, around half participating by age 11–12, and over a substantial majority by age 13–14. This is in sharp contrast to girls where virtually none are engaging in masturbation before age 13, and only around 20% by age 13–14.People in their 60s and early 70s generally retain a healthy sex drive, but this may start to decline in the early to mid-70s. Older adults generally develop a reduced libido due to declining health and environmental or social factors. In contrast to common belief, postmenopausal women often report an increase in sexual desire and an increased willingness to satisfy their partner. Women often report family responsibilities, health, relationship problems, and well-being as inhibitors to their sexual desires. Aging adults often have more positive attitudes towards sex in older age due to being more relaxed about it, freedom from other responsibilities, and increased self-confidence. Those exhibiting negative attitudes generally cite health as one of the main reasons. Stereotypes about aging adults and sexuality often regard seniors as asexual beings, doing them no favors when they try to talk about sexual interest with caregivers and medical professionals. Non-western cultures often follow a narrative of older women having a much lower libido, thus not encouraging any sort of sexual behavior for women. Residence in retirement homes has affects on residents libidos. In these homes, sex occurs, but it is not encouraged by the staff or other residents. Lack of privacy and resident gender imbalance are the main factors lowering desire. Generally, for older adults, being excited about sex, good health, sexual self-esteem and having a sexually talented partner can be factors.

Sexual desire disorders
A sexual desire disorder is more common in women than in men, and women tend to exhibit less frequent and less intense sexual desires than men </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Embolic and thrombotic events after COVID-19 vaccination and explain in detail? [/INST] Post-vaccination embolic and thrombotic events, termed vaccine-induced immune thrombotic thrombocytopenia (VITT), vaccine-induced prothrombotic immune thrombocytopenia (VIPIT), thrombosis with thrombocytopenia syndrome (TTS), vaccine-induced immune thrombocytopenia and thrombosis (VITT), or vaccine-associated thrombotic thrombocytopenia (VATT), are rare types of blood clotting syndromes that were initially observed in a number of people who had previously received the Oxford–AstraZeneca COVID‑19 vaccine (AZD1222) during the COVID‑19 pandemic. It was subsequently also described in the Janssen COVID‑19 vaccine (Johnson & Johnson) leading to suspension of its use until its safety had been reassessed. On 5 May 2022 the FDA posted a bulletin limiting the use of the Janssen Vaccine to very specific cases due to further reassesment of the risks of TTS, although the FDA also stated in the same bulletin that the benefits of the vaccine outweigh the risks.In April 2021, AstraZeneca and the European Medicines Agency (EMA) updated their information for healthcare professionals about AZD1222, saying it is "considered plausible" that there is a causal relationship between the vaccination and the occurrence of thrombosis in combination with thrombocytopenia and that, "although such adverse reactions are very rare, they exceeded what would be expected in the general population".

Signs and symptoms
The thrombosis events associated with the COVID‑19 vaccine may occur 4–28 days after its administration and mainly affects women under 55. Several relatively unusual types of thrombosis were specifically reported to be occurring in those with the reaction: cerebral venous sinus thrombosis and thrombosis of the splanchnic veins. Cerebral venous sinus thrombosis may cause severe headache, stroke-like symptoms (weakness of a limb and/or facial muscles), seizures and coma. Splanchnic vein thrombosis may cause abdominal pain, accumulation of fluid in the abdominal cavity, and gastrointestinal bleeding.Other forms of thrombosis, such as the more common pulmonary embolism, may also occur. Arterial thrombosis has also been reported. The low platelet count may manifest as petechia (tiny blood spots under the skin) beyond the site of the injection.Disseminated intravascular coagulation (DIC), diffuse formation of blood clots throughout the blood vessels of the body, has been reported as part of the syndrome. DIC may cause a range of symptoms, including abnormal bleeding, breathlessness, chest pain, neurological symptoms, low blood pressure, or swelling.COVID‑19 vaccines have some adverse effects that are listed as common in the two or three days following vaccination which are usually mild and temporary.

Causes
The rare simultaneous occurrence of thrombocytopenia (low blood platelets) with blood clots after vaccination raised the original concern about this condition. In many cases where acute thrombosis and thrombocytopenia have been found together after COVID‑19 vaccination, an antibody against platelet factor 4 has been identified. This phenomenon is mostly encountered in some people who have been administered heparin, but none of the reported cases had received heparin. More rarely, this phenomenon had previously been described as an autoimmune phenomenon in people who had not been exposed to heparin. One striking feature of thrombocytopenia in the presence of anti-PF4 antibodies is the propensity of some to develop thrombosis, a phenomenon called heparin-induced thrombocytopenia if heparin is involved.Thrombocytopenia is generally a common symptom after or during many viral infections, and it "has been consistently reported" after intravenous administration of adenoviral gene transfer vectors, although its mechanisms are not yet clear.
There is no confirmed causal link to the syndrome and any COVID‑19 vaccination, however EMA is conducting investigations into AZD1222 and the Janssen COVID‑19 vaccine (Johnson & Johnson) for possible causal links.On 7 April 2021, the EMA noted one "plausible explanation" for the combination of blood clots and low blood platelets is "an immune response, leading to a condition similar to one seen sometimes in people treated with heparin", that is heparin induced thrombocytopenia (HIT).

Diagnosis
In the United Kingdom, professional societies led by the Royal College of Emergency Medicine have issued a guideline for suspected cases. Someone presenting with concerning symptoms between five and 28 days after administration of the vaccine is assessed for a possible thrombotic complication, with a full blood count (which includes a platelet count) as the initial investigation. If the platelet count is decreased, determination of the D-dimer and fibrinogen levels may be performed, with hematology expert advice recommended if these are elevated above specific cut offs.

Management
Guidelines from professional societies recommend treatment with alternative anticoagulants instead of heparin, as there is a possibility that it may aggravate the phenomenon. Alternative options as the directly acting oral anticoagulants (DOACs), argatroban, fondaparinux or danaparoid depending on the circumstances. Platelet transfusion is discouraged, as this too may aggravate thrombosis. UK guidelines by the British Society for Haematology recommend the administration of intravenous immunoglobulin (IVIG) to reduce levels of the pathogenic antibody. Low fibrinogen levels may require correction with fibrinogen concentrate or cryoprecipitate.

Epidemiology
The Paul Ehrlich Institute has recorded 31 cerebral venous sinus thromboses (CVST) and nine deaths out of 2.7 million vaccinated in Germany with the AZD1222. On 2 April 2021, the UKs Medicines and Healthcare products Regulatory Agency reported 22 cases of CVST and a further eight cases of clotting problems both associated with a low level of blood platelets following a "rigorous review" of its Yellow Card reporting. The institute also reported finding no events of this type which occurred after vaccination with the Pfizer–BioNTech COVID‑19 vaccine. The EMA had earlier said that a link between certain very rare blood clots and the AstraZeneca vaccine is "not proven, but is possible".Observations in Germany of these rare events seemed to relate mostly women aged under 55. However, because Germany had previously restricted AZD1222 to under 65s, the population vaccinated there with AZD1222 is comparatively younger, and consequently contained a higher proportion of women taking the contraceptive pill. As CVSTs are more likely in women using hormonal contraceptives, this inherent risk factor may be an influence on the reported preponderance of women experiencing these events following vaccination. The UK, in contrast, has applied its Pfizer and AZD1222 vaccines generally to older groups first, then by decreasing age.The UK Medicines and Healthcare products Regulatory Agency (MHRA) reporting regards AZD1222 to 3 November 2021, recording 73 deaths out of 425 cases (17%) in the context of 24.9 million first doses administered.

Regulatory status
According to the European Medicines Agency (EMA), as of 28 March 2021, the reported number of cases of embolic and thrombotic events after vaccination is lower than the rate of such events in the general population overall. However, the specific syndrome - of embolic and thrombotic events in combination with low levels of blood platelets - presenting in post-vaccination cases raised the possibility of an association between the vaccine and the relatively rare syndrome. The EMA also said that there is no proof that these events are caused by the vaccines, but that the possibility could not yet be ruled out completely. Accordingly, the EMA advised that people who received the vaccine and experienced symptoms suggestive of thrombosis, including shortness of breath, blurred vision and severe or persistent headache, should seek medical attention.In a press briefing on 7 April 2021, Emer Cooke, the executive director of the European Medicines Agency (EMA) began by stating "Our safety committee, the Pharmacovigilance Risk Assessment Committee (PRAC) of the European Medicines Agency, has confirmed that the benefits of the AstraZeneca vaccine in preventing COVID‑19 overall outweigh the risks of side effects. COVID‑19 is a very serious disease with high hospitalization and death rates and every day COVID is still causing thousands of deaths across the EU. This vaccine has proven to be highly effective, it prevents severe disease and hospitalization, and it is saving lives. Vaccination is extremely important in helping us in the fight against COVID‑19 and we need to use the vaccines we have to protect us from the devastating effects". She went on to say "The PRAC after a very in-depth analysis has concluded that the reported cases of unusual blood clotting following vaccination with the AstraZeneca vaccine should be listed as possible side effects of the vaccine". At the same briefing Dr. Samina Strauss of PRAC confirmed "our conclusion is that these clotting disorders are very rare side effects of the vaccine".The UK Medicines and Healthcare products Regulatory Agency (MHRA) held a news conference on 7 April 2021, and while there is no proof that the AZD1222 vaccination caused the rare blood clots, they indicated the possibility of a link is getting stronger. The UK is to offer under 30s alternative vaccines. The reasoning is because in the 20-29 age range the benefits to individual of vaccination were less as their likelihood of harm from COVID‑19 is less and closer to the potential risk of harm from the vaccine (at a medium exposure risk with COVID‑19 infection cases running at a rate of 60 per 100,000). For higher age groups the benefit to risk ratio increased.Also on 7 April 2021, an interim statement from the WHO said its advisory body, GACVS, found any "causal relationship" between the rare blood clot cases and AZD1222 to be "plausible but is not confirmed".On 20 April 2021, the safety committee of the EMA (PRAC) found a "possible link to very rare cases of unusual blood clots with low blood platelets" for the Johnson & Johnson Janssen vaccine; and required that these rare events, similar to those noted for AZD1222, should be listed as a very rare side effect. The EMA states the overall risk-benefit for the Janssen vaccine remains positive.On 16 December 2021, the US Centers for Disease Control and Prevention (CDC) recommended the Moderna and Pfizer-BioNTech vaccines should be preferred over the Janssen vaccine, following growing concerns about rare blood clots. Janssen should still be offered to people who specifically request it.

History
Organizations
Global vaccine safety comes under the remit of the World Health Organization (WHO), and in particular its Global Advisory Committee on Vaccine Safety (GAVCS). Other drug regulatory agencies significantly involved include:
European Medicines Agency (EMA), the regional regulatory authority for the EU.
Medicines and Healthcare products Regulatory Agency (MHRA), the medical authority for the United Kingdom.
Paul Ehrlich Institute (PEI), a German federal agency supervised by the Federal Ministry of Health with expertise in vaccines and biomedicines. It is a WHO collaborating centre.

Syndrome identification
A number of COVID‑19 vaccines began to become approved and available at scale in December 2020, with vaccinations beginning to ramp up at scale from the beginning of 2021, among them the Oxford–AstraZeneca COVID‑19 vaccine, based on an adenovirus vector and internally termed AZD1222.On 11 March 2021, the EMA issued a statement noting Denmark had suspended AZD1222 vaccinations due to a vaccinated patient dying with blood clots. While noting there had been reports of other vaccinated people having blood clots and that its safety committee is already reviewing such cases, the number of thromboembolic events in vaccinated people is no higher than in the general population.The World Health Organization (WHO) Global Advisory Committee on Vaccine Safety on 19 March 2021, issued a statement relating to safety signals related to AZD1222 relating to thromboembolic events and thrombocytopenia following review of available data and conclusions included that AZD1222 "a positive benefit-risk profile, with tremendous potential to prevent infections and reduce deaths across the world".In its safety update of 29 March 2021, the EMA indicated it had initiated investigations into the very rare cases of specific embolic and thrombotic events in combination with thrombocytopenia (low levels of blood platelets) and related bleeding including disseminated intravascular coagulation and cerebral venous sinus thrombosis (CVST), noting any link with AZD1222 is not proven but could not be excluded. The EMA also initiated an assessment for all COVID‑19 vaccines used in the EU for immune thrombocytopenia (ITP), described as low blood platelet levels that could lead to bruising and bleeding, as a possible side effect, whilst also stating that up to this point no link with any COVID‑19 had been established.On 7 April 2021, the EMA determined that unusual blood clots with low blood platelets should be listed as very rare side effects of AZD1222, with WHO and UK EHRA issuing generally similar statements on the same day. None of the agencies found a confirmed causal link between the vaccine and these incidents at the time, but were listing them out of an abundance of caution.A highlight of minutes of the EMAs Pharmacovigilance Risk Assessment Committee (PRAC) concluding 9 April 2021, indicating they also were investigating four cases of unusual blood clots with low blood platelets, including one death, amongst people who had taken the Janssen COVID‑19 vaccine. The Janssen vaccine is approved but not yet deployed in the EU, though vaccinations are in progress in the US. PRAC has determined that it is not clear if there is a causal association. Should regulatory action prove necessary, PRAC have indicated the likely outcome would be an update to product information characteristics.

Vaccination campaign responses
Early reports of the events of concern seemed to indicate the presentation rate for the specific blood clots of concern might be higher for women of younger ages, UK Medicines and Healthcare products Regulatory Agency (MHRA) found examples across all genders and ages, their data skewing towards these specific blood clots being more prevalent in AZD1222 vaccinated persons of younger ages.The WHO has continued to stress the administration of vaccines is based on risk versus benefit analysis. Some variables that may be factored into such analysis include risk of an individual from catching COVID‑19, which relate to the infection rate in that area, and the benefits to that individual if vaccinated and exposed to COVID‑19 which varies with age, versus whatever the risks of vaccination are to that individual.

Regional and national responses
The advisory panel for the government of Ontario, Canada has recommended against the use of heparin for management of thrombosis after vaccination until more is known.In response to the concerns over the adverse effects relating to rare blood clotting types Germany has suspended use of the AZD1222 in those under 60 years of age; in contrast to a period previously having suspended use of AZD1222 to over–65s due to limited data of the efficacy of the vaccine to this age group at that time.Following a few days of suspended use of AZD1222, the Ministry of Health, Welfare and Sport of the Netherlands decided to continue administering the vaccine only to persons above the age of 60.On 8 April 2021, the Australian Technical Advisory Group on Immunisation (ATAGI) advised the Australian Government that the Pfizer COVID‑19 vaccine is recommended over AZD1222 for adults aged under 50 years. The advice is "based on the increasing risk of severe outcomes from COVID‑19 in older adults (and hence a higher benefit from vaccination) and a potentially increased risk of thrombosis with thrombocytopenia following AstraZeneca vaccination in those under 50 years." AZD1222 is still recommended by ATAGI for people over 50, and those under 50 who have already had their first dose with no ill effects. In the state of Victoria, there were reports of some, aged under 50, being turned away from vaccination centres, despite having confirmed appointments. It is understood a special consent process will be developed by the Australian Government for people under 50 who choose to receive the AZD1222 vaccine.

Studies
A study convened by a group of British hematologists on 19 March 2021, just two days after the acknowledgement of the condition, published its finding in The New England Journal of Medicine, establishing case definition criteria. The study included 294 participants who presented with symptoms of thrombocytopenia and thrombosis after receipt of the first dose of the Oxford–AstraZeneca COVID‑19 vaccine, showing an independent association between baseline platelet count and the presence of intracranial hemorrhage. The study established that 85% of the participants effected by the condition were aged younger than 60 years, and that those participants with a history of thrombosis or prothrombotic disorders did not appear to be at increased risk. The study showed an overall mortality rate of 22% and set out plans for additional research to determine the genetic factors that may increase risk of the condition and identify potential therapeutic agents.

References
Notes
Footnotes
Further reading
Aleem A, Nadeem AJ (July 2021). "Coronavirus (COVID-19) Vaccine-Induced Immune Thrombotic Thrombocytopenia (VITT)". StatPearls. PMID 34033367.
Arepally GM, Ortel TL (July 2021). "Vaccine-induced immune thrombotic thrombocytopenia: what we know and do not know". Blood. 138 (4): 293–8. doi:10.1182/blood.2021012152. PMC 8172307. PMID 34323940.
Iba T, Levy JH, Warkentin TE (January 2022). "Recognizing Vaccine-Induced Immune Thrombotic Thrombocytopenia". Crit Care Med. 50 (1): e80–e86. doi:10.1097/CCM.0000000000005211. PMC 8670081. PMID 34259661.
Schultz NH, Sørvoll IH, Michelsen AE, Munthe LA, Lund-Johansen F, Ahlen MT,  et al. (June 2021). "Thrombosis and Thrombocytopenia after ChAdOx1 nCoV-19 Vaccination". N Engl J Med. 384 (22): 2124–30 </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Vasospasm and explain in detail? [/INST] Vasospasm refers to a condition in which an arterial spasm leads to vasoconstriction. This can lead to tissue ischemia and tissue death (necrosis). Cerebral vasospasm may arise in the context of subarachnoid hemorrhage.  Symptomatic vasospasm or delayed cerebral ischemia is a major contributor to post-operative stroke and death especially after aneurysmal subarachnoid hemorrhage.  Vasospasm typically appears 4 to 10 days after subarachnoid hemorrhage.
Along with physical resistance, vasospasm is a main cause of ischemia. Like physical resistance, vasospasms can occur due to atherosclerosis. Vasospasm is the major cause of Prinzmetals angina.

Pathophysiology
Normally endothelial cells release prostacyclin and nitric oxide (NO) which induce relaxation of the smooth muscle cells, and reduce aggregation of platelets. Aggregating platelets stimulate ADP to act on endothelial cells and help them induce relaxation of the smooth muscle cells. However, aggregating platelets also stimulate thromboxane A2 and serotonin which can induce contraction of the smooth muscle cells.  In general, the relaxations outweighs the contractions.
In atherosclerosis, a dysfunctional endothelium is observed on examination. It does not stimulate as much prostacyclin and NO to induce relaxation on smooth muscle cells. Also there is not as much inhibition of aggregation of platelets. In this case, the greater aggregation of platelets produce ADP, serotonin, and thromboxane A2. However the serotonin and the thromboxane A2 cause more contraction of the smooth muscle cells and as a result contractions outweigh the relaxations.

Complications
Vasospasm can occur in a wide variety of peripheral vascular beds under poorly understood mechanisms. Prinzmetal angina, Buergers disease, contrast mediated selective renal vasospasm, hypercoagulability and cryoglobulinemia likely represent just a few of the known pieces of this puzzling phenomena. Ischemia in the heart due to prolonged coronary vasospasm can lead to angina, myocardial infarction and even death. Vasospasm in the hands and fingers due to prolonged exposure to vibration (30 – 300 Hz) and triggered by cold can lead to Hand-arm vibration syndrome in which feeling and manual dexterity are lost.

Angiography
In angiography, vascular access through femoral and axillary arteries are preferred because they are less prone to vasospasm. Meanwhile, brachial artery is more prone to vasospasm during instrumental access.

Hypothermia Rewarming
In a case study in 2000, following surgery for head trauma, a patient developed mild hypothermia, a typical defense mechanism the brain uses to protect itself after injury. After the hypothermia rewarming period, the patient died from increased intracranial pressure and anisocoria. A sample of the cerebrospinal fluid and autopsy results indicated cerebral vasospasm.

Treatment
The occurrence of vasospasm can be reduced by preventing the occurrence of atherosclerosis. This can be done in several ways, the most important being lifestyle modifications—decreasing low-density lipoprotein (LDL), quitting smoking, physical activity, and control for other risk factors including diabetes, obesity, and hypertension. Pharmacological therapies include hypolipidemic agents, thrombolytics and anticoagulants. Pharmacological options for reducing the severity and occurrence of ischemic episodes include the organic nitrates, which are rapidly metabolized to release nitric oxide in many tissues, and are classified as having either long-acting (i.e. isosorbide dinitrate) or short-acting (i.e. nitroglycerin) durations of action.
These drugs work by increasing nitric oxide levels in the blood and inducing coronary vasodilation which will allow for more coronary blood flow due to a decreased coronary resistance, allowing for increased oxygen supply to the vital organs (myocardium). The nitric oxide increase in the blood resulting from these drugs also causes dilation of systemic veins which in turn causes a reduction in venous return, ventricular work load and ventricular radius. All of these reductions contribute to the decrease in ventricular wall stress which is significant because this causes the demand of oxygen to decrease. In general organic nitrates decrease oxygen demand and increase oxygen supply. It is this favourable change to the body that can decrease the severity of ischemic symptoms, particularly angina.
Other medications used to reduce the occurrence and severity of vasospasm and ultimately ischemia include L-type calcium channel blockers (notably nimodipine, as well as verapamil, diltiazem, nifedipine) and beta-receptor antagonists (more commonly known as beta blockers or β-blockers) such as propranolol.
L-type calcium channel blockers can induce dilation of the coronary arteries while also decreasing the hearts demand for oxygen by reducing contractility, heart rate, and wall stress. The reduction of these latter three factors decreases the contractile force that the myocardium must exert in order to achieve the same level of cardiac output.
Beta-receptor antagonists do not cause vasodilation, but like L-type calcium channel blockers, they do reduce the hearts demand for oxygen </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Hypohidrosis and explain in detail? [/INST] Hypohidrosis is a disorder in which a person exhibits diminished sweating in response to appropriate stimuli. In contrast with hyperhidrosis, which is a socially troubling yet often benign condition, the consequences of untreated hypohidrosis include hyperthermia, heat stroke and death. An extreme case of hypohidrosis in which there is a complete absence of sweating and the skin is dry is termed anhidrosis.

Causes
Diagnosis
Sweat is readily visualized by a topical indicator such as iodinated starch (Minor test) or sodium alizarin sulphonate, both of which undergo a dramatic colour change when moistened by sweat. A thermoregulatory sweat test can evaluate the body’s response to a thermal stimulus by inducing sweating through a hot box ⁄ room, thermal blanket or exercise. Failure of the topical indicator to undergo a colour change during thermoregulatory sweat testing indicates hypohidrosis, and further tests may be required to localize the lesion.
Magnetic resonance imaging of the brain and ⁄ or spinal cord is the best modality for evaluation when the lesion is suspected to be localized to the central nervous system.
Skin biopsies are useful when anhidrosis occurs as part of a dermatological disorder </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Hydronephrosis and explain in detail? [/INST] Hydronephrosis describes hydrostatic dilation of the renal pelvis and calyces as a result of obstruction to urine flow downstream.  Alternatively, hydroureter describes the dilation of the ureter, and hydronephroureter describes the dilation of the entire upper urinary tract (both the renal pelvicalyceal system and the ureter).

Signs and symptoms
The signs and symptoms of hydronephrosis depend upon whether the obstruction is acute or chronic, partial or complete, unilateral or bilateral. Hydronephrosis that occurs acutely with sudden onset (as caused by a kidney stone) can cause intense pain in the flank area (between the hips and ribs) known as a renal colic.  Historically, this type of pain has been described as "Dietls crisis". Conversely, hydronephrosis that develops gradually over time will generally cause either a dull discomfort or no pain.  Nausea and vomiting may also occur.  An obstruction that occurs at the urethra or bladder outlet can cause pain and pressure resulting from distension of the bladder.  Blocking the flow of urine will commonly be prone to urinary tract infections which can lead to further development of stones, fever, and blood or pus in the urine.  If complete obstruction occurs, a postrenal kidney failure (obstructive nephropathy) may follow.Blood tests may show impaired kidney function (elevated urea or creatinine) or electrolyte imbalances such as hyponatremia or hyperchloremic metabolic acidosis.  Urinalysis may indicate an elevated pH due to the secondary destruction of nephrons within the affected kidney, which impairs acid excretion.  Physical examination in a thin patient may detect a palpable abdominal or flank mass caused by the enlarged kidney.

Causes
Hydronephrosis is the result of any of several abnormal pathophysiological occurrences.  Structural abnormalities of the junctions between the kidney, ureter and bladder that lead to hydronephrosis can occur during fetal development.  Some of these congenital defects have been identified as inherited conditions, however, the benefits of linking genetic testing to early diagnosis have not been determined.  Other structural abnormalities could be caused by injury, surgery, or radiation therapy.The most common causes of hydronephrosis in children are anatomical abnormalities. These include vesicoureteral reflux, urethral stricture, and stenosis. The most common cause of hydronephrosis in young adults is kidney stones. In older adults, the most common cause of hydronephrosis is benign prostate hyperplasia (BPH), or intrapelvic neoplasms such as prostate cancer. Compression of one or both ureters can also be caused by other developmental defects not completely occurring during the fetal stage such as an abnormally placed vein, artery, or tumor.  Bilateral compression of the ureters can occur during pregnancy due to enlargement of the uterus.  Changes in hormone levels during this time may also affect the muscle contractions of the bladder, further complicating this condition.Sources of obstruction that can arise from other various causes include kidney stones, blood clots or retroperitoneal fibrosis.The obstruction may be either partial or complete, and can occur anywhere from the urethral meatus to the renal calyces.  Hydronephrosis can also result from the retrograde flow of urine from the bladder back into the kidneys (vesicoureteral reflux), which can be caused by some of the factors listed above as well as compression of the bladder outlet into the urethra by prostate enlargement or fecal impaction in the rectum (which sits immediately behind the prostate), as well as abnormal contractions of bladder detrusor muscles resulting from neurological dysfunction (neurogenic bladder) or other muscular disorders.

Pathophysiology
Hydronephrosis is caused by obstruction of urine before the renal pelvis. The obstruction causes dilation of the nephron tubules and flattening of the lining of the tubules within the kidneys which in turn causes swelling of the renal calyces. Hydronephrosis can either be acute or chronic. In acute hydronephrosis full recovery of kidney function is seen. However, with chronic hydronephrosis, permanent loss of kidney function is seen even once obstruction is removed. Obstruction that occurs anywhere along the upper urinary tract will lead to increased pressure within the structures of the kidney due to the inability to pass urine from the kidney to the bladder.  Common causes of upper tract obstruction include obstructing stones and ureteropelvic junction (UPJ) obstruction caused by intrinsic narrowing of the ureters or an overlying vessel.
Obstruction occurring in the lower urinary tract can also cause this increased pressure through the reflux of urine into the kidney.  Common causes include bladder dysfunction (such as neurogenic bladder) and urethral obstruction (such as posterior urethral valves in male infants) or compression (such as from prostatic hypertrophy in older male adults).
In pregnancy, dextrorotation (rotation to the right) of the uterus can cause compression on the right ureter, thus making hydronephrosis more common in right kidney than left kidney. Besides, hormones such as oestrogen, progestrerone, and prostaglandin can cause ureter dilatation, thus causing hydronephrosis despite the absence of visible obstruction along the urinary tract.

Diagnosis
Prenatal diagnosis is possible, and in fact, most cases in pediatric patients are incidentally detected by routine screening ultrasounds obtained during pregnancy.  However, approximately half of all prenatally identified hydronephrosis is transient, and resolves by the time the infant is born, and in another 15%, the hydronephrosis persists but is not associated with urinary tract obstruction (so-called non-refluxing, non-obstructive hydronephrosis).  For these children, regression of the hydronephrosis occurs spontaneously, usually by age 3.  However, in the remaining 35% of cases of prenatal hydronephrosis, a pathological condition can be identified postnatally.Diagnostic workup depends on the age of the patient, as well as whether the hydronephrosis was detected incidentally or prenatally or is associated with other symptoms.  Blood tests (such measurement of creatinine) are typically indicated, though they must be interpreted cautiously.  Even in cases of severe unilateral hydronephrosis, the overall kidney function may remain normal since the unaffected kidney will compensate for the obstructed kidney.Urinalysis is usually performed to determine the presence of blood (which is typical for kidney stones) or signs of infection (such as a positive leukocyte esterase or nitrite).  Impaired concentrating ability or elevated urine pH (distal renal tubular acidosis) are also commonly found due to tubular stress and injury.

Imaging studies
Imaging studies, such as an intravenous urogram (IVU), renal ultrasonography, CT, or MRI, are also important investigations in determining the presence and/ or cause of hydronephrosis. Whilst ultrasound allows for visualisation of the ureters and kidneys (and determine the presence of hydronephrosis and / or hydroureter), an IVU is useful for assessing the anatomical location of the obstruction. Antegrade or retrograde pyelography will show similar findings to an IVU but offer a therapeutic option as well. Real-time ultrasounds and Doppler ultrasound tests in association with vascular resistance testing helps determine how a given obstruction is effecting urinary functionality in hydronephrotic patients.In determining the cause of hydronephrosis, the location of obstruction can be determined with a Whittaker (or pressure perfusion) test, wherein the collecting system of the kidney is accessed percutaneously, and the liquid is introduced at high pressure and constant rate of 10ml/min while measuring the pressure within the renal pelvis. A rise in pressure above 22 cm H2O suggests that the urinary collection system is obstructed. When arriving at this pressure measurement, bladder pressure is subtracted from the initial reading of internal pressure. (The test was first described by Whittaker in 1973 to test the hypothesis that patients whose hydronephrosis persists after the posterior urethral valves have been ablated usually have ureters that are not obstructed, even though they may be dilated.)Kay recommends that a neonate born with untreated in utero hydronephrosis receive a renal ultrasound within two days of birth.  A renal pelvis greater than 12mm in a neonate is considered abnormal and suggests significant dilation and possible abnormalities such as obstruction or morphological abnormalities in the urinary tract.The choice of imaging depends on the clinical presentation (history, symptoms and examination findings).  In the case of renal colic (one sided loin pain usually accompanied by a trace of blood in the urine) the initial investigation is usually a spiral or helical CT scan.  This has the advantage of showing whether there is any obstruction of flow of urine causing hydronephrosis as well as demonstrating the function of the other kidney.  Many stones are not visible on plain X-ray or IVU but 99% of stones are visible on CT and therefore CT is becoming a common choice of initial investigation.  CT is not used, however, when there is a reason to avoid radiation exposure, e.g. in pregnancy.For incidentally detected prenatal hydronephrosis, the first study to obtain is a postnatal renal ultrasound, since as noted, many cases of prenatal hydronephrosis resolve spontaneously.  This is generally done within the first few days after birth, although there is some risk that obtaining an imaging study this early may miss some cases of mild hydronephrosis due to the relative oliguria of a newborn.  Thus, some experts recommend obtaining a follow-up ultrasound at 4–6 weeks to reduce the false-negative rate of the initial ultrasound </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Penile pain and explain in detail? [/INST]  </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Tracheoesophageal fistula and explain in detail? [/INST] A tracheoesophageal fistula (TEF, or TOF; see spelling differences) is an abnormal connection (fistula) between the esophagus and the trachea. TEF is a common congenital abnormality, but when occurring late in life is usually the sequela of surgical procedures such as a laryngectomy.

Presentation
Tracheoesophageal fistula is suggested in a newborn by copious salivation associated with choking, coughing, vomiting, and cyanosis coincident with the onset of feeding. Esophageal atresia and the subsequent inability to swallow typically cause polyhydramnios in utero. Rarely it may present in an adult.

Complications
Surgical repair can sometimes result in complications, including:
Stricture, due to gastric acid erosion of the shortened esophagus
Leak of contents at the point of anastomosis
Recurrence of fistula
Gastro-esophageal reflux disease
Dysphagia
Asthma-like symptoms, such as persistent coughing/wheezing
Recurrent chest infections
Tracheomalacia

Associations
Neonates with TEF or esophageal atresia are unable to feed properly. Once diagnosed, prompt surgery is required to allow the food intake. Some children experience problems following TEF surgery; they can develop dysphagia and thoracic problems. Children with TEF can also be born with other abnormalities, most commonly those described in VACTERL association - a group of anomalies which often occur together, including heart, kidney and limb deformities </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Hemoperitoneum and explain in detail? [/INST] Hemoperitoneum  (also haemoperitoneum, sometimes also hematoperitoneum) is the presence of blood in the peritoneal cavity. The blood accumulates in the space between the inner lining of the abdominal wall and the internal abdominal organs.  Hemoperitoneum is generally classified as a surgical emergency; in most cases, urgent laparotomy is needed to identify and control the source of the bleeding </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Orthostatic hypotension and explain in detail? [/INST] Orthostatic hypotension, also known as postural hypotension, is a medical condition wherein a persons blood pressure drops when standing up or sitting down. Primary orthostatic hypertension is also often referred to as neurogenic orthostatic hypotension. The drop in blood pressure may be sudden (vasovagal orthostatic hypotension), within 3 minutes (classic orthostatic hypotension) or gradual (delayed orthostatic hypotension). It is defined as a fall in systolic blood pressure of at least 20 mmHg or diastolic blood pressure of at least 10 mmHg when a person assumes a standing position. It occurs predominantly by delayed (or absent) constriction of the lower body blood vessels, which is normally required to maintain adequate blood pressure when changing the position to standing. As a result, blood pools in the blood vessels of the legs for a longer period, and less is returned to the heart, thereby leading to a reduced cardiac output and inadequate blood flow to the brain.
Very mild occasional orthostatic hypotension is common and can occur briefly in anyone, although it is prevalent in particular among the elderly and those with known low blood pressure. Severe drops in blood pressure can lead to fainting, with a possibility of injury. Moderate drops in blood pressure can cause confusion/inattention, delirium, and episodes of ataxia. Chronic orthostatic hypotension is associated with cerebral hypoperfusion that may accelerate the pathophysiology of dementia. Whether it is a causative factor in dementia is unclear.The numerous possible causes for orthostatic hypotension include certain medications (e.g. alpha blockers), autonomic neuropathy, decreased blood volume, multiple system atrophy,  and age-related blood-vessel stiffness.
Apart from addressing the underlying cause, orthostatic hypotension may be treated with a recommendation to increase salt and water intake (to increase the blood volume), wearing compression stockings, and sometimes medication (fludrocortisone, midodrine, or others). Salt loading (dramatic increases in salt intake) must be supervised by a doctor, as this can cause severe neurological problems if done too aggressively.

Signs and symptoms
Orthostatic hypotension is characterized by symptoms that occur after standing (from lying or sitting), particularly when done rapidly. Many report lightheadedness (a feeling that one might be about to faint), sometimes severe, or even actual fainting with associated fall risk. With chronic orthostatic hypotension, the condition and its effects may worsen even as fainting and many other symptoms become less frequent. Generalized weakness or tiredness may also occur. Some also report difficulty concentrating, blurred vision, tremulousness, vertigo, anxiety, palpitations (awareness of the heartbeat), unsteadiness, feeling sweaty or clammy, and sometimes nausea. A person may look pale. Some people may experience severe orthostatic hypotension with the only symptoms being confusion or extreme fatigue. Chronic severe orthostatic hypotension may present as fluctuating cognition/delirium.  Women who are pregnant are also susceptible to orthostatic hypotension.

Associated diseases
The disorder may be associated with Addisons disease, atherosclerosis (build-up of fatty deposits in the arteries), diabetes, pheochromocytoma, porphyria, and certain neurological disorders, including  autoimmune autonomic ganglionopathy, multiple system atrophy, and other forms of dysautonomia.  It is also associated with Ehlers–Danlos syndrome and anorexia nervosa. It is also present in many patients with Parkinsons disease or Lewy body dementia resulting from sympathetic denervation of the heart or as a side effect of dopaminomimetic therapy. This rarely leads to fainting unless the person has developed true autonomic failure or has an unrelated heart problem.Another disease, dopamine beta hydroxylase deficiency, also thought to be underdiagnosed, causes loss of sympathetic noradrenergic function and is characterized by low or extremely low levels of norepinephrine, but an excess of dopamine.Quadriplegics and paraplegics also might experience these symptoms due to multiple systems inability to maintain normal blood pressure and blood flow to the upper part of the body.

Causes
Some causes of orthostatic hypotension include neurodegenerative disorders, low blood volume (e.g. caused by dehydration, bleeding, or the use of diuretics), drugs that cause vasodilation, other types of drugs (notably, narcotics and marijuana), discontinuation of vasoconstrictors, prolonged bed rest (immobility), significant recent weight loss,  anemia, vitamin B12 deficiency, or recent bariatric surgery.

Medication
Orthostatic hypotension can be a side effect of certain antidepressants, such as tricyclics or monoamine oxidase inhibitors (MAOIs). Marijuana and tetrahydrocannabinol can on occasion produce marked orthostatic hypotension. Alcohol can potentiate orthostatic hypotension to the point of syncope. Orthostatic hypotension can also be a side effect of alpha-1 blockers (alpha1 adrenergic blocking agents).  Alpha1 blockers inhibit vasoconstriction normally initiated by the baroreceptor reflex upon postural change and the subsequent drop in pressure.

Other factors
Patients prone to orthostatic hypotension are the elderly, post partum mothers, and those having been on bed rest. People with anorexia nervosa and bulimia nervosa often develop orthostatic hypotension as a common side effect. Consuming alcohol may also lead to orthostatic hypotension due to its dehydrating effects.

Mechanism
Orthostatic hypotension happens when gravity causes blood to pool in the lower extremities, which in turn compromises venous return, resulting in decreased cardiac output and subsequent lowering of arterial pressure. For example, changing from a lying position to standing loses about 700 ml of blood from the thorax, with a decrease in systolic and diastolic blood pressures. The overall effect is insufficient blood perfusion in the upper part of the body.Normally, a series of cardiac, vascular, neurologic, muscular, and neurohumoral responses occurs quickly so the blood pressure does not fall very much.  One response is a vasoconstriction (baroreceptor reflex), pressing the blood up into the body again. (Often, this mechanism is exaggerated and is why diastolic blood pressure is a bit higher when a person is standing up, compared to a person in the horizontal position.) Therefore, some factor that inhibits one of these responses and causes a greater than normal fall in blood pressure is required. Such factors include low blood volume, diseases, and medications.

Diagnosis
Orthostatic hypotension can be confirmed by measuring a persons blood pressure after lying flat for 5 minutes, then 1 minute after standing, and 3 minutes after standing. Orthostatic hypotension is defined as a fall in systolic blood pressure of at least 20 mmHg or the diastolic blood pressure of at least 10 mmHg between the supine reading and the upright reading.  Also, the heart rate should be measured for both positions.  A significant increase in heart rate from supine to standing may indicate a compensatory effort by the heart to maintain cardiac output. A related syndrome, postural orthostatic tachycardia syndrome (POTS), is diagnosed when at least a 30 bpm increase in heart rate occurs with little or no change in blood pressure. A tilt table test may also be performed.

Definition
Orthostatic hypotension (or postural hypotension) is a drop in blood pressure upon standing.  One definition (AAFP) calls for a systolic blood pressure decrease of at least 20 mm Hg or a diastolic blood pressure decrease of at least 10 mm Hg within 3 minutes of standing. A common first symptom is lightheadedness upon standing, possibly followed by more severe symptoms: narrowing or loss of vision, dizziness, weakness, and even syncope (fainting).

Subcategories
Orthostatic hypotension can be subcategorized into three groups – initial, classic, and delayed.Initial orthostatic hypotension is frequently characterized by a systolic blood pressure decrease of ≥40 mmHg or diastolic blood pressure decrease of ≥20 mmHg within 15 seconds of standing </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Hyposmia and explain in detail? [/INST] Hyposmia, or microsmia, is a reduced ability to smell and to detect odors. A related condition is anosmia, in which no odors can be detected.  Some of the causes of olfaction problems are allergies, nasal polyps, viral infections and head trauma.  In 2012 an estimated 9.8 million people aged 40 and older in the United States had hyposmia and an additional 3.4 million had anosmia/severe hyposmia.Hyposmia might be a very early sign of Parkinsons disease.  Hyposmia is also an early and almost universal finding in Alzheimers disease and dementia with Lewy bodies. Lifelong hyposmia could be caused by Kallmann syndrome or Autism Spectrum Disorder. Along with other chemosensory disturbances, hyposmia can be a key indicator of COVID-19.

Epidemiology
The National Health and Nutrition Examination Survey (NHANES) collected data on chemosensory function (taste and smell) in a nationally-representative sample of US civilian, non-institutionalized persons in 2012 </s>