<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Necrotizing fasciitis and can you explain it in depth? [/INST] Necrotizing fasciitis (NF), also known as flesh-eating disease, is a bacterial infection that results in the death of parts of the bodys soft tissue. It is a severe disease of sudden onset that spreads rapidly. Symptoms usually include red or purple skin in the affected area, severe pain, fever, and vomiting. The most commonly affected areas are the limbs and perineum.Typically, the infection enters the body through a break in the skin such as a cut or burn. Risk factors include poor immune function such as from diabetes or cancer, obesity, alcoholism, intravenous drug use, and peripheral artery disease. It does not typically spread between people. The disease is classified into four types, depending on the infecting organism. Between 55 and 80% of cases involve more than one type of bacteria. Methicillin-resistant Staphylococcus aureus (MRSA) is involved in up to a third of cases. Medical imaging is often helpful to confirm the diagnosis.Necrotizing fasciitis may be prevented with proper wound care and handwashing. It is usually treated with surgery to remove the infected tissue, and intravenous antibiotics. Often, a combination of antibiotics is used, such as penicillin G, clindamycin, IV vancomycin, and gentamicin. Delays in surgery are associated with a much higher risk of death. Despite high-quality treatment, the risk of death is between 25 and 35%.Necrotizing fasciitis occurs in about 0.4 people per 100,000 per year in the U.S., and about 1 per 100,000 in Western Europe. Both sexes are affected equally. It becomes more common among older people and is rare in children. It has been described at least since the time of Hippocrates. The term "necrotizing fasciitis" first came into use in 1952.

Signs and symptoms
Symptoms may include fever, swelling, and complaints of excessive pain. The initial skin changes are similar to cellulitis or abscess, thus making the diagnosis at early stages difficult. Hardening of the skin and soft tissue and swelling beyond the area of skin changes are commonly present in those with early necrotizing changes. The redness and swelling usually blend into surrounding normal tissues. The overlying skin may appear shiny and tense. Other signs which are more suggestive of necrotizing changes (but present in later stages in 7 to 44% of the cases) are: formation of bullae, bleeding into the skin which is present before skin necrosis (skin turning from red to purple and black due to thrombosis of blood vessels), presence of gas in tissues, and reduced or absent sensation over the skin (due to the necrosis of the underlying nerves). Rapid progression to shock despite antibiotic therapy is another indication of necrotizing fasciitis. Necrotizing changes affecting the groin are known as Fournier gangrene.However, those who are immunocompromised (have cancer, use corticosteroid, on radiotherapy, chemotherapy, HIV/AIDS, or prior organ or bone marrow transplantation) may not show typical symptoms. Immunocompromised persons also have twice the risk of death from necrotizing infections, so higher suspicion should be maintained in this group.

Cause
Risk factors
More than 70% of cases are recorded in people with at least one of these clinical situations: immunosuppression, diabetes, alcoholism/drug abuse/smoking, malignancies, and chronic systemic diseases. For reasons that are unclear, it occasionally occurs in people with an apparently normal general condition.Necrotizing fasciitis can occur at any part of the body, but it is more commonly seen at the extremities, perineum, and genitals. Only a few of such cases arise from the chest and abdomen. Trauma is the usual cause of the infection, such as from intravenous drug injection, insulin injection, animal and insect bites, catheter insertion over the skin, or a fistula connecting skin to the internal body organs. Skin infections such as abscess and ulcers can also complicate necrotizing fasciitis. Spreading of infection through blood has been suggested for those with streptococcal pharyngitis. For infection of the perineum and genitals (Fournier gangrene), trauma, surgery, urinary tract infection, stones, and Bartholin gland abscess are the usual causes.The risk of developing necrotizing fasciitis from a wound can be reduced by good wound care and handwashing.

Bacteria
Types of soft-tissue necrotizing infection can be divided into four classes according to the types of bacteria infecting the soft tissue. This classification system was first described by Giuliano and  his colleagues in 1977.Type I infection: This is the most common type of infection, and accounts for 70 to 80% of cases. It is caused by a mixture of bacterial types, usually in abdominal or groin areas. This type of infection is usually caused by various species of Gram-positive cocci, (Staphylococcus aureus, Streptococcus pyogenes, and enterococci), Gram-negative rods,  (Escherichia coli, Pseudomonas aeruginosa), and anaerobes, (Bacteroides and Clostridium species). Populations of those affected are typically older with medical comorbidities such as diabetes mellitus, obesity, and immunodeficiency. Usually, trauma is not the cause of such infections. Previous history of abscess infection or gut perforation with bacterial translocation may be elicited. Clostridial infection accounts for 10% of type I infection.  Clostridium species involved are Clostridium perfringens, Clostridium septicum, and Clostridium sordellii, which typically cause gas gangrene (also known as myonecrosis). Clostridium perfringens produces two deadly toxins: alpha-toxin and theta-toxin. Alpha-toxin causes excessive platelet aggregation which blocks blood vessels and deprives the vital organs of oxygen supply. This creates an acidic, oxygen-deficient environment for the proliferation of bacteria. When alpha-toxin is absorbed by soft tissues, it can inhibit the migration of white blood cells from blood vessels into the soft tissue, thus impairing phagocyte function. The two toxins together can cause destruction of red blood cells in blood vessels, damage to the integrity of the blood vessels, and suppression of heart function.Clostridium sordellii can also produce two major toxins: all known virulent strains produce the essential virulence factor lethal toxin (TcsL), and a number also produce haemorrhagic toxin (TcsH). TcsL and TcsH are both members of the large clostridial cytotoxin (LCC) family. The key Clostridium septicum virulence factor is a pore-forming toxin called alpha-toxin, though it is unrelated to the Clostridium perfringens alpha-toxin. Myonecrotic infections caused by these clostridial species commonly occur in injecting heroin users. Those with clostridial infections typically have severe pain at the wound site, where the wound typically drains foul-smelling blood mixed with serum (serosanguinous discharge). Shock can progress rapidly after initial injury or infection, and once the state of shock is established, the chance of dying exceeds 50%. Another bacterium associated with similar rapid disease progression is group A streptococcal infection (mostly Streptococcus pyogenes). Meanwhile, other bacterial infections require two or more days to become symptomatic.Type II infection: This infection accounts for 20 to 30% of cases, mainly involving the extremities. This mainly involves  Streptococcus pyogenes bacteria, alone or in combination with staphylococcal infections. Both types of bacteria can progress rapidly and manifest as toxic shock syndrome. Streptococcus species produce M protein, which acts as a superantigen, stimulating a massive systemic immune response which is not effective against the bacterial antigen, precipitating shock. Type II infection more commonly affects young, healthy adults with a history of injury.Type III infection: Vibrio vulnificus, a bacterium found in saltwater, is a rare cause of this infection, which occurs through a break in the skin.  Disease progression is similar to type II but sometimes with little visible skin changes.Type IV infection: Some authors have described the type IV infection as fungal in nature.

Diagnosis
Early diagnosis is difficult, as the disease often looks early on like a simple superficial skin infection. While a number of laboratory and imaging modalities can raise the suspicion for necrotizing fasciitis, none can rule it out. The gold standard for diagnosis is a surgical exploration in a setting of high suspicion. When in doubt, a small incision can be made into the affected tissue, and if a finger easily separates the tissue along the fascial plane, the diagnosis is confirmed and an extensive debridement should be performed.

Medical imaging
Imaging has a limited role in the diagnosis of necrotizing fasciitis. The time delay in performing imaging is a major concern. Plain radiography may show subcutaneous emphysema (gas in the subcutaneous tissue), which is strongly suggestive of necrotizing changes, but it is not sensitive enough to detect all the cases, because necrotizing skin infections caused by bacteria other than clostridial infections usually do not show subcutaneous emphysema. If the diagnosis is still in doubt, computed tomography (CT) scans and magnetic resonance imaging (MRI) are more sensitive modalities than plain radiography. However, both the CT scan and MRI are not sensitive enough to rule out necrotizing changes completely. CT scan may show fascial thickening, edema, subcutaneous gas, and abscess formation. In MRI, when fluid collection with deep fascia involvement occurs, thickening or enhancement with contrast injection, necrotizing fasciitis should be strongly suspected. Meanwhile, ultrasonography can show superficial abscess formation, but is not sensitive enough to diagnose necrotizing fasciitis. CT scan is able to detect about 80% of cases, while MRI may pick up slightly more.

Scoring system
A white blood cell count greater than 15,000 cells/mm3 and serum sodium level less than 135 mmol/L have a sensitivity of 90% in detecting the necrotizing soft tissue infection. It also has a 99% chance of ruling out necrotizing changes if the values have shown otherwise. Various scoring systems are being developed to determine the likelihood of getting necrotizing fasciitis, but a scoring system developed by Wong and colleagues in 2004 is the most commonly used. It is the laboratory risk indicator for necrotizing fasciitis (LRINEC) score, which can be used to stratify by risk those people having signs of severe cellulitis or abscess to determine the likelihood of necrotizing fasciitis being present. It uses six laboratory values: C-reactive protein, total white blood cell count, hemoglobin, sodium, creatinine, and blood glucose. A score of 6 or more indicates that necrotizing fasciitis should be seriously considered. The scoring criteria are:

CRP (mg/L) ≥150: 4 points
WBC count (×103/mm3)
<15: 0 points
15–25: 1 point
>25: 2 points
Hemoglobin (g/dL)
>13.5: 0 points
11–13.5: 1 point
<11: 2 points
Sodium (mmol/L) <135: 2 points
Creatinine (umol/L) >141: 2 points
Glucose (mmol/L) >10: 1 pointHowever, the scoring system has not been validated. The values would be falsely positive if any other inflammatory conditions are present. Therefore, the values derived from this scoring system should be interpreted with caution. About 10% of patients with necrotizing fasciitis in the original study still had a LRINEC score <6. A validation study showed that patients with a LRINEC score ≥6 have a higher rate of both death and amputation.

Prevention
Necrotizing fasciitis can be partly prevented by good wound care and handwashing.

Treatment
Surgical debridement (cutting away affected tissue) is the mainstay of treatment for necrotizing fasciitis. Early medical treatment is often presumptive; thus, antibiotics should be started as soon as this condition is suspected. Tissue cultures (rather than wound swabs) are taken to determine appropriate antibiotic coverage, and antibiotics may be changed in light of results. Besides blood pressure control and hydration, support should be initiated for those with unstable vital signs and low urine output.

Surgery
Aggressive wound debridement should be performed early, usually as soon as the diagnosis of necrotizing soft tissue infection (NSTI) is made. Surgical incisions often extend beyond the areas of induration (the hardened tissue) to remove the damaged blood vessels that are responsible for the induration. However, cellulitic soft tissues are sometimes spared from debridement for later skin coverage of the wound. More than one operation may be used to remove additional necrotic tissue. In some cases when an extremity is affected by a NSTI, amputation may be the surgical treatment of choice. After the wound debridement, adequate dressings should be applied to prevent exposure of bones, tendons, and cartilage so that such structures do not dry out and to promote wound healing.For necrotizing infection of the perineal area (Fourniers gangrene), wound debridement and wound care in this area can be difficult because of the excretory products that often render this area dirty and affect the wound-healing process. Therefore, regular dressing changes with a fecal management system can help to keep the wound at the perineal area clean. Sometimes, colostomy may be necessary to divert the excretory products to keep the wound at the perineal area clean.

Antibiotics
Empiric antibiotics are usually initiated as soon as the diagnosis of NSTI has been made, and then later changed to culture-guided antibiotic therapy. In the case of NSTIs, empiric antibiotics are broad-spectrum, covering gram-positive (including MRSA), gram-negative, and anaerobic bacteria.While studies have compared moxifloxacin (a fluoroquinolone) and amoxicillin-clavulanate (a penicillin) and evaluated appropriate duration of treatment (varying from 7 to 21 days), no definitive conclusions on the efficacy of treatment, ideal duration of treatment, or the adverse effects could be made due to poor-quality evidence.

Add-on therapy
Hyperbaric oxygen: While human and animal studies have shown that high oxygen tension in tissues helps to reduce edema, stimulate fibroblast growth, increase the killing ability of white blood cells, inhibit bacterial toxin release, and increase antibiotic efficacy, no high-quality trials have been shown to support or refute the use of hyperbaric oxygen therapy in patients with NSTIs.
Intravenous immunoglobulin (IVIG): No clear difference between using IVIG and placebo has been shown in the treatment of NSTIs, and one study showed serious adverse effects with IVIG use, including acute kidney injury, allergic reactions, aseptic meningitis syndrome, haemolytic anaemia, thrombi, and transmissible agents.
AB103: One study assessed the efficacy of a new type of treatment that affects the immune response, called AB103. The study showed no difference in mortality with use of this therapy, but it is difficult to draw definitive conclusions due to low-quality evidence.
Supportive therapy: Supportive therapy, often including intravenous hydration, wound care, anticoagulants to prevent thromboembolic events, pain control, etc. should always be provided to patients when appropriate.

Epidemiology
Necrotizing fasciitis affects about 0.4 in every 100,000 people per year in the United States. About 1,000 cases of necrotizing fasciitis occur per year in the United States, but the rates have been increasing. This could be due to increasing awareness of this condition, leading to increased reporting, or  bacterial virulence or increasing bacterial resistance against antibiotics. In some areas of the world, it is as common as one in every 100,000 people.Higher rates of necrotizing fasciitis are seen in those with obesity or diabetes, and those who are immunocompromised or alcoholic, or have peripheral artery disease. However, the disease may also occur in young, healthy adults with no underlying illnesses. NSAIDs may increase the rates of necrotizing infections due to the modification of immune response in the body, because NSAIDs inhibit the cycloxygenase-1 and cycloxygenase-2 enzymes which are important in producing thromboxane and prostaglandin E2. Prostaglandin has been responsible for fever, inflammation, and pain. The inhibition of prostaglandin E2 production reduces inflammatory response and leukocyte adhesion, and thus reduces immune response against bacterial invasion, giving rise to soft-tissue infection.

History
In the fifth century BCE, Hippocrates described necrotizing soft tissue infection as a disease where those affected would have "erysipelas all over the body while the cause was only a trivial accident. Bones, flesh, and sinew (cord, tendon, or nerve) would fall off from the body and there were many deaths". The first English description for necrotizing soft-tissue infection was by British surgeon Leonard Gillespie and British physicians Gilbert Blaine and Thomas Trotter in the 18th century. At that time, necrotizing soft-tissue infections were known variously as "phagedaenic ulcer" (ulceration that spreads and destroys surrounding tissue), "gangrenous phagedena", "gangrenous ulcer", "malignant ulcer", "putrid ulcer", "fulminating gangrene", "necrotizing erysipelas", "gangrenous erysipelas", "crepitant cellulitis", "gangrenous cellulitis", "Meleney cellulitis", "necrotizing synergistic cellulitis", "hemolytic streptococcal gangrene", "progressive bacterial synergistic gangrene", "necrotizing abscess", "galloping gangrene", or "hospital gangrene". Later, "hospital gangrene" became more commonly used. In 1871 Confederate States Army surgeon Joseph Jones reported 2,642 cases of hospital gangrene with a mortality rate of 46%. In 1883, Dr Jean-Alfred Fournier described the necrotizing infection of the perineum and scrotum, now called Fournier gangrene. The term "necrotizing fasciitis" was first coined by Wilson in 1952. Its definition has become broader, to include not only infection of fascia, but also other soft-tissue infection. Despite being disfavored by the medical community, the term "galloping gangrene" is frequently used in sensationalistic news media to refer to outbreaks of necrotizing fasciitis.

Society and culture
Notable cases
1994 Lucien Bouchard, former premier of Québec, Canada, who was infected while leader of the federal official opposition Bloc Québécois party, lost a leg to the illness.
1994 A cluster of cases occurred in Gloucestershire, in the west of England. Of five confirmed and one probable infection, two died. The cases were believed to be connected. The first two had acquired the Streptococcus pyogenes bacteria during surgery; the remaining four were community-acquired. The cases generated much newspaper coverage, with lurid headlines such as "Flesh Eating Bug Ate My Face".
1997 Ken Kendrick, former agent and partial owner of the San Diego Padres and Arizona Diamondbacks, contracted the disease. He had seven surgeries in a little more than a week and later fully recovered.
2004 Don Rickles, American stand-up comedian, actor, and author, known especially for his insult comedy, contracted the disease in his left leg. He had six operations and later recovered. The condition confined him in his later years to performing comedy from a chair.
2004 Eric Allin Cornell, winner of the 2001 Nobel Prize in Physics, lost his left arm and shoulder to the disease.
2005 Alexandru Marin, an experimental particle physicist, professor at MIT, Boston University, and Harvard University, and researcher at CERN and JINR, died from the disease.
2006 Alan Coren, British writer and satirist, announced in his Christmas column for The Times that his long absence as a columnist had been caused by his contracting the disease while on holiday in France.
2009 R. W. Johnson, British journalist and historian, contracted the disease in March after injuring his foot while swimming. His leg was amputated above the knee.
2011 Jeff Hanneman, guitarist for the thrash metal band Slayer, contracted the disease </s>


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<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Iatrogenesis and can you explain it in depth? [/INST] Iatrogenesis is the causation of a disease, a harmful complication, or other ill effect by any medical activity, including diagnosis, intervention, error, or negligence. First used in this sense in 1924, the term was introduced to sociology in 1976 by Ivan Illich, alleging that industrialized societies impair quality of life by overmedicalizing life. Iatrogenesis may thus include mental suffering via medical beliefs or a practitioners statements. Some iatrogenic events are obvious, like amputation of the wrong limb, whereas others, like drug interactions, can evade recognition. In a 2013 estimate, about 20 million negative effects from treatment had occurred globally. In 2013, an estimated 142,000 persons died from adverse effects of medical treatment, up from an estimated 94,000 in 1990.

Iatrogenic avenues
Risk associated with medical interventions
Adverse effects of prescription drugs
Overuse of drugs (causing, for example, antibiotic resistance in bacteria)
Prescription drug interaction

Medical errors
Incorrect prescription, perhaps due to illegible handwriting or computer typos
Faulty procedures, techniques, information, methods, or equipment
Negligence
Hospital-acquired infections

Causes and consequences
Medical error and negligence
Iatrogenic conditions need not result from medical errors, such as mistakes made in surgery, or the prescription or dispensing of the wrong therapy, such as a drug. In fact, intrinsic and sometimes adverse effects of a medical treatment are iatrogenic. For example, radiation therapy and chemotherapy—necessarily aggressive for therapeutic effect – frequently produce such iatrogenic effects as hair loss, hemolytic anemia, diabetes insipidus, vomiting, nausea, brain damage, lymphedema, infertility, etc. The loss of function resulting from the required removal of a diseased organ is iatrogenic, as in the case of diabetes consequential to the removal of all or part of the pancreas.
The incidence of iatrogenesis may be misleading in some cases. For example, a ruptured aortic aneurysm is fatal in most cases; the survival rate for treatment of a ruptured aortic aneurysm is under 25%. Patients who die during or after an operation will still be considered iatrogenic deaths, but the procedure itself remains a better bet than the probability of death if left untreated.
Other situations may involve actual negligence or faulty procedures, such as when pharmacotherapists produce handwritten prescriptions for drugs.

Adverse effects
A very common iatrogenic effect is caused by drug interaction, i.e., when pharmacotherapists fail to check for all medications a patient is taking and prescribe new ones that interact agonistically or antagonistically (thereby potentiating or attenuating the intended therapeutic effect). Such situations can cause significant morbidity and mortality. Adverse reactions, such as allergic reactions to drugs, even when unexpected by pharmacotherapists, are also classified as iatrogenic.
The evolution of antibiotic resistance in bacteria is iatrogenic as well. Bacterial strains resistant to antibiotics have evolved in response to the over prescription of antibiotic drugs.Certain drugs are toxic in their own right in therapeutic doses because of their mechanism of action. Alkylating antineoplastic agents, for example, cause DNA damage, which is more harmful to cancer cells than regular cells. However, alkylation causes severe side-effects and is actually carcinogenic in its own right, with potential to lead to the development of secondary tumors. In a similar manner, arsenic-based medications like melarsoprol, used to treat trypanosomiasis, can cause arsenic poisoning.
Adverse effects can appear mechanically. The design of some surgical instruments may be decades old, hence certain adverse effects (such as tissue trauma) may never have been properly characterized.

Psychiatry
In psychiatry, iatrogenesis can occur due to misdiagnosis (including diagnosis with a false condition, as was the case of hystero-epilepsy). An example of a partially iatrogenic condition due to common misdiagnosis is bipolar disorder, especially in pediatric patients. Other conditions such as somatoform disorder and chronic fatigue syndrome are theorized to have significant sociocultural and iatrogenic components. Posttraumatic stress disorder is hypothesized to be prone to iatrogenic complications based on treatment modality. Even use of antipsychotic drugs leads to loss of brain mass.The psychiatric treatment of some conditions and populations, such as substance abuse are regarded as carrying risks for iatrogenesis. At the other end of the spectrum, dissociative identity disorder is considered by a minority of theorists to be a wholly iatrogenic disorder with the bulk of diagnoses arising from a tiny fraction of practitioners.The degree of association of any particular condition with iatrogenesis is unclear and in some cases controversial. The over-diagnosis of psychiatric conditions (with the assignment of mental illness terminology) may relate primarily to clinician dependence on subjective criteria. The assignment of pathological nomenclature is rarely a benign process and can easily rise to the level of emotional iatrogenesis, especially when no alternatives outside of the diagnostic naming process have been considered. Many former patients come to the conclusion that their difficulties are largely the result of the power relationships inherent in psychiatric treatment, which has led to the rise of the anti-psychiatry movement.

Iatrogenic poverty
Meessen et al. used the term "iatrogenic poverty" to describe impoverishment induced by medical care. Impoverishment is described for households exposed to catastrophic health expenditure or to hardship financing. Every year, worldwide, over 100,000 households fall into poverty due to health care expenses. A study reported that in the United States in 2001, illness and medical debt caused half of all personal bankruptcies. Especially in countries in economic transition, the willingness to pay for health care is increasing, and the supply side does not stay behind and develops very fast. But the regulatory and protective capacity in those countries is often lagging behind. Patients easily fall into a vicious cycle of illness, ineffective therapies, consumption of savings, indebtedness, sale of productive assets, and eventually poverty.

Social and cultural iatrogenesis
The 20th-century social critic Ivan Illich broadened the concept of medical iatrogenesis in his 1974 book Medical Nemesis: The Expropriation of Health by defining it at three levels.

First, clinical iatrogenesis is the injury done to patients by ineffective, unsafe, and erroneous treatments as described above. In this regard, he described the need for evidence-based medicine 20 years before the term was coined.
Second, at another level social iatrogenesis is the medicalization of life in which medical professionals, pharmaceutical companies, and medical device companies have a vested interest in sponsoring sickness by creating unrealistic health demands that require more treatments or treating non-diseases that are part of the normal human experience, such as age-related declines. In this way, aspects of medical practice and medical industries can produce social harm in which society members ultimately become less healthy or excessively dependent on institutional care </s>


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<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Uterine atony and can you explain it in depth? [/INST] Uterine atony is the failure of the uterus to contract adequately following delivery. Contraction of the uterine muscles during labor compresses the blood vessels and slows flow, which helps prevent hemorrhage and facilitates coagulation. Therefore, a lack of uterine muscle contraction can lead to an acute hemorrhage, as the vasculature is not being sufficiently compressed. Uterine atony is the most common cause of postpartum hemorrhage, which is an emergency and potential cause of fatality. Across the globe, postpartum hemorrhage is among the top five causes of maternal death. Recognition of the warning signs of uterine atony in the setting of extensive postpartum bleeding should initiate interventions aimed at regaining stable uterine contraction.

Risk factors
There are many risk factors for uterine atony and several are due to the type of labor a mother experiences such as prolonged labor, labor lasting less than 3 hours, uterine inversion, the use of magnesium sulfate infusions, and extended use of oxytocin. Uterine distention caused by things like more than one fetus present, polyhydramnios, fetal macrosomia, uterine fibroids, chorioamnionitis can also lead to decreased uterine function and atony. Retained placental tissue or placental disorders, such as an adherent placenta, placenta previa, and abruption placentae increase the mothers risk of PPH.  Body mass index (BMI) above 40 and coagulopathies are known risk factors.Magnesium sulfate is used often in patients with preeclampsia and eclampsia, can inadvertently inhibit uterine contractions. In addition, preeclampsia can lead to blood disorders such as  thrombocytopenia, platelet abnormalities, and disseminated intravascular coagulation. Cesarean delivery, especially after prolonged labor, may cause the muscles of the uterus to become tired and stop contracting or contraction can be inhibited at the surgical site.

Epidemiology
Uterine atony occurs during 1 in 40 births in the United States and is responsible for at least 80% of cases of postpartum hemorrhage.

Pathophysiology
The uterus is composed of an interconnected muscle fibers known as the myometrium. The blood vessels that provide the blood supply to the placenta pass through this muscle.  After labor it is the contraction of these muscles that physically squeeze the blood vessels so that hemostasis can occur after the delivery of the fetus and the placenta.  Local hemostatic factors like tissue factor type-1 plasminogen activator inhibitor and platelets and clotting factors aid in stopping the blood flow.This physiological contraction does not occur if the myometrium becomes atonic. Oxytocin is released continuously during labor to stimulate uterine muscle contraction so the that the fetus can be delivered and it is continued to be released after delivery to stop blood flow.  If the oxytocin receptors become desensitized and no longer respond to the hormone then the uterus does not contract. The uterus can also be structurally damaged or distended to prevent contraction. Therefore, as placenta is delivered arteries are damaged and without the muscle contractions hemostasis cannot be reached.Blood loss is an expected part of labor and less than 500 mL is considered normal. Generally, primary PPH is classified as being more than 500 mL of blood lost in the first 24 hours following delivery. Those who have a caesarean section typically have more blood loss than a vaginal birth; so 1000 mL is commonly used to determine excessive blood loss. It is easy to underestimate maternal blood loss because the primary method of assessment is visual observation.

Evaluation and diagnosis
Identifying risk factors early in the pregnancy is essential in managing uterine atony and PPH. This allows for planning and organizing the necessary resources including staff, medicines, assistive devices, and the proper blood products. The delivery plan should also be cognizant of the ability of the hospital or facility to provide an appropriate level of care if any complications occur.Most diagnosis of uterine atony are made during the physical exam directly upon completion of the delivery. Diffuse uterine atony is typically diagnosed by patient observation rather than blood loss. The uterus can be directly palpated or observed indirectly using a bimanual examination post delivery. An atonic uterus can feel soft, "boggy" and/or enlarged. Bleeding from the cervical os is also common. If the atony is localized to one area of the uterus, the upper, fundal region may be still be squeezing while the lower uterine segment is non functional. This can be difficult to see with a cursory abdominal examination and easily overlooked. Therefore, a comprehensive vaginal, abdominal, and rectal examination should be performed. The physical examination may include  ultrasound imaging for rapid visualization of the uterus and other causes of bleeding. Expulsion of gestational products such as the placenta and rapid identification of obstetric lacerations, helps exclude other causes of PPH. Laboratory tests can be drawn if coagulopathies are suspected.

Treatment and management
Prevention
Before delivery all patients should be screened for risk factors and then assigned a postpartum hemorrhage risk stratification based on the American College of Obstetricians and Gynecologists recommendations. If the woman is at a medium risk, blood should be typed and screened. Those assessed to be high risk should be typed and cross-matched.
Active management of the third stage of labor is routinely implemented and is considered the standard for patient care. It can be utilized to reduce the risk of PPH. Active management of the third stage includes uterine massage and a IV low dose oxytocin. Whether it is given just before or after the delivery of the placenta is subject to provider preference. It is suggested that using an uterotonic, such as oxytocin, prophylactically will help reduce blood loss and the need for a blood transfusion after delivery.A uterine massage is performed by placing a hand on the lower abdomen and using repetitive massaging or squeezing movements in attempt to stimulate the uterus. It is theorized, the massaging motion stimulates uterine contraction and may also trigger the release of local prostaglandins to help hemostasis.

Treatment
If uterine atony occurs even after all preventative measures have been taken, medical management should be implemented. Uterine fundal massage and compression should be maintained, while drugs are administered. An intravenous catheter should also be started to administer fluids, medications, and blood productsThere are several different types of uterotonic drugs that may be given, and the each has its own advantages and disadvantages. Moreover, the use of combination uterotonic therapy is a common practice and might be more effective at controlling bleeding than monotherapy. Some combinations might include oxytocin plus misoprostol, oxytocin plus ergometrine, and carbetocin.Medications used for PPH include the following:
Oxytocin (Pitocin) Stimulation of oxytocin receptors in the uterine muscle leads to contractions. The number of these receptors increases during pregnancy and with labor. There are also more in the fundus than in the lower uterine segment. Oxytocin has a quick onset of action, within a few minutes, but also loses effectiveness quickly because of a short half-life. The medicine is given in a rapid infusion and may cause hypotension. Oxytocin alone is the usually treatment of atony in the US. However, if bleeding is uncontrolled  after administration of oxytocin, then a second uterotonic is given.
Carbetocin: A synthetic analog of oxytocin, works similarly to oxytocin but the half-life is much longer. It binds to smooth muscle receptors of the uterus, like oxytocin and has been reported to produce a stable uterine contraction, followed by rhythmic contractions. It is not available in the US but is available in many countries for the prevention of uterine atony and hemorrhage.
Methylergonovine: This is an ergot alkaloid and has multiple mechanisms of action to induce fast, regular uterine contractions which leads to sustained uterine contraction. It can cause peripheral vasoconstriction and is contraindicated in patients with hypertension or pregnancy related hypertension.
15-methyl-PGF2-alpha (Hemabate, Carboprost)  Highly effective but it is expensive. It can cause bronchospasm and it should be avoided in asthmatics. May cause diarrhea, fevers, or tachycardia.
Misoprostol (Cytotec):  A synthetic prostaglandin E1 analog oral medication that can stimulate uterine contractions. Misoprostol does not need to be refrigerated because it is heat stable. It is easy to administer compared with oxytocin and ergot alkaloids in low-resource areas where refrigeration and sterile needles are not available. May cause a low-grade fever.
Dinoprostone (Prostin E2): An alternative prostaglandin to misoprostol.After the medication is administered, the mother should be closely observed for to confirm the bleeding has stopped. If the bleeding has not stopped or physical exam does not show signs of restored uterine function within 30 minutes of medication administration, immediate invasive interventions are recommended.Tamponade techniques include uterine packing (extending into the vagina) with gauze that also has a Foley catheter in place to allow for bladder drainage. It is inexpensive and readily available. Balloon tamponade is the suggested method of tamponade in guidelines for management of PPH. A bakri balloon to tamponade (also with vaginal packing) can be used with Foley catheter insertion to facilitate bladder drainage. Vacuum-induced uterine tamponade is newer technique that uses low-level vacuum to evacuate blood from the uterine cavity and facilitate uterine contractionSurgical management techniques include:

Compression sutures such as the B-Lynch
Uterine curettage to remove retained placental products
Uterine artery ligation, with or without ligation of the tubo-ovarian vessels. Ligation of the uterine and utero-ovarian arteries can decrease uterine bleeding by reducing the pressure of arterial blood flow in the uterus </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Gonadotropin-resistant ovary syndrome and can you explain it in depth? [/INST]  </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Trevor disease and can you explain it in depth? [/INST] Trevor disease, also known as dysplasia epiphysealis hemimelica and Trevors disease, is a congenital bone developmental disorder. There is 1 case per million population. The condition is three times more common in males than in females.

Presentation
This disorder is rare, and is characterised by an asymmetrical limb deformity due to localized overgrowth of cartilage, histologically resembling osteochondroma. It is believed to affect the limb bud in early fetal life. The condition occurs mostly in the ankle or knee region and it is always confined to a single limb </s>


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<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Qigong and can you explain it in depth? [/INST] Qigong (), qi gong, chi kung, chi ung, or chi gung (simplified Chinese: 气功; traditional Chinese: 氣功; pinyin: qìgōng; Wade–Giles: ch‘i kung; lit. life-energy cultivation) is a system of coordinated body-posture and movement, breathing, and meditation used for the purposes of health, spirituality, and martial-arts training. With roots in Chinese medicine, philosophy, and martial arts, qigong is traditionally viewed by the Chinese and throughout Asia as a practice to cultivate and balance qi (pronounced approximately as "chi" or "chee"), translated as "life energy".Qigong practice typically involves moving meditation, coordinating slow-flowing movement, deep rhythmic breathing, and a calm meditative state of mind. People practice qigong throughout China and worldwide for recreation, exercise, relaxation, preventive medicine, self-healing, alternative medicine, meditation, self-cultivation, and training for martial arts.

Etymology
Qigong (Pinyin), chi kung (Wade-Giles), and chi gung (Yale) are Romanized words for two Chinese characters: qì (气／氣) and gōng (功).
Qi (or chi) primarily means air, gas or breath but is often translated as a metaphysical concept of vital energy, referring to a supposed energy circulating through the body; though a more general definition is universal energy, including heat, light, and electromagnetic energy; and definitions often involve breath, air, gas, or the relationship between matter, energy, and spirit. Qi is the central underlying principle in traditional Chinese medicine and martial arts. Gong (or kung) is often translated as cultivation or work, and definitions include practice, skill, mastery, merit, achievement, service, result, or accomplishment, and is often used to mean gongfu (kung fu) in the traditional sense of achievement through great effort. The two words are combined to describe systems to cultivate and balance life energy, especially for health and wellbeing.The term qigong as currently used was promoted in the late 1940s through the 1950s to refer to a broad range of Chinese self-cultivation exercises, and to emphasize health and scientific approaches, while de-emphasizing spiritual practices, mysticism, and elite lineages.

History and origins
With roots in ancient Chinese culture dating back more than 4,000 years, a wide variety of qigong forms have developed within different segments of Chinese society: in traditional Chinese medicine for preventive and curative functions; in Confucianism to promote longevity and improve moral character; in Daoism and Buddhism as part of meditative practice; and in Chinese martial arts to enhance self defending abilities. Contemporary qigong blends diverse and sometimes disparate traditions, in particular the Daoist meditative practice of "internal alchemy" (Neidan 內丹術), the ancient meditative practices of "circulating qi" (Xing qi 行氣) and "standing meditation" (Zhan zhuang 站桩), and the slow gymnastic breathing exercise of "guiding and pulling" (Dao yin 導引). Traditionally, qigong was taught by master to students through training and oral transmission, with an emphasis on meditative practice by scholars and gymnastic or dynamic practice by the working masses.Starting in the late 1940s and the 1950s, the mainland Chinese government tried to integrate disparate qigong approaches into one coherent system, with the intention of establishing a firm scientific basis for qigong practice. In 1949, Liu Guizhen established the name "Qigong" to refer to the system of life-preserving practices that he and his associates developed, based on Dao yin and other philosophical traditions. This attempt is considered by some sinologists as the start of the modern or scientific interpretation of qigong.  During the Great Leap Forward (1958–1963) and the Cultural Revolution (1966–1976), qigong, along with other traditional Chinese medicine, was under tight control with limited access among the general public, but was encouraged in state-run rehabilitation centers and spread to universities and hospitals. After the Cultural Revolution, qigong, along with tai chi, was popularized as daily morning exercise practiced en masse throughout China.
Popularity of qigong grew rapidly during the Deng and Jiang eras after Mao Zedongs death in 1976 through the 1990s, with estimates of between 60 and 200 million practitioners throughout China.  Along with popularity and state sanction came controversy and problems: claims of extraordinary abilities bordering on the supernatural, pseudoscience explanations to build credibility, a mental condition labeled qigong deviation, formation of cults, and exaggeration of claims by masters for personal benefit. In 1985, the state-run National Qigong Science and Research Organization was established to regulate the nations qigong denominations. In 1999, in response to widespread revival of old traditions of spirituality, morality, and mysticism, and perceived challenges to State control, the Chinese government took measures to enforce control of public qigong practice, including shutting down qigong clinics and hospitals, and banning groups such as Zhong Gong and Falun Gong.: 161–174
Since the 1999 crackdown, qigong research and practice have only been officially supported in the context of health and traditional Chinese medicine. The Chinese Health Qigong Association, established in 2000, strictly regulates public qigong practice, with limitation of public gatherings, requirement of state approved training and certification of instructors, and restriction of practice to state-approved forms.Through the forces of migration of the Chinese diaspora, tourism in China, and globalization, the practice of qigong spread from the Chinese community to the world. Today, millions of people around the world practice qigong and believe in the benefits of qigong to varying degrees. Similar to its historical origin, those interested in qigong come from diverse backgrounds and practice it for different reasons, including for recreation, exercise, relaxation, preventive medicine, self-healing, alternative medicine, self-cultivation, meditation, spirituality, and martial arts training.

Overview
Practices
Qigong comprises a diverse set of practices that coordinate body (調身), breath (調息), and mind (調心) based on Chinese philosophy. Practices include moving and still meditation, massage, chanting, sound meditation, and non-contact treatments, performed in a broad array of body postures. Qigong is commonly classified into two foundational categories: 1) dynamic or active qigong (dong gong), with slow flowing movement; and 2) meditative or passive qigong (jing gong), with still positions and inner movement of the breath.: 21770–21772  From a therapeutic perspective, qigong can be classified into two systems:
1) internal qigong, which focuses on self-care and self-cultivation, and;
2) external qigong, which involves treatment by a therapist who directs or transmits qi.: 21777–21781 As moving meditation, qigong practice typically coordinates slow stylized movement, deep diaphragmatic breathing, and calm mental focus, with visualization of guiding qi through the body. While implementation details vary, generally qigong forms can be characterized as a mix of four types of practice: dynamic, static, meditative, and activities requiring external aids.

Dynamic practiceinvolves fluid movement, usually carefully choreographed, coordinated with breath and awareness. Examples include the slow stylized movements of Tai chi chuan, Baguazhang, and Xing Yi Quan. Other examples include graceful movement that mimics the motion of animals in Five Animals (Wu Qin Xi qigong), White Crane, and Wild Goose (Dayan) Qigong. As a form of gentle exercise, qigong is composed of movements that are typically repeated, strengthening and stretching the body, increasing fluid movement (blood, synovial, and lymph), enhancing balance and proprioception, and improving the awareness of how the body moves through space.Static practiceinvolves holding postures for sustained periods of time.  In some cases this bears resemblance to the practice of Yoga and its continuation in the Buddhist tradition. For example Yiquan, a Chinese martial art derived from xingyiquan, emphasizes static stance training. In another example, the healing form Eight Pieces of Brocade (Baduanjin qigong) is based on a series of static postures.Meditative practiceutilizes breath awareness, visualization, mantra, chanting, sound, and focus on philosophical concepts such as qi circulation, aesthetics, or moral values. In traditional Chinese medicine and Daoist practice, the meditative focus is commonly on cultivating qi in dantian energy centers and balancing qi flow in meridian and other pathways.  In various Buddhist traditions, the aim is to still the mind, either through outward focus, for example on a place, or through inward focus on the breath, a mantra, a koan, emptiness, or the idea of the eternal. In the Confucius scholar tradition, meditation is focused on humanity and virtue, with the aim of self-enlightenment.Use of external agentsMany systems of qigong practice include the use of external agents such as ingestion of herbs, massage, physical manipulation, or interaction with other living organisms.  For example, specialized food and drinks are used in some medical and Daoist forms, whereas massage and body manipulation are sometimes used in martial arts forms. In some medical systems a qigong master uses non-contact treatment, purportedly guiding qi through his or her own body into the body of another person.

Forms
There are numerous qigong forms. 75 ancient forms that can be found in ancient literature and also 56 common or contemporary forms have been described in a qigong compendium.: 203–433  The list is by no means exhaustive. Many contemporary forms were developed by people who had recovered from their illness after qigong practice.
Most of the qigong forms come under the following categories:
Medical qigong
Martial qigong
Spiritual qigong
Intellectual qigong
Life nourishing qigong

Development of "health qigong"
In 1995, there was Qigong Talent Bank, an organization of Science Research of Chinese Qigong, functioning as network system of the senior Chinese qigong talents in China. In order to promote qigong exercises in a standardised and effective way with a scientific approach, The Chinese Health Qigong Association (CHQA) appointed panels of Qigong experts, Chinese medicine doctors and sport science professors from different hospitals, universities and qigong lineage across China to research and develop new sets of qigong exercises. In 2003 the CHQA officially promoted a new system called "health qigong", which consisted of four newly developed health qigong forms:

Health Qigong Muscle-Tendon Change Classic (Health Qigong Yì Jīn Jīng 易筋經).
Health Qigong Five Animals Frolics (Health qigong Wu Qin Xi 五禽戲).
Health Qigong Six Healing Sounds (Health Qigong Liu Zi Jue 六字訣).
Health Qigong Eight Pieces of Brocade (Health Qigong Ba Duan Jin 八段錦).In 2010, the Chinese Health Qigong Association officially introduced five additional health qigong forms:
Health Qigong Tai Chi Yang Sheng Zhang (太極養生杖): a tai chi form from the stick tradition.
Health Qigong Shi Er Duan Jin (十二段錦): seated exercises to strengthen the neck, shoulders, waist, and legs.
Health Qigong Daoyin Yang Sheng Gong Shi Er Fa (導引養生功十二法): 12 routines from Daoyin tradition of guiding and pulling qi.
Health Qigong Mawangdui Daoyin (馬王堆導引术): guiding qi along the meridians with synchronous movement and awareness.
Health Qigong Da Wu (大舞): choreographed exercises to lubricate joints and guide qi.Other commonly practised qigong styles and forms include:

Soaring Crane Qigong
Wisdom Healing Qigong
Pan Gu Mystical Qigong
Wild Goose (Dayan) Qigong
Dragon and Tiger Qigong
Primordial Qigong (Wujigong)
Chilel Qigong
Phoenix Qigong
Yuan Qigong
Zhong Yuan Qigong

Techniques
Whether viewed from the perspective of exercise, health, philosophy, or martial arts training, several main principles emerge concerning the practice of qigong:
Intentional movement: careful, flowing balanced style
Rhythmic breathing: slow, deep, coordinated with fluid movement
Awareness: calm, focused meditative state
Visualization: of qi flow, philosophical tenets, aesthetics
Chanting/Sound: use of sound as a focal pointAdditional principles:

Softness: soft gaze, expressionless face
Solid Stance: firm footing, erect spine
Relaxation: relaxed muscles, slightly bent joints
Balance and Counterbalance: motion over the center of gravityAdvanced goals:

Equanimity: more fluid, more relaxed
Tranquility: empty mind, high awareness
Stillness: smaller and smaller movements, eventually to complete stillnessThe most advanced practice is generally considered to be with little or no motion.

Traditional and classical theory
Over time, five distinct traditions or schools of qigong developed in China, each with its own theories and characteristics: Chinese Medical Qigong, Daoist Qigong, Buddhist Qigong, Confucian Qigong, and Martial Qigong.: 30–80  All of these qigong traditions include practices intended to cultivate and balance qi.

Traditional Chinese medicine
The theories of ancient Chinese qigong include the Yin-Yang and Five Phases Theory, Essence-Qi-Spirit Theory, Zang-Xiang Theory, and Meridians and Qi-Blood Theory, which have been synthesized as part of Traditional Chinese Medicine (TCM).: 45–57  TCM focuses on tracing and correcting underlying disharmony, in terms of deficiency and excess, using the complementary and opposing forces of yin and yang  (陰陽), to create a balanced flow of qi. Qi is believed to be cultivated and stored in three main dantian energy centers and to travel through the body along twelve main meridians (Jīng Luò 經絡), with numerous smaller branches and tributaries.  The main meridians correspond to twelve main organs ) (Zàng fǔ 臟腑). Qi is balanced in terms of yin and yang in the context of the traditional system of Five Phases (Wu xing 五行). A person is believed to become ill or die when qi becomes diminished or unbalanced.  Health is believed to be returned by rebuilding qi, eliminating qi blockages, and correcting qi imbalances. These TCM concepts do not translate readily to modern science and medicine.

Daoism
In Daoism, various practices now known as Daoist qigong are claimed to provide a way to achieve longevity and spiritual enlightenment, as well as a closer connection with the natural world.

Buddhism
In Buddhism meditative practices now known as Buddhist qigong are part of a spiritual path that leads to spiritual enlightenment or Buddhahood.

Confucianism
In Confucianism practices now known as Confucian qigong provide a means to become a Junzi (君子) through awareness of morality.

Contemporary qigong
In contemporary China, the emphasis of qigong practice has shifted away from traditional philosophy, spiritual attainment, and folklore, and increasingly to health benefits, traditional medicine and martial arts applications, and a scientific perspective. Qigong is now practiced by millions worldwide, primarily for its health benefits, though many practitioners have also adopted traditional philosophical, medical, or martial arts perspectives, and even use the long history of qigong as evidence of its effectiveness.

Contemporary Chinese medical qigong
Qigong has been recognized as a "standard medical technique" in China since 1989, and is sometimes included in the medical curriculum of major universities in China.: 34  The 2013 English translation of the official Chinese Medical Qigong textbook used in China: iv, 385  defines CMQ as "the skill of body-mind exercise that integrates body, breath, and mind adjustments into one" and emphasizes that qigong is based on "adjustment" (tiao 調, also translated as "regulation", "tuning", or "alignment") of body, breath, and mind.: 16–18   As such, qigong is viewed by practitioners as being more than common physical exercise, because qigong combines postural, breathing, and mental training in one to produce a particular psychophysiological state of being.: 15   While CMQ is still based on traditional and classical theory, modern practitioners also emphasize the importance of a strong scientific basis.: 81–89   According to the 2013 CMQ textbook, physiological effects of qigong are numerous, and include improvement of respiratory and cardiovascular function, and possibly neurophysiological function.: 89–102

Conventional medicine
Especially since the 1990s, conventional or mainstream Western medicine often strives to heed the model of evidence-based medicine, EBM, which demotes medical theory, clinical experience, and physiological data to prioritize the results of controlled, and especially randomized, clinical trials of the treatment itself. Although some clinical trials support qigongs effectiveness in treating conditions diagnosed in Western medicine, the quality of these studies is mostly low and, overall, their results are mixed.

Integrative, complementary, and alternative medicine
Integrative medicine (IM) refers to "the blending of conventional and complementary medicines and therapies with the aim of using the most appropriate of either or both modalities to care for the patient as a whole",: 455–456  whereas complementary is using a non-mainstream approach together with conventional medicine, while alternative is using a non-mainstream approach in place of conventional medicine. Qigong is used by integrative medicine practitioners to complement conventional medical treatment, based on complementary and alternative medicine interpretations of the effectiveness and safety of qigong.: 22278–22306

Scientific basis
Scientists interested in qigong have sought to describe or verify the effects of qigong, to explore mechanisms of effects, to form scientific theory with respect to qigong, and to identify appropriate research methodology for further study.: 81–89  In terms of traditional theory, the existence of qi has not been independently verified in an experimental setting. In any case, some researches have reported effects on pathophysiological parameters of biomedical interest.

Practitioners, uses and cautions
Recreation and popular use
People practice qigong for many different reasons, including for recreation, exercise and relaxation, preventive medicine and self-healing, meditation and self-cultivation, and training for martial arts. Practitioners range from athletes to people with disabilities. Because it is low impact and can be done lying, sitting, or standing, qigong is accessible for people with disabilities, seniors, and people recovering from injuries.

Therapeutic use
Therapeutic use of qigong is directed by TCM, CAM, integrative medicine, and other health practitioners. In China, where it is considered a "standard medical technique",: 34  qigong is commonly prescribed to treat a wide variety of conditions, and clinical applications include hypertension, coronary artery disease, peptic ulcers, chronic liver diseases, diabetes mellitus, obesity, menopause syndrome, chronic fatigue syndrome, insomnia, tumors and cancer, lower back and leg pain, cervical spondylosis, and myopia.: 261–391   Outside China qigong is used in integrative medicine to complement or supplement accepted medical treatments, including for relaxation, fitness, rehabilitation, and treatment of specific conditions. However, there is no high-quality evidence that qigong is actually effective for these conditions. Based on systematic reviews of clinical research, there is insufficient evidence for the effectiveness of using qigong as a therapy for any medical condition.

Safety and cost
Qigong is generally viewed as safe. No adverse effects have been observed in clinical trials, such that qigong is considered safe for use across diverse populations. Cost for self-care is minimal, and cost efficiencies are high for group delivered care. Typically the cautions associated with qigong are the same as those associated with any physical activity, including risk of muscle strains or sprains, advisability of stretching to prevent injury, general safety for use alongside conventional medical treatments, and consulting with a physician when combining with conventional treatment.

Clinical research
Overview
Although there is ongoing clinical research examining the potential health effects of qigong, there is little financial or medical incentive to support high-quality research, and still only a limited number of studies meet accepted medical and scientific standards of randomized controlled trials (RCTs). Clinical research concerning qigong has been conducted for a wide range of medical conditions, including bone density, cardiopulmonary effects, physical function, falls and related risk factors, quality of life, immune function, inflammation, hypertension, pain, and cancer treatment.

Systematic reviews
A 2009 systematic review on the effect of qigong exercises on reducing pain concluded that "the existing trial evidence is not convincing enough to suggest that internal qigong is an effective modality for pain management."A 2010 systematic review of the effect of qigong exercises on cancer treatment concluded "the effectiveness of qigong in cancer care is not yet supported by the evidence from rigorous clinical trials." A separate systematic review that looked at the effects of qigong exercises on various physiological or psychological outcomes found that the available studies were poorly designed, with a high risk of bias in the results. Therefore, the authors concluded, "Due to limited number of RCTs in the field and methodological problems and high risk of bias in the included studies, it is still too early to reach a conclusion about the efficacy and the effectiveness of qigong exercise as a form of health practice adopted by the cancer patients during their curative, palliative, and rehabilitative phases of the cancer journey."A 2011 overview of systematic reviews of controlled clinical trials, Lee et al. concluded that "the effectiveness of qigong is based mostly on poor quality research" and "therefore, it would be unwise to draw firm conclusions at this stage."  Although a 2010 comprehensive literature review found 77 peer-reviewed RCTs, Lee et al.s overview of systematic reviews as to particular health conditions found problems like sample size, lack of proper control groups, with lack of blinding associated with high risk of bias.A 2015 systematic review of the effect of qigong exercises on cardiovascular diseases and hypertension found no conclusive evidence for effect. Also in 2015, a systemic review into the effects on hypertension suggested that it may be effective, but that the evidence was not conclusive because of the poor quality of the trials it included, and advised more rigorous research in the future </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Panophthalmitis and can you explain it in depth? [/INST] Panophthalmitis is the inflammation of all coats of the animal eye including intraocular structures. It can be caused by infection, particularly from Pseudomonas species, such as Pseudomonas aeruginosa, Clostridium species, Whipples disease, and also fungi </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Cardiorenal syndrome and can you explain it in depth? [/INST] Cardiorenal syndrome (CRS) is an umbrella term used in the medical field that defines disorders of the heart and kidneys whereby "acute or chronic dysfunction in one organ may induce acute or chronic dysfunction of the other". The kidney and the heart are compared to a marriage that has "bumps" in the road, some may even say it can come to an end. The heart and kidney play vital functions that contribute to the wellbeing of the body in a healthy person. When one of these organs fail, the other subsequently fails as well, like a domino affect. The heart and the kidneys are involved in maintaining hemodynamic stability and organ perfusion through an intricate network. Patients who have renal failure first may be hard to determine if Heart Failure is concurrent. These two organs communicate with one another through a variety of pathways in an interdependent relationship. In a 2004 report from National Heart, Lung and Blood Institute, CRS was defined as a condition where treatment of congestive heart failure is limited by decline in kidney function. This definition has since been challenged repeatedly but there still remains little consensus over a universally accepted definition for CRS. At a consensus conference of the Acute Dialysis Quality Initiative (ADQI), the CRS was classified into five subtypes primarily based upon the organ that initiated the insult as well as the acuity of disease.

Signs and symptoms
Risk factors
The following risk factors have been associated with increased incidence of CRS.
Older age
Comorbid conditions (diabetes mellitus, uncontrolled hypertension, anemia)
Drugs (anti-inflammatory agents, diuretics, ACE inhibitors, ARBs)
History of heart failure with impaired left ventricular ejection fraction
Prior myocardial infarction
Elevated New York Heart Association (NYHA) functional class
Elevated cardiac troponins
Chronic kidney disease (reduced eGFR, elevated BUN, creatinine, or cystatin)

Pathophysiology
The pathophysiology of CRS can be attributed to two broad categories of "hemodynamic factors" such as low cardiac output, elevation of both intra-abdominal and central venous pressures, and non-hemodynamic factors or "cardiorenal connectors" such as neurohormonal and inflammatory activation. It was previously believed that low cardiac output in heart failure patients result in decreased blood flow to the kidneys which can lead to progressive deterioration of kidney function. As a result, diuresis of these patients will result in hypovolemia and pre-renal azotemia. However, several studies did not find an association between kidney dysfunction and cardiac output or other hemodynamic parameters. In addition, CRS has been observed in patients with diastolic dysfunction who have normal left ventricular systolic function. Therefore, there must be additional mechanisms involved in the progression of CRS. Elevated intra-abdominal pressures resulting from ascites and abdominal wall edema may be associated with worsening kidney functions in heart failure patients. Several studies have shown that as a result of this increased intra-abdominal pressure there is increased central venous pressure and congestion of the kidneys veins, which can lead to worsening kidney function. In addition, many neurohormonal and inflammatory agents are implicated in the progression of CRS. These include increased formation of reactive oxygen species, endothelin, arginine vasopressin, and excessive sympathetic activity which can result in myocardial hypertrophy and necrosis. Other cardiorenal connectors include renin-angiotensin-system activation, nitric oxide/reactive oxygen species imbalance, inflammatory factors and abnormal activation of the sympathetic nervous system, which can cause structural and functional abnormalities in both heart and/or the kidney. There is a close interaction within these cardiorenal connectors as well as between these factors and the hemodynamic factors which makes the study of CRS pathophysiology complicated.

Diagnosis
It is critical to diagnose CRS at an early stage in order to achieve optimal therapeutic efficacy. However, unlike markers of heart damage or stress such as troponin, creatine kinase, natriuretic peptides, reliable markers for acute kidney injury are lacking. Recently, research has found several biomarkers that can be used for early detection of acute kidney injury before serious loss of organ function may occur. Several of these biomarkers include neutrophil gelatinase-associated lipocalin (NGAL), N-acetyl-B-D-glucosaminidase (NAG), Cystatin C, and kidney injury molecule-1 (KIM-1) which have been shown to be involved in tubular damage. Other biomarkers that have been shown to be useful include BNP, IL-18, and fatty acid binding protein (FABP). However, there is great variability in the measurement of these biomarkers and their use in diagnosing CRS must be assessed.

Classification
Ronco et al. first proposed a five-part classification system for CRS in 2008 which was also accepted at ADQI consensus conference in 2010. These include:

The distinction between CRS type 2 and CRS type 4 is based on the assumption that, also in advanced and chronic disease, two different pathophysiological mechanisms can be distinguished, whereas both CKD and HF often develop due to a common pathophysiological background, most notably hypertension and diabetes mellitus. Furthermore, the feasibility of the distinction between CRS type 2 and 4 in terms of diagnosis can be questioned.Braam et al. argue that classifying the CRS based on the order in which the organs are affected and the timeframe (acute vs chronic) is too simplistic and without a mechanistic classification it is difficult to study CRS. They view the cardiorenal syndrome in a more holistic, integrative manner. They defined the cardiorenal syndrome as a pathophysiological condition in which combined heart and kidney dysfunction amplifies progression of failure of the individual organ, by inducing similar pathophysiological mechanisms. Therefore, regardless of which organ fails first, the same neurohormonal systems are activated causing accelerated cardiovascular disease, and progression of damage and failure of both organs. These systems are broken down into two broad categories of "hemodynamic factors" and non-hemodynamic factors or "cardiorenal connectors".

Management
Medical management of patients with CRS is often challenging as focus on treatment of one organ may have worsening outcome on the other. It is known that many of the medications used to treat HF may worsen kidney function. "As the population ages and the burden of renal disease and cardiovascular disease continue to rise, efforts to better understand the complicated relationship between these two organ systems are greatly needed." In addition, many trials on HF excluded patients with advanced kidney dysfunction. Therefore, our understanding of CRS management is still limited to this date. One study showes how ACE inhibitors and angiotensin II receptor antagonists have been found to prevent nephropathy in patients who have diabetes. Patients with kidney failure are less likely to get all guide-lined base therapies. Patients who have moderate to sever CKD was seen to have similar care when compared to those patients who had normal kidney function. This helps show how healthcare workers can do more to increase the outcome of those suffering.
Diuretics
Used in the treatment of heart failure and CRS patients, however must be carefully dosed to prevent kidney injury. Diuretic resistance is frequently a challenge for physicians to overcome which they may tackle by changing the dosage, frequency, or adding a second drug.ACEI, ARB, renin inhibitors, aldosterone inhibitors
The use of ACE inhibitors have long term protective effect on kidney and heart tissue. However, they should be used with caution in patients with CRS and kidney failure. Although patients with kidney failure may experience slight deterioration of kidney function in the short term, the use of ACE inhibitors is shown to have prognostic benefit over the long term. Two studies have suggested that the use of ACEI alongside statins might be an effective regimen to prevent a substantial number of CRS cases in high risk patients and improve survival and quality of life in these people. There are data suggesting combined use of statin and an ACEI improves clinical outcome more than a statin alone and considerably more than ACE inhibitor alone.Natriuretic peptides
Nesiritide which is an analogue of brain natriuretic peptide (BNP) was shown to result in poorer kidney outcome or have no effect.Vasopressin antagonists
Tolvaptan showed to have no benefit </s>