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Deep Learning Technology: Sebastian Arnold, Betty van Aken, Paul Grundmann, Felix A. Gers and Alexander Löser. Learning Contextualized Document Representations for Healthcare Answer Retrieval. The Web Conference 2020 (WWW'20)
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Treatment is based
on the stage of the disease. Stage 1 does not
require treatment and
should be observed. 4
Neovascularization
(stage 2) responds well
to laser ablation or
cryotherapy.2,4 Eyes
with retinal detachments (stages
3 through 5) require surgery, with
earlier stages requiring scleral
buckles and later stages ultimately
needing vitrectomy. 2,4
More recently, the efficacy of
anti-VEGF intravitreal injections
has been studied. In one study,
these injections, as an in adjunct
with laser, helped early stages
achieve stabilization, but further
investigation is needed.6
The aim of acute treatment is to halt progression of the edema as quickly as possible, which can be life-saving, particularly if the swelling is in the larynx. In Germany, most acute treatment consists of C1 inhibitor concentrate from donor blood, which must be administered intravenously; however, in most European countries, C1 inhibitor concentrate is only available to patients who are participating in special programs. In emergency situations where C1 inhibitor concentrate is not available, fresh frozen plasma (FFP) can be used as an alternative, as it also contains C1 inhibitor.
Other treatment modalities can stimulate the synthesis of C1 inhibitor, or reduce C1 inhibitor consumption. Purified C1 inhibitor, derived from human blood, has been used in Europe since 1979. Several C1 inhibitor treatments are now available in the U.S. Food and Drug Administration and two C1 inhibitor products are now available in Canada. Berinert P (CSL Behring), which is pasteurized, was approved by the F.D.A. in 2009 for acute attacks. Cinryze (ViroPharma), which is nanofiltered, was approved by the F.D.A. in 2008 for prophylaxis. Ruconest (Pharming) is a recombinant C1 inhibitor approved in the US and Europe that does not carry the risk of infectious disease transmission due to human blood-borne pathogens.
The medication ecallantide inhibits plasma kallikrein, and was approved by the F.D.A. (but not in Europe) for acute attacks in 2009. Icatibant inhibits the bradykinin B2 receptor, and was approved in Europe and the USA.
In hereditary angioedema, specific stimuli that have previously led to attacks may need to be avoided in the future. It does not respond to antihistamines, corticosteroids, or epinephrine.
Shampoos use a combination of special ingredients to control dandruff.
Antifungal treatments including ketoconazole, zinc pyrithione and selenium disulfide have been found to be effective. Ketoconazole appears to have a longer duration of effect.
Ketoconazole is a broad spectrum antimycotic agent that is active against "Candida" and "M. furfur". Of all the antifungals of the imidazole class, ketoconazole has become the leading contender among treatment options because of its effectiveness in treating seborrheic dermatitis as well.
Ciclopirox is widely used as an anti-dandruff agent in most preparations.
Cerebellar abiotrophy (CA), also referred to as the cerebellar cortical abiotrophy (CCA), is a genetic neurological disease in animals best known to affect certain breeds of horses, dogs and cats. It can also develop in humans. It develops when the neurons known as Purkinje cells, located in the cerebellum of the brain, begin to die off. These cells affect balance and coordination. They have a critical role to play in the brain. The Purkinje layer allows communication between the granular and molecular cortical layers in the cerebellum. Put simply, without Purkinje cells, an animal loses its sense of space and distance, making balance and coordination difficult. People with damage to the cerebellum can experience symptoms like unsteady gait, poor muscle control, and trouble speaking or swallowing.
"Abiotrophy" means the loss of a vital nutritive factor. The exact cause of cerebellar abiotrophy is not known, but it is thought to be due to an intrinsic metabolic defect.
In most cases, the Purkinje neurons begin to die off shortly after the animal is born and the condition is noticeable when the animal is less than six months old, though sometimes the onset of symptoms is gradual and the animal is much older before the owner or caretaker notices a problem.
CA cannot be prevented, other than by selective breeding to avoid the gene, and it cannot be cured. Genetic testing can detect carriers. In addition to dogs and horses, there also have been cases of cerebellar abiotrophy in Siamese and Domestic shorthair cats; in Angus, Polled Hereford, Charolais and Holstein Friesian cattle; Merino and Wiltshire sheep; and Yorkshire pigs.
XX females with lipoid CAH may need estrogen replacement at or after puberty. Active intervention has been used to preserve the possibility of fertility and conception in lipoid CAH females. In a case report in 2009, a woman with late onset lipoid CAH due to StAR deficiency underwent hormone replacement therapy in combination with an assisted fertility technique, intracytoplasmic sperm injection. This led to ovulation and with implantation of the in vitro fertilized egg, a successful birth.
Symptoms of cerebellar abiotrophy include ataxia or lack of balance, an awkward wide-legged stance, a head tremor (intention tremor) (in dogs, body tremors also occur), hyperreactivity, lack of menace reflex, stiff or high-stepping gait, coarse or jerky head bob when in motion (or in very young animals, when attempting to nurse), apparent lack of awareness of where the feet are (sometimes standing or trying to walk with a foot knuckled over), poor depth perception, and a general inability to determine space and distance. The symptoms, when taken as a group, are distinctive and not easily mimicked by other illnesses, though certain types of neurological injury and infection need to be ruled out. Verifying the diagnosis in a laboratory setting is possible only by examining the brain post-mortem to determine if there has been a loss of Purkinje cells.
Most affected animals have normal intelligence and mildly affected animals can, in theory, live out a normal lifespan. However, affected animals are quite accident-prone, and for this reason many animals that develop CA, particularly horses, are euthanized for humane reasons. Horses may experience difficulty stepping up and over objects, run into fences, fall easily, and even if allowed to mature to full growth, are generally considered unsafe to ride. Dogs may need lifetime assistance with tasks such as climbing stairs.
In horses, the symptoms may worsen from the time of onset for six to 12 months, but if not severe enough to mandate euthansia, they stabilize over time. In some dog breeds, symptoms appear to progressively worsen, but research is not consistent on this point. There also is some evidence that affected animals partially compensate for the condition by cognitively learning alternative methods for moving or to determine distance, and thus appear to improve because they become less accident-prone.
In terms of hemophilia C medication cyklokapron is often used for both treatment after an incident of bleeding and as a preventative measure to avoid excessive bleeding during oral surgery.
Treatment is usually not necessary, except in relation to operations, leading to many of those having the condition not being aware of it. In these cases, fresh frozen plasma or recombinant factor XI may be used, but only if necessary.
The afflicted may often suffer nosebleeds, while females can experience unusual menstrual bleeding which can be avoided by taking birth control such as: IUDs and oral or injected contraceptives to increase coagulation ability by adjusting hormones to levels similar to pregnancy.
Short-term prevention is normally administered before surgery or dental treatment. In Germany, C1-INH concentrate is used for this and given 1–1.5 hours before the procedure. In countries where C1-inhibitor concentrate is not available or only available in an emergency (laryngeal edema), high-dose androgen treatment is administered for 5–7 days.
X-linked myotubular myopathy (MTM) is a form of centronuclear myopathy (CNM) associated with myotubularin 1.
Genetically inherited traits and conditions are often referred to based upon whether they are located on the "sex chromosomes" (the X or Y chromosomes) versus whether they are located on "autosomal" chromosomes (chromosomes other than the X or Y). Thus, genetically inherited conditions are categorized as being sex-linked (e.g., X-linked) or autosomal. Females have two X-chromosomes, while males only have a single X chromosome, and a genetic abnormality located on the X chromosome is much more likely to cause clinical disease in a male (who lacks the possibility of having the normal gene present on any other chromosome) than in a female (who is able to compensate for the one abnormal X chromosome).
The X-linked form of MTM is the most commonly diagnosed type. Almost all cases of X-linked MTM occurs in males. Females can be "carriers" for an X-linked genetic abnormality, but usually they will not be clinically affected themselves. Two exceptions for a female with a X-linked recessive abnormality to have clinical symptoms: one is a manifesting carrier and the other is X-inactivation. A manifesting carrier usually has no noticeable problems at birth; symptoms show up later in life. In X-inactivation, the female (who would otherwise be a carrier, without any symptoms), actually presents with full-blown X-linked MTM. Thus, she congenitally presents (is born with) MTM.
Thus, although" MTM1" mutations most commonly cause problems in boys, these mutations can also cause clinical myopathy in girls, for the reasons noted above. Girls with myopathy and a muscle biopsy showing a centronuclear pattern should be tested for "MTM1" mutations.
Many clinicians and researchers use the abbreviations XL-MTM, XLMTM or X-MTM to emphasize that the genetic abnormality for myotubular myopathy (MTM) is X-linked (XL), having been identified as occurring on the X chromosome. The specific gene on the X chromosome is referred to as MTM-1. In theory, some cases of CNM may be caused by an abnormality on the X chromosome, but located at a different site from the gene "MTM1", but currently "MTM1" is the only X-linked genetic mutation site identified for myotubular or centronuclear myopathy. Clinical suspicion for X-linked inheritance would be a disease affecting multiple boys (but no girls) and a pedigree chart showing inheritance only through the maternal (mother’s) side of each generation.
Many herbal and antioxidant remedies have been advocated for chronic liver disease but the evidence is not conclusive. Some support may be found in the orthodox medical use of two of these: N-acetyl cysteine (NAC), is the treatment of choice for acetaminophen overdose; both NAC and milk-thistle (Silybum marianum) or its derivative silibinin are used in liver poisoning from certain mushrooms, notably amanita phalloides, although the use of milk-thistle is controversial. Some common herbs are known or suspected to be harmful to the liver, including black cohosh, ma huang, chaparral, comfrey, germander, greater celandine, kava, mistletoe, pennyroyal, skull cap and valerian.
The treatment of chronic liver disease depends on the cause. Specific conditions may be treated with medications including corticosteroids, interferon, antivirals, bile acids or other drugs. Supportive therapy for complications of cirrhosis include diuretics, albumin, vitamin K, blood products, antibiotics and nutritional therapy. Other patients may require surgery or a transplant. Transplant is required when the liver fails and there is no other alternative.
X-linked adrenal hypoplasia congenita is a genetic disorder that mainly affects males. It involves many endocrine tissues in the body, especially the adrenal glands.
A genetic predisposition is a genetic characteristic which influences the possible phenotypic development of an individual organism within a species or population under the influence of environmental conditions. In medicine, genetic susceptibility to a disease refers to a genetic predisposition to a health problem, which may eventually be triggered by particular environmental or lifestyle factors, such as tobacco smoking or diet. Genetic testing is able to identify individuals who are genetically predisposed to certain diseases.
Treatment of all forms of CAH may include any of:
1. supplying enough glucocorticoid to reduce hyperplasia and overproduction of androgens or mineralocorticoids
2. providing replacement mineralocorticoid and extra salt if the person is deficient
3. providing replacement testosterone or estrogen at puberty if the person is deficient
4. additional treatments to optimize growth by delaying puberty or delaying bone maturation
All of these management issues are discussed in more detail in congenital adrenal hyperplasia due to 21-hydroxylase deficiency.
Dexamethasone is used as an off-label early pre-natal treatment for the symptoms of CAH in female fetuses, but it does not treat the underlying congenital disorder. A 2007 Swedish clinical trial found that treatment may cause cognitive and behavioural defects, but the small number of test subjects means the study cannot be considered definitive. A 2012 American study found no negative short term outcomes, but "lower cognitive processing in CAH girls and women with long-term DEX exposure." Administration of pre-natal dexamethasone has been the subject of controversy over issues of informed consent and because treatment must predate a clinical diagnosis of CAH in the female fetus, especially because in utero dexamethasone may cause metabolic problems that are not evident until later in life; Swedish clinics ceased recruitment for research in 2010.
The treatment has also raised concerns in LGBT and bioethics communities following publication of an essay posted to the forum of the Hastings Center, and research in the Journal of Bioethical Inquiry, which found that pre-natal treatment of female fetuses was suggested to prevent those fetuses from becoming lesbians after birth, may make them more likely to engage in "traditionally" female-identified behaviour and careers, and more interested in bearing and raising children. Citing a known attempt by a man using his knowledge of the fraternal birth order effect to avoid having a homosexual son by using a surrogate, the essayists (Professor Alice Dreger of Northwestern University's Feinberg School of Medicine, Professor Ellen Feder of American University and attorney Anne Tamar-Mattis) suggest that pre-natal "dex" treatments constitute the first known attempt to use "in utero" protocols to reduce the incidence of homosexuality and bisexuality in humans. Research on the use of prenatal hormone treatments to prevent homosexuality stretches back to the early 1990s or earlier.
Since CAH is a recessive gene, both the mother and father must be recessive carriers of CAH for a child to have CAH. Due to advances in modern medicine, those couples with the recessive CAH genes have an option to prevent CAH in their offspring through preimplantation genetic diagnosis (PGD). In PGD, the egg is fertilized outside the women's body in a petri dish (IVF). On the 3rd day, when the embryo has developed from one cell to about 4 to 6 cells, one of those cells is removed from the embryo without harming the embryo. The embryo continues to grow until day 5 when it is either frozen or implanted into the mother. Meanwhile, the removed cell is analyzed to determine if the embryo has CAH. If the embryo is determined to have CAH, the parents may make a decision as to whether they wish to have it implanted in the mother or not.
Meta-analysis of the studies supporting the use of dexamethasone on CAH at-risk fetuses found "less than one half of one percent of published 'studies' of this intervention were regarded as being of high enough quality to provide meaningful data for a meta-analysis. Even these four studies were of low quality" ... "in ways so slipshod as to breach professional standards of medical ethics" and "there were no data on long-term follow-up of physical and metabolic outcomes in children exposed to dexamethasone".
Dextromethorphan hydrobromide is a generic drug that affects the signals in the brain that trigger the cough reflex. It is generally used as a cough suppressant, although it can sometimes be used, medicinally, as a pain reliever, and is also used as a recreational drug. "Dextromethorphan (DM) is a sigma-1 receptor agonist and an uncompetitive NMDA receptor antagonist."
Quinidine sulfate affects the way the heart beats, and is generally used in people with certain heart rhythm disorders. It is also used to treat malaria. Quinidine sulfate, as a metabolic inhibitor, "increases plasma levels of dextromethorphan by competitively inhibiting cytochrome P450 2D6, which catalyzes a major biotransformation pathway for dextromethorphan," enabling therapeutic dextromethorphan concentrations.
Nuedexta is a patented combination of these two generic drugs, and is the first FDA-approved drug for the treatment of PBA, approved on October 29, 2010. In December 2007, clinical study information for Nuedexta was first submitted to ClinicalTrials.gov, (a Web-based resource maintained by the National Library of Medicine (NLM) at the National Institutes of Health (NIH)). Sponsored by Avanir Pharmaceuticals, (with brief title, "Safety and Efficacy of AVP-923 in PBA Patients With ALS or MS"), the study was assigned NCT Number NCT00573443. Final updates and verifications occurred in June 2013 on the ClinicalTrials.gov site.
For this multicenter study, the "Objectives...[were] to evaluate the safety, tolerability, and efficacy of two different doses of AVP-923 [Dextromethorphan/quinidine combination]...when compared to placebo." The conditions and results of that study are as follows:
Other studies have confirmed the results of NCT00573443, but, "The mechanism by which dextromethorphan exerts therapeutic effects in patients with pseudobulbar affect is unknown."
Because hormone treatment rarely achieves average size, several surgical techniques similar to phalloplasty for penis enlargement have been devised and performed; but they are not generally considered successful enough to be widely adopted and are rarely performed in childhood.
In extreme cases of micropenis, there is barely any shaft, and the glans appears to sit almost on the pubic skin. From the 1960s until the late 1970s, it was common for sex reassignment and surgery to be recommended. This was especially likely if evidence suggested that response to additional testosterone and pubertal testosterone would be poor. With parental acceptance, the boy would be reassigned and renamed as a girl, and surgery performed to remove the testes and construct an artificial vagina. This was based on the now-questioned idea that gender identity was shaped entirely from socialization, and that a man with a small penis can find no acceptable place in society.
Johns Hopkins Hospital, the center most known for this approach, performed twelve such reassignments from 1960 to 1980, most notably that of David Reimer (whose penis was destroyed by a circumcision accident), overseen by John Money. By the mid-1990s, reassignment was less often offered, and all three premises had been challenged. Former subjects of such surgery, vocal about their dissatisfaction with the adult outcome, played a large part in discouraging this practice. Sexual reassignment is rarely performed today for severe micropenis (although the question of raising the boy as a girl is sometimes still discussed.) (See "History of intersex surgery" for a fuller discussion.)
A treatment option for micropenis is the insertion of a subcutaneous soft silicone implant under the penile skin. The procedure was developed by urologist James J. Elist.
Management of salt-wasting crises and mineralocorticoid treatment are as for other forms of salt-wasting congenital adrenal hyperplasias: saline and fludrocortisone.
Glucocorticoids can be provided at minimal replacement doses because there is no need for suppression of excessive adrenal androgens or mineralocorticoids. As with other forms of adrenal insufficiency, extra glucocorticoid is needed for stress coverage.
Treatment for both pregnant and non-pregnant women is usually with metronidazole, by mouth once. Caution should be used in pregnancy, especially in the first trimester. Sexual partners, even if they have no symptoms, should also be treated.
For 95-97% of cases, infection is resolved after one dose of metronidazole. Studies suggest that 4-5% of trichomonas cases are resistant to metronidazole, which may account for some “repeat” cases. Without treatment, trichomoniasis can persist for months to years in women, and is thought to improve without treatment in men. Women living with HIV infection have better cure rates if treated for 7 days rather than with one dose.
Topical treatments are less effective than oral antibiotics due to Skene's gland and other genitourinary structures acting as a reservoir.
Treatment consists primarily of immunosuppressive drugs (e.g., hydroxychloroquine and corticosteroids). An interesting second line drug is methotrexate in its low-dose schedule. In 2011, the U.S. Food and Drug Administration (FDA) approved the first new drug for lupus in more than 50 years to be used in the US, belimumab. In addition to medicative therapy, due to the psychological and social impacts that Lupus may have on an individual, Cognitive Behavioural Therapy (CBT) has also been demonstrated to be effective in reducing stress, anxiety, and depression in lupus sufferers.
In the case of rape, the person can be treated prophylacticly with antibiotics.
An option for treating partners of patients (index cases) diagnosed with chlamydia or gonorrhea is patient-delivered partner therapy, which is the clinical practice of treating the sex partners of index cases by providing prescriptions or medications to the patient to take to his/her partner without the health care provider first examining the partner.
As with other forms of CAH, the primary therapy of 11β-hydroxylase deficient CAH is lifelong glucocorticoid replacement in sufficient doses to prevent adrenal insufficiency and suppress excess mineralocorticoid and androgen production.
Salt-wasting in infancy responds to intravenous saline, dextrose, and high dose hydrocortisone, but prolonged fludrocortisone replacement is usually not necessary. The hypertension is ameliorated by glucocorticoid suppression of DOC.
Long term glucocorticoid replacement issues are similar to those of 21-hydroxylase CAH, and involve careful balance between doses sufficient to suppress androgens while avoiding suppression of growth. Because the enzyme defect does not affect sex steroid synthesis, gonadal function at puberty and long-term fertility should be normal if adrenal androgen production is controlled. See congenital adrenal hyperplasia for a more detailed discussion of androgen suppression and fertility potential in adolescent and adult women.
One of the main characteristics of this disorder is adrenal insufficiency, which is a reduction in adrenal gland function resulting from incomplete development of the gland's outer layer (the adrenal cortex). Adrenal insufficiency typically begins in infancy or in childhood and can cause vomiting, difficulty with feeding, dehydration, extremely low blood sugar (hypoglycemia), low sodium levels, and shock. However, adult-onset cases have also been described. See also Addison's Disease.
Affected males may also lack male sex hormones, which leads to underdeveloped reproductive tissues, undescended testicles (cryptorchidism), delayed puberty, and an inability to father children (infertility). These characteristics are known as hypogonadotropic hypogonadism. Females are rarely affected by this disorder, but a few cases have been reported of adrenal insufficiency or a lack of female sex hormones, resulting in underdeveloped reproductive tissues, delayed puberty, and an absence of menstruation.
Growth of the penis both before birth and during childhood and puberty is strongly influenced by testosterone and, to a lesser degree, the growth hormone. However, later endogenous hormones mainly have value in the treatment of micropenis caused by hormone deficiencies, such as hypopituitarism or hypogonadism.
Regardless of the cause of micropenis, if it is recognized in infancy, a brief course of testosterone is often prescribed (usually no more than 3 months). This usually induces a small amount of growth, confirming the likelihood of further growth at puberty, but rarely achieves normal size. No additional testosterone is given during childhood, to avoid unwanted virilization and bone maturation. (There is also some evidence that premature administration of testosterone can lead to reduced penis size in the adult.)
Testosterone treatment is resumed in adolescence only for boys with hypogonadism. Penile growth is completed at the end of puberty, similar to the completion of height growth, and provision of extra testosterone to post-pubertal adults produces little or no further growth.
In China, traditional treatment based on the causes suggested by cultural beliefs are administrated to the patient. Praying to gods and asking Taoist priests to perform exorcism is common. If a fox spirit is believed to be involved, people may hit gongs or beat the person to drive it out. The person will receive a yang- or yin-augmenting Chinese medicine potion, usually including herbs, pilose antler (stag of deer) or deer tail, and tiger penis, deer penis, or fur seal penis. Other foods for therapy are pepper soup, ginger soup and liquor.