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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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Curettage is performed on some patients, and is sufficient for inactive lesions. The recurrence rate with curettage is significant in active lesions, and marginal resection has been advised. Liquid nitrogen, phenol, methyl methacrylate are considered for use to kill cells at margins of resected cyst.
Recurrence rate of solid form of tumour is lower than classic form.
Constant care is required to moisturise and protect the skin. The hard outer layer eventually peels off, leaving the vulnerable inner layers of the dermis exposed. Early complications result from infection due to fissuring of the hyperkeratotic plates and respiratory distress due to physical restriction of chest wall expansion.
Management includes supportive care and treatment of hyperkeratosis and skin barrier dysfunction. A humidified incubator is generally used. Intubation is often required until nares are patent. Nutritional support with tube feeds is essential until eclabium resolves and infants can begin nursing. Ophthalmology consultation is useful for the early management of ectropion, which is initially pronounced and resolves as scale is shed. Liberal application of petrolatum is needed multiple times a day. In addition, careful debridement of constrictive bands of hyperkeratosis should be performed to avoid digital ischemia. Cases of digital autoamputation or necrosis have been reported due to cutaneous constriction bands. Relaxation incisions have been used to prevent this morbid complication.
In the past, the disorder was nearly always fatal, whether due to dehydration, infection (sepsis), restricted breathing due to the plating, or other related causes. The most common cause of death was systemic infection and sufferers rarely survived for more than a few days. However, improved neonatal intensive care and early treatment with oral retinoids, such as the drug Isotretinoin (Isotrex), may improve survival. Early oral retinoid therapy has been shown to soften scales and encourage desquamation. After as little as two weeks of daily oral isotretinoin, fissures in the skin can heal, and plate-like scales can nearly resolve. Improvement in the eclabium and ectropion can also be seen in a matter of weeks. Children who survive the neonatal period usually evolve to a less severe phenotype, resembling a severe congenital ichthyosiform erythroderma. Patients continue to suffer from temperature dysregulation and may have heat and cold intolerance. Patients can also have generalized poor hair growth, scarring alopecia, contractures of digits, arthralgias, failure to thrive, hypothyroidism, and short stature. Some patients develop a rheumatoid factor-positive polyarthritis. Survivors can also develop fish-like scales and retention of a waxy, yellowish material in seborrheic areas, with ear adhered to the scalp.
The oldest known survivor is Nusrit "Nelly" Shaheen, who was born in 1984 and is in relatively good health as of April 2016. Lifespan limitations have not yet been determined with the new treatments.
A study published in 2011 in the Archives of Dermatology concluded, "Harlequin ichthyosis should be regarded as a severe chronic disease that is not invariably fatal. With improved neonatal care and probably the early introduction of oral retinoids, the number of survivors is increasing."
The disorder is treated by strictly reducing the intake of foods rich in plant sterols (e.g., vegetable oils, olives and avocados). However, dietary therapy is often never fully sufficient to control this disease since plant sterols are constituents of all plant-based foods. Statins have been used, and while these lower cholesterol levels and may ameliorate atherosclerotic disease, plant sterol levels are insufficiently lowered by their use alone.
If dietary treatment alone is insufficient, bile acid-binding resins (e.g., cholestyramine, colestipol) could be considered. In October 2002, a new cholesterol absorption inhibitor, ezetimibe, received US Food and Drug Administration (FDA) approval for use in sitosterolemia. This drug is now the standard of care, as it blocks sterol entry and can be used in combination with bile-acid resins.
Finally, ileal bypass has been performed in select cases to decrease the levels of plant sterols in the body, though this therapy was undertaken prior to the advent of ezetimibe.
Many people with CF are on one or more antibiotics at all times, even when healthy, to prophylactically suppress infection. Antibiotics are absolutely necessary whenever pneumonia is suspected or a noticeable decline in lung function is seen, and are usually chosen based on the results of a sputum analysis and the person's past response. This prolonged therapy often necessitates hospitalization and insertion of a more permanent IV such as a peripherally inserted central catheter or Port-a-Cath. Inhaled therapy with antibiotics such as tobramycin, colistin, and aztreonam is often given for months at a time to improve lung function by impeding the growth of colonized bacteria. Inhaled antibiotic therapy helps lung function by fighting infection, but also has significant drawbacks such as development of antibiotic resistance, tinnitus, and changes in the voice. Inhaled levofloxacin may be used to treat "Pseudomonas aeruginosa" in people with cystic fibrosis who are infected.
Antibiotics by mouth such as ciprofloxacin or azithromycin are given to help prevent infection or to control ongoing infection. The aminoglycoside antibiotics (e.g. tobramycin) used can cause hearing loss, damage to the balance system in the inner ear or kidney failure with long-term use. To prevent these side-effects, the amount of antibiotics in the blood is routinely measured and adjusted accordingly.
While no cures for CF are known, several treatment methods are used. The management of CF has improved significantly over the past 70 years. While infants born with it 70 years ago would have been unlikely to live beyond their first year, infants today are likely to live well into adulthood. Recent advances in the treatment of cystic fibrosis have meant that individuals with cystic fibrosis can live a fuller life less encumbered by their condition. The cornerstones of management are the proactive treatment of airway infection, and encouragement of good nutrition and an active lifestyle. Pulmonary rehabilitation as a management of CF continues throughout a person's life, and is aimed at maximizing organ function, and therefore the quality of life. At best, current treatments delay the decline in organ function. Because of the wide variation in disease symptoms, treatment typically occurs at specialist multidisciplinary centers and is tailored to the individual. Targets for therapy are the lungs, gastrointestinal tract (including pancreatic enzyme supplements), the reproductive organs (including assisted reproductive technology), and psychological support.
The most consistent aspect of therapy in CF is limiting and treating the lung damage caused by thick mucus and infection, with the goal of maintaining quality of life. Intravenous, inhaled, and oral antibiotics are used to treat chronic and acute infections. Mechanical devices and inhalation medications are used to alter and clear the thickened mucus. These therapies, while effective, can be extremely time-consuming.
CFTR has been a drug target in efforts to find treatments for related conditions. Ivacaftor (trade name Kalydeco, developed as VX-770) is a drug approved by the FDA in 2012 for people with cystic fibrosis who have specific CFTR mutations Ivacaftor was developed by Vertex Pharmaceuticals in conjunction with the Cystic Fibrosis Foundation and is the first drug that treats the underlying cause rather than the symptoms of the disease. Called "the most important new drug of 2012", and "a wonder drug" it is one of the most expensive drugs, costing over US$300,000 per year, which has led to criticism of Vertex for the high cost.
Radiation therapy is often part of the treatment for DLBCL. It is commonly used after the completion of chemotherapy. Radiation therapy alone is not an effective treatment for this disease.
Medical treatments often focus on alleviating symptoms. However measures which focus on decreasing underlying atherosclerosis—as opposed to simply treating symptoms—are more effective. Non-pharmaceutical means are usually the first method of treatment, such as stopping smoking and practicing regular exercise. If these methods do not work, medicines are usually the next step in treating cardiovascular diseases, and, with improvements, have increasingly become the most effective method over the long term.
The key to the more effective approaches is to combine multiple different treatment strategies. In addition, for those approaches, such as lipoprotein transport behaviors, which have been shown to produce the most success, adopting more aggressive combination treatment strategies taken on a daily basis and indefinitely has generally produced better results, both before and especially after people are symptomatic.
Current treatment typically includes R-CHOP, which consists of the traditional CHOP, to which rituximab has been added. This regimen has increased the rate of complete response for DLBCL patients, particularly in elderly patients.R-CHOP is a combination of one monoclonal antibody (rituximab), three chemotherapy agents (cyclophosphamide, doxorubicin, vincristine), and one steroid (prednisone). These drugs are administered intravenously, and the regimen is most effective when it is administered multiple times over a period of months. People often receive this type of chemotherapy through a PICC line (peripherally inserted central catheter) in their arm near the elbow or a surgically implanted venous access port. The number of cycles of chemotherapy given depends on the stage of the disease — patients with limited disease typically receive three cycles of chemotherapy, while patients with extensive disease may need to undergo six to eight cycles. A recent approach involves obtaining a PET scan after the completion of two cycles of chemotherapy, to assist the treatment team in making further decisions about the future course of treatment.Older people often have more difficulty tolerating therapy than younger people. Lower intensity regimens have been attempted in this age group.
With many different types of leukodystrophies and causes, treatment therapies vary for each type. Many studies and clinical trials are in progress to find treatment and therapies for each of the different leukodystrophies. Stem cell transplants and gene therapy appear to be the most promising in treating all leukodystrophies providing it is done as early as possible.
For hypomyelinating leukodystrophies, therapeutic research into cell-based therapies appears promising. Oligodendrocyte precursor cells and neural stem cells have been transplanted successfully and have shown to be healthy a year later. Fractional anisotropy and radial diffusivity maps showed possible myelination in the region of the transplant. Induced pluripotent stem cells, oligodendrocyte precursor cells, gene correction, and transplantation to promote the maturation, survival, and myelination of oligodendrocytes seem to be the primary routes for possible treatments.
For three types of leukodystrophies (X-linked adrenoleukodystrophy (X-ALD), metachromatic leukodystrophy (MLD) and Krabbe Disease (globoid cell leukodystrophy - GLD), gene therapy using autologous hematopoietic stem cells to transfer the disease gene with lentiviral vectors have shown to be successful and are currently being used in clinical trials for X-ALD and MLD. The progression of X-ALD has shown to be disrupted with hematopoietic stem cell gene therapy but the exact reason why demyelination stops and the amount of stem cells needed is unclear. While there is an accumulation of very long chain fatty acids in the brain, it does not seem to be the reason behind the disease as gene therapy does not correct it.
Adeno-associated vectors have also been used in intracerebral injections to treat MLD. In some patients with MLD, their IQ increased, nerve conduction improved, their MRIs appeared stable, and had normal enzyme levels. Although the greater majority of patients seem to improve after the transplant, some do not respond well to treatment, which may cause devastating outcomes. For those leukodystrophies that result from a deficiency of lysozyme enzymes, such as Krabbes disease, enzyme replacement therapy seems hopeful, however, this proves difficult as the blood-brain barrier severely limits what can pass through into the central nervous system. Due to this obstacle, most research and clinical trials are turning to allogeneic hematopoietic stem cell transplantation.
Changes in diet may help prevent the development of atherosclerosis. Tentative evidence suggests that a diet containing dairy products has no effect on or decreases the risk of cardiovascular disease.
A diet high in fruits and vegetables decreases the risk of cardiovascular disease and death. Evidence suggests that the Mediterranean diet may improve cardiovascular results. There is also evidence that a Mediterranean diet may be better than a low-fat diet in bringing about long-term changes to cardiovascular risk factors (e.g., lower cholesterol level and blood pressure).
Topical treatment for the skin changes of scleroderma do not alter the disease course, but may improve pain and ulceration. A range of NSAIDs (nonsteroidal anti-inflammatory drugs) can be used to ease painful symptoms, such as naproxen. There is limited benefit from steroids such as prednisone. Episodes of Raynaud's phenomenon sometimes respond to nifedipine or other calcium channel blockers; severe digital ulceration may respond to prostacyclin analogue iloprost, and the dual endothelin-receptor antagonist bosentan may be beneficial for Raynaud's phenomenon. The skin tightness may be treated systemically with methotrexate and ciclosporin. and the skin thickness treated with penicillamine.
Scleroderma renal crisis, the occurrence of acute renal failure and malignant hypertension (very high blood pressure with evidence of organ damage) in people with scleroderma, is effectively treated with drugs from the class of the ACE inhibitors. The benefit of ACE inhibitors extends even to those who have to commence dialysis to treat their kidney disease, and may give sufficient benefit to allow the discontinuation of renal replacement therapy.
mTOR inhibitors :
- Everolimus
- Temsirolimus
mTOR is a kinase enzyme inside the cell that regulates cell growth, proliferation, and survival. mTOR inhibitors lead to cell cycle arrest in the G1 phase and also inhibits tumor angiogenesis by reducing synthesis of VEGF.
A Phase II trial of Evorolimus on relapsed DLBCL patients showed a 30% Overall Response Rate (ORR).
Harlequin-type ichthyosis is a genetic disorder which results in thickened skin over nearly the entire body at birth. The skin forms large, diamond-shaped plates that are separated by deep cracks. They affect the shape of the eyelids, nose, mouth, and ears, and limit movement of the arms and legs. Restricted movement of the chest can lead to breathing difficulties. These plates fall off over weeks. Other complications can include premature birth, infection, problems with body temperature, and dehydration.
Harlequin-type ichthyosis is due to mutations of the "ABCA12" genes. It is inherited from a person's parents in an autosomal recessive manner. Diagnosis is often based on appearance at birth and confirmed by genetic testing. Before birth amniocentesis or ultrasound may support the diagnosis.
There is no cure. Early in life constant supportive care is typically required. Treatments may include moisturizing cream, antibiotics, etretinate, or retinoids. It affects about 1 per 300,000 births. Both sexes are affected equally commonly. Long term problems are common. Death in the first month is relatively common. The condition was first documented in 1750.
Lithium and the anticonvulsants carbamazepine, lamotrigine, and valproic acid are used as mood stabilizers to treat bipolar disorder. These mood stabilizers are used for long-term mood stabilization but have not demonstrated the ability to quickly treat acute bipolar depression. Lithium is preferred for long-term mood stabilization. Carbamazepine effectively treats manic episodes, with some evidence it has greater benefit in rapid-cycling bipolar disorder, or those with more psychotic symptoms or a more schizoaffective clinical picture. It is less effective in preventing relapse than lithium or valproate. Since then, valproate has become a commonly prescribed treatment, and is effective in treating manic episodes. Lamotrigine has some efficacy in treating bipolar depression, and this benefit is greatest in more severe depression. It has also been shown to have some benefit in preventing bipolar disorder relapses, though there are concerns about the studies done, and is of no benefit in rapid cycling subtype of bipolar disorder. The effectiveness of topiramate is unknown.
Antipsychotic medications are effective for short-term treatment of bipolar manic episodes and appear to be superior to lithium and anticonvulsants for this purpose. Atypical antipsychotics are also indicated for bipolar depression refractory to treatment with mood stabilizers. Olanzapine is effective in preventing relapses, although the supporting evidence is weaker than the evidence for lithium.
Apoptosis is one of the major mechanisms of cell death targeted by cancer therapies. Reduced susceptibility to apoptosis increases the resistance of cancer cells to radiation and cytotoxic agents. B-cell lymphoma-2 (Bcl-2) family members create a balance between pro and anti-apoptotic proteins. Pro-apoptotic proteins include Bax and Bak. Anti-apoptotic proteins include Bcl-2, Bcl-X, Bcl-w, Mcl-1. When anti-apoptotic family members are overexpressed, apoptotic cell death becomes less likely.
- Oblimersen sodium (G3139, Genasense) targets BCL-2 mRNA
- ABT-737 (oral form navitoclax, ABT-263). A small molecule that targets anti-apoptotic Bcl-2 family proteins (Bcl-2, Bcl-X and Bcl-w). ABT-737 binds anti-apoptotic Bcl-2 proteins with an affinity two or three orders of magnitude more potent than previously reported compounds. High basal levels of Mcl-1 expression are associated with resistance to ABT-737. Combining ABT-737 with second agents that inactivate Mcl-1 may reduce this effect. ABT-737 has demonstrated single-agent efficacy against cell lines from lymphoid malignancies known to express high levels of Bcl-2, including DLBCL. It has also been found to be synergistic with proteasome inhibitors.
- Fenretinide. A synthetic retinoid that induces apoptosis of cancer cells and acts synergistically with chemotherapeutic drugs by triggering the activation of 12-Lox (12-lipoxygenase) leading to oxidative stress and apoptosis via the induction of the transcription factor Gadd153 and the Bcl-2-family member protein Bak.
Cystic fibrosis transmembrane conductance regulator has been shown to interact with:
- DNAJC5,
- GOPC,
- PDZK1,
- PRKCE,
- SLC4A8,
- SNAP23,
- SLC9A3R1,
- SLC9A3R2, and
- STX1A,
It is inhibited by the anti-diarrhoea drug crofelemer.
Antimicrobial stewardship teams in hospitals are encouraging optimal use of antimicrobials. The goals of antimicrobial stewardship are to help practitioners pick the right drug at the right dose and duration of therapy while preventing misuse and minimizing the development of resistance. Stewardship may reduce the length of stay by an average of slightly over 1 day while not increasing the risk of death.
Antibiotic stewardship programmes appear useful in reducing rates of antibiotic resistance.
Excessive antibiotic use has become one of the top contributors to the development of antibiotic resistance. Since the beginning of the antibiotic era, antibiotics have been used to treat a wide range of disease. Overuse of antibiotics has become the primary cause of rising levels of antibiotic resistance. The main problem is that doctors are willing to prescribe antibiotics to ill-informed individuals who believe that antibiotics can cure nearly all illnesses, including viral infections like the common cold. In an analysis of drug prescriptions, 36% of individuals with a cold or an upper respiratory infection (both viral in origin) were given prescriptions for antibiotics. These prescriptions accomplished nothing other than increasing the risk of further evolution of antibiotic resistant bacteria.
No medications have been shown to prevent or cure dementia. Medications may be used to treat the behavioural and cognitive symptoms but have no effect on the underlying disease process.
Acetylcholinesterase inhibitors, such as donepezil, may be useful for Alzheimer disease and dementia in Parkinson's, DLB, or vascular dementia. The quality of the evidence however is poor and the benefit is small. No difference has been shown between the agents in this family. In a minority of people side effects include a slow heart rate and fainting.
As assessment for an underlying cause of the behavior is a needed before prescribing antipsychotic medication for symptoms of dementia. Antipsychotic drugs should be used to treat dementia only if non-drug therapies have not worked, and the person's actions threaten themselves or others. Aggressive behavior changes are sometimes the result of other solvable problems, that could make treatment with antipsychotics unnecessary. Because people with dementia can be aggressive, resistant to their treatment, and otherwise disruptive, sometimes antipsychotic drugs are considered as a therapy in response. These drugs have risky adverse effects, including increasing the patient's chance of stroke and death. Generally, stopping antipsychotics for people with dementia does not cause problems, even in those who have been on them a long time.
N-methyl-D-aspartate (NMDA) receptor blockers such as memantine may be of benefit but the evidence is less conclusive than for AChEIs. Due to their differing mechanisms of action memantine and acetylcholinesterase inhibitors can be used in combination however the benefit is slight.
While depression is frequently associated with dementia, selective serotonin reuptake inhibitors (SSRIs) do not appear to affect outcomes.
The use of medications to alleviate sleep disturbances that people with dementia often experience has not been well researched, even for medications that are commonly prescribed. In 2012 the American Geriatrics Society recommended that benzodiazepines such as diazepam, and non-benzodiazepine hypnotics, be avoided for people with dementia due to the risks of increased cognitive impairment and falls. Additionally, there is little evidence for the effectiveness of benzodiazepines in this population. There is no clear evidence that melatonin or ramelteon improves sleep for people with dementia due to Alzheimer's disease. There is limited evidence that a low dose of trazodone may improve sleep, however more research is needed.
There is no solid evidence that folate or vitamin B12 improves outcomes in those with cognitive problems. Statins also have no benefit in dementia. Medications for other health conditions may need to be managed differently for a person who also has a diagnosis of dementia. The MATCH-D criteria can help identify ways that a diagnosis of dementia changes medication management for other health conditions. It is unclear if there is a link between blood pressure medication and dementia. There is a possibility that people may experience an increase in cardiovascular-related events if these medications are withdrawn.
Aromatherapy and massage have unclear evidence. There have been studies on the efficacy and safety of cannabinoids in relieving behavioral and psychological symptoms of dementia.
Omega-3 fatty acid supplements from plants or fish sources do not appear to benefit or harm people with mild to moderate Alzheimer's disease. It is unclear if taking omega-3 fatty acid supplements can improve other types of dementia.
On June 30, 2009, an FDA advisory panel recommended that Vicodin and another painkiller, Percocet, be removed from the market because they have allegedly caused over 400 deaths a year. The problem is with paracetamol (acetaminophen/Tylenol for example ) overdose and liver damage. These two drugs, in combination with other drugs like Nyquil and Theraflu, can cause death by multiple drug intake and/or drug overdose. Another solution would be to not include paracetamol with Vicodin or Percocet.