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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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Recommended regimen is doxycycline 100 mg orally twice a day, alternatively azithromycin 1 g orally once per week or ciprofloxacin 750 mg orally twice a day or erythromycin base 500 mg orally four times a day or trimethoprim-sulfamethoxazole one double-strength (160 mg/800 mg) tablet orally twice a day. All antibiotic regimens should last for at least 3 weeks and until all lesions have completely healed. Normally, the infection will begin to subside within a week of treatment, but the full treatment period must be followed to minimize the possibility of relapse.
According to the CDC 2015 guidelines Azithromycin is the antibiotic of choice.
The disease is effectively treated with antibiotics, therefore, developed countries have a very low incidence of donovanosis; about 100 cases reported each year in the United States. However, sexual contacts with individuals in endemic regions dramatically increases the risk of contracting the disease. Avoidance of these sexual contacts, and sexually transmitted disease testing before beginning a sexual relationship, are effective preventative measures for donovanosis.
Geotrichosis generally has a good prognosis and patients generally have successful recovery. However, there is not a standard treatment for geotrichosis. There are several types of antimicrobial or antifungal compounds that can be used for geotrichosis treatment. One type of treatment of geotrichosis can involve miconazole and ketoconazole, which has shown to improve cutaneous, branchopulmonary, intestinal and joint conditions. Another method of treatment involves symptomatic care, bed rest, iodine therapy, aerosol nystatin and amphotericin B. Azole drugs including isoconazole and clotrimazole are used for geotrichosis treatment. Associated treatment for pulmonary geotrichosis includes the use of potassium iodide, sulfonamides or colistin. The associated asthma can be treated with desensitization and prednisolone. Amphotericin B, clotrimazole and S-fluorocytosine have become more susceptible to "G. candidum". Antimycotic resistance can appear due to repeated treatment.
Although it is a self-limited illness, oral or intravenous antiviral treatments, particularly acyclovir, have been used in the management of immunocompromised or severely infected patients. Topical acyclovir has not been shown to be effective in management of herpetic whitlow. Famciclovir has been demonstrated to effectively treat and prevent recurrent episodes. Lancing or surgically debriding the lesion may make it worse by causing a superinfection or encephalitis.
In the US, approximately 60% of people with HIV use various forms of complementary or alternative medicine, even though the effectiveness of most of these therapies has not been established. There is not enough evidence to support the use of herbal medicines. There is insufficient evidence to recommend or support the use of medical cannabis to try to increase appetite or weight gain.
Macrolide antibiotics, such as erythromycin, are an effective treatment for DPB when taken regularly over an extended period of time. Clarithromycin or roxithromycin are also commonly used. The successful results of macrolides in DPB and similar lung diseases stems from managing certain symptoms through immunomodulation (adjusting the immune response), which can be achieved by taking the antibiotics in low doses. Treatment consists of daily oral administration of erythromycin for two to three years, an extended period that has been shown to dramatically improve the effects of DPB. This is apparent when an individual undergoing treatment for DPB, among a number of disease-related remission criteria, has a normal neutrophil count detected in BAL fluid, and blood gas (an arterial blood test that measures the amount of oxygen and carbon dioxide in the blood) readings show that free oxygen in the blood is within the normal range. Allowing a temporary break from erythromycin therapy in these instances has been suggested, to reduce the formation of macrolide-resistant "P. aeruginosa". However, DPB symptoms usually return, and treatment would need to be resumed. Although highly effective, erythromycin may not prove successful in all individuals with the disease, particularly if macrolide-resistant "P. aeruginosa" is present or previously untreated DPB has progressed to the point where respiratory failure is occurring.
With erythromycin therapy in DPB, great reduction in bronchiolar inflammation and damage is achieved through suppression of not only neutrophil proliferation, but also lymphocyte activity and obstructive mucus and water secretions in airways. The antibiotic effects of macrolides are not involved in their beneficial effects toward reducing inflammation in DPB. This is evident because the treatment dosage is much too low to fight infection, and in DPB cases with the occurrence of macrolide-resistant "P. aeruginosa", erythromycin therapy still reduces inflammation.
A number of factors are involved in suppression of inflammation by erythromycin and other macrolides. They are especially effective at inhibiting the proliferation of neutrophils, by diminishing the ability of interleukin 8 and leukotriene B4 to attract them. Macrolides also reduce the efficiency of adhesion molecules that allow neutrophils to stick to bronchiolar tissue linings. Mucus production in the airways is a major culprit in the morbidity and mortality of DPB and other respiratory diseases. The significant reduction of inflammation in DPB attributed to erythromycin therapy also helps to inhibit the production of excess mucus.
Current HAART options are combinations (or "cocktails") consisting of at least three medications belonging to at least two types, or "classes," of antiretroviral agents. Initially treatment is typically a non-nucleoside reverse transcriptase inhibitor (NNRTI) plus two nucleoside analog reverse transcriptase inhibitors (NRTIs). Typical NRTIs include: zidovudine (AZT) or tenofovir (TDF) and lamivudine (3TC) or emtricitabine (FTC). Combinations of agents which include protease inhibitors (PI) are used if the above regimen loses effectiveness.
The World Health Organization and United States recommends antiretrovirals in people of all ages including pregnant women as soon as the diagnosis is made regardless of CD4 count. Once treatment is begun it is recommended that it is continued without breaks or "holidays". Many people are diagnosed only after treatment ideally should have begun. The desired outcome of treatment is a long term plasma HIV-RNA count below 50 copies/mL. Levels to determine if treatment is effective are initially recommended after four weeks and once levels fall below 50 copies/mL checks every three to six months are typically adequate. Inadequate control is deemed to be greater than 400 copies/mL. Based on these criteria treatment is effective in more than 95% of people during the first year.
Benefits of treatment include a decreased risk of progression to AIDS and a decreased risk of death. In the developing world treatment also improves physical and mental health. With treatment there is a 70% reduced risk of acquiring tuberculosis. Additional benefits include a decreased risk of transmission of the disease to sexual partners and a decrease in mother-to-child transmission. The effectiveness of treatment depends to a large part on compliance. Reasons for non-adherence include poor access to medical care, inadequate social supports, mental illness and drug abuse. The complexity of treatment regimens (due to pill numbers and dosing frequency) and adverse effects may reduce adherence. Even though cost is an important issue with some medications, 47% of those who needed them were taking them in low and middle income countries as of 2010 and the rate of adherence is similar in low-income and high-income countries.
Specific adverse events are related to the antiretroviral agent taken. Some relatively common adverse events include: lipodystrophy syndrome, dyslipidemia, and diabetes mellitus, especially with protease inhibitors. Other common symptoms include diarrhea, and an increased risk of cardiovascular disease. Newer recommended treatments are associated with fewer adverse effects. Certain medications may be associated with birth defects and therefore may be unsuitable for women hoping to have children.
Treatment recommendations for children are somewhat different from those for adults. The World Health Organization recommends treating all children less than 5 years of age; children above 5 are treated like adults. The United States guidelines recommend treating all children less than 12 months of age and all those with HIV RNA counts greater than 100,000 copies/mL between one year and five years of age.
The side effects of penicillin can be altered by taking other medications at the same time. Taking oral contraceptives along with penicillin may lower the effects of the contraceptive. When probenecid is used concurrently with penicillin, kidney excretion of probenecid is increase resulting in higher blood levels of penicillin in the circulation. In some instances, this would be intended therapeutic effect. In other instances, this is an unintended side effect. Neomycin can lower the absorption of penicillin from the gastrointestinal tract resulting in lower than expected levels of penicillin in the circulation. This side effect may result in an ineffective therapeutic effect of penicillin. When methotrexate is administered with penicillin, toxicity may occur related to methotrexante.
A superinfection is a second infection superimposed on an earlier one, especially by a different microbial agent of exogenous or endogenous origin, that is resistant to the treatment being used against the first infection. Examples of this in bacteriology are the overgrowth of endogenous "Clostridium difficile" which occurs following treatment with a broad-spectrum antibiotic, and pneumonia or septicemia from "Pseudomonas aeruginosa" in some immuno-compromised patients.
In virology, the definition is slightly different. Superinfection is the process by which a cell that has previously been infected by one virus gets co-infected with a different strain of the virus, or another virus, at a later point in time. Viral superinfections may be resistant to the antiviral drug or drugs that were being used to treat the original infection. Viral superinfections may also be less susceptible to the host's immune response.
There is no treatment currently available. The virus generally resolves itself within a five to seven day period. The use of steroids can actually cause a corneal microbial superinfection which then requires antimicrobial therapy to eliminate.
Proper diagnosis is essential for optimal treatment. Bacterial corneal ulcer require intensive fortified antibiotic therapy to treat the infection. Fungal corneal ulcers require intensive application of topical anti-fungal agents. Viral corneal ulceration caused by herpes virus may respond to antivirals like topical acyclovir ointment instilled at least five times a day. Alongside, supportive therapy like pain medications are given, including topical cycloplegics like atropine or homatropine to dilate the pupil and thereby stop spasms of the ciliary muscle. Superficial ulcers may heal in less than a week. Deep ulcers and descemetoceles may require conjunctival grafts or conjunctival flaps, soft contact lenses, or corneal transplant. Proper nutrition, including protein intake and Vitamin C are usually advised. In cases of Keratomalacia, where the corneal ulceration is due to a deficiency of Vitamin A, supplementation of the Vitamin A by oral or intramuscular route is given. Drugs that are usually contraindicated in corneal ulcer are topical corticosteroids and anesthetics - these should not be used on any type of corneal ulcer because they prevent healing, may lead to superinfection with fungi and other bacteria and will often make the condition much worse.
When penicillin is used at high doses hypokalemia, metabolic acidosis, and hyperkalemia can occur. Developing hypernatremia after administering high doses of penicillin can be a serious side effect.
Untreated DPB leads to bronchiectasis, respiratory failure, and death. A journal report from 1983 indicated that untreated DPB had a five-year survival rate of 62.1%, while the 10-year survival rate was 33.2%. With erythromycin treatment, individuals with DPB now have a much longer life expectancy due to better management of symptoms, delay of progression, and prevention of associated infections like "P. aeruginosa". The 10-year survival rate for treated DPB is about 90%. In DPB cases where treatment has resulted in significant improvement, which sometimes happens after about two years, treatment has been allowed to end for a while. However, individuals allowed to stop treatment during this time are closely monitored. As DPB has been proven to recur, erythromycin therapy must be promptly resumed once disease symptoms begin to reappear. In spite of the improved prognosis when treated, DPB currently has no known cure.
The main treatment for acral erythema is discontinuation of the offending drug, and symptomatic treatment to provide analgesia, lessen edema, and prevent superinfection. However, the treatment for the underlying cancer of the patient must not be neglected. Often, the discontinued drug can be substituted with another cancer drug or cancer treatment.
Symptomatic treatment can include wound care, elevation, and pain medication. Corticosteroids and pyridoxine have also been used to relieve symptoms. Other studies do not support the conclusion.
A number of additional remedies are listed in recent medical literature. Among them henna and 10% uridine ointment which went through clinical trial.
It is unknown what aspects of the natural immune response to HIV may protect someone from superinfection, but it has been shown that cytotoxic lymphocyte responses do not seem to be protective. In addition, it has been demonstrated that superinfection can occur in individuals that demonstrate a robust anti-HIV antibody response. The anti-HIV antibody response broadens and strengthens in individuals post-superinfection.
Taken with the finding that super-infection is common and occurs within and between HIV subtypes it has been suggested that the immune response elicited by primary infection may confer limited protection and raises concerns that HIV-vaccine strategies designed to replicate the natural anti-HIV immune response may have limited effectiveness in preventing new infections. However at the same time, HIV-infected individuals at high risk for super-infection who do not become superinfected may also provide a very interesting avenue for new vaccine research.
Topical antibiotics are used at hourly intervals to treat infectious corneal ulcers. Cycloplegic eye drops are applied to give rest to the eye. Pain medications are given as needed. Loose epithelium and ulcer base can be scraped off and sent for culture sensitivity studies to find out the pathogenic organism. This helps in choosing appropriate antibiotics. Complete healing takes anywhere from about a few weeks to several months.
Refractory corneal ulcers can take a long time to heal, sometimes months. In case of progressive or non-healing ulcers, surgical intervention by an ophthalmologist with corneal transplantation may be required to save the eye. In all corneal ulcers it is important to rule out predisposing factors like diabetes mellitus and immunodeficiency.
PPE invariably recurs with the resumption of chemotherapy. Long-term chemotherapy may also result in reversible palmoplantar keratoderma. Symptoms resolve 1–2 weeks after cessation of chemotherapy (Apisarnthanarax and Duvic 2003).
The primary remedy for miliaria is to wear lighter clothing, move to a cooler climate, or otherwise avoid overheating one's body. The immediate treatment of the involved skin areas involves the use of a soothing ointment such as calamine lotion.
Medical assistance should be sought for the first episode of a rash with the appearance of miliaria. The differential diagnosis includes several conditions that an experienced practitioner should be able to recognise and may require treatment distinct from the usual measures taken for miliaria. In most cases the rash of miliaria will resolve without intervention. However, severe cases can last for weeks and cause significant disability. General measures should be recommended for all patients, including moving to an air-conditioned environment if possible, avoiding sweat-provoking activities and occlusive clothing, and taking frequent cool showers.
It has been suggested that the use of topical antibacterials (including antibacterial soaps) may shorten the duration of symptoms in miliaria rubra even in the absence of obvious superinfection. Other topical agents that may reduce the severity of symptoms include anti-itch preparations such as calamine or menthol- or camphor-based preparations, and topical steroid creams. However, caution should be used with oil-based preparations (ointments and oily creams as opposed to water-based or aqueous lotions) that may increase blockage to the sweat glands and prolong duration of illness. Other agents have been investigated including supplemental vitamin A and C and vitamin A based medications, but it is worth noting that there is little scientific evidence supporting any of the above treatments in reducing the duration of symptoms or frequency of complications.
In most cases, doctors will recommend that any pimple-like blisters that may form should have the fluid drained out of them (either through in-office procedure or at home in a sterile environment) to avoid the rash from spreading underneath the skin, leading to an increased state of dermatitis. Left untreated, the blisters may spread and take on an increased red appearance, with the fluid inside increasing in viscosity. It is recommended by physicians to sanitize the infected area and then drain the blisters with a sterilized needle or lancet.
In most tropical areas the local dispensaries sell prickly heat powder, a talc admixture containing drying milk proteins (Labilin) and Triclosan to fight the infection. These include cooling menthol to help alleviate difficulty getting to sleep. This is an effective treatment—the powder stays on the skin longer and treats bacteria dispersed into bed linens, providing a reasonably dry refuge area for healing. Miliaria often covers large areas, and generous use of Cortisone may be contraindicated for reasons stated on package warnings. Regular talcum powder will not reduce the rash but can alleviate burning and itching.
In cases where the rash has developed into open blisters or pustular lesions a doctor should be consulted since more aggressive, medically monitored treatment may be required.
The cornerstone of prevention and treatment of podoconiosis is avoidance of exposure to irritant soils. Wearing shoes in the presence of irritant soils is the primary method of exposure reduction. In Rwanda, a country of high disease prevalence, the government has banned walking barefoot in public, in order to curtail podoconiosis and other soil-borne diseases.
Once the disease has developed, rigorous foot hygiene including daily washing with soap and water, application of an emollient, and nightly elevation of the affected extremity has been shown to reduce swelling and disability. Compression wrapping and decongestive physiotherapy of the affected extremity has been shown to be effective in other forms of lymphedema, but the benefits of these therapies have not been rigorously studied in podoconiosis. Nodules will not resolve with these conservative measures, although surgical removal of the nodules can be performed.
Chronic hepatitis B management aims to control viral replication, which is correlated with progression of disease. There have been 7 drug treatments approved to date in the United States:
- Injectable interferon alpha was the first therapy approved for chronic hepatitis B. It has several side effects, most of which are reversible with removal of therapy, but it has been supplanted by newer treatments for this indication. These include long-acting interferon bound to polyethylene glycol (pegylated interferon) and the oral nucleoside analogues.
- Pegylated interferon (PEG IFN) is dosed just once a week as a subcutaneous injection and is both more convenient and effective than standard interferon. Although it does not develop resistance as do many of the oral antivirals, it is poorly tolerated and requires close monitoring. PEG IFN is estimated to cost about $18,000 per year in the United States, compared to $2,500-8,700 for the oral medications; however, its treatment duration is 48 weeks as opposed to the oral antivirals, which require indefinite treatment for most patients (minimum 1 year). PEG IFN is not effective in patients with high levels of viral activity and cannot be used in immunosuppressed patients or those with cirrhosis.
- Lamivudine was the first approved oral nucleoside analogue. While effective and potent, lamivudine has been replaced by newer, more potent treatments in the Western world and is no longer recommended as first-line treatment. However, it is still used in areas where newer agents either have not been approved or are too costly. Generally, the course of treatment is a minimum of one year with a minimum of six additional months of "consolidation therapy." Based on viral response, longer therapy may be required, and certain patients require indefinite long-term therapy. Due to a less robust response in Asian patients, consolidation therapy is recommended to be extended to at least a year. All patients should be monitored for viral reactivation, which if identified, requires restarting treatment. Lamivudine is generally safe and well-tolerated. Many patients develop resistance, which is correlated with longer treatment duration. If this occurs, an additional antiviral is added. Lamivudine as a single treatment is contraindicated in patients coinfected with HIV, as resistance develops rapidly, but it can be used as part of a multidrug regimen.
- Adefovir dipivoxil, a nucleotide analogue, has been used to supplement lamivudine in patients who develop resistance, but is no longer recommended as first-line therapy.
- Entecavir is safe, well tolerated, less prone to developing resistance, and the most potent of the existing hepatitis B antivirals; it is thus a first-line treatment choice. It is not recommended for lamivudine-resistant patients or as monotherapy in patients who are HIV positive.
- Telbivudine is effective but not recommended as first-line treatment; as compared to entecavir, it is both less potent and more resistance prone.
- Tenofovir is a nucleotide analogue and an antiretroviral drug that is also used to treat HIV infection. It is preferred to adefovir both in lamivudine-resistant patients and as initial treatment since it is both more potent and less likely to develop resistance.
First-line treatments currently used include PEG IFN, entecavir, and tenofovir, subject to patient and physician preference. Treatment initiation is guided by recommendations issued by The American Association for the Study of Liver Diseases (AASLD) and the European Association for the Study of the Liver (EASL) and is based on detectable viral levels, HBeAg positive or negative status, ALT levels, and in certain cases, family history of HCC and liver biopsy. In patients with compensated cirrhosis, treatment is recommended regardless of HBeAg status or ALT level, but recommendations differ regarding HBV DNA levels; AASLD recommends treating at DNA levels detectable above 2x10 IU/mL; EASL and WHO recommend treating when HBV DNA levels are detectable at any level. In patients with decompensated cirrhosis, treatment and evaluation for liver transplantation are recommended in all cases if HBV DNA is detectable. Currently, multidrug treatment is not recommended in treatment of chronic HBV as it is no more effective in the long term than individual treatment with entecavir or tenofovir.
Hepatitis D is difficult to treat, and effective treatments are lacking. Interferon alpha has proven effective at inhibiting viral activity but only on a temporary basis.
HIV superinfection (also called HIV reinfection) is a condition in which a person with an established human immunodeficiency virus infection acquires a second strain of HIV, often of a different subtype. The HIV superinfection strain (a recombinant strain) appears when a person becomes simultaneously infected by two different strains, allowing the two viruses to exchange genetic material, resulting in a new unique strain that can possess the resistances of both previous strains. This new strain co-exists with the two prior strains and may cause more rapid disease progression or carry multiple resistances to certain HIV medications.
People with HIV risk superinfection by the same actions that would place a non-infected person at risk of acquiring HIV. These include sharing needles and forgoing condoms with HIV-positive sexual partners. For many years superinfection was thought to occur mainly in high-risk populations. Research from Uganda published in 2012 indicates that HIV superinfection among HIV-infected individuals within a general population remains unknown. Further research from "The Journal of Infectious Diseases" indicates that there have been 16 documented cases of superinfection since 2002.
In microbiology, coinfection is the simultaneous infection of a host by multiple pathogen species. In virology, coinfection includes simultaneous infection of a single cell by two or more virus particles. An example is the coinfection of liver cells with Hepatitis B virus and Hepatitis D virus, which can arise incrementally by initial infection followed by superinfection.
Global prevalence or incidence of coinfection among humans is unknown, but it is thought to be commonplace, sometimes more common than single infection. Coinfection with helminths affects around 800 million people worldwide.
Coinfection is of particular human health importance because pathogen species can interact within the host. The net effect of coinfection on human health is thought to be negative. Interactions can have either positive or negative effects on other parasites. Under positive parasite interactions, disease transmission and progression are enhanced and this is also known as syndemism. Negative parasite interactions include microbial interference when one bacterial species suppresses the virulence or colonisation of other bacteria, such as "Pseudomonas aeruginosa" suppressing pathogenic "Staphylococcus aureus" colony formation. The general patterns of ecological interactions between parasite species are unknown, even among common coinfections such as those between sexually transmitted infections. However, network analysis of a food web of coinfection in humans suggests that there is greater potential for interactions via shared food sources than via the immune system.
A globally common coinfection involves tuberculosis and HIV. In some countries, up to 80% of tuberculosis patients are also HIV-positive. The potential for dynamics of these two infectious diseases to be linked has been known for decades. Other common examples of coinfections are AIDS, which involves coinfection of end-stage HIV with opportunistic parasites and polymicrobial infections like Lyme disease with other diseases.
When a cell is undergoing the lysogenic cycle and infected with a lambda phage (making it a lambda lysogen), other lambda phages that infect it are not able to undergo lytic development and produce progeny. The incoming phage can inject its DNA into the cell, but the DNA is immediately repressed and no transcription of genes or translation of phage proteins initiates. Therefore, lambda lysogens are immune to infection by other lambda phage particles. This occurs because the lambda lysogen is continuously producing cI repressor proteins to the point where the amount of cI proteins in the cell exceeds the amount needed to inhibit the replication of more than one phage. These repressor proteins bind to the superinfecting phage DNA operators to block transcription of the phage's genes by the cell and viral polymerase enzymes.
The narrow range of treatable diseases or "spectrum of activity" of the penicillins, along with the poor activity of the orally active phenoxymethylpenicillin, led to the search for derivatives of penicillin that could treat a wider range of infections. The isolation of 6-APA, the nucleus of penicillin, allowed for the preparation of semisynthetic penicillins, with various improvements over benzylpenicillin (bioavailability, spectrum, stability, tolerance).
The first major development was ampicillin in 1961. It offered a broader spectrum of activity than either of the original penicillins. Further development yielded β-lactamase-resistant penicillins, including flucloxacillin, dicloxacillin, and methicillin. These were significant for their activity against β-lactamase-producing bacterial species, but were ineffective against the methicillin-resistant "Staphylococcus aureus" (MRSA) strains that subsequently emerged.
Another development of the line of true penicillins was the antipseudomonal penicillins, such as carbenicillin, ticarcillin, and piperacillin, useful for their activity against Gram-negative bacteria. However, the usefulness of the β-lactam ring was such that related antibiotics, including the mecillinams, the carbapenems and, most important, the cephalosporins, still retain it at the center of their structures.