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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)
Funded by The Federal Ministry for Economic Affairs and Energy; Grant: 01MD19013D, Smart-MD Project, Digital Technologies
More than 300 million people worldwide have asthma. The rate of asthma increases as countries become more urbanized and in many parts of the world those who develop asthma do not have access to medication and medical care. Within the United States, African Americans and Latinos are four times more likely to suffer from severe asthma than whites. The disease is closely tied to poverty and poor living conditions. Asthma is also prevalent in children in low income countries. Homes with roaches and mice, as well as mold and mildew put children at risk for developing asthma as well as exposure to cigarette smoke.
Unlike many other Western countries, the mortality rate for asthma has steadily risen in the United States over the last two decades. Mortality rates for African American children due to asthma are also far higher than that of other racial groups. For African Americans, the rate of visits to the emergency room is 330 percent higher than their white counterparts. The hospitalization rate is 220 percent higher and the death rate is 190 percent higher. Among Hispanics, Puerto Ricans are disporpotionatly affected by asthma with a disease rate that is 113 percent higher than non-Hispanic Whites and 50 percent higher than non-Hispanic Blacks. Studies have shown that asthma morbidity and mortality are concentrated in inner city neighborhoods characterized by poverty and large minority populations and this affects both genders at all ages. Asthma continues to have an adverse effects on the health of the poor and school attendance rates among poor children. 10.5 million days of school are missed each year due to asthma.
Though heart disease is not exclusive to the poor, there are aspects of a life of poverty that contribute to its development. This category includes coronary heart disease, stroke and heart attack. Heart disease is the leading cause of death worldwide and there are disparities of morbidity between the rich and poor. Studies from around the world link heart disease to poverty. Low neighborhood income and education were associated with higher risk factors. Poor diet, lack of exercise and limited (or no) access to a specialist were all factors related to poverty, though to contribute to heart disease.
Both low income and low education were predictors of coronary heart disease, a subset of cardiovascular disease. Of those admitted to hospital in the United States for heart failure, women and African Americans were more likely to reside in lower income neighborhoods. In the developing world, there is a 10 fold increase in cardiac events in the black and urban populations.
Specific types of enteropathy include:
- Enteropathy-associated T-cell lymphoma
- Environmental enteropathy
- Eosinophilic enteropathy
- Gluten-sensitive enteropathy (which can progress to coeliac disease)
- Coeliac disease
- Human immunodeficiency virus (HIV) HIV Enteropathy
- Immunodysregulation polyendocrinopathy and enteropathy, X-linked (see FOXP3)
- Protein-losing enteropathy
- Radiation enteropathy
- Tropical enteropathy
If the condition also involves the stomach, it is known as "gastroenteropathy".
In pigs, porcine proliferative enteropathy is a diarrheal disease.
HIV is transmitted by three main routes: sexual contact, significant exposure to infected body fluids or tissues, and from mother to child during pregnancy, delivery, or breastfeeding (known as vertical transmission). There is no risk of acquiring HIV if exposed to feces, nasal secretions, saliva, sputum, sweat, tears, urine, or vomit unless these are contaminated with blood. It is possible to be co-infected by more than one strain of HIV—a condition known as HIV superinfection.
HIV can be transmitted from mother to child during pregnancy, during delivery, or through breast milk, resulting in the baby also contracting HIV. This is the third most common way in which HIV is transmitted globally. In the absence of treatment, the risk of transmission before or during birth is around 20% and in those who also breastfeed 35%. As of 2008, vertical transmission accounted for about 90% of cases of HIV in children. With appropriate treatment the risk of mother-to-child infection can be reduced to about 1%. Preventive treatment involves the mother taking antiretrovirals during pregnancy and delivery, an elective caesarean section, avoiding breastfeeding, and administering antiretroviral drugs to the newborn. Antiretrovirals when taken by either the mother or the infant decrease the risk of transmission in those who do breastfeed. However, many of these measures are not available in the developing world. If blood contaminates food during pre-chewing it may pose a risk of transmission.
If a woman is untreated, two years of breastfeeding results in an HIV/AIDS risk in her baby of about 17%. Treatment decreases this risk to 1 to 2% per year. Due to the increased risk of death without breastfeeding in many areas in the developing world, the World Health Organization recommends either: (1) the mother and baby being treated with antiretroviral medication while breastfeeding being continued (2) the provision of safe formula. Infection with HIV during pregnancy is also associated with miscarriage.
GSE can result in high risk pregnancies and infertility. Some infertile women have GSE and iron deficiency anemia others have zinc deficiency and birth defects may be attributed to folic acid deficiencies.
It has also been found to be a rare cause of amenorrhea.
GSE, particularly coeliac disease, increases the risk of cancers of specific types. There are two predominant cancers associated with coeliac disease, cancer of the esophagus and lymphoproliferative diseases such as gluten-sensitive enteropathy-associated T-cell lymphoma (EATL). For non-EATL cancers it is thought the mineralemias such as zinc and selenium may play a role in increasing risk. GSE associated cancers are invariably associated with advanced coeliac disease, however, in de-novo EATL, the cancer is frequently detected in advance of the coeliac diagnosis, also EATL is the most common neoplasm.
When HIV-negative children take isoniazid after they have been exposed to tuberculosis, their risk to contract tuberculosis is reduced. A Cochrane review investigated whether giving isoniazid to HIV-positive children can help to prevent this vulnerable group from getting tuberculosis. They included three trials conducted in South Africa and Botswana and found that isoniazid given to all children diagnosed with HIV may reduce the risk of active tuberculosis and death in children who are not on antiretroviral treatment. For children taking antiretroviral medication, no clear benefit was detected.
Long-term nonprogressors (LTNPs), sometimes also called "elite controllers", are individuals infected with HIV, who maintain a CD4 count greater than 500 without antiretroviral therapy with a detectable viral load. Many of these patients have been HIV positive for 30 years without progressing to the point of needing to take medication in order not to develop AIDS. They have been the subject of a great deal of research, since an understanding of their ability to control HIV infection may lead to the development of immune therapies or a therapeutic vaccine. The classification "Long-term non-progressor" is not permanent, because some patients in this category have gone on to develop AIDS.
Long-term nonprogressors typically have viral loads under 10,000 copies RNA/ml blood, do not take antiretrovirals, and have CD4+ counts within the normal range. Most people with HIV not on medication have viral loads which are much higher.
It is estimated that around 1 in 300 people with HIV are long-term nonprogressors. Without the symptoms of AIDS, many LTNP patients may not know they are infected.
Genetic traits that confer greater resistance or more robust immune response to HIV are thought to explain why LTNP patients are able to live much longer with HIV than patients who are not LTNP. Some LTNP are infected with a weakened or inactive form of HIV, but it is now known that many LTNP patients carry a fully virulent form of the virus. Genetic traits that may affect progression include:
- Gene mutation. A mutation in the FUT2 gene affects the progression of HIV-1 infection. 20% of Europeans who have that mutation are called "non secretor" because of their absence of a certain type of antigen that also provides strong resistance against norovirus.
- Mitochondrial DNA. Different mitochondrial DNA haplotypes in humans may increase or decrease rates of AIDS progression. Haplotypes associated with more loosely coupled mitochondrial respiration, with reduced ATP and ROS generation, have been associated with faster progression and vice versa.
- Receptor mutations. A low percentage of long-term nonprogressors have been shown to have inherited mutations of the CCR5 receptor of T cell lymphocytes. HIV uses CCR5 to enter these cells. It is believed that the Δ32 (delta 32) variant of CCR5 impairs HIV ability to infect cells and cause disease. An understanding of this mechanism led to the development of a class of HIV medicines, the entry inhibitors. The presence of this mutation, however, is not a unifying theme among LTNPs and is observed in an exceedingly small number of these patients.
- HLA type has also been correlated with long-term non-progressor cohorts. In particular, strong correlations have been found between possessing the class 1 HLA-B*5701, HLA-B*5703, and/or HLA-B*2705 alleles and ability to exert control over HIV.
- Antibody production. All individuals with HIV make antibodies against the virus. In most patients, broadly neutralizing antibodies do not emerge until approximately 2–4 years after the initial infection. At this point, the latent reservoir has already been established and the presence of broadly neutralizing antibodies is not enough to prevent disease progression. In some rare patients, these antibodies emerge earlier and can result in a delayed disease course. These patients, however, are not typically classified as LTNPs, but rather as slow progressors, who will eventually develop AIDS. Induction of broadly neutralizing antibodies in healthy individuals is a potential strategy for a preventive HIV vaccine, as is the elicitation of these antibodies through rationally designed immunogens. Direct production of these antibodies in somatic tissue through plasmid transfection also pose a viable method for making these antibodies available in a large number of humans.
- APOBEC3G protein production. In a small number of people infected with HIV, the virus is naturally suppressed without medical treatment. These people may carry high quantities of a protein called APOBEC3G that disrupts viral replication in cells. APOBEC3G, or "A3" for short, is a protein that sabotages reverse transcription, the process HIV relies on for its replication. This process involves the virus transcribing its singe-stranded RNA genome into double-stranded DNA that is incorporated into the cell's genome. A3 usually stops dormant viruses in the human genome, called endogenous retroviruses, from reawakening and causing infections.
A study conducted on 452 patients revealed that the genotype responsible for higher IL-10 expression makes HIV infected people more susceptible to tuberculosis infection. Another study on HIV-TB co-infected patients also concluded that higher level of IL-10 and IL-22 makes TB patient more susceptible to Immune reconstitution inflammatory syndrome (IRIS). It is also seen that HIV co-infection with tuberculosis also reduces concentration of immunopathogenic matrix metalloproteinase (MMPs) leading to reduced inflammatory immunopathology.
Environmental enteropathy is believed to result in chronic malnutrition and subsequent growth stunting (low height-for-age measurement) as well as other child development deficits.
Enteropathy refers to any pathology of the intestine. Although enteritis specifically refers to an inflammation of the intestine, and is thus a more specific term than "enteropathy", the two phrases are sometimes used interchangeably.
HIV infection rates in central Africa are generally moderate to high.
The prognosis for tropical sprue may be excellent after treatment. It usually does not recur in people who get it during travel to affected regions. The recurrence rate for natives is about 20%, but another study showed changes can persist for several years.
HIV infection rates in eastern Africa are generally moderate to high.
HIV-SGD is more prevalent in HIV positive children than HIV positive adults, at about 19% and 1% respectively. Unlike other oral manifestations of HIV/AIDS such as Kaposi sarcoma, oral hairy leukoplakia and oral candidiasis, which decreased following the introduction of highly active antiretroviral therapy (HAART), HIV-SGD has increased.
AIDS-related complex, or ARC, was introduced after discovery of the HIV (Human Immunodeficiency Virus) when the medical community became aware of the inherent difficulties associated with treating patients suffering from an advanced case of HIV which gave rise to the term Acquired Immune Deficiency Syndrome (AIDS). The necessity for doctors to quickly and accurately understand the special needs of unknown patients suffering from AIDS in an emergency room situation was addressed with the creation of the term ARC.
ARC is "A prodromal phase of infection with the human immunodeficiency virus (HIV). Laboratory criteria separating AIDS-related complex ( ARC) from AIDS include elevated or hyperactive B-cell humoral immune responses, compared to depressed or normal antibody reactivity in AIDS; follicular or mixed hyperplasia in ARC lymph nodes, leading to lymphocyte degeneration and depletion more typical of AIDS; evolving succession of histopathological lesions such as localization of Kaposi's sarcoma, signaling the transition to the full-blown AIDS."
Clinical use of this term was widely discontinued by the year 2000 in the United States after having been replaced by modern laboratory criteria.
Preventive measures for visitors to tropical areas where the condition exists include steps to reduce the likelihood of gastroenteritis. These may comprise using only bottled water for drinking, brushing teeth, and washing food, and avoiding fruits washed with tap water (or consuming only peeled fruits, such as bananas and oranges). Basic sanitation is necessary to reduce fecal-oral contamination and the impact of environmental enteropathy in the developing world.
Current research is aimed at studying large cohorts of people with CVID in an attempt to better understand age of onset, as well as mechanism, genetic factors, and progression of the disease.
Funding for research in the US is provided by the National Institutes of Health. Key research in the UK was previously funded by the Primary Immunodeficiency Association (PiA) until its closure in January 2012, and funding is raised through the annual Jeans for Genes campaign. Current efforts are aimed at studying the following:
- Causes of complications. Little is known about why such diverse complications arise during treatment
- Underlying genetic factors. Though many polymorphisms and mutations have been identified, their respective roles in CVID development are poorly understood, and not represented in all people with CVID.
- Finding new ways to study CVID. Given that CVID arises from more than one gene, gene knock-out methods are unlikely to be helpful. It is necessary to seek out disease related polymorphisms by screening large populations of people with CVID, but this is challenging given the rarity of the disease.
EE is rarely symptomatic and is considered a subclinical condition. However, adults may have mild symptoms or malabsorption such as altered stool consistency, increased stool frequency and weight loss.
CVID has an estimated prevalence of about 1:50,000 in caucasians. The disease seems to be less prevalent amongst Asians and African-Americans. Males and females are equally affected; however, among children, boys predominate. A recent study of people in European with primary immunodeficiencies found that 30% had CVID, as opposed to a different immunodeficiency. 10-25% of people inherited the disease, typically through autosomal-dominant inheritance. Given the rarity of the disease, it is not yet possible to generalize on disease prevalence among ethnic and racial groups. CVID shortens the life-span; the median age of death for men and women is 42 and 44 years old, respectively. Those people with accompanying disorders had the worst prognosis and those people with CVID only had frequent infections had the longest survival rates, with life expectancy almost equalling that of the general UK population. Additionally, people with CVID with one or more noninfectious complications have an 11 times higher risk of death as compared to people with only infections.
In 1994, Stephen Crohn became the first person discovered to be completely resistant to HIV in all tests performed. In early 2000, researchers discovered a small group of sex workers in Nairobi, Kenya who were estimated to have sexual contact with 60 to 70 HIV positive clients a year without signs of infection. Researchers from Public Health Agency of Canada have identified 15 proteins unique to those virus-free sex workers. Later, however some sex workers were discovered to have contracted the virus, leading Oxford University researcher Sarah Rowland-Jones to believe continual exposure is a requirement for maintaining immunity.
In couples where the male and female are both HIV positive, conception may occur normally without concern for disease transmission. However, in couples where only one partner is HIV positive, there is risk of transmitting the infection to the uninfected partner. These couples, known as serodiscordant couples, are advised not to engage in unprotected intercourse. Instead, assisted reproductive methods are recommended. In all serodiscordant couples, the infected partner is advised to begin ART so that levels of the infection are undetectable prior to attempting conception.
In couples where the woman is HIV negative and the man is HIV positive, sperm is collected from the male partner using a technique called sperm washing. This process is then followed by intrauterine insemination (IUI) or in vitro fertilization (IVF). Couples may also use donor sperm from a non-infected male if desired.
In couples where the woman is HIV positive and the man is HIV negative, artificial insemination is recommended.
In areas where assisted reproductive techniques such as IUI or IVF are not available, techniques to reduce the transmission of HIV during conception can be attempted to reduce, but not eliminate, the risks. Most importantly, the HPTN 052 trial showed that when HIV infected partners were on ART there was 96% less transmission of HIV and none from partners with undetectable viral loads.
Many serodiscordant couples use pre-exposure prophylaxis (PrEP) to limit transmission of the infection to the uninfected partner. Daily use of PrEP has been shown to decrease transmission of the infection by an average of 63-75%. However, use of PrEP during pregnancy has not yet been studied and its long-term effects are unknown and should not be the only safety feature in the prevention process.
Although assisted reproductive techniques are available for serodiscordant couples, there are still limitations to achieving a successful pregnancy. Women with HIV have been shown to have decreased fertility which can affect available reproductive options. Women with HIV are also more likely to be infected with other sexually transmitted diseases, placing them at higher risk for infertility. Males with HIV appear to have decreased semen volume and sperm motility which decreases their fertility. Antiretroviral drugs may also affect both male and female fertility and some drugs can be toxic to newly developed embryos. Additionally, there have been cases where an HIV-negative partner was infected with the disease despite using processed artificial insemination.
Many of these viruses are controlled through laboratory screening tests. These fall into three basic varieties: antibody tests, nucleic acid tests (NAT), and surrogate tests. Antibody tests look for the immune system's response to the infection. Nucleic acid tests look for the genetic material of the virus itself. The third variety are tests that are not specific to the disease but look for other related conditions.
High risk activities for transfusion transmitted infections vary, and the amount of caution used for screening donors varies based on how dangerous the disease is. Most of the viral diseases are spread by either sexual contact or by contact with blood, usually either drug use, accidental needle injuries among health care workers, unsterilized tattoo and body piercing equipment, or through a blood transfusion or transplant. Other vectors exist.
Whether a donor is considered to be at "too high" of a risk for a disease to be allowed to donate is sometimes controversial, especially for sexual contact. High risk sexual activity is defined in many different ways, but usually includes:
- Sex in exchange for money or drugs.
- Men who have sex with men, the most controversial criterion.
- A recent history of sexually transmitted disease.
- Sex with a person who has had a positive test or was at high risk for a disease that can be spread in blood transfusions.
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.