Made by DATEXIS (Data Science and Text-based Information Systems) at Beuth University of Applied Sciences Berlin
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
The treatment of BLS follows two basic principles. When a patient presents with symptoms of BLS, the treating physician basically has two recognized options for management:
- Test-and-treat
- Treat empirically
The "treat empirically" route also has its difficulties, which have all come under wide debate and study. Recommendations are varied but seem to find some common ground around the notion that treatment should be individualized to the specific circumstances under which a patient has developed BLS since these circumstances affect the complex microbial make up of the affected bowel.
Tetracyclines have been the mainstay of treatment for BLS, but recent studies have concluded Rifaximin to be very effective in the treatment of BLS. One study by Di Stefano et al., however, concluded Metronidazole to be more effective than Rifaximin in the treatment of BLS.
Treatment focuses on addressing the underlying cause of symptoms.
Treatment of gastritis that leads to pernicious anemia consists of parenteral vitamin B-12 injection. Associated immune-mediated conditions (e.g., insulin dependent diabetes mellitus, autoimmune thyroiditis) should also be treated. However, treatment of these disorders has no known effect in the treatment of achlorhydria.
Achlorhydria associated with "Helicobacter pylori" infection may respond to H pylori eradication therapy, although resumption of gastric acid secretion may only be partial and it may not always reverse the condition completely.
Antimicrobial agents, including metronidazole, amoxicillin/clavulanate potassium, ciprofloxacin, and rifaximin, can be used to treat bacterial overgrowth.
Achlorhydria resulting from long-term proton-pump inhibitor (PPI) use may be treated by dose reduction or withdrawal of the PPI.
Secondary chronic intestinal pseudo-obstruction is managed by treating the underlying condition.
There is no cure for primary chronic intestinal pseudo-obstruction. It is important that nutrition and hydration is maintained, and pain relief is given. Drugs that increase the propulsive force of the intestines have been tried, as have different types of surgery.
Prucalopride, pyridostigmine, metoclopramide, cisapride, and erythromycin may be used, but they have not been shown to have great efficacy. In such cases, treatment is aimed at managing the complications. Linaclotide is a new drug that received approval from Food and Drug Administration in August 2012 and looks promising in the treatment of chronic intestinal pseudo-obstruction, gastroparesis and inertia coli.
Intestinal stasis, which may lead to bacterial overgrowth and subsequently, diarrhea or malabsorption, is treated with antibiotics.
Nutritional deficiencies are treated by encouraging patients to avoid food high in fat and fibre, which are harder to digest and increase abdominal distention and discomfort, and have small, frequent meals (5–6 per day), focusing on liquids and soft food. Reducing intake of poorly absorbed sugar alcohols may be of benefit. Referral to an accredited dietitian is recommended. If dietary changes are unsuccessful in meeting nutritional requirements and stemming weight loss, enteral nutrition is used. Many patients eventually require parenteral nutrition.
Total parenteral nutrition (TPN) is a form of long-term nutritional treatment needed for patients that have severe pseudoobstruction. After a period of no improvement of intestinal function or motility the decision to start TPN will be made, and the surgical procedure to add a long-term, more permanent IV to administer TPN will occur. Types of IV catheters to be placed will be a PICC line or central line which include mediports, Broviac, or Hickman lines depending on how long the physicians believe the patient will require TPN. Patients that are deemed TPN dependent will require constant checkups to monitor the catheter is working properly, check liver enzyme levels and look for signs of blood infections, as catheter blockage, liver damage, and infections of catheters are the main complications associated with long term TPN use and can result in sepsis and/or additional surgeries if not properly monitored. TPN nutritional feeds are given over a period of several hours to all day infusions, and are a mixture of all the vitamins, minerals, and calories similar to what one would get eating orally daily as well as any other specific nutritional needs the patient has at the moment. TPN format is typically changed depending on loss/gain of weight and bloodwork results, and is specially formulated to meet each individual patient's needs.
Use of octreotide has been described.
Cannabis has long been known to limit or prevent nausea and vomiting from a variety of causes. This has led to extensive investigations that have revealed an important role for cannabinoids and their receptors in the regulation of nausea and emesis. With the discovery of the endocannabinoid system, novel ways to regulate both nausea and vomiting have been discovered that involve the production of endogenous cannabinoids acting centrally. The plant cannabis has been used in clinics for centuries, and has been known to be beneficial in a variety of gastrointestinal diseases, such as emesis, diarrhea, inflammatory bowel disease and intestinal pain. Moreover, modulation of the endogenous cannabinoid system in the gastrointestinal tract may provide a useful therapeutic target for gastrointestinal disorders. While some GI disorders may be controlled by diet and pharmaceutical medications, others are poorly moderated by conventional treatments. Symptoms of GI disorders often include cramping, abdominal pain, inflammation of the lining of the large and/or small intestine, chronic diarrhea, rectal bleeding and weight loss. Patients with these disorders frequently report using cannabis therapeutically.
In a 2012 animal study, cannabichromene was shown to normalize gastrointestinal hypermotility without reducing the transit time. The study notes that this result is of potential clinical interest, as the only drugs available for intestinal dysmotility are often associated with constipation.
Bacterial overgrowth is usually treated with a course of antibiotics although whether antibiotics should be a first line treatment is a matter of debate. Some experts recommend probiotics as first line therapy with antibiotics being reserved as a second line treatment for more severe cases of SIBO. Prokinetic drugs are other options but research in humans is limited. A variety of antibiotics, including tetracycline, amoxicillin-clavulanate, fluoroquinolones, metronidazole, neomycin, cephalexin, trimethoprim-sulfamethoxazole, and nitazoxanide have been used; however, the best evidence is for the use of rifaximin.
A course of one week of antibiotics is usually sufficient to treat the condition. However, if the condition recurs, antibiotics can be given in a cyclical fashion in order to prevent tolerance. For example, antibiotics may be given for a week, followed by three weeks off antibiotics, followed by another week of treatment. Alternatively, the choice of antibiotic used can be cycled.
The condition that predisposed the patient to bacterial overgrowth should also be treated. For example, if the bacterial overgrowth is caused by chronic pancreatitis, the patient should be treated with coated pancreatic enzyme supplements.
Probiotics are bacterial preparations that alter the bacterial flora in the bowel to cause a beneficial effect. Animal research has demonstrated that probiotics have barrier enhancing, antibacterial, immune modulating and anti-inflammatory effects which may have a positive effect in the management of SIBO in humans. "Lactobacillus casei" has been found to be effective in improving breath hydrogen scores after 6 weeks of treatment presumably by suppressing levels of a small intestinal bacterial overgrowth of fermenting bacteria. The multi-strain preparation VSL#3 was found to be effective in suppressing SIBO. "Lactobacillus plantarum", "Lactobacillus acidophilus", and "Lactobacillus casei" have all demonstrated effectiveness in the treatment and management of SIBO. Conversely, "Lactobacillus fermentum" and "Saccharomyces boulardii" have been found to be ineffective. A combination of "Lactobacillus plantarum" and "Lactobacillus rhamnosus" has been found to be effective in suppressing bacterial overgrowth of abnormal gas producing organisms in the small intestine.
Probiotics are superior to antibiotics in the treatment of SIBO. A combination of probiotic strains has been found to produce better results than therapy with the antibiotic drug metronidazole and probiotics have been found to be effective in treating and preventing secondary lactase deficiency and small intestinal bacteria overgrowth in individuals suffering from post-infectious irritable bowel syndrome. Probiotics taken in uncomplicated cases of SIBO can usually result in the individual becoming symptom free. Probiotic therapy may need to be taken continuously to prevent the return of overgrowth of gas producing bacteria. A study by the probiotic yogurt producer Nestlé found that probiotic yogurt may also be effective in treating SIBO with evidence of reduced inflammation after 4 weeks of treatment.
An elemental diet taken for two weeks is an alternative to antibiotics for eliminating SIBO. An elemental diet works via providing nutrition for the individual while depriving the bacteria of a food source. Additional treatment options include the use of prokinetic drugs such as 5-HT4 receptor agonists or motilin agonists to extend the SIBO free period after treatment with an elemental diet or antibiotics. A diet void of certain foods that feed the bacteria can help alleviate the symptoms. For example, if the symptoms are caused by bacterial overgrowth feeding on indigestible carbohydrate rich foods, following a FODMAP restriction diet may help.
Bile acid sequestrants are the main agents used to treat bile acid malabsorption. Cholestyramine and colestipol, both in powder form, have been used for many years. Unfortunately many patients find them difficult to tolerate; although the diarrhea may improve, other symptoms such as pain and bloating may worsen. Colesevelam is a tablet and some patients tolerate this more easily. A proof of concept study of the farnesoid X receptor agonist obeticholic acid has shown clinical and biochemical benefit.
As of March 15, 2016, Novartis Pharmaceuticals is conducting a phase II clinical study involving a farnesoid X receptor agonist named LJN452.
Medications may consist of stool softeners and laxatives in IBS-C and antidiarrheals (e.g., opiate, opioid, or opioid analogs such as loperamide, codeine, diphenoxylate) if diarrhea is predominant.
Drugs affecting serotonin (5-HT) in the intestines can help reduce symptoms. On the other hand, many IBS-D patients report that SSRI type medications exacerbate spasms and diarrhea. This is thought to be due to the large number of serotonin receptors in the gut. 5HT3 antagonists such as ondansetron are effective in postinfectious IBS and diarrhea-dominant IBS due to their blockade of serotonin on 5HT3 receptors in the gut; the reason for their benefit is believed to be that excessive serotonin in the gut is thought to play a role in the pathogenesis of some subtypes of IBS. Certain atypical antipsychotic medications, such as clozapine and olanzapine, may also provide relief due to serotonergic properties these agents possess, acting on the same receptors as other medications in this specific category. Benefits may include reduced diarrhea, reduced abdominal cramps, and improved general well-being. Any nausea present may also respond to 5HT3 antagonists owing to their antiemetic properties. Serotonin stimulates the gut motility and so agonists can help constipation-predominant irritable bowel, while antagonists can help diarrhea-predominant irritable bowel. Selective serotonin reuptake inhibitors, SSRIs, frequently prescribed for panic and/or anxiety disorder and depression, affect serotonin in the gut, as well as the brain. The bowels are highly dependent on serotonin for neural communication. "Selective serotonin reuptake inhibitor antidepressants seem to promote global well-being in some patients with irritable bowel syndrome and, possibly, some improvement in abdominal pain and bowel symptoms, but this effect appears to be independent of improved depression. Further research is required."
Mast cells and the compound that they secrete are central to the pathophysiology and implicated in the treatment of IBS; some of the secreted mast cell mediators (and associated receptors) which have been implicated in symptoms of IBS or specific subtypes include: histamine (HRH1, HRH2, HRH3), tryptase and chymase (PAR2), serotonin (5-HT3), PGD2 (DP1). Histamine also causes epithelial secretion of chloride ions and water (associated with secretory diarrhea) by signaling through a receptor or ligand-gated ion channel that has not been identified as of 2015. A 2015 review noted that both H1-antihistamines and mast cell stabilizers have shown efficacy in reducing pain associated with visceral hypersensitivity in IBS; other lower quality studies have also suggested the benefit of these agents for IBS. In a related review on idiopathic mast cell activation syndromes (including IBS), a combined treatment approach using antileukotrienes, H1/H2-antihistamines, and a mast cell stabilizer are suggested.
For patients who do not adequately respond to dietary fiber, osmotic laxatives such as polyethylene glycol, sorbitol, and lactulose can help avoid "cathartic colon" which has been associated with stimulant laxatives. Among the osmotic laxatives, doses of 17–26 g/d of polyethylene glycol have been well studied. Lubiprostone (Amitiza) is a gastrointestinal agent used for the treatment of idiopathic chronic constipation and constipation-predominant IBS. It is well tolerated in adults, including elderly patients. As of July 20, 2006, lubiprostone had not been studied in pediatric patients. Lubiprostone is a bicyclic fatty acid (prostaglandin E1 derivative) that acts by specifically activating ClC-2 chloride channels on the apical aspect of gastrointestinal epithelial cells, producing a chloride-rich fluid secretion. These secretions soften the stool, increase motility, and promote spontaneous bowel movements. Unlike many laxative products, lubiprostone does not show signs of tolerance, dependency, or altered serum electrolyte concentration.
Prevention focuses on improving sanitation of water and food sources.
Treatment focuses on addressing the central components of intestinal inflammation, bacterial overgrowth and nutritional supplementation.
Treatment includes dietary changes (low fiber diets) and, in some cases, restrictions on fat and/or solids. Eating smaller meals, spaced two to three hours apart has proved helpful. Avoiding foods that cause the individual problems, such as pain in the abdomen, or constipation, such as rice or beef, will help avoid symptoms.
Metoclopramide, a dopamine D receptor antagonist, increases contractility and resting tone within the GI tract to improve gastric emptying. In addition, dopamine antagonist action in the central nervous system prevents nausea and vomiting. Similarly, the dopamine receptor antagonist domperidone is also used to treat gastroparesis. Erythromycin is known to improve emptying of the stomach but its effects are temporary due to tachyphylaxis and wane after a few weeks of consistent use.
Sildenafil citrate, which increases blood flow to the genital area in men, is being used by some practitioners to stimulate the gastrointestinal tract in cases of diabetic gastroparesis.
The antidepressant mirtazapine has proven effective in the treatment of gastroparesis unresponsive to conventional treatment. This is due to its antiemetic and appetite stimulant properties. Mirtazapine acts on the same serotonin receptor (5-HT3) as does the popular anti-emetic ondansetron.
In specific cases where treatment of chronic nausea and vomiting proves resistant to drugs, implantable gastric stimulation may be utilized. A medical device is implanted that applies neurostimulation to the muscles of the lower stomach to reduce the symptoms. This is only done in refractory cases that have failed all medical management (usually at least 2 years of treatment). Medically refractory gastroparesis may also be treated with a pyloromyotomy, which widens the gastric outlet by cutting the circular pylorus muscle. This can be done laparoscopically or endoscopically.
In people presenting with symptoms compatible with radiation enteropathy, the initial step is to identify what is responsible for causing the symptoms. Management is best with a multidisciplinary team including gastroenterologists, nurses, dietitians, surgeons and others.
Medical treatments include the use of hyperbaric oxygen which has beneficial effects in radiation proctitis or anal damage. Nutritional therapies include treatments directed at specific malabsorptive disorders such as low fat diets and vitamin B12 or vitamin D supplements, together with bile acid sequestrants for bile acid diarrhea and possibly antibiotics for small intestinal bacterial overgrowth. Probiotics have all been suggested as another therapeutic avenue.
Endoscopic therapies including argon plasma coagulation have been used for bleeding telangiectasia in radiation proctitis and at other intestinal sites, although there is a rick of perforation. Sucralfate enemas look promising in proctitis.
Surgical treatment may be needed for intestinal obstruction, fistulae, or perforation, which can happen in more severe cases. These can be fatal if patients present as an emergency, but with improved radiotherapy techniques are now less common.
Optimal treatment usually produces significant improvements in quality of life.
Prevention of radiation injury to the small bowel is a key aim of techniques such as brachytherapy, field size, multiple field arrangements, conformal radiotherapy techniques and intensity-modulated radiotherapy. Medications including ACE inhibitors, statins and probiotics have also been studied and reviewed.
There are multiple large-field, multi-country research initiatives focusing on strategies to prevent and treat EE.
- The MAL-ED project
- The Alive and Thrive nutrition project
- The Sanitation, Hygiene and Infant Nutrition Efficacy (SHINE) Trial (ClinicalTrials.gov identifier: NCT01824940)
- The WASH Benefits Study
Gastroparesis can be diagnosed with tests such as x-rays, manometry, and gastric emptying scans. The clinical definition for gastroparesis is based solely on the emptying time of the stomach (and not on other symptoms), and severity of symptoms does not necessarily correlate with the severity of gastroparesis. Therefore, some patients may have marked gastroparesis with few, if any, serious complications.
Antimotility drugs such as loperamide and diphenoxylate reduce the symptoms of diarrhea by slowing transit time in the gut. They may be taken to slow the frequency of stools, but not enough to stop bowel movements completely, which delays expulsion of the causative organisms from the intestines. They should be avoided in patients with fever, bloody diarrhea, and possible inflammatory diarrhea. Adverse reactions may include nausea, vomiting, abdominal pain, hives or rash, and loss of appetite. Antimotility agents should not, as a rule, be taken by children under age two.
The most reliable test for EPI in dogs and cats is serum trypsin-like immunoreactivity (TLI). A low value indicates EPI. Fecal elastase levels may also be used for diagnosis in dogs.
In dogs, the best treatment is to supplement its food with dried pancreatic extracts. There are commercial preparations available, but chopped bovine pancreas from the butcher can also be used (pork pancreas should not be used because of the rare transmission of pseudorabies). Symptoms usually improve within a few days, but lifelong treatment is required to manage the condition. A rare side-effect of use of dried pancreatic extracts is oral ulceration and bleeding.
Because of malabsorption, serum levels of cyanocobalamin (vitamin B12) and tocopherol (vitamin E) may be low. These may be supplemented, although since cyanocobalamin contains the toxic chemical cyanide, dogs that have serious cobalamin issues should instead be treated with hydroxocobalamin or methylcobalamin. Cyanocobalamin deficiency is very common in cats with EPI because about 99 percent of intrinsic factor (which is required for cyanocobalamin absorption from the intestine) is secreted by the pancreas. In dogs, this figure is about 90 percent, and only about 50 percent of dogs have this deficiency. Cats may suffer from Vitamin K deficiencies. If there is bacterial overgrowth in the intestine, antibiotics should be used, especially if treatment is not working. In dogs failing to gain weight or continuing to show symptoms, modifying the diet to make it low-fiber and highly digestible may help. Despite previous belief that low-fat diets are beneficial in dogs with EPI, more recent studies have shown that a high-fat diet may increase absorption of nutrients and better manage the disease. However, it has been shown that different dogs respond to different dietary modifications, so the best diet must be determined on a case-by-case basis.
One possible sequela, volvulus (mesenteric torsion) is a rare consequence of EPI in dogs.
Little is known on the prognosis of achlorhydria, although there have been reports of an increased risk of gastric cancer.
A 2007 review article noted that non-"Helicobacter" bacterial species can be cultured from achlorhydric (pH > 4.0) stomachs, whereas normal stomach pH only permits the growth of "Helicobacter" species. Bacterial overgrowth may cause false positive H. Pylori test results due to the change in pH from urease activity.
Small bowel bacterial overgrowth is a chronic condition. Retreatment may be necessary once every 1–6 months. Prudent use of antibacterials now calls for an antibacterial stewardship policy to manage antibiotic resistance.
If diarrhea becomes severe (typically defined as three or more loose stools in an eight-hour period), especially if associated with nausea, vomiting, abdominal cramps, fever, or blood in stools, medical treatment should be sought. Such patients may benefit from antimicrobial therapy. A 2000 literature review found that antibiotic treatment shortens the duration and severity of TD; most reported side effects were minor, or resolved on stopping the antibiotic.
Fluoroquinolone antibiotics are the drugs of choice. Trimethoprim–sulfamethoxazole and doxycycline are no longer recommended because of high levels of resistance to these agents. Antibiotics are typically given for three to five days, but single doses of azithromycin or levofloxacin have been used. Rifaximin is approved in the U.S. for treatment of TD caused by ETEC. If diarrhea persists despite therapy, travelers should be evaluated for bacterial strains resistant to the prescribed antibiotic, possible viral or parasitic infections, bacterial or amoebic dysentery, "Giardia", helminths, or cholera.
Once diagnosed, tropical sprue can be treated by a course of the antibiotic tetracycline or sulphamethoxazole/trimethoprim (co-trimoxazole) for 3 to 6 months.
Supplementation of vitamins B and folic acid improves appetite and leads to a gain in weight.
Treatment is multifactorial. A diet very low in fat and high in high quality protein is essential. Treatment of humans can also involve the use of MCT (medium-chain triglycerides) oil and/or the drug octreotide. In dogs, fat soluble vitamins (A, D, E, and K) should be supplemented. Corticosteroid treatment may be required for life. Antibiotics can be used to treat bacterial overgrowth. With a very low serum albumin, transfusion with blood plasma or an infusion of hetastarch may be necessary to treat the signs until the diet can take effect. Lymphangiectasia is rarely cured but can remain in remission for a long time. It can be fatal when unresponsive to treatment.
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.
Intestinal bacteria may play a causal role in the dermatological condition rosacea. A recent study subjected patients to a hydrogen breath test to detect the occurrence of SIBO. It was found that significantly more patients were hydrogen-positive than controls indicating the presence of bacterial overgrowth (47% v. 5%, p<0.001).
Hydrogen-positive patients were then given a 10-day course of rifaximin, a non-absorbable antibiotic that does not leave the digestive tract and therefore does not enter the circulation or reach the skin. 96% of patients experienced a complete remission of rosacea symptoms that lasted beyond 9 months. These patients were also negative when retested for bacterial overgrowth. In the 4% of patients that experienced relapse, it was found that bacterial overgrowth had returned. These patients were given a second course of rifaximin which again cleared rosacea symptoms and normalized hydrogen excretion.
In another study, it was found that some rosacea patients that tested hydrogen-negative were still positive for bacterial overgrowth when using a methane breath test instead. These patients showed little improvement with rifaximin, as found in the previous study, but experienced clearance of rosacea symptoms and normalization of methane excretion following administration of the antibiotic metronidazole, which is effective at targeting methanogenic intestinal bacteria.
These results suggest that optimal antibiotic therapy may vary between patients and that diverse species of intestinal bacteria appear to be capable of mediating rosacea symptoms.
This may also explain the improvement in symptoms experienced by some patients when given a reduced carbohydrate diet. Such a diet would restrict the available material necessary for bacterial fermentation and thereby reduce intestinal bacterial populations.
Cefotaxim s DOC. After confirmation of SBP, patients need hospital admission for intravenous antibiotics. They will often also receive intravenous albumin. A repeat paracentesis in 48 hours is sometimes performed to ensure control of infection. Once patients have recovered from SBP, they require regular prophylactic antibiotics as long as they still have ascites.
The addition of a prokinetic drug to an antibiotic regime reduces the incidence of spontaneous bacterial peritonitis possibly via decreasing small intestinal bacterial overgrowth.