Anti-tuberculosis Drug-induced Liver Injury (ATLI) Effects

Anti-tuberculosis Drug-induced Liver Injury (ATLI) Effects Abstract Tuberculosis (TB) is world’s deadliest communicable disease, with 9 million incident cases and 1.5 million deaths globally in 2013. Most of the cases of TB were reported from Asian (56%), and African (29%) continents. In Saudi Arabia the annual incidence rate of TB ranged between 14 and 17/100,000. Two provinces, Makkah and Jazan showed the highest incidence around 20/100,000 over the last one decade. Jazan region showed more than double the incidence rate of TB compared to rest of the Southern province. Jazan share border with Yemen, and receives many illegal immigrants. Studies showed that non-Saudi Arabians had 2-3 times higher incidence of TB than Saudi national. The large number of Non-Saudis came from countries with high incidence of TB such as Bangladesh, Pakistan, India, Indonesia, Philippines, Yemen, Ethiopia, Somalia, Chad, Nigeria and other African countries. The active TB patients can be treated safely and effectively through the directly-observed therapy strategy (DOTS). DOTS is a short course of standard anti-TB treatment which consist of taking drug combinations of Isoniazid, Rifampicin, Pyrazinamide, Ethambutol and Streptomycin for 6–9 months. The drug isoniazid, rifampicin and pyrazinamide have the potential to induce liver damage.This anti-tuberculosis drug-induced liver injury (ATLI) ranges from mild to severe forms, and can even be fatal. The incidence of ATLI during standard anti-TB treatment range from 2.0% to 28.0% according to different populations. Moreover, ATLI reduce the efficacy of anti-TB treatment, as they may cause treatment failure, relapse and drug-resistance which could significantly reduce the effects of TB control. To the best of our knowledge, there is no known published data on the incidence of anti-tuberculosis drug-induced liver injury (ATLI) and risk factors from Saudi population. Identification of patients at increased risk for ATLI is important because hepatotoxicity causes significant morbidity and mort ality and may require modification of the therapeutic regimen. The aim of this study will to estimate the incidence of ATLI and the risk factors associated with anti-TB treatment. The findings of this study will allow us to enhance TB treatment, monitoring and control of the TB in KSA. Introduction Tuberculosis (TB) is world’s deadliest communicable disease, with 9 million incident cases and 1.5 million deaths globally in 2013 [1]. Most of the cases of TB were reported from Asian (56%), and African (29%) continents [1]. In Saudi Arabia the annual incidence rate of TB ranged between 14 and 17/100,000 [2]. Two provinces, Makkah and Jazan showed the highest incidence around 20/100,000 over the last one decade [2]. Jazan region showed more than double the incidence rate of TB compared to rest of the Southern province. Jazan share border with Yemen, and receives many illegal immigrants. Studies showed that non-Saudi Arabians had 2-3 times higher incidence of TB than Saudi national. [3]. The large number of Non-Saudis came from countries with high incidence of TB such as Bangladesh, Pakistan, India, Indonesia, Philippines, Yemen, Ethiopia, Somalia, Chad, Nigeria and other African countries. Patients with active TB disease can be treated safely and effectively through the directly-observed therapy strategy (DOTS) which started in 2000. DOTS is a short course of standard anti-TB treatment which consist of taking drug combinations of Isoniazid, Rifampicin, Pyrazinamide, Ethambutol and Streptomycin for 6–9 months [4]. These drugs effectively kills the bacteria but it induced hepatotoxicity known as anti-tuberculosis drug-induced liver injury (ATLI) [5.tostmann 2008]. The ATLI ranges from mild to severe forms, and can even be fatal. The incidence of ATLI during standard anti-TB treatment range from 2.0% to 28.0% according to different populations. [5,6]. The incidence is higher in the developing countries (8% to 39%), compared to developed countries (3%–4%) (7-11). Moreover, ATLI reduce the efficacy of anti-TB treatment, as they may cause treatment failure, relapse and drug-resistance which could significantly reduce the effects of TB control. [5,6]. Many risk factors have been implicated for ATLI. These include older age, female gender, poor nutritional status, pre-existing liver disease, high alcohol intake, hepatitis B, malnutrition, hypoalbuminaemia and advanced TB (12-16). Inappropriate use of drugs, acetylator status, and recently, immunogenetic factor, have also been implicated (17,18). Infections with hepatitis C virus and human immunodeficiency virus (HIV) have also been said to increase the risk (19). It is very important to understand the risk factors of ATLI, in order to detect the adverse events earlier and deliver timely intervention. The identification of high-risk patients would be useful to allow early detection of hepatotoxicity and reduce the morbidity and mortality of this condition. Hence we plan this study to identify the risk factors associated with anti-tuberculosis drug induced liver injury in patients who receive anti-TB treatment. To the best of our knowledge, there is no known published data on the incidence of anti-tuberculosis drug-induced liver injury (ATLI) and risk factors from Saudi population. The aim of this study will to estimate the incidence of ATLI and the risk factors associated with anti-TB treatment. The findings of this study will allow us to enhance TB treatment, monitoring and control of the TB in KSA. 2. PROJECT OBJECTIVES This study aimed to estimate the incidence and risk factors of anti-tuberculosis Drug Induced Liver Injury (ATLI) in patient receiving anti-TB treatment in Jazan population. 1. To estimate the incidence of abnormal liver function tests (LFTs) in patient receiving anti-TB treatment. 2. To identify the risk factors associated with anti-tuberculosis Drug Induced Liver Injury (ATLI) in patient receiving anti-TB treatment. Review of Literature Incidence The first line drugs used to treat TB were isoniazid (INH), rifampicin (RIF), pyrazinamide (PZY) and ethambutol (EMB). Most of the TB patients tolerate the drugs but some develop hepatotoxicity known as anti-tuberculosis drug-induced liver injury (ATLI). [Forget 2006].The ATLI ranges from mild to severe forms, and can even be fatal. Data from the literature shows that the incidence of ATLI is 3.0% in Canada (Asia population accounted for 42%)[Yee 2003], China 2.5% [Shang 2011], 5.0% in Hong Kong[ Chang 2008], 5.3% in Singapore[teleman 2002], 16.1% in Taiwan [Huang 2003], 9.7% in Malaysia [Marzuki 2008],36% in Japan [Ellard 1978], 8-36 per cent in India [Parthasarthy 1986, Mehta 1990], 13% Iran [Baghaei]. The risk of developing ATLI was fivefold for hepatitis C patients, fourfold for HIV positive patients, and 14 fold for patients co-infected with hepatitis C and HIV [Ungo 1998]. The incidence is higher in the developing countries (8% to 39%), compared to developed countries (3%–4%) (7-11). Moreover, ATLI reduce the efficacy of anti-TB treatment, as they may cause treatment failure, relapse and drug-resistance which could significantly reduce the effects of TB control. [5,6]. Definition of ATLI The criteria for the diagnosis of ATLI in the absence of symptoms is elevation of transaminases up to 5 times the upper limit of normal (ULN) and in the presence of symptoms up to three times the ULN or twice the ULN of bilirubin in the blood [Saukkonen 2006]. Mechanism of toxicity Among Isoniazid, rifampicin, pyrazinamide and ethambutol, the first three drugs have the potential for hepatotoxicity with pyrazinamide (PZA) being the most hepatotoxic followed by isoniazid (INH) and rifampicin.[Yee]Rifampicin combined with PZA is more hepatotoxic than with INH.[ Jasmer 2002]Pyrazinamide contributes significantly to acute liver failure [ Durand 1995].The most important adverse effects of isoniazid are hepatic toxicity and potentially fatal drug-induced hepatitis[Nolan 1999], especially when associated with rifampicin. The frequency of occurrence of isoniazid-associated hepatitis depends on age. Other factors linked to a predisposition to isoniazid-associated hepatotoxicity include alcohol abuse, use of illegal drugs and a previous history of liver disease. Clinical features ATLI usually take place in the first 2 months of treatment but it may happen at any time during the treatment period. Clinical and biochemical features of ATLI are difficult to differentiate form viral hepatitis [Mitchell 1976]. The signs and symptoms of ATLI are jaundice, abdominal pain, nausea, vomiting and Weakness. Risk factors for ATLI Many risk factors have been implicated for ATLI. These include older age, female gender, poor nutritional status, pre-existing liver disease, high alcohol intake, hepatitis B, malnutrition, hypoalbuminaemia and advanced TB (12-16). Inappropriate use of drugs, acetylator status, and recently, immunogenetic factor, have also been implicated (17,18). Infections with hepatitis C virus and human immunodeficiency virus (HIV) have also been said to increase the risk (19).

Diet Aids and FDA Approval

The diet industry is huge, a multimillion dollar industry. The introduction to products that help individuals lose weight will always be popular and interest never wanes because of the frequency in which new products arise from the market. Now comes the big question, just how important is it for diet aids to have Food & Drug Agency (FDA) claims? Most health supplements, vitamin supplements, and diet aids do not have FDA approved on them. But does this really matter? In some cases, yes and in others no. The FDA is an organization that is part of the US department of Health and Human Services.The center for drug evaluation and research (CDER) makes sure that all prescription and over the counter drugs are safe for consumers, including diet supplements. Most diet aides are released without being regulated from the FDA but every now and then one is, the most recent being ephedra, and its ban. It is important to remember two things when reading claims whether they are for health benefits or for dangerous side effects. The first is that if there is a warning on the label it is unknown whether 50% of all those that used the product or if on 0.1% had side effects. Companies must put the side effect warning on the label if only one person in the study had side effects. This is mainly for insurance, if you take the diet aid and experiences side effects out of thousands of individuals that don’t then you can’t sue the company; the warning was on the label. Secondly just because there are health benefit claims on the label doesn’t actually mean that they will happen to the individual taking the product. It simple means that it may happen not that it definitely will.However having FDA approval is always a good thing. Unlike a company the FDA will conduct research or contract researchers to conduct a thorough and correctly structured clinical study. Any results will show good conclusions that can be trusted. The FDA is looking out for the consumer, not t he companies whose bottom line is to make as much product as possible. Here is an outline of the regulation of diet aids with ephedra. Ephedra was a popular weight loss product, particularly when paired with caffeine and aspirin.However the use of ephedra was linked to heart problems and over 155 deaths. Like many diet aids it increases your metabolism by increasing your heart rate, which causes many problems. The FDA could not actually ban ephedra but it sent out a ruling that the FDA does not support and products containing ephedra as it had unreasonable risks of illness or death associated with it. The FDA collected information about ephedra from independent experts and studies on both the benefits and dangers of ephedra.However it should be noted that Chinese herbal medicines and teas that contain ephedra are not regulated under this ruling. (Nelson, 135). Now it is very likely that a vast majority of individuals using ephedra did not experience any side effects or heart problem s at all. However there was enough of the population that did, and most importantly quite a few deaths were found to be directly linked to ephedra in diet supplements that the FDA felt there was a significant cause for concern.Due to it’s ruling many states in the US banned the selling of ephedra products causing many companies to reformulate their diet products. Also if you look at the history of the FDA and its rulings you will find a very tangled web. The FDA during the 1940s and 50s in diet aids approved amphetamines and amphetamine like products. Since then the FDA has been trying to define the parameters in which these products can be safely taken (Colman, 380-385). The FDA has been found to change its mind over time, particularly as science is improving and research tools are becoming available.Now I should let you know that a product containing ephedra is still all-natural because ephedra comes from the Ma Huang plants. Incidentally most health supplements and diet ai ds all come from plants, so they are â€Å"all natural†. Just because it is labeled all natural doesn’t mean it isn’t dangerous. Almost anything at the wrong level will kill you. It is simply the products that are dangerous at small amounts that cause the most concern. Eating carrots can cause blindness and eventually death, but you have to eat a lot of carrots for a long time.Many of the substances found in diet aids are at concentration higher than they would be found in nature and this is what can make them harmful. Now comes the consumer, just who should they believe. You are standing in a store reading a label that lists some pretty fantastic benefits, but it is not FDA approved (Allen). Many products are being marketed as helping you lose weight, improve your life span or have anti-aging properties. Without the correct clinical trials, which can take years, it is unknown if the benefits outweigh the risks.As previously stated Ephedra was first approved and then found to be dangerous as was another product called Fen-phen. (Keim). There are many health claims available to help your memory, expand your age, make your heart healthier etc. You can achieve this by taking ginkgo boloba, cinnamon extract, grapefruit extract, acai juice, resveratrol etc. There are other diet aids that act as appetite suppressants or are thermogentic (raise your metabolism), fat blockers, and meal replacement.The real danger is not using the diet aids in a correct manner as there are significant risks of developing eating disorders when using dieting aid (Celio, 492-497). This takes away from the benefits you will have by losing weight because you will be lighter but you won’t be healthy. It is amusing to actually read the directions on diet aids. The majority of the time the directions give dosage information and then state that it is only effective eating a healthy diet and exercise. Now most medicinal practitioners and athletes can get an individual to lose weight by eating sensible and exercising.The diet aid may actually work not because of the diet aid but because you are eating a healthy diet and exercising. There is a large psychological part to dieting that many people do not understand. On a personal note I would feel much more secure and confident using a diet aid that was approved by the FDA but that does not mean that I would rule out using other products. I would first research and collect some information about products. I would stear clear of any product that says has side effects relating to heart problems or internal organ failure.If the side effects are not minor and research shows that cultures have been using it successfully for years then I probably would try it. It is important to pay attention to detail such as concentration in the diet aid as well as follow the directions and pay attention to what is going on in your body. If I had any concerns I would see about speaking to a nutritionist or doctor about any risks. It is fine to use diet aids but don’t just pick one on a whim. You do need to be careful and determine what the risks are and if you think the benefits are greater than the risks.

Civil War (Ken Burns Review) Essay

Episode V ,†The Universe of Battle†, of The Civil War series directed by Ken Burns reflects on how the Battle of Gettysburg in 1863 was a major turning point in the Civil War. He details how the Union defeat at Gettysburg, the work of women, and the entry of black men into the Union army enabled the North to significantly weaken the Confederacy. The Union and Confederacy both suffered thousands of casualties in the bloody battles that took place. However, by the end of 1863, the North was led to a â€Å"new birth of freedom† while the South had to come to the realization that the â€Å"bottom rail was on top†, now. Burns begins the episode with the first of three battles that took place in the rural town of Gettysburg, Pennsylvania on July 1, 1863. The Union was led by Commander Meade who served under General Grant and the Confederacy by General Lee. Due to Lee’s commanders not delivering tactical support on the first day of battle, the North was able to hold their high ground, but did this not compare to what was going to happen in the following two days. The second day of battle the number of soldiers present in Gettysburg grew substantially, on both sides. A significant part of this battle is when the Union stopped the Confederacy form gaining position of Little Round Top. This was long day of battle, whole regiments in the Confederacy were lost this day. By third day of battle Lee was acting as if he was invincible and this was detrimental for his men. Union soldiers slaughtered the Confederacy and they never entered that far into Union territory again. Lee had failed his men and he knew it. This must have been very hard on Lee. It was shocking to hear that he tried to resign after he lost this battle. I thought it was very interesting that the Confederacy’s need for shoes is was what led them in to Gettysburg. I bet they never thought that the result of this stop would end up in 150,000 men fighting 51,000 men dying in the greatest battle ever fought in the northern hemisphere. The actual pictures, paintings, and simulated video used while describing these battles were really good and the helped me to gain a sense of what it was like to be there. I also enjoyed the irony in the fact that the North entered Gettysburg from the south and the South entered from the north. It was also interesting that the troops fighting over the Little Round Top were both from equal distances from Gettysburg in the opposite directions. Next, the importance of women supporting the war was examined. Women not only held down the farms and houses when the men were off at war, but many women also left their homes to care for the soldiers. In the north women started the Sanitary Commission and demanded better treatment and better food for the soldiers. This commission was made up of hundreds and thousands of women. In the south Sally Tompkins and a staff of six, nursed 1,333 wounded men. Unlike the North, the South did not have a Sanitary Commission and most men were treated in houses. In the north, Mary Ann Bickerdyke was a important female figure in the war. She traveled with the Union army for four years and sixteen battles. General Sherman stated, â€Å"She ranks me†. This statement by Sherman was extraordinary, especially for this era. It makes me happy that she received the credit that was due to her. Many women served as nurses, food gathers, and cooks, but I am exceptionally impressed with Mary Ann Bickerdyke’s story. I imagine she gave up a lot and the fact that she stayed strong during all of the gruesome battles she saw really says a lot about her character. Following the role of women in the Civil War, Burns details the forty-eight day siege of Vicksburg. During this battle the residents of Vicksburg were cut off from the world and were in desperate need of supplies. When Union had control over the well being of the Vicksburg residents, 31,000 Confederate soldiers under the command of General John C. Pemberton withdrew due to the concern of the health of the Vicksburg residents. The Union victory of this battle was significant because the Confederacy was now cut in two. I was surprised that Pemberton was a northern man fighting for the Confederacy. I would expect that soldiers would support their states. I also found it very interesting that after this siege, the fourth of July would not be celebrated in Vicksburg for eighty-one years. That is just crazy to me! Burns goes on to examine the first black regiment and the first federal draft call. In New York, a mostly Irish mob held an uprising over the draft. They were opposed to abolition because they feared blacks taking their jobs. It also made them angry that the draft favored the rich in that they could easily hire substitutes to take their place. Meanwhile, the uprising in New York was ended and the enlistment of the first blacks into the Union army had begun, this was a huge blow to the Confederacy. However, the blacks did not receive fair treatment, but they were key to the war. I am not surprised that black soldiers would fight without pay, but it was surprising that they declined it because it was not equal to the pay of the white soldiers. I like the pictures of the black soldiers. You could see by their facial expressions that their pride was different from that of the white men. In some of their pictures some of them were actually smiling unlike the pictures of white soldiers I have seen. I think it because they were truly happy to be fighting for their cause. Frederick Douglass put it best when he stated that blacks were, â€Å"the pivot upon which the whole rebellion turns, this war, disguise it as they may, is virtually nothing more or less then perpetual slavery against universal freedom and to this end the free states will have to come.† The 650 men of the all black 54th Massachusetts regiment proved to the Union that blacks were useful soldiers during the battle at Battery Wagner in South Carolina. Even though the Confederates were ahead in this battle, the battle ultimately ended in a protracted siege that was enabled by the 54th. It was because of their battle other black regiments were deemed worthy to fight. Finally, the episode ends with Lincoln’s Gettysburg Address. On November 19, 1863 Lincoln delivered one of the most memorable speeches in American history. Lincoln declared the love he had for his people and his unwavering pursuit for equality in just 269 words. I never realized that this speech was just a â€Å"side speech† at a dedication ceremony. It is almost unbelievable that Lincoln thought that this was a failed speech considering that even today most Americans know at least the first line of the Gettysburg Address. It is a shame that the photographer was not able to capture him delivering his speech, it would have been a great image to reflect upon today.

Life in the 1940s - 912 Words

1940’s When you think of the 1940’s, what comes to your mind? Maybe an image of a time where everything was boring and nothing interesting was happening. However, this is not the case. It was a time where people were on the move for a World War, and inventions were being made daily. The 40’s were a time when the United States was becoming a leader in new technologies to simplify the country’s way of life and to protect its citizens from other countries as well as the people who might think that they are better than you just because they are white. People in the United States were starting to invent gadgets to make life easier. In 1945, one of the main inventions was a computer named ENIAC (Electronic Numerical Integrator And Computer). This was a huge step for the United States, and it allowed new technology to be made that could not be before. The ENIAC was a giant computer that stood two stories tall and weighed thirty tons. 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