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Cell r Toxic:Alcohol-inducedhepatitis(rare) 80mg super levitra erectile dysfunction testosterone injections,drug-induced death is by apoptosis and results in the formation of hepatitis (methyldopa generic super levitra 80mg amex why smoking causes erectile dysfunction, isoniazid, ketoconazole, anti- Councilman bodies. Complications Clinical features Fulminant liver failure, chronic hepatitis, and cirrhosis. Patients may present with non-specific symptoms (malaise, anorexia and weight loss) or with the compli- Investigations r cations of cirrhosis such as portal hypertension (bleed- Serum bilirubin and transaminases (aspartate ing oesophageal varices, ascites, encephalopathy). Asymp- Ultrasound may be needed to exclude obstructive tomatic patients with chronic viral hepatitis may be de- jaundice, if applicable. This includes careful fluid balance, which is likely to progress rapidly to cirrhosis with adequate nutrition and anti-emetics. Where possible re- chronic inflammatory cells infiltrating the portal moval of the causative agent, e. Patients require se- to central veins or central veins to each other (bridging rial liver function tests (including clotting) to follow the necrosis). Chapter 5: Disorders of the liver 195 Inflammation of the portal tracts with spotty inflam- disease, galactosaemia, cystic fibrosis, Wilson’s disease mation in the parenchyma of the lobules, but there is and drugs. Pathophysiology Complications All the liver functions are impaired (bilirubin meta- Cirrhosis is the most common complication. There is bolism, bile salt synthesis, specialised protein synthesis, increased risk of hepatocellular carcinoma in patients detoxification of hormones, drugs and toxins). Femini- Investigations sation in males and amenorrhea in females are common Chronic hepatitis is diagnosed by a combination of per- in alcoholic liver disease and haemochromatosis due to sistently abnormal liver function tests and the findings alterations in the hypothalamic–pituitary–gonadal axis. Other investigations are aimed at diag- Reduced immune competence and increased suscepti- nosing the underlying cause and providing a prediction bility to infection also occur. Patients may present with complications such as bleed- ingfromoesophagealvaricesorencephalopathy. Patients Management withactivechronichepatitismaypresentwithfeaturesof r Symptomatic management includes adequate nutri- chronic liver disease before cirrhosis is established. Cirrhosis 2 Hands: Leuconychia (if hypoalbuminaemic), club- Definition bing,palmarerythema,Dupuytren’scontracture,hep- Cirrhosis is an irreversible change of the liver architec- atic flap (asterixis, sign of hepatic encephalopathy), ture,characterisedbynodulesofregeneratedlivercells tremor may occur in alcoholism and Wilson’s disease. The liver is usually enlarged, firm and irregular, but is shrunken Aetiology in late disease. The spleen may be enlarged due to Cirrhosis results from continued hepatocellular necro- portal hypertension. Fibrous scarring causes disruption of the normal architecture, although regen- eration of hepatocytes occurs between the fibrous tracts, Macroscopy their function, which depends on intact architecture, is The liver is often enlarged and nodular, with a bosselated impaired. The cut surface shows nodules of liver tissue, r Alcohol accounts for more than 80% of cirrhosis in separatedbyfineorcoarsefibrousstrands. Other rare but impor- Grading system 1 2 3 tant drug-induced causes are halothane, isoniazid and rifampicin. Hepatic time (seconds encephalopathy is thought to be due to failure of the over control) liver to metabolise toxins. Serum amino acid levels rise Child–Pugh grade A = score of 5–6; Child–Pugh grade B = score affectingthebalanceofcerebralneurotransmitters. Hep- of 7–9; Child–Pugh grade C = score of 10–15 atic dysfunction also results in renal failure (hepatorenal syndrome). Investigations Aimed at diagnosis of underlying cause and assessment of severity/degree of reversible liver injury. The severity Clinical features of liver disease may be graded A–C by means of a mod- Patients may have altered behaviour, euphoria or se- ified Child–Pugh grading system (see Table 5. On examination patients are jaundiced, there may be Management fetor hepaticus (sickly sweet odour on breath), flapping Treatment is largely supportive. Withdrawal from alco- tremor, slurred speech, difficulty in writing and copy- hol is essential in all patients. Malnutrition is common ing simple diagrams (constructional apraxia) and gen- and may require nutritional support. Prognosis Complications Cirrhosis is an irreversible, progressive condition which r Central nervous system: Cerebral oedema in 80% oftencontinuestoend-stageliverfailuredespitethewith- causing raised intracranial pressure. The higher the Child– r Cardiovascular system: Hypotension, arrhythmias Pugh grade, the worse the prognosis, particularly for due to hypokalaemia including cardiac arrest.

Raising “sin” taxes has a protective effect as it has been shown quantitatively that it reduces the consumption of tobacco and alcohol products (Anderson order 80mg super levitra with visa iief questionnaire erectile function, Bruijn cheap super levitra 80 mg with mastercard erectile dysfunction devices diabetes, Angus, Gordon, & Hasting, 2009). This means that fiscal instruments can, to a large extent, be used to combat youth substance abuse. The legislative laws and instruments also play a significant part in the illegal drug abuse challenge. Van der Vorst, Vermulst, Meeus, Deković, & Engels, (2009) have shown that community disorganization, poverty and high levels of unemployment are risk factors for illegal substances abuse. When a community is well organized, few economic and social problems occur, and young people are less likely to abuse illegal substances. Similarly if the 19 community is intolerant of illegal drug abuse, the likelihood of youth accessing such substances is quite low. Although empirical evidence is sketchy, it has been observed that culture can be permissive or protective of drug abuse. They migrate to urban areas to escape drudgery associated with rural life and in search of employment. But with the current prevailing economic constraints, a significant proportion of such migrants do not find work. Finally, it is not implausible to imagine that globalisation and other open market economy policies contribute indirectly to drug abuse by youth. Globalisation implies greater access to drug markets with the high circulation of people acting as a key drivers of drug trade and consumption (Spooner & Heatherington, 2005). In fact, recent United Nations reports indicate that the population of illicit drug users continues to grow globally, especially as economies rapidly urbanize. Globalisation through encouraging competition, is affecting families and causing children-parent bonding and communication to take a strain. By its very nature globalisation fosters competitive behaviour that discourages social and family cohesion. Sectors in the economy compete rigorously, with workers being forced to work long hours with less job security. Part-time, casual and outsourcing of jobs is becoming the norm, and less and less benefits are accruing to workers, forcing workers to take multiple jobs. Parents are finding it difficult to balance work and family, and more often child care obligations are compromised (Daly, 2004). Parents are spending less time with their adolescent children, leading to boredom, frustration and depression and increased substance use problems (Spooner & Heatherington, 2005) and Ramsoomar, 2015). Table 3 Risk and protective factors for substance abuse by adolescents Risk Factors Individual Family School Community Societal Exposure to public Advertising that Delinquency Parental drug use Deviant peer affiliation drunkenness promotes drug use Abundance of free, Peer Pressure Family conflict Skipping school unstructured time Neighbourhood Availability of drugs in or affirmation of substance Moral and Social Rebelliousness Poverty / Affluence around school premises use Degeneration Rejecting parental Family Context/Structure authority and cohesion Low academic aspirations Few job opportunities Sensation seeking Low Expectation Poor school performance Ease of access to drugs Impulsiveness Aggression Poor sense of well being Protective Factors Good relationship between School policy on substance Community disapproval Self confidence caregiver & child use of substance use Taxation 20 Good communication Access to positive Controlling availability High self esteem between caregiver & child Code of Conduct leisure activities and access to substances Increasing minimum Good Parental monitoring (e. Quality of Educational legal age of alcohol relationships setting rules) Experience consumption Effective policy implementation Source: Department of Basic Education (2013) Missing Evidence Although literature provides a fair understanding of the dynamics surrounding many drugs, our understanding of the determinants of Nyaope remain unexplored. As anecdotal evidence suggests that Nyaope has many causalities, further research is required to understand the incidence (by gender, race and age) and key drivers of this drug usage. Although in South Africa we know much about the negative effects of alcohol and tobacco on individuals, community and society at large, there is still a dearth on knowledge on the effects of other substance such as cannabis, heroin, cocaine, inhalants, nicotine, opioids, and many other drugs. At a theoretical level, drugs affect the individual, community, and society at large. Needless to say, all its negative effects straddle all sectors of the economy, including the health sector. This section reviews literature on the consequences of substance abuse to the individual, household/community and society at large. On the onset it has to be borne in mind that this distinction is only made to frame our analysis, in reality the lines dividing individual, community or societal effects of substance abuse are quite blurred. At the onset, it is critical to point out that literature is clear that the consequences of substance abuse differ between women and men, which implies any treatment or intervention programme has to factor in gender differences. Empirical evidence has also pointed out to a strong association between substance abuse by youth and a number of accidental injuries including traffic, drowning, poisoning, burns and falls, as well as premeditated injuries such as interpersonal violence, suicides, child abuse and sexual violence. Seedat et al, (2009) has demonstrated the link between drug misuse and homicide, abuse of children and partners, as well as rape and other violent acts. Lack of resources to sustain drug addiction has also been singled out as a major cause of many serious crimes, such as murder and robbery. A decade ago, Parry et al, 2004 and Parry et al, 2005 noted that violence was strongly related to use of illicit drugs (45%) and 40% cannabis.

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Aetiology Whilst adequate nutrition is essential the protein in- By far the most common cause in the United Kingdom take should be restricted to 0 purchase super levitra 80mg free shipping erectile dysfunction drugs causing. Causes may be divided into those tulose and phosphate enemas may be used to empty due to obstruction of blood flow cheap super levitra 80mg visa erectile dysfunction nitric oxide, and rare cases due to the bowel and minimise the absorption of nitroge- increased blood flow (see Fig. Venous blood from the gastrointestinal tract, spleen and r Complications should be anticipated and avoided pancreas (and a small amount from the skin via the pa- wherever possible. Regular monitoring of blood glu- raumbilical veins) enters the liver via the portal vein. As cose and 10% dextrose infusions are used to avoid the portal vein becomes congested, the pressure within hypoglycaemia. Other electrolyte imbalances should it rises and the veins that drain into the portal vein be- be corrected. If the portal pressure continues to rise travenous vitamin K (although this may not be effec- the flow in these vessels reverses and blood bypasses the tive due to poor synthetic liver function), fresh frozen liver through the porto-systemic anastamoses (paraum- plasma should be avoided unless active bleeding is bilical,oesophageal,rectal). Thisportosystemicshunting present or prior to invasive procedures as it can pre- eventually results in encephalopathy. H2 antagonists or proton pump inhibitors may reduce Clinical features the risk of gastrointestinal haemorrhage. Renal sup- The presenting symptoms and signs may be those of port may be necessary. Portal hypertension causes oesophageal varices, r Liver support using cellular and non-cellular systems splenomegaly, distended paraumbilical veins (caput areunderdevelopment;however,livertransplantation medusa), ascites and encephalopathy. Complications Prognosis Oesophageal varices can cause acute, massive gastroin- Outcome is dependent on the degree of encephalopa- testinal bleeding in approximately 40% of patients with thy. Anorectalvaricesarecommon,butrarelycause 198 Chapter 5: Hepatic, biliary and pancreatic systems Causes of portal hypertension Obstructed blood flow Increased blood flow (rare) Prehepatic Hepatic Posthepatic (portal vein) (liver sinusoids) (hepatic veins) Hepatitis Budd–Chiari syndrome Cirrhosis Constrictive pericarditis Schistosomiasis Extrinsic Wall Intrinsic Arteriovenous fistula Hypersplenism Pancreatic Congenital disease Portal vein atresia of the Biliary tract thrombosis portal vein tumours Figure 5. Surgical shunting may exacerbate por- 1 β-blockers, in particular propranolol, cause splanch- tosystemic encephalopathy. This reduces the portal pressure gradient, the azygos blood Investigations flow and variceal pressure, which reduces the likeli- These are aimed at discovering the cause of the por- hood of variceal bleeding. The in patients with significant varices who are unable to severity of liver disease may be graded A–C by means tolerate β-blockers. Ultrasound of the liver and spleen is performed traindicated isosorbide mononitrate has been shown to assess size and appearance. Liver biopsy may be re- ascites (see page 188), bleeding varices (see page 199) quired. There are various r Portal hypertension is significantly improved by ab- techniques, for example connecting the: stinence from alcohol in cases of alcohol-induced dis- 1 Portal vein to inferior vena cava. A transjugu- lar approach is used to pass a guidewire through the Management hepatic vein piercing the wall to the intrahepatic Resuscitation: branches of the portal vein, a stent is then passed r At least two large bore peripheral cannulae should over the guidewire. Packed red blood cells the same as for other shunts, but operative morbid- should be given as soon as possible, O −ve blood may ity and mortality is improved. Oesophageal varices are dilated vessels at the junction r Elective intubation may be required in severe uncon- between the oesophagus and the stomach and occur in trolled variceal bleeding, severe encephalopathy, in portal hypertension. They may rupture and cause an patients unable to maintain oxygen saturation above acute and severe upper gastrointestinal bleed. Incidence/prevalence Further management: 30–50% of patients with portal hypertension will bleed r An upper gastrointestinal endoscopy should be per- from varices. Aetiology If banding is not possible, the varices should be in- Varicesresult from portal hypertension, the most com- jected with a sclerosant. Factorspredictingbleed- r If endoscopy is unavailable, vasoconstrictors, such as ing in varices include pressure within the varix, variceal octreotide or glypressin, or a Sengstaken tube may be size and severity of the underlying liver disease. Signs of r Infection may occur following a variceal haemorrhage chronic liver disease may be present (jaundice, pallor in cirrhotic patients resulting in significant morbidity spider naevi, liver palms, opaque nails, clubbing). All patients should receive a course of features of portal hypertension may be seen. Secondary prophylaxis following a variceal bleed in cir- Investigations rhosis: The diagnostic investigation is endoscopy, which may r Following control of active bleeding the varices also be therapeutic during an acute bleed. The varices should be eradicated using endoscopic band liga- must be confirmed to be the source of bleeding, because tion (sclerotherapy if banding unavailable).

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Recognizing the presence or absence of conflict of interest in these commentaries is of utmost importance discount super levitra 80mg without prescription impotence cures. These are for patients who are at low risk of having a myocardial infarction and for whom a stay of 48 hours in an intensive care unit is very expensive and probably unnecessary buy 80mg super levitra overnight delivery erectile dysfunction treatment in kl. They have done cost-effectiveness analyses that show only a slight overall increase in costs under the assumptions of the current admission rate of these patients to the hospital. Clearly there must be a search for some other method of dealing with these patients, which will be cost-effective and result in decreased hospital-bed utilization. John Milton (1608–1674): Paradise Lost Learning objectives In this chapter you will learn: r how to describe various outcome measures such as survival and prognosis of illness r the ways outcomes may be compared r the steps in reviewing an article which measures survival or prognosis One of the most important pieces of information that patients want is to know what is going to happen to them during their illness. The clinician must be able to provide information about prognosis to the patient in all medical encounters. Patients want to know the details of the outcomes they can expect from their dis- ease and treatment. Evaluation of the clinical research literature on prognosis is a required skill for the health-care provider of the future. Outcome analysis looks at the interplay of three factors: the patient, the intervention, and the outcome. We want to know how long a patient with the given illness will survive if given one of two possible treatments. The patient: the inception cohort To start an outcome study, an appropriate inception cohort must be assembled. This means a group of patients for whom the disease is identified at a uniform 359 360 Essential Evidence-Based Medicine point in the course of the disease, called the inception. This can occur at the appearance of the first unambiguous sign or symptom of a disease or at the first application of testing or therapy. However, it should be at a stage where most reasonably prudent providers can make the diagnosis and not sooner as most providers won’t be able to make the diagnosis and initiate therapy at that earlier stage of disease. Collec- tion of the cohort after the occurrence of the outcome event and looking back- ward will distort the results either in a positive or negative way if some patients with the disease die before diagnosis or commonly have spontaneous remis- sions soon after diagnosis. A study of survival of patients with acute myocardial infarction who are studied from the time they arrive in the coronary care unit will miss those who die suddenly either before seeking care or in the emergency department. Incidence/prevalence bias can be a fatal flaw in the study if the inception cohort is assembled at different stages of illness. There may be very different prognoses for patients at these various stages of the illness. Lead-time and length-time bias occurring as the result of screening programs should be avoided by proper randomization. Diagnostic criteria, disease severity, referral pattern, comorbidity, and demo- graphic details for inclusion of patients into the study must be specified. Patients referred from a primary-care center may be different than those referred from a specialty or tertiary-care center. Termed referral filter bias, this is due to an over- representation of patients with later stages of disease or more complex illness who are more likely to have poor results. Centripetal bias is another name for cases referred to tertiary-care centers because of the need for special expertise. Popularity bias occurs when the more challenging and interesting cases only are referred to the experts in the tertiary care center. The results of these biases limit external validity in other settings where most patients will present with earlier or milder disease. All members of the inception cohort should be accounted for at the end of the study and their outcomes known. This is much more important in these types of studies as we really want to know all of the possible outcomes of the illness. These include recovery, death, refusal of therapy due to the disease, side effects of therapy, loss of interest, or moving away.

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