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Incidence 1 The first priority is resuscitation – stabilise airway fildena 150mg without a prescription, Common discount fildena 25 mg free shipping;basedonhospitalattendancesandadmissions breathing and circulation and check the glucose level the incidence is ∼250 per 100 discount fildena 50mg amex,000 population buy 150mg fildena. Hypoxia, hypoglycaemia or hypotension are reversible causes of coma and will exacerbate any Age other cause. Chapter 7: Disorders of conciousness and memory 313 r Penetrating trauma: Penetration of the skull by an ex- swelling of the brain. Pathophysiology The pathology of head injury can be divided into two groups: Complications r Primary brain damage: Short term: Vascular, e. Subarachnoid and intracerebral ticularly on the side of the trauma (coup lesion) and haemorrhage may also occur. Long term: ii Diffuse axonal injury due to shearing forces caus- r Posttraumatic epilepsy. Patients r Chronic traumatic encephalopathy (the punch drunk who survive such injury may have severe brain syndrome seen in professional boxers). Ifneckinjuryissuspected,thepatientshould cal treatment, whereas primary brain damage occurs be immobilised until a spinal cord injury or unstable at the time of injury and therefore can only be in- cervical spine has been excluded. Followingtrauma,thebrainismuch Coma Scale, and full neurological and general exami- more susceptible to hypoxia and hypotension due to nation. The decision to admit for observation is based disruption of autoregulation and impaired vascular on the history and assessment at presentation. Osmotic diuretics such as mannitol Clinical features may also be used to reduce brain oedema. In more severe injuries, there is persistent post- mission to intensive care for intracerebral pressure traumatic amnesia. Patients All patients require close monitoring to check for devel- may have other injuries depending on the nature of the opment of complications that require urgent treatment. Over a period of several hours there is oozing of r the patient is difficult to assess, e. Apathy and/or depression are common, there may be Prognosis disturbances of sleep, confusion of day & night, with Recovery may take weeks to months. Other neurological signs with a persisting disability or impairment is 100 such as hemiparesis, seizures tend to occur very late in per 100,000. Generally, in the early stages, the patient is aware of a loss of their memory and may become very frus- Dementia trated and anxious. They lose the ability to function in daily life grad- Definition ually, and in later stages they become more apathetic, Asyndromeofacquiredcognitiveimpairment,withpro- with little spontaneous effort and therefore require full gressive global loss of cognitive function in the context personal care such as feeding, washing, dressing and of normal arousal. Acollateral history from a relative or close carer who Incidence has known the patient for a long time is essential. The 1% of those aged 65–74 years, 10% of those over 75 and carer is often the one most emotionally affected by the 25% of those over 85 years. Aetiology There are numerous causes of dementia, including Investigations r Alzheimer’s disease (most common >60%). These are to exclude any treatable causes of chronic con- r multi-infarct dementia caused by multiple small in- fusion. Management The specific management strategies are covered under Clinical features specific causes but general treatment includes the fol- See also under specific causes of dementia. Patients may lowing: have impairment of the following cognitive functions: r Multidisciplinary assessment. Chapter 7: Disorders of conciousness and memory 315 r Antidepressantsmayimprovefunctionallevelinthose r Neurochemical analysis reveals that patients with with low mood. The features are those of dementia, but with an insidious onset and progressive decline in memory and at least one of: Alzheimer’s disease r Dysphasia: Loss in language skills, especially with Definition names and understanding speech. Most common neurodegenerative disorder and cause of r Agnosia: Loss of ability to recognise objects, people, dementia. The onset can be in middle age, but the incidence rises r Disturbance in executive functioning (higher mental with age.

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These were both abbreviated versions of the texts: Conditions of Women  omit- ted the contraceptives and the following paragraph on the development of the fetus (¶¶–) discount fildena 25 mg with mastercard; Women’s Cosmetics  abbreviated the text throughout fildena 50mg online, mostly by omission of the detailed instructions for preparations buy cheap fildena 100 mg on-line. The Trotula ensemble proper was probably first created in the late twelfth century order fildena 100 mg without a prescription, for we find manuscripts of it from the turn of the thirteenth cen- tury. The compiler of this proto-ensemble, whoever he or she was, combined the already-paired Conditions of Women  and Women’s Cosmetics  with a copy of Treatments for Women . Although this editor made no major revisions of the texts, s/he did introduce several substantive additions and rearrangements that transformed the ensemble into something more than a simple linking of the three original Salernitan texts. This compiler first compared Conditions of Women  with a copy of Conditions of Women  in order to check certain read- ings and fill in lacunae, particularly the deleted contraceptive section. First was ¶, which describes the month-by-month development of the fetus; this was excerpted from an embryological work attributed to the late-fourth-century North African writer Vindician. Paragraphs –, on the care of the new- born and choice of a wet nurse, were drawn out of The Book for al-Mansur (Liber ad Almansorem), a large medical compendium by the Persian physician Abū Bakr Muḥammad ibn Zakarīyā’ ar-Rāzī (d. The Book for al-Mansur had only re- cently been translated from Arabic into Latin in Spain, and its use by the Tro- tula compiler is one of the first witnesses to its circulation. The last three sections of the expanded Conditions of Women, ¶¶– on male and female infertility, were drawn from the work of the Salernitan writer Co- pho. Though theydid not contradict the other material in Conditions of Women, these new chapters slightly shifted the emphasis of the original, from the dis- eases of women (women’s sufferings being the chief concern) to procreation (the successful production and rearing of children). With Treatments for Women, the compiler of the proto-ensemble excised chapters on hair and skin care and placed them instead within the third, cos- metic section of the newly constructed text (in the present edition, ¶¶, , –, –, –, –, and ). The surviving manuscripts show Introduction  that the proto-ensemble was left incomplete: the compiler never finished what was apparently a planned integration of all the cosmetic chapters from Treat- ments for Women with those of Women’s Cosmetics. Perhaps the most important feature of this first version of the ensemble is that it was here that ‘‘Trotula’’ first came into being. Tro(c)ta, as I have already noted, was a popular woman’s name in late-eleventh- and twelfth- century southern Italy; ‘‘Trotula’’ (which literally means ‘‘little Trota’’) has thus far been documented only twice, and in one case it is clearly used as a child’s name. Both Conditions of Women and Women’s Cosmetics,aswe have seen,were anonymous,while Treatments forWomen was regularlyascribed to Trota. The compilerof the proto-ensemble probably thus had only the name of Trota to associate with the three works. Thus we find early forms of the ensemble with the title ‘‘The Trotula of Women’’ (Trotula mulierum) or ‘‘The Book Which Is Called the Trotula’’ (Liber qui dici- tur Trotula or Summa que dicitur Trotula). Already by the early thirteenth cen- tury, however, the title ‘‘Trotula’’ was misunderstood as the author’s name— an author who, moreover, was responsible not just for one text but for the whole ensemble. From this point on, even though many scribes continued to differentiate between the Trotula major (i. The internal reference to Trota in ¶ was also changed to ‘‘Trotula,’’ very few scribes or readers bothering to puzzle through why the work’s author should describe one of her own successful cures in a distant third person rather than with the proud ‘‘I’’ of the first person. In the ‘‘transitional’’ ensemble, an editor went back to Women’s Cosmetics  and incorporated it in full (together with his/her own substantive revisions), thus finally completing the third section of the ensemble. This editoralso inserted some new material, such as two cosmetic practices that the early-thirteenth-century author Bernard of Provence had attributed to the Salernitan women. This, then, is the magnet effect of the Trotula, attracting all manner of miscellaneous recipes on women’s medicine. Some time before the middle of the thirteenth century, yet another form of the ensemble emerged. Using copies of both the transitional and the inter- mediate ensembles as a base, the editor of this ‘‘revised ensemble’’ went back to manuscripts of the three original independent treatises in order to establish a purer form of the texts. In Conditions of Women, for example, the editor noticed that a group of recipes (here ¶¶–) had been omitted from the section on aids for difficult birth. The editor of the revised ensemble copied the abbrevi- ated section as s/he found it, then added the missing recipes from Conditions of Women . In the opening sentence (¶), for example, s/he clarified that the subsequent test was for differentiating ‘‘hot’’ women from ‘‘cold’’ in order that they might be properly aided in conception. The editor of the revised ensemble also suppressed several recipes, such as the treatments for impetigo (a skin condition), worms in infants, and snake- bite in Treatments for Women, as well as many of the cosmetics and obstetrical chapters that had closed Women’s Cosmetics in the intermediate ensemble (in- cluding the chapter on sexual hygiene discussed above).

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The group randomized to radical prostatectomy surgery or complete removal of the prostate gland fildena 25mg visa, did much better than the group randomized to either radiation therapy or watchful waiting with no treatment fildena 25mg amex. Some patients who were initially randomized to the surgery arm of the trial were switched to the radiation or watchful waiting arm of the trial when generic fildena 50mg free shipping, during the surgery generic fildena 100mg amex, it was discovered that they had advanced and inoperable disease. These patients should have been kept in their original surgery group even though their cancerous prostates were not removed. When the study was re-analyzed using an intention-to-treat analysis, the survival in all three groups was identical. Removing those patients biased the original study results since patients with similarly advanced cancer spread were not removed from the other two groups. Remov- ing patients after randomization for reasons associated with the outcome is patently biased and grounds to invalidate the study. Leaving them in the analysis as an intention-to-treat is honest and will not inflate the results. However, if the outcomes of patients who left the study are not known, a best case/worst case scenario should be applied and clearly described so that the reader can deter- mine the range of effects applicable to the therapy. In the best case/worst case analysis, the results are re-analyzed considering that all patients who dropped out or crossed over had the best outcome possible or worst outcome possible. This should be done by adding the drop-outs of the intervention group to the successful patients in the intervention group and at the same time subtracting the drop-outs of the comparison group from the success- ful patients in that group. The opposite process, subtracting drop out patients from the intervention group and adding them to the comparison group, should then be done. If this range is very large, we say that the results are sensitive to small changes that Randomized clinical trials 173 could result from drop-outs or crossovers. If the range is very small, we call the results robust, as they are not likely to change drastically because of drop-outs or crossovers. Lack of compliance may influence outcomes since the reason for non-compliance may be directly related to the intervention. Other clinically important outcomes that should be measured include adverse effects, direct and indirect costs, invasiveness, and monitoring of an intervention. A blinded and independent observer should measure these outcomes, since if the outcome is not objectively measured, it may limit the usefulness of the therapy. Remember, no adverse effects among n patients could signify as many as 3/n adverse events in actual practice. Results should be interpreted using the techniques discussed in the sections on statistical significance (Chapters 9–12). Discussion and conclusions The discussion and conclusions should be based upon the study data and lim- ited to settings and subjects with characteristics similar to the study setting and subjects. Good studies will also list weaknesses of the current research and offer directions for future research in the discussion section. Also, the author should compare the current study to other studies done on the same intervention or with the same disease. In summary, no study is perfect, all studies have flaws, but not all flaws are fatal. After evaluating a study using the standardized format presented in this chapter, the reader must decide if the merits of a study outweigh the flaws before accepting the conclusions as valid. Dimensions of methodological quality associated with estimates of treatment effects in controlled trials. An example of this phenomenon can be seen in the systematic review of studies of acupuncture for back pain that was described earlier. L’Abbep´ lotsare a graphic technique for presenting the results of many indi- vidual clinical trials. It is a way of looking for the presence of bias in the studies done on a single question. The plot shows the propor- tion of patients in each study who improved taking the control therapy against the proportion who improved taking the active treatment. Each study is repre- sented by one point and the size of the circle around that point is proportional to the sample size of the study. The studies closest to the diagonal show the least effect of therapy, and farther from the diagonal show a greater effect.

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Cholecystectomy is also considered in The functions of the liver are carried out by the hepa- younger patients with asymptomatic gallstones in or- tocytes generic fildena 50mg on-line, which have a special architectural arrangement buy 25 mg fildena visa. Blood enters the liver through the portal tracts buy 100mg fildena with mastercard, which Carcinoma of the gallbladder is treated by wider resec- contain the triad of hepatic artery 25 mg fildena with visa, portal vein and bile tion, including neighbouring segments of the liver and duct. The lobule is classically used to Open cholecystectomy is usually performed through describe the histology of the liver (see Fig. Cholangiography may be used to The hepatocytes in zone 1 of the acinus receive well- visualise the duct system. The gallbladder is removed oxygenated blood from the portal triads, whereas the with ligation and division of the cystic duct and artery. The liver has multiple functions, which may be im- Aetiology paired or disrupted by liver disease: The causes of acute hepatitis: r Carbohydrate metabolism: The liver is one of the ma- r Acute viral hepatitis may be caused by the hepa- jor organs in glucose homeostasis under the control totrophic viruses (A, B and E) or other viruses such as of pancreatic insulin. Excess glucose following a meal Epstein–Barr virus, cytomegalovirus and yellow fever is converted to glycogen and stored within the liver. The liver is also involved in the breakdown of amino acids producing ammonia, which is converted Pathophysiology to urea and excreted by the kidneys. Cellular damage results in impairment of normal liver r Fat: The liver is involved in synthesis of lipoproteins function: bilirubin is not excreted properly resulting in (lipid protein complexes), triglycerides and choles- jaundice and conjugated bilirubin in the urine, which terol. Swelling of the liver results in stretching of the liver capsule which may result in pain. Patterns of liver disease Clinical features The features of acute liver damage are malaise, jaundice, Acute hepatitis anorexia, nausea, right upper quadrant pain and in se- Definition vere cases, evidence of liver failure. However,itissometimesdiagnosed may be an enlarged, tender liver, pale stools and dark earlier than this. Stigmata of chronic liver disease should be looked for to exclude acute on chronic liver disease. Aetiology The main causes of chronic hepatitis: Microscopy r Viral hepatitis: Hepatitis B virus (+/− hepatitis D), Acute viral hepatitis has a histological appearance which hepatitis C virus. Cell r Toxic:Alcohol-inducedhepatitis(rare),drug-induced death is by apoptosis and results in the formation of hepatitis (methyldopa, 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.

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