Traumatic bowel perforation with symptoms lasting at least 12 hours before operation erectile dysfunction ring 130mg malegra dxt with visa. No more than 1 dose of an antibiotic (single broad-spectrum agent or 1 dose of each antibiotic in a combination regimen such as metronidazole erectile dysfunction treatment vitamins cheap malegra dxt 130 mg online, ampicillin impotence emedicine discount malegra dxt 130mg without a prescription,gentamicin) after the baseline intra-abdominal culture was obtained from the infected site erectile dysfunction diabetes malegra dxt 130 mg sale. Subjects suspected preoperatively to have had a diagnosis of spontaneous bacterial peritonitis erectile dysfunction and age purchase 130mg malegra dxt with mastercard, simple cholecystitis erectile dysfunction doctor el paso order malegra dxt in united states online, gangrenous cholecystitis without rupture erectile dysfunction at age 20 130mg malegra dxt otc, simple appendicitis erectile dysfunction drugs generic generic 130mg malegra dxt visa, acute suppurative cholangitis, pancreatic abscess, or infected necrotizing pancreatitis. Subjects with neutrophil counts as low as 500/mm3 were permitted if the investigator thought the reduction was due to the acute infectious process. Intra-abdominal infection known to be caused by 1 or more bacterial pathogens not susceptible to both of the study drugs. Subjects were randomly assigned (1:1) to receive either tigecycline (an initial 100-mg dose, followed by 50 mg twice a day) or imipenem/cilastatin (200 to 500 mg, dose based on body weight and calculated creatinine clearance) every 6 hours via intravenous administration for up to 14 days. Infection type, etiology of disease, and comorbid conditions were comparable between treatment groups in each study. In study 301, 39% of subjects were white and 61% were of other ethnic origin (primarily Hispanic). Approximately 8% (safety population, pooled data of studies 301 and 306) of subjects were older than 75 years. As the number of patients in the strata > 15 is small, the overall, unadjusted difference has been highlighted in the following figures. When adjusted for type of infection, the difference in eradication rates between the 2 treatment groups was 0. When adjusted for type of infection, the difference in eradication rates between the 2 treatment groups was -1. Isolate Response Tigecycline Imipenem/cilastatin n/N % n/N % Bacteroides fragilis Eradication 68/87 78. No isolates demonstrated the development of decreased susceptibility to tigecycline in study 301. In study 306, 2 subjects in the study were identified with isolates deemed to have developed indeterminate or resistant susceptibility to tigecycline, as defined by the per-protocol provisional breakpoints. Subgroup analysis In the analysis of clinical response by clinical diagnosis, the highest rates of clinical cure were achieved in complicated cholecistytis and gastric and duodenal perforation. In general, these analyses can be considered consistent with the main analysis of clinical response although they should be interpreted with caution due to limited size of patient groups. Both phase 3 studies were multicenter, multinational, double blind (third-party unblinded) in which 1129 patients (approximately 500 patients per trial) were randomised to receive either tigecycline (an initial dose of 100 mg followed by 50 mg every 12 hours, iv) or vancomycin/aztreonam (1 gram of vancomycin iv followed by 2 g of aztreonam iv administered every 12 hours) for up to 14 days. Infected ulcers that had developed signs of erythema, swelling, tenderness, pus, or warmth. In study 300 subjects with burns up to 25% of body surface area (nonfull-skin thickness) could be enrolled at selected study centers. Deep or extensive cellulitis, either associated with an underlying disease state or greater than 10 cm in width or length. Subjects who had not received more than 2 doses of any nonstudy antibacterial drug after the original culture of the infected site had been obtained, except for subjects who were considered prior antibiotic failures. For subjects who were considered therapeutic failures for prior antibiotic therapy with another agent at entry, a Gram stain or baseline culture of the infected site showing a potential pathogen was obtained before the first dose of study drug was administered. Once a subject began treatment with study drug, no other concomitant antibiotics could be given. Infected diabetic foot ulcers or decubitus ulcers where the infection was present for longer than 1 week or chronically infected ulcers in subjects who could not be compliant with measures necessary for chronic wound healing. An uncomplicated skin and/or skin structure infection (eg, simple abscesses, folliculitis, impetiginous lesions, furunculosis, superficial cellulitis). Subjects with acute hepatic failure or acute decompensation of chronic hepatic failure. This is justified based on vancomycin broad activity against aerobic gram-positive pathogen whereas aztreonam provides broad activity against gram-negative pathogens, including some strains of P. The use of vancomycin for treating infections caused by gram-positive cocci susceptible to methicillin is questionable. Consequently, whether the use of a beta-lactam would have rendered similar or different results if compared with tigecycline remains unknown. Results Demographic and baseline disease characteristics were similar between the treatment groups in each study, excepting differences in ethnic origin. In study 300, 53% of subjects were white and 38% were of other ethnic origin (primarily Hispanic). Approximately 7% of subjects were 75 years or older (safety population, pooled data of studies 300 and 305). About half of all infections were diagnosed as deep soft tissue infections involving cellulitis covering more than 10 cm in area (where anatomically applicable). Limited numbers of patients with co-morbid factors such as diabetes mellitus (20%), peripheral vascular disease (7%) and with bacteraemia (3%) were enrolled. Consequently, the limited data on relevant subpopulations (patients with diabetic foot infection, with decubitus ulcer infection, patients with wound infection and patients with bacteraemia) and severely ill patients is stated in section 4. Microbiological response the number (%) of subjects who were microbiologically evaluable for analysis is fairly low (study 300: 39% vs. No isolates demonstrated the development of decreased susceptibility to tigecycline during these studies. As a consequence it is difficult to draw adequate conclusions based on these results. Efficacy evaluations were performed at the end of treatment and at 12 to 37 days after the last dose of study drug for the Test-of-Cure assessment, unless the subject was deemed a clinical failure. Any subject who received at least 1 dose of study drug was included in the evaluation for safety. In subjects with complicated skin and soft tissue infections, tigecycline cured 83. The mean duration of therapy was 7 to 8 days for both the total tigecycline and comparator groups. The age distribution was similar between the 2 treatment groups, with an overall mean age of 47 years. Approximately 19% of subjects were age 65 or older; about 8% were aged 75 years or older. About 65% of the subjects were white, 7% black, and the remainder Asian and others. The demographic and baseline characteristics were similar for the tigecycline and comparator subjects (p > 0. The adverse events most commonly reported in patients on tigecycline in phase 3 clinical trials were nausea (33. The Applicant was requested to further elaborate on the cause of the gastrointestinal adverse effects, in particular to discuss to which extent gastrointestinal symptoms may be due to vestibular toxicity. No conclusions can be made about the use of prophylactic antiemetic therapy because of the small number of patients who received prophylactic antiemetic medications before tigecycline administration. Clostridium difficile-associated diarrhoea and colitis caused by overgrowth of toxin-producing clostridia, have rarely been reported with the administration of oral or parenteral tetracyclines. No cases of pseudomembranous colitis were reported in patients on tigecycline in phase 3 clinical trials but one case of Clostridium difficile-associated diarrhoea, considered as serious, was reported in a phase 2 clinical trial. Hypersensitivity reactions have rarely been reported with tetracyclines and include a wide variety of symptoms. This fact may be complicated by the known histamine-release potential of tetracyclines. These allergic reactions characterized as rash and/or pruritus and/or generalized redness. Additionally, the timing of the event (6th day of therapy) complicates causality assessment. According to clinical evaluation, possible histamine release does not appear likely to be a clinical safety concern when the drug is infused slowly. Hypersensitivity to tetracycline class of antibiotics is considered a contraindication for tigecycline (section 4. Photosensitivity, manifested as an exaggerated sunburn reaction on sun-exposed areas of the body, has been described with tetracyclines. These reactions, if they occur, develop at any time from within a few minutes up to several hours after exposure to sun and usually persist 1 or 2 days after discontinuance of tetracyclines. No cases of photosensitivity or phototoxicity were reported in phase 3 clinical trials with tigecycline. As most patients included in these clinical trials are likely to be treated in hospital it is unlikely that patients were exposed to the sun. Therefore, at present, photosensitivity cannot be ruled out in patients receiving tigecycline. Significantly more tigecycline-treated subjects (14, 1%) than comparator-treated subjects (3, 0. One hundred and eleven (111) patients died during phase 3 trials, 67 in tigecycline group and 44 in comparators group. Although the percentage of death was not statistically different between treatment groups more patients treated with tigecycline died in all indications. A total of 21 patients (14 in the tigecycline group and 7 in the comparator group) died because of worsening of the infection. Of these patients, 12 had sepsis (8 tigecycline and 4 comparator), 5 had pneumonia (all tigecycline-treated), and 3 had both sepsis and pneumonia (all in tigecycline). Resistance of the baseline isolates do not contribute to these deaths as for the exception of two P. As a consequence, there remains a concern of lack of efficacy in severely ill patients with fulminant and rapid disease. Since glycycyclines are structurally similar to tetracyclines, certain adverse reactions such as pancreatitis may be causally associated with tigecycline. There were 3 cases of pancreatitis reported in the tigecycline-treated subjects versus 3 cases of pancreatitis in the comparator-treated subjects (see also Post-Marketing experience below). Of note, increased amylase was reported in a significantly greater number of tigecycline-treated subjects (38; 2. Hepatotoxicity, a known adverse event reported with tetracyclines, was specifically assessed in tigecycline clinical trials. It is known that certain tetracyclines diminish prothrombin activity and that could imply an increase in bleeding risk in patients. These findings, frequently reported with tetracycline class antibiotics, are not usually of clinical importance in patients with normal renal function but further deterioration of renal function has been observed when some tetracyclines are administered to patients with impaired renal function. In animal studies it has been shown, that there is bone-marrow toxicity as class-effect of tetracyclines. Bone marrow suppression was not identified as a safety concern during the clinical trials conducted with tigecycline. At high, suprapharmacological doses, tigecycline would be expected to induce some levelof immunocompetence in animals based on the observation of lymphoid depletion/atrophy of lymph nodes, spleen, and thymus in high-dose animal studies. These findings do not suggest that subjects treated with tigecycline are at any increased risk for cardiovascular events compared to comparator-treated subjects. No bleeding was associated with this increase and none required treatment/intervention. Both in the tigecycline group and comparator group other events and failure/refusal to return for a follow- up visit were the most common reasons for withdrawal. There was no significant difference between the treatment groups for the primary reasons for withdrawal (pfi0. Post marketing experience At the time of initial submission of the dossier, tigecycline was not marketed in any country. Three cases of acute pancreatitis have been reported in the post-marketing setting and considered to be tigecycline-related. The company must ensure that this system is in place and functioning before the product is placed on the market. The Safety Specification covers all the issues that are considered relevant for the use of tigecycline in clinical practice. There are no unresolved quality issues with a negative impact on the Benefit Risk balance of the product Non-clinical pharmacology and toxicology Efficacy Overall, it can be concluded that the efficacy of tigecycline in the claimed indications has been established. In complicated skin and soft tissue infections the comparator group was vancomycin/aztreonam. Currently, the empirical use of vancomycin against gram-positive infections is driven by the knowledge of local prevalence patterns and/or for the presence of certain risk factors. In addition limited numbers of patients with co-morbid factors such as diabetes mellitus (20%), peripheral vascular disease (7%) and with bacteraemia (3%) were enrolled. Patients with severe underlying disease, such as immunocompromised, patients with decubitus ulcer infection or patients that had infections requiring longer than 14 days of treatment. Consequently, the limited data on relevant subpopulations (patients with diagnoses other than cellulites, patients with bacteraemia) and severely ill patients is stated in section 4. Safety the Safety Specification covers most of the issues that are considered relevant for the use of tigecycline in clinical practice. Within the Pharmacovigilance Plan most of the activities planned are routine pharmacovigilance practices. An appropriate risk management plan for identified risks associated with the use of tigecycline has been agreed upon. Risk-benefit assessment the benefits of tigecycline has been sufficiently demonstrated in complicated skin and soft tissue infections and in complicated intra-abdominal infections. Also, concerns on whether the patients enrolled in such trials are representative of the target population in terms of the possible clinical diagnoses were raised. No additional risk minimisation activities were required beyond those included in the product information with the exception of a specific surveillance study for the European Union aimed at monitoring emerging resistance. Necrotizing fasciitis: a fourteen-year retrospective study of 163 consecutive patients. Diabetes present in 18- 60% >50% cases in healthy individuals 1Bellapianta, Joseph M. Necrotizing Soft Tissue Infections- Bacteriology Streptococcal Group A strep (Strep. Short incubation period Necrotizing Soft Tissue Infections- Bacteriology Clostridial species a. Streptococcal toxic shock syndrome presenting as septic knee arthritis in a 5-year-old child. Successful treatment of severe streptococcal toxic shock syndrome with a combination of intravenous immunoglobulin, dexamethasone and antibiotics. Toxic shock syndrome following thoracic surgery for lung cancer: report of a case. Misiakos, 3rd signs and symptoms of severe septic shock and multiple organ dysfunction. The clinical Department of Surgery, Attikon condition is the most important clue for diagnosis. Developing in the lower or upper extremities, a mortality rate of approximately 46% (6). In 1924, Meleney reported an majority of cases present anaerobic bacteria that proliferate in a association with beta-hemolytic streptococcus A in a study of a hypoxic environment and produce gas, which accumulates in the series of hospitalized cases in Beijing. The late 1980s witnessed a fatal, given its association with more extensive surgery, higher renewed interest in this pathology. It is seen to have a predilection serum creatinine, along with elevated blood urea, is also strongly for men, with a male-to-female ratio of 3:1; this ratio is mainly associated with higher mortality rates (22). However, its range in the litera- are significant parameters for an unfavorable outcome, particu- ture is extensive, varying from 8. The majority population-basedstudieshaveshownthatadvancedageisastrong, of patients have a history of minor or major traumas, gener- independent predictor of mortality (26). Other studies have hernia, perforated diverticulitis, necrotic cholecystitis, gastroduo- concurred that advanced age is a risk factor for higher mortality, denal perforation, small bowel perforation, and obstructive colon but only when accompanied by other risk factors such as renal cancer with perforation rank among the most frequent causes failure, or delayed surgical debridement (24). Such cases present a high risk of with regard to mortality is also a topic of debate. Other causes include a possible the extension and variability of infection are assumed to urethral stricture and a trauma from an indwelling Foley catheter. Other common Infection begins in the hypodermis or the superficial fascia, as the co-morbidities include liver cirrhosis, chronic heart failure, obe- more superficial layers (dermis and epidermis) are not affected at sity,alcoholabuse,immunodeficiency,systemiclupus erythemato- the beginning (34). Invasive bacteria cause thrombosis of the nutrient vessels, is a marine bacterium frequently isolated in Asia (21).
Syndromes
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How quickly you recover
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Drug abuse
Stool examination for cause of diarrhea and electrolyte levels
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In addition erectile dysfunction zoloft purchase discount malegra dxt online, we propose that neuropsychology is a paradigm of how to explain and research behavior what causes erectile dysfunction yahoo cheap malegra dxt 130mg with visa, not just a body of knowledge erectile dysfunction age young 130mg malegra dxt fast delivery. Neuropsychology is also not a separate area of re- search to be pursued in isolation from other models of psychology erectile dysfunction protocol guide cheap 130mg malegra dxt with amex. It is distinct from physiology erectile dysfunction doctor sydney cheap malegra dxt 130mg overnight delivery, however erectile dysfunction oil purchase malegra dxt online pills, because its direct concern is not with synapses but with behavior erectile dysfunction age 21 discount 130mg malegra dxt mastercard. We still know relatively little about the 3-pound organ that defines us impotent rage definition malegra dxt 130mg fast delivery, but many significant advances in recent years have brought the field to a new threshold of knowledge that has allowed researchers to identify many of the anatomic areas and functional systems within the brain that help determine behavior. Critical Thinking Questions How does localization brain theory differ from equipotentiality brain theoryfi This site includes information on doctoral programs in neuropsychology, annual meetings, member- ship information, and more. Overview the primary constraint in unlocking the secrets of the brain has been the limit of available techniques and examination procedures for investigating the brain. This was certainly true for early scientists, who struggled with how inaccessible the living brain is to direct visualization. Short of performing in vivo neurosurgical procedures or postmortem examinations immediately after death, early scientists simply could not examine the living brain. As a result, study of the brain was largely speculative and inferential, and researchers have made many errors (see Chapter 1). Because of such difficulties, many famous psychologists, including William James and B. Since the 1970s, an explosion in technology has allowed more precise examination of the brain. During the end of the nineteenth century, researchers developed staining techniques by which they could visualize neurons. In the early part of the twentieth century, X-ray technology and pneumoencephalography allowed scientists to visualize the skull and the ventricles. These two procedures, although crude in their initial stages of devel- opment, were soon refined so that visualizing specific and detailed brain structures became possible, in- cluding visualizing asymmetries in the living brain. More recently, the structural imaging of brain anatomy has been correlated with functional parameters of the brain, which created a new direction in brain research, namely, that of functional imaging. These recent advances in neuroimaging dramatically changed how scientists investigate neural corre- lates of human behavior. These spectacular new developments are akin to changing filters in a camera, resulting in new and different images of the same picture. This chapter summarizes the major technologic methods of examining the brain, and Chapter 3 exam- ines neuropsychological techniques of studying the brain. This chapter provides the neuropsychology student with background on the various investiga- tional procedures he or she will likely encounter in the literature, research laboratory, or in clinical practice. Neuropsychologists should familiarize themselves with the basic information these techniques can provide. In fact, neuropsychologists play an important role in advancing this technology and are working side by side with radiologists and neurologists to unlock the secrets of the brain. For neuroscientists, the key to understanding the structures that make up the brain lies in technology that facilitates visualization of differ- ent aspects of neural tissue. One of the first ways to study neural processes involves stains; stains are chemi- cals that attach to specific cell structures, thereby mak- ing it possible for researchers to examine the cells visu- ally and even count them. For more than a century, neuroscientists have developed several staining tech- niques to help visualize mapping fiber connections. Ini- tially, the light microscope, invented in the 1890s, gave birth to the pioneering works of Cajal (1937) and Brod- mann (1909) in cellular neuroanatomy. The introduc- tion of the powerful electron microscope in the 1950s made it possible to analyze in detail the synaptic con- tacts between individual neurons. Next, we outline this remarkable progress for several classic histologic tech- niques. Biological psy- One of the most remarkable developments in the neuro- chology, [6th ed. Golgi, an Italian physician, discovered in the early 1870s that silver chromate stained dead neurons black. The Golgi method enabled detailed study of cell process, often One drawback of the Golgi stain is that it provides little allowing a 3-D view of the cell and its processes. Practi- information about the number of neurons in a specific cally overnight, the basic building blocks of the nervous brain region, because it only affects a few neurons. More recently, researchers have permits a view only of neural tissue in silhouette and does even been able to stain single neurons in a Golgi-like fash- not allow visualization of the inner structure of the neu- ion and visualize many of the different cells that make up ron. Using this method, they found that Purkinje histologist, discovered that a simple dye will selectively cells reside in the cerebellum and have a remarkably dif- stain cell bodies in neurons. The Golgi adapted several different stains, originally developed for method also led to the classification of neurons based on dyeing cloth, for histologic purposes. Golgi type I neurons, for exam- for example, is a neural stain that has an affinity for the ple, have long axons that transfer information from one inner structures of neural cell bodies. The Golgi method selective for neural cell bodies, but stains all central ner- has remained in use for more than 100 years to character- vous system cells. Cresyl violet facilitates the differentia- ize specific cell types in different regions of the nervous tion of fiber bundles, which appear lighter, and nuclei, system. The Nissl method has become the classic microscopic method for studying the cell body and one of the most valu- able techniques for studying neurons in both normal and pathologic states. The Nissl stain outlines all cell bodies and selectively stains the nucleus but not the axon. For example, motor neurons have larger Nissl bodies, and sen- sory neurons have smaller ones. The appearance of the Nissl substance also varies with cell activity; that is, Nissl bodies disintegrate when the axon of the neuron is injured. The Nissl method Text not available due to copyright restrictions shows the cell body, specifically the cell nucleus. The Golgi method is particularly useful for investigating the distribution of dendrites and axons in individual neurons, which appear pitch-black. Scientists have developed other staining procedures specifically for studying axons. As a result, white matter, which consists of myelinated axons, is stained black, whereas other areas of the brain that consist primar- ily of cell bodies and nuclei are not (Figure 2. Since the 1970s, researchers have introduced new tracing methods based on the principle of axonal trans- port to chart previously unexplored regions and circuits of the brain. Using the ax- onal transport technique, neuroscientists can study the tracing of pathways in the brain. Rontgen (or Roentgen, to transliterate the German o into English) quite serendipitously produced an invisible ray that, unlike heat or light waves, could pass through wood, metal, and other solid materials. The principle of X-ray technology is the generation of Roentgen rays, electromag- netic vibrations of very short wavelength that can penetrate biological tissue and can be detected on a photographic plate. At the basis of its medical application was the prin- ciple that the diagnostic rays travel through the body at different rates according to the density of organs. The re- sulting picture would show clear contrast between bones and, to a lesser degree, soft parts. Researchers discovered that X-rays pass easily though low-density tissue (water) but are absorbed by high-density tissue (bone). In addition, they found that the possible harmful effects of X-rays could Figure 2. Diagnostic X-ray films are useful for clinical work on the gas has filled the ventricles, a technician takes a stan- various parts of the body, because they demonstrate the dard X-ray film of the head. Because the gas is of much presence and position of bones, fractures, and foreign lower density than the surrounding brain, the ventricles bodies. A clinical disadvantage of X-ray films, specifically appear as a dark shadow on the X-ray film and clearly out- of the head, is that they are two-dimensional (2-D). Using this approach, a positive diagnosis of a 3-D clinical pathology is difficult. The air encephalo- Second, an X-ray film of the head shows little differentia- gram represented an advance on the standard X-ray film tion between brain structures and cerebrospinal fiuid because it allowed visualization of the ventricular system. Furthermore, X-rays are potentially awkwardly, and invert them in 3-D space to advance the dangerous, because they are cumulatively absorbed by gas to a specific ventricle before the technician could take high-density tissue. The technician does not take the images at a perfect horizontal perspective of the head. Rather, he or she slightly tilts the images at a 20-degree angle to avoid scanning the air-containing sinuses, which produce distortion because of the combination of low (air) and high (bone) density (Figure 2. The first (low- est) image selected is usually at the level of the foramen magnum, the base of the brain. This al- often pinpointing density changes as small as 2 mm in lows for the segmentation of the brain into many different diameter. From these data, the computer generates a picture of the brain that can be in any orientation (sagittal, hori- zontal, or coronal). The complicated calculations the com- puter performs use the mathematics for computing solid 3-D structures based on data from a 2-D source. This can take any form, in- cluding numbers or colors, but radiologists, not surpris- ingly, have favored an end result similar to the familiar X-ray film, with black-and-white shadings that refiect structure density. Neurora- diologists also closely examine the scans for sites of ab- only on autopsy. For example, small strokes, previously undetectable with X-ray technology, were all of a sudden Enhanced Computed easily diagnosed, which increased the prevalence of diag- Transaxial Tomography nosed multi-infarct dementia. In the intact cardiovascular system, contrast material into the arterial or venous bloodstream. Because the blood vessels of the brain barrier, that area shows increased contrast. Using this technique, the specialist blood vessels themselves or in their arrangement. Angiography also can detect frontal and lateral planes, providing visualization of the shifts in cerebral arteries, which may indicate a mass- injected vessels and their complex intracranial branches. Digital subtraction angiography, compared with con- ventional film angiography, is particularly effective in en- Technique hancing visualization of blood vessels, including the mor- Femorocerebral angiography, developed in the mid- phologic and physiologic states of the arterial, capillary, 1950s, introduces a catheter into the arterial system. The resulting visualization cialist passes the preshaped, semirigid catheter through a of the vascular system is easily distinguished from that of needle inserted in the femoral artery, and then guides it brain tissue. The specialist can then place cated than femorocerebral angiography; therefore, clini- the catheter into any of the three major arteries arising cians do not use it as routinely. Angiography is an invasive procedure, yet include low resolution of brain anatomy; advantages include low cost, it is relatively safe and well tolerated by the patient, who availability, and its use in the diagnosis of skull fractures, which are easily is awake but slightly sedated. An improvement over the skull X-ray, but because of its invasive nature block the fiow of blood, leading to an embolism. In gen- readily available and can be used with almost anyone, provides a three- dimensional perspective of the brain with acceptable differentiation of brain eral, for initial diagnosis, clinicians prefer noninvasive structures. Thus, it is particularly useful in di- are it is invasive and some patients may not tolerate the contrast agent well. Angiography: the roentgenographic visualization of blood vessels in the brain after introducing contrast material into the arterial or venous bloodstream. Angiography is the most useful technique for examining the blood supply to and from the brain. This is primarily a research lar to the angiogram in that the examiner places a technique. It is used clinically to determine the lateralization of language before temporal lobectomy is performed. It is a complicated medical proce- catheter, typically in the left or right internal carotid dure that requires placing an arterial catheter. Then, a barbiturate sodium amytal is injected, which temporarily anesthetizes one hemisphere. Only one hemisphere is affected, even though vascular struc- tures connect the two hemispheres (Wada & Rasmussen, 1960). This difference relates to that the pressure gradi- of the brain through electrodes attached to various loca- ents along cerebral arteries in both hemispheres are the tions on the scalp. The Austrian psychiatrist Hans Berger same; thus, there is no cross-filling (or crossover) of blood first discovered in 1924 that patterns of electrical activity from one hemisphere to the other, except if there is a can be recorded using metal electrodes placed on the stroke or other damage to the vascular system. In principle, each electrode measures the summed signal of electrical activ- ity of groups of neuronal dendrites. Researchers have established a system of dividing amplifies the electrical potential of neurons recording brain wave activity that is based on its frequency and am- their activity on moving paper, a polygraph. Modern electrodes used with con- general, they correlate with distinct divisions of subjective ductive gel have proved to be just as effective. Several different basic ple, each pair of electrodes can act as its own recording types have been established that vary according to whether site, measuring the electrical activity of millions of neu- a person is alert, wakeful, drowsy, or sleeping (Table 2. Pyramidal nerve rhythms are the fastest and are often associated with peak performance cells, which have somewhat conical cell bodies, make up states and hyperarousal. Seizures and Because alpha and theta waves are characteristic of a per- Electroencephalography son being relaxed, isolation fiotation tanks and relaxation Neurons can organize their rate of electrical activity in two audio cassette tapes, among other tools, have proved ef- fundamental ways. First, groups of neurons can fire in syn- fective in helping achieve such brain states. In athletics, chronized oscillations by taking cues from other cells, also researchers have demonstrated that peak performance is known as pacemaker cells or k neurons (k for constant). Cor- associated with specific cortical arousal levels (Van Raalte tical neurons also take cues from other brain structures such & Brewer, 1996). Alpha waves, in contrast, are incompat- as the thalamus, which can act as a powerful pacemaker, ible with being alert and focused. The activity rate of in a consistent rhythmic pattern in response to collective cortical neurons should be high, but also unsynchronized, behavior, such as a large group of people clapping in a syn- because neurons may be involved in different aspects of chronized way without a cheerleader being present. During beta waves, Seizures are the most extreme form of synchronous neurons fire rapidly, but not in concert with each other. Seizures themselves are best conceptual- slowing of activity, as well as the presence of epileptiform ized as a symptom, not unlike a fever, and may be activity. For example, it is abnormal to find delta activity triggered by dozens of different causes. These variables include known as epilepsy (see Chapter 16 for a detailed discus- amplitude configuration of the polygraph, speed of sion of epilepsy). Thus, surface scalp right in front of closed eyes, that is set at different fre- electrode placement is the first and least invasive electro- quencies to infiuence the base-rate activation pattern of physiologic study of the brain. Once epilepsy is identified, doctors most com- monly treat it with anticonvulsant medication to reduce spiking activity. See inside covers for trodes (64, 128, and even up to 256) placed over the color image. In response to the auditory stimulus, scans (less metabolism) in the frontal regions of the brain. An al- from left ear right ear ternating light/dark reversing checkerboard pattern pro- vides the visual stimulus. Note the different nuclei along the tion of the electrodes over the occipital cortex is about pathways that form the basis for measuring integration 100 milliseconds.
Corneal Refiex the corneal refiex consists of a bilateral blink response elicited by touching the cornea lightly erectile dysfunction young age causes order 130mg malegra dxt visa, for example impotence blood pressure 130mg malegra dxt overnight delivery, with a piece of cotton wool erectile dysfunction and pump safe malegra dxt 130 mg. As well as observing whether the patient blinks erectile dysfunction protocol does it work cheap malegra dxt 130 mg line, the examiner should also ask whether the stimulus was felt: a difference in corneal sensitivity may be the earliest abnormality in this refiex erectile dysfunction vitamin deficiency malegra dxt 130 mg sale. The fibres subserving -93 C Corneomandibular Refiex the corneal refiex seem to be the most sensitive to trigeminal nerve compression or distortion: an intact corneal refiex with a complaint of facial numbness leads to suspicion of a non-organic cause erectile dysfunction on molly proven 130 mg malegra dxt. Trigeminal nerve lesions cause both ipsilateral and contralateral corneal refiex loss erectile dysfunction in the young malegra dxt 130 mg discount. Cerebral hemisphere (but not thalamic) lesions causing hemiparesis and hemisensory loss may also be associated with a decreased corneal refiex erectile dysfunction pump nhs cost of malegra dxt. The corneal refiex has a high threshold in comatose patients and is usually preserved until late (unless coma is due to drug overdose), in which case its loss is a poor prognostic sign. The patient may assert that they are dead and able to smell rotten fiesh or feel worms crawling over their skin. Although this may occur in the context of psychiatric disease, especially depression and schizophrenia, it may also occur in association with organic brain abnormalities, specifically lesions of the non-dominant temporoparietal cortex, or migraine. Cross References Capgras syndrome; Delusion; Disconnection syndromes Coup de Poignard Coup de poignard, or dagger thrust, refers to a sudden precordial pain, as may occur in myocardial infarction or aortic dissection, also described with spinal subarachnoid haemorrhage. Subarachnoid haemorrhage presenting as acute chest pain: a variant of le coup de poignard. Coup de Sabre Coup de sabre is a localized form of scleroderma manifest as a linear, atrophic lesion on the forehead which may be mistaken for a scar. This lesion may be associated with hemifacial atrophy and epilepsy, and neuroimaging may -95 C Cover Tests show hemiatrophy and intracranial calcification. Whether these changes refiect infiammation or a neurocutaneous syndrome is not known. The cover test demonstrates tropias: the uncovered eye is forced to adopt fixation; any movement therefore represents a manifest strabismus (heterotropia). The alternate cover or cross-cover test, in which the hand or occluder moves back and forth between the eyes, repeatedly breaking and re-establishing fixa- tion, is more dissociating, preventing binocular viewing, and therefore helpful in demonstrating whether or not there is strabismus. It should be performed in the nine cardinal positions of gaze to determine the direction that elicits maxi- mal deviation. Cross References Heterophoria; Heterotropia Cramp Cramps are defined as involuntary contractions of a number of muscle units which results in a hardening of the muscle with pain due to a local lactic aci- dosis. Cramps are not uncommon in normal individuals but in a minority of cases they are associated with an underlying neurological or metabolic disorder. Symptomatic treatment of cramps may include use of quinine sulphate, vitamin B, naftidrofuryl, and calcium channel antagonists such as diltiazem; carba- mazepine, phenytoin, and procainamide have also been tried. Assessment: symptomatic treatment for muscle cramps (an evidence-based review): report of the Therapeutics and Technology Subcommittee of the American Academy of Neurology. Cross References Fasciculation; Myokymia; Neuromyotonia; Spasm; Stiffness Cremasteric Refiex the cremasteric refiex is a superficial or cutaneous refiex consisting of con- traction of the cremaster muscle causing elevation of the testicle, following stimulation of the skin of the upper inner aspect of the thigh from above downwards. The cremasteric refiex is lost when the corticospinal pathways are damaged above T12 or following lesions of the genitofemoral nerve. It may also be absent in elderly men or with local pathology such as hydrocele, varicocele, orchitis, or epididymitis. Cross Reference Refiexes -97 C Crossed Aphasia Crossed Aphasia Aphasia from a right-sided lesion in a right-handed patient, crossed aphasia, is rare, presumably a refiection of crossed or mixed cerebral dominance. Cross Reference Aphasia Crossed Apraxia A name given to apraxia in right-handed patients with right-sided lesions; apraxia is more commonly associated with left-sided brain injury. Cross Reference Lid retraction Dazzle Dazzle is a painless intolerance of the eyes to bright light (cf. It may be peripheral in origin (retinal disease; opacities within cornea, lens, vitreous); or central (lesions anywhere from optic nerve to occipitotemporal region). Cross Reference Photophobia Decerebrate Rigidity Decerebrate rigidity is a posture observed in comatose patients in which there is extension and pronation of the upper extremities, extension of the legs, and plantar fiexion of the feet (= extensor posturing), which is taken to be an exagger- ation of the normal standing position. Painful stimuli may induce opisthotonos, hyperextension, and hyperpronation of the upper limbs. Decerebrate rigidity occurs in severe metabolic disorders of the upper brain- stem (anoxia/ischaemia, trauma, structural lesions, drug intoxication). A similar picture was first observed by Sherrington (1898) following section of the brain- stem of cats at the collicular level, below the red nuclei, such that the vestibular nuclei were intact. The action of the vestibular nuclei, unchecked by higher centres, may be responsible for the profound extensor tone. Decerebrate rigidity indicates a deeper level of coma than decorticate rigid- ity; the transition from the latter to the former is associated with a worsening of prognosis. The lesion responsible for decorticate rigidity is higher in the neuraxis than that causing decerebrate rigidity, often being diffuse cerebral hemisphere or diencephalic disease, although, despite the name, it may occur with upper brainstem lesions. Cross References Coma; Decerebrate rigidity Deja Entendu A sensation of familiarity akin to deja vu but referring to auditory rather than visual experiences. Recurrent hallucinations or vivid dream-like imagery may also enter the differential diagnosis. Epileptic deja vu may last longer and be more frequent and may be associated with other features such as depersonalization and derealization, strong emotion such as fear, epigastric aura, or olfactory hallucinations. Epileptic deja vu is a complex aura of focal onset epilepsy; specifically, it is indicative of temporal lobe onset of seizures and is said by some authors to be the only epileptic aura of reli- able lateralizing significance (right). Deja vu has also been reported to occur in several psychiatric disorders, such as anxiety, depression, and schizophrenia. Cross References Aura; Hallucination; Jamais vu Delirium Delirium, also sometimes known as acute confusional state, acute organic reaction, acute brain syndrome, or toxic-metabolic encephalopathy, is a neurobe- havioural syndrome of which the cardinal feature is a deficit of attention, the ability to focus on specific stimuli. Diagnostic criteria also require a concurrent 102 Delirium D alteration in level of awareness, which may range from lethargy to hypervigilance, although delirium is not primarily a disorder of arousal or alertness (cf. The course of delirium is usually brief (seldom more than a few days, often only hours). On recovery the patient may have no recollection of events, although islands of recall may be preserved, corresponding with lucid intervals (a useful, if retrospective, diagnostic feature). However, it should be noted that in the elderly delirium is often superimposed on dementia, which is a predisposing factor for the development of delirium, perhaps refiecting impaired cerebral reserve. Risk factors for the development of delirium may be categorized as either predisposing or precipitating. It is suggested that optimal nursing of delirious patients should aim at envi- ronmental modulation to avoid both understimulation and overstimulation; a side room is probably best (if possible). However, if the patient poses a risk to him/herself, other patients, or staff which cannot be addressed by other means, regular low-dose oral haloperidol may be used, probably in preference to atypical neuroleptics, benzodiazepines (lorazepam), or cholinesterase inhibitors. Occurrence and outcome of delirium in medical in-patients: a systematic literature review. Cross References Delirium; Dementia; Hallucination; Illusion; Intermetamorphosis; Misidentification syndromes; Reduplicative paramnesia Dementia Dementia is a syndrome characterized by loss of intellectual (cognitive) func- tions sufficient to interfere with social and occupational functioning. Cognition encompasses multiple functions including language, memory, perception, praxis, attentional mechanisms, and executive function (planning, reasoning). These elements may be affected selectively or globally: older definitions of dementia requiring global cognitive decline have now been superseded. Amnesia may or may not, depending on the classification system used, be a sine qua non for the diagnosis of dementia. Attentional mechanisms are largely preserved, cer- tainly in comparison with delirium, a condition which precludes meaningful neuropsychological assessment because of profound attentional deficits. Multiple neuropsychological tests are available to test different areas of cognition. Although more common in the elderly, dementia can also occur in the pre- senium and in children who may lose cognitive skills as a result of hereditary metabolic disorders. A distinction is drawn by some authors between cortical and subcortical dementia: in the former the pathology is predominantly cortical and neuropsychological findings are characterized by amnesia, agnosia, apraxia, and aphasia. However, not all authors subscribe to this distinction and considerable overlap may be observed clinically. Cognitive deficits also occur in affective disorders such as depression, usually as a consequence of impaired attentional mechanisms. It may be difficult to differentiate dementia origi- nating from depressive or neurodegenerative disease, since depression may also -105 D Dementia be a feature of the latter. Impaired attentional mechanisms may account for the common complaint of not recalling conversations or instructions immediately after they happen (aprosexia). Behavioural abnormalities are common in demen- tias due to degenerative brain disease and may require treatment in their own right. Because of the possibility of progression, reversible causes are regularly sought though very rare. Depersonalization is a very common symptom in the general population and may contribute to neurological presentations described as dizziness, numbness, and forgetfulness, with the broad differential diagnoses that such symptoms encompass. Such self-induced symptoms may occur in the context of meditation and self-suggestion. Cross References Derealization; Dissociation Derealization Derealization, a form of dissociation, is the experience of feeling that the world around is unreal. Cross References Alien hand, Alien limb; Intermanual confiict Diamond on Quadriceps Sign Diamond on quadriceps sign may be seen in patients with dysferlinopathies (limb girdle muscular dystrophy type 2B, Miyoshi myopathy): with the knees slightly bent so that the quadriceps are in moderate action, an asymmetric diamond- shaped bulge may be seen, with wasting above and below, indicative of the selectivity of the dystrophic process in these conditions. Cross Reference Calf head sign Diaphoresis Diaphoresis is sweating, either physiological as in sympathetic activation. Diaphoresis may be seen in syncope, delirium tremens, or may be induced by certain drugs. Anticholinergics decrease diaphoresis but increase core temperature, resulting in a warm dry patient. Forced vital capacity measured in the supine and sitting positions is often used to assess diaphragmatic function, a drop of 25% being taken as indicating diaphragmatic weakness. The spatial and temporal characteristics of the diplopia may help to ascertain its cause. Diplopia may be monocular, in which case ocular causes are most likely (although monocular diplopia may be cortical or functional in origin), or binoc- ular, implying a divergence of the visual axes of the two eyes. With binocular diplopia, it is of great importance to ask the patient whether the images are sep- arated horizontally, vertically, or obliquely (tilted), since this may indicate the extraocular muscle(s) most likely to be affected. Whether the two images are 108 Diplopia D separate or overlapping is important when trying to ascertain the direction of maximum diplopia. The effect of gaze direction on diplopia should always be sought, since images are most separated when looking in the direction of a paretic mus- cle. Conversely, diplopia resulting from the breakdown of a latent tendency for the visual axes to deviate (latent strabismus, squint) results in diplopia in all directions of gaze. Examination of the eye movements should include asking the patient to look at a target, such as a pen, in the various directions of gaze (versions) to ascertain where diplopia is maximum. Then, each eye may be alternately covered to try to demonstrate which of the two images is the false one, namely that from the non-fixing eye. Manifest squints (heterotropia) are obvious but seldom a cause of diplopia if long-standing. Transient diplopia (minutes to hours) suggests the possibility of myasthenia gravis. Divergence of the visual axes or ophthalmoplegia without diplopia sug- gests a long-standing problem, such as amblyopia or chronic progressive external ophthalmoplegia. Cross References Motor neglect; Neglect Disc Swelling Swelling or oedema of the optic nerve head may be visualized by ophthal- moscopy. It produces haziness of the nerve fibre layer obscuring the underlying vessels; there may also be haemorrhages and loss of spontaneous retinal venous pulsation. Disc swelling due to oedema must be distinguished from pseudopapil- loedema, elevation of the optic disc not due to oedema, in which the nerve fibre layer is clearly seen. The clinical history, visual acuity, and visual fields may help determine the cause of disc swelling. The disinhibited patient may be inap- propriately jocular (witzelsucht), short-tempered (verbally abusive, physically aggressive), distractible (impaired attentional mechanisms), and show emo- tional lability. A Disinhibition Scale encompassing various domains (motor, intellectual, instinctive, affective, sensitive) has been described. Disinhibition is a feature of frontal lobe, particularly orbitofrontal, dysfunc- tion. Cross References Attention; Emotionalism, Emotional lability; Frontal lobe syndromes; Witzelsucht Dissociated Sensory Loss Dissociated sensory loss refers to impairment of selected sensory modalities with preservation, or sparing, of others. Conversely, pathologies confined, largely or exclusively, to the dorsal columns (classically tabes dorsalis and subacute combined degenera- tion of the cord from vitamin B12 deficiency, but probably most commonly seen with compressive cervical myelopathy) impair proprioception, sometimes suffi- cient to produce pseudoathetosis or sensory ataxia, whilst pain and temperature sensation is preserved. Small fibre peripheral neuropathies may selectively affect the fibres which transmit pain and temperature sensation, leading to a glove-and-stocking impair- ment to these modalities. Neuropathic (Charcot) joints and skin ulceration may occur in this situation; tendon refiexes may be preserved. Common in psychiatric disorders (depression, anxiety, schizophre- nia), these symptoms are also encountered in neurological conditions (epilepsy, migraine, presyncope), conditions such as functional weakness and non-epilpetic attacks, and in isolation by a significant proportion of the general population. Symptoms of dizziness and blankness may well be the result of dissociative states rather than neurological disease. The superior division or ramus supplies the superior rectus and levator palpebrae superioris muscles; the inferior division or ramus supplies medial rectus, inferior rectus and inferior oblique muscles. Isolated dys- function of these muscular groups allows diagnosis of a divisional palsy and suggests pathology at the superior orbital fissure or anterior cavernous sinus. However, occasionally this division may occur more proximally, at the fascicu- lar level.
Prioritization should be adapted to local conditions and should consider intensity and duration of exposure online erectile dysfunction drugs reviews effective 130mg malegra dxt, personal health risk factors for complications of infection erectile dysfunction kya hota hai cheap malegra dxt on line, and vaccination status causes of erectile dysfunction in your 20s purchase malegra dxt 130 mg visa. Facemasks for healthcare personnel who are not provided a respirator due to the implementation of prioritized respirator use: If a facility is in prioritized respirator use mode and unable to provide respirators to healthcare personnel who provide care to suspected and confirmed infiuenza cases erectile dysfunction vascular causes buy line malegra dxt, the facility should provide those personnel with facemasks erectile dysfunction caused by hydrocodone 130 mg malegra dxt overnight delivery. Aerosol-generating procedures Some procedures performed on patients are more likely to generate higher concentrations of respiratory aerosols than coughing erectile dysfunction medication nz malegra dxt 130 mg overnight delivery, sneezing erectile dysfunction doctor in patna cheap 130mg malegra dxt, talking medication that causes erectile dysfunction buy cheap malegra dxt on-line, or breathing, presenting healthcare personnel with an increased risk of exposure to infectious agents present in the aerosol. The availability of N95 respirators should be taken into account in this decision. Information on air fiow/air entrainment performance should be evaluated for such devices. Environmental surface cleaning also is necessary to ensure that environmental contamination does not lead to infection transmission. Duration of Isolation Precautions for Patients Isolation precautions for patients who have infiuenza symptoms should be continued for the 7 days after illness onset or until 24 hours after the resolution of fever and respiratory symptoms, whichever is longer, while a patient is in a healthcare facility. Shedding of infiuenza viruses generally diminishes over the course of 7 days, with transmission apparently correlating with fever. Patients should be discharged from medical care when clinically appropriate, not based on the period of isolation. In some cases, facilities may choose to continue isolation precautions for longer periods such as in the case of young children or severely immunocompromised patients, who may shed infiuenza virus for longer periods of time and who might be shedding antiviral resistant virus. Clinical judgment should be used to determine the need for continued isolation precautions for such patients. Home-healthcare agencies, long-term care facilities) as well as transporting agencies is essential. Monitor and Manage Ill Healthcare Personnel In most cases, decisions about work restrictions and assignments for personnel with respiratory illness should be guided by clinical signs and symptoms rather than by laboratory testing for infiuenza. Personnel should be provided with information about risk factors for complications of infiuenza, so those at higher risk know to promptly seek medical attention and be evaluated for early treatment if they develop symptoms of infiuenza. All personnel should be provided with specific instructions to follow in the event of respiratory illness with rapid progression, particularly when experiencing shortness of breath. In this case they should be considered for temporary reassignment or exclusion from work for 7 days from symptom onset or until the resolution of symptoms, whichever is longer. Clinical judgment should be used for personnel with only cough as a symptom, since cough after infiuenza infection may be prolonged and may not be an indicator of viral shedding. Additional information on diagnostic testing for infiuenza infection can be found at. Antiviral Treatment and Chemoprophylaxis of Healthcare Personnel Please refer to . Training and education of healthcare personnel All healthcare personnel should receive training on infiuenza prevention and risks for complications of infiuenza. The training should include information on risk assessment; isolation precautions; vaccination protocols; use of engineering and administrative controls and personal protective equipment; protection during high-risk aerosol- generating procedures; signs, symptoms, and complications of infiuenza; and to promptly seek medical attention for any concerns about symptoms of infiuenza. Healthcare Personnel at Higher Risk for Complications of Infiuenza Personnel at higher risk for complications from infiuenza infection include pregnant women, persons 65 years old and older, and persons with chronic diseases such as asthma, heart disease, diabetes, diseases that suppress the immune system, and certain other chronic medical conditions. Vaccination and early treatment with antiviral medications are very important for healthcare personnel at higher risk for infiuenza complications because they can prevent hospitalizations and deaths. Healthcare personnel at higher risk for complications should check with their healthcare provider if they become ill so that they can receive early treatment. Environmental Infection Control Routine cleaning and disinfection strategies used during infiuenza seasons can be applied to the environmental management of infiuenza. Management of laundry, utensils and medical waste should also be performed in accordance with procedures followed for seasonal infiuenza. Advance planning is critical to efficient implementation of prioritized use during supply shortages. Consider including those with immunosuppressive conditions or treatment with immunosuppressive therapies anticipated to impair vaccine response in this group. This generally includes personnel working in settings where cases of suspected or confirmed infiuenza are routinely seen. This generally includes personnel working in settings where cases of suspected or confirmed infiuenza are not routinely seen and/or having job duties not involving close contact. Clinical awareness of novel or pandemic infiuenza disease can also benefit the individual patient, as rapid initiation of treatment can avert potentially severe complications. Clinical management of patients during pandemic infiuenza will follow many of the same principles of patient care in cases of seasonal strains of infiuenza. The management of infiuenza is based primarily on sound clinical judgment regarding the individual patient as well as the availability of local resources, such as rapid diagnostic tests, antiviral drugs, and hospital beds. Health care providers who are well trained in managing seasonal infiuenza will be better able to effectively diagnose and care for patients with pandemic infiuenza. The Appendices add additional information on the clinical presentation and complications of infiuenza; the clinical features of human infection with novel infiuenza; management of secondary bacterial pneumonia during a pandemic; and respiratory etiquette posters. During periods in which no human infections with a novel infiuenza A virus strain have occurred anywhere in the world, or when sporadic cases of animal-to-human transmission or rare instances of limited human-to-human transmission of a novel infiuenza virus have occurred in the world, the risk to travelers is low. Updates will be provided, as needed, on the Arizona Department of Health Services website ( To limit evaluating an overwhelming number of patients, screening criteria should rely on a combination of clinical and epidemiologic features. Febrile respiratory illnesses are one of the most common reasons for medical evaluation during the winter. Laboratory testing should be done for those with severe respiratory illness, such as pneumonia. Thus additional testing to evaluate acute febrile respiratory illnesses for coccidioidomycosis shall be considered. Criteria for evaluation of patients with possible novel infiuenza Human infections with novel infiuenza viruses will be uncommon. Recommendations for the evaluation of patients with respiratory illnesses are provided in Box 5. When such patients have a strong epidemiologic risk factor, novel infiuenza should be considered with almost any change in health status, even in the absence of typical clinical features. Conjunctivitis has been reported in patients with infiuenza A (H7N7) and (H7N3) infections. Infants may present with fever or apnea alone, without other respiratory symptoms, and should be evaluated if there is an otherwise increased suspicion of novel infiuenza. Epidemiologic criteria Epidemiologic criteria for evaluation of patients with possible novel infiuenza focus on the risk of exposure to a novel infiuenza virus with pandemic potential. Although the incubation period for seasonal infiuenza ranges from one to four days, the incubation periods for novel types of infiuenza are currently unknown and might be longer. Therefore, the maximum interval between potential exposure and symptom onset is set conservatively at 10 days. The majority of human cases of novel infiuenza will result from animal-to-human transmission (see Box 5. Therefore, a history of direct contact with animals associated with infiuenza (well-appearing, sick, or dead), consumption of uncooked animals associated with infiuenza, or direct exposure to environmental contamination with animal feces in an affected area will be important to ascertain. During Initiation Intervals, a history of close contact with an ill person suspected or confirmed to have novel infiuenza in an affected area will be even more important. Exposure risks fall into three categories: travel; direct contact with animal-associated infiuenza; and occupational. Close contact with a person from an infected area with confirmed or suspected novel infiuenza is defined as being within 3 feet (as a practical matter one arms length is a useful estimate) of that person during their illness. Human infiuenza viruses circulate worldwide and year-round, including in countries with outbreaks of avian infiuenza A (H5N1) among poultry. This includes travelers returning from areas affected by poultry outbreaks of highly pathogenic avian infiuenza A (H5N1) in Asia. As of December 2005, such persons are currently more likely to have infection with human infiuenza viruses than with avian infiuenza A (H5N1) viruses. Initial management of patients who meet the criteria for novel infiuenza When a patient meets both the clinical and epidemiologic criteria for a suspected case of novel infiuenza, health care personnel should initiate the following activities: Implement infection control precautions for novel infiuenza, including respiratory hygiene/cough etiquette Patients shall be placed on Droplet Precautions for a minimum of 14 days, unless there is full resolution of illness or another etiology has been identified before that period has elapsed. Obtain clinical specimens and notify the local and state health departments to arrange testing Testing of suspected novel or pandemic infiuenza shall be directed by public health authorities (see Supplement 2, Laboratory Diagnostics, for more detailed guidelines). Rapid infiuenza tests have relatively low sensitivity for detecting seasonal infiuenza, and their ability to detect novel infiuenza subtypes is unknown. Such tests can identify infiuenza viruses but cannot distinguish between human infection with seasonal and novel infiuenza viruses. A negative rapid infiuenza test result does not necessarily exclude human infection with either seasonal or novel infiuenza viruses. A positive rapid infiuenza test result could be a false positive or represent infection with either seasonal or novel infiuenza viruses. Evaluate alternative diagnoses An alternative diagnosis should be based only on laboratory tests with high positive-predictive value. If an alternate etiology is identified, the possibility of co-infection with a novel infiuenza virus may still be considered if there is a strong epidemiologic link to exposure to novel infiuenza. Initiate antiviral treatment as soon as possible, even if laboratory results are not yet available Clinical trials have shown that these drugs can decrease the illness due to seasonal infiuenza duration by several days when initiated within 48 hours of illness onset. The clinical effectiveness of antiviral drugs for treatment of novel infiuenza is unknown, but it is likely that early treatment will be beneficial. In general, persons in close contact with the case-patient at any time beginning one day before the onset of illness are considered at risk. Close contacts might include household and social contacts, family members, workplace or school contacts, fellow travelers, and/or health care providers (see Supplement 8 and Supplement 9). Therefore, if test results are negative but the clinical and epidemiologic suspicion for a novel infiuenza virus remains high, continue antiviral treatment and isolation procedures. The general work-up for febrile respiratory illnesses described below should evaluate the most common alternate causes. In hospitalized patients who test negative for novel infiuenza but have no alternate diagnosis established, novel- infiuenza-directed management should be continued if clinical suspicion is high and there is a strong epidemiologic link to exposure to novel infiuenza. Outpatient clinics and emergency departments may be overwhelmed with suspected cases, restricting the time and laboratory resources available for evaluation. In addition, if the pandemic infiuenza virus exhibits transmission characteristics similar to those of seasonal infiuenza viruses, illnesses will likely spread throughout the community too rapidly to allow the identification of obvious exposures or contacts. Evaluation will therefore focus predominantly on clinical and basic laboratory findings, with less emphasis on laboratory diagnostic testing for infiuenza (which may be in short supply). Clinicians in communities without pandemic infiuenza activity might consider asking patients about recent travel from a community with pandemic infiuenza activity or close contact with a suspected or confirmed pandemic infiuenza case. The main features of clinical management during these phases are outlined in Figure 5. Past infiuenza pandemics have most frequently resulted in respiratory illness,but the next pandemic infiuenza virus strain might present with a different clinical syndrome (see Appendix 5. During a pandemic, updates on other clinical presentations will be provided at: When such patients have a strong epidemiologic risk factor, novel infiuenza should be considered with any substantial change in health status, even in the absence of typical clinical features. For example conjunctivitis has been reported in patients with infiuenza A (H7N7) and (H7N3) infections. In young children, gastrointestinal manifestations such as vomiting and diarrhea might be present. Once pandemic infiuenza has arrived in a particular locality, clinical criteria will be sufficient for classifying the patient as a suspected pandemic infiuenza case. If the patient is hospitalized, implement infection control precautions for pandemic infiuenza, including Respiratory Hygiene/Cough Etiquette. Therefore test results need to be interpreted within the overall clinical context. For example, it may not be optimal to withhold antiviral treatment from a seriously ill high-risk patient on the basis of a negative test. Guidelines on cohorting and infection control for admitted patients can be found in Supplement 3, Healthcare Coordination and Surge Capacity, and Supplement 4, Infection Control. The primary caregiver would ideally be someone who does not have an underlying condition that places them at increased risk of severe infiuenza disease. Clinical management of pandemic infiuenza patients See Supplement 7, Antiviral Drug Distribution and Use for current antiviral information and treatment strategies. In addition to the use of antivirals, clinical management of severe infiuenza should address supportive care and the rapid identification and treatment of secondary complications. Complications related to seasonal human infiuenza occur more commonly in persons with certain underlying medical conditions, such as chronic respiratory or cardiovascular disease, extremes of age, pregnancy, and neuromuscular disease are described in Appendix 5. Limited data are available on risk factors and complications related to infection with novel infiuenza viruses, and these may change as individual strains evolve. These agents frequently have severe adverse effects, such as bone marrow and hepatic toxicity, while the benefits of these therapies are unknown. Interpandemic Phase Phases 1 through 3 range from no infection in humans to small clusters or limited human transmission. During these phases, the risk of human infection with a novel infiuenza virus is extremely low. Alert Phase Human-to-human transmission of an animal or human-animal infiuenza reassortant virus is able to sustain community-level outbreaks and has been verified. During these phases, the risk of human infection with a novel infiuenza virus is elevated. The risk of human infection with human infiuenza viruses or other viruses is much higher in persons living in or traveling to affected areas. Those without a history of immunization should receive these vaccines before discharge, if indicated. Appropriate personal protective equipment should be used when evaluating patients with suspected novel infiuenza, including during collection of specimens. Further evaluation and diagnostic testing should also be considered for outpatients with strong epidemiologic risk factors and mild or moderate illness. For persons who live in or visit affected areas, close contact includes touching live poultry (well- appearing, sick or dead) or touching or consuming uncooked poultry products, including blood. For animal or market workers, it includes touching surfaces contaminated with bird feces. In recent years, most instances of human infection with a novel infiuenza A virus having pandemic potential, including infiuenza A (H5N1), are thought to have occurred through direct transmission from domestic poultry. A small number of cases are also thought to have occurred through limited person-to-person transmission or consumption of uncooked poultry products. Transmission of novel infiuenza viruses from other infected animal populations or by contact with fecally contaminated surfaces remains a possibility. These guidelines will be updated as needed if alternate sources of novel infiuenza viruses are suspected or confirmed. Close contact includes direct physical contact, or approach within 3 feet (1 meter) of a person with suspected or confirmed novel infiuenza. Standard and Droplet Precautions should be used when caring for patients with novel infiuenza or seasonal infiuenza (Table and Supplement 4). Information on infection precautions that should be implemented for all respiratory illnesses. Hospitalization should be based on all clinical factors, including the potential for infectiousness and the ability to practice adequate infection control. If hospitalization is not clinically necessary, and treatment and infection control is feasible in the home, the patient may be managed as an outpatient. The patient and his or her household should be provided with information on infection control procedures to follow at home (Supplement 4). The patient and close contacts should be monitored for illness by local public health department staff. Guidance on how to report suspected cases of novel infiuenza is provided in Supplement 1.
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