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By G. Thorus. Louisiana Tech University. 2018.

If you find that fiddling with the data like this in various ways m akes little or no difference to the review’s overall results purchase valtrex 500 mg with visa, you can assum e that the review’s conclusions are relatively robust order valtrex 500mg with visa. If, however, the key findings disappear when any of the what ifs change, the conclusions should be expressed far m ore cautiously and you should hesitate before changing your practice in the light of them. Question 5 Have the numerical results been interpreted with common sense and due regard to the broader aspects of the problem? As the next section shows, it is easy to be "phased" by the figures and graphs in a system atic review. But any num erical result, however precise, accurate, "significant" or otherwise incontrovertible, m ust be placed in the context of the painfully sim ple and (often) frustratingly general question which the review addressed. The clinician m ust decide how (if at all) this num erical result, whether significant or not, should influence the care of an individual patient. A particularly im portant feature to consider when undertaking or appraising a system atic review is the external validity of included trials (see Box 8. A trial m ay be of high m ethodological quality and have a precise and num erically im pressive result but it m ay, for exam ple, have been conducted on participants under the age of 60 and hence m ay not be valid for people over 75. The inclusion in system atic reviews of irrelevant studies is guaranteed to lead to absurdities and reduce the credibility of secondary research, as Professor Sir John G rim ley Evans argued (see section 9. The 128 PAPERS TH AT SU M M ARISE OTH ER PAPERS m etaanalysis, defined as a statistical synthesis of the numerical results of several trials which all addressed the same question, is the statisticians’ chance to pull a double wham m y on you. First, they phase you with all the statistical tests in the individual papers and then they use a whole new battery of tests to produce a new set of odds ratios, confidence intervals, and values for significance. As I confessed in Chapter 5, I too tend to go into panic m ode at the sight of ratios, square root signs, and half-forgotten G reek letters. But before you consign m etaanalysis to the set of newfangled techniques which you will never understand, rem em ber two things. A good m etaanalysis is often easier for the non-statistician to understand than the stack of prim ary research papers from which it was derived, for reasons which I am about to explain. Second, the underlying statistical techniques used for m etaanalysis are exactly the sam e as the ones for any other data analysis – it’s just that som e of the num bers are bigger. H elpfully, an international advisory group have com e up with a standard form at for m eta-analyses (the QU OROM statem ent,20 analogous to the CON SORT form at for random ised controlled trials I m entioned in Chapter 4). The first task of the m etaanalyst, after following the prelim inary steps for system atic review in Figure 8. In trials of a particular chem otherapy regim en for breast cancer, for exam ple, som e authors will have published cum ulative m ortality figures (i. The m etaanalyst m ight decide to concentrate on 12 m onth m ortality because this result can be easily extracted from all the papers. H e or she m ay, however, decide that three m onth m ortality is a clinically im portant endpoint and would need to write to the authors of the rem aining trials asking for the raw data from which to calculate these figures. In addition to crunching the num bers, part of the m etaanalyst’s job description is to tabulate relevant inform ation on the inclusion criteria, sam ple size, baseline patient characteristics, withdrawal ("dropout") rate, and results of prim ary and secondary endpoints of all the studies included. If this task has been done properly, you 129 H OW TO READ A PAPER will be able to com pare both the m ethods and the results of two trials whose authors wrote up their research in different ways. Although such tables are often visually daunting, they save you having to plough through the m ethods sections of each paper and com pare one author’s tabulated results with another author’s pie chart or histogram. These days, the results of m eta-analyses tend to be presented in a fairly standard form. This is partly because m etaanalysts often use com puter software to do the calculations for them ,21 and this software includes a standard graphics package which presents results as illustrated in Figure 8. I have reproduced in the form at of one com m only used software package (with the authors’ perm ission) this pictorial representation (colloquially known as a "forest plot" or "blobbogram ") of the pooled odds ratios of eight RCTs which each com pared coronary artery bypass graft (CABG ) with percutaneous coronary angioplasty (PTCA) in the treatm ent of severe angina. The horizontal line corresponding to each trial shows the relative risk of death or heart attack at one year in patients random ised to PTCA com pared to patients random ised to CABG. The "blob" in the m iddle of each line is the point estim ate of the difference between the groups (the best single estim ate of the benefit in lives saved by offering CABG rather than PTCA) and the width of the line represents the 95% confidence interval of this estim ate (see section 5.

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If the block results in numbness but no pain relief cheap valtrex 500mg on line, we presume the pain generator is proxi- mal or collateral to the anesthetized site buy 500mg valtrex free shipping. Differential epidural blocks can reveal whether pain is arising from the somatic nerves, the sympathetic nervous system, or the central ner- vous system. If the placebo relief is long lasting, it is possible that the pain is centrally main- tained or psychogenic. If the placebo provides no pain relief, we ad- minister three injections of successively higher concentrations of local anesthetic. If the lowest concentration of anesthetic provides pain relief, we consider the pain to be sympathetically maintained. If the next level of anesthetic provides relief, we presume that the pain is somatosensory. If the pain persists, we inject the highest concentration, which usually causes a temporary loss of motor function. If this fails to provide relief, we presume the pain is centrally maintained or psychogenic. Psychological Evaluation Pain is, by definition, a sensory and emotional experience of actual or perceived tissue damage. The challenge for the pain practitioner is to differentiate between the component that is biologi- cally driven and the component that is magnified by emotions. This evaluation is an important part of a medical approach to their pain and is essential before they receive interventional therapies. Medical Therapies 47 Patients with major depressed mood, anxiety, or other negative af- fective states report more pain with noxious stimuli than do controls with positive affective states. We believe that emotionally depressed patients can be appropriate candidates for interventional therapies; it is simply necessary to be especially careful when offering them thera- pies that carry significant risks. While it may be obvious that patients with severe pain caused by a peripheral pain generator will also ex- perience depression or anxiety, it is less obvious that the same nega- tive affective states actually increase the experience of pain itself. De- pressed affective states can also maintain pain and cause it to take on a life of its own by dramatically amplifying what would otherwise be a relatively minor pain generator. Frequently, a physician can determine the severity of emotional dys- function during an initial encounter. If the patient reports anhedonia, depressed or increased appetite, a history of major depression, or dif- ficulty sleeping, a physician should be alert to the possibility that de- pressed mood is an exacerbating component of the pain. When a ma- jor depression is suspected, it should be treated prior to initiating interventional techniques, directly or by referral to a competent physi- cian who can help with this aspect of pain. Pain Management To reiterate: in order to determine the most appropriate therapeutic strategy, it is vital to begin by making an accurate and comprehensive pain diagnosis. The treatment of neuropathic pain might be very dif- ferent from that of nociceptive pain. Likewise, the treatment of myo- fascial pain is very different from that of discogenic pain, and so forth. Frequently, the tools just discussed are sufficient to establish the diag- nosis, the severity of symptoms, and the prognosis of the patient with pain. Once the diagnosis has been established, it is important to de- sign the most appropriate strategy. This involves choosing the best strategy for the patient and selecting the appropriate patient for a given procedure. In other words, certain conditions may call for certain ther- apies, but for a specific patient suffering from one such condition, the usual therapies may be inappropriate. In addition, some therapies may fail in some patients and succeed in others with the same condition. It is, thus, important that the physician involved in interventional pain medicine be familiar with the full spectrum of diagnostic and ther- apeutic care and with ways to determine appropriate patient selection for any given procedure. They should be considered as tools in a toolbox, however, not as a list of medica- tions that must be tried prior to initiating interventional therapies. When applied to peripheral pain fibers, prostaglandins (PGE2 in particular) amplify the experience of pain. Nonsteroidals block the cyclooxygenase (COX) enzymes that oversee production of PGE2 and, thus decrease the amount of prostaglandin. These pharmaceuticals are commonly used to treat pain syndromes characterized by inflammation or by mild pain.

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J Physiol 377:575–588 Burstein R purchase 1000 mg valtrex overnight delivery, Giesler GJ (1989) Retrogradely labeling of neurons in spinal cord that project directly to nucleus accumbens or the septal nuclei in the rat discount 1000 mg valtrex amex. Brain Res 497:149–154 Burstein R, Potrebic S (1993) Retrograde labeling of neurons in spinal cord that project directly to the amygdala or the orbital cortex in the rat. J Comp Neurol 335:469–485 Burstein R, Cliffer KD, Giesler GJ (1990a) Cells of origin of the spinohypothalamic tract in the rat. J Comp Neurol 291:329–344 Burstein R, Dado RJ, Giesler GJ (1990b) The cells of origin of the spinothalamic tract of the rat: a quantitative reexamination. Brain Res 511:329–337 Burstein R, Dado RJ, Cliffer KD, Giesler GJ (1991) Physiological characterization of spinohy- pothalamic tract neurons in the lumbar enlargement of rats. J Neurophysiol 66:261–284 Burstein R, Falkowsky O, Borsook D, Strassman A (1996) Distinct lateral and medial pro- jections of the spinohypothalamic tract of the rat. J Comp Neurol 373:549–574 Bushnell MC, Duncan GH, Hofbauer RK, Ha B, Chen JI, Carrier B (1999) Pain perception: is there a role for primary somatosensory cortex? Int Rev Neurobiol 25:39–94 Byers MR, Dong WK (1983) Autoradiographic location of sensory nerve endings in dentin of monkey teeth. Anat Rec 205:441–454 Cain DM, Wacnik PW, Turner M, Wendelschafer-Crabb G, Kennedy WR, Wilcox GL, Simone DA (2001) Functional interactions between tumor and peripheral nerve: changes in excitability and morphology of primary afferent fibers in a murine model of cancer pain. J Neurosci 21:9367–9376 Calcutt NA (2002) Potential mechanisms of neuropathic pain in diabetes. Int Rev Neurobiol 50:205–228 Cameron AA, Cliffer KD, Dougherty PM, Willis WD, Carlton SM (1991) Changes in lectin, GAP-43 and neuropeptide staining in the rat superficial dorsal horn following experi- mental peripheral neuropathy. Neurosci Lett 131:249–252 Cameron AA, Pover CM, Willis WD, Coggeshall RE (1992) Evidence that fine primary affer- ent axons innervate a wider territory in the superficial dorsal horn following peripheral axotomy. Oxford University Press, Oxford, pp 117–145 References 77 Cao YQ, Mantyh PW, Carlson EJ, Gillespie AM, Epstein CJ, Basbaum AI (1998) Primary afferenttachykininsarerequiredtoexperiencemoderatetointensepain. Nature392:334– 335 Capra NF, Dessem D (1992) Central connections of trigeminal primary afferent neurons: topographical and functional considerations. Crit Rev Oral Biol Med 4:1–52 Carlstedt T, Cullheim S, Risling M (2004) Spinal cord in relation to the peripheral nervous system. Elsevier Academic Press, Amsterdam, pp 250–263 Carlton SM, Coggeshall RE (1999) Inflammation-induced changes in peripheral glutamate receptor populations. Brain Res 820:63–70 Carlton SM, Hargett GL, Coggeshall RE (2001) Localization of metabotropic glutamate receptors 2/3 on primary afferent axons in the rat. Neuroscience 105:957–969 Carstens E, Trevino DL (1978a) Laminar origins of spinothalamic projections in the cat as determined by the retrograde transport of horseradish peroxidase. J Comp Neurol 182:151–166 Carstens E, Trevino DL (1978b) Anatomical and physiological properties of ipsilaterally projecting spinothalamic neurons in the second cervical of the cat’s spinal cord. J Comp Neurol 182:167–184 Casey KL (2000) Concepts of pain mechanisms: the contribution of functional imaging of the human brain. Prog Brain Res 129:277–287 CaseyKL,MinoshimaS,BergerKL,KoeppeRA,MorrowTJ,FreyA(1994)Positron emission tomographic analysis of cerebral structures activated specifically by repetitive noxious heat stimuli. J Neurophysiol 71:802–807 Casey KL, Minoshima S, Morrow TJ, Koeppe RA (1996) Comparison of human cerebral acti- vation pattern during cutaneous warmth, heat pain, and deep cold pain. Harvard University Press, Cambridge Castro-Lopes JM, Coimbra A, Grant G, Arvidsson J (1990) Ultrastructural changes of the central scalloped (C1) primary afferent endings of synaptic glomeruli in the substantia gelatinosa Rolandi of the rat after peripheral neurotomy. J Neurocytol 19:329–337 Castro-Lopes JM, Tavares I, Coimbra A (1993) GABA decreases in the spinal cord dorsal horn after peripheral neurectomy. Brain Res 620:287–291 Castro-Lopes JM, Malcangio M, Pan BH, Bowery NG (1995) Complex changes of GABA A and GABA B receptor binding in the spinal cord dorsal horn following peripheral inflammation or neuroectomy. Brain Res 679:289–297 Catania MV, Tölle TR, Monyer H (1995) Differential expression of AMPA receptor subunit in NOS-positive neurons of cortex, striatum, and hippocampus. Annu Rev Neurosci 24:487–517 Caterina MJ, Schumacher MA, Tominaga M, Rosen TA, Levine JD, Julius D (1997) The capsaicin receptor: a heat activated ion channel in the pain pathway. Nature 389:816–824 Caterina MJ, Rosen TA, Tominaga M, Brake AJ, Julius D (1999) A capsaicin receptor homo- logue with a high threshold for noxious heat. Nature 398:436–441 Caterina MJ, Leffler A, Malmberg AB, Martin WJ, Trafton J, Petersen-Zeitz KR, Koltzenburg M, Basbaum AI, Julius D (2000) Impaired nociception and pain sensation in mice lacking the capsaicin receptor. Science 288:306–313 Cauna N (1973) The free penicillate nerve endings of the human hairy skin. J Anat 115:277– 288 78 References Cauna N (1980) Fine morphological characteristics and microtopography of the free nerve endings of the human digital skin. Oxford University Press, Oxford, pp 220–240 Cervero F, Jänig W (1992) Visceral nociceptors: a new world order?

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Tsementzis purchase 1000 mg valtrex with visa, Differential Diagnosis in Neurology and Neurosurgery © 2000 Thieme All rights reserved generic 1000 mg valtrex fast delivery. Carpal tunnel syndrome oc- curs as a result of compression of the median nerve beneath the carpal tunnel ligament, and affects 1% of the population. The following physical tests can be helpful in the diagnosis of carpal tunnel syndrome. The test is positive when tapping the area over the median nerve at the wrist produces paresthesia in the median nerve dis- tribution. The test is considered positive when the patient’s sensory symptoms are duplicated after pressure is applied over the carpal tunnel for 30 seconds. This test is positive when full flexion of the wrist for 60 seconds produces the patient’s symptoms. Sensory conduction studies are the most sensitive physiological technique for diagnosing carpal tunnel syndrome. Abnormal sensory testing can be found in 80% of patients with minimal symptoms and in over 80% of severe cases, in which "no recordable sensory potentials" are observed. Normal nerve conduction studies are found in 15–25% of cases of carpal tunnel syndrome Electromyography is normal in up to 31% of patients with carpal tunnel syn- drome. Abnormal electromyography with increased polyphasic quality, positive waves, fibrillation potentials, and decreased motor unit numbers of maximal thenar muscle contraction, is regarded as severe and as an indication for surgery Contributing factors Ligamentous or synovial thickening Trauma Tsementzis, Differential Diagnosis in Neurology and Neurosurgery © 2000 Thieme All rights reserved. Carpal Tunnel Syndrome 235 Obesity Diabetes Scleroderma Thyroid disease Lupus Amyloidosis Gout Acromegaly Paget’s disease Mucopolysaccharidoses Differential diagnosis Cervical radiculopathy (C6, C7) Sensory symptoms Numbness and paresthesia. May involve the thumb and index and middle fingers, as in carpal tunnel syn- drome, but they may often radiate along the lateral forearm and occasionally the radial dorsum of the hand Pain In contrast to carpal tunnel syndrome, pain in cervical radiculopathy frequently involves the neck, and may be precipitated by neck movements. Patients with radicular pain tend to keep their arm and neck still, whereas in carpal tunnel syn- drome they shake their arms and rub their hands to relieve the pain Weakness and atrophy This involves muscles innervated by C6 and C7, not the muscles innervated by C8. Brachioradialis and tri- ceps tendon reflexes may be decreased or absent in radiculopathy Provocation tests In carpal tunnel syndrome, the symptoms can be re- produced by provocative tests – By tapping over the carpal tunnel (Tinel’s sign) – By flexion of the wrist (Phalen’s sign) – When a blood pressure cuff is applied to the arm and compression above systolic pressure is used, median paresthesias and pain can be aggravated (the Gilliatt and Wilson cuff compression test) Tsementzis, Differential Diagnosis in Neurology and Neurosurgery © 2000 Thieme All rights reserved. Somatosensory evoked response (SSER), electromyog- raphy (EMG), orthodromic/antidromic tests, etc. Brachial plexopathy This is usually incomplete, and characterized by the in- volvement of more than one spinal or peripheral nerve, producing clinical deficits such as muscle pare- sis and atrophy, loss of muscle stretch reflexes, patchy sensory changes, and often shoulder and arm pain, which is usually accentuated by arm movement – Upper plexus Erb–Duchenne type paralysis! There may be some sensory loss over the deltoid muscle area – Lower plexus Dejerine–Klumpke type paralysis! Sensation may be intact or lost over the medial arm, forearm, and ulnar aspect of the hand! There is an ipsilateral Horner’s syndrome with in- jury of the T1 root – Neuralgic amyo- Parsonage–Turner syndrome. This is characterized by trophy acute, severe pain in the shoulder, radiating into the arm, neck, and back. The pain is followed within several hours or days by paresis of the shoulder and proximal musculature. The condition is idiopathic, but is thought to be a plexitis, and may follow viral illness or immunization Tsementzis, Differential Diagnosis in Neurology and Neurosurgery © 2000 Thieme All rights reserved. Carpal Tunnel Syndrome 237 – Thoracic outlet Also known as cervicobrachial neurovascular compres- syndrome sion syndrome. The thoracic outlet syndrome may be purely vascular, purely neuropathic, or rarely, mixed. The true neurogenic thoracic outlet syndrome is rare, occurring more frequently in young women, and af- fecting the lower trunk of the brachial plexus. Inter- mittent pain is the most common symptom, referred to the medial arm and forearm and the ulnar border of the hand. The motor and reflex findings are essentially those of a lower brachial plexus palsy, with particular involvement of the C8 root causing weak- ness and wasting of the thenar muscles, similar to car- pal tunnel syndrome. However, in contrast to the lat- ter, in the thoracic outlet syndrome wasting and pare- sis also tend to involve the hypothenar muscles, which derive their innervation from the C8 and T1 roots, and the sensory symptoms involve the medial arm and forearm, whereas the arm discomfort is made worse with movement.

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