Lioresal

By F. Jens. University of Chicago.

The logical time to give up is when editors and reviewers continue to make the same objection – insuffi- cient numbers in the sample purchase lioresal 25mg, for instance order lioresal 10 mg overnight delivery, or offensive to public taste – and you cannot (or will not) do anything about it. This is the time to hold a ceremonial burning – and get on with your life. While unpleasant at the time, they are good for the soul and better for the writing. And it does make that acceptance letter – when it comes – that much more worth while (see acceptance). Generally these will review a situation (or problem), analyse it, and then put some recommendations. This is a specialized type of writing; once you master the technique, you have a powerful tool. Some reports, sadly, are written only because someone has been told to write them; these are pointless. Are you writing to obtain an extra piece of equipment or new member of staff, or to change an existing policy? Are you writing to raise awareness of an issue, or to persuade people to take drastic action, like closing down a hospital? Whatever you decide, be clear in your mind how you will judge success (see effective writing). The more focused you are, the greater the chances of your report being successful (see marketing). Examples might include introduction, background/history, current situation/problem, discussion, recommendations. Look at the reports that have worked before for your audience, and follow the style of the 113 THE A–Z OF MEDICAL WRITING successful ones. Approach each section as if it were a separate piece of writing (see process of writing). Some documents run into trouble because they have to appeal, say, to an audience of professional colleagues who have one set of expectations (see jargon), while at the same time having to convince the non-professionals who will make the decisions. Fortunately there is a solution: write the report for your professional peers, and use the executive summary as your selling tool for the decision makers. Research All types of writing – not just science writing – will fail if the research is inadequate (see bad writing). Research into writing Even those steeped in the harshest traditions of evidence-based medicine can become remarkably cavalier when it comes to making decisions about their writing. But a wide range of evidence exists, both from psychological experiments into readability and from market research carried out privately for commercial publishers. Here is a short selection of some of the main findings: • Long sentences. For going across an A4 page, for instance, you should have a type size of 12 point. BOOKLIST: research into writing • Designing public documents: a review of research, by Elaine Kempson and Nick Moore, London: Policy Studies Institute, 114 RESEARCH INTO WRITING 1994. Useful advice for those designing forms and other docu- ments, with details of many of the experiments on which this advice is based. This classic ranges over typo- graphy and layout, illustrations and tables, effective writing and evaluating design. Resignation letters These can be wonderfully liberating to do, especially when you are deeply unhappy. We also have systematic reviews, but these are written in the form of scientific papers and the term really refers to a research technique rather than a type of writing. If you are asked to do so, look carefully at other review articles that have already appeared in that journal (see evidence-based writing). Make sure you have in writing what the editor wants you to do – the precise topic, and in what form. You will also need to know such details as length, charts or tables, degree of original statistical analysis required, deadline for the article and other relevant conditions (such as will you get paid? Look in particular at the structure: most review articles (though not systematic reviews) move away from the traditional IMRAD structure and follow the structure for editorials and feature articles. In general they start off with a first sentence that should attract attention, go on to set up the question they are to address, develop an 115 THE A–Z OF MEDICAL WRITING argument that addresses it (one step per paragraph) and finally, at the end of the article, come to rest with the message.

The focus so far has been on randomised con- trolled trials in patients with medical conditions LARGE SIMPLE TRIALS requiring treatment or a medical intervention of some sort cheap 25mg lioresal mastercard. Such designs do apply to situa- It has become recognised over time 10mg lioresal for sale, particularly tions such as trials in normal healthy women in the fields of cardiovascular disease and cancer, in which alternative forms of contraception are being tested. In terms of trial size, the smaller the uate alternative strategies for preventing disease potential benefit, essentially the effect size, then or for detecting its presence earlier than is rou- the larger the trial must be in order to be rea- tine. In such cases, it may be impossible to be practical, they must be in common diseases in randomise on an individual subject basis. Thus an order to recruit the required numbers of patients investigator may have to randomise communities in a reasonable time frame. They must be testing to test out different types of health promotion a treatment that has wide applicability and can be or different types of vaccines, when problems easily administered by the clinicians responsible of contamination or logistics, respectively, mean or the patients themselves. The treatments must that it is better to randomise a group rather than be relatively non-toxic else the small benefit will an individual. The trials must be simple in structure and restricted as antenatal care model with a standard care model. They also need to be simple in this respect, for the responsible PHASE IV TRIALS – POST-MARKETING trial centre to cope with the large amounts of SURVEILLANCE patient data collected. One example of such a trial tests the value of aspirin in patients with cardiovascular disease. However, within this estimates of absolute survival gain were (as post-registration period studies may be carried expected) small but the benefits in public health out for a variety of purposes, some within GENERAL ISSUES 17 their existing licence and others out-with that how is the size of a trial comparing three treat- licence. Studies may also be undertaken in ments, A, B and C, determined, since there are countries where a marketing authorisation has now three possible anticipated effect sizes that not been approved, in which case they are one can use for planning purposes? These corre- regulatory or Phase III-type studies, at least spond to the treatment comparisons A–B, A–C for that country. The number of patients required for expand the indications listed on a marketing each of these comparisons may give three very authorisation either for a different disease or a different sample sizes. They decide which of these will form the basis for the may be undertaken to gain more safety data for final trial recruitment target, N. The trial will then newly registered products: this latter situation is randomise the patients equally into the three treat- more usually what is considered as a true Phase ment groups. A good ceutical companies may be to increase sales, but example of the use of such a design is the previ- if the means of doing so is via answering a useful ously mentioned trial in post-menopausal patients scientific or medical question then this should be with breast cancer in which three options are of benefit both to society and to the company. Classic examples such as the RISC particular problems in data monitoring. For Group trials13 looking at the cardiovascular ben- example, if an early advantage appears to favour efits of aspirin are studies of licensed products to one particular treatment and this suggests the trial expand their use. Then it may not be clear whether the randomisation between the other treatment groups should or ALTERNATIVE DESIGNS should not continue. Were the trial to stop early, then the questions relating to the other For illustrative purposes we have used the two- comparisons are unlikely to have been resolved arm parallel group RCT but these designs can be at this stage. Should the (reduced) trial continue generalised to compare three or more groups as then there may be very complex issues associated appropriate. At the onset of the trial, the clinician has to assess whether or not all the MORE THAN TWO GROUPS three options (A, B or C) available for treatment are suitable for the particular patient under Although not strictly a different design, a parallel examination. If any one of these were not thought group trial with more than two treatments to com- to be appropriate (for whatever reason), then the pare does pose some difficulties. Suppose later in I - Placebo the trial, an interim analysis suggests recruitment to A is no longer necessary and that arm is Eligible and closed. For future patients, the clinician now has consenting Random II - Atorovastin patients with allocation alone to assess whether or not only the two options (B dyslipidaemia to or C) are suitable for the particular patient under in visceral treatment III - Fish oil alone examination. As a consequence, the patients now obsesity going into the trial are no longer potentials for A and hence may be somewhat different than those IV - Atorovastin and fish oil entering at the earlier stages. Although this will not bias the final comparison between B and C,it Figure 2. Randomised 2 × 2 factorial trial to does imply that there will be a bias if the patients determine the value of atorovastin, fish oil or both entering at this stage are compared with those in patients with dyslipidaemia in visceral obesity. However, if they were related, for example, III) and this estimates the so-called fish oil by perhaps three doses of the same drug, then a atorovastin interaction. For example, suppose both note of this structure may change the approach the main effect of fish oil alone and the main to design from that outlined here. As is the situation here, factorial randomised to either atorovastin alone, fish oil designs can be of a double placebo type, where alone, both or neither (placebo) to investigate subjects of Group I of Figure 2.

CHAPTER 43 IMMUNIZING AGENTS 653 for healthy older adults and those with chronic respiratory 25mg lioresal fast delivery, immune globulin or varicella-zoster immune globulin may be cardiovascular cheap 10mg lioresal with visa, and other diseases. Compared to healthy, immunocompetent individuals, the an- tibody response to immunization is usually adequate but re- Use in Cancer duced in immunosuppressed persons. Also, with hepatitis For patients with active malignant disease, live vaccines B vaccine, antibody concentrations should be measured and should not be given. Although killed vaccines and toxoids booster doses given if antibody concentrations fall. When possible, patients should receive (MMR, varicella, yellow fever) should generally not be given needed immunizations 2 weeks before or 3 months after im- to people with HIV infection, other immune diseases, or im- munosuppressive radiation or chemotherapy treatments. In addition, patients who have not received HIV infection should receive inactivated vaccines. If an im- chemotherapy for 3 to 4 weeks may have an adequate anti- munosuppressed person is exposed to measles or varicella, body response to influenza vaccine. NURSING Immunizing Agents ACTIONS NURSING ACTIONS RATIONALE/EXPLANATION 1. Read the package insert, and check the expiration date on Concentration, dosage, and administration of biologic products all biologic products (eg, vaccines, toxoids, and human im- often vary with the products. Also, use reconstituted prod- ucts within designated time limits because they are usually stable for only a few hours. The vastus lateralis is the largest skeletal muscle mass in the infant and the preferred site for all intramuscular (IM) injections. With measles, mumps, rubella (MMR) vaccine, use only The reconstituted preparation is stable for approximately 8 h. If not the diluent provided by the manufacturer, and administer the used within 8 h, discard the solution. Give hepatitis B vaccine IM in the anterolateral thigh of in- Higher blood levels of protective antibodies are produced when the fants and young children and in the deltoid of older children vaccine is given in the thigh or deltoid than when it is given in the and adults. Although the IM route is preferred, the drug can be buttocks, probably because of injection into fatty tissue rather than given SC in people at high risk of bleeding from IM injections gluteal muscles. Give IM human immune serum globulin with an 18- to To promote absorption and minimize tissue irritation and other ad- 20-gauge needle, preferably in gluteal muscles. If the dose is verse reactions 5 mL or more, divide it and inject it into two or more IM sites. Aspirate carefully before IM or SC injection of any immu- To avoid inadvertent IV administration and greatly increased risks nizing agent. Have aqueous epinephrine 1:1000 readily available before For immediate treatment of allergic reactions administering any vaccine. After administration of an immunizing agent in a clinic or To observe for allergic reactions, which usually occur within 30 min office setting, have the client stay in the area for at least 30 min. Decreased incidence and severity of symptoms when given to modify disease processes 3. Observe for adverse effects Most adverse effects are mild and transient. The risk of serious adverse effects from immunization is usually much smaller than the risk of the disease immunized against. Adverse effects may be caused by the immunizing agent or by foreign protein incorporated with the immunizing agent (eg, egg protein in viral vaccines grown in chick embryos). General reactions (1) Pain, tenderness, redness at injection sites Local tissue irritation may occur with injected immunizing agents. It is a edema, urticaria, angioneurotic edema, severe respiratory medical emergency that requires immediate treatment with SC epi- distress) nephrine (0. Anaphy- laxis is most likely to occur within 30 min after immunizing agents are injected. Symptoms are usually relieved by acetaminophen, antihistamines, and corticosteroids. With DtaP (1) Soreness, erythema, edema at injection sites These effects are common (2) Anorexia, nausea (3) Severe fever, encephalopathy, seizures These are rare adverse reactions and less likely to occur with the acellular pertussis component now used. If they occur, they are thought to be caused by the pertussis antigen, and further admin- istration of pertussis vaccine or DTP may be contraindicated. With Haemophilus influenzae b vaccine—pain and erythema These effects occur in about 25% of recipients but are usually mild at injection sites and resolve within 24 hours.

In order to record from cell bodies deeper within neural tissues discount lioresal 10 mg with amex, Kruger (Kruger and Aiple buy lioresal 25 mg with amex, 1988), Wise (Wise and Najafi, 1991), Normann (Jones and Norman, 1992), Eckhorn (Eckhorn et al. These electrode arrays have enabled the simultaneous recording of multi- and single-unit activity from large numbers of neurons in anesthetized animals and in behaving animals. Furthermore, the signal-to-noise ratio of this technique allows one to directly record the neural activity patterns in limited areas of the cerebral cor- tex in real time, and in response to single presentations of sensory stimuli in only moderately restrained animals. It is hoped that the technique will allow systems-level neuroscientists to begin to understand the role of the temporal features of the ensem- ble responses in distributed neural processing. This chapter explores the use of an array of 100 penetrating electrodes (the Utah Electrode Array or UEA) to simultaneously record from large numbers of multiple and single units in the visual cortex of the anesthetized cat. This number of electrodes is su‰ciently large that imaging of the neural activity of localized regions of the ce- rebral cortex is becoming possible. While this microelectrode array currently is being used to study many di¤erent aspects of cortical information processing, we summa- rize here how it can be used to study three basic features of the cortical functional architecture: the neural representations of ocular dominance, orientation sensitivity, and spatial visuotopy. We also demonstrate its use in recording ensemble responses to single presentations of simple visual stimuli. The data obtained from these studies are directly relevant to the problems of devel- oping cortically based sensory and motor neuroprostheses where large numbers of individual neurons must be selectively recorded from or stimulated. We conclude the Imaging 2-D Neural Activity Patterns 45 chapter with a discussion of the use of these microelectrode arrays as a means for restoring a lost sensory sense in those with profound blindness. When implanted in motor pathways, these arrays could also enhance limited or lost motor function in individuals with spinal cord injury or with demyelinating disorders. Measurement Techniques and Instrumentation Experiments were performed under animal care and experimental guidelines that conformed to those set by the National Institutes of Health. Only a brief description of the animal preparation, maintenance, and surgical procedures is given here be- cause they have been fully described elsewhere (Nordhausen et al. Felines were inducted with Telazol, cannulated, intubated, and their heads immobilized. The animals were artificially ventilated and anesthesia was maintained with halothane (approximately 0. The visual cortex was ex- posed by a 1- to 2-cm-diameter craniotomy and the dura reflected. The pupils were dilated, the nictitating membranes were retracted, and the eyelids were sutured open. Gas- permeable contact lenses were placed in each eye to protect the corneas. The retinas were back-refracted onto a tangent screen and the locations of retinal landmarks were recorded on the screen to locate the area centralis (Bishop et al. An acute configuration of the Utah Electrode Array (Cyberkinetics Neurotech- nology Systems, Inc. An electron micrograph of the UEA and a light micrograph of the implant array system are shown in figure 3. The electrode impedance measured with a 1-kHz, 100-nA, sinusoidal signal ranged between 200 and 400 kW, with the typical impedance around 300 kW. The UEA was implanted to a depth of approximately 1 mm at the junction of the lateral and posterior lateral gyri. Neural activity as well as the state of the visual stimulus was recorded by a 100- channel data acquisition system (Cyberkinetics Neurotechnology Systems, Inc. Further details of the data acquisition system are available elsewhere (Guillory and Normann, 1999). In the experiments described in this chapter, we collected data from both eyes and recorded activity on 98 of the possible 100 electrodes. No data were recorded on the remaining two channels because these two amplifiers had known problems. The array is connected to a connector board by 100, 25-mm- diameter insulated wires. Visual Stimulus All stimuli were provided by a 17-inch computer monitor placed at the approximate visual space representation of the area centralis and 95 cm from the eye. A number of di¤erent visual stimuli were produced by software devel- oped by the authors. The stimuli used to evoke the responses described in this chap- ter were sinusoidal gratings, single drifting bars, and a random checkerboard pattern.