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By U. Sugut. Saint Norbert College. 2019.

The services that make up a None of the rising indicators of research national health system are usually too numer- activity described in Chapter 2 is discount sildigra online mastercard, on its own cheap 120mg sildigra with mastercard, a ous to monitor comprehensively purchase sildigra 25 mg visa. The practi- guarantee of products and strategies that will help cal alternative is to choose a set of measurable us reach universal health coverage. Collectively, coverage indicators to represent, as tracers, the however, these upward trends signal the grow- overall quantity, quality and equitable delivery ing volume of information and evidence that will of the services to be provided, including ways infuence health policy and practice in low- and to ensure financial protection. Most countries around pragmatic interpretation of universal coverage the world now have, at least, the foundations on in any given setting so that each representa- which to build efective national health research tive intervention, whether a health service or systems. Some have much more than the founda- a mechanism of financial protection, is acces- tions; they have thriving research communities. However, when coverage is partial, questions will grow as the changing causes of ill- some people may beneft more than others. For health are tracked by new interventions and tech- this reason, measures of coverage should reveal, nologies. Te response to previous successes and not simply the average accessibility of services in new challenges is to formulate a more ambitious a population, but also the coverage among difer- defnition of universal coverage – a new research ent groups of people classifed by income, gender, agenda – and to generate yet more evidence to ethnicity, geography and so on. Seeking uni- that the greatest progress in providing services versal health coverage is a powerful mechanism for maternal and child health has been made by for continuing to seek better health. Tis is a form of “progressive universalism” in which The path to universal the poorest individuals gain at least as much as health coverage, and the the richest on the way to universal coverage (6). Te point about measurement, however, is that path to better health disaggregated data must be applied to the right indicators in order to monitor the implementa- Chapter 3 presented 12 case-studies that showed, tion of a chosen policy on equity. Te frst group of ques- actually, or potentially, infuence health policy tions deals with improving health. Tere are many such exam- burden of disease in any setting, what services ples that are not described in this report, but two are needed, how can universal coverage of these from Chapter 3 that deal with service coverage and services be achieved, and how does wider cov- fnancing are revisited here. Tis frst group of trolled trials conducted in Ethiopia, Kenya, Sudan questions is the principal concern of this report. Te answers will come partly the basis of this evidence, WHO recommended from the large body of existing information on that SSG and PM could be used as a frst-line treat- specifc indicators, but new research will also be ment for visceral leishmaniasis in East Africa. One product of this research will be a Second, a systematic review of evidence from set of common indicators for comparing progress Brazil, Colombia, Honduras, Malawi, Mexico and towards universal coverage across all countries. Nicaragua found that conditional cash transfers It will ofen be possible to satisfy the defnition (CCTs) were associated with increased use of health of universal coverage with regard to one, several services and better health outcomes (8). Tese fnd- or perhaps all monitored health services – immu- ings will stimulate further research studies of the nization against measles, access to antiretroviral utility of CCTs in other countries. The questions about how to achieve research that will show how to make health universal health coverage range from ques- systems more resilient to environmental threats tions about the causes of ill-health, through such as extreme climate events, or research methods for prevention and treatment, to ques- into how health systems can reduce their own tions about the performance of health services. Tese are important Research must find out how to improve the subjects for research, but ancillary to the main coverage of current interventions and how to theme of research for universal health coverage. Research must explore the development and use of both “software” (such as schemes for service provision) and “hard- Research for universal health ware” (R&D for commodities and technology). In general, erage will be made by fnding local answers to successful research stimulates, and is stimu- local questions. For this reason, all nations need lated by, a cycle of enquiry in which questions to be producers as well as consumers of research. To become productive in research requires Te design of a research study is usually a com- a functional national research system. Such a promise because the most robust evidence and system must have the capacity to set priorities; the strongest inferences typically come from to recruit staf and build research institutions; the most costly and lengthy studies (e. Te choice of design ards; to use research to infuence health policy also depends on the need to generalize from and practice; and to monitor and report on the one setting to another; results are more likely processes, the outputs, the outcomes and impact. Although curiosity-driven investi- for instance, to assess the efcacy of drugs and gations have an essential place in the research vaccines (governed by physiological factors), but landscape, this report places high value on stud- observational studies are ofen used to resolve ies that address major health concerns and which operational questions about how drugs and respond to present and future gaps in service vaccines are best delivered by health services coverage and fnancial risk protection. Standard (infuenced by local systems and behaviours). To address the research age, it has also highlighted the co-benefts for priorities, once they have been chosen, inves- health of research done in other sectors, such as tigations are needed throughout the research 133 Research for universal health coverage cycle: measuring the size of the health problem; is easier in a common research language, understanding its cause(s); devising solutions; which would require a uniform and systematic translating the evidence into policy, practice approach to the classifcation, collection and and products; and evaluating efectiveness afer collation of data. Tose with a stake in Its purpose is to transmit the facts and fndings the research process are diverse; they include of health research in a standard way to sponsors, decision-makers, implementers, civil society, governments and the public; to identify gaps and funding agencies, pharmaceutical companies, opportunities for research, which are vital in set- product development partnerships, and research- ting research priorities; to carry out compara- ers themselves. Te roles of national and inter- ble analyses of the quality and productivity of national research funding agencies – who have research output; to identify instances of research substantial leverage – include promoting high collaboration; and to streamline peer review and standards of objectivity, rigour and account- scientifc recruitment. Te new trend is that Efective research requires transparent and long-established “north–south” links are being accountable methods for allocating funds, and supplemented by “south–south” collaboration. However, it is the people who do research tinue to be important because, for example, the who are most critical to the success of the research burden of noncommunicable diseases, up to now enterprise. Consequently, the process of build- largely a concern of the rich world, is growing ing research capacity should be spearheaded by in low-income countries. High-income countries staf recruitment and training, with mechanisms also have a pool of trained researchers from low- to retain the best researchers. Codes of between diferent kinds of international linkages research ethics have been written to uphold hon- is becoming less relevant. Connections of all esty, objectivity, integrity, justice, accountability, sorts are needed to enhance peer-to-peer learn- intellectual property, professional courtesy and ing, to foster joint research endeavours, and to fairness, and good stewardship of research on share resources. Te essential codes of practice as forces in research, initiating a multinational are already in use in many countries. Although collaboration, rather than simply joining as an internationally agreed standards will ofen need invited participant, is a statement of growing to be updated and adjusted to local circum- research confdence. When the too few formal publications of routine opera- fndings of research are turned into policy and tional research. Translational research could be boosted with Although a wide range of fundamental and stronger incentives for the research community. Incentives should Implementation and operational research, and make reference, not only to publications in high- health policy and systems research – bringing impact scientifc and medical journals, but also to scientists and decision-makers together – are measures of infuence on policy and practice. In making the link between research and To accelerate the process, research should be policy, private for-proft research companies (in strengthened not only in academic centres but areas such as biotechnology, pharmaceuticals, also in public health programmes that are close etc. A growing number of health Te greater the contact between researchers and products are being created through partner- policy-makers, the greater will be the mutual ships between the public and private sectors, understanding. A variety of methods can be used making explicit links between various organi- to train decision-makers to use evidence from zations involved in the discovery, development research, and to train researchers to understand and delivery of new technologies. Te use of data Chapter 2 described the role of DNDi in coordi- (especially the large volume of data that are col- nating the development of anthelmintic drugs by lected routinely), evidence and information can several pharmaceutical companies. It has been pointed out that civil positions where they can help to frame policy- society has a role in setting research priorities, related questions which lend themselves to spe- but public engagement in research should be cifc research studies, and to challenge decisions wider in scope. Staf rotations between health the source of government funds for research, are ministries and research institutions are an aid entitled to share in all aspects of the investiga- to communication, and research staf employed tive process; their continued backing depends on explicitly to carry out knowledge translation will being able to listen to, understand, believe in and help to bridge the gap. Public engagement via Te application of research fndings is the media, policy debates and open evaluations, more likely if there are formal procedures for works towards these ends.

If not order sildigra visa, as a rule 120mg sildigra, you should first write the text in your mother tongue purchase sildigra 100 mg overnight delivery. If you happen to have the available capacity and/or uncommitted items in your budget, you should also plan an English version in the mid- term. The reason: a text that goes around the world has 10 to 100 times as many readers as a text that does not exist in English. Furthermore, you can only remove the copyright for other languages if you translate your text into English. Therefore, the road to multilingualism leads via the English version. The editorial team Editors The editors structure the material, define the chapters and choose the authors. As soon as the authors have supplied their texts, the editors review the contents, discuss any questions not yet clarified and send the chapter to be proof-read. The number of doctors who only write moderately well is higher than you would think. This is not surprising, for a doctor does not need to be a brilliant writer in order to be a good doctor. Someone who writes a textbook has to put the contents in order and then write it all down in simple sentences. A textbook editor who has skilled authors who present their material in an inadequate order and in a form that is barely comprehensible, has to take the revision of the chapters into his own hands. In some cases, he will edit texts very carefully indeed. But what if the editor is not able to absorb the stylistic and didactic finish, and achieve the linguistic harmony of the chapters? Then revision is delegated to external assistants, usually to medical editors. This incurs additional costs which need to be allowed for at the planning stage. Over and above the textual and stylistic supervision of the project, the editor has an additional sacred duty. He has to bring the texts submitted by his authors into the public domain. Everyone who has ever been involved in writing a medical textbook knows from stories or from his own experience about those exasperating cases where good texts evolve during long nights of work and then are published either years later or not at all. This means that as soon as an author submits a text, you are under obligation. You must publish the text and increase the fame and reputation of your authors to the best of your ability. If you have decided to publish finished texts on the internet before publishing them in a book, you should put them on the internet very quickly, preferably within 4 weeks of submission. The world needs one hundred doctors assured and the project accounts are well-filled, it would be a graceful gesture to pay the authors their agreed fee, or at least an instalment. Editors should be grateful to their authors and demonstrate this gratitude freely. The editor is not only there to organise and delegate: the third duty of the editor is to bear a part of the work on his own shoulders. The more the editors write, the better they understand their authors and the more qualified they are to give advice. Mentor A young editor profits from discussing his textbook project with an experienced colleague; an older editor should seek the advice of a good friend and colleague. It is possible to publish a book as a lone wolf, but it is easier to lose your way alone than in pairs. It is not only the younger colleagues who refuse the help of the older ones; sometimes the older ones no longer possess the mellow goodwill to watch their younger colleagues working on projects for which they themselves are too old. Medical Readers In the section on editors, we saw that medical readers may be needed to help with the stylistic and didactic finishing of a book. Medical readers are often doctors themselves, and a proof-reader with 20 years experience can be a valuable addition to an editorial team. The additional financial burden should be allowed for in the budget, but it is worth every penny when editors are unable to perfect texts for the final print version due to lack of time. Proofreaders There is no such thing as an error-free book, but you should make every effort to produce as perfect a text as possible – gifted proofreaders can help you. Proofreaders are the last ones to work on the chapters before they are put together as a whole. It is not easy to 30 Time frame find good proofreaders. Secretariat A text passes through several stages before it is published. The stages which it must complete before it is incorporated in HIV Medicine are shown in Table 2. For each text, a careful account is kept of the stage it has reached. In the production of HIV Medicine, this task is performed by the editors; other projects have a project secretariat. If all the authors get to work straight away, a textbook project can theoretically be completed in 6 months. For the first edition, this can be anything from 100 to 400 hours. However you organise it: the first edition means work and stress. The world needs one hundred doctors and more so in the subsequent ones, that the workload is reduced to between a third and a quarter of the initial number of hours. Deadline The co-authors have to read up on their subject, structure the material, write and correct the text. This needs to be organised and fitted in to the full schedule of a busy hospital doctor. If the circumstances are good – the colleague is highly motivated, happens to be on holiday and throws himself enthusiastically into his work – it is realistic that a chapter of 20 pages can be written in 6 weeks. So do not be afraid to ask your co-authors if they can submit their text “at the end of next month”. In other cases, more time may be required, but it does not make sense to set a deadline too far in the future. If you give someone 12 months, he will rarely start work before the last four weeks. Therefore, a deadline of four months should only be extended to six months in justified exceptions (post-doctoral lecture qualification, work on an important publication, etc.

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Epilepsia 1997; tin on brain GABA order sildigra 100 mg without prescription, homocarnosine generic sildigra 25 mg without prescription, and pyrrolidinone in epi- 38:399–407 cheap sildigra amex. Acute and chronic molecule resonances in 1H NMRspectra of human brain. Magn alterations in human cerebral GABA levels in response to topira- Reson Med 1994;32:294–302. GABA changes with viga- spectroscopic study of rat brain in vivo. J Cereb Blood Flow batrin in the developing human brain. GABA levels in the brain: a target for vigabatrin-induced increases in cerebral GABA. New NMR measure- assessed using 1H-magnetic resonance spectroscopy. Measuring brain GABA in patients with com- Psychiatry 1999;56:1043. Measuring human brain GABA dence of reduced cortical GABA levels in localized 1-H-MR in vivo: effects of GABA-transaminase inhibition with vigaba- spectra of alcohol-dependent and hepatic encephalopathy pa- trin. Functional imaging in the epilepsies proton MRS: GABA and glutamate. Adv Neurol measurements of 2-pyrrolidinone in human brain in vivo. Nonoxidative glucose and the measurement of neuronal pH in patients with epilepsy. Wenner-Gren International Symposium regulatory properties of the brain glutamate decarboxylases. Two forms of the gamma- functional magnetic resonance imaging of the brain. Annu Rev aminobutyric acid synthetic enzyme glutamate decarboxylase Biophys Biomol Struct 1998;27:447–474. Adv Exp Med Biol 1999;471:99–109 into tricarboxylic acid cycle derived metabolic pools in neurons 136. Lactate rise and glia during and after sensory stimulation. Proceedings of detected by 1H NMRin human visual cortex during physiologi- the International Society for Neurochemistry 3rd International cal stimulation. Proc Natl Acad Sci USA 1991;88:5829–5831 Conference on Brain Energy Metabolism, 1997. Sensory stimulation stimulation on human visual cortex lactate and phosphates using induces local cerebral glycogenolysis: demonstration by autora- 1H and 31P magnetic resonance spectroscopy. Dynamic uncoupling metabolism in astrocytes: physiological, pharmacological and and recoupling of perfusion and oxidative metabolism during pathological aspects. Astrocytes: pharmacology focal brain activation in man. Functional imaging studies: linking mind and muscle glycogen during low-intensity exercise. A model for the regula- blood flow and Metabolism before and after global ischemia of tion of cerebral oxygen delivery. Stimulated changes in delivery on blood flow in rat brain: a 7 Tesla nuclear magnetic localized cerebral energy consumption under anesthesia. Localized energetic sumption in visual cortex of living humans. Adv Exp Med Biol changes with brain activation from anesthesia II: relative BOLD 1997;413:205–208. New York: Freeman, tional MRI: mapping the dynamics of oxidative metabolism. Positron emission tomographic studies of abnormal glucose metabolism in schizophrenia. Infusing cognitive neuroscience into cognitive psy- cerebral blood flow and oxygen consumption in activated chology. Human brain tive CMRO2 from CBF and BOLD changes: significant in- function. Cognitive subtrac- Magn Reson Med 1999;41:1152–1161. Comparison of blood oxygenation and ing and response mode. The physiological basis of atten- K, Lassen NA, Jones T, eds. Quantification of brain function: tional modulation in extrastriate visual areas. Nature Neurosci tracer kinetics and image analysis in brain PET. The glycogen shunt activity of single cortical neurons and the underlying functional and brain energetics. Putative functions of temporal correlations in neo- muscle: a novel role for glycogen in muscle energetics and fa- cortical processing. BANDETTINI Since the inception of functional magnetic resonance imag- CONTRAST IN fMRI ing (fMRI) in 1991, an explosive growth in the number of users has been accompanied bysteadywidening of its range Several types of physiologic information can be mapped of applications. A recent search of the National Libraryof with fMRI. This information includes baseline cerebral Medicine database for articles with fMRI or BOLD (blood blood volume (1–3), changes in blood volume (4), baseline oxygenation-dependent) in the title revealed more than and changes in cerebral perfusion (5–10), and changes in 1,000 citations. Improvements continue in pulse sequence blood oxygenation (11–17). Recent advances in fMRI pulse design, data processing, data interpretation, and the tailor- sequence and experimental manipulation have allowed ing of cognitive paradigms to the unique advantages and quantitative measures of cerebral metabolic rate of oxygen limits of the technique. This chapter describes the receding (CMRO2) changes and dynamic, noninvasive measures of limits of fMRI. Specifically, the limits of spatial resolution, blood volume with activation to be extracted from fMRI temporal resolution, interpretability, and implementation data (18–20). The goal is to give the reader a perspective of the evolution of fMRI in the past 9 years and a sense of excitement regarding its ultimate potential. Blood Volume A user of fMRI primarilyis interested in extracting at In the late 1980s, the use of rapid MRI allowed tracking least one of three types of neuronal information: where neu- of transient signal intensitychanges over time. One applica- ronal activityis happening, when it is happening, and the tion of this utilitywas to follow the T2*- or T2-weighted degree to which it is happening. To extract this information signal intensityas a bolus of an intravascular paramagnetic optimally, an understanding of the basics of some of the contrast agent passed through the tissue of interest (2). As more esoteric details is necessary, which are presented in it passed through, susceptibility-related dephasing increased this chapter. The area under Second, the keyof fMRI interpretation, the neuronal–hemo- these signal attenuation curves is proportional to the relative dynamic transfer function, is described.

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The first is to value the consequences in mone- tary terms as indirect or productivity costs and intangible Target Population and Comparators costs 25 mg sildigra fast delivery. The second is to combine data about length of life and morbidity to provide a single buy 120 mg sildigra, nonmonetary measure The population considered in the analysis should be repre- of impact order sildigra 50 mg on-line. The interventions compared should be relevant to the health and social care choices faced by decision makers. Unless 'do nothing' is Monetary Valuation a valid management strategy, comparison of a new interven- tion with placebo is not appropriate for an economic evalua- Indirect costs represent the value of changes in the amount tion. They are also called productivity or time costs (18,19). With AD, the ability to engage in the normal daily activities of life and leisure is reduced by Opportunity Cost impaired cognitive function and, in some cases, early death. The economic concept of cost is the value of a good or The physical and mental health of carers may also be af- service in terms of its best alternative use, or opportunity fected. Typically, these costs are valued in the same way as cost. Often, the market price or value of the resources used, the time costs of unpaid carers, by using market values of the such as the time of a health care professional, facilities, or time in full health lost, such as average wage rates. However, medicines, is a reasonable approximation of the opportunity indirect or productivity costs do not include the costs of cost or value to society of the services provided. Chapter 89: Cost-Effectiveness of Therapeutics for Alzheimer Disease 1271 Intangible costs represent the monetary value to individu- intervention; current treatment patterns; relevant compara- als and society of health and life per se. In practical terms, tors; and the costs and benefits of current treatment or a determination of intangible costs requires an assessment health care. The initial assessment should be based on a of the amount of money that individuals would accept as synthesis of available data and expert opinion, which re- compensation for reductions in health or life expectancy, quires the development of internally and externally valid or the amount they would be prepared to pay for improve- and logical models that are consistent and robust. Best Nonmonetary Valuation and worst case scenarios should be incorporated to ensure An alternative approach is to estimate individual and social that interactions between key parameters are explored. This approach If the modeling study indicates that clinical or economic combines measures of life-years lost because of early mortal- evidence is highly uncertain, the prospective collection of ity with a value for the morbidity or ill health associated data is required. The objective is to establish whether differ- with the remaining years of life. Examples are quality- ences in clinical and economic endpoints are directly attrib- adjusted life-years (QALYs) and disability-adjusted life- utable to the interventions compared. These are calculated as the number of years controlled evaluations with a high level of internal validity of remaining life weighted by the quality or utility of that are required, such as an integrated economic and clinical life. The utility weight is the relative value of society for controlled trial. Whether randomized, controlled trial states less than full health. If the correlation between The costs and consequences of a disease and health and resource use and the interventions studied is high, even social interventions can occur at different times. For analyses tightly defined explanatory clinical trials may be appropriate that include a time frame of more than 1 year, it is conven- to address the question of efficiency. Alternatively, if the tional to discount the costs and outcomes to present values, correlation is low and other factors, such as patient charac- so that the relative importance of events occurring in the teristics, comorbidities, and organization of health care ser- future, rather than the present, is reduced. Discounting is vices, are equally important determinants of service use, based on the assumption that individuals and society prefer then the most pragmatic trial may fail to provide usable to receive benefits sooner rather than later and to delay economic information. There is some debate about whether outcomes and The costs of the interventions studied should be esti- costs should be discounted at the same rate. The rule of mated from activity data, which quantify resources used, thumb is to use a discount rate of 5% for both and repeat and price or unit cost data. All health and social care activity the analysis with alternative rates for the costs and outcomes. These have focused primarily on the nomic evaluations should ensure that the results are timely, direct costs of illness and so are partial analyses. The economic study have been updated to 1997 figures, with the use of health can use modeling techniques to synthesize secondary and and social care inflation indices, to provide a common price primary data from several sources, or it can analyze data year for comparison. The Which of these techniques is used depends on the type of PPP is the rate of currency conversion that ensures that the question addressed. The advantage of PPPs about the relative costs and outcomes of current and new over conventional exchange rates is that they reflect the price forms of health and social care. The existing literature and levels and purchasing power of the currencies converted data should be reviewed to determine the following: natural (21). The variations 1272 Neuropsychopharmacology: The Fifth Generation of Progress TABLE 89. CARE SETTING, INFORMAL CARE, AND COST PER PERSON (U. DOLLARS, 1997) Mild/Moderate Severe All Source Cost %ICC %CS Cost %ICC %CS Cost %ICC %CS United Kingdom Gray and Fenn, 1993 (7) Community — — 89–94% — — 54% 4,747 — — Long-stay care — — 6–11% — — 46% 45,405 — — Kavanagh et al. Chapter 89: Cost-Effectiveness of Therapeutics for Alzheimer Disease 1273 TABLE 89. ESTIMATED INCREMENTAL COSTS OF ALZHEIMER DISEASE (U. DOLLARS, 1997) Annual Incremental Cost of Care Per Persona No Cognitive Source Disability Mild/Moderate Severe All United Kingdom Kavanagh and Knapp, 1999b (23) Total cost 25,299 35,341 42,886 — Incremental cost — 10,042 17,587 — Souêtre et al. The average cost per person ranges between from large-scale national surveys (22,23,26,27). These variations reflect differences in the establishments (n 3,037) that had been conducted in methods used to collect and analyze the epidemiologic and the middle to late 1980s (22,23). The Canadian studies cost data (31), the range of costs included, timing of the both used the Canadian Study of Health and Ageing, which study, and disease severity and setting of care of the sample surveyed a total of 10,263randomly selected Canadians of people with AD included in the study. Resource use information was collected by interviewing people with disability and their carers. The samples of respond- were derived from a number of sources. One study used ents varied in size from 64 to 679 people. Similar methods secondary analysis of administrative databases in the United were used to identify resource use. These gave aggregate measures of the use lected data prospectively from respondents during 6-month of hospital inpatient care, residential and nursing home ad- (30) and 2-year periods (28). Most studies included vali- missions, and general practitioner consultations for people dated measures to determine the presence and severity of with mental disorders in 1984 and 1985. Cost data from other sources were used to First, the use of screening instruments allows a clear identifi- estimate total expenditure for people with AD (7,33). The cation of people with cognitive disability or AD. However, primary disadvantages of this approach are that the data for the use of a variety of instruments may lead to differences resource use may not be detailed enough to allow a complete in the categorization of people with cognitive problems, so measurement of the range of resources used. In addition, that the comparability of results is reduced.

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Some investigators have found neuropsycho- engagement buy sildigra 100 mg with amex, spatial attention) are also disrupted order 25 mg sildigra visa. However purchase 120 mg sildigra overnight delivery, a large number of studies have found Working Memory subtle or no differences in neuropsychological functioning between asymptomatic HIV-seropositive and HIV-seroneg- One critical cognitive function is 'working memory,' the ative subjects (23–33). Evidence suggests that HIV-seropositive patients may show cognitive deficits (12, persons with HIV infection demonstrate deficits in working 16,20,34,35). In other words, HIV may have a deleterious memory because of the affinity of HIV-1 for frontal–sub- effect on brain function in certain asymptomatic HIV- cortical circuits (45). Given the anatomic evidence for in- infected persons. Evaluating group differences in overall im- volvement of frontal and related subcortical structures in pairment ratings may be the most sensitive and accurate executive functioning and HIV infection, it is not surprising method of assessing neurocognitive impairment in asymp- that executive processes are affected by HIV infection. In a review of 57 studies that examined fact, recent studies have found evidence for the selective im- neuropsychological functioning in asymptomatic persons, pairment of verbal and spatial working memory processes in the median percentage of impaired test performances in HIV-seropositive persons (13,45–49). Deficits of working asymptomatic persons was 35%, and in seronegative persons memory tend to be observed in the later stages of HIV it was 12% (36). In another review of 36 cross-sectional infection (i. In the majority of longi- Patients with subcortical disorders (e. Methodologic differences in study design recognition memory but show fewer false-positive errors and analysis probably account for discrepancies between than are typically seen in patients with cortical dysfunction studies. This pattern, which supposedly reflects a problem Asymptomatic persons at risk for neurocognitive impair- with the retrieval of information rather than difficulties with ment have been found to display one of two patterns of encoding, is also seen in patients with HIV infection (5,7, deficits: (a) depression, psychomotor slowing, and dimin- 12,51). Current research indicates that cognitive impairment is uncommon in asymptomatic HIV-seropositive persons Psychomotor slowing appears to be the most common HIV- (22,37), is not associated with deficits in social or occupa- related neurocognitive deficit and may underlie deficits in tional functioning (9,11), and, when present, is subtle and higher-order cognitive processes (52). Slowed complex cog- limited to a few cognitive domains. Psychomotor and motor impairment in HIV- neurocognitive deficits (9,16). Objective impairments in infected persons has been well documented (5,53) and may HIV disease include psychomotor slowing, forgetfulness, be evident even in the earliest stages of HIV infection (31, and difficulties with attention and concentration. Reaction time tasks have been particularly helpful in later stages of HIV infection (symptomatic HIV and detecting HIV-related cognitive slowing because they allow Chapter 90: Neuropsychiatric Manifestations of HIV-1 Infection and AIDS 1283 for a more precise analysis of the effects of HIV on psycho- TABLE 90. CRITERIA FOR A CLINICAL DIAGNOSIS OF HIV-1-ASSOCIATED DEMENTIAa motor processing (42). Sufficient for diagnosis of AIDS Progression of Neurocognitive Deficits A. HIV-1-associated dementia complex Probable (must have each of the following): The progression of HIV disease is associated with neurologic 1. Acquired abnormality in at least two of the following deficits (54) and deteriorating neurocognitive performance cognitive abilities (present for at least 1 month): attention/concentration, speed or processing of (9,14,36,55). Neurocognitive impairment is a proximal pre- information, abstraction/reasoning visuospatial skills, dictor of AIDS and mortality in HIV-infected persons memory/learning, and speech/language (56–58). Slowed information processing and memory defi- The decline should be verified by reliable history cits before the development of AIDS have been associated and mental status examination. In all cases, when with mortality independently of Centers for Disease Con- possible, history should be obtained from an informant, and examination should be supplemented by trol and Prevention (CDC) clinical stage, CD4 T-lym- neuropsychological testing. At least one of the following: or sociodemographic variables such as age, education, and a. Acquired abnormality in motor function or performance socioeconomic status (58). Patients with advanced HIV dis- verified by clinical examination (e. In addition, prominent psycho- dexterity, perceptual motor skills) or both. Decline in motivation or emotional control or change logic progression in persons with HIV-associated dementia in social behavior. Absence of clouding of consciousness during a period long In 1986, Navia et al. Evidence of another etiology, including active central nervous system opportunistic infection or malignancy, (ADC). These symptoms included cognitive impairment, psychiatric disorders (e. In this landmark study of 70 patients withdrawal; must be sought from history, physical and with AIDS subjected to autopsy, 46 were characterized as psychiatric examination, and appropriate laboratory demented. The majority of the patients with ADC (63%) and radiologic investigation (e. This finding led to problems with the ADC label Possible (must have one of the following): because it was evident from the Navia study that a subgroup 1. Other potential etiology present (must have each of the of patients who did not meet diagnostic criteria for AIDS following): displayed cognitive symptoms associated with HIV infec- a. Other potential etiology is present but the cause of #1 tion. In addition, certain patients displayed some, but not above is uncertain. Incomplete clinical evaluation (must have each of the ADC. Etiology cannot be determined (appropriate laboratory or radiologic investigations not performed). The American Academy of Neurology also adopted this new term for research pur- aFrom the Working Group of the American Academy of Neurology poses (62) (Table 90. However, because the progression of HIV infection to AIDS can now be delayed with aggressive antiretroviral therapy, a focus on HIV rather than on AIDS may be a more appropriate way to classify neurocognitive of symptomatology. Before the introduction of highly active impairment. It has an insidious onset, and patients often exhibit apathy, cognitive and motor slow- although persons with HADmay experience an acceleration ing, and impaired memory, abstract reasoning, and judg- 1284 Neuropsychopharmacology: The Fifth Generation of Progress TABLE 90. DIAGNOSTIC CRITERIA FOR concentration, forgetfulness, mental slowing). In some pa- DEMENTIA DUE TO HIV DISEASE tients, HADprogresses rapidly after the diagnosis has been made (within weeks to months), whereas other patients A. The development of multiple cognitive deficits manifested by both show cognitive stability for months or years or very slow 1. Per- information or to recall previously learned information) and sons in the early stages of HADoften complain of poor 2. They typically present with significantly less impair- b. The cognitive deficits in criteria A1 and A2 each cause significant impairment in social or occupational functioning The later stage of HADcorresponds to ADC as originally and represent a significant decline from a previous level of functioning. Evidence from the history and physical examination or laboratory findings indicate that the disturbance is the direct TABLE 90.

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