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There is no particular reason to examine such things except to acquire a better knowledge of how these processes occur order lithium american express symptoms xxy. Applied research is research that investigates issues that have implications for everyday life and provides solutions to everyday problems generic lithium 300 mg with mastercard medications restless leg syndrome. Applied research has been conducted to study lithium 150mg visa treatment 5th metatarsal avulsion fracture, among many other things, the most effective methods for reducing depression, the types of advertising campaigns that serve to reduce drug and alcohol abuse, the key predictors of managerial success in business, and the indicators of effective government programs, such as Head Start. Basic research and applied research inform each other, and advances in science occur more [7] rapidly when each type of research is conducted (Lewin, 1999). The results of psychological research are reported primarily in research articles published in scientific journals, and your instructor may require you to read some of these. The research reported in scientific journals has been evaluated, critiqued, and improved by scientists in the field through the process of peer review. In this book there are many citations to original research articles, and I encourage you to read those reports when you find a topic interesting. Most of these papers are readily available online through your college or university library. It is only by reading the original reports that you will really see how the research process works. Some of the most important journals in psychology are provided here for your information. Psychological Journals The following is a list of some of the most important journals in various subdisciplines of psychology. The research articles in these journals are likely to be available in your college library. You should try to read the primary source material in these journals when you can. General Psychology American Journal of Psychology American Psychologist Behavioral and Brain Sciences Psychological Bulletin Psychological Methods Psychological Review Psychological Science Biopsychology and Neuroscience Attributed to Charles Stangor Saylor. To really understand psychology, you must also understand how and why the research you are reading about was conducted and what the collected data mean. Learning about the principles and practices of psychological research will allow you to critically read, interpret, and evaluate research. In addition to helping you learn the material in this course, the ability to interpret and conduct research is also useful in many of the careers that you might choose. For instance, advertising and marketing researchers study how to make advertising more effective, health and medical researchers study the impact of behaviors such as drug use and smoking on illness, and computer scientists study how people interact with computers. Furthermore, even if you are not planning a career as a researcher, jobs in almost any area of social, medical, or mental health science require that a worker be informed about psychological research. Social science research on trial: Use of sex stereotyping research in Price Waterhouse v. Journal of Experimental Psychology: Human Perception and Performance, 29(2), 343–362. Describe the principles of the scientific method and explain its importance in conducting and interpreting research. Differentiate laws from theories and explain how research hypotheses are developed and tested. Discuss the procedures that researchers use to ensure that their research with humans and with animals is ethical. Psychologists aren’t the only people who seek to understand human behavior and solve social problems. Philosophers, religious leaders, and politicians, among others, also strive to provide explanations for human behavior. But psychologists believe that research is the best tool for understanding human beings and their relationships with others. Rather than accepting the claim of a philosopher that people do (or do not) have free will, a psychologist would collect data to empirically test whether or not people are able to actively control their own behavior. Rather than accepting a politician‘s contention that creating (or abandoning) a new center for mental health will improve the lives of individuals in the inner city, a psychologist would empirically assess the effects of receiving mental health treatment on the quality of life of the recipients. The statements made by psychologists are empirical, which means they are based on systematic collection and analysis of data. The methods used by scientists have developed over many years and provide a common framework for developing, organizing, and sharing information. The scientific method is the set of assumptions, rules, and procedures scientists use to conduct research. In addition to requiring that science be empirical, the scientific method demands that the procedures used be objective, or free from the personal bias or emotions of the scientist. The scientific method proscribes how scientists collect and analyze data, how they draw conclusions from data, and how they share data with others. These rules increase objectivity by placing data under the scrutiny of other scientists and even the public at large. Because data are reported objectively, other scientists know exactly how the scientist collected and analyzed the data. This means that they do not have to rely only on the scientist’s own interpretation of the data; they may draw their own, potentially different, conclusions. Most new research is designed to replicate—that is, to repeat, add to, or modify—previous research findings. The scientific method therefore results in an accumulation of scientific knowledge through the reporting of research and the addition to and modifications of these reported findings by other scientists. Laws and Theories as Organizing Principles One goal of research is to organize information into meaningful statements that can be applied in many situations. Principles that are so general as to apply to all situations in a given domain of inquiry are known as laws. There are well-known laws in the physical sciences, such as the law of gravity and the laws of thermodynamics, and there are some universally accepted laws in psychology, such as the law of effect and Weber’s law. But because laws are very general principles and their validity has already been well established, they are themselves rarely directly subjected to scientific test. A theory is an integrated set of principles that explains and predicts many, but not all, observed relationships within a given domain of inquiry. One example of an important theory in psychology is the stage theory of cognitive development proposed by the Swiss psychologist Jean Piaget. The theory states that children pass through a series of cognitive stages as they grow, each of which must be mastered in succession before movement to the next cognitive stage can occur. This is an extremely useful theory in human development because it can be applied to many different content areas and can be tested in many different ways. Second, they are parsimonious, meaning they provide the simplest possible account of those outcomes. It can account for developmental changes in behavior across a wide variety of domains, and yet it does so parsimoniously—by hypothesizing a simple set of cognitive stages. The stage theory of cognitive development has been applied not only to learning about cognitive skills, but also to [1] the study of children’s moral (Kohlberg, 1966) and gender (Ruble & Martin, [2] 1998) development.
Diseases
If lowing a bolus purchase lithium australia medications medicaid covers, it applies only when a single-compartment the data are plotted on semi-logarithmic graph paper generic 150mg lithium with visa symptoms xeroderma pigmentosum, with model with first-order elimination kinetics is applicable order lithium australia treatment 7. Extrapolation back to zero time gives the concentration (c0) that would have occurred at time zero, and Key points this is used to calculate Vd: • The ‘one-compartment’ model treats the body as a single, well-stirred compartment. Immediately d following a bolus dose D, the plasma concentration Vd rises to a peak (C ) theoretically equal to D/V and then c 0 d 0 declines exponentially. Half-life can be read off the graph as the time between any kel is inversely related to t1/2, which is given by 0. The slope of the line is the similar to that observed with constant-rate infusion, elimination rate constant, kel: but with oscillations in plasma concentration rather than a smooth rise. This is the case with several of the benzodi- state concentration greater than some threshold value is often azepines (Chapter 18), which have active metabolites with needed to produce a consistent effect throughout the dose half-lives of many days. The mean concentration rises toward a plateau, incorrectly be ascribed to cognitive decline associated with as if the drug were being administered by constant-rate infu- ageing, but resolve when the drug is stopped. That is, after one half-life the mean concentration is 50% Knowing the half-life helps a prescriber to decide whether of the plateau (steady-state) concentration, after two half-lives or not to initiate treatment with a loading dose. However, unlike the constant-rate infu- prescribed once daily, resulting in a less than two-fold varia- sion situation, the actual plasma concentration at any time tion in maximum and minimum plasma concentrations, and swings above or below the mean level. Increasing the dosing reaching 90% of the mean steady-state concentration in frequency smoothes out the peaks and troughs between doses, approximately one week (i. In more urgent peaks are too high, toxicity may result, while if the troughs are situations a more rapid response can be achieved by using a too low there may be a loss of efficacy. Again, these compartments have no precise anatomical meaning, although the central compartment is assumed to consist of 60 (a) 50 Mainly distribution 40 some elimination 30 Mainly elimination some distribution (kinetic homogeneity attained) 20 10 0 1 2 3 4 5 6 7 8 9 10 (b) Time, t Time Figure 3. The eral compartment consists of less well-perfused tissues into same applies when a drug is eliminated by a saturable trans- which drug permeates more slowly. In clinical practice, drugs that exhibit non-linear The initial rapid fall is called the α phase, and mainly kinetics are the exception rather than the rule. This is because reflects distribution from the central to the peripheral com- most drugs are used therapeutically at doses that give rise to partment. Drugs that show non-linear kinetics in the therapeutic range include heparin, phenytoin and ethanol. Implications of non-linear pharmacokinetics include: Although many drugs are eliminated at a rate that is approxi- mately proportional to their concentration (‘first-order’ kinet- 1. Instead, elimination Consider a drug that is eliminated by conversion to an inactive metabolite by an enzyme. The drug concentration and reac- 100 tion velocity are related by the Michaelis–Menten equation (Figure 3. At low concentrations, the rate is linearly related Blood sample 10 Drug Central Peripheral (tissue) compartment compartment 1 Elimination Time Figure 3. The time required to eliminate 50% of a dose increases A young man develops idiopathic epilepsy and treatment is started with phenytoin, 200mg daily, given as a single with increasing dose, so half-life is not constant. A modest increase in dose of such a drug disproportionately phenytoin concentration is 25μmol/L. This is very week later he is complaining of unsteadiness, there is nys- important clinically when using plasma concentrations of, tagmus and the serum concentration is 125μmol/L. Comment Key points Phenytoin shows dose-dependent kinetics; the serum con- centration at the lower dose was below the therapeutic • Two-compartment model. Despite the apparently plasma concentration falls bi-exponentially, instead modest increase (to 150% of the original dose), the plasma of a single exponential as in the one-compartment concentration rose disproportionately, causing symptoms model. In: Clinical pharmacoki- Consequently, increasing the dose causes a netics: concepts and applications, 3rd edn. These are permeable to lipid-soluble drugs, whilst pre- senting a barrier to more water-soluble drugs. The most convenient route of drug administration is usually by mouth, and absorption processes in the gastro-intestinal tract are among the best understood. Unless administered intravenously, most drugs are in gut wall absorbed incompletely (Figure 4. However, differences in bioavailability did account for an epi- Bioavailability of a drug formulation can be measured experi- demic of phenytoin intoxication in Australia in 1968–69. Restoring the original manufactur- ing conditions restored potency but led to some confusion, with Many factors in the manufacture of the drug formulation influ- both toxicity and underdosing. Pharmaceutical factors are therefore important should be by generic name or by proprietary (brand) name. This is determined by the lipid solubility of Time→ the drug and the area of membrane available for Figure 4. Sometimes polar drugs can be absorbed via specific transport processes (carriers). It is usually available only from the company liver, which can extract drug from the portal blood that introduced it until the patent expires. After this, other com- before it reaches the systemic circulation via the hepatic vein. This is called presystemic (or ‘first-pass’) panies can manufacture and market the product, sometimes metabolism. At this time, pharmacists usually shop • ‘Bioavailability’ describes the completeness of around for the best buy. If a hospital doctor prescribes by propri- absorption into the systemic circulation. The amount of etary name, the same drug produced by another company may drug absorbed is determined by measuring the plasma be substituted. The for- bioavailability implies that no drug enters the systemic mulation of a drug (i. This is a particular concern with slow-release or drugs and different pharmaceutical formulations of the sustained-release preparations, or preparations to be adminis- same drug, but also from one individual to another, tered by different routes. Drug regulatory bodies have strict cri- depending on factors such as dose, whether the dose teria to assess whether such products can be licensed without is taken on an empty stomach, and the presence of gastro-intestinal disease, or other drugs. The rate at which a drug enters the body determines for another may give rise to clinical problems unless the the onset of its pharmacological action, and also influences the preparations are ‘bioequivalent’. Regulatory authorities intensity and sometimes the duration of its action, and is therefore require evidence of bioequivalence before important in addition to the completeness of absorption. They provide an approach to improving (brand named or generic) are sufficiently similar for their sub- absorption and distribution. If evidence is presented that a new One approach to improving absorption or distribution to a rel- generic product can be treated as therapeutically equivalent to atively inaccessible tissue (e. This does not imply that all possible pharmacokinetic absorbed and from which active drug is liberated after absorp- parameters are identical between the two products, but that tion. There are two main mechanisms of Oral drug administration may be used to produce local effects drug absorption by the gut (Figure 4.
The specification is essen- a small number of normal volunteers and the rele- tially a problem statement discount lithium 300mg treatment gout. How- should then be accompanied by a pharmacovigi- ever purchase lithium now treatment 4 stomach virus, when the new product is challenging the lance plan purchase lithium line medications on carry on luggage. The plan might include routine adverse position of an older one, then equivalency trials event reporting and periodic safety updates to be usually require very large numbers of patients provided to regulators, and/or recommendations (often hundreds per treatment group). The study may have been a condition of product approval, and it is both reasonable and wise to ensure that the study design Mega-trials can be expected to provide the information that is needed both by the sponsor and the regulators. When it is suspected that there may only be small Unblinded designs that imitate the ordinary clin- differences between active treatments, and when ical situation are the norm. Instead, huge numbers of Finding a new indication is an obvious opportu- patients (tens of thousands) are randomized, ‘the nity to increase market size by enlarging the poten- cards are allowed to fall where they may’, and faith tial pool of patients that can benefit from the is placed in the notion that a large n will automa- product. In this case, two pivotal, well-controlled tically lead to well-balanced treatment groups. If there is the potential demonstrated between treatment groups of even for a new type of clinical hazard to be associated several thousands when enough concomitant con- with new disease being studied, then a safety data- founding factors are analysed (Charlton, 1966). In this for old drugs is often done when companies offer case, efficacy data will normally be required of investigator research grants. The decision to launch a new formulation to observe such niche uses under organized circum- has to be based not only on its technical success but stances can lead to new indications. At the very also according to a financial analysis of the type least, such programs encourage disclosure of new referred to above for new indications. Crucial ideas to the company and allow for some review of information on that question can usually only be the safety aspects of what these inventive indivi- obtained by studying the new formulation using duals are getting up to! New dosage forms Special populations Initial dosage forms are usually those that are most easily developed, most stable and at least reason- Special populations have their own chapters in this ably acceptable to adult patients. In the United tions can often be improved upon, whether for States, many product approvals now come with the matters of convenience (e. Traditional pharmacokinetic approaches are A variety of regulatory approaches are needed usually the first step in assessing whether these when adding to the range of formulations, and events will alter product efficacy or safety. Pharmacokinetic studies are typi- standing commercialization team with representa- cally done at small scale. If the ultimate goal of a given study is mation that can lead to a competitive advantage. It is the marketing team that data are intended to be promoted to ensure that the is the keeper of the strategy, aware of the compe- trial is designed to ultimately allow for those titive environment (both current and future compe- promotional messages. It is especially important Effective collaboration between clinical develop- when entering a very competitive, highly devel- ment and marketing teams in the context of phase oped market place (e. It is also important for new classes when there will be a within-class competi- The clinical–legal interface tor launching within a short timeframe. If, on the one years to have drugs within the same class have hand, the sudden exposure of large numbers of similar labeling verbiage (i. Furthermore, sometimes, when such a signal is observed, a retrospective trawl through the preclinical and 10. International Conference on Harmonization Draft Guidance E2E: Pharmacovigilance planning. To some degree, the location where clinical trials are conducted, its location of the study is dictated by the complexity purpose is to produce clean, reproducible clinical of the protocol, the types of procedures required data in a timely and safe manner. But there ates these data by performing the study protocol can be other factors at play that determine where a on human subjects that it recruits. In other regions, such as This chapter describes different kinds of inves- the United States, there are many public and private tigative sites around the globe and makes the case clinical trial options. Data suggest that in the that operating a successful site requires an infra- United States, approximately 35% of studies take structure that enables the generation of good qual- place at academic medical centers (Figure 11. The infrastructure must include critical The rest occur at a combination of public and business functions such as budgeting, patient re- private, dedicated and part-time investigative sites. Substantial investment in staff and equipment is required to conduct these studies • Phase I site as the phase I site often houses inpatients, and Figure 11. They offer community-based, required in Europe, as it was and continues to be in actual use settings, a feature that sponsors find the United States. Europe’s then more lenient reg- attractive (Zisson, 2002), and can be profitable ulatory environment attracted business (Neuer, because they tend to require less infrastructure 2000), but with the advent of the European Direc- than their dedicated site counterparts. With research studies becoming more pharmaceutical sponsors seek to limit costs and complex and entailing more procedures per subject risk by weeding out weak drug candidates earlier, (Figure 11. Data suggest that phase I spending is rising it takes to perform good-quality clinical research more rapidly than other sectors of the clinical in a timely, ethical and fiscally responsible manner. The clinical investigator is ultimately responsible To complicate matters further, there is a high rate for clinical research conducted at the site. The reasons cited are that clin- accomplished through activities such as obtaining ical research interferes too much with other informed consent, administering study drug, main- responsibilities such as private practice medicine taining and storing medical records and reporting or academic obligations, or they lack the infra- adverse and serious adverse events. The Tufts Center research mostly because it is scientifically reward- study reveals that the number of investigators in ing, but they are also attracted to the financial many regions of the world is actually rising. In rewards and the opportunities to improve patient addition, there are now certification programs for care (Lamberti, 2005). With clinical trials number- investigators, so it is possible that those who invest ing in the tens of thousands, there is industry-wide in preparing for and receiving certification by concern that there may be a 15% shortfall in the examination may be less likely to drop out. The examinations test knowl- patient recruitment activities edge in study conduct, regulations and ethical issues. Because of transmitting study data the ever growing number of details that comprise clinical studies, coordinators can easily become scheduling patient visits bogged down and, ultimately, very frustrated. This situation can lead to a decline in work quality meeting with principal investigators or a high level of employee turnover. According to a recent survey, 53% of study coordinators have meeting with study monitors been in their jobs for three years or less (Borfitz, 2004). This includes offering good closing out the study compensation and benefits, offering ongoing train- ing and making decisions to hire more full- or part- participating in preparing proposals for solicit- time coordinators if the workload expands beyond ing new studies the capacity of the existing staff complement. He is the individual who interfaces with sponsors, investigators, study coordinators collecting metrics. Clinical trials cannot operate without regulatory Attention to detail will also serve to improve the oversight. As part of that chain, to and that the clinical data are properly collected, investigative sites share the responsibility for con- recorded and forwarded (Miskin and Neuer, 2002). Estimates vary as to the percentage • Master charts of electronic solutions used to collect and submit • Source documents clinical data, but they are generally in the range of 15–20% of clinical trials (Borfitz, 2004). Data tify creating a position for a full-time regulatory that are missing, placed in the wrong field or out of manager, but once the number of studies con- range are immediately spotted, thereby reducing ducted annually approaches eight or more, a full- the number of queries. And, to facilitate the more or part-time regulatory affairs position needs to be rapid sending of electronic data to sponsors or created. Records critical to safety evaluations should be may be retained for even longer periods if required reported to the sponsor according to the reporting requirements and within the by applicable regulatory requirements or if time periods specified by the sponsor in required by the sponsor. In particular, a visiting study monitor will expect to have direct access to trial documents, requiring suspected serious unexpected adverse so having them readily available is important. Complying with these reporting requirements work, but the essence of clinical research is defined can be greatly facilitated if they are done electro- by specific tasks such as nically.
