By J. Cronos. Simpson College, Redding California.
The next step involves FDA re- pecially for drugs used to treat acquired immunodeﬁciency view of the data obtained in the animal studies discount 400mg hoodia with mastercard herbals soaps. Since then order hoodia 400 mg with visa queen herbals, new drugs are categorized according to undergoes clinical trials in humans. Most clinical trials use a their review priority and therapeutic potential. Most newly approved drugs are 1S pre- In Phase I, a few doses are given to a few healthy volun- scription drugs. In Phase II, ing the transfer of drugs from prescription to OTC status, and a few doses are given to a few subjects with the disease or may require additional clinical trials to determine safety and symptom for which the drug is being studied, and responses effectiveness of OTC use. Numerous drugs have been trans- are compared with those of healthy subjects. In Phase III, ferred from prescription to OTC status in recent years and the the drug is given to a larger and more representative group trend is likely to continue. In double-blind, placebo-controlled designs, for use may be different, and recommended doses are usually half the subjects receive the new drug and half receive a lower for the OTC formulation. For example, for OTC ibupro- placebo, with neither subjects nor researchers knowing who fen, which is available under its generic and several trade receives which formulation. In crossover studies, subjects names (eg, Advil) in 200-mg tablets and used for pain, fever, serve as their own controls; each subject receives the ex- and dysmenorrhea, the recommended dose is usually 200 to perimental drug during half the study and a placebo during 400 mg three or four times daily. Other research methods include control stud- Motrin is the common trade name and dosage may be 400, 600, ies, in which some clients receive a known drug rather than or 800 mg three or four times daily. Phase III studies help evaluation of evidence that the consumer can use the drug to determine whether the potential benefits of the drug out- safely, using information on the product label, and shifts pri- weigh the risks. With OTC drugs, the may become evident during the postmarketing phase as the client must make these decisions, with or without consulta- drug is more widely used. Questions to be answered in- in recent years, partly or mainly because of the increased post- clude the following: marketing surveillance. Can consumers accurately self-diagnose the condition to streamline the approval process have allowed unsafe drugs for which a drug is indicated? Can consumers read and understand the label well helps clients with serious diseases to gain effective treatment enough to determine the dosage, interpret warnings and more quickly. Relating the unknown to the known Having drugs available OTC has potential advantages and aids learning and retention of knowledge. This autonomy; faster and more convenient access to effective allows you to predict therapeutic effects and to predict, treatment; possibly earlier resumption of usual activities of prevent, or minimize adverse effects by early detection daily living; fewer visits to a health care provider; and pos- and treatment. Concentrate your study efforts on major characteris- symptoms/conditions and recommended treatments. These include the main indications for use, com- advantages include inaccurate self-diagnoses and potential mon and potentially serious adverse effects, conditions risks of choosing a wrong or contraindicated drug, delaying in which the drug is contraindicated or must be used treatment by a health care professional, and developing ad- cautiously, and related nursing care needs. Keep an authoritative, up-to-date drug reference read- When a drug is switched from prescription to OTC status, ily available, preferably at work and home. Use the refer- increase because health insurance policies do not cover OTC ence freely whenever you encounter an unfamiliar drug drugs. For the year 2000, it was estimated that Americans or when a question arises about a familiar one. Also, write notes, answers to review questions, deﬁnitions of new terms, and trade names of SOURCES OF DRUG INFORMATION drugs encountered in clinical practice settings directly into your pharmacology textbook. The mental pro- There are many sources of drug data, including pharmacol- cessing required for these activities helps in both initial ogy textbooks, drug reference books, journal articles, and learning and later retention of knowledge. Mentally rehearse applying drug knowledge in nursing textbook is usually the best source of information because it care by asking yourself, What if I have a client who is describes groups of drugs in relation to therapeutic uses. What must I do to safely administer reference books are most helpful in relation to individual the drug? Two authoritative sources are the American Hospital the drug and for what must I observe the client after drug Formulary Service and Drug Facts and Comparisons.
What makes Six Sigma appear new is the rigor of tying improvement projects to key busi- ness processes and clear roles and responsibilities for executives discount 400mg hoodia herbs chips, champi- ons hoodia 400 mg with visa wicked x herbal, master black belts, black belts, and green belts. The aim of Six Sigma is to reduce variation (eliminate defects) in key business processes. By using a set of statistical tools to understand the fluctuation of a process, management can begin to predict the expected outcome of that process. If the outcome is not satisfactory, associated tools can be used to further understand the elements influencing that process. Six Sigma includes five steps—define, measure, analyze, improve, and con- trol—commonly known as DMAIC: • Define: Practitioners begin by defining the process. They identify the key characteristics important to the customer along with the processes that support those key characteristics. They then identify existing output conditions along with the process elements. Key character- istics are categorized, measurement systems are verified, and data are collected. The intent is to convert the raw data into information that provides insights into the process. These insights include identifying the fundamental and most important causes of the defects or problems. Solutions to the problem are developed, and changes are made to the process. In this step, the company can judge whether the changes are beneficial or if another set of changes is necessary. Quality Im provem ent System s, Theories, and Tools 73 • Control: If the process is performing at a desired and predictable level, it is put under control. For Six Sigma, the primary theory is, If we focus on reducing vari- ation, we will have more uniform process output. Theory of Constraints Theory of constraints (TOC) is a thinking process that focuses on system improvement to maximize customer value while minimizing expense. An analogy for a system is the chain—a group of interdependent links work- ing together toward the overall goal. The constraint is a weak link; the per- formance of the entire chain is limited by the strength of the weakest link. TOC concentrates on the process that slows the speed of product through the system (Nave 2002). The amount of work in queue ahead of a process opera- tion is a classic indicator; another example is where products are processed in batches. Once the constraint is identified, the process is improved or otherwise supported to achieve its utmost capacity without major expensive upgrades or changes. When the constraining process is working at maximum capacity, the speeds of other subordi- nate processes are paced to the speed or capacity of the constraint. Some processes will sacrifice individual productivity for the benefit of the entire system. Subordinate processes are usually found ahead of the constraint in the value stream. Processes after the constraint are not a major concern—they are probably already producing under capacity because they have to wait for the constraining process. If the output of the overall system is not satis- factory, further improvement is required. Changes can involve capital improvement, reorganization, or other major expenditures of time or money. Elevating the constraint involves taking whatever action is necessary to eliminate it. Once the first constraint is broken, another part of the system or process chain becomes the new constraint. The performance of the 74 The Healthcare Quality Book entire system is reevaluated by searching for the new constraint process, exploiting the process, subordinating, and elevating. By focusing on constraints, this methodology produces positive effects on the flow time of the product or service through the system. Reduction of waste in the constraint increases throughput and improves throughput time.
Blinding is more likely to be used in an explanatory trial such as one comparing CROSSOVER oral metformin with placebo in women with polycystic ovarian syndrome buy hoodia 400mg with amex herbals india. Pragmatic trials Crossover trials have the advantage of using may also be blinded order hoodia 400mg fast delivery himalaya herbals india, but this is often not feasible women as their own controls, thus reducing (for example, in surgical versus medical trials), the sample size required. There is also less of a exposed to either the control or the intervention compulsion to use placebos, as the objective is arm ﬁrst, followed by the other. Clinician and patient this design is more suited for medical treatments biases caused by the absence of blinding may of chronic conditions as opposed to surgical not necessarily be detrimental to the trial, but trials or infertility trials. In the ﬁrst group the could actually be seen to be part of the response practicalities of the situation render such a design to treatment. In the second, a deﬁnite outcome such as one comparing oral clomiphene citrate such as pregnancy has the natural effect of (a drug treatment) versus expectant management preventing women from completing later phases of the trial. From a practical the treatment as well as the associated placebo point of view, only data from the ﬁrst phase effect as this best reﬂects the likely clinical of the crossover trial may be valid. TRIAL DESIGN SIMPLE PARALLEL GROUP FACTORIAL This is the simplest and commonest trial design Factorial designs are often efﬁcient as they can involving a comparison between two groups, address two questions within the context of a 340 TEXTBOOK OF CLINICAL TRIALS Women with unexplained infertility Randomisation A B Expectant management Clomiphene C D Intra-uterine insemination Clomiphene + intra-uterine (IUI) insemination (IUI) Figure 21. Women with unexplained infertility is not targeted at individual patients, but at can be randomised to receive either expectant groups of patients. This can happen where the management (no treatment), insemination alone, intervention is an information package for the clomiphene alone or clomiphene and insemina- management of menorrhagia in primary care9 tion treatment as shown in Figure 21. In been expected to manage both study (information this case, the effect of IUI alone can be assessed leaﬂet, clinical guidelines) and control patients. Cluster C and D with A and B, while the effect of randomisation should only be carried out when clomiphene can be evaluated by comparing B and there is a strong justiﬁcation for doing so. The primary implication of cluster randomised trials is that the measurements on individuals CLUSTER RANDOMISED TRIALS IN are not statistically independent of one another; GYNAECOLOGY AND INFERTILITY that is measurements from individuals within the A potential problem that can occur with ran- same cluster will be correlated to one another. Cluster randomised trials should ence in implantation rates was likely to be wider adjust for this clustering when determining the than that reported due to failure to adjust for number of patients required. The sample size the clustering of embryos/oocytes transferred to that would be required if patients were to be each woman. Studies where oocytes have been randomised must be inﬂated by a factor which randomised have no clustering implications since takes into account the extent of the clustering oocytes retrieved from the same women are ran- and the size of the cluster. When there is implicit clustering that fail to adequately inﬂate the sample size will in the data, the statistical analysis should account for this using the methods described above. Similarly, the correlated responses obtained from each cluster have an implication for the QUASI-RANDOMISED TRIALS statistical analysis, since standard statistical tests These are controlled experimental studies where (e. There are a number of patient unit numbers or days of the week when approaches to analysing cluster randomised tri- 13 the patients are recruited. Failure to treatment allocation affords an element of chance, account for the correlated responses in the anal- it cannot be considered to be genuine randomi- yses will result in an increased type I error. This type of design may still appeal to Clustering of outcomes can also occur in infer- those involved in laboratory trials involving incu- tility trials where alternative treatments are being bation or cryopreservation of human embryos. For example, in randomised controlled In these cases, it may be easier and cheaper to trials comparing IVF with ICSI the unit of allo- 14 15 use a certain protocol for all embryos on alter- cation varies between patients, oocytes and 16 nate days or alternate weeks rather than change cycles. Often, outcomes such as implantation the protocol or a freezer setting for each embryo rate and fertilisation rate are considered. The consequent loss of allo- are both expressed as percentages out of the total cation concealment will lead to serious inclu- number of oocytes retrieved. Hence, in trials that sion bias as some patients may be deliberately randomise patients (couples) or cycles and report excluded. This, is turn, can exaggerate treatment implantation or fertilisation rates, there will be effects. In trials that randomise by patients and be randomised on grounds of strong treatment report fertilisation of implantation rates, some preferences. However, for outcomes affect the generalisability of the results as par- such as live birth rate or pregnancy rate no ticipants may not be representative. Yet recruit- adjustment is required since the percentages are ment of these patients may introduce substantial expressed out of the total number of patients ran- bias especially when it is impossible to blind domised. In addition, compliance and satisfaction and reported implantation rates per transferred may be higher with the preferred intervention. Dissatisfaction number of patients into either the randomised or with the allocation may lead to differential com- the preference arms is also a problem, as the trial pliance and follow-up resulting in groups which will not be completed unless the appropriate num- cannot then be assumed to be similar.
The technique Electrical stimuli is suitable for comparing the reﬂex effects of cuta- Electrical stimuli are artiﬁcial and purchase hoodia 400 mg with mastercard vindhya herbals, when stimulat- neous volleys in different motor tasks hoodia 400mg with amex yashwanth herbals, at equivalent ing a nerve trunk, other afferents are almost cer- levels of background EMG activity (cf. However, there are drawbacks to the ing the sural or digital nerves, and muscle and joint technique. The RII-like response produced in fore- This technique does not introduce volitional bias. Despite these drawbacks, electri- (ii) activation by pathways transmitting late FRA cal stimulation is the only method that allows accu- effects(cf. Inaddition,amonosynapticreﬂex ratemeasurementofresponselatenciesandisthere- cannot be obtained in all muscles, and plotting the fore usually preferred. Responses recorded at rest Arecording at rest is made under conditions similar to those of the routine clinical examination. How- Recordings of single units ever, only excitatory responses can be so disclosed. PSTHs of single units should be recorded because of the opposite effect of some cutaneous stimuli on slow- and fast-twitch motor units. However, it is dif- Modulation of the average rectiﬁed EMG ﬁcult to keep the same motor unit recording during This is the most commonly used method, because it a withdrawal reﬂex, and no data are available on the rapidly reveals the full-time course of excitatory and projectionsofnociceptiveafferentstodifferenttypes inhibitory effects produced by the cutaneous volley. Withdrawal reﬂexes 399 Conclusions and the long-latency responses (see Figs. Long-latency reﬂexes are considered separ- (i) When nociceptive reﬂexes are used to scale ately on pp. These latter results are therefore (ii) Task-related changes in exteroceptive path- considered in the subsections discussing the spinal ways are best investigated with the modulation of pathways mediating withdrawal reﬂexes. However, such studies Afferent pathway of withdrawal reﬂexes should be complemented by studies of the modula- tion of monosynaptic reﬂexes to estimate the extent The afferent pathway of the RIII reﬂex of the short of volitional bias and, when possible, by studies on head of the biceps femoris to stimulation of the sural single units to see whether the distribution of the nerve has been investigated in detail (Willer, 1977, cutaneous input is homogeneous or not among the 1983;Willer, Boureau & Albe-Fessard, 1978). Once again, this emphasises the necessity of using different methods Parallel between pain sensation and in studies on human subjects. The protective nature of these liminalpainsensation,describedasasharppinprick reﬂexes has long been appreciated. In 1899,Collier localised to the point of stimulation (occurring at proposed that the function of the ﬂexion reﬂex of ∼3onthe scale sensation, Willer, 1977), occur at the the leg was to withdraw the foot from an offending same stimulus intensity (∼10 mA). Pioneering EMG studies by the Scandinavian ulus intensity produces a continuous and almost school in the early 1960s demonstrated that the pro- linear increase in both the reﬂex size and the pain tectivefunctionofwithdrawalreﬂexeswasconsider- sensation up to a maximum, corresponding to the ablymorereﬁnedthanhadpreviouslybeenassumed threshold for intolerable pain, above which further (see pp. There are two Stimuli delivered to the skin classes of withdrawal reﬂexes in the lower limbs: the early reﬂexes occurring with a latency less than When the stimulus is delivered to the skin in the 100 ms, reﬂexes which are almost certainly spinal, receptive ﬁeld of the sural nerve instead of the nerve, 400 Cutaneomuscular and withdrawal reﬂexes the thresholds for the reﬂex and the pain sensation a single shock (Fig. Accordingly, it was are reduced to ∼5 mA, and curves similar to those found that stimulation of the sural nerve by a train at in Fig. This shift has been attributed produced both an RIII reﬂex and a pain sensation to an inhibitory action of low-threshold afferents in which increased with the number of pulses in the the trunk nerve on transmission in the pathway of conditioning train. With single lem in determining the pathway and central delay of shocks of 0. It is therefore not sation was not painful and no RIII response was surprising that a crucial question about the cen- recorded. Pain and the RIII reﬂex appeared at high tral pathway of human withdrawal responses is the stimulus intensities of 40–50 mA, when a small extent to which withdrawal responses are spinal delayed response could be recorded in the neuro- reﬂexes. That the recruitment of A ﬁbres Central delay was necessary to evoke both the RIII reﬂex and pain Superﬁcial abdominal reﬂexes was conﬁrmed by their disappearance after a lido- caine block of small afferents (Fig. Similarly, Abdominal reﬂexes have been unequivocally it is probable that the afferent ﬁbres responsible for demonstrated to be spinal. With strong stimuli their abdominalskinreﬂexesarewithintheA range,since latency may be as short as 24 ms (Fig. Possible contribution of Aβ ﬁbres The central delay of the withdrawal reﬂexes of the limbs is less well deﬁned A ﬁbres may contribute to both the RIII reﬂex and pain, provided that they are repetitively stimulated (i) The gradual decrease in the latency of the inhi- (Willer, Boureau & Albe-Fessard, 1978). Thus, 10 min bition of knee extensors when the nociceptive after a lidocaine block of the A ﬁbres, pain and the stimulus is moved up the limb has been one of RIII reﬂex could be produced by double-shock stim- theﬁrstargumentsinfavourofaspinalpathway ulation activating only A ﬁbres, although not by for the withdrawal response (Hagbarth, 1960). Patients with complete spinal transection This would correspond to a conduction velocity of 33–40 m s−1, further suggesting that afferents Reﬂexes with similar features can be recorded in the largerthanA sizeareinvolvedintheproduction tibialis anterior and the biceps femoris in patients of withdrawal responses. Given (i) the long conduction time of in normal awake subjects and spinal patients (see theslowA volleyoverthelongdistancefromthe pp. However, some uncertainties remain: the exact central delay remains unknown, and it (i) In investigations using stimulation of the tibial could be argued that 80 ms is also the latency of nerveattheankleorofitsbranches,particularly transcortical responses elicited by A ﬁbres (see the medial plantar nerve, group II muscle affer- pp.
Drug therapy is usually continued as long as the transplanted tissue is in Corticosteroids are contraindicated in systemic fungal infec- place hoodia 400mg low cost jb herbals. When symptoms are controlled generic hoodia 400mg with mastercard herbals world, reduce dosage to lowest effective maintenance dose. After a few days, reduce dosage to 100 mcg daily (1 spray each nostril once daily) for maintenance therapy. Hydrocortisone PO 20–240 mg daily, depending on condition and (Hydrocortone, Cortef) response Hydrocortisone sodium IV, IM, SC 15–240 mg daily in 2 divided doses phosphate Hydrocortisone sodium IV, IM 100–400 mg initially, repeated at 2, 4, or succinate 6 hour intervals if necessary Hydrocortisone retention Rectally, one enema (100 mg) nightly for 21 d or enema (Cortenema) until optimal response Hydrocortisone acetate 1 applicatorful 1–2 times daily for 2–3 wks, then once intrarectal foam (Cortifoam) every 2–3 days if needed Methylprednisolone (Medrol) PO 4–48 mg daily initially, gradually reduced to lowest effective level Methylprednisolone sodium IV, IM 10–40 mg initially, adjusted to condition and Infants and children: IV, IM not less than succinate (Solu-Medrol) response 0. Oral inhalation (Azmacort) 2 inhalations (200 mcg) 3–4 times daily or 4 inhala- 6–12 y: 1–2 inhalations (100–200 mcg) 3–4 times tions (400 mcg) 2 times daily daily or 2–4 inhalations (200–400 mcg) 2 times daily. Nasal inhalation (Nasacort) 2 sprays (110 mcg) in each nostril once daily (total ≥6 y: 2 sprays (110 mcg) in each nostril once daily dose 220 mcg/d). May increase to maximal daily (220 mcg/day) initially, reduce to 1 spray per dose of 440 mcg if indicated. They should be used with caution in clients at risk for This may include diagnostic tests for diabetes mellitus, infections (they may decrease resistance), clients with infec- tuberculosis, and peptic ulcer disease because these con- tions (they may mask signs and symptoms so that infections ditions may develop from or be exacerbated by adminis- become more severe before they are recognized and treated), tration of corticosteroid drugs. If one of these conditions diabetes mellitus (they cause or increase hyperglycemia), is present, corticosteroid therapy must be altered and peptic ulcer disease, inﬂammatory bowel disorders, hyper- other drugs given concomitantly. This is necessary because corticosteroids may mask symptoms of infection and impair healing. Thus, even minor infections can become serious if left un- Kim Wilson, 62 years of age, was admitted for elective abdominal treated during corticosteroid therapy. In- during long-term corticosteroid therapy, appropriate anti- dividualize a postoperative plan of care for Kim considering her biotic therapy (as determined by culture of the causative chronic steroid use. Also, increased doses of corticosteroids are usually indicated to cope with the added stress of the infection. Nursing Process Assessment Related to Previous Assessment Related to Initiation or Current Corticosteroid Therapy of Corticosteroid Therapy Initial assessment of every client should include informa- • For a client expected to receive short-term corticosteroid tion about previous or current treatment with systemic cor- therapy, the major focus of assessment is the extent and ticosteroids. Such data can then be used to eval- the client or reviewing medical records. Such infor- • Risk for Injury related to adverse drug effects of impaired mation is necessary for planning nursing care. If the client wound healing; increased susceptibility to infection; weak- had an acute illness and received an oral or injected cor- ening of skin and muscles; osteoporosis, gastrointestinal ticosteroid for approximately 1 week or received corti- ulceration, diabetes mellitus, hypertension, and acute costeroids by local injection or application to skin lesions, adrenocortical insufﬁciency no special nursing care is likely to be required. If, how- • Ineffective Coping related to chronic illness, long-term ever, the client took systemic corticosteroids 2 weeks or drug therapy and drug-induced mood changes, irritability longer during the past year, nursing observations must be and insomnia. Such a client may be at higher risk for • Deficient Knowledge related to disease process and development of acute adrenocortical insufﬁciency during corticosteroid drug therapy stressful situations. If the client is having surgery, corti- costeroid therapy is restarted either before or on the day Planning/Goals of surgery and continued, in decreasing dosage, for a few The client will: days after surgery. In addition to anesthesia and surgery, potentially signiﬁcant sources of stress include hospital- • Receive or take the drug correctly ization, various diagnostic tests, concurrent infection or • Receive and practice measures to decrease the need for other illnesses, and family problems. Once this • Verbalize or demonstrate essential drug information basic information is obtained, the nurse can further assess client status and plan nursing care. Some speciﬁc factors Interventions include the following: For clients on long-term, systemic corticosteroid therapy, • If the client will undergo anesthesia and surgery, expect use supplementary drugs as ordered and nondrug measures that higher doses of corticosteroids will be given for to decrease dosage and adverse effects of corticosteroid several days. Some speciﬁc measures include the following: the route of administration, and the dosage. For regimens vary according to type of anesthesia, surgical example, partial relief of symptoms may be better than procedure, client condition, physician preference, and complete relief if the latter requires larger doses or longer other variables. A client having major abdominal surgery periods of treatment with systemic drugs. One extra dose may be adequate • In clients with rheumatoid arthritis, rest, physical therapy, for a short-term stress situation, such as an angiogram and salicylates or other nonsteroid anti-inﬂammatory drugs or other invasive diagnostic test. Systemic corticosteroid therapy is reserved • Using all available data, assess the likelihood of the for severe, acute exacerbations when possible.