Computer software for pharmacy oncology services

A computer program designed to manage the informational, clinical, and data requirements for a pharmacy oncology service is described. Specialized pharmacy oncology software was developed at Rhode Island Hospital and implemented in a multihospital, integrated health system. The software performs various safety functions, supplies on-screen access to pertinent drug and patient information, manages data, and assists in the product formulation process. The programmed safeguards can be modified to meet changing requirements. The system has been in use for more than seven years and has helped detect prescribing errors and prevent preparation and administration errors. A pharmacy oncology computer program streamlines pharmacists' work and helps prevent errors in antineoplastic drug therapy.     

Medications and nutrition in the elderly

Single drug and drug combinations taken by elderly individuals may impose nutritional risk. Nutritional risk induced by drug intake include anorexia, excessive increase in appetite, drug-induced nutritional deficiencies, and toxic reactions. Drug side effects, such as postural hypotension, may interfere with food shopping or cooking ability. Prescribed diets may also impose a risk of drug-induced side effects or diminished drug efficacy. Unwanted outcomes of drug-food and drug-nutrient interactions can be minimized by instructing elderly men and women and their caregivers to avoid timing errors in drug-taking behavior and toxic reactions due to food incompatibility. In addition, drug-induced nutritional deficiencies can be avoided by advising drug-taking elderly on the appropriate levels of nutrient intake.     

Therapeutic drug monitoring in special populations

Therapeutic drug monitoring (TDM) is commonly used to maintain "therapeutic" drug concentrations. Even in compliant patients, with "average" drug kinetics, TDM is useful to identify the causes of unwanted or unexpected responses, prevent unnecessary diagnostic testing, improve clinical outcomes, and even save lives. TDM has greatest promise in certain special populations who are: (a) prone to under- or overrespond to usual dosing regimens, (b) least able to tolerate, recognize, or communicate drug effects, or who are (c) intentionally or accidentally misdosed. TDM is especially useful in patients at the extremes of age, in adolescents, and in patients who are either taking multiple drugs or expressing unusual pharmacokinetics as a result of physiological, environmental, or genetic causes. Less-well-appreciated uses of TDM include prevention of dangerous underdosing of patients, investigation of adverse drug reactions, and identification of serious medication errors, even for a number of drugs that are not traditionally monitored. TDM can be useful for some drugs in any patient and for most drugs in some special populations.     

Therapeutic drug monitoring in pediatrics: a need for improvement

Therapeutic drug monitoring (TDM) is practiced for a number of frequently used drugs in infants and children. It is believed that monitoring drug levels will increase the probability of a therapeutic response and minimize the probability of adverse drug sequelae. Dose adjustments are based on measured drug levels interpreted relative to published therapeutic ranges which may or may not reflect the true relationship with either therapeutic or adverse effects. Potential errors derive from many sources, some amenable to solutions based on current knowledge, others awaiting improved understanding of the causes and consequences of unreliable therapeutic ranges.     

Selective deficits in reflective cognition of polydrug abusers: Preliminary findings.

The goal of this study was to determine if drug abusers exhibited specific deficits in reflective cognition similar to that observed in detoxified alcoholics who were otherwise cognitively intact. Fifteen drug abusers and 15 non-drug-abusing control participants were administered a series of cognitive tests, which assessed various learning and memory functions. Drug abusers did not differ from controls with respect to most cognitive domains. However, drug abusers exhibited selective deficits in processing unstructured information and in inhibiting intrusion errors during word recall. Such deficits in reflective functioning may play a role in the initiation of drug use or maintenance of drug dependence. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Acute nicotinic blockade produces cognitive impairment in normal humans

Single oral doses of the central and peripheral nicotinic antagonist mecamylamine were administered to healthy young normal males in doses of 5, 10, and 20 mg in a placebo-controlled, double-blind study. The 20 mg dose caused a significant increase in errors in the learning condition of the Repeated Acquisition task, producing a slower acquisition curve. The lower doses produced less errors, but more than in the placebo condition. There was no effect of drug on the performance component (retrieval of previously learned information). On the recognition memory task, dose-related increases in false-alarms during the delay period were seen, with little effect on misses or hits. Reaction time measures suggested a dose-related slowing of RT on several tasks. Behavioral effects were minimal and physiologic measures were consistent with dose-related ganglionic blockade. We interpret these results to indicate that acute blockade of nicotinic receptor function can produce measurable and significant cognitive impairment, even in non-smoking normals.     

Chronic sparing of delayed alternation performance and choline acetyltransferase activity by CEP-1347/KT-7515 in rats with lesions of nucleus basalis magnocellularis

Peripheral injection of the indolocarbazole CEP-1347/KT-7515 into rats that have sustained ibotenic acid lesions of the nucleus basalis magnocellularis has been shown to prevent the loss of cortically-projecting neurons in that basal forebrain region. The present study tested whether this neuroprotective activity would lead to chronic sparing of a behaviour known to be impaired by that lesion, as well as to chronic maintenance of cholinergic activity in cortical target regions of the nucleus basalis. CEP-1347/KT-7515 was injected into adult rats that had sustained bilateral ibotenic acid lesions of the nucleus basalis magnocellularis; the first injection occurred 18-24 h after lesioning, with subsequent injections of CEP-1347/KT-7515 occurring every other day over 12 days. One day following the last injection the animals were tested for retention of a previously-learned delayed alternation task. Animals that received CEP-1347/KT-7515 committed significantly fewer errors than lesioned animals receiving vehicle. These same animals were tested again eight to 10 weeks later (which was 10-12 weeks post-dosing), without receiving further drug or behaviour training during the test-retest interval. The animals that had received CEP-1347/KT-7515 continued to commit significantly fewer errors than vehicle animals. Furthermore their performance at this time point was indistinguishable from normal controls. Analysis of errors showed that CEP-1347/KT-7515 prevented a lesion-induced increase in perseverative errors, suggesting the drug improved attention in the lesioned animals. Choline acetyltransferase activity in the frontal cortex of the behaviourally tested animals that received CEP-1347/KT-7515 three months previously showed a significant 40% recovery of the lesion-induced loss seen in the vehicle animals. These results demonstrate that treatment with CEP-1347/KT-7515 over 12 days following excitotoxic damage to the nucleus basalis magnocellularis produces long-term sparing of an attention-demanding behaviour.     

Repeated acquisition of behavioral chains: effects of methylphenidate and imipramine

A method involving repeated acquistion of behavioral chain was used to assess the effects of methylphenidate and imipramine in individual animals. Pigeons obtained food for completing a 4-response chain, which was changed from session to session. Learning was defined by the decrease in errors across trials within a session; overall accuracy was measured by total errors per session. For comparison, the drug tests were also conducted under a performance condition, in which the 4-response chain was the same from session to session. In general, both drugs increased total errors per session as a function of dose under both the learning and performance conditions. The error-increasing effect was greater with imipramine than with methylphenidate and was detected at lower doses under the learning condition than under the performance condition. Under the learning condition, the higher doses of both drugs decreased the rate of within-session error reduction. Although neither drug enhanced accuracy at any of the doses tested, the lower doses of methylphenidate slightly decreased total trial time under both the learning and performance conditions.     

Withdrawal of maintenance drugs with long-term hospitalized mental patients: A critical review.

The advisability of drug withdrawal has recently become an important issue in light of several effects of long-term drug maintenance, including undesirable side effects, unexplained deaths, mounting costs, problems in drug-state learning and transfer of learning to the nondrug state, and questionable utility. Methodological flaws that pervade the literature on drug withdrawal are discussed. It is argued that the conclusion of the majority of these studies that withdrawal contributes to significant deterioration is not warranted because of frequently repeated design errors. (5 p ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Nonlinear perpendicular least-squares regression in pharmacodynamics

Currently available software for nonlinear regression does not account for errors in both the independent and the dependent variables. In pharmacodynamics, measurement errors are involved in the drug concentrations as well as in the effects. Instead of minimizing the sum of squared vertical errors (OLS), a Fortran program was written to find the closest distance from a measured data point to the tangent line of an estimated nonlinear curve and to minimize the sum of squared perpendicular distances (PLS). A Monte Carlo simulation was conducted with the sigmoidal Emax model to compare the OLS and PLS methods. The area between the true pharmacodynamic relationship and the fitted curve was compared as a measure of goodness of fit. The PLS demonstrated an improvement over the OLS by 20.8% with small differences in the parameter estimates when the random noise level had a standard deviation of five for both concentration and effect. Consideration of errors in both concentrations and effects with the PLS could lead to a more rational estimation of pharmacodynamic parameters.     

Surgical injuries registered in the Norwegian system for patient injuries. Possibilities of the use of the material for quality improvement in Norwegian hospitals

328 surgical "errors" reported to the Norwegian System of Compensation for Injuries to Patients were analysed in order to find out how the errors can be exploited for the purpose of quality improvement. In 8% of the cases the patients had been treated as emergency cases. 7% of the patients had been treated as out-patients. 30% of the patients had become more than 15% permanently disabled as a consequence of the "error". The Norwegian System of Compensation for Injuries to Patients operates with five different categories of errors defined by medical specialty, of which surgery is one. We found that among "surgical errors" 16% of the patients had been treated by an anaesthetist or by a specialist in internal medicine, and 13% had been treated by a gynaecologist. There were several recurring "errors" such as nerve injuries and complications related to general atherosclerosis. A system for categorising errors with a view to quality improvement should be different from other systems of categorisation. We suggest a system based on not only five but all medical specialties. Data from such a system could be used to prepare "pedagogic reports" that can be sent to the managers of services and education in each medical specialty. Thus, by turning surgical errors into "medical treasures", the errors can be exploited to promote quality improvement.     

Are there cytopathic features associated with cytomegalovirus infection predictive of resistance to antiviral therapy?

In recent years, identifying the origins of medical errors has been aided by a growing awareness that such errors are frequently the result of flaws in the system. In short, they are "accidents waiting to happen." Despite the value of the systems approach in identifying and preventing errors, it creates a difficult ethical problem for medical educators. Evidence suggests that when physicians ascribe errors to systemic causes, they may be less likely to modify their future behaviors and thus will be more likely to repeat past errors. Therefore, academic medical centers (i.e., teaching hospitals) must achieve a delicate balance that protects patients from the error that a systems approach can identify, yet provides optimal education for house officers by teaching them to focus also on personal reasons for errors. The authors suggest that this balance can be achieved by having residency programs work aggressively to remove the obstacles that house officers predictably encounter when they look for the personal causes of error (e.g., being shamed, feeling fear and inadequacy). Programs must also encourage house staff to disclose their errors and make constructive changes in their own behaviors, encouraged and guided by role models. The article concludes with discussion of these and related strategies to achieve the desired balance between the use of a systems approach and a personal-responsibility approach to managing errors in academic medical centers.     

Purification of a novel phospholipase A2 from bovine seminal plasma

Therapeutic drug monitoring in the newborn infant is necessary because dose requirements differ greatly from those for older children. These differences stem from major changes in kinetic disposition at the absorption, distribution, and elimination phases. The small blood volume of neonates makes them sensitive to iatrogenic blood loss. Similarly, the small size of these patients means that medication errors frequently lead to morbidity and even mortality. The clinical laboratory must set up strict, high-standard, carefully updated guidelines to ensure the safety of infants who need drug therapy at this very vulnerable phase of their lives.     

Follicular tissues reduce drug effects on ion channels in oocytes of Xenopus laevis

The influence of follicular tissues on drug effects on ion channels in Xenopus oocytes was tested by investigating the pharmacological properties of a cloned potassium channel in oocytes with and without follicular tissues. The data show that the efficacy of blocking agents (ranging from metal ions to peptides) is drastically reduced by the follicular tissues (reductions by as much as 90% and increases of the IC50 values up to 30-fold). Furthermore, the time course of the blocking effect was slowed down by the tissues (increases of the t50 values up to 40-fold). The described impairment could be mitigated, but not abolished by partial removal of the follicular tissues (so-called defolliculation, leaving only the vitelline envelope and part of the follicle cells on the oocyte surface). The results indicate that the follicular tissues can induce significant errors in pharmacological measurements on membrane proteins in Xenopus oocytes.     

A novel class of mosquitocidal delta-endotoxin, Cry19B, encoded by a Bacillus thuringiensis serovar higo gene

Construction of computational blood flow models from magnetic resonance (MR) scans of real arteries is a powerful tool for studying arterial hemodynamics. In this report we experimentally determine a lower bound for errors associated with such an approach, and present techniques for minimizing such errors. A known, simple three-dimensional geometry (cylindrical tube) was imaged using a commercial MR scanner, and the resulting images were used to construct finite element flow models. Computed wall-shear stresses were compared to known values and peak errors of 40-60% were found. These errors can be attributed to limited spatial resolution, image segmentation and model construction. A simple smoothing technique markedly reduced these peak errors. We conclude that smoothing is required in the construction of arterial models from in vivo MR images. If used appropriately, such images can be used to construct acceptably accurate computational models of realistic arterial geometries.     

Physostigmine, but not 3,4-diaminopyridine, improves radial maze performance in memory-impaired rats

The results of some studies suggest that 3,4-diaminopyridine (3,4-DAP), a drug that enhances the release of acetylcholine, may improve memory. The present study examined the ability of 3,4-DAP to reverse the memory impairment produced by scopolamine and the ability of 3,4-DAP and physostigmine to reverse the memory impairment produced by quinolinic acid lesions of the nucleus basalis magnocellularis (nbm) in rats. Mnemonic functioning was assessed with the use of a partially baited eight-arm radial maze. Entries into arms that were never baited were defined as reference memory errors; entries into baited arms from which the food already had been eaten were defined as working memory errors. In Experiment 1, 0.1 mg/kg scopolamine produced a significant increase in working and reference memory errors. Various doses of 3,4-DAP had no significant ameliorative effect on the mnemonic deficit. In Experiment 2, cholinergic function was impaired using a unilateral intra-nbm injection of quinolinic acid (120 nmol in 1.0 microliter). These lesions reduced the levels of the cholinergic marker, choline acetyltransferase, in the cortex by more than 40%. Results showed that the nbm lesion animals were significantly more impaired on the working than reference memory component of the task. Physostigmine (0.01, 0.05, 0.10, 0.20, 0.50 mg/kg) dose-dependently decreased the number of working but not reference memory errors. 3,4-DAP (10(-8), 10(-6), 10(-4), 10(-2), 10(0) mg/kg) had no reliable effect. It was concluded that physostigmine, but not 3,4-DAP, ameliorates memory impairments following decreases in cholinergic function.