Dependence Levels as Interim Clinical Milestones Along the Continuum of Alzheimer's Disease: 18-Month Results from the GERAS Observational Study.

BACKGROUND: While functional loss forms part of the current diagnostic criteria used to identify dementia due to Alzheimer's disease, the gradual and progressive nature of the disease makes it difficult to recognize clinically relevant signposts that could be helpful in making treatment and management decisions. Having previously observed a significant relationship between stages of functional dependence (the level of assistance patients require consequent to Alzheimer's disease deficits, derived from the Alzheimer's Disease Cooperative Study - Activities of Daily Living Scale) and cognitive severity, we investigated whether measures of functional dependence could be utilized to identify clinical milestones of Alzheimer's disease progression. OBJECTIVES: To describe the patterns of change in dependence over the course of 18 months in groups stratified according to cognitive Alzheimer's disease dementia severity (determined using the Mini-Mental State Examination score) and to identify characteristics associated with patients showing worsening dependence (progressors) versus those showing no change or improvement (non-progressors). DESIGN: Analysis of longitudinal data from the GERAS study. SETTING: GERAS is an 18-month prospective, multicenter, naturalistic, observational cohort study reflecting the routine care of patients with Alzheimer's disease in France, Germany, and the United Kingdom. PARTICIPANTS: 1495 community-living patients, aged ≥55 years, diagnosed with probable Alzheimer's disease dementia, and their caregivers. MEASUREMENTS: Dependence levels, cognitive function, behavioral symptoms, caregiver burden, and cost were assessed at baseline and at 18 months. RESULTS: Of 971 patients having both baseline and 18-month data, 42% (408) were progressors and 563 (58%) were non-progressors. This general pattern held for all three levels of baseline Alzheimer's disease dementia severity - mild (Mini-Mental State Examination score 21-26), moderate (15-20) or moderately severe/severe (<15) - with 40-45% of each group identified as progressors and 55-60% as non-progressors. No baseline differences were seen between progressors and non-progressors in cognitive scores or behavioral symptoms, although progressors had significantly shorter times since diagnosis and showed milder functional impairment. Baseline factors predictive of increasing dependence over 18 months included more severe cognitive impairment, living with others, and having multiple caregivers. A higher level of initial dependence was associated with less risk of dependence progression. Total societal costs of care also increased with greater dependence. CONCLUSIONS: In this large cohort, 42% of Alzheimer's disease dementia patients at all levels of cognitive severity became more dependent within 18 months of observation while 58% did not progress. Dependence levels may be considered as meaningful interim clinical milestones that reflect Alzheimer's disease-related functional deficits, although a time frame that extends beyond 18 months may be necessary to observe changes if used in clinical trials or other longitudinal studies. Recognition of predictors of greater dependence offers opportunities for intervention.

Clinical and Economic Characteristics of Milestones along the Continuum of Alzheimer's Disease: Transforming Functional Scores into Levels of Dependence.

BACKGROUND: Because Alzheimer's disease (AD) is characterized by a gradual decline, it can be difficult to identify distinct clinical milestones that signal disease advancement. Adapting a functional scale may be a useful way of staging disease progression that is more informative for healthcare systems. OBJECTIVES: To adapt functional scale scores into discrete levels of dependence as a way of staging disease progression that is more informative to care providers and stakeholders who rely on the functional impact of diseases to determine access to supportive services and interventions. DESIGN: Analysis of data from the GERAS study. SETTING: GERAS is an 18-month prospective, multicenter, naturalistic, observational cohort study reflecting the routine care of patients with AD in France, Germany, and the United Kingdom. PARTICIPANTS: Data were from baseline results of 1497 community-living patients, aged ≥55 years, diagnosed with probable AD and their caregivers. MEASUREMENTS: We used data from the Alzheimer's Disease Cooperative Study Activities of Daily Living Inventory (ADCS-ADL) and mapped items onto established categories of functional dependence, validated using clinical and economic measures. Cognitive function, behavioral symptoms, caregiver burden, and cost were assessed. Based on stages of functional dependence described by the Dependence Scale, individual ADCS-ADL items were used to approximate 6 dependence levels. RESULTS: There was a significant relationship between assigned level of dependence derived from the ADCS-ADL score and cognitive severity category. As the assigned level of dependence increased, the associated clinical and economic indicators demonstrated a pattern of greater disease severity. CONCLUSIONS: This mapping provides initial support for dependence levels as appropriate interim clinical milestones that characterize the functional deficits associated with AD.

Clinical evolution of beta cell function in youth with diabetes: the SEARCH for Diabetes in Youth study.

AIMS/HYPOTHESIS: Few studies have explored the epidemiology of beta cell loss in youth with diabetes. This report describes the evolution and major determinants of beta cell function, assessed by fasting C-peptide (FCP), in the SEARCH for Diabetes in Youth study. METHODS: Participants were 1,277 youth with diabetes (948 positive for diabetes autoantibodies [DAs] and 329 negative for DAs), diagnosed when aged <20 years, who were followed from a median of 8 months post diagnosis, for approximately 30 months. We modelled the relationship between rate of change in log FCP and determinants of interest using repeated measures general linear models. RESULTS: Among DA-positive youth, there was a progressive decline in beta cell function of 4% per month, independent of demographics (age, sex, race/ethnicity), genetic susceptibility to autoimmunity (HLA risk), HbA(1c) and BMI z score, or presence of insulin resistance. Among DA-negative youth, there was marked heterogeneity in beta cell loss, reflecting an aetiologically mixed group. This group likely includes youths with undetected autoimmunity (whose decline is similar to that of DA-positive youth) and youth with non-autoimmune, insulin-resistant diabetes, with limited decline (~0.7% per month). CONCLUSIONS/INTERPRETATION: SEARCH provides unique estimates of beta cell function decline in a large sample of youth with diabetes, indicating that autoimmunity is the major contributor. These data contribute to a better understanding of clinical evolution of beta cell function in youth with diabetes, provide strong support for the aetiological classification of diabetes type and may inform tertiary prevention efforts targeted at high-risk groups.

The differential effects of atypical antipsychotics on prolactin elevation are explained by their differential blood-brain disposition: a pharmacological analysis in rats.

All atypical antipsychotics avoid extrapyramidal side-effects yet differ in their propensity to cause other side-effects, like prolactin elevation. We proposed that the atypical antipsychotics with a propensity for prolactin elevation would show a higher pituitary versus striatal D2 receptor occupancy. To investigate this hypothesis, we tested four atypical antipsychotics, two that are commonly associated with prolactin elevation (amisulpride and risperidone) and two that are less frequently associated (quetiapine and olanzapine). In particular, we calculated their ED(50) values to increase plasma prolactin and block peripheral pituitary D2 receptors to their ED(50) values to antagonize apomorphine-induced stereotypy and occupy central striatal D2 receptors. All antipsychotics dose dependently increased prolactin levels and antagonized apomorphine-induced stereotypy. However, the central to peripheral potency (ED(50) for apomorphine antagonism to ED(50) for prolactin elevation) differed remarkably across these drugs: amisulpride (21764), risperidone (14), quetiapine (10), and olanzapine (1.7). Compounds displaying a higher peripheral potency brought about higher prolactin levels for a given level of functional central antagonism. This dissociation between central and peripheral effects was explained by the differential occupancy of D2 receptors in the striatum versus in the pituitary [ratio of striatal/pituitary ED(50) values (milligram per kilogram) for D2 occupancy): amisulpride (17/0.026 = 654), risperidone (0.89/0.081 = 14), quetiapine (24/4.1 = 6), olanzapine (0.30/0.43 = 0.7). These results indicate that dissociation between central and peripheral D2 receptor occupancy is a major determinant of the degree of prolactin elevation observed at therapeutic doses.

Randomized trial of enhanced anticipatory guidance for injury prevention.

OBJECTIVE: To develop and evaluate an injury prevention anticipatory guidance training program for pediatric residents. DESIGN: Thirty-one residents were randomly assigned to an intervention or control group. Both groups attended a 1-hour seminar about injury prevention and the American Academy of Pediatrics TIPP (The Injury Prevention Program) materials. The intervention group also received 5 hours of experiential instruction on injury prevention content and counseling skills (SAFE Counseling Framework). Families with infants from birth to age 6 months were enrolled in the study (N = 196); they were followed up until the child was aged 12 to 18 months. Data were collected by means of baseline and follow-up interviews, audiotapes of medical visits, parent exit surveys, and home observations. SETTING: A hospital-based continuity clinic that serves families living in low-income, inner-city neighborhoods. OUTCOMES: Physician counseling and parent satisfaction, knowledge, beliefs, and behaviors. RESULTS: Parents seen by physicians in the intervention group received significantly more injury prevention counseling for 5 of the 6 safety practices, and they were significantly more satisfied with the help their physicians provided on safety topics. They were no less satisfied with their physicians' counseling on other anticipatory guidance topics. Parents' knowledge, beliefs, and home safety behaviors did not differ between the 2 groups. CONCLUSIONS: The frequency and impact of pediatric counseling can be enhanced by experiential training that targets specific injury hazards. Because low-income families face many barriers to carrying out the recommended safety practices, supplemental strategies are needed to ensure safer homes.

Rehospitalization of children with asthma.

BACKGROUND: Although some children with asthma experience multiple admissions, asthma is considered a preventable cause of hospitalization. OBJECTIVE: To assess whether components of medical histories, ambulatory care prior to hospitalization, or ambulatory care after discharge are associated with repeated hospitalizations for children admitted with asthma. DESIGN: Nested case-control study of a cohort of children hospitalized for asthma, comparing those who were rehospitalized within 1 year with those not rehospitalized. SETTING: Urban pediatric primary care clinic. PARTICIPANTS AND METHODS: Subjects were 119 children, aged 0 to 14 years, who had an inpatient admission with a diagnosis of asthma between July 1, 1993, and June 30, 1995 (index hospitalization). Data sources included medical charts, computerized patient records, and administrative data. Use of health care services was compared among children who were rehospitalized within 1 year of the index admission and those who were not. MAIN OUTCOME MEASURE: Repeated hospitalizations. RESULTS: The proportions of children who received general pediatric, allergy, or pulmonary care in the year prior to the index hospitalization were 86%, 7%, and 8%, respectively. By report, half of all children did not receive prescribed therapies, more than half were exposed to cigarette smoke at home, and one fourth were not up-to-date with immunizations at the time of admission. Thirty-five of the 119 children hospitalized with asthma were subsequently readmitted with asthma within 1 year of the index hospitalization. Children readmitted did not differ from those with a single admission in terms of the above characteristics. However, significantly more children subsequently readmitted had a pulmonary consultation during the index admission (23% vs 4%; P = .001) or in the year following discharge (37% vs 12%; P = .002). In addition, children readmitted were more likely to have other chronic conditions (69% vs 49%; P= .048). CONCLUSION: Among low-income urban children, readmission for asthma is not associated with receipt of prescribed therapies or pediatric care.

Haloperidol-induced within-session response decrement patterns and catalepsy in rats: behavioural dissociation.

The typical antipsychotic haloperidol is known to induce extra-pyramidal side-effects (EPS). Catalepsy in rats is generally regarded as a valid model for detecting the EPS liability of compounds in humans. Together with its antipsychotic and cataleptogenic actions, haloperidol causes an attenuation of instrumental responding which becomes larger in the course of a session: a within-session response decrement. The present study compared the time-course of haloperidol-induced catalepsy, measured by a bar test, to the haloperidol-induced within-session response decrements, measured by operant behaviour under a fixed ratio 10 schedule of reinforcement. Rats were trained to press a lever on a Fixed Ratio 10 schedule of food reinforcement during sessions of 15 min. When responding was stable, saline or haloperidol in 0.03 mg/kg, 0.1 mg/kg, or 0.3 mg/kg was administered intra-peritoneally either 30, 90 or 180 min prior to behavioural testing. The number of lever presses, food tray visits and latency to press the lever and to visit the food tray were analysed in five successive blocks of 3 min. Catalepsy was tested 30, 60, 90, 120, and 180 min. after injection, by placing a rat with its forepaws on a horizontal bar. The latency to remove both forepaws from the bar was scored. Within-session response decrements were present at 0.1 mg/kg and at 0.3 mg/kg, from 30 min after administration onward. At these doses, latency to press the lever was increased after 30 and 90 min, but not significantly after 180 min. Latency to visit the tray was affected only after 30 min, at 0.3 mg/kg. Haloperidol induced a dose-dependent increase in catalepsy from 60 min onwards, with maximal effect after 120 min. A dissociation between the time-course of occurrence of within-session response decrement and the cataleptogenic action of haloperidol, as well as between the latter and both latency measures, was found. Consequently, the present data suggest that within-session response decrements are not obviously caused by catalepsy-related impairments.

Synthesis, and in vitro and in vivo muscarinic pharmacological properties of a series of 1,6-dihydro-5-(4H)-pyrimidinone oximes.

A series of 1,6-dihydro-5-(4H)-pyrimidinone oxime derivatives I was synthesized (Scheme 1, Tables 1 and 2) and tested for muscarinic activity (Table 3) in receptor binding assays using [3H]-oxotremorine-M (Oxo-M) and [3H]-pirenzepine (Pz) as ligands. Potential muscarinic agonistic or antagonistic properties of the compounds were determined using binding studies that measured their potencies to inhibit the binding of Oxo-M and Pz. Preferential inhibition of Oxo-M binding was used as an indicator for potential muscarinic agonistic properties; this potential was confirmed in functional studies on isolated organs. The series produced a wide range of active compounds with differing degrees of selectivity in M1, M2, and M3 functional models. Several compounds that have mixed agonist/antagonist profiles were able to reduce cholinergic-related cognitive impairments in models of mnemonic function. Substitutions (I, e.g. R2 or R3 = Me) at the 1,6-dihydro-5-(4H)pyrimidine ring disrupted binding and efficacy, whereas systematic variation of the oximes substituent R1 resulted in various degrees of potency and selectivity dependent on the nature of the substitution.

Findings from the American College of Epidemiology's survey on Ethics guidelines. The American College of Epidemiology Ethics and Standards of Practice Committee.

PURPOSE: A survey to establish both the need and subject areas for a possible new set of ethics guidelines for epidemiologists was conducted among a random sample of 300 North American (Canada, Mexico, and United States) members of three major United States-based professional epidemiology organizations. METHODS: An 88% response rate revealed wide agreement on topics to be included in any new set of guidelines, but uncertainty prevailed about the need for new guidelines; 41% agreed that there was a need to develop a new set, 43% had no opinion, and 16% disagreed. RESULTS: There was almost no difference in preferences between men and women for topics to be included in a new set of guidelines, or between those aware or unaware of extant ethics guidelines in epidemiology. Fifty-four percent were aware of such guidelines and only 29% of these said they could describe the content of the guidelines. CONCLUSION: More needs to be done to evaluate the utility of ethics codes in epidemiology.

5-HT2C receptor agonists: pharmacological characteristics and therapeutic potential.

In vitro, (S)-2-(chloro-5-fluoro-indol-1-yl)-1-methylethylamine 1:1 C4H4O4 and (S)-2-(4,4,7-trimethyl-1,4-dihydro-indeno[1, 2-b]pyrrol-1-yl)-1-methylethylamine 1:1 C4H4O4 exhibited high-affinity binding to the serotonin2C (5HT2C) receptors and stimulated turnover of inositol 1,4,5-triphosphate. Affinity to several of the other 5-HT receptor subtypes and to numerous nonserotonergic receptors was much lower. In rats, both compounds elicited behavioral signs of 5-HT2C receptor agonism but not 5-HT2A receptor agonism. Hypomotility induced in rats by high doses of these compounds was reversed by the 5-HT2C receptor antagonist N-(2-naphthyl)-N'-(3-pyridyl)-urea 1:1 HCI. In addition, these compounds were active in tests used to demonstrate anticompulsive effects: reducing schedule-induced polydipsia in rats (prevented by the 5-HT2C/2B receptor antagonist N-(1-methyl-5'-indolyl)-(3-pyridyl)urea 1:1 HCl, reversing increased scratching induced with 8-hydroxy-dipropylaminotetralin 1:1 HCl in squirrel monkeys (no tolerance developed), decreasing responding in the marble-burying task in mice, and decreasing excessive eating of palatable food in rats. In contrast to these compounds, fluoxetine was much less potent, and in some tasks less efficacious, in reducing excessive behavior in these models. These two 5-HT2C receptor agonists do not show anxiogenic effects in the plus-maze in rats. (S)-2-(4,4,7-trimethyl-1,4-dihydro-indeno[1, 2-b]pyrrol-1-yl)-1-methylethylamine 1:1 C4H4O4 reduced the olfactory bulbectomy-induced passive avoidance impairment in rats, a result that indicates antidepressant potential. Similarly, in the differential-reinforcement-of-low rate 72-s operant schedule task in rats, (S)-2-(chloro-5-fluoro-indol-1-yl)-1-methylethylamine 1:1 C4H4O4 increased (and (S)-2-(4,4,7-trimethyl-1,4-dihydro-indeno[1, 2-b]pyrrol-1-yl)-1-methylethylamine 1:1 C4H4O4 showed a tendency to increase) total reinforcements received, which is suggestive of antidepressant activity. The electroencephalography defined sleep-waking pattern in rats produced by these two 5-HT2C agonists, as well as fluoxetine, included increased quiet-waking and decreased rapid-eye-movement sleep, which is characteristic of antidepressant drugs. These results suggest that 5-HT2C receptor agonism is associated with therapeutic potential in obsessive compulsive disorder and depression.

The father's role during infancy. Factors that influence maternal expectations.

OBJECTIVE: To describe factors that influence maternal expectations of the father's role during infancy. RESEARCH DESIGN: Cross-sectional survey. SETTING: Postpartum obstetric ward of an inner-city teaching hospital. SUBJECTS: Mothers who were residents in the inner-city communities that surround the hospital and who were recently delivered of a newborn. SELECTION PROCEDURE: Consecutive sampling from March to May 1992. MEASUREMENTS: Through structured maternal interviews, the father's expected role was measured in terms of accessibility, engagement in child care tasks, and decision-making responsibility. Influences included demographics, the mother's desire for the father's involvement, and her perceptions of his motivation, prenatal support, and ability to parent. RESULTS: Of 226 eligible mothers, 197 (87%) were interviewed. Expectations varied widely. Concerning accessibility, 48% and 18% of the mothers expected to see the father daily and less than weekly, respectively. Concerning engagement, 81% of the mothers expected some paternal involvement; the average mother assumed that the father would participate in one third of child care tasks. Concerning decision-making responsibility, 34% of the mothers expected to share all decisions; 30% expected to share none. In all areas, expectations were positively associated with the mother's desires, the strength of the parents' relationship, and the mother's perceptions of the father's motivation and ability to parent and the father's prenatal involvement (all, P < .001). Expected accessibility and engagement were greater for fathers who worked; expected engagement and decision-making responsibility were greater for fathers without children from other relationships (all, P < .03). CONCLUSIONS: The maternal desire for the father's participation, the strength of the parents' relationship, the mother's perception of the father as a parent, and the father's prenatal involvement are all consistently associated with the maternal expectations of the father's role. The demographic characteristics of either parent are not as strongly or consistently associated with the maternal expectations.

Pediatric carve outs. The use of disease-specific conditions as risk adjusters in capitated payment systems.

OBJECTIVE: To address the issue of adverse selection in capitated payment systems by developing a list of disease-specific pediatric conditions (i.e., "carve outs") to be considered for separate reimbursement. DESIGN: A descriptive study using a large Medicaid database. INTERVENTION: With the use of fiscal year 1993 Washington State Medicaid cost data for 302,240 pediatric patients, a list of disease-specific carve outs was developed to meet the following criteria: high cost, low variability in cost, and association with a large proportion of medical spending. RESULTS: Six-hundred seventy-three patients (0.2%) in the database had annual costs totaling $25,000 or more. Ten percent of the cases accounted for approximately two thirds of spending, while the least expensive 70% of cases made up only 15% of the expenditures. Prematurity and complications of prematurity, neoplasms, congenital heart disease, organ transplantations, congenital anomalies, and respiratory problems were general categories of disease that met our criteria for a carve out. The association of a major surgical procedure with a diagnosis increased the predictive accuracy for high cost. CONCLUSION: Lists of disease-specific carve outs such as this one can be used by Medicaid plans and other insurers who are concerned about risk selection to identify conditions for separate reimbursement in capitated payment systems.

Possible confounding influence of strain, age and gender on cognitive performance in rats.

There are substantial differences in the performance of various rat strains in tasks of learning, memory and attention. Strain, age and sex differences are not consistent over procedures: poor performance in one paradigm does not predict poor performance in a different paradigm. Some strain differences are not readily apparent until a direct comparison is made between one or more strains. Moreover, large differences in nominally the same strain but obtained from different suppliers have been observed in behavioural, pharmacological and physiological parameters and can have important consequences for interpretation of drug effects. Longevity, and the effects of ageing can differ dramatically from one strain to another; drug effects can alter radically with increasing age and show strain (and individual) differences in their action. Sex can further complicate interpretation of results. Thus, non-cognitive factors may exert a major effect on results in cognitive testing, and strain-dependent effects may account for many conflicting results in the literature concerning mnemonic performance. Strain differences in particular must be identified and used to help identify fundamental effects on memory, rather than continue to be ignored and allowed to obscure interpretation of drug effects on cognitive processes.

Synthesis and muscarinic activities of 3-(pyrazolyl)-1,2,5,6-tetrahydropyridine derivatives.

A series of 3-(pyrazolyl)-1,2,5,6-tetrahydropyridine derivatives (B) was synthesized and tested for muscarinic activity in receptor binding assays using [3H]-oxotremorine-M (3H-OXO-M) and [3H]-pirenzepine (3H-PZ) as ligands. Potential muscarinic agonistic or antagonistic properties of the compounds were determined using binding studies measuring their potencies to inhibit the binding of 3H-OXO-M and 3H-PZ. Preferential inhibition of 3H-OXO-M binding was used as an indicator for potential muscarinic agonistic properties; this potential was confirmed in functional studies on isolated organs. All compounds with agonistic properties showed 3H-PZ/3H-OXO-M potency ratios in excess of 20. In contrast, for antagonists this ratio was found to be close to unity. Mono-halogenation resulted in compounds (4b and 4d) with M3 agonistic properties as shown by their atropine sensitive stimulant properties in the guinea pig ileum, but with very little or no M1 activity. Some minor in vivo effects were observed for both these compounds, with the iodinated compound 4d inducing salivation. Compound 4d also showed some positive mnemonic properties in rats where spatial short-term memory had been compromised by temporary cholinergic depletion. These data indicate that some M3 agonism may be desired in therapeutic agents aimed at the treatment of the cognitive deficits of Alzheimer's disease patients.

Synthesis and muscarinic M3 pharmacological activities of 1-azabicyclo[2.2.2]octan-3-one oxime derivatives.

A series of 1-azabicyclo[2.2.2]octan-3-one oximes and related 1-azabicyclo-[2.2.2]-octan-3-one hydroxylamines were synthesized and tested for muscarinic M3 activity. All compounds showed at least some muscarinic binding properties, however, only one member of the series demonstrated mucarinic M3 agonistic properties in vitro (contraction of guinea pig ileum) and in vivo (mydriasis, salivation). In addition, this compound partially reversed the cognitive deficit induced by central cholinergic depletion in two procedures testing memory in the rat, namely the delayed matching to position and swim maze tasks of spatial memory in the rat.

Effects of selective antagonism or depletion of the cholinergic system on visual discrimination performance in rats.

A two-lever simultaneous visual discrimination task was used to study the effects on performance in Long-Evans rats of the muscarinic antagonists scopolamine (0.0125, 0.05, 0.2 and 0.8mg/kg s.c.), the M(1) antagonist pirenzepine, the M(2) antagonist AF-DX 116, the M(3) antagonist UH-AH 37 (each 3.2, 10, 32µg/rat, i.c.v.), and the cholinergic depleting agent, hemicholinium-3 (0.04, 0.2, 1.0 and 5.0µg/rat i.c.v.). Scopolamine dose-dependently decreased accuracy, increased the number of trials on which the rats failed to respond, and significantly lengthened latency to respond. Only the highest doses of hemicholinium-3, pirenzepine and AF-DX 116 reduced accuracy and increased errors of omission as well as response latency. UH-AH 37 reduced overall task performance at 10 and 32µg, suggesting that antagonism of both M(3) and other muscarinic receptors (including M(1)) had a greater effect on performance than selective antagonism of the M(1) or M(2) receptors. These data indicate that the disruptive effects of cholinergic antagonism on attentionally demanding tasks are strengthened by activity at multiple subtypes of the receptor.

Pediatrics.

Children of mothers who smoked during pregnancy had IQ scores that were lower than the scores of children born to mothers who did not smoke. Routine use of nebulized steroids for croup can potentially reduce the need for hospitalization.

Conscious sedation in the pediatric emergency department.

Anxiety-provoking and painful emergency department procedures such as laceration repair are made more tolerable to the pediatric patient and easier for the practitioner through the judicious use of pharmacologic agents for conscious sedation and analgesia. Both the American Academy of Pediatrics and the American College of Emergency Physicians have published documents that guide the physician in the use of these agents in the care of children. Most new information concerns the evaluation of new drugs for use in the pediatric emergency department, adverse effects of familiar products, and evaluation of sedative and analgesic antagonist medications that may increase a practitioner's control when conscious sedation is used. Large controlled trials of protocols and drugs are necessary to establish safe, appropriate standards for conscious sedation in the pediatric emergency department.