Protection of privacy and confidentiality.

A multistate, cooperative program seeking to develop better methods for the effective and efficient gathering. storing, analyzing, and utilizing of mental patient records has made a comprehensive effort to protect the confidentiality and privacy of these psychiatric patient records. Administrative, technical, and legal safeguards have been implemented. The discussion of legal safeguards involves two areas: the protection of the system itself, located at Rockland State Hospital; and the specific legal environment of confidentiality and privacy of mental health records and information in the group of cooperating jurisdictions. On the whole, adequate legal and administrative protection can be afforded the confidentiality and privacy of an electronic data system in the mental health field, and access to the records can be restricted for the welfare of the patients. At the same time, access to aggregate data in the system can be allowed, under proper standards, for important research and planning purposes. The methods adopted by MSIS to preserve confidentiality and privacy by limiting access to such records could well prove an important model for the development of protective methods in other electronic data programs-not only those in psychiatry, but those in other fields where the data collected are sensitive and confidential.

Automated review system for orders of psychotropic drugs.

A computerized drug-review system both reviews drug orders and notifies clinicians of orders that are considered exceptions to some clinical guidelines. The impact of this system in a psychiatric center in which it has been used since December 1975 is examined in terms of the reduction of the percentage of orders of psychotropic drugs that involve polypharmacy or dose-range exceptions. The results show a substantial reduction in orders in exception since the implementation of the system.

Haloperidol blood levels and clinical effects.

This study explored the relationships between plasma levels and the clinical effects of haloperidol in 176 acutely exacerbated schizophrenic or schizoaffective patients. After a single-blind placebo period of 1 week (period 1), they entered the double-blind period 2 randomly assigned to one of three plasma levels of haloperidol: low (2 to 13 ng/mL), medium (13.1 to 24 ng/mL), or high (24.1 to 35 ng/mL). Patients whose conditions did not improve in period 2 continued on one of the three haloperidol levels (period 3). Periods 2 and 3 lasted 6 weeks each. Only minor differences in clinical responses were noted among the three levels of haloperidol. These results imply that low or moderate doses of neuroleptics are appropriate for many acutely psychotic patients.

Acute d-amphetamine challenge in schizophrenia: effects on cerebral glucose utilization and clinical symptomatology.

The effects of d-amphetamine (0.5 mg/kg orally) on regional cerebral glucose utilization were measured with positron emission tomography (PET) in 17 schizophrenics (along with a placebo-control group of an additional six schizophrenic patients). The acute d-amphetamine challenge tended to decrease glucose utilization throughout much of the brain, with a regional effect that was statistically significant in the left temporal cortex. There was no apparent relationship between the effects of amphetamine-induced changes in regional cerebral metabolism and psychotic symptom exacerbation. An exploratory analysis suggested that features characteristic of Crow's type II syndrome were significant predictors of cerebral hyporesponsivity to stimulant challenge, however.

Reproducibility of cerebral glucose metabolic measurements in resting human subjects.

Positron emission tomography with 11C-2-deoxyglucose was used to determine the test-retest variability of regional cerebral glucose metabolism in 22 young normal right-handed men scanned twice in a 24-h period under baseline (resting) conditions. To assess the effects of scan order and time of day on variability, 12 subjects were scanned in the morning and afternoon of the same day (a.m.-p.m.) and 10 in the reverse order (p.m.-a.m.) with a night in between. The effect of anxiety on metabolism was also assessed. Seventy-three percent of the total subject group showed changes in whole brain metabolism from the first to the second measurement of 10% or less, with comparable changes in various cortical and subcortical regions. When a scaling factor was used to equate the whole brain metabolism in the two scans for each individual, the resulting average regional changes for each group were no more than 1%. This suggests that the proportion of the whole brain metabolism utilized regionally is stable in a group of subjects over time. Both groups of subjects had lower morning than afternoon metabolism, but the differences were slight in the p.m.-a.m. group. One measure of anxiety (pulse at run 1) was correlated with run 1 metabolism and with the percentage of change from run 1 to run 2. No significant run 2 correlations were observed. This is the first study to measure test-retest variability in cerebral glucose metabolism in a large sample of young normal subjects. It demonstrates that the deoxyglucose method yields low intrasubject variability and high stability over a 24-h period.

The spectral signature method for the analysis of PET brain images.

We introduce the concept of the metabolic centroid spectrum as the feature space to characterize the distribution of metabolic activity in three-dimensional brains. The method computes the metabolic centroid of a brain subvolume for each increment of metabolic activity occurring in the whole brain. The result is the metabolic spectral signature, a continuous three-dimensional curve whose shape reflects the distribution of metabolic rates in the brain. The method's sensitivity to metabolic distribution asymmetries is greatly increased over that of the metabolic centroid method, while retaining its advantages; it is almost invariant to head size, head positioning, photon scatter, and the positron emission tomography (PET) camera's full width at half-maximum. It does not require magnetic resonance, computed tomography, or x-ray images. To test the method we analyzed the metabolic PET images of 40 normal subjects and 20 schizophrenics. The results show a unification of several metabolic characteristics of schizophrenic brains, such as laterality, hypofrontality, cortical/subcortical abnormalities, and overall brain hypometabolism, which were identified by different laboratories in separate studies using differing methodologies. Here they are presented by a single automatic objective method.

The metabolic centroid method for PET brain image analysis.

The method of centroids is an approach to the analysis of three-dimensional whole-brain positron emission tomography (PET) metabolic images. It utilizes the brain's geometric centroid and metabolic centroid so as to objectively characterize the central tendency of the distribution of metabolic activity in the brain. The method characterizes the three-dimensional PET metabolic image in terms of four parameters: the coordinates of the metabolic centroid and the mean metabolic rate of the whole brain. These parameters are not sensitive to spatially uniform random noise or to the position of the subject's head within a uniform PET camera field of view. The method has been applied to 40 normal subjects, 22 schizophrenics who were treated with neuroleptics, and 20 schizophrenics who were neuroleptic-free. The mean metabolic centroid of the normal subjects was found to be superior to the mean geometric centroid of the brain. The mean metabolic centroid of chronic schizophrenics is lower and more posterior to the mean geometric centroid than is that of normals. This difference is greater in medicated than in unmedicated schizophrenics. The posterior and downward displacement of the mean metabolic centroid is consistent with the concepts of hypofrontality, hyperactivity of subcortical structures, and neuroleptic effect in schizophrenics.

Nefopam and morphine in man.

A new analgesic, nefopam, is chemically distinct and pharmacologically unrelated to any presently known analgesic. A comparison was made of morphine and nefopam in 74 patients who required parenteral analgesia for moderate to severe postoperative and somatic pain, using a single administration, 2-dose level, double-blind design. A significant dose-response curve was obtained with nefopam and with morphine, and there was no significant deviation from parallelism. The time-effect curves for the 2 drugs were similar. The estimated relative potency of nefopam to morphine indicates that 20 mg of nefopam HCl is the approximate analgesic equal of 12 mg of morphine SO4. There were no adverse effects with nefopam and one adverse reaction to morphine.

Oral nefopam and aspirin.

Analgesia through nefopam (30 mg, 60 mg, 90 mg), aspirin (325 mg, 650 mg), and placebo were compared in 122 hospitalized patients with moderate to severe postoperative, fracture, or other somatic pain. A double-blind noncrossover study design was used, and patients were evaluated for pain intensity and pain relief over a 6-hr period. Based on sum of pain intensity differences (SPID) scores, treatment effects were consistent and indicative of good dose response to both active medications. Pain relief scores were more variable but were generally in accordance with SPID values. Time-effect curves were similar. Estimated relative potency of nefopam to aspirin was 10.4 with a 95% confidence interval of 6.3 to 20.8 for SPID, indicating that the analgesic potency of nefopam, 60 mg, was equivalent to that of aspirin, 650 mg. Side effects were minimal.

Fenoprofen and codeine analgesia.

Studies were conducted on postpartum and postoperative patients to estimate the dose-response line of fenoprofen and to contrast it with codeine and placebo. The postpartum patients included women with episiotomy pain and with uterine cramping. This mix allowed contrast of ability of the various pain models to distinguish codeine from placebo. The methodology for the studies was single-dose parallel groups design with interviews conducted by trained nurse observers to obtain subjective responses. More than 850 patients participated in the trial. The results indicate that fenoprofen at doses as low as 12.5 mg has analgesic properties. In each of the five studies, the mean value of 100- and/or 200-mg doses of fenoprofen for the variable sum of the pain intensity difference (SPID) was higher than that of 65 mg codeine. The pooled relative potency calculation based on SPID suggests that 100 mg fenoprofen is approximately equivalent to 60 mg codeine. In their ability to distinguish codeine from placebo, patients with uterine cramp, episiotomy, or surgical pain did not appear to differ.

The correlation between blood levels of ibuprofen and clinical analgesic response.

A clinical trial comparing ibuprofen, 400, 600, and 800 mg, with aluminum ibuprofen, 400 mg, and placebo was conducted in patients with moderate or severe pain subsequent to third molar extraction. Pain intensity ratings and ibuprofen serum levels were obtained at baseline, 30 minutes, 1 hour, and hourly thereafter for 3 hours. Pain intensity ratings were also obtained at hours 4, 5, and 6. Serum levels at 1, 2, and 3 hours correlated significantly with the log dose of ibuprofen (r = 0.35, 0.49, and 0.48, respectively) and with global analgesic response as measured by the percentage of the sum of the pain intensity scores (r = 0.28, 0.34, and 0.26, respectively). However, possibly because of differences in drug formulation, the percentage of the sum of the pain intensity scores did not correlate significantly with log dose. The highest correlations were found between contemporaneous serum levels and pain intensity difference values, particularly at hour 1 (r = 0.54). Our results support the proposition that increased ibuprofen serum levels lead to increased analgesia.

Analgesic efficacy of two ibuprofen-codeine combinations for the treatment of postepisiotomy and postoperative pain.

Our purpose was to compare the analgesic efficacy and safety of single oral doses of the combination of ibuprofen 400 mg plus codeine 60 mg and the combination of ibuprofen 200 mg plus codeine 30 mg with ibuprofen 400 mg alone, codeine sulfate 60 mg alone, and placebo. One hundred ninety-five patients with severe pain resulting from episiotomy, cesarean section, or gynecologic surgery completed a randomized, double-blind, stratified, parallel-group study. Patients were observed during a 4-hour period after medication. Based on the sum of the pain intensity differences (SPID), total pain relief (TOTPAR), and most of the hourly direct measures of pain and relief, both doses of the combination and ibuprofen 400 mg alone were statistically superior to placebo. Codeine 60 mg was statistically superior to placebo based on TOTPAR, the global ratings, and a few hourly measures. The mean effect of the combination of ibuprofen 400 mg plus codeine 60 mg was significantly superior to the mean effect of ibuprofen 400 mg alone 1/2, 1, and 2 hours after medication and to the mean effect of ibuprofen 400 mg alone and codeine 60 mg alone for SPID, TOTPAR, and other measures as well. The low-dose combination was significantly more effective than codeine 60 mg for a few hourly measures but was not significantly superior to ibuprofen 400 mg. Based on these findings it appears that the combination of ibuprofen 400 mg plus codeine 60 mg, particularly in the first few hours after medication, is more efficacious than its constituents.

Ibuprofen, zomepirac, aspirin, and placebo in the relief of postepisiotomy pain.

Our purpose was to compare the analgesic efficacy of single oral doses of ibuprofen, zomepirac, aspirin, and placebo in severe postepisiotomy pain. One hundred twenty subjects participated in a double-blind, single-dose, parallel-group, 4-hr trial comparing 400 mg ibuprofen, 100 mg zomepirac sodium, 600 mg aspirin, and placebo. For most parameters, including the sum of the pain intensity differences (SPID) and the sum of the hourly pain relief values (TOTAL), which are summary variables, each of the drugs was more effective than placebo. Ibuprofen was more effective than aspirin and zomepirac. Zomepirac and aspirin were equally effective for most of the analgesic variables. There were no adverse effects. Ibuprofen, 400 mg, is an effective oral analgesic and is more effective than 100 mg zomepirac and 600 mg aspirin in most parameters of pain.

Effect of caffeine on acetaminophen analgesia.

Our objective was to determine the value of caffeine in combination with acetaminophen in the relief of pain from uterine cramping, episiotomy, and third molar extraction. In the dental study, 173 patients received two or four tablets of 500 mg acetaminophen or the combination of 500 mg acetaminophen and 65 mg caffeine. In the three postpartum studies, 1345 patients received one, two, or three tablets of acetaminophen, the combination, or a placebo. The mean scores for the summary variable percent sum of the pain intensity differences (% SPID) were higher in all for the combination than for acetaminophen alone, and in two studies the null hypothesis of no differences was rejected. The relative potency estimates for % SPID were 1.9, 1.8, and 1.3 for the three studies in which bioassays could be performed and the pooled relative potency was 1.7 with a 95% confidence interval of 1.1 to 3.1. The results were essentially the same among pain models and among patient groups with similar habitual caffeine consumption. Onset of analgesia was also faster with the combination. We conclude that caffeine enhances the analgesic efficacy of acetaminophen.

Blunted change in cerebral glucose utilization after haloperidol treatment in schizophrenic patients with prominent negative symptoms.

OBJECTIVE: The purpose of this report was to determine 1) the effects of chronic haloperidol treatment on cerebral metabolism in schizophrenic patients, 2) the relation between negative symptoms and haloperidol-induced regional changes in cerebral glucose utilization, and 3) the relation between metabolic change and clinical antipsychotic effect. METHOD: Cerebral glucose utilization, as determined by position emission tomography (PET), was studied in 18 male schizophrenic subjects before and after chronic treatment with haloperidol at a standardized plasma level. RESULTS: Overall, haloperidol caused a widespread decrease in absolute cerebral glucose metabolism. The cerebral metabolic response to haloperidol was blunted in patients with high pretreatment negative symptom scores. CONCLUSIONS: Taken together with the results from a previously reported PET study of the effects of an acute amphetamine challenge (in which 14 of the current subjects participated), these data suggest that the negative symptom complex is associated with diminished cerebral response to change in dopaminergic activity. This deficit cannot be solely accounted for by structural differences.

Effects of prenatal exposure to neuroleptic drugs on children's growth.

The effect of prenatal exposure to neuroleptic drugs on height and weight from birth to 7 years was examined in children of psychiatrically normal parents and of parents with a history of psychiatric treatment, using data from the Collaborative Perinatal Project of the National Institute of Neurological Diseases, Communicative Disorders, and Stroke. Analysis of covariance was used to control for potential confounding factors. We found that prenatal exposure to dopamine receptor-blocking neuroleptic drugs was associated with increased height in one or more of our groups at 4 months, 1 year, and 7 years and less consistently with increased weight. Seven-year-old children who had been exposed to these drugs for more than 2 months during gestation were approximately 3 cm taller than unexposed controls (p less than 0.05). Prenatal exposure to dopamine-depleting agents was associated with decreased height at 4 months but not later. Possible mechanisms for these effects, including a permanent decrease in the number of brain dopamine receptors and effects on various hormones, are discussed.

Comparative study of flurbiprofen, zomepirac sodium, acetaminophen plus codeine, and acetaminophen for the relief of postsurgical dental pain.

The relative analgesic efficacy and safety of single oral doses of 50 and 100 mg of flurbiprofen (Ansaid, Upjohn) were compared with 100 mg of zomepirac sodium, 650 mg of acetaminophen plus 60 mg of codeine, 650 mg of acetaminophen alone, and placebo in a randomized, double-blind, parallel-group study. A total of 182 patients entered the study with moderate pain from a third molar extraction and were evaluated for six hours. For many efficacy variables, all active treatments were significantly (p less than or equal to 0.05) more effective than placebo. The two doses of flurbiprofen gave approximately similar results, suggesting a plateau effect above 50 mg. With the exception of relief at one hour, there were no significant differences between zomepirac and either dose of flurbiprofen. However, the mean response with zomepirac was greater than with either 50 or 100 mg of flurbiprofen during the first four hours and lower during the last two hours. The analgesic effects of acetaminophen alone were not significantly different from acetaminophen in combination with codeine. At the first hour, acetaminophen plus codeine led to significantly better pain relief than did 100 mg of flurbiprofen. After the first hour, flurbiprofen resulted in greater mean scores than acetaminophen alone or acetaminophen plus codeine, and these differences were significant at the fifth and sixth hours. Five patients had adverse reactions while receiving acetaminophen, acetaminophen plus codeine, or placebo. There were no adverse effects with flurbiprofen or zomepirac.

Analgesic efficacy of piroxicam in the treatment of postoperative pain.

Two randomized, double-blind, single-dose studies were conducted to assess the analgesic efficacy and safety of piroxicam for the treatment of moderate or severe postoperative pain. Study 1 evaluated the analgesic efficacy of piroxicam 20 mg compared with that of codeine sulfate 60 mg and placebo. A final patient population of 149 subjects rated pain intensity and pain relief at one half hour and one hour following treatment and then hourly for six hours, with a global assessment made at the completion of 24 hours. Piroxicam 20 mg was significantly more efficacious than placebo for all analgesic variables, including the sum of the pain intensity differences (SPID), total pain relief (TOTAL), percent SPID, duration of effect, and time to remedication. Codeine 60 mg was significantly superior to placebo for percent SPID and some hourly measures. Piroxicam 20 mg was significantly more effective than codeine 60 mg for percent SPID and a few hourly measures including time to remedication. Study 2 assessed the efficacy of piroxicam 20 mg or 40 mg compared with aspirin 648 mg and placebo. Sixty patients rated their pain intensity and relief hourly for 12 hours and at 24 hours after administration of study medication. Both doses of piroxicam were significantly more effective than placebo from Hours 2 to 12 for pain intensity difference (PID) and relief scores, as well as for SPID and TOTAL. Aspirin was significantly more effective than placebo from Hours 2 to 8 for relief and Hours 2 to 10 for PID as well as SPID and TOTAL. Piroxicam 40 mg was significantly more effective than aspirin 648 mg for SPID, TOTAL, and hourly measures beginning with Hour 6 through Hour 12. Piroxicam 20 mg was significantly better than aspirin for a few hourly measures: Hours 7 to 9 for relief and Hour 7 for PID. In addition, effects of piroxicam 20 mg had a significantly longer duration than aspirin. Similarly, piroxicam 20 mg had a significantly longer time to remedication compared with aspirin and placebo. The results of these studies provide evidence in support of the longer duration of analgesic efficacy of piroxicam compared with codeine or aspirin in patients with postoperative pain.

Estimating the size of a population from a single sample: methodology and practical issues.

In contrast to classical capture recapture methods, the single-sample method of Laska, Meisner, and Siegel (1988) (LMS) enables estimation of the size of a population, N*, on the basis of a single survey. For example, it may be desired to estimate the unduplicated number of individuals served by a mental health center during the last year on the basis of a 1-week sample. The time since each of the sampled individuals last engaged in the activity that defines the population is ascertained. The LMS estimator of N* and its unbiasedness property are motivated in a simple way, and an improved LMS estimator is introduced if additional information is available. An empirical assessment of the procedure is made using mental health service data for which the true population size is known. The performance of the extended LMS estimator is a substantial improvement over the standard LMS estimator.

Hypnotic activity of diphenhydramine, methapyrilene, and placebo.

In a double-blind controlled study, an oral dose of diphenhydramine hydrochloride (12.5, 25, or 50 mg), methapyrilene fumarate (36, 72, or 144 mg), or placebo was administered to 1295 post-partum patients if they complained of, or anticipated, a sleep problem. Hypnotic activity was assessed clinically by subjective and objective techniques. Methapyrilene and diphenhydramine, at all doses, were found to be effective hypnotics in comparison to placebo, based on sleep latency, sleep duration, awakening in the night, global evaluation, and morning alertness. Increasing the dose of these drugs, in the range studied, produced a minimal increase in effectiveness.