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.

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.

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.

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.

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.

Quantitative differences in aspirin analgesia in three models of clinical pain.

An analysis was made of data from over 4000 postepisiotomy, uterine cramping, and postsurgical patients complaining of moderate or severe pain. They had received 325, 650, or 1300 mg aspirin or placebo while they were subjects in 10 analgesic clinical trials. On the average, for the same verbally expressed pain intensity level and the same treatment, more relief was obtained by a patient with uterine cramping than one with episiotomy pain, who in turn obtained more relief than a patient with surgical pain. A new mathematical model which characterizes the probability that an analgesic provides complete relief as a function of dose, severity of pain intensity, and pain etiology is developed. The model utilizes the data itself to estimate the numerical score corresponding to verbal pain intensities. The results indicate that the numerical score quantifying severe surgical pain is 1.4 times greater than the score for severe episiotomy pain, which in turn is 3.2 times greater than the score for severe uterine cramping. Clinical trials must be designed to take these differences into account. Also, clinicians must be cognizant of such differences when choosing among drugs and dosages for patients with different pain intensity and etiology.

Placebo washout in trials of antipsychotic drugs.

For antipsychotic phase 3 clinical trials, we compare the relative merits of a placebo washout period with an alternate design strategy using a low-dose antipsychotic treatment. Evaluations are made with respect to the achievement of specific clinical trial design goals including the effect on power for detecting between-treatment and within-treatment pre-post differences. The relative merits of these two designs are discussed separately for those patients who enter the initial leadin period after withdrawal from previous antipsychotic medication and for those not on medication immediately before that period.

An analytic approach to quantifying pain scores.

Statistical problems in clinical trials frequently involve fitting regression lines when the underlying data are categorical or ordinal response variables. Usually an ad hoc a priori quantification is used to assign values to these ordinal responses. For pain intensity data collected in analgesic trials, the usual approach is to set none equal to 0, mild equal to 1, moderate equal to 2, and severe equal to 3. While this scheme has been generally accepted, on the basis that for similar clinical trials reasonably similar results are obtained by different investigators, concern exists that the distances between pain scores are probably not equal. A method is presented for quantifying categorical responses so that the resulting scores maximize the simultaneous fit of the dose-response regression lines. The optimal scores derived by this technique may then be used in a bioassay analysis to estimate the relative potency of 2 compounds. As illustrative examples, this method was applied to data from 2 clinical trials and the results were compared to the usual method.

Analgesic effect of graded doses of flurbiprofen in post-episiotomy pain.

Our purpose was to evaluate the analgesic efficacy and safety of single oral doses of flurbiprofen 25, 50 and 100 mg, aspirin 600 mg, and placebo in the relief of moderate to severe post-episiotomy pain. One hundred and fifty-two evaluable patients completed a randomized, double-blind, stratified, parallel groups study. They were observed over a six hour period by one nurse-observer. Based upon each of the summary efficacy measures SPID, TOTAL and PEAK % and most of the hourly direct measures of pain intensity and pain relief, each of the four active treatments were statistically superior to placebo. Flurbiprofen 25 mg appeared to be slightly less effective than aspirin 600 mg, but the differences were not statistically significant. Flurbiprofen 50 and 100 mg were quite similar and were significantly more effective than aspirin 600 mg and flurbiprofen 25 mg. There were no observed or reported adverse effects.

Analgesic effects of oral propiram fumarate, codeine sulfate and placebo in postoperative pain.

Our purpose was to evaluate the analgesic efficacy and safety of single oral doses of propiram fumarate 50 mg, codeine sulfate 60 mg and placebo in the relief of moderate to severe postoperative pain. One hundred and twenty patients completed a randomized, double-blind, single-dose, stratified, parallel-groups trial and were observed for either 4 or 6 hours. Based upon each of the summary efficacy measures--SPID, % SPID and TOTAL--propiram and codeine were approximately equally effective and both were statistically superior to placebo. Propiram was significantly more effective than codeine at hour 5 for Pain Intensity Difference. Two adverse effects were attributed to propiram. Propiram fumarate 50 mg is an effective oral analgesic similar to codeine sulfate 60 mg, with the possibility of a longer duration of action.

The prevalence and correlates of untreated serious mental illness.

OBJECTIVE: To identify the number of people in the United States with untreated serious mental illness (SMI) and the reasons for their lack of treatment. DATA SOURCE/STUDY DESIGN: The National Comorbidity Survey; cross-sectional, nationally representative household survey. DATA COLLECTION: An operationalization of the SMI definition set forth in the Alcohol, Drug Abuse, and Mental Health Administration Reorganization Act identified individuals with SMI in the 12 months prior to the interview. The presence of SMI then was related to the use of mental health services in the past 12 months. PRINCIPAL FINDINGS: Of the 6.2 percent of respondents who had SMI in the year prior to interview, fewer than 40 percent received stable treatment. Young adults and those living in nonrural areas were more likely to have unmet needs for treatment. The majority of those who received no treatment felt that they did not have an emotional problem requiring treatment. Among those who did recognize this need, 52 percent reported situational barriers, 46 percent reported financial barriers, and 45 percent reported perceived lack of effectiveness as reasons for not seeking treatment. The most commonly reported reason both for failing to seek treatment (72 percent) and for treatment dropout (58 percent) was wanting to solve the problem on their own. CONCLUSIONS: Although changes in the financing of services are important, they are unlikely by themselves to eradicate unmet need for treatment of SMI. Efforts to increase both self-recognition of need for treatment and the patient centeredness of care also are needed.

Power and sample size in cost-effectiveness analysis.

For resource allocation under a constrained budget, optimal decision rules for mutually exclusive programs require that the treatment with the highest incremental cost-effectiveness ratio (ICER) below a willingness-to-pay (WTP) criterion be funded. This is equivalent to determining the treatment with the smallest net health cost. The designer of a cost-effectiveness study needs to select a sample size so that the power to reject the null hypothesis, the equality of the net health costs of two treatments, is high. A recently published formula derived under normal distribution theory overstates sample-size requirements. Using net health costs, the authors present simple methods for power analysis based on conventional normal and on nonparametric statistical theory.

Importance of pharmacologic control in PET studies: effects of thiothixene and haloperidol on cerebral glucose utilization in chronic schizophrenia.

This study compares the effects of two neuroleptic drugs with different pharmacologic characteristics (thiothixene and haloperidol) on cerebral glucose utilization in chronic schizophrenic inpatients. Positron emission tomographic (PET) scans were obtained from all subjects in a neuroleptic-free condition and again after 4-6 weeks of neuroleptic treatment. Eight subjects were treated with thiothixene and 12 with haloperidol. Thiothixene and haloperidol had different metabolic effects. For example, all thiothixene-treated subjects showed increased whole brain glucose utilization; all but one haloperidol-treated subject showed decreased utilization. Different patterns of relative prefrontal and striatal metabolism were also observed. These results highlight the importance of controlling for the effects of neuroleptic treatment and indicate the difficulty of interpreting data from studies with complex or poorly defined drug regimens.

29. The Multi-State Information System for Psychiatric patients.

The Multi-State Information System for Psychiatric Patients (MSIS) is a computer based, clinical and administrative management information system used by numerous mental health programs and facilities for patient and program management. Structured forms are used for the collection of core information on patients, on services rendered, on affiliated agencies, and on fiscal and administrative processes. A variety of output reports and general retrieval techniques are being used to help administer and evaluate patient care programs, monitor clinical and program management functions, refer clients to other service agencies, and review individual cases, as well as for administrative functions such as cost finding, rate setting, billing, and inventory control. MSIS is currently field testing an automated problem-oriented psychiatric record, and a goal-oriented record to be used with the mentally retarded is under development.

Assessing the onset of relief of a treatment for migraine.

It is common for clinical trials designed to compare treatments for migraine to incorporate a component for estimating onset. Our objective is to describe a stopwatch method for collecting data on time to meaningful relief and a conceptual framework for describing and analysing the results. The survival distribution of onset is modelled in two parts: the probability that onset does not occur, and the survival distribution conditional on its occurrence. Using data from a clinical trial comparing an active treatment and placebo, we illustrate the method and find that the distributions of onset among those with onset do not differ, but the probabilities that onset occurs are substantially different. We illustrate how the model can be used to help determine how long patients without onset should wait before further intervention, how patients interpret the phrase meaningful relief, and how baseline clinical characteristics affect the onset.

Nonparametric estimation and testing in a cure model.

Nonparametric generalized maximum likelihood product limit point estimators and confidence intervals are given for a cure model with random censorship. One-, two-, and K-sample likelihood ratio tests for inference on the cure rates are developed. In the two-sample case its power is compared to the power of several alternatives, including the log-rank and Gray and Tsiatis (1989, Biometrics 45, 899-904) tests. Implications for the use of the likelihood ratio test in a clinical trial designed to compare cure rates are discussed.