Metyrapone and cocaine: a double-blind, placebo-controlled drug interaction study.

Pre-clinical research suggests that suppression of adrenocorticosteroid synthesis might decrease susceptibility to stress-induced relapse. Metyrapone effectively suppresses cortisol synthesis and thus might have promise as a cocaine dependence treatment. The present inpatient study evaluated the interaction of metyrapone and cocaine to assess the safety of conducting an outpatient trial. Twelve nontreatment-seeking cocaine-dependent individuals completed this double-blind, placebo-controlled, crossover study with two factors: medication (750 mg of metyrapone vs. placebo) and infusion (40 mg of cocaine vs. saline). Safety measures included vital signs, adverse events, and electrocardiogram. Efficacy measures included visual analog scale (VAS) ratings of craving and drug effect. Neuroendocrine measures included cortisol and ACTH. As predicted, metyrapone was well tolerated and did not exacerbate cocaine's physiological effects. Also as predicted, metyrapone did not significantly alter cocaine's subjective effects. The results of the present study suggest that metyrapone at the dose studied can likely be used safely in an outpatient study with active cocaine users.

The HPA axis in cocaine use: implications for pharmacotherapy.

The role of the hypothalamic-pituitary-adrenal (HPA) axis in cocaine use is reviewed within the context of two approaches to developing pharmacological treatments in humans: (1) reducing the reinforcing effects of cocaine and (2) reducing cocaine addict's susceptibility to stress-induced relapse. This review suggests that HPA-axis-suppressing medications are unlikely to block cocaine's reinforcing effects completely but may be useful in decreasing the frequency of use by increasing the addicted individual's resistance to stress-induced relapse. Implications for designing inpatient studies to test the safety and efficacy of candidate pharmacological agents are discussed.

The measurement of craving.

This article presents an overview of the definition and measurement of "craving" as it is applied to drug and alcohol abuse research. Examples of craving measures are described and organized in terms of whether they structure craving as a single factor or as a multifactorial construct. The application of craving scales in cue-conditioning studies, in medication treatment trials, and as outcome measures in other treatment studies is considered. It is concluded that no single craving scale, or type of scale, has unequivocal support, because few studies have administered more than one scale to the same population. It is suggested that our understanding of craving will be advanced by designing studies that compare and contrast several craving scales within the same study. Likewise, craving is only one possible cause of relapse. Future studies should compare several alternate relapse mechanisms within the same study.

Understanding birthing mode decision making using artificial neural networks.

BACKGROUND: This study examined obstetricians' decisions to perform or not to perform cesarean sections. The aim was to determine whether an artificial neural network could be constructed to accurately and reliably predict the birthing mode decisions of expert clinicians and to elucidate which factors were most important in deciding the birth mode. METHODS: Mothers with singleton, live births who were privately insured, nonclinic, non-Medicaid patients at a major tertiary care private hospital were included in the study (N = 1508). These mothers were patients of 2 physician groups: a 7-obstetrician multispecialtygroup practice and a physician group of 79 independently practicing obstetricians affiliated with the same hospital. A feedforward, multilayer artificial neural network (ANN) was developed and trained. It was then tested and optimized until the most parsimonious network was identified that retained a similar level of predictive power and classification accuracy. The performance of this network was further optimized using the methods of receiver operating characteristic (ROC) analysis and information theory to find the cutoff that maximized the information gain. The performance of the final ANN at this cutoff was measured using sensitivity, specificity, classification accuracy, area under the ROC curve, and maximum information gain. RESULTS: The final neural network had excellent predictive accuracy for the birthing mode (classification accuracy = 83.5%; area under the ROC curve = 0.924; maximum information = 40.4% of a perfect diagnostic test). CONCLUSION: This study demonstrated that a properly optimized ANN is able to accurately predict the birthing mode decisions of expert clinicians. In addition to previously identified clinical factors (cephalopelvic disproportion, maternal medical condition necessitating a cesarean section, arrest of labor, malpresentation of the baby, fetal distress, andfailed induction), nonclinical factors such as the mothers' views on birthing mode were also found to be important in determining the birthing mode.

Diabetes mellitus en el anciano: problemática en la atención primaria / Diabetes mellitus in the elderly: primary attention problem

La diabetes mellitus en los ancianos es una enfermedad de elevada prevalencia, morbilidad y mortalidad. Con el objetivo de conocer la problemática de esta enfermedad en ancianos atendidos en el Policlínico "Puentes Grandes" se seleccionaron a 246 por muestreo simple aleatorioen una sola etapa, de los 1,581 ancianos que se atienden en dicha área. A los mismos se les realizó interrogatorio para conocer aspectos generales, demográficos, historia médica, funcionamiento físico, hábitos tóxicos, uso de medicamentos y servicios de salud, niveles de tensión arterial y se evaluó su capacidad funcional. Los datos obtenidos fueron introducidos en una aplicación realizada en Foxpro 2.0 para DOS y analizadas en el paquete EPI-INFO 6.0 (CDC-Atlanta). Para analizar variables cualitativas se realizó una prueba de independencia de chi cuadrado o Prueba de Fisher. Para analizar las variables cuantitativas se realizó comparación de medidas en grupos independientes. El 16,6 porciento de los ancianos refirieron ser diabéticos y en ellos predominaron, cuando se les camparó con los ancianos no diabéticos, loa antecedentes de enfermedades de etiología aterosclerótica, la hipertensión arterial, las dificultades para la visión cercana, y la presencia de discapacidades funcionales. Asimismo tuvieron edades medias mayores, y habían usado con mayor frecuencia los servicios de salud. Se concluye que la elevada prevalencia de casos conocidos y su morbilidad, además de la alta frecuencia de discapacidades hacen de la Diabetes mellitus un problema de salud en los ancianos estudiados (AU)

Identifying personality disorders: towards the development of a clinical screening instrument.

The study objective was to identify a set of personality disorder (PD) criteria from the DSM PD diagnostic sets that can be used to detect subjects with an increased likelihood of having a PD diagnosis. In a series of outpatients evaluated systematically in two waves for every criteria item for 12 DSM-III-R PDs, stepwise logistic regression identified 45 criteria as discriminative for their specific PDs, which are selected for further analysis to assess their ability to discriminate for any PD. Receiver operating characteristic (ROC) analysis is used to evaluate their discriminative power in an independent conjoined sample (N = 1,342) from six centers that assessed every PD criteria item by structured instrument (Structured Clinical Interview for DSM-III-R PDs [SCID-II, Personality Disorder Examination [PDE], and Structured Interview for DSM-III-R PDs [SIDP-R]). The cutoff that maximizes information gain is used to determine the diagnostic threshold (DT). Initially, 15 of 45 criteria are identified. At the 0.43 PD prevalence, a DT of 2 or more of the 15 PD criteria across samples is optimal. The maximum information gain (MIG) is .42 bits, and the AUR is 0.94+/-.007. Other performance indices at this cutoff are .90 sensitivity, .84 specificity, .81 positive predictive power (PPP), .91 negative predictive power (NPP), and .86 hit rate (HR). Taken collectively, the 15 PD criteria selected by the data reduction techniques suggest a narrowed set to be assessed in screening for the presence or absence of any PD with comparable or better psychometric properties than other tests routinely used for diagnosing medical and psychiatric disorders. If specific PD categorization is needed, a second-step comprehensive assessment should follow.

Prevalencia del hipotiroidismo del anciano en un área de atención primaria de Ciudad de La Habana / Prevalence of hyperthyroidism in the elderly in a primary attention area of the city of Havana

El hipotiroidismo constituye un problema prevalente y subvalorado en los ancianos, y por no conocer la frecuencia de esta enfermedad en población general cubana, decidimos realizar el presente estudio. Entre los pacientes atendidos en un Grupo Básica de Trabajo del policlínico "Alumna Aleida Fernández Chardiet" (Municipio Lisa-Ciudad de La Habana) que atiende 1 912 ancianos, se seleccionaron 71 por muestreo simple aleatorio monoetápico, a los cuales se le realizaron determinaciones de hormonas tiroideas por radioinmunoanálisis (Kits diagnósticos del Instituto Nacional de Endocrinología, Ciudad de La Habana, Cuba). Los resultados fueron incluidos en una aplicación realizada en Foxpro 2.0 para DOS y analizados en Epi-info 6.04 (CDC-Atlanta). El 30,9 porciento de los ancianos presentó hipotiroidismo, lo cual es muy superior a lo señalado en otros estudios. El 1.3 porciento de los ancianos presentó hipotiroidismo clínico, con predominio de pacientes del sexo femenino (p<0.001). La prevalencia del hipotiroidismo en ancianos atendidos en el nivel primario fue significativamente elevada, con amplio predominio de casos subclínicos y del sexo femenino. Se requieren estudios que profundicen en el conocimiento de esta enfermedad en los ancianos cubanos (AU)

Protein bound iodine in normal pregnancy

Protein-bound iodine (PBI) has been reported to be evaluated during normal pregnancy by foreign investigators. This study on 103 normal pregnant Filipino women, however, showed the mean PBI value to be within normal limits, 6.76 +/- 0.1754 ugms/100 ml serum. The mean PBI values of each trimester was found to be also within normal limits; 6.03 +/- .3331 in the first trimester; 6.96 +/- .2983 in the second trimester and 6.89 +/- .2618 in the third trimester. (Summary)

Plans, designs, and analyses for clinical trials of anti-cocaine medications: where we are today. NIDA/VA/SU Working Group on Design and Analysis.

Increased interest in addiction psychopharmacology has raised unique methodologic issues in the design, conduct, and analysis of outcomes in clinical trials of therapeutic agents for drug dependence. This article summarizes issues raised at a meeting in Palo Alto, California, on November 4, 1996, that was sponsored by the Medication Development Division of the National Institute on Drug Abuse and the Department of Veterans Affairs Cooperative Studies Program to discuss the methodologic issues in clinical trials of cocaine pharmacotherapy.

Treatment outcome of an outpatient treatment program for dually-diagnosed veterans: the Cincinnati Veterans Affairs Medical Center.

The Dual Diagnosis Clinic at the Cincinnati VA Medical Center is an integrated treatment program for veterans who have an Axis I psychiatric illness in addition to a substance dependence problem. With a high staff-to-patient ratio and an individualized approach, the DDC treats many dual diagnosis patients effectively. To demonstrate the effectiveness of this approach, an outcome study was conducted looking at the psychiatric emergency room visits, hospitalization rates, and the average length of stay for 557 DDC patients. Patients were divided into two groups: those who completed the assessment period, and those who did not. Equal periods of time before and after this assessment period were studied. Those who completed were more likely to have had fewer psychiatric emergency room visits (p < 0.000001) after the assessment period than before when compared to dropouts. The engaged group had the same or more hospital admissions after the assessment period than before, while the dropout group had fewer. This suggests that there is a significant disorder of engagement for the dual diagnosis populations, and that the first impact of successful treatment is engagement.

What would it take for electrophysiology to become clinically useful?

In this article we discuss the procedures that should be followed in order to develop diagnostic tests based on electrophysiologic parameters that would be useful to practicing psychiatrists in their efforts to diagnose mental disorders. To do this, we start by giving an overview of receiver operating characteristic (ROC) analysis, with which a candidate diagnostic test can be characterized mathematically. This methodology allows for an estimate of the overall discriminating power of the diagnostic test and thus can be used to compare the performance of one diagnostic test with that of another. However, ROC analysis cannot be used for optimizing a given diagnostic test (ie, determining the "best" cut-off) and, because it does not incorporate Bayes' theorem, it cannot be used to compare the performances of diagnostic tests when it is given to different risk groups for the target disorder. Both of these problems can be solved by using the concept of information theory. The equation for information gain automatically takes Bayes' theorem into consideration and also provides an intrinsic criterion for finding the cut-off that best discriminates between individuals who do and those who do not have the target disorder. Neither ROC analysis nor information theory are model dependent; however, if the equation for the frequency distribution of the electrophysiologic variable is known for the disease-positive and disease-negative populations, the calculations are greatly simplified. Therefore, the assumption is often made that both of these distributions (or transformations of the distributions) are Gaussian. However, studies have shown that the results of ROC analysis are quite robust to deviations from normality of the underlying distributions.

Cerebrospinal fluid neuroendocrinology of alcohol misusers.

Cerebrospinal fluid (CSF) neurohumors reflect central nervous system physiology in a way that peripheral indices can not. We reviewed clinical studies of CSF biogenic amines and neurohormones in alcohol misusers during various stages of withdrawal or abstinence and found them difficult to compare because of highly variable experimental methods, reliance on single time collections (lumbar punctures) that fail to control for potential stress-induced effects of the procedure, lack of control for tobacco use, and a paucity of non-alcoholmisusing controls. However, taken together, the data thus far show that a variety of neuroactive substances are reduced in concentration in the CSF of some alcohol misusers. Low CSF levels of corticotropinreleasing hormone, beta-endorphin, norepinephrine, diazepam-binding inhibitor, 5-hydroxyindoleacetic acid and somatostatin have all been reported. Whether the decreased CSF levels of these neurohormones and neurotransmitters are a cause or consequence of alcoholism has not been determined. In fact, further studies using serial or continuous CSF sampling techniques with homogeneous, better-characterized patients and normal volunteers are still needed to establish the precise CSF neurochemical abnormalities in alcohol misusers.

Eccentric diagnostic tests: redefining sensitivity and specificity.

Diagnostic tests exist for which the current definitions of sensitivity and specificity are inadequate. Such tests are called eccentric to distinguish them from normal diagnostic tests, for which the standard definitions are satisfactory. It is shown that when the standard definitions are used with eccentric tests there will be an appreciable range of cutoff values over which the test has no discriminating power. This is demonstrated with ROC analysis and information theory. New definitions of sensitivity and specificity that are valid for both normal and eccentric tests are proposed. These definitions require the use of two cutoffs to distinguish test-positive from test-negative individuals. When the new definitions are used with eccentric tests, performance improves significantly and the anomalous regions of zero discriminating power disappear. In the limit of zero eccentricity the new definitions become identical to the old.

A computerized procedure for developing and administering time perception protocols: application to a sample of adults and adolescents.

The principal goals of this work are: (a) To describe an integrated computerized procedure for designing, administering, and recording time perception experiments (more specifically, reaction time and time estimation) on human subjects; (b) To present the results of applying this procedure to the study of fourteen normal adolescents and fourteen normal adults. Individualized time perception protocols can be designed with this menu-driven highly interactive computer-program. Such protocols can then be used for testing experimental subjects. The programs run on any IBM-compatible computer, and the resulting test data are stored in ASCII format. As an example of the use of this procedure, reaction time with five regular and irregular preparatory intervals (PIs), and time estimation of 10 s with and without feedback was measured on normal adolescents and adults. For short PIs the adolescents had reaction times (RTs) similar to adults, but significant longer RTs than adults for long PIs. In the case of time estimation no differences between the two groups were observed; however, both groups underestimated time when no feedback was provided; that is, they thought that less time had elapsed than really had.

Differentiating major depression and panic disorders by self-report and clinical rating scales: ROC analysis and information theory.

The revised Beck Depression Inventory, Beck Anxiety Inventory, the Cognition Checklist Depression and Anxiety subscales, revised Hamilton Psychiatric Rating Scale for Depression (HRSD-R), and the revised Hamilton Anxiety Rating Scale were administered to 92 outpatients diagnosed only with major depression disorders and 50 outpatients diagnosed only with panic disorders. A receiver operating characteristic (ROC) analysis was used to evaluate each instrument's ability to discriminate the two diagnostic groups. The optimum cut-off score for each scale was determined as a function of prevalence by maximizing information gain. The results indicated that the depression scales were better than the anxiety scales in discriminating the two groups. The HRSD-R was superior to the other depression scales, whereas all the anxiety scales displayed similar discriminating power.

Classification of diagnostic tests.

A method is described for classifying diagnostic tests. It is valid for the large subgroup of tests for which the measured diagnostic variable has a normal distribution for the affected and non-affected individuals. It is based on placing each diagnostic test as a point on a two-dimensional graph, called a separation-asymmetry (SA) diagram, whose x-axis is the separation between the two normal distributions and whose y-axis is the logarithm of the ratio of their standard deviations. The SA diagram is partitioned into functional regions by curves of constant performance, as measured by the percent overlap between the two normal distributions. The concept of 'eccentricity' in a diagnostic test is defined, and the relationship between eccentricity and test validity is discussed. This quantity is also incorporated into SA diagrams, thus allowing a clinician to determine, by inspection, if a given diagnostic test positioned on an SA diagram is valid for clinical use. The logic engine used for calculating iso-performance curves is given, as well as the computer programs which utilize it. Possible ways of using this classification scheme are suggested.

Classifying binormal diagnostic tests using separation-asymmetry diagrams with constant-performance curves.

A method is proposed for classifying diagnostic tests that have underlying binormal distributions. The method involves using the parameters that characterize these distributions as axes of a two-dimensional graph called a separation-asymmetry (S-A) diagram. Each point on an S-A diagram corresponds to a possible diagnostic test. The diagram also has superimposed on it any of three possible families of curves of constant performance: curves of constant area under the ROC graph (iso-AUR), curves of constant overlap area (iso-OA), and curves of constant maximum information (iso-MaxInfo). Thus, the performance of any test can be determined immediately by identifying the iso-performance curve of the desired type that passes through the corresponding point of the S-A diagram. The concept of "eccentric" diagnostic tests is defined and incorporated into the S-A diagrams. The classification scheme is applied to 28 diagnostic tests. Excellent agreement is found in the ranking between the iso-OA and iso-MaxInfo measures of performance, but the iso-AUR produces markedly different results. Only three of the 28 tests were found to be eccentric. Several other interesting patterns emerged.

A neural-network approach to predicting admission decisions in a psychiatric emergency room.

Clinical decision making is based on recognizing complex patterns of patients' signs and symptoms. Neural networks have been shown to be very effective at this type of pattern recognition, and in this study a neural-network approach was used to predict which patients seen in a psychiatric emergency room required admission and which did not. Data from all walk-in patients (N = 658) evaluated during normal working hours in a psychiatric emergency room during a one-year period were used either to train a neural network or to test its performance. The network had 53 input nodes, one hidden layer, and an output layer with a single node. The back-propagation method was used to train the network. The neural network's admitting decisions were in substantial agreement with those of the clinicians (kappa coefficient = 0.63). When used as a diagnostic test for admission it had a specificity of 94%, a sensitivity of 70%, and an overall accuracy of 91%. The information gain was 35% of that of a perfect diagnostic test. These results show that a neural network can be trained to make clinical decisions that are in substantial agreement with those of experienced clinicians.