Examining the reliability of alcohol/drug use and HIV-risk behaviors using Timeline Follow-Back in a pilot sample.

Research on the course of substance use disorders (SUDs) faces challenges in assessing behavior over lengthy time periods. Calendar-based methods, like the Timeline Followback (TLFB), may overcome these challenges. This study assessed the reliability of self-reported weekly alcohol use, drug use, and HIV-risk behaviors over the past 90 days using an interview TLFB. Individuals with SUD in outpatient treatment (N = 26) completed the TLFB at baseline and then a week later with separate interviewers. Weekly ratings were aggregated across 4 week intervals for each administration. Intra-class correlations were used to compare agreement between the two administrations. Reliabilities for alcohol and drug use ratings ranged from good to excellent for most drug categories (ICCs = 0.76 - 1.00), except opioid use (other than heroin) and sedative use produced sub-standard reliabilities (ICCs = 0.29 - 0.74). HIV-risk behavior reliabilities also ranged from good to excellent (ICCs = 0.70 - 0.97), but were substandard for the number of casual sex partners for some intervals (ICCs = 0.29, 0.63). Findings extend support for the use of TLFB to produce reliable assessments of many drugs and HIV-risk behaviors across longitudinal intervals.

A 4-year prospective observational follow-up study of course and predictors of course in body dysmorphic disorder.

BACKGROUND: This report prospectively examines the 4-year course, and predictors of course, of body dysmorphic disorder (BDD), a common and often severe disorder. No prior studies have prospectively examined the course of BDD in individuals ascertained for BDD. Method The Longitudinal Interval Follow-Up Evaluation (LIFE) assessed weekly BDD symptoms and treatment received over 4 years for 166 broadly ascertained adults and adolescents with current BDD at intake. Kaplan-Meier life tables were constructed for time to remission and relapse. Full remission was defined as minimal or no BDD symptoms, and partial remission as less than full DSM-IV criteria, for at least 8 consecutive weeks. Full relapse and partial relapse were defined as meeting full BDD criteria for at least 2 consecutive weeks after attaining full or partial remission respectively. Cox proportional hazards regression examined predictors of remission and relapse. RESULTS: Over 4 years, the cumulative probability was 0.20 for full remission and 0.55 for full or partial remission from BDD. A lower likelihood of full or partial remission was predicted by more severe BDD symptoms at intake, longer lifetime duration of BDD, and being an adult. Among partially or fully remitted subjects, the cumulative probability was 0.42 for subsequent full relapse and 0.63 for subsequent full or partial relapse. More severe BDD at intake and earlier age at BDD onset predicted full or partial relapse. Eighty-eight percent of subjects received mental health treatment during the follow-up period. CONCLUSIONS: In this observational study, BDD tended to be chronic. Several intake variables predicted greater chronicity of BDD.

Personality traits as prospective predictors of suicide attempts.

OBJECTIVE: To examine higher order personality factors of negative affectivity (NA) and disinhibition (DIS), as well as lower order facets of impulsivity, as prospective predictors of suicide attempts in a predominantly personality disordered sample. METHOD: Data were analyzed from 701 participants of the Collaborative Longitudinal Personality Disorders Study with available follow-up data for up to 7 years. Cox proportional hazards regression analyses was used to examine NA and DIS, and facets of impulsivity (e.g. urgency, lack of perseverance, lack of premeditation and sensation seeking), as prospective predictors of suicide attempts. RESULTS: NA, DIS and all facets of impulsivity except for sensation seeking were significant in univariate analyses. In multivariate models which included sex, childhood sexual abuse, course of major depressive disorder and substance use disorders, only NA and lack of premeditation remained significant in predicting suicide attempts. DIS and the remaining impulsivity facets were not significant. CONCLUSION: NA emerged as a stronger and more robust predictor of suicide attempts than DIS and impulsivity, and warrants greater attention in suicide risk assessment. Distinguishing between facets of impulsivity is important for clinical risk assessment.

Long-term recall of social relationships related to addiction and HIV risk behaviors.

BACKGROUND: Social relationships have been demonstrated as a key predictor of relapse among addicted persons and are likely to be important determinants of HIV risk behaviors also. However, the degree to which this population can reliably and consistently identify important people (IPs) in retrospect has been understudied. METHODS: Using the modified Important People and Activities questionnaire, we investigated to what degree IPs were dropped, added, or retained, and whether data about individual IPs were reported accurately on 6- and 12-month follow up periods using a sample of 50 drug or alcohol abusing participants. RESULTS: We found that IPs were largely retained, and that those retained versus dropped/added differed by their reaction to participant alcohol/drug use, as well as frequency of contact. We further found that there were differences in reliability of data describing specific IPs. While both 6- and 12-month follow up periods led to reliabilities ranging from excellent to fair, we found poorer reliability on responses to recall of "frequency of contact" and "reactions to drinking", as well as "reactions to drug use". CONCLUSION: Future investigations of reliability of social relationships recalled retrospectively should attempt to examine possible systematic biases in addition to the reliability of specific IP data. More sophisticated studies are needed on factors associated with systematic variation in reporting of aspects of social relationships that are associated with addictions or HIV risk outcomes.

Delusional versus nondelusional body dysmorphic disorder: clinical features and course of illness.

DSM-IV's classification of body dysmorphic disorder (BDD) is controversial. Whereas BDD is classified as a somatoform disorder, its delusional variant is classified as a psychotic disorder. However, the relationship between these BDD variants has received little investigation. In this study, we compared BDD's delusional and nondelusional variants in 191 subjects using reliable and valid measures that assessed a variety of domains. Subjects with delusional BDD were similar to those with nondelusional BDD in terms of most variables, including most demographic features, BDD characteristics, most measures of functional impairment and quality of life, comorbidity, and family history. Delusional and nondelusional subjects also had a similar probability of remitting from BDD over 1 year of prospective follow-up. However, delusional subjects had significantly lower educational attainment, were more likely to have attempted suicide, had poorer social functioning on several measures, were more likely to have drug abuse or dependence, were less likely to currently be receiving mental health treatment, and had more severe BDD symptoms. However, when controlling for BDD symptom severity, the two groups differed only in terms of educational attainment. These findings indicate that BDD's delusional and nondelusional forms have many more similarities than differences, although on several measures delusional subjects evidenced greater morbidity, which appeared accounted for by their more severe BDD symptoms. Thus, these findings offer some support for the hypothesis that these two BDD variants may constitute the same disorder. Additional studies are needed to examine this issue, which may have relevance for other disorders with both delusional and nondelusional variants in DSM.

Sulindac kinetics and effects on renal function and prostaglandin excretion in renal insufficiency.

The purpose of this study was to evaluate the pharmacokinetics of sulindac, a purported "renal sparing" nonsteroidal anti-inflammatory drug, and its effects on renal function and prostaglandin excretion in patients with reduced glomerular filtration rate. Twelve female patients (glomerular filtration rate 37 +/- 4 mL/min) were treated with sulindac 200 mg bid for 11 days. Urinary PGE2, 6-keto-PGF1 alpha and serum thromboxane (TxB2) generation were measured by radioimmunoassay (RIA) following extraction on C-18 columns. Glomerular filtration rate and effective renal plasma flow were measured by 99TC-DPTA and 131I-para-aminohippuric acid clearance. In six patients serum and urine levels of sulindac and its metabolites were measured by high-pressure liquid chromatography (HPLC). Sulindac was rapidly absorbed and converted to sulindac sulfide with peak levels 2 hours after a single dose, but steady state levels were not reached prior to drug discontinuation. Sulindac sulfide AUC (0-5 hours micrograms min/mL) progressively increased from 382 to 3,030 on day 11. It did not appear in the urine. Baseline urinary PGE2 and 6-keto-PGF1 alpha excretion were 23.8 +/- 5.6 and 18.9 +/- 2.7 ng/hr respectively and were reduced by 68% and 47% by day 4 of therapy. TxB2 generation fell by 34% after one dose and by 67% by day 11. There was a significant increase in serum creatinine from 1.88 +/- 0.13 mg/dl before treatment to 2.16 +/- 0.15 mg/dL (P less than .05) after eleven days.(ABSTRACT TRUNCATED AT 250 WORDS)

The novel therapeutic implications of azlocillin's dose-dependent pharmacokinetics: contributing physiologic mechanisms and a prospective, cross-over designed trial.

Azlocillin is an important acylureido penicillin antibiotic for the management of complex gram-negative infections particularly those caused by Pseudomonas species. The current studies demonstrate that it manifests dose-dependent pharmacokinetics during the usual regimens of clinical dosing, that enterohepatic recirculation does not occur and that renal tubular secretion (maximum renal tubular secretory capacity 300 +/- 30 micrograms/min) and hepatic metabolism appear to be the dominant contributors to the dose-dependent nature of azlocillin. The possible therapeutic implications of azlocillin's dose dependency were evaluated by undertaking a six-day randomized, prospective, cross-over design study to evaluate the pharmacokinetic disposition of the drug during a 3-g q4h (typically used in adults) regimen versus a 5-g q8h regimen. By using the area under the serum-time concentration curve (AUC) as the major comparative parameter for these two regimens, the results demonstrate that both regimens provide approximately equal quantitative amounts of the drug systemically as a result of azlocillin's dose dependency. The AUC values, although not therapeutic end points, nonetheless correlate well with clinical response to antibiotic therapy. The 5-g q8h regimen was well tolerated. It is less disruptive for patients, requires half the number of intravenous administrations, 17% less drug, and is more cost effective than the 3-g q4h regimen.

Calcium channel blockade in experimental aminoglycoside nephrotoxicity.

Calcium channel blocker therapy has proved protective in certain models of ischemic-induced acute renal failure. This effect may be related to the prevention of calcium influx into injured cells or by the vasodilatory effects of verapamil that may result in an improvement in renal blood flow. In the current study, the effect of verapamil treatment on the development of renal insufficiency and renal tissue calcium accumulation following aminoglycoside administration was investigated. The degree of functional damage and cortical tissue calcium accumulation after six or nine days of gentamicin administration (120 mg/kg body weight/day) was not significantly different in rats whose drinking water contained verapamil (10 mg/100 cc) than corresponding values in control animals. The tissue calcium accumulation correlated with the degree of reduction of creatinine clearance and probably reflects the extent of lethal tubular cell injury.

Dibekacin intrarenal distribution characteristics and renal cortical elution kinetics. Comparison with gentamicin and tobramycin.

Dibekacin (3',4-dideoxykanamycin B) is a new semisynthetic aminoglycoside developed in Japan and one which has found wide clinical acceptance in that country. The antibacterial activity of this compound indicates that it is relatively similar to gentamicin. Since it appears that the intrarenal distributional characteristics and renal cortical kinetics of aminoglycosides provide some predictive information concerning the clinical incidence of nephrotoxicity, we designed a series of pharmacokinetic studies in healthy mongrel dogs which would define such kinetic information for dibekacin and would contrast the results with similar studies for gentamicin and tobramycin. The renal cortical kinetics of dibekacin, as developed in these studies, show that in a canine model the behavior of dibekacin is similar to that of gentamicin and significantly different from tobramycin. Dibekacin and gentamicin show reproducibly higher renal cortical tissue concentrations than tobramycin in both the acute infusion studies and multiple dosing studies. The results suggest that dibekacin may possess the same inherent nephrotoxic potential as that of gentamicin. In order to show any difference in clinical toxicity between gentamicin and dibekacin, a very extensive randomized, double-blind, prospective clinical trial of efficacy and toxicity will be needed.

Reliability and validity of the longitudinal interval follow-up evaluation for assessing outcome of anxiety disorders.

The LIFE-UP, an instrument for prospectively following course for psychiatric disorders, has been extended to include Psychiatric Status Ratings (PSRs) for the DSM-III-R anxiety disorders panic (with and without agoraphobia), agoraphobia without panic, generalized anxiety disorder, social phobia, and simple phobia. This paper reports data on the reliability and validity of the LIFE-UP as used in the Harvard/Brown Anxiety Disorders Research Program. We found generally good reliability for the PSRs, both inter-rater and long-term test-retest. The reliability coefficients for the rater-administered instruments were very similar to those for the self-reports, suggesting that a large proportion of the variance was due to subject variability rather than rater variability. Reliability for the beginning of the year of follow-up was very similar to that for the time just before the interview. In addition, correlations with other measures of psychosocial function or anxiety symptomatology provided evidence for the external validity of the PSRs as measures of psychiatric morbidity.

Maintaining reliability in a long-term psychiatric study: an ongoing inter-rater reliability monitoring program using the longitudinal interval follow-up evaluation.

The Longitudinal Interval Follow-up Evaluation (LIFE), has been shown to be a valid and reliable instrument for characterizing the week-by-week course of anxiety disorders examined retrospectively over the period of 1 year. Due to the chronic nature of these disorders, there is a need for reliable, valid instruments for measuring course over periods of several years if we are to learn more about the natural history of these disorders. This paper describes a rater-monitoring program designed to ensure long-term inter-rater reliability and prevent "rater drift". In this program, clinical interviewers score taped interviews and are required to maintain a median intra-class correlation coefficient (ICC) of at least 0.80 with the other raters. Raters also assess tapes from previous years, to ensure that they are using the same diagnostic criteria as earlier generations of interviewers. A reliability study was conducted to compare psychiatric status ratings (PSRs) collected using biweekly telephone interviews with the semi-annual interviews. The ICCs for panic, agoraphobia, social phobia, and generalized anxiety disorder were very good to excellent. Another reliability study examined the PSRs of subjects who had been previously lost to follow-up. ICCs for panic, agoraphobia, generalized anxiety disorder and depression were good to excellent. These results show that the LIFE, when used in conjunction with an intensive training and rater monitoring system, is a reliable instrument for use in longitudinal studies of the course of anxiety disorders.

Replication and extension of Marlatt's taxonomy of relapse precipitants: overview of procedures and results. The Relapse Research Group.

The Relapse Replication and Extension Project (RREP) was a multisite study to replicate and extend Marlatt's taxonomy of relapse precipitants. In addition to replicating Marlatt's original taxonomic system, three independent research teams utilized prospective designs to identify additional predictors of relapse and developed and evaluated two alternative systems for assessing high risk relapse situations. This overview describes the replication methodology, summarizes seven RREP studies completed by the three research groups, and discusses five cross-cutting conclusions emerging from the studies. These conclusions are: (1) reliability of Marlatt's taxonomic system was variable both within and across the three research sites; (2) Marlatt's taxonomic system showed little predictive validity in analyses that used pretreatment relapse data to predict post-treatment relapse, but there are important unresolved issues; (3) an alternative taxonomy provided little more predictive validity than the original taxonomy even though it measured more dimensions of relapse situations and provided greater analytic flexibility; (4) the Reasons for Drinking Questionnaire appeared to be a successful psychometric transformation of Marlatt's taxonomy, one which did demonstrate predictive validity; and (5) Marlatt's taxonomy was based on a time-intensive model of relapse prediction whereas RREP prospective analyses represented time-extensive models of relapse prediction. Coping responses are noted to be effective predictors of relapse under both models.

Predictive validity of Marlatt's relapse taxonomy versus a more general relapse code.

Marlatt's system for classifying relapses involves integrating information about the context of a relapse into a judgment about the most critical aspects of the situation. Constraints in this taxonomy, however, may limit its validity. On a sample of 300 subjects drawn from six treatment facilities, we compared the predictive validity of Marlatt's taxonomy with that of a coding scheme with fewer constraints. Marlatt's taxonomy does not significantly predict drinking outcome, nor does it predict time to relapse. There is weak evidence, however, that under some circumstances Marlatt's taxonomy can predict the type of relapse subsequently observed. The alternative coding system also does not seem useful for predicting drinking outcome, although a possible association was found between internal attribution and time to return to heavy drinking. The alternative system does seem to be able to detect repetitive aspects of subsequent relapse situations; lack of social interactions, family setting, anxiety and depression were most likely to repeat. It may be useful to consider these relapse attributes in treatment planning. The minimal predictive validity for both the Marlatt and the alternative relapse code may be due to weaknesses in the relatively unstructured interview used to gather the data, or to failure to assess the most critical dimensions relating to subsequent relapse.

Gender differences in relapse situations.

Gender differences in variables relating to alcohol treatment are receiving increased attention. Most reports indicate gender differences in both intrapersonal, interpersonal and environmental trans-situational variables that relate specifically to women's drinking. This study investigates gender differences in the immediate relapse situation itself. These differences are then examined in the context of trans-situational (i.e. across time) affective and cognitive variables and social support. This report is part of a larger study designed to replicate Marlatt's taxonomy of high risk situations for relapse, and to examine alternative methods of describing relapse situations. Three hundred subjects (169 men, 131 women) were recruited from six different inpatient and outpatient programs. Subjects were asked to identify their last relapse before entering the index treatment. Details of the drinking episode itself were also obtained, e.g. number of drinking days in episode, drinking to intoxication, presence of others. Measures of state and trait affect, expectancies, and social support were also collected. There were no gender differences in Marlatt's taxonomy, or in drinking topography during relapse. At baseline, women reported drinking less, and drinking less often than men. However, women drank to intoxication more often than men. Surprisingly, men relapsed alone more often than did women. Men and women report relapsing frequently with same sex friends, and women showed a tendency to relapse in the presence of romantic partners. Men also tend to report more positive mood states during relapse than women, which is congruent with the finding that women report more depression. Severity of drinking pattern was found to be an important confounding variable in these analyses. It is suggested that gender differences found in individuals in treatment for alcohol problems may reflect societal differences between men and women, and that taking these differences into account in designing treatment programs may improve outcomes.

Network support for drinking, Alcoholics Anonymous and long-term matching effects.

AIMS: (1) To examine the matching hypothesis that Twelve Step Facilitation Therapy (TSF) is more effective than Motivational Enhancement Therapy (MET) for alcohol-dependent clients with networks highly supportive of drinking 3 years following treatment; (2) to test a causal chain providing the rationale for this effect. DESIGN: Outpatients were re-interviewed 3 years following treatment. ANCOVAs tested the matching hypothesis. SETTING: Outpatients from five clinical research units distributed across the United States. PARTICIPANTS: Eight hundred and six alcohol-dependent clients. INTERVENTION: Clients were randomly assigned to one of three 12-week, manually-guided, individual treatments: TSF, MET or Cognitive Behavioral Coping Skills Therapy (CBT). MEASUREMENTS: Network support for drinking prior to treatment, Alcoholics Anonymous (AA) involvement during and following treatment, percentage of days abstinent and drinks per drinking day during months 37-39. FINDINGS: (1) The a priori matching hypothesis that TSF is more effective than MET for clients with networks supportive of drinking was supported at the 3 year follow-up; (2) AA involvement was a partial mediator of this effect; clients with networks supportive of drinking assigned to TSF were more likely to be involved in AA; AA involvement was associated with better 3-year drinking outcomes for such clients. CONCLUSIONS: (1) In the long-term TSF may be the treatment of choice for alcohol-dependent clients with networks supportive of drinking; (2) involvement in AA should be given special consideration for clients with networks supportive of drinking, irrespective of the therapy they will receive.

Alcoholism treatment and medical care costs from Project MATCH.

AIMS: This paper examines the costs of medical care prior to and following initiation of alcoholism treatment as part of a study of patient matching to treatment modality. DESIGN: Longitudinal study with pre- and post-treatment initiation. MEASUREMENTS: The total medical care costs for inpatient and outpatient treatment for patients participating over a span of 3 years post-treatment. SETTING: Three treatment sites at two of the nine Project MATCH locations (Milwaukee, WI and Providence, RI). PARTICIPANTS: Two hundred and seventy-nine patients. INTERVENTION: Patients were randomly assigned to one of three treatment modalities: a 12-session cognitive behavioral therapy (CBT), a four-session motivational enhancement therapy (MET) or a 12-session Twelve-Step facilitation (TSF) treatment over 12 weeks. FINDINGS: Total medical care costs declined from pre- to post-treatment overall and for each modality. Matching effects independent of clinical prognosis showed that MET has potential for medical-care cost-savings. However, patients with poor prognostic characteristics (alcohol dependence, psychiatric severity and/or social network support for drinking) have better cost-savings potential with CBT and/or TSF. CONCLUSIONS: Matching variables have significant importance in increasing the potential for medical-care cost-reductions following alcoholism treatment.

The reliability of Marlatt's taxonomy for classifying relapses.

Marlatt's focus on the relapse situation has had a major impact upon research and clinical practice in treating addictions. One component of his work was the development of a taxonomy for classifying precipitants of relapse. This taxonomy has been incorporated into the nomenclature of clinicians and clinical researchers as part of an explanatory framework for understanding relapses. Despite the taxonomy's influence it has never been examined for the reliability of its use across research studies. The present study compared the reliability of independent classifications of 149 relapse episodes by trained raters at three research laboratories. Despite considerable across-laboratory training, reliability was found to be inconsistent for research purposes. It is concluded that comparability of results based on Marlatt's relapse taxonomy across independent studies must be subject to question, and assumptions necessary for the aggregation of a knowledge base are not supported. Recommendations are offered for improving the reliability of the taxonomy and the methods used to collect taxonomy data. More generally, questions regarding the value of the specific relapse categories, as well as the overall taxonomy, are raised.

Determinants of research follow-up participation in an alcohol treatment outcome trial.

This study examined factors associated with research attrition in a long-term follow-up study (48 months). Researchers attempted to contact all randomized participants, not just those who completed treatment. The processes by which baseline characteristics, early treatment-research experiences, and short-term outcome affected subsequent participations were examined using logistic regression. The analyses deal primarily with refusal, the main reason for attrition. Baseline characteristics had small effects on likelihood of refusal; research engagement had some impact; but treatment participation had strong effect. Short-term outcome did not predict refusal. These findings, if generalizable, have implications for the conduct and reporting of outcome studies. By directly studying bias, rather than presuming its absence on skimpy evidence, researchers can achieve a better understanding of the strengths and limitations of outcome results.

Ensuring balanced distribution of prognostic factors in treatment outcome research.

In comparative or matching research involving two or more treatments, the equivalence of the patient groups is of critical importance. In the past, equivalence has either been imposed by matching or balancing, or has been assured statistically by randomization. Matching and balancing, while useful in many contexts, nonetheless have important limitations, as does simple randomization. In recent years, a new tool has been developed that represents a compromise between balancing and randomization. This method, urn randomization, gives clinical investigators new options for improving the credibility of studies at a relatively modest cost. Urn randomization is randomization that is systematically based in favor of balancing. It can be used with several covariates, both marginally and jointly, producing optimal multivariate equivalence of treatment groups for large sample sizes. It preserves randomization as the primary basis for assignment to treatment and is less susceptible to experimenter bias or manipulation of the allocation process by staff than is balancing. Disadvantages include the fact that it is more difficult to implement, and that it violates the simple probability model of simple randomization. A number of research studies on addictions, including client-treatment matching trials, have used urn randomization. A summary of the mechanics of urn randomization is presented, and guidelines for its use in treatment studies are discussed.

Alternative analytical methods for detecting matching effects in treatment outcomes.

Project MATCH presented a unique opportunity for a team of statisticians, data analysts and content experts to come together and explore the strengths and weaknesses of the application of various statistical models to the data of the type being collected in this large trial. The following models were evaluated: multilevel models, event history models, multiple were structural equation modeling, time series models, ordinal repeated measures designs and generalized estimating equations. No one model was found to be the perfect solution and each seemed to have something to recommend it. Future research on these methods will shed light on many issues raised. It is hoped that alcohol researchers will find useful guidelines within this chapter as they plan and carry out their studies.