What we know, what we do not know, and where are we heading? Efficacy and acceptability of psychological interventions for depression.

In the past several decades, increasing evidence supports the efficacy of psychotherapies for depression. The vast majority of findings from meta-analyses, randomized clinical trials (RCTs) and naturalistic studies have demonstrated that well-established psychotherapies (behavioural activation, problem-solving therapy, psychodynamic therapy, cognitive-behavioural therapy, interpersonal therapy and emotion-focused therapy) are superior to no-treatment and control conditions, and are in most cases equally effective in treating depression. However, despite this abundant support for psychotherapies, studies have also consistently shown high drop-out rates, high percentages of non-respondent patients who experience treatment failures, and mixed findings regarding the enduring effects of psychotherapy. Thus, there is a need to develop more personalised treatment models tailored to patients' needs. A new integrative sequential stepwise approach to the treatment of depression is suggested.

Induction of acute lymphocytic leukemia differentiation by maintenance therapy.

Despite extensive study in many malignancies, maintenance therapy has clinically benefited only two diseases: acute lymphocytic leukemia (ALL) and acute promyelocytic leukemia (APL). ALL maintenance therapy utilizes low-dose 6-mercaptopurine (6MP) and methotrexate (MTX), while maintenance in APL primarily consists of all-trans-retinoic acid (ATRA). 6MP and MTX as used in ALL are also now usually added to maintenance ATRA for APL, based on data suggesting an improved disease-free survival. Although the mechanism of action of MTX and 6MP as maintenance is unknown, low-dose cytotoxic agents are potent inducers of differentiation in vitro. Thus, we studied whether maintenance therapy in ALL, like ATRA in APL, may be inducing terminal differentiation of ALL progenitors. The APL cell line NB4, the ALL cell lines REH and RS4;11, and patients' ALL blasts were incubated with ATRA, 6MP, and MTX in vitro. All three drugs inhibited the clonogenic growth of the APL and ALL cell lines without inducing immediate apoptosis, but associated with induction of phenotypic differentiation. The three drugs similarly upregulated lymphoid antigen expression, while decreasing CD34 expression, on patients' ALL blasts. These data suggest that induction of leukemia progenitor differentiation plays an important role in the mechanism of action of maintenance therapy in ALL.

Planar thin film device for capillary electrophoresis.

Hollow tubular microfluidic channels were fabricated on quartz substrates using sacrificial layer, planar micromachining processes. The channels were created using a bottom-up fabrication technique, namely patterning a photoresist/aluminum sacrificial layer and depositing SiO(2) over the substrate. The photoresist/aluminum layer was removed by etching first with HCl/HNO(3), followed by etching in Nano-Strip, a more stable form of piranha (H(2)SO(4)/H(2)O(2)) stripper. Rapid separation of fluorescently labeled amino acids was performed on a device made with these channels. The fabrication process presented here provides unique control over channel composition and geometry. Future work should allow the fabrication of highly complex and precise devices with integrated analytical capabilities essential for the development of micro-total analysis systems.

Pretreatment expectations, interpersonal functioning, and symptoms in the prediction of the therapeutic alliance across supportive-expressive psychotherapy and cognitive therapy.

Therapeutic alliance has been a robust predictor of therapy outcome, yet little is known about which patient variables predict the development of an alliance between patient and therapist in time-limited manualized therapies. The authors evaluated pretreatment predictors of therapeutic alliance, controlling for symptom change before its assessment, using a large sample of patients treated with either supportive-expressive (SE) dynamic psychotherapy or cognitive therapy. They found that SE patients with greater pretreatment expectations of improvement formed better alliances with their therapist at Session 2, and expectations significantly predicted alliance at Session 10 for both treatment groups. Further, patients in the SE condition demonstrated a significant relation between positive expectations and growth in alliance. Women achieved better alliances at Session 10. Finally, hostile-dominant interpersonal problems significantly predicted poor alliance. Pretreatment symptom level was not significantly predictive of alliance.

Clinical oncologists favour radical radiotherapy for localized prostate cancer: a questionnaire survey.

OBJECTIVE: To explore the treatment preferences of clinical oncologists for managing early prostate cancer and to compare the results with the preferences of urologists. METHODS: A postal questionnaire survey was conducted of consultant clinical oncologists in the UK. RESULTS: Consultant clinical oncologists favour radical radiotherapy in most men aged < 70 years, whereas a previous study showed that consultant urologists had a greater preference for radical surgery. CONCLUSION: There is little consensus about which treatment should be used for managing early prostate cancer. There is an urgent need for results from randomized clinical trials to determine the optimum treatment.

Multilineage glycosylphosphatidylinositol anchor-deficient haematopoiesis in untreated aplastic anaemia.

Aplastic anaemia and paroxysmal nocturnal haemoglobinuria (PNH) are closely related disorders. In PNH, haematopoietic stem cells that harbour PIGA mutations give rise to blood elements that are unable to synthesize glycosylphosphatidylinositol (GPI) anchors. Because the GPI anchor is the receptor for the channel-forming protein aerolysin, PNH cells do not bind the toxin and are unaffected by concentrations that lyse normal cells. Exploiting these biological differences, we have developed two novel aerolysin-based assays to detect small populations of PNH cells. CD59 populations as small as 0.004% of total red cells could be detected when cells were pretreated with aerolysin to enrich the PNH population. All PNH patients displayed CD59-deficient erythrocytes, but no myelodysplastic syndrome (MDS) patient or control had detectable PNH cells before or after enrichment in aerolysin. Only one aplastic anaemia patient had detectable PNH red cells before exposure to aerolysin. However, 14 (61%) had detectable PNH cells after enrichment in aerolysin. The inactive fluorescent proaerolysin variant (FLAER) that binds the GPI anchors of a number of proteins on normal cells was used to detect a global GPI anchor deficit on granulocytes. Flow cytometry with FLAER showed that 12 out of 18 (67%) aplastic anaemia patients had FLAER-negative granulocytes, but none of the MDS patients or normal control subjects had GPI anchor-deficient cells. These studies demonstrate that aerolysin-based assays can reveal previously undetectable multilineage PNH cells in patients with untreated aplastic anaemia. Thus, clonality appears to be an early feature of aplastic anaemia.

Impact of psychosocial treatments on associated problems of cocaine-dependent patients.

A previous report from the National Institute on Drug Abuse Collaborative Cocaine Treatment Study (P. Crits-Christoph et al., 1999) found relatively superior cocaine and drug use outcomes for individual drug counseling plus group drug counseling compared with other treatments. Using data from that study, the authors examined the relative efficacy of 4 treatments for cocaine dependence on psychosocial and other addiction-associated problems. The 487 patients were randomly assigned to 6 months of treatment with cognitive therapy, supportive-expressive therapy, or individual drug counseling (each with additional group drug counseling), or to group drug counseling alone. Assessments were made at baseline and monthly for 6 months during the acute treatment phase, with follow-up visits at 9 and 12 months. No significant differences between treatments were found on measures of psychiatric symptoms, employment, medical, legal, family-social, interpersonal, or alcohol use problems. The authors concluded that the superiority of individual drug counseling in modifying cocaine use does not extend broadly to other addiction-associated problems.

Early improvement during manual-guided cognitive and dynamic psychotherapies predicts 16-week remission status.

This study examined the extent to which improvement from baseline to weeks 2, 3, and 4 on the Beck Depression Inventory and Beck Anxiety Inventory predict week 16 clinical remission for patients with major depressive disorder, generalized anxiety disorder, and/or obsessive-compulsive or avoidant personality disorders who were receiving manual-based psychotherapies. Logistic regression and receiver-operator characteristic analyses revealed relatively accurate identification of remitters and nonremitters based on improvement from baseline to sessions 2 to 4 in both original and cross-validation samples. Predictive success did not vary as a function of diagnosis, treatment type (cognitive or dynamic), or treatment status (short-term or long-term). The clinical implications of the results are discussed.

Supportive techniques: are they found in different therapies?

Therapists of different persuasions use various techniques. Although many of these techniques are specific to their theory of treatment, others are practiced in common among different forms of psychotherapy. Many of these common techniques have been previously described, but supportive techniques have been largely ignored. The authors distinguish between the use of supportive techniques and the therapeutic alliance. Using Luborsky's definition of supportive techniques, they examine the empirical literature on the use of these supportive techniques in various therapies. They conclude that supportive techniques are often used in different forms of psychotherapy or counseling.

Therapeutic alliance as a predictor of outcome and retention in the National Institute on Drug Abuse Collaborative Cocaine Treatment Study.

The authors examined the relation between therapeutic alliance, retention, and outcome for 308 cocaine-dependent outpatients participating in the National Institute on Drug Abuse Collaborative Cocaine Treatment Study. High levels of alliance were observed in supportive-expressive therapy (SE), cognitive therapy (CT), and individual drug counseling (IDC), and alliance levels increased slightly but significantly from Session 2 to Session 5 in all groups. In contrast to other studies, alliance was not a significant predictor of drug outcome. However, alliance did predict patient retention differentially across the 3 treatments. In SE and IDC, either higher levels of alliance were associated with increased retention or no relationship between alliance and retention was found, depending on the time alliance was measured. In CT, higher levels of alliance were associated with decreased retention.

Change in compensatory skills in cognitive therapy for depression.

The Ways of Responding (WOR) was developed to assess change in compensatory or metacognitive skills taught by cognitive therapists. Thus, one would expect WOR scores to change during cognitive therapy (CT) and to be associated with change in depression level. Twenty-seven patients with a DSM-III-R diagnosis of major depression who had received CT filled out the WOR and other measures of cognition. After 12 weeks of CT, the patients exhibited change in the WOR, the Attributional Style Questionnaire, the Dysfunctional Attitude Scale, and the Self-Control Scale. Furthermore, there were indications that change in depression was associated with changes in these measures of cognition, including the WOR. The WOR appears to be a sensitive measure of change during CT that covaries with change in depression. It remains to be tested whether change on the WOR is specific to CT.

The central relationship questionnaire (CRQ): psychometric properties in a Swedish sample and cross-cultural studies.

The Core Conflictual Relationship Theme (CCRT) method is one of the most widely used and tested instruments developed within a psychoanalytic context for assessing central relationship patterns or characteristic patterns of relating to others. The Swedish version of the Central Relationship Questionnaire (CRQ), a recently developed self-report instrument based on the CCRT, was tested in a sample of Swedish psychology students (31 men, 60 women) and compared with responses of Swedish outpatients (15 men, 15 women) and North American students (49 men, 49 women). The subscales of the Swedish CRQ showed acceptable internal consistency and correlated with each other in a predictable fashion, displaying a pattern of intercorrelations similar to the English version. The CRQ showed meaningful patterns of correspondence with self-reported interpersonal problems as well as meaningful differences between the Swedish students and Swedish outpatients, indicating preliminary convergent and divergent validity.

Self-help group attendance and participation among cocaine dependent patients.

The authors examined frequency and patterns of self-help group attendance and active participation over a 6-month period among 411 patients receiving treatment in the NIDA Collaborative Cocaine Treatment Study. Nearly two-thirds of patients attended at least one self-help group, and nearly all of these actively participated. Alcoholics Anonymous and Narcotics Anonymous meetings were attended most frequently. Statistical analyses included chi square, one-way analyses of variance, and cluster techniques. While patterns of attendance were relatively consistent over time, findings suggest that a treatment emphasizing the importance of self-help groups is likely to encourage more self-help group attendance and participation over time.

The role of therapist characteristics in training effects in cognitive, supportive-expressive, and drug counseling therapies for cocaine dependence.

The role of therapist characteristics in therapy training was examined for 62 therapists in a multisite psychotherapy outcome study that included cognitive therapy (CT), supportive-expressive (SE) psychodynamic therapy, and individual drug counseling (IDC) for cocaine-dependent patients. Demographic variables and experience and competence ratings prior to training were correlated with measures of change in competence during the training phase. Higher competence ratings before training were associated with greater change in competence for SE and higher average competence for IDC. More years of experience were associated with greater change in competence for CT therapists, but more hours of pre-training supervision in the CT treatment modality were associated with less change.

Alliance predicts patients' outcome beyond in-treatment change in symptoms.

The authors examined the relations among therapeutic alliance, outcome, and early-in-treatment symptomatic improvement in a group of 86 patients with generalized anxiety disorders, chronic depression, or avoidant or obsessive-compulsive personality disorder who received supportive-expressive dynamic psychotherapy. Although alliance at Sessions 5 and 10, but not at Session 2, was associated with prior change in depression, alliance at all sessions significantly predicted subsequent change in depression when prior change in depression was partialed out. The results are discussed in terms of the causal role of the alliance in therapeutic outcome.

Issues in research on short-term dynamic psychotherapy.

In this article, we review the development of short-term dynamic psychotherapy (STDP) and introduce some of the important questions to be addressed in studying STDP. We begin by surveying some of the areas not covered in this special edition (e.g., the efficacy of STDP, recent developments in dynamic formulation) because they were recently reviewed elsewhere. We then introduce the four articles included in this special mini-series. We conclude by looking at which questions could benefit from further study and recommend that more data be gathered regarding (a) the differences between the many different forms of STDP; (b) the efficacy of these forms of therapies for specific disorders, including personality disorders; (c) the essential theoretically relevant processes occurring in those treatments; (d) matching patients to different therapies; (e) the interrelations between different therapeutic processes; and (f) the different strategies for teaching STDP.

Acquisition of adaptive skills: psychotherapeutic change in cognitive and dynamic therapies.

We argue that there are important areas of overlap in the types of patient change processes that occur in cognitive therapy and dynamic therapy. These common processes of patient change have been obscured by differences in language and theoretical constructs between the two traditions. We suggest that the acquisition of adaptive skills describes patient change processes that are common to both therapies. More specifically, we propose that the concept of adaptive skills encompasses both the compensatory skills model of cognitive therapy (Barber & DeRubeis, 1989) and some of the patient changes that occur in dynamic therapies. In clarifying these areas of overlap between cognitive and dynamic therapies encompassed by the adaptive skills acquired in both, the present article highlights the fact that the two therapeutic traditions employ radically different techniques to achieve some of the same outcomes. Recognizing the overlap between change processes in the two types of therapy, and adopting a common language for them, allows for further theoretical and empirical investigation of therapy process and outcome.

Psychosocial treatments for cocaine dependence: National Institute on Drug Abuse Collaborative Cocaine Treatment Study.

BACKGROUND: This was a multicenter investigation examining the efficacy of 4 psychosocial treatments for cocaine-dependent patients. METHODS: Four hundred eighty-seven patients were randomly assigned to 1 of 4 manual-guided treatments: individual drug counseling plus group drug counseling (GDC), cognitive therapy plus GDC, supportive-expressive therapy plus GDC, or GDC alone. Treatment was intensive, including 36 possible individual sessions and 24 group sessions for 6 months. Patients were assessed monthly during active treatment and at 9 and 12 months after baseline. Primary outcome measures were the Addiction Severity Index-Drug Use Composite score and the number of days of cocaine use in the past month. RESULTS: Compared with the 2 psychotherapies and with GDC alone, individual drug counseling plus GDC showed the greatest improvement on the Addiction Severity Index-Drug Use Composite score. Individual group counseling plus GDC was also superior to the 2 psychotherapies on the number of days of cocaine use in the past month. Hypotheses regarding the superiority of psychotherapy to GDC for patients with greater psychiatric severity and the superiority of cognitive therapy plus GDC compared with supportive-expressive therapy plus GDC for patients with antisocial personality traits or external coping style were not confirmed. CONCLUSION: Compared with professional psychotherapy, a manual-guided combination of intensive individual drug counseling and GDC has promise for the treatment of cocaine dependence.

Self and observer reports of interpersonal problems in couples.

This study investigated self-partner agreement on a measure of interpersonal problems as well as the relationship between discrepancy in self-partner ratings and self-reported symptomatology. Both partners of 49 young adult couples rated themselves and their partners on the Inventory of Interpersonal Problems(IIP Horowitz, Rosenberg, Baer, Ureño, & Villaseñor, 1988). The results demonstrated that couples generally evidenced significant agreement in characterizing the interpersonal problems of each target person, suggesting that the substantial self-partner agreement previously reported for personality traits generalizes to the domain of interpersonal problems. Results also indicated that the relationship between self-partner discrepancy and symptomatology depended on the target person's gender. Finally, the data provide preliminary evidence of the psychometric properties of an observer form of the IIP, including its circular structure.

Therapist interventions in early sessions of brief supportive-expressive psychotherapy for depression.

Although psychotherapy manuals provide treatment guidelines, detailed descriptions of therapist interventions in manual-guided therapies are lacking. The purpose of the present investigation was to evaluate the types of therapist interventions in Supportive-Expressive (SE) psychotherapy for depression by using a molecular method of assessment and then to compare the results with those attained with a molar method. Four percent of therapist statements per session early in treatment were interpretations, which most often focused on the patient's parents, significant others, and self in the present time frame. This molecular method for assessing therapist interventions did converge with the molar adherence/competence method.