Differential effectiveness of group, individual, and conjoint treatments: An archival analysis of OQ-45 change trajectories.

OBJECTIVE: While empirically-supported treatment (EST) choices are continually expanding, choices regarding formats for delivery (individual only, group only, or conjoint [simultaneous individual & group]) are often determined by agency resources or clinician preference. Studies comparing individual and group formats have produced mixed results, while recent meta-analytic reviews support format equivalence. METHOD: We employed a multilevel model to test for outcome differences using the OQ-45 on an outpatient archival data set of clients receiving individual-only (n = 11,764), group-only (n = 152) or conjoint (n = 1557). RESULTS: Individual and group outcomes were equivalent with some analyses showing conjoint trailing. Moderators of change included initial distress, treatment duration, intra-group dependency, and format. CONCLUSIONS: Results support meta-analytic findings of format equivalence in a naturalistic setting for group and individual. Referral practices and future results are discussed.

Youth psychotherapy change trajectories and early warning system accuracy in a managed care setting.

OBJECTIVES: To examine change trajectories in routine outpatient mental health services for children and adolescents in a managed care setting, and to use these trajectories to test the accuracy of two variations of an early warning system designed to identify cases at risk for deterioration. METHOD: Multilevel modeling procedures were used to examine longitudinal Youth Outcome Questionnaire (YOQ) data for 16,091 youth aged 4-17 years (39% female, mean age 10.5) referred for treatment in a managed care system. RESULTS: Clients with more frequent YOQ administrations had slightly lower baselines and faster rates of change. Both the traditional and simplified versions of the early warning system demonstrated good accuracy in identifying clients who deteriorated, with a sensitivity of .63, specificity of .83, and hit rate of .81. CONCLUSIONS: Results provide further evidence that patient-focused early warning systems can accurately identify most youth who are at risk for negative outcomes in routine mental health services.

The Group Questionnaire: a clinical and empirically derived measure of group relationship.

The Group Questionnaire (GQ) is a recently developed self-report measure of the therapeutic relationship based on Johnson and colleagues (2005) three-factor model; Positive Bonding, Positive Working, and Negative Relationship. This study validated Johnson's model with a new and extended sample and created a shorter 40-item trial version. SEM analysis of the GQ tested whether it produced the same three-factor structure found in three earlier studies with 486 participants from three populations-outpatient university counseling center, non-patient AGPA process groups, and inpatient state hospital. Results of further SEM refinements demonstrated that a final 30-item version had good fit to the three-factor model although distinct differences in response pattern were found between the three populations. Implications for future utility and clinical relevance of the GQ are discussed.

Clinical prediction in group psychotherapy.

Prior research in individual therapy has provided evidence that therapists are poor predictors of client outcome and often misjudge clients' perceptions of the therapeutic relationship. The focus of the current research was to conduct a similar predictive study in a group setting. Group therapists were recruited from a university counseling center and a state psychiatric hospital; 64 group members and 10 group leaders participated in the study. We tested therapist accuracy in predicting client outcome and perceived quality of therapeutic relationship. Results suggested that therapists underestimate the number of clients who deteriorate during therapy and were unable to accurately predict client perceptions of the group relationship, replicating findings from larger samples in the individual literature. Results suggest that using outcome and process measures as feedback tools may be also useful for clinicians leading groups.

Synthesis of quaternary stereogenic centres via stereoselective intermolecular Friedel-Crafts reactions.

Highly stereoselective Friedel-Crafts reactions have been performed using a chiral anthracene template to control the selectivity of the reaction. In the case of additions to fully substituted N-acyliminium ions, competitive elimination and condensation reactions were observed. Retro-Diels-Alder reaction of one of the reaction products led to a precursor that could be used for the construction of pyroglutamic acids bearing quaternary stereogenic centres.

Synthesis and biological activity of a series of tetrasubstituted-imidazoles as P2X(7) antagonists.

A series of analogues of the pyrazole lead 1 were synthesized in which the heterocyclic core was replaced with an imidazole. A number of potent antagonists were identified and structure-activity relationships (SAR) were investigated both with respect to activity at the P2X(7) receptor and in vitro metabolic stability. Compound 10 was identified as a potent P2X(7) antagonist with reduced in vitro metabolism and high solubility.

Synthesis and evaluation of 3-amino-6-aryl-pyridazines as selective CB(2) agonists for the treatment of inflammatory pain.

A series of 3-amino-6-aryl-pyridazines have been identified as CB(2) agonists with high efficacy and selectivity against the CB(1) receptor. Details of the investigation of structure-activity relationships (SAR) are disclosed, which led to the identification of pyridazine analogue 35, a compound with high potency in an in vivo model of inflammatory pain.

Structure-activity relationships and in vivo activity of (1H-pyrazol-4-yl)acetamide antagonists of the P2X(7) receptor.

Structure-activity relationships (SAR) of analogues of lead compound 1 were investigated and compound 16 was selected for further study in animal models of pain. Compound 16 was shown to be a potent antihyperalgesic agent in both the rat acute complete Freund's adjuvant (CFA) model of inflammatory pain [Iadarola, M. J.; Douglass, J.; Civelli, O.; Naranjo, J. R. rain Res.1988, 455, 205] and the knee joint model of chronic inflammatory pain [Wilson, A. W.; Medhurst, S. J.; Dixon, C. I.; Bontoft, N. C.; Winyard, L. A.; Brackenborough, K. T.; De Alba, J.; Clarke, C. J.; Gunthorpe, M. J.; Hicks, G. A.; Bountra, C.; McQueen, D. S.; Chessell, I. P. Eur. J. Pain2006, 10, 537].

Synthesis and structure-activity relationships of a series of (1H-pyrazol-4-yl)acetamide antagonists of the P2X7 receptor.

High-throughput screening identified compound 1 as a potent P2X(7) receptor antagonist suitable for lead optimisation. Structure-activity relationships (SAR) of a series of (1H-pyrazol-4-yl)acetamides were investigated and compound 32 was identified as a potent P2X(7) antagonist with enhanced potency and favourable physicochemical and pharmacokinetic properties.

Identification of 2-oxo-N-(phenylmethyl)-4-imidazolidinecarboxamide antagonists of the P2X(7) receptor.

A backup molecule to compound 2 was sought by targeting the most likely metabolically vulnerable site in this molecule. Compound 18 was subsequently identified as a potent P2X(7) antagonist with very low in vivo clearance and high oral bioavailability in all species examined. Some evidence to support the role of P2X(7) in the etiology of pain is also presented.

Discovery and structure-activity relationships of a series of pyroglutamic acid amide antagonists of the P2X7 receptor.

A computational lead-hopping exercise identified compound 4 as a structurally distinct P2X(7) receptor antagonist. Structure-activity relationships (SAR) of a series of pyroglutamic acid amide analogues of 4 were investigated and compound 31 was identified as a potent P2X(7) antagonist with excellent in vivo activity in animal models of pain, and a profile suitable for progression to clinical studies.

2-Amino-5-aryl-pyridines as selective CB2 agonists: synthesis and investigation of structure-activity relationships.

2-Amino-5-aryl-pyridines, exemplified by compound 1, had been identified as a synthetically tractable series of CB(2) agonists from a high-throughput screen of the GlaxoSmithKline compound collection. Described herein are the results of an investigation of the structure-activity relationships (SAR) which led to the identification a number of potent and selective agonists.

Identification and optimisation of a novel series of pyrimidine based cyclooxygenase-2 (COX-2) inhibitors. Utilisation of a biotransformation approach.

Many years of work have been invested in the identification of potent and selective COX-2 inhibitors for the treatment of chronic inflammatory pain. One issue faced by workers is the balance between the lipophilicity required for potent enzyme inhibition and the physical properties necessary for drug absorption and distribution in vivo. Frequently approaches to reduce lipophilicity through introduction of polar functionality is hampered by highly challenging chemistry to prepare key molecules. We have complemented traditional synthetic chemistry with a biotransformations approach which efficiently provided access to an array of key target molecules.

Identification of [4-[4-(methylsulfonyl)phenyl]-6-(trifluoromethyl)-2-pyrimidinyl] amines and ethers as potent and selective cyclooxygenase-2 inhibitors.

A novel series of [4-[4-(methylsulfonyl)phenyl]-6-(trifluoromethyl)-2-pyrimidine-based cyclooxygenase-2 (COX-2) inhibitors, which have a different arrangement of substituents compared to the more common 1,2-diarylheterocycle based molecules, have been discovered. For example, 2-(butyloxy)-4-[4-(methylsulfonyl)phenyl]-6-(trifluoromethyl)pyrimidine (47), a member of the 2-pyrimidinyl ether series, has been shown to be a potent and selective inhibitor with a favourable pharmacokinetic profile, high brain penetration and good efficacy in rat models of hypersensitivity.

BACE-1 inhibitors part 3: identification of hydroxy ethylamines (HEAs) with nanomolar potency in cells.

This article is focusing on further optimization of previously described hydroxy ethylamine (HEA) BACE-1 inhibitors obtained from a focused library with the support of X-ray crystallography. Optimization of the non-prime side of our inhibitors and introduction of a 6-membered sultam substituent binding to Asn-294 as well as a fluorine in the C-2 position led to derivatives with nanomolar potency in cell-based assays.

Rhodium catalysed conjugate addition of a chiral alkenyltrifluoroborate salt: the enantioselective synthesis of hermitamides A and B.

The concise enantioselective synthesis of hermitamides A and B is presented utilising a rhodium catalysed conjugate addition reaction to introduce the side chain and chiral information in a single step via an alkenyltrifluoroborate salt.

The effects of relationship and progress feedback in group psychotherapy using the Group Questionnaire and Outcome Questionnaire-45: A randomized clinical trial.

Routine outcome monitoring (ROM) systems that identify clients at-risk for treatment failure using outcome and therapeutic process measures are a recognized evidence-based practice. However, only 3 empirical studies have tested ROMs in group therapy, producing mixed results. This randomized clinical trial tested the Outcome Questionnaire System, the ROM system with the most empirical support for individual therapy patients, with 430 group therapy patients who were randomly assigned to 2 experimental arms (Group Questionnaire [GQ] + Outcome Questionnaire-45 [OQ-45] vs. OQ-45). Given the strong evidence for progress feedback, the primary purpose of this study was to ascertain if therapeutic relationship feedback using the GQ reduced rates of relationship deterioration and failure when progress feedback was held constant. Group leaders simultaneously ran pairs of groups that were randomly assigned to the 2 conditions. Of the 430 patients enrolled in 58 groups, 374 attended more than 4 sessions. Results showed that therapeutic relationship predicted improvement in outcome and that feedback reversed the course of relationship deterioration and reduced rates of relationship failure. Although there were no effects on attendance and dropout for feedback, the 2 experimental arms produced mixed results for the OQ-45 not-on-track cases. The combined relationship and progress feedback (GQ/OQ-45) was associated with fewer outcome deterioration cases, while the progress feedback condition (OQ-45) showed higher outcome improvement cases. Findings are discussed with respect to previous group ROM studies, clinical implications, and future research. (PsycINFO Database Record

Practice-based evidence can help! Using the Group Questionnaire to enhance clinical practice.

Practice-based evidence (Burlingame & Beecher, 2008) is an approach to evidence-based practice that addresses treatment efficacy to remediate clinicians' inability to predict treatment response (Chapman et al., 2012; Hannan et al., 2005). The Group Questionnaire (GQ; Bormann, Burlingame, & Straub, 2011; Johnson, Burlingame, Olsen, Davies, & Gleave, 2005) is one practice-based evidence measure that supports clinical judgment to enhance psychotherapy outcomes by measuring 3 important group constructs: Positive Bond, Positive Work, and Negative Relationship. A clinical example of how one group leader used GQ data provided by group members regarding their weekly group experiences to support her interventions in a process-oriented therapy group for adults includes verbatim clinical exchanges among group members and the leader. The example also includes a GQ report with explanations of the group members' scores and numerical and graphical data. The authors detail how the leader used the data from the measure to promote curiosity about group cohesion and movement toward treatment goals, to reframe perceptions of group interaction, and to gauge outcomes of shared group experience. The group leader's examination of the GQ data outside the group allowed her to use this information for positive impact inside the group to guide interventions and explore content and process, warranting additional attention. The authors encourage curiosity about other interactions among other group members reflected in the GQ report and how this information could be used to positively impact the group in other ways. (PsycINFO Database Record

Rhodium-catalyzed conjugate addition-enantioselective protonation: the synthesis of alpha,alpha'-dibenzyl esters.

Alpha-benzyl acrylates, which are conveniently prepared from the corresponding aldehydes, can be employed as substrates in a tandem rhodium-catalyzed conjugate addition-enantioselective protonation protocol to afford enantiomerically enriched alpha,alpha'-dibenzyl esters. The synergistic effect of enantiopure ligand and proton source was rapidly optimized with use of a microwave reactor.

Exploring interactions of improvers and deteriorators in the group therapy process: a qualitative analysis.

This study examined the interactions of individuals who showed symptom improvement and those who showed deterioration during the course of short-term group psychotherapy. A qualitative hermeneutic analysis was used to identify and describe themes from the group interactions. Both broad group themes, as well as themes specific to improvers and deteriorators, were found. Findings suggest that the differences in group behavior between those who get worse and those who improve are subtle and thus difficult for group leaders to detect. Although the differences were not immediately apparent, a deeper examination of group process did reveal distinct patterns for deteriorators that were different from those of improvers. These patterns of interaction are discussed as well as variables related to client, leader, and group as a whole that may have contributed to the outcome of group members.