The current state of evidence appears to support the efficacy and effectiveness of feedback interventions in enhancing treatment outcome.

Many branches of medicine rely heavily on lab tests to monitor client treatment response and use this information to modify their treatment. By contrast, those who offer psychological interventions seldom rely on formal assessments (lab tests) to monitor their clients' response to treatment. Data are presented that demonstrate that clinicians rarely accurately predict who will not benefit from psychotherapy. This finding is contrasted with the use of a questionnaire (lab test data) and decision rules on the basis of a client's expected progress. Results have indicated that formal methods of monitoring were able to identify 100% of the patients whose condition had deteriorated at termination, and 85% by the time they had attended three treatment sessions. Practitioners are encouraged to consider formal methods of identifying the deteriorating client.

While highly effective, psychotherapy outcome studies suggest 5-14% of clients worsen while in treatment and that therapists are unable to identify a substantial portion of such cases. Methods to systematically collect feedback from psychotherapy clients are discussed and two systems for monitoring treatment response, feeding back this information, and assisting in problem-solving with such cases are described. Within these systems, obtaining client ratings of their relationship appear to be highly important. We summarize meta-analyses of the effects of these feedback systems (The combined weighted random effect size for the Partners for Change Outcome Management System was r = .23, 95% CI [.15, .31], p < .001, k = 3, n = 558; the effect size for the Feedback condition of the Outcome Questionnaire (OQ) system among not-on-track patients was r = .25, 95% CI [.15, .34], p < .001, k = 4, n = 454; the effect size for the Patient/Therapist Feedback condition of the OQ system among not-on-track patients was r = .25, 95% CI [.15, .34], p < .001, k = 3, n = 495; the effect size for the Clinical Support Tools feedback condition among not-on-track patients was r = .33, 95% CI [.25, .40], p < .001, k = 3, n = 535). The number of psychotherapy patients who deteriorate can be cut in half by use of these systems. We conclude with a series of practice implications, including that clinicians seriously consider making formal methods of collecting client feedback a routine part of their daily practice.

The matrix metalloproteinase (MMP) family has been implicated in the process of a variety of diseases such as arthritis, atherosclerosis, and tumor cell metastasis. To study the mechanisms of MMP action on collagenous substrates, we have constructed homotrimeric triplehelical peptide (THP) models of the collagenase cleavage sites in types I and II collagen. The THPs incorporate either the ␣1(I)772-786 or the ␣1(II)772-783 sequence. The ␣1(I)772-786 and ␣1(II)772-783 THPs were hydrolyzed by MMP-1 at the Gly-Ile and Gly-Leu bonds, respectively, analogous to the bonds cleaved in corresponding native collagens. Thus, the THPs contained all necessary information to direct MMP-1 binding and proteolysis. Subsequent investigations using the ␣1 ( . We propose that the COOH-terminal domain of MMPs is necessary for orienting whole, native collagen molecules but may not be necessary for binding to and cleaving a THP. This proposal is consistent with the large distance between the MMP-1 catalytic and COOHterminal domains observed by three-dimensional structural analysis and supports previous suggestions that the features of the catalytic domain contribute significantly toward enzyme specificity. The matrix metalloproteinase (MMP)1 family plays an integral role in both normal and pathological connective tissue remodeling (1). This accelerated local turnover of the extracellular matrix can be found in such diverse diseases as arthritis, glomerulonephritis, periodontal disease, and tumor cell invasion and metastasis (2, 3). There are suggestions that, based on their substrate specificities, MMPs may act on the matrix components in a sequential manner (4). In particular, MMPs are believed to initiate interstitial collagen catabolism and participate in denatured collagen (gelatin) degradation. Interstitial collagens (types I-III) are hydrolyzed at a single locus by MMP-1 (collagenase 1) (5), MMP-8 (collagenase 2) (5), and MMP-18 (collagenase 4) (6). MMP-2 hydrolyzes type I collagen with a similar k cat and a slightly higher K m values than those of MMP-1 at the same single locus (7). MMP-3 binds to type I collagen but does not cleave the triple-helical domain (8, 9). MMP-13 (collagenase 3) hydrolyzes type II collagen at both the same site as MMP-1 and at a site three residues proximal (the 778 -779 bond) (10, 11). MMP-13 cleaves types I and III collagen as well, but not as rapidly as type II (12). Membrane type 1 MMP (MMP-14) also cleaves interstitial collagens (13). MMP-14 is 5-7-fold less efficient at hydrolyzing type I collagen than MMP-1 (13). Several investigations have attempted to define which MMP domains are required for collagenolytic activity. Deletion of the COOH-terminal hemopexin-like domain from MMP-1 (residues 243-450), MMP-8 (residues 243-467), or MMP-13 (residues 249 -451) results in a loss of collagenolytic activity (9,(13)(14)(15)(16). A chimeric MMP-8 whose linker region (16 residues) between the catalytic and COOH-terminal domains is replaced with the corresponding MMP-3 sequence (25 residues) lost activity t...

Matrix metalloproteinase 1 (MMP-1) cleaves types I, II, and III collagen triple helices into 3 ⁄4 and 1 ⁄4 fragments. To understand the structural elements responsible for this activity, various lengths of MMP-1 segments have been introduced into MMP-3 (stromelysin 1) starting from the C-terminal end. MMP-3/MMP-1 chimeras and variants were overexpressed in Escherichia coli, folded from inclusion bodies, and isolated as zymogens. After activation, recombinant chimeras were tested for their ability to digest triple helical type I collagen at 25°C. The results indicate that the nine residues 183 RWTNNFREY191 located between the fifth ␤-strand and the second ␣-helix in the catalytic domain of MMP-1 are critical for the expression of collagenolytic activity. Mutation of Tyr191 of MMP-1 to Thr, the corresponding residue in MMP-3, reduced collagenolytic activity about 5-fold. Replacement of the nine residues with those of the MMP-3 sequence further decreased the activity 2-fold. Those variants exhibited significant changes in substrate specificity and activity against gelatin and synthetic substrates, further supporting the notion that this region plays a critical role in the expression of collagenolytic activity. However, introduction of this sequence into MMP-3 or a chimera consisting of the catalytic domain of MMP-3 with the hinge region and the C-terminal hemopexin domain of MMP-1 did not express any collagenolytic activity. It is therefore concluded that RWTNNFREY, together with the C-terminal hemopexin domain, is essential for collagenolytic activity but that additional structural elements in the catalytic domain are also required. These elements probably act in a concerted manner to cleave the collagen triple helix.Interstitial collagen types I, II, and III are the major structural proteins in connective tissues such as tendon, skin, bone, cartilage, and blood vessels. They consist of three ␣ chains with repeating Gly-X-Y triplets where X and Y are frequently Pro and Hyp, respectively. Each chain of the repeating tripeptide adopts a left-handed poly-Pro II helix conformation, and three left-handed chains then intertwine to form a right-handed superhelix (1-3). This triple helical conformation makes interstitial collagens resistant to most proteinases in vertebrates except for collagenases, cathepsin K (4), and neutrophil elastase (5). The action of cathepsin K is probably important in collagen breakdown in specialized environments such as during bone resorption in an acidic pH environment. Neutrophil elastase may degrade telopeptides of interstitial collagen (6) and the triple-helical region of type I collagen under inflammatory conditions, but the latter activity is much weaker than that of collagenase (5). Vertebrate collagenases, on the other hand, are synthesized by many cell types such as stromal fibroblasts, chondrocytes, keratinocytes, osteoblasts, endothelial cells, and macrophages in response to inflammatory cytokines, growth factors, cellular transformation, and other chemical and physical stimuli ...