Perioperative psychotherapy for persistent post-surgical pain and physical impairment: a meta-analysis of randomised trials.

BACKGROUND: Persistent post-surgical pain affects 10-80% of individuals after common operations, and is more common among patients with psychological factors such as depression, anxiety, or catastrophising. METHODS: We conducted a systematic review and meta-analysis of randomised, controlled trials to evaluate the efficacy of perioperative psychotherapy for persistent post-surgical pain and physical impairment. Paired independent reviewers identified studies, extracted data, and assessed risk of bias. The Grading of Recommendations, Assessment, Development and Evaluation system was used to assess the quality of evidence. RESULTS: Our search of five electronic databases, up to September 1, 2016, found 15 trials (2220 patients) that were eligible for review. For both persistent post-surgical pain and physical impairment, perioperative education was ineffective, while active psychotherapy suggested a benefit (test of interaction P=0.01 for both outcomes). Moderate quality evidence showed that active perioperative psychotherapy (cognitive-behaviour therapy, relaxation therapy, or both) significantly reduced persistent post-surgical pain [weighted mean difference (WMD) -1.06 cm on a 10 cm visual analogue scale for pain, 95% confidence interval (CI) -1.56 to -0.55 cm; risk difference (RD) for achieving no more than mild pain (≤3 cm) 14%, 95% CI 8-21%] and physical impairment [WMD -9.87% on the 0-100% Oswestry Disability Index, 95% CI -13.42 to -6.32%, RD for achieving no more than mild disability (≤20%) 21%, 95% CI 13-29%]. CONCLUSIONS: Perioperative cognitive behavioural therapy and relaxation therapy are effective for reducing persistent pain and physical impairment after surgery. Future studies should explore targeted psychotherapy for surgical patients at higher risk for poor outcome. CLINICAL TRIAL REGISTRATION: PROSPERO CRD42016047335.

Effective ingredients of verbal de-escalation: validating an English modified version of the 'De-Escalating Aggressive Behaviour Scale'.

WHAT IS KNOWN ON THE SUBJECT?: Verbal de-escalation is an intervention aimed at calmly managing an agitated client to prevent violence. Effective de-escalation can help reduce the use of seclusion and restraint in psychiatric settings. Despite its importance in practice, there is little agreement on the necessary techniques of de-escalation and most of the research on the topic is based on expert opinion. To our knowledge, only one attempt at quantifying de-escalation skill has been pursued through the German-language De-Escalating Aggressive Behaviour Scale (DABS). While the DABS identified seven qualities necessary for de-escalation, it has not been validated in English and may lack important descriptors. WHAT THIS PAPER ADDS TO EXISTING KNOWLEDGE?: The present study enhanced the original DABS with best, acceptable and least desirable staff de-escalation practice descriptions for each of the seven items. This enhancement of the DABS lead to the creation of the English modified DABS (EMDABS). The EMDABS was psychometrically validated for use in research and practice: raters could use the EMDABS with a high level of agreement and consistency. Also, the scale appeared to measure a single cohesive construct - de-escalation. WHAT ARE THE IMPLICATIONS FOR PRACTICE?: With further validation, the EMDABS has potential to be the first English quantitative measure of de-escalation. The EMDABS offers seven items, with associated best practice descriptions, that may be used to inform de-escalation practice. The EMDABS can be used to evaluate training and education programmes and inform how these programmes and independent de-escalation practice may be improved. ABSTRACT: Introduction Verbal de-escalation is crucial to a non-coercive psychiatric environment. Despite its importance, the literature on de-escalation is sparse and mostly qualitative. To address this, Nau et al. (2009) quantified de-escalation by creating the German-language De-Escalating Aggressive Behaviour Scale (DABS). The DABS provides seven skills necessary for de-escalation, however it has not been validated in English and lacks the necessary anchor descriptions to make it useful. Aim To modify the DABS to include descriptions of best, acceptable and least desirable staff practice and to validate the English modified DABS (EMDABS). Method To develop item descriptions for the EMDABS, 50 conflictual staff-patient interactions were reviewed, summarized and cross-referenced with the literature (n = 19). Three raters then used the EMDABS to evaluate 272 simulations depicting these interactions. Results The EMDABS demonstrated very good inter-rater reliability [ICC (3, 1) = 0.752] and strong internal consistency (α = 0.901). A factor analysis revealed that the seven items were best represented by a single factor. Discussion The EMDABS was validated for future use in research and practice. Additional validation and future research directions are discussed. Implications for practice The EMDABS holds promise as a quantitative measure of de-escalation. Its seven items and best practice guidelines have clinical implications for improving practice and training.

Ten remarks on peptide bond formation on the ribosome.

Peptide-bond formation is the enzymatic activity of the ribosome. The catalytic site is made up of ribosomal RNA, indicating that the ribosome is a ribozyme. This review summarizes the recent progress in understanding the mechanism of peptide bond formation. The results of biochemical and kinetic experiments, mutagenesis studies and ribosome crystallography suggest that the approx. 10(7)-fold rate enhancement of peptide bond formation by the ribosome is mainly due to substrate positioning within the active site, rather than to chemical catalysis.

Group cognitive behavioral therapy for bipolar disorder: a feasibility and effectiveness study.

BACKGROUND: Bipolar disorder (BD) is a common disorder that results in significant psychosocial impairment, including diminished quality of life and functioning, despite aggressive pharmacotherapy. Psychosocial interventions that target functional factors could be beneficial for this population, and we hypothesized that the addition of group cognitive behavioral therapy (CBT) to maintenance pharmacotherapy would improve functioning and quality of life. METHODS: Patients diagnosed (by SCID) with bipolar disorder attending an outpatient clinic of a mood disorders program participated in the study. All patients were on maintenance mood stabilizers, and were required to have controlled symptoms before entering the study. Mood symptoms were assessed with the Hamilton Depression Rating scale and Young Mania scale at baseline and 14 weeks. Objective and subjective functioning was rated at the same interval using the Global Assessment of Functioning scale and the Medical Outcomes Survey SF-36. Treatment was provided via a specific manual based on CBT principles that could be applied to this population. RESULTS: Forty nine patients participated in this open trial, and 38 patients completed treatment. Objective and subjective indices of impairment showed improvement after 14 weeks. Both GAF and MOS scores increased significantly by the end of treatment. LIMITATIONS: This study was an open trial, and lack of control groups limits the interpretation of results. Because the study concerned effectiveness, the results do not clarify whether the improvement represents the normal course of illness or whether it is the result of the CBT intervention. CONCLUSIONS: The addition of group CBT to standard pharmacological treatment was acceptable to patients, and nearly 80% of patients complied with treatment. Despite the fact that mood symptoms were controlled at entry into the study, psychosocial functioning increased significantly at the end of treatment. Adjunctive CBT should be further investigated in this population.

When reviews attack: ethics, free speech, and the peer review process.

The peer review process, whether formally applied in publication and grant review, or informally, such as exchange of ideas in scientific and professional newsgroups, has sparked controversy. Writers in this area agree that scholarly reviews that are inappropriate in tone are not uncommon. Indeed, commentators have suggested rules and guidelines that can be used to improve the review process and to make reviewers more accountable. In this paper, we examine the relevance and impact of ethical codes on the conduct of peer review. It is our contention that the peer review process can be improved, not by a new set of rules but through closer attention to the ethical principles to which we, as psychologists, already subscribe.

Improved outcome in haemophagocytic lymphohistiocytosis after bone marrow transplantation from related and unrelated donors: a single-centre experience of 12 patients.

Haemophagocytic lymphohistiocytosis (HLH) is an autosomal recessive disease with histiocytic and lymphocytic infiltrations in multiple organs. Cure seems possible only by allogeneic bone marrow transplantation (BMT), but matched sibling donors (MSD) are restricted and high mortality rates are associated with BMT from unrelated donors (URD). We report on 12 consecutive HLH patients with an improved outcome following URD transplants. Eight patients received BMT from URD, four from MSD. Five patients had signs of active HLH at the time of BMT. The conditioning regimen consisted of 20 mg/kg busulphan, 60 mg/kg VP-16 and 120 mg/kg cyclophosphamide and, in case of URD, 90 mg/kg antithymocyte globulin. The doses of busulphan and VP-16 were reduced during the programme to 16 mg/kg and 30 mg/kg, respectively. Using a fivefold graft-versus-host disease (GVHD) prophylaxis, GVHD was absent or mild in 10, and moderate or severe in two patients undergoing unrelated transplants. One patient with URD experienced graft failure and was retransplanted on day 37. Major toxicities were hepatic veno-occlusive disease in five, capillary leak syndrome in two, pneumonia in three, sepsis in one, severe mucositis in one and seizures in two patients. All patients are alive without HLH after a median follow-up of 24.5 months. One patient has chronic GVHD, another patient has severe retardation. Three patients show slight to moderate development delay. These results indicate that in HLH, BMT from matched unrelated donors should be performed. Incomplete resolution of disease activity need not impede a successful outcome.

Long-term results of the co-operative German-Austrian-Swiss osteosarcoma study group's protocol COSS-86 of intensive multidrug chemotherapy and surgery for osteosarcoma of the limbs.

BACKGROUND: In an effort to intensify osteosarcoma therapy, systemic ifosfamide was added pre- and postoperatively to an already aggressive three-drug regimen. In a subgroup of patients, loco-regional treatment intensification was attempted by using the intraarterial route to give cisplatin. PATIENTS AND METHODS: Patients < or = 40 years at diagnosis of a localised, de novo high-grade central extremity osteosarcoma were eligible for inclusion into study COSS-86 if registered within three weeks from biopsy. Doxorubicin, high-dose methotrexate, and cisplatin were given to all patients. Patients who fulfilled one or more of three defined high-risk criteria received early systemic treatment intensification by adding ifosfamide as the fourth agent. Preoperatively, these high-risk patients received cisplatin either intraarterially or intravenously. RESULTS: 171 eligible patients were entered, of which 128 were stratified into the high-risk group. When all 171 were analysed by intention-to-treat, actuarial overall and event-free survival rates at ten years were 72% and 66%, respectively. No benefit of intraarterial cisplatin application was detected. Cumulative treatment toxicity was considerable. CONCLUSIONS: In a multicenter setting, intensive treatment of osteosarcoma according to protocol COSS-86 led to long-term disease-free survival for two thirds of patients. We saw no benefit of using the intraarterial route to administer cisplatin.

The State-Trait Anxiety Inventory, Trait version: structure and content re-examined.

Although the State-Trait Anxiety Inventory (STAI) is a popular measure of anxiety, some previous research suggests that the trait scale may assess depression, as well as anxiety. The factor structure of the trait items was initially examined using factor analytic procedures. Confirmatory factor analytic methods suggested that a hierarchical solution best fit the data, with one overall factor and two lower order factors. The lower order subscales created from this factor solution were examined in a sample of individuals diagnosed with an anxiety disorder. Overall, the results offered good support for the notion that the trait scale of the STAI assesses depression, as well as anxiety. One set of items appeared to assess anxiety and worry, whereas the other assessed sadness and self-deprecation. The two subscales correlated differentially with other measures of anxiety and depression in a manner that was consistent with their content. Finally, diagnostic groups and controls could be meaningfully distinguished on these subscales. Implications for the use of this measure are discussed.

Interpersonal consequences of the pursuit of safety.

Socially anxious (N = 41) and non-anxious (N = 41) individuals participated in a getting acquainted situation that was based on the reciprocity self-disclosure paradigm. Subjects' appraisals of the situation were manipulated to be either positive or negative by highlighting the likelihood of positive or negative social outcomes. Subjects' social goals and use of safety behaviors were assessed, as were others' reaction to the subjects. As predicted, socially anxious individuals elicited significantly more negative responses from others in the negative appraisal condition, where they employed safety behaviors, than in the positive appraisal condition, where they did not. The results supported a cognitive model of social anxiety, rather than alternative explanations.

The consequences of perfectionism for patients with social phobia.

OBJECTIVES: To examine levels of perfectionism in social phobics and to explore the consequences of perfectionism for such individuals. DESIGN: A between-groups laboratory design was used to provide a level of comparison between phobic and non-phobic individuals in a controlled setting. METHOD: Participants for the phobic group (N = 28) were recruited from waiting lists for treatment programmes, and matched controls (N = 29) were recruited from community advertisements. Volunteers for the study completed measures of perfectionism (Multidimensional Perfectionism Scale) and then completed a laboratory session in which they were asked to rate others' social standards for them and their own social ability. RESULTS: Social phobic individuals scored higher on socially prescribed perfectionism. Perfectionistic traits were associated with higher standards in social phobics, but not in controls. Finally, social phobia was associated with lowered perceptions of social ability. CONCLUSIONS: Although social phobia and socially prescribed perfectionism were intertwined, the two conditions appeared to contribute to negative self-appraisal through different processes. Social phobics who are perfectionistic are likely not only to have low levels of efficacy, but also to feel that others will have high expectations for them in social situations.

Tumor size and prognosis in aggressively treated osteosarcoma.

PURPOSE: The aim of this retrospective analysis was to investigate the prognostic significance and optimal measures of tumor size in osteosarcoma treated with intensive neoadjuvant chemotherapy. PATIENTS AND METHODS: Initial anterior-posterior (AP) and lateral x-ray films of 128 patients treated within the trials Cooperative Osteosarcoma Study (COSS)-80, -82, and -86, were evaluated for the following three tumor diameters: length, width, and depth. Metastasis-free survival (MFS) analyses were performed in univariate and multivariate models with one, two, and three dimensions of the tumor as absolute or relative measures (tumor length, referred to bone length, plane and volume to body-surface area). RESULTS: Univariate analyses of MFS showed a high prognostic significance of all absolute measures. Relative measures, at best, showed a comparable predictive value. Cox regression analysis indicated the high prognostic significance of absolute tumor volume (ATV; P < .0001) and histologic response (P < .0001). None of 19 patients with an ATV < or = 70 cm3 and only four of 53 with an ATV < or = 150 cm3 relapsed, while in patients with an ATV more than 150 cm3, the relapse rate remained 40% to 60%, irrespective of further increase in volume. CONCLUSION: Initial tumor size is an important and easily obtainable prognostic factor in osteosarcoma and may serve as a basis for risk-adapted therapy. It is best represented by the absolute three-dimensional measure ATV. There is a cut-off point regarding the incidence of metastases at a tumor volume of approximately 150 cm3 as calculated from two-plane x-ray films.

[The prognostic significance of tumor volume in osteosarcoma with neoadjuvant chemotherapy]. / Die prognostische Bedeutung des Tumorvolumens beim Osteosarkom unter neoadjuvanter Chemotherapie.

In a retrospective analysis on 128 patients from the trials COSS-80, -82, -85 and -86 initial x-ray pictures were evaluated for tumor diameters in three planes and the prognostic meaning on survival was assessed. In a subset of patients (n = 27) the measured values were compared to values obtained by CT-Scan and a good correlation (r = 0.69) was found. Several parameters for tumor size were defined: absolute tumor length (ATL), relative tumor length (RTL, proportion of tumor to the length of the involved bone), absolute tumor volume (ATV, calculated by the ellipsoid formula) and relative tumor volume (RTL, tumor volume referred to the body surface area) and univariate and multivariate survival analysis were performed. Univariate analysis of metastasis free survival (MFS) revealed a high prognostic significance of the ATL, the ATV and the RTV. The RTL in this patient group demonstrated a tendency only toward an inferior prognosis in larger tumors. None of the patients with a ATV < 70 ml (n = 19) and only one of 33 patients with an ATV < 100 ml relapsed. Cox regression analysis was performed including the variables age, sex, site and response (> 90% tumor necrosis) in 84 patients. ATL and RTL do not enter the model, while the response proves its significance as a valid prognostic factor with a p-value of 0.0004. Adding the ATV as the measure of tumor size to the model it enters as the first term (p = 0.0000) followed by the response (p = 0.0002).(ABSTRACT TRUNCATED AT 250 WORDS)

Intraarterial chemotherapy for osteosarcoma: does the result really justify the effort?

The use of multiagent chemotherapy has led to improved survival for osteosarcoma patients. Infusion of cisplatin by the intraarterial route in order to devitalize the primary tumor more effectively has been advocated in this context. While systemic drug levels do not seem to be compromised by this regional approach, the envisioned increase in platinum content of osteosarcoma tissue has not been substantiated. As far as clinical results are concerned, neither a comparison of various protocols including cisplatin by either intraarterial or intravenous application, nor the only controlled study dealing with the subject (COSS 86), were able to demonstrate a correlation between the route of cisplatin administration and tumor response to chemotherapy. Therefore, the use of the intraarterial route for cisplatin treatment of osteosarcoma cannot be considered standard therapy but is still an investigational approach without proven benefits. In addition, the risk of side effects and the increased cost of this procedure should be considered before deciding to use intraarterial treatment for osteosarcoma.

[Chemotherapy of osteosarcoma]. / Die Chemotherapie des Osteosarkoms.

Intensified adjuvant chemotherapy increased the 4-year metastasis-free survival probability from 50% (COSS-77) to roughly 80% (COSS-86). Preoperative chemotherapy was found without recognizable hazard and promoting conservative surgery. Following resection the local failure rate ist significantly higher than after demolitive procedures, including rotation plasty (10.5% vs. 2.5%). Local failures bare a very poor prognosis (19/23 DOD). The acute therapy related mortality is less than 3%. Late toxicities like ototoxicity and cardiotoxicity are intriguing and deserve increased attention. The management of the osteosarcoma patient is a complex and difficult interdisciplinary task which is best performed in centers experienced in the treatment of malignant musculo-skeletal tumors.

Local control and survival from the Cooperative Osteosarcoma Study Group studies of the German Society of Pediatric Oncology and the Vienna Bone Tumor Registry.

The use of aggressive chemotherapy undoubtedly has brought about a dramatic increase in the cure rate of osteosarcoma. The authors' investigations have increased the authors' knowledge of chemotherapy for osteosarcoma, the differential efficacy of currently used agents, and the pronounced schedule dependency and relative route independency of their efficiency. The authors were able to confirm the prognostic significance of tumor response after preoperative chemotherapy. Preoperative chemotherapy in itself has facilitated and promoted limb-salvage surgery. Also, more patients can be cured today by use of aggressive thoracic surgery in case of primary or secondary pulmonary metastases. The authors' efforts to steadily increase metastasis-free survival rates by intensifying chemotherapy in this series of studies, however, have been only moderately successful. Still, chemotherapy-related acute toxicity is considerable and increases with aggressiveness of treatment, and the manifestations of late toxicity may continue to increase with follow-up time. Future trials should be targeted toward exploration of the minimum indispensable amount of toxic treatment yielding comparable or even better results than those currently attainable.

[Neoadjuvant chemotherapy of osteosarcoma. Preliminary results of the cooperative COSS-86 osteosarcoma study]. / Neoadjuvante Chemotherapie des Osteosarkoms. Vorläufige Ergebnisse der kooperativen Osteosarkom-Studie COSS-86.

The neoadjuvant study COSS-86 was undertaken aiming at (1) improving the cure rate in osteosarcoma by early intensification of chemotherapy in high risk patients and (2) investigating the effect of intraarterial (i.a.) versus intravenous (i.v.) administration of cisplatinum. (1) Ifosfamide was added to the well proven drugs in osteosarcoma such as doxorubicin, high-dose methotrexate and cisplatinum in patients with large tumor size or/and high portion of chondroid groundsubstance or/and scintigraphic nonresponse after 4 weeks of preoperative chemotherapy. It was given in combination with cisplatinum. (2) The same patients were allocated to either the intraarterial study arm or the intravenous control arm of the study. The response rate (greater than 90% tumor necrosis) of all patients was 75% (88/118). No advantage in response rate was achieved by i.a. infusion of cis-platinum within this highly efficient 4-drug regimen (i.a. 75% (33/44) vs. i.v. 74% (35/47)). The significantly improved response rate in this study results in a better metastasis free survival (MFS) of 77% (+/- 4) at 4 years.

In-vitro and in-vivo studies on the induction of neopterin biosynthesis by cytokines, alloantigens and lipopolysaccharide (LPS).

Recently we presented evidence that cellular immune responses are associated with increased in-vitro and in-vivo excretion of neopterin (Huber et al., 1983) and that, in vitro at least, macrophages and IFN-gamma play a key role in the induction of this phenomenon (Huber et al., 1984). Although this marker is increasingly applied for monitoring of human disease, there is limited knowledge about the mechanism(s) responsible for its increased biosynthesis during inflammatory states. To further elucidate this question we evaluated neopterin and IFN-levels in culture supernatants of human blood cells and in patients' sera. Cells or patients were exposed to a panel of recombinant cytokines, alloantigens or lipopolysaccharide. To investigate indirect stimulation by induction of production of endogenous IFNs, the impact of neutralization of IFNs by addition of specific antibodies was also studied. The data confirm our previous results which identified the monocyte/macrophage as the main producer cell among human blood cells. They further demonstrate that, at least in vitro, IFN-gamma, IFN-alpha and LPS can all stimulate neopterin release independently from each other. Thirdly, they indicate that stimuli such as alloantigens or TNF-alpha can indirectly enhance neopterin release by their capacity to induce production of endogenous IFN-gamma. On the basis of these data we conclude that enhanced neopterin biosynthesis does not necessarily relate to activation of T cells but can also be caused by non-immune stimuli.

Cytokines in the control of beta-2 microglobulin release. I. In vitro studies on various haemopoietic cells.

The role of cytokines in the control of beta-2 microglobulin release from various haemopoietic cells was studied in vitro. Cell types investigated were resting cells or blasts of the T cell, B cell or monocyte-macrophage lineage. Mediators used in these experiments were r-IFN-alpha 2c, r-IFN-gamma, r-TNF-alpha, r-TNF-beta, r-IL1, r-IL2 and r-GM-CSF. Nanogram amounts of some of these mediators strongly affected beta-2 microglobulin release in vitro. r-IFN-gamma, r-IFN-alpha 2c and r-IL2 strongly enhanced and r-TNF-alpha and r-TNF-beta occasionally increased shedding of beta-2 microglobulin. r-IL1 and high concentrations of r-IFN-alpha 2c were inhibitory, whereas r-GM-CSF was ineffective. The impact of antigenic stimulation on beta-2 microglobulin release in mixed lymphocyte culture (MLC) was also studied. Stimulation with alloantigens in MLC greatly enhanced beta-2 microglobulin shedding, and this enhancement could be inhibited by a monoclonal antibody neutralizing human IFN-gamma. Among the various cell types studied, macrophages derived from peripheral blood monocytes were most susceptible to cytokine-induced alterations of beta-2 microglobulin shedding. From these data, we conclude that cytokines not only control the static expression of beta-2 microglobulin on the surface of haemopoietic cells but also largely affect their shedding.