Measurement of the 171Tm beta spectrum.

The beta spectrum of the main transition of the ß- decay of 171Tm was measured using a double focalizing spectrometer. The instrument was lately improved in order to reduce its low energy threshold to 34 keV. We used the spectrometer to measure the beta spectrum end-point energy of the main transition of 171Tm decay using the Kurie plot formalism. We report a new value of 97.60(38) keV, which is in agreement with previous measurements. In addition, the spectrum shape was compared with the ξ-approximation calculation where the shape factor is equal to 1 and good agreement was found between the theory and the measurement at the 1% level.

Predicting optimal treatment outcomes in phase-based treatment and direct trauma-focused treatment among patients with posttraumatic stress disorder stemming from childhood abuse.

Research over the last few decades has demonstrated the effectiveness of various treatments for posttraumatic stress disorder (PTSD). However, the question of which treatment works best remains, especially for patients with PTSD stemming from childhood abuse. Using the Personalized Advantage Index (PAI), we explored which patients benefit more from phase-based treatment and which benefit more from direct trauma-focused treatment. Data were obtained from a multicenter randomized controlled trial (RCT) comparing a phase-based treatment condition (i.e., eye-movement desensitization and reprocessing [EMDR] therapy preceded by Skills Training in Affect and Interpersonal Regulation [STAIR]; n = 57) and a direct trauma-focused treatment (EMDR only; n = 64) among individuals with PTSD related to childhood abuse. Machine learning techniques were used to examine all pretreatment variables included in the trial as potential predictors and moderators, with selected variables combined to build the PAI model. The utility of the PAI was tested by comparing actual posttreatment outcomes of individuals who received PAI-indicated treatment with those allocated to a non-PAI-indicated treatment. Although eight pretreatment variables between PTSD treatment outcome and treatment condition were selected as moderators, there was no significant difference between participants assigned to their PAI-indicated treatment and those randomized to a non-PAI-indicated treatment, d = 0.25, p = .213. Hence, the results of this study do not support the need for personalized medicine for patients with PTSD and a history of childhood abuse. Further research with larger sample sizes and external validation is warranted.

Predictors of treatment dropout in patients with posttraumatic stress disorder due to childhood abuse.

Background: Knowledge about patient characteristics predicting treatment dropout for post-traumatic stress disorder (PTSD) is scarce, whereas more understanding about this topic may give direction to address this important issue. Method: Data were obtained from a randomized controlled trial in which a phase-based treatment condition (Eye Movement Desensitization and Reprocessing [EMDR] therapy preceded by Skills Training in Affect and Interpersonal Regulation [STAIR]; n = 57) was compared with a direct trauma-focused treatment (EMDR therapy only; n = 64) in people with a PTSD due to childhood abuse. All pre-treatment variables included in the trial were examined as possible predictors for dropout using machine learning techniques. Results: For the dropout prediction, a model was developed using Elastic Net Regularization. The ENR model correctly predicted dropout in 81.6% of all individuals. Males, with a low education level, suicidal thoughts, problems in emotion regulation, high levels of general psychopathology and not using benzodiazepine medication at screening proved to have higher scores on dropout. Conclusion: Our results provide directions for the development of future programs in addition to PTSD treatment or for the adaptation of current treatments, aiming to reduce treatment dropout among patients with PTSD due to childhood abuse.

Exploring therapist characteristics as potential moderators of the effects of client feedback on treatment outcome.

Although studies have shown that client feedback can improve treatment outcome, little is known about which factors might possibly moderate the effects of such feedback. The present study investigated potential therapist variables that might influence whether frequent client feedback is effective, including the Big Five personality traits, internal/external feedback propensity and self-efficacy. Data from two previous studies, a quasi-experimental study and a randomized controlled trial, were combined. The sample consisted of 38 therapists and 843 clients (55.4% females, mean age = 42.05 years, SD = 11.75) from an outpatient mental health institution. The control condition consisted of cognitive-behavioural therapies combined with low frequency monitoring of clients' symptoms. In the experimental condition, high-intensity (i.e., frequent) client feedback as an add-on to treatment as usual was provided. Outcomes were measured as adjusted post-treatment symptom severity on the Symptom Checklist-90 and drop out from treatment. The final model of the multilevel analyses showed that therapists with higher levels of self-efficacy had poorer treatment outcomes, but when high-intensity client feedback was provided, their effectiveness improved. Furthermore, higher self-efficacy was associated with a higher estimation of therapists' own effectiveness, but therapists' self-assessment of effectiveness was not correlated with their actual effectiveness. The results of this study might indicate that therapists with high levels of self-efficacy benefit from client feedback because it can correct their biases. However, for therapists with low self-efficacy, client feedback might be less beneficial, possibly because it can make them more insecure. These hypotheses need to be investigated in future research.

Economic evaluation of preventive cognitive therapy versus care as usual in cognitive behavioral therapy responders.

Background: The highly recurrent nature of Major Depressive Disorder is a major contributor to disability and health care costs. Several studies indicate that recurrence may be prevented with Preventive Cognitive Therapy (PCT). This study is the first to perform an economic evaluation of PCT in comparison with care as usual for recurrently depressed patients who experienced two or more depressive episodes and remitted after receiving Cognitive Behavioural Therapy. Methods: An economic evaluation from the societal perspective was performed alongside a randomized trial (N = 214). Health-related quality of life (QALYs), depression-free days, health care utilization, and productivity losses were measured between randomization and 15 months follow-up. The costs were indexed to the reference year 2014. Results: QALY gains did not differ significantly between the groups (p = 0.69). Depression-free days were higher after PCT (p = 0.02). Societal costs of PCT were 10,417 euro and for care as usual 9,545 euro per person. We found a 47% likelihood that PCT led to additional QALYs at higher costs, and there was a 26% likelihood that PCT led to fewer QALYs at higher costs. When depression-free days was used as an outcome, we found PCT had a 72% likelihood of leading to more depression-free days at higher costs than care as usual and a 27% likelihood of leading to more depression-free days at lower societal costs. Limitations: The 15-month follow-up might be too short to draw long-term conclusions about the cost-effectiveness of the PCT. The data collected for this study is part of an RCT to examine the effectiveness of adding PCT to care as usual. Therefore, the study was powered primarily to detect an effect in time to relapse/recurrences. Conclusion: The economic evaluation is slightly in favour of the PCT condition when depression-free days is used as an outcome. PCT is not cost-effective given the high costs per additional QALYs from the societal perspective when QALYs are the effect measure. Clinical trial registration: https://www.onderzoekmetmensen.nl/en, identifier NL2482.

Predictors and moderators of treatment outcomes in phase-based treatment and trauma-focused treatments in patients with childhood abuse-related post-traumatic stress disorder.

Background: Knowledge of treatment predictors and moderators is important for improving the effectiveness of treatment for PTSD due to childhood abuse.Objective: The first aim of this study was to test the potential predictive value of variables commonly associated with PTSD resulting from a history of repeated childhood abuse, in relation to treatment outcomes. The second aim was to examine if complex PTSD symptoms act as potential moderators between treatment conditions and outcomes.Method: Data were obtained from a randomized controlled trial comparing a phase-based treatment (Skills Training in Affect and Interpersonal Regulation [STAIR] followed by Eye Movement Desensitization and Reprocessing [EMDR] therapy; n = 57) with a direct trauma-focused treatment (EMDR therapy only; n = 64) in people with PTSD due to childhood abuse. The possible predictive effects of the presence of borderline personality disorder, dissociative symptoms, and suicidal and self-injurious behaviours were examined. In addition, it was determined whether symptoms of emotion regulation difficulties, self-esteem, and interpersonal problems moderated the relation between the treatment condition and PTSD post-treatment, corrected for pre-treatment PTSD severity.Results: Pre-treatment PTSD severity proved to be a significant predictor of less profitable PTSD treatment outcomes. The same was true for the severity of dissociative symptoms, but only post-treatment, and not when corrected for false positives. Complex PTSD symptoms did not moderate the relationship between the treatment conditions and PTSD treatment outcomes.Conclusions: The current findings suggest that regardless of the common comorbid symptoms studied, immediate trauma-focused treatment is a safe and effective option for individuals with childhood-related PTSD. However, individuals experiencing severe symptoms of PTSD may benefit from additional treatment sessions or the addition of other evidence-based PTSD treatment approaches. The predictive influence of dissociative sequelae needs further research.The study design was registered in The Dutch trial register (https://www.trialregister.nl/trialreg/admin/rctview.asp?TC = 5991) NTR5991 and was approved by the medical ethics committee of Twente NL 56641.044.16 CCMO.

One of first studies that aimed to identify multiple potential predictors and moderators in patients with PTSD related to childhood abuse.Only severe PTSD predicted worse treatment outcomes.The predictive influence of dissociative sequelae needs further research.

Treatment of severe acute ulcerative colitis in SARS-CoV-2 infected patients: report of three cases and discussion of treatment options.

In the wake of the coronavirus disease 2019 (COVID-19) pandemic, it is unclear how asymptomatic severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)-infected patients who present with acute severe ulcerative colitis (UC) can be treated effectively and safely. Standard treatment regimens consist of steroids, immunomodulatory drugs, and biological therapies, but therapeutic decision-making becomes challenging as there are uncertainties about how to deal with these drugs in patients with COVID-19 and active UC. Importantly, guidelines for this particular group of patients with UC are still lacking. To inform therapeutic decision-making, we describe three consecutive cases of patients with active UC and COVID-19 and discuss their treatments based on theoretical knowledge, currently available evidence and clinical observations. Three patients were identified through our national inflammatory bowel disease network [Initiative on Crohn's and Colitis (ICC)] for whom diagnosis of SARS-CoV-2-infection was established by reverse transcription-polymerase chain reaction (RT-PCR) testing in nasopharynx, stools, and/or biopsies. Acute severe UC was diagnosed by clinical parameters, endoscopy, and histopathology. Clinical guidelines for SARS-CoV-2-negative patients advocate the use of steroids, calcineurin inhibitors, or tumor necrosis factor alpha (TNF-α)-antagonists as induction therapy, and experiences from the current three cases show that steroids and TNF-α-antagonists could also be used in patients with COVID-19. This could potentially be followed by TNF-α-antagonists, vedolizumab, or ustekinumab as maintenance therapy in these patients. Future research is warranted to investigate if, and which, immunomodulatory drugs should be used for COVID-19 patients that present with active UC. To answer this question, it is of utmost importance that future cases of patients with UC and COVID-19 are documented carefully in international registries, such as the SECURE-IBD registry.

Clinical Outcomes of Covid-19 in Patients With Inflammatory Bowel Disease: A Nationwide Cohort Study.

BACKGROUND AND AIMS: The COVID-19 risk and disease course in inflammatory bowel disease [IBD] patients remains uncertain. Therefore, we aimed to assess the clinical presentation, disease course, and outcomes of COVID-19 in IBD patients. Second, we determined COVID-19 incidences in IBD patients and compared this with the general population. METHODS: We conducted a multicentre, nationwide IBD cohort study in The Netherlands and identified patients with COVID-19. First, we assessed the COVID-19 disease course and outcomes. Second, we compared COVID-19 incidences between our IBD study cohort and the general Dutch population. RESULTS: We established an IBD cohort of 34 763 patients. COVID-19 was diagnosed in 100/34 763 patients [0.29%]; 20/100 of these patients [20%] had severe COVID-19 defined as admission to the intensive care unit, mechanical ventilation, and/or death. Hospitalisation occurred in 59/100 [59.0%] patients and 13/100 [13.0%] died. All patients who died had comorbidities and all but one were ≥65 years old. In line, we identified ≥1 comorbidity as an independent risk factor for hospitalisation (odds ratio [OR] 4.20, 95% confidence interval [CI] 1.58-11.17,; p = 0.004). Incidences of COVID-19 between the IBD study cohort and the general population were comparable (287.6 [95% CI 236.6-349.7] versus 333.0 [95% CI 329.3-336.7] per 100000 patients, respectively; p = 0.15). CONCLUSIONS: Of 100 cases with IBD and COVID-19, 20% developed severe COVID-19, 59% were hospitalised and 13% died. A comparable COVID-19 risk was found between the IBD cohort [100/34 763 = 0.29%] and the general Dutch population. The presence of ≥1 comorbidities was an independent risk factor for hospitalisation due to COVID-19.

The effect of feedback-informed cognitive behavioral therapy on treatment outcome: A randomized controlled trial.

OBJECTIVE: Previous studies have shown that feedback-informed treatment can improve outcomes of psychological treatments. This randomized controlled effectiveness trial evaluated the effect of progress feedback on treatment duration, symptom reduction, and dropout in individual cognitive behavioral therapies (CBTs). A control condition where CBT was combined with low-intensive monitoring of progress was compared to an experimental condition where CBT was combined with a high-intensive form of feedback. METHOD: Data of 368 outpatients (57.9% female, mean age 41.4 years, SD = 12.2) in secondary care were analyzed using multilevel analyses. Treatment duration was assessed with the number of sessions clients received. Symptom reduction was measured with the Symptom Checklist Revised. Possible moderators of the effect of intensive progress feedback on outcome were explored. RESULTS: Clients achieved the same amount of symptom reduction in significantly fewer sessions in the high-intensive feedback condition. Additionally, dropout was significantly lower in the high-intensive feedback condition. Post hoc analyses assessing clients' diagnoses as a possible moderator showed that clients with personality disorders (mainly Cluster C) achieved more symptom reduction in fewer sessions when high-intensity feedback was provided. Also, a high degree of implementation within the experimental condition was associated with fewer treatment sessions. CONCLUSION: In sum, the use of high-intensive client feedback reduced treatment duration and reduced dropout of CBT. Thus, feedback-informed CBTs seem to be a promising adaptation of conventional CBT. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Preventive cognitive therapy versus care as usual in cognitive behavioral therapy responders: A randomized controlled trial.

OBJECTIVE: The optimization of long-term outcomes is an important goal in the treatment of major depressive disorder. Offering subsequent preventive cognitive therapy (PCT) to patients who responded to acute cognitive behavioral therapy (CBT) may reduce the risk of relapse/recurrence. METHOD: Therefore, a multicenter randomized controlled trial was conducted comparing the addition of eight weekly sessions of PCT to care as usual (CAU) versus CAU alone in patients with a history of depression in remission following treatment with CBT. A total of 214 recurrently depressed patients who remitted following treatment with CBT were randomized to PCT (n = 107) or CAU (n = 107). Primary outcome was time to relapse/recurrence over 15 months and was assessed by the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I). Secondary outcomes were depressive symptoms measured by the Inventory of Depressive Symptomatology-Self Report and number and severity of relapses/recurrences measured by the SCID-I. RESULTS: Over the 15-month follow-up, the addition of PCT significantly delayed time to relapse/recurrence relative to CAU alone, hazard ratio = 1.807 (number needed to treat = 8.1), p = .02, 95% CI [1.029, 3.174]. No significant differences were found between the conditions on number or severity of relapses/recurrences and residual symptoms. CONCLUSION: Adding PCT was significantly more effective than CAU alone in delaying time to relapse/recurrence of depression over a period of 15 months among CBT responders. After response on CBT, therapists should consider providing PCT to recurrently depressed patients. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Phase-based treatment versus immediate trauma-focused treatment in patients with childhood trauma-related posttraumatic stress disorder: study protocol for a randomized controlled trial.

BACKGROUND: The treatment of posttraumatic stress disorder (PTSD) related to a history of sexual and/or physical abuse in childhood is the subject of international debate, with some favouring a phase-based approach as their preferred treatment, while others argue for immediate trauma-focused treatment. A history of (chronic) traumatisation during childhood has been linked to the development of distinct symptoms that are often labelled as symptoms of complex PTSD. Many therapists associate the presence of symptoms of complex PTSD with a less favourable treatment prognosis. The purpose of this study is to determine whether a phase-based approach is more effective than stand-alone trauma-focused therapy in individuals with PTSD and possible symptoms of complex PTSD resulting from a history of repeated sexual and/or physical abuse in childhood. An additional aim is to investigate moderators, predictors of treatment (non) response and drop-out. METHOD: The sample consists of patients between 18 and 65 years old with a diagnosis of PTSD who report a history of repeated sexual and/or physical abuse in childhood (N = 122). Patients will be blindly allocated to either 16 sessions of eye movement desensitization and reprocessing (EMDR) therapy preceded by a stabilization phase (eight sessions of Skills Training in Affect and Interpersonal Regulation (STAIR)) or only 16 sessions of EMDR therapy. Assessments are carried out pre-treatment, after every eighth session, post-treatment, and at 3 and 6 months follow up. The main parameter will be the severity of PTSD symptoms (PTSD Symptoms Scale-Self Report). Secondary outcome variables are the presence of a PTSD diagnosis (Clinician-Administered PTSD Scale for DSM-5), severity of complex PTSD symptoms (Structured Interview for Disorders of Extreme Stress-Revised and symptoms-specific questionnaires), changes in symptoms of general psychopathology (Brief Symptom Inventory), and quality of life (Euroqol-5D). Health care consumption and productivity loss in patients will also be indexed. DISCUSSION: The study results may help to inform the ongoing debate about whether a phase-based approach has added value over immediate trauma-focused therapy in patients suffering from PTSD due to childhood abuse. Furthermore, the results will contribute to knowledge about the safety, efficacy, and cost-effectiveness of treatments in this target group. TRIAL REGISTRATION: Nederlands Trialregister, NTR5991 . Registered on 23 august 2016. http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=5991.

The effect of shorter exposure versus prolonged exposure on treatment outcome in Tourette syndrome and chronic tic disorders - an open trial.

Background: Exposure and response prevention has shown to be an effective strategy and is considered a first-line intervention in the behavioural treatment of tic disorders. Prior research demonstrated significant tic reduction after 12 two hour sessions. Objective: In this open trial, the question is addressed whether, relative to these prolonged sessions, exposure sessions of shorter duration yield differential outcome for patients with tic disorders. Methods: A total of 29 patients diagnosed with Tourette syndrome (TS) or chronic tic disorder were treated with shorter exposure sessions (1 h), and these data were compared to the data from a study about prolonged exposure (2 h, n = 21). Outcome was measured by the Yale Global Tic Severity Scale (YGTSS). Results: Results suggest that after taking the difference in illness duration between the two groups into account, the effectiveness of shorter exposure sessions is not inferior to that of prolonged exposure. Conclusions: Results suggest that treatment with shorter exposure might be more efficient and more patients can be reached. Future research is needed to gain more insight into the mechanisms underlying the efficacy of behavioural treatments for tics.

Intradiscal application of a PCLA-PEG-PCLA hydrogel loaded with celecoxib for the treatment of back pain in canines: What's in it for humans?

Chronic low back pain is a common clinical problem in both the human and canine population. Current pharmaceutical treatment often consists of oral anti-inflammatory drugs to alleviate pain. Novel treatments for degenerative disc disease focus on local application of sustained released drug formulations. The aim of this study was to determine safety and feasibility of intradiscal application of a poly(ε-caprolactone-co-lactide)-b-poly(ethylene glycol)-bpoly(ε-caprolactone-co-lactide) PCLA-PEG-PCLA hydrogel releasing celecoxib, a COX-2 inhibitor. Biocompatibility was evaluated after subcutaneous injection in mice, and safety of intradiscal injection of the hydrogel was evaluated in experimental dogs with early spontaneous intervertebral disc (IVD) degeneration. COX-2 expression was increased in IVD samples surgically obtained from canine patients, indicating a role of COX-2 in clinical IVD disease. Ten client-owned dogs with chronic low back pain related to IVD degeneration received an intradiscal injection with the celecoxib-loaded hydrogel. None of the dogs showed adverse reactions after intradiscal injection. The hydrogel did not influence magnetic resonance imaging signal at long-term follow-up. Clinical improvement was achieved by reduction of back pain in 9 of 10 dogs, as was shown by clinical examination and owner questionnaires. In 3 of 10 dogs, back pain recurred after 3 months. This study showed the safety and effectiveness of intradiscal injections in vivo with a thermoresponsive PCLA-PEG-PCLA hydrogel loaded with celecoxib. In this set-up, the dog can be used as a model for the development of novel treatment modalities in both canine and human patients with chronic low back pain.

Improving the efficiency of cognitive-behavioural therapy by using formal client feedback.

OBJECTIVE: Feedback from clients on their view of progress and the therapeutic relationship can improve effectiveness and efficiency of psychological treatments in general. However, what the added value is of client feedback specifically within cognitive-behavioural therapy (CBT), is not known. Therefore, the extent to which the outcome of CBT can be improved is investigated by providing feedback from clients to therapists using the Outcome Rating Scale (ORS) and Session Rating Scale (SRS). METHOD: Outpatients (n = 1006) of a Dutch mental health organization either participated in the "treatment as usual" (TAU) condition, or in Feedback condition of the study. Clients were invited to fill in the ORS and SRS and in the Feedback condition therapists were asked to frequently discuss client feedback. RESULTS: Outcome on the SCL-90 was only improved specifically with mood disorders in the Feedback condition. Also, in the Feedback condition, in terms of process, the total number of required treatment sessions was on average two sessions fewer. CONCLUSION: Frequently asking feedback from clients using the ORS/SRS does not necessarily result in a better treatment outcome in CBT. However, for an equal treatment outcome significantly fewer sessions are needed within the Feedback condition, thus improving efficiency of CBT.

Safety of intradiscal injection and biocompatibility of polyester amide microspheres in a canine model predisposed to intervertebral disc degeneration.

Repair of degenerated intervertebral discs (IVD) might be established via intradiscal delivery of biologic therapies. Polyester amide polymers (PEA) were evaluated for in vitro cytotoxicity and in vivo biocompatibility, and thereafter intradiscal application of PEA microspheres (PEAMs) in a canine model predisposed to IVD degeneration at long-term (6 months) follow-up. PEA extracts did not induce cytotoxicity in mouse fibroblast cells (microscopy and XTT assay), while a slight foreign body reaction was demonstrated by histopathology after intramuscular implantation in rabbits. Intradiscal injection of a volume of 40 µL through 26 and 27G needles induced no degenerative changes in acanine model susceptible to IVD disease. Although sham-injected IVDs showed increased CAV1 expression compared with noninjected IVDs, which may indicate increased cell senescence, these findings were not supported by immunohistochemistry, biomolecular analysis of genes related to apoptosis, biochemical and histopathological results. PEAM-injected IVDs showed significantly higher BAX/BCL2 ratio vs sham-injected IVDs suggestive of an anti-apoptotic effect of the PEAMs. These findings were not supported by other analyses (clinical signs, disc height index, T2 values, biomolecular and biochemical analyses, and IVD histopathology). PEAs showed a good cytocompatibility and biocompatibility. PEAMs are considered safe sustained release systems for intradiscal delivery of biological treatments. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 707-714, 2017.

Osteogenic protein 1 does not stimulate a regenerative effect in cultured human degenerated nucleus pulposus tissue.

Low back pain is a major cause of disability and is heavily associated with intervertebral disc degeneration. Osteogenic protein 1 (OP-1) is a growth factor that has shown potential to regenerate the intervertebral disc in human cells and animal models. However, high doses are required, presumably due to clearance from the tissue; controlled release may be a solution to this problem. In this study, we developed a preclinical, pathophysiological human tissue explant culture model of degenerated nucleus pulposus (NP). The NP explants were cultured for 28 days and injected with 100 µg OP-1 as a bolus, or with sustained-release biodegradable microspheres loaded with 16 or 1.6 µg OP-1. After culture, the tissue explants were analysed for biochemical content [water, sulphated glycosaminoglycans (GAGs), hydroxyproline and DNA], histology, cell viability and gene expression (disc matrix anabolic and catabolic markers). Untreated degenerated NP explants lost some of their GAG content when cultured for 4 weeks, but maintained other tissue constituents. Gene expression levels were close to native values. A bolus injection of OP-1 partially restored GAG content to the native level in half of the donors, while the sustained release of OP-1 did not affect the NP explants. No effect of treatment was observed on anabolic or catabolic gene expression at day 28. These results demonstrated that the regenerative potential of OP-1 is donor dependent, and only at very high doses. This questions the clinical use of OP-1 as a regenerative agent, as these high doses may increase the incidence of complications. Copyright © 2015 John Wiley & Sons, Ltd.

The effectiveness of a convergence dialogue meeting with the employer in promoting return to work as part of the cognitive-behavioural treatment of common mental disorders: A randomized controlled trial.

BACKGROUND: Dialogue between supervisor and employee is of great importance for occupational rehabilitation. OBJECTIVE: To evaluate the effectiveness of a convergence dialogue meeting (CDM) of employee, therapist and supervisor aimed at facilitating return to work (RTW) as part of cognitive-behavioural treatment. METHODS: Randomized controlled trial including 60 employees sick-listed with common mental disorders and referred for specialized mental healthcare. Employees were randomly allocated either to an intervention group (n = 31) receiving work-focused cognitive-behavioural therapy plus CDM or a control group (n = 29) receiving work-focused cognitive-behavioural therapy without CDM. RESULTS: The time to first RTW was 12 days shorter (p = 0.334) in the intervention group, although full (i.e., at equal earnings as before reporting sick) RTW took 41 days longer (p = 0.122) than the control group. The odds of full RTW at the end of treatment were only 7% higher (p = 0.910) in the intervention group as compared to the control group. CONCLUSIONS: CDM did not significantly reduce the time to RTW. We recommend that therapists who are trained on CDM focus on barriers and solutions for RTW.

[Chronic diarrhoea due to microscopic colitis: awareness pays]. / Chronische diarree door microscopische colitis: alertheid loont.

The incidence of microscopic colitis (MC) in The Netherlands is increasing, yet the numbers are low compared to other countries. Awareness is likely to play a role. We describe two cases to illustrate the benefit of MC awareness among physicians and pathologists. In a 45-year-old female who presented with chronic diarrhoea, no cause could be identified despite extensive examinations in other hospitals. A biopsy revision, performed in our centre, revealed MC. Treatment with budesonide was immediately effective. A 76-year-old female with chronic diarrhoea was also diagnosed with MC. Because a relationship with NSAID use was suspected, the drug was withdrawn and the diarrhoea resolved. These cases illustrate that awareness of MC might accelerate the diagnosis of patients with chronic diarrhoea, consequently enabling the prescription of oral budesonide, a highly effective treatment. Some drugs are associated with an increased risk of MC. Withdrawal of these drugs could be another successful treatment strategy.

Reduced tonicity stimulates an inflammatory response in nucleus pulposus tissue that can be limited by a COX-2-specific inhibitor.

In intervertebral disc herniation with nucleus pulposus (NP) extrusion, the elicited inflammatory response is considered a key pain mechanism. However, inflammatory cytokines are reported in extruded herniated tissue, even before monocyte infiltration, suggesting that the tissue itself initiates the inflammation. Since herniated tissue swells, we investigated whether this simple mechanobiological stimulus alone could provoke an inflammatory response that could cause pain. Furthermore, we investigated whether sustained-release cyclooxygenase-2 (COX2) inhibitor would be beneficial in such conditions. Healthy bovine NP explants were allowed to swell freely or confined. The swelling explants were treated with Celecoxib, applied either as a bolus or in sustained-release. Swelling explants produced elevated levels of interleukin-6 (IL-6) and prostaglandin E2 (PGE2 ) for 28 days, while confined explants did not. Both a high concentration bolus and 10 times lower concentration in sustained release completely inhibited PGE2 production, but did not affect IL-6 production. Swelling of NP tissue, without the inflammatory system response, can trigger cytokine production and Celecoxib, even in bolus form, may be useful for pain control in extruded disc herniation.

Applicability of a newly developed bioassay for determining bioactivity of anti-inflammatory compounds in release studies--celecoxib and triamcinolone acetonide released from novel PLGA-based microspheres.

PURPOSE: To develop a bio-assay for measuring long-term bioactivity of released anti-inflammatory compounds and to test the bioactivity of celecoxib (CXB) and triamcinolone acetonide (TA) released from a new PLGA-based microsphere platform. METHODS: Human osteoarthritic chondrocytes were plated according to standardized procedures after batch-wise harvest and cultured for 3 days to prevent cell confluency and changes in cell behaviour. Prostaglandin E2 (PGE2) production stimulated by TNFα was used as a parameter of inflammation. A novel microsphere platform based on PTE-functionalised PLGA was used to incorporate CXB and TA. Loaded microspheres were added to transwells overlying the cells, with transfer of the wells to new cell cultures every 3 days. Inhibition of PGE2 production was determined over a period of 21 days. RESULTS: PLGA(75:25)-PTE microspheres were prepared and loaded with CXB and TA at 86 and 97% loading efficiency, respectively. In the bioactivity assay, PGE2 levels induced by TNFα were reduced to an average of 30% using microspheres loaded with 0.1 nmol CXB per transwell; with microspheres loaded with 0.1 nmol TA, PGE2 production was initially reduced to 3% and gradually recovered to 30% reduction. At 1 nmol loading, PGE2 was inhibited to 0-7% for CXB-loaded microspheres, and 0-28% for TA-loaded microspheres. CONCLUSIONS: We present a novel sustained release bioactivity assay which provides an essential link between in vitro buffer-based release kinetics and in vivo application. Novel PLGA-based microspheres loaded with TA and CXB showed efficient anti-inflammatory effects over time.