Differences in the delivery of motivational interviewing across three countries.

We do not know if the delivery of Motivational Interviewing (MI) differs across countries. In an international study targeting Elderly people with Alcohol Use Disorder, The Elderly Study, MI was part of the treatment applied. Treatment delivery was measured by means of the Motivational Interviewing Treatment Integrity code version 4 (MITI 4). Mixed effects models explored potential differences in delivery of MI between the countries. Delivery of MI differed significantly between participating countries: Denmark, Germany and the US. These findings are important to consider when comparing measures of MI integrity across studies from different cultures.

Is fidelity to motivational interviewing associated with alcohol outcomes in treatment-seeking 60+ year-old citizens?

BACKGROUND: Part of the variability in treatment outcomes for Motivational Interviewing (MI) may be explained by differences in the fidelity to MI. The Motivational Interviewing Treatment Integrity manual version 4 (MITI 4) is an improved measure of fidelity to elements of MI. It is not known whether the fidelity to MI, as measured by the MITI 4, is related to treatment outcome. OBJECTIVES: To examine whether fidelity to MI is associated with alcohol use outcomes - predictive validity of the MITI 4. METHOD: Twenty percent of the recorded sessions at the Danish sites of the Elderly Study were randomly drawn and coded for fidelity to MI with the MITI 4. The Elderly Study was an international, randomized controlled trial, in which people 60 years or older with Alcohol Use Disorders received either four weeks of Motivational Enhancement Therapy (MET) or four weeks of MET combined with up to eight additional sessions of the Community Reinforcement Approach- Senior (MET+CRA-S). Elements of MI and summary scores of the MITI 4 were used as predictors in a mixed effects regression analysis. Treatment outcomes were use of alcohol and consequences of drinking at 26-weeks follow-up. RESULTS: In total, 423 sessions representing 238 participants were randomly drawn and coded for fidelity to MI. Mean values of the treatment elements indicated high fidelity to MI, with higher fidelity to MI in the MET sessions, as compared to CRA-S sessions. None of the predictors in the multilevel model analyses were associated with outcome at follow-up. Exploratory analysis indicated reverse associations between one measure of MI-fidelity and drinking outcomes in the combined treatment (CRAS). CONCLUSION: The fidelity of the MI intervention, received by participants in this study, did not predict better treatment outcomes. MI may be less effective in populations which are already committed to change behavior. As expected and validating for the MITI 4, fidelity to MI-elements was lower in the combination of MI with other treatment approaches. Additionally, the timing of MI in these combined settings might be important for effectiveness.

Reduced Plasma Amino Acid Levels During Allogeneic Hematopoietic Stem Cell Transplantation Are Associated with Systemic Inflammation and Treatment-Related Complications.

Patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT) are challenged by cytotoxic effects of the conditioning regimen, resulting in tissue damage, systemic inflammation, and increased metabolic demands for amino acids to regenerate damaged tissues, reconstitute hematopoietic cells, and establish antioxidant defenses. To date, few studies have addressed the role of plasma amino acid (PAA) levels during transplantation, and it remains unknown if amino acid deficiency can aggravate treatment-related morbidity. We determined plasma levels of the 23 human amino acids in 80 HSCT recipients (age 1.1 to 55.4 years) before conditioning and on days +7 and +21 post-transplant along with C-reactive protein (CRP) and IL-6 levels on day +7. Significant changes were observed in plasma concentrations of several human amino acids during HSCT. On day +7, numerous amino acids were inversely correlated with both CRP and IL-6, including glutamic acid, serine, alanine, glutamine, arginine, cysteine, glycine, histidine, lysine, tryptophan, threonine, taurine, proline, and methionine (r = -.22 to -.66; all P < .05). Patients who developed sinusoidal obstruction syndrome (SOS) had significantly lower mean total PAA levels compared with patients without SOS (2013 ng/L [95% confidence interval (CI), 1709 to 2318 ng/L] versus 2706 ng/L [95% CI, 2261 to 3150 ng/L]; P = .006), along with lower individual levels of glutamic acid, serine, arginine, glycine, lysine, valine, tryptophan, threonine, and proline on day +7 (all P < .05). Patients with severe acute graft-versus-host disease had a lower mean total PAA level (1922 ng/L [95% CI, 1738 to 2106 ng/L] versus 2649 ng/L [95% CI, 2244 to 3055 ng/L]; P = .014) and lower levels of serine, glutamine, cysteine, glycine, lysine, and threonine on day +7 (all P < .05). These results indicate a relationship between low concentrations of certain amino acids and the risk of treatment-related complications.

Lessons learned from measuring fidelity with the Motivational Interviewing Treatment Integrity code (MITI 4).

BACKGROUND AND AIMS: The Motivational Interviewing Treatment Integrity code (MITI) measures fidelity to, and the quality of, Motivational Interviewing (MI), and can also be used when MI is combined with other treatment methods. The current study presents a fidelity measurement with the MITI 4.2.1, in both Motivational Enhancement Therapy sessions and the combined Community Reinforcement Approach-Senior (CRAS). METHOD: The MITI 4.2.1 was used to evaluate treatment sessions provided in the Elderly Study, a multi-national randomized trial evaluating treatment for alcohol use disorders in the elderly. Following expert recommendations, training was conducted at two international sites as well as at the Danish site. Twenty percent of the sessions at the Danish study site were rated. Twelve percent were multiply rated by all raters. Interrater reliability was assessed by the Intraclass Correlations Coefficient (ICC). RESULTS: Mean ICC of the 52 sessions rated by all raters was 0.78 (95% CI: 0.70; 0.86). The rare measures confront and emphasize autonomy, and the global measure softening sustain talk only reached fair levels of ICC, while the remaining measures were good or excellent. In the sessions of MI combined with other treatment approaches in the CRAS, the MITI 4.2.1 has a similar reliability as in MET sessions only, except for the measure persuade with permission. CONCLUSION: The MITI 4.2.1 is a reliable instrument for measuring fidelity to Motivational Interviewing elements, also in the context of Community Reinforcement Approach Senior. However, in softening sustain talk, the rare measures, and persuade with permission it has proved more difficult to reach high levels of interrater reliability.

Duration of therapy - Does it matter?: A systematic review and meta-regression of the duration of psychosocial treatments for alcohol use disorder.

BACKGROUND: The recommendations in clinical guidelines for duration of therapy for alcohol use disorder (AUD) are based on consensus decisions. In reality, we do not know the optimal duration of an alcohol treatment course. METHODS: A systematic review and meta-regression of randomized controlled trials of psychosocial treatment in alcohol outpatient treatment centers. The population consisted of adults suffering from AUD, treated in an outpatient facility with at least two sessions of therapy. Meta-regression analysis was performed with treatment outcome as a function of duration of therapy across studies. Treatment outcome was defined as long-term alcohol use measured in percentage of days abstinent (PDA), percentage of heavy days drinking (PHD), and/or proportion of participants abstinent (ABS). RESULTS: 48 studies encompassing 8984 participants. Mean planned duration of therapy: 18 (8-82) weeks and 14 (2-36) sessions. Mean actual attended sessions: 9 (1-26). Mean follow-up time: 43 (8-104) weeks with a mean of 6 (2-18) research assessments. Neither planned weeks, duration of sessions, frequency of sessions per week, nor actual attended sessions were associated with long-term alcohol use outcomes. However, frequency of research assessments was positively associated with PDA and PHD. CONCLUSION: No associations between long-term alcohol use outcomes and planned or actual attended duration of psychosocial treatment in outpatient care. Research assessments and, accordingly, the research project in itself may influence outcome in studies of psychosocial treatment for alcohol use disorder.

Cell-contact dependent inhibition of monocytes by airway epithelial cells and reversion by infection with Respiratory Syncytial Virus.

Airway epithelial cells (AEC) are the first line of defense against airborne infectious microbes and play an important role in regulating the local immune response. However, the interplay of epithelial cells and professional immune cells during both homeostasis and infection has only been partially studied. The present study was performed to determine how bronchial epithelial cells affect the activation of monocytes. Under healthy conditions, AECs were shown to inhibit reactivity of monocytes. We hypothesized that upon infection, monocytes might be released from inhibition by AECs. We report that direct contact of monocytes with unstimulated BEAS2B epithelial cells results in inhibition of TNF secretion by activated monocytes. In addition to the known soluble modulators, we show that cell contacts between epithelial cells and monocytes or macrophages also contribute to homeostatic inhibitory actions. We find AECs to express the inhibitory molecule PD-L1 and blockade of PD-L1 results in increased secretion of pro-inflammatory cytokines from monocytes. Contrary to the inhibitory activities during homeostasis, epithelial cells infected with Respiratory Syncitial Virus (RSV) induce a significant release of inhibition. However, release of inhibition was not due to modulation of PD-L1 expression in AECs. We conclude that airway epithelial cells control the reactivity of monocytes through direct and indirect interactions; however tonic inhibition can be reverted upon stimulation of AECs with RSV and thereof derived molecular patterns. The study confirms the important role of airway epithelial cells for local immune reactions.

Bronchial epithelial cells induce alternatively activated dendritic cells dependent on glucocorticoid receptor signaling.

Airway epithelial cells mount a tolerogenic microenvironment that reduces the proinflammatory potential of respiratory dendritic cells (DCs). We recently demonstrated that tracheal epithelial cells continuously secrete soluble mediators that affect the reactivity of local innate immune cells. Using transcriptional profiling, we now observed that conditioning of DCs by tracheal epithelial cells regulated 98 genes under homeostatic conditions. Among the most upregulated genes were Ms4a8a and Ym1, marker genes of alternatively activated myeloid cells. Ex vivo analysis of respiratory DCs from nonchallenged mice confirmed a phenotype of alternative activation. Bioinformatic analysis showed an overrepresentation of hormone-nuclear receptors within the regulated genes, among which was the glucocorticoid receptor. In line with a role for glucocorticoids, pharmacological blockade as well as genetic manipulation of the glucocorticoid receptor within DCs inhibited Ms4a8a and Ym1 expression as well as MHC class II and CD86 regulation upon epithelial cell conditioning. Within epithelial cell-conditioned medium, low amounts of glucocorticoids were present. Further analysis showed that airway epithelial cells did not produce glucocorticoids de novo, yet were able to reactivate inactive dehydrocorticosterone enzymatically. The results show that airway epithelial cells regulate local immune responses, and this modulation involves local production of glucocorticoids and induction of an alternative activation phenotype in DCs.

Bronchial epithelial cell-derived prostaglandin E2 dampens the reactivity of dendritic cells.

Airway epithelial cells regulate immune reactivity of local dendritic cells (DCs), thus contributing to microenvironment homeostasis. In this study, we set out to identify factors that mediate this regulatory interaction. We show that tracheal epithelial cells secrete soluble factors that downregulate TNF-α and IL-12p40 secretion by bone marrow-derived DCs but upregulate IL-10 and arginase-1. Size exclusion chromatography identified small secreted molecules having high modulatory activity on DCs. We observed that airway tracheal epithelial cells constitutively release the lipid mediator PGE(2). Blocking the synthesis of PGs within airway epithelial cells relieved DCs from inhibition. Cyclooxygenase-2 was found to be expressed in primary tracheal epithelial cell cultures in vitro and in vivo as shown by microdissection of epithelial cells followed by real-time PCR. Paralleling these findings we observed that DCs treated with an antagonist for E-prostanoid 4 receptor as well as DCs lacking E-prostanoid 4 receptor showed reduced inhibition by airway epithelial cells with respect to secretion of proinflammatory cytokines measured by ELISA. Furthermore, PGE(2) mimicked the effects of epithelial cells on DCs. The results indicate that airway epithelial cell-derived PGE(2) contributes to the modulation of DCs under homeostatic conditions.

Airway epithelial cells modify immune responses by inducing an anti-inflammatory microenvironment.

The upper airways are prone to contact with pathogenic as well as non-pathogenic microbes, therefore immune recognition principles have to be tightly controlled. Here we show that human BEAS-2B bronchial epithelial cells inhibited secretion of the pro-inflammatory cytokines TNF-alpha and IL-12 by monocytes, macrophages and dendritic cells. This inhibitory effect could be transferred by supernatant of resting BEAS-2B cells and was also observed when primary murine tracheal epithelial cells were prepared. In contrast to inhibition of pro-inflammatory cytokine secretion epithelial cell-conditioned dendritic cells showed increased expression of IL-10 and arginase-1, thus displaying properties of alternative activation. Accordingly, Toll-like receptor-mediated up-regulation of CD40, CD86 and PD-L2 (CD273) on murine dendritic cells was reduced in the presence of bronchial epithelial cell supernatant. However, expression of negative regulatory PD-L1 (CD274) was increased and dendritic cell induced proliferation of T lymphocytes was diminished. Epithelial cells also showed a direct inhibitory effect on T lymphocyte proliferation and this was due to the constitutive secretion of TGF-beta by bronchial epithelial cells. Moreover, epithelial cell-conditioned T lymphocytes showed increased differentiation towards IL-10-producing Tr1 cells. The results indicate that bronchial epithelial cells induce a non-inflammatory microenvironment that regulates local immune homeostasis.