The Working Alliance Inventory's Measurement Properties:A Systematic Review

Measurement properties of the Working Alliance Inventory (WAI) and its various translations and adaptations for specific target groups have been investigated for over 30 years. No systematic review analyzing studies on measurement properties of the WAI has been conducted to date. COnsensus-based Standards for the selection of health Measurements INstruments (COSMIN) were developed for conducting high-quality systematic reviews on measurement properties in a transparent and standardized way. Aim of this study was to systematically review studies on measurement properties of the WAI, and its adapted versions, within psychotherapy, and other healthcare contexts using COSMIN criteria. PsycINFO, Medline, and EMBASE were searched (1989-2021). In all phases of the review procedure, study selection, data extraction, risk of bias assessment, rating of the quality of measurement properties, and rating of the quality of evidence for measurement properties, disagreement between reviewers was resolved by discussion. Results on validity, internal structure, reliability, construct validity, and responsiveness were analyzed. In total 66 studies were included. In most studies, evidence for measurement properties was according to COSMIN criteria, insufficient, lacking, or conflicting. Content validity was rated insufficient because neither patients nor healthcare professionals were involved in the development and validation process. Hence evidence for content validity of the WAI is unknown. Conflicting evidence was found for structural validity. Evidence for internal consistency could not be established. Limited evidence was found for inter-rater reliability and convergent validity. Conflicting evidence was also found for test-retest reliability and divergent validity. COSMIN criteria exposed persistent problems in validation studies of the WAI. These findings may indicate that measurement properties of the WAI are not up to current standards, or that COSMIN criteria may be less appropriate for assessing measurement properties of the WAI, or it could indicate both. The results of this systematic review suggest that WAI outcomes should be interpreted with caution and further research is needed regarding the content validity and hypotheses development. For the future, the theoretical framework underlying the measurement of the working alliance needs to be studied in psychotherapy and other health contexts, and tested in methodologically sound studies

Innate responses induced by whole inactivated virus or subunit influenza vaccines in cultured dendritic cells correlate with immune responses in vivo

Vaccine development involves time-consuming and expensive evaluation of candidate vaccines in animal models. As mediators of both innate and adaptive immune responses dendritic cells (DCs) are considered to be highly important for vaccine performance. Here we evaluated how far the response of DCs to a vaccine in vitro is in line with the immune response the vaccine evokes in vivo. To this end, we investigated the response of murine bone marrow-derived DCs to whole inactivated virus (WIV) and subunit (SU) influenza vaccine preparations. These vaccine preparations were chosen because they differ in the immune response they evoke in mice with WIV being superior to SU vaccine through induction of higher virus-neutralizing antibody titers and a more favorable Th1-skewed response phenotype. Stimulation of DCs with WIV, but not SU vaccine, resulted in a cytokine response that was comparable to that of DCs stimulated with live virus. Similarly, the gene expression profiles of DCs treated with WIV or live virus were similar and differed from that of SU vaccine-treated DCs. More specifically, exposure of DCs to WIV resulted in differential expression of genes in known antiviral pathways, whereas SU vaccine did not. The stronger antiviral and more Th1-related response of DCs to WIV as compared to SU vaccine correlates well with the superior immune response found in mice. These results indicate that in vitro stimulation of DCs with novel vaccine candidates combined with the assessment of multiple parameters, including gene signatures, may be a valuable tool for the selection of vaccine candidates

Goal-oriented cognitive rehabilitation in early-stage dementia: study protocol for a multi-centre single-blind randomised controlled trial (GREAT).

yesBackground: Preliminary evidence suggests that goal-oriented cognitive rehabilitation (CR) may be a clinically effective intervention for people with early-stage Alzheimer's disease, vascular or mixed dementia and their carers. This study aims to establish whether CR is a clinically effective and cost-effective intervention for people with early-stage dementia and their carers. Methods/design: In this multi-centre, single-blind randomised controlled trial, 480 people with early-stage dementia, each with a carer, will be randomised to receive either treatment as usual or cognitive rehabilitation (10 therapy sessions over 3 months, followed by 4 maintenance sessions over 6 months). We will compare the effectiveness of cognitive rehabilitation with that of treatment as usual with regard to improving self-reported and carer-rated goal performance in areas identified as causing concern by people with early-stage dementia; improving quality of life, self-efficacy, mood and cognition of people with early-stage dementia; and reducing stress levels and ameliorating quality of life for carers of participants with early-stage dementia. The incremental cost-effectiveness of goal-oriented cognitive rehabilitation compared to treatment as usual will also be examined. Discussion: If the study confirms the benefits and cost-effectiveness of cognitive rehabilitation, it will be important to examine how the goal-oriented cognitive rehabilitation approach can most effectively be integrated into routine health-care provision. Our aim is to provide training and develop materials to support the implementation of this approach following trial completion. Trial registration: Current Controlled Trials ISRCTN2102748

Interexaminer Agreement and Reliability of an Internationally Endorsed Screening Framework for Cervical Vascular Risks Following Manual Therapy and Exercise:The Go4Safe Project

Objective: Clinicians are recommended to use the clinical reasoning framework developed by the International Federation of Orthopaedic Manipulative Physical Therapists (IFOMPT) to provide guidance regarding assessment of the cervical spine and potential for cervical artery dysfunction prior to manual therapy and exercise. However, the interexaminer agreement and reliability of this framework is unknown. This study aimed to estimate the interexaminer agreement and reliability of the IFOMPT framework among physical therapists in primary care. Methods: Ninety-six patients who consulted a physical therapist for neck pain or headache were included in the study. Each patient was tested independently by 2 physical therapists, from a group of 17 physical therapists (10 pairs) across The Netherlands. Patients and examiners were blinded to the test results. The overall interexaminer agreement, specific agreement per risk category (high-, intermediate-, and low-risk), and interexaminer reliability (weighted κ) were calculated. Results: Overall agreement was 71% (specific agreement in high-risk category = 63%; specific agreement in intermediate-risk category = 38%; specific agreement in low-risk category = 84%). Overall reliability was moderate (weighted κ = 0.39; 95% CI = 0.21-0.57) and varied considerably between pairs of physical therapists (κ = 0.14-1.00). Conclusion: The IFOMPT framework showed an insufficient interexaminer agreement and fair interexaminer reliability among physical therapists when screening the increased risks for vascular complications following manual therapy and exercise prior to treatment. Impact: The IFOMPT framework contributes to the safety of manual therapy and exercise. It is widely adopted in clinical practice and educational programs, but the measurement properties are unknown. This project describes the agreement and reliability of the IFOMPT framework

Opioids in patients with COPD and refractory dyspnea:literature review and design of a multicenter double blind study of low dosed morphine and fentanyl (MoreFoRCOPD)

BACKGROUND: Refractory dyspnea or breathlessness is a common symptom in patients with advanced chronic obstructive pulmonary disease (COPD), with a high negative impact on quality of life (QoL). Low dosed opioids have been investigated for refractory dyspnea in COPD and other life-limiting conditions, and some positive effects were demonstrated. However, upon first assessment of the literature, the quality of evidence in COPD seemed low or inconclusive, and focused mainly on morphine which may have more side effects than other opioids such as fentanyl. For the current publication we performed a systematic literature search. We searched for placebo-controlled randomized clinical trials investigating opioids for refractory dyspnea caused by COPD. We included trials reporting on dyspnea, health status and/or QoL. Three of fifteen trials demonstrated a significant positive effect of opioids on dyspnea. Only one of four trials reporting on QoL or health status, demonstrated a significant positive effect. Two-thirds of included trials investigated morphine. We found no placebo-controlled RCT on transdermal fentanyl. Subsequently, we hypothesized that both fentanyl and morphine provide a greater reduction of dyspnea than placebo, and that fentanyl has less side effects than morphine.METHODS: We describe the design of a robust, multi-center, double blind, double-dummy, cross-over, randomized, placebo-controlled clinical trial with three study arms investigating transdermal fentanyl 12 mcg/h and morphine sustained-release 10 mg b.i.d. The primary endpoint is change in daily mean dyspnea sensation measured on a numeric rating scale. Secondary endpoints are change in daily worst dyspnea, QoL, anxiety, sleep quality, hypercapnia, side effects, patient preference, and continued opioid use. Sixty patients with severe stable COPD and refractory dyspnea (FEV1 &lt; 50%, mMRC ≥ 3, on optimal standard therapy) will be included.DISCUSSION: Evidence for opioids for refractory dyspnea in COPD is not as robust as usually appreciated. We designed a study comparing both the more commonly used opioid morphine, and transdermal fentanyl to placebo. The cross-over design will help to get a better impression of patient preferences. We believe our study design to investigate both sustained-release morphine and transdermal fentanyl for refractory dyspnea will provide valuable information for better treatment of refractory dyspnea in COPD. Trial registration NCT03834363 (ClinicalTrials.gov), registred at 7 Feb 2019, https://clinicaltrials.gov/ct2/show/NCT03834363 .</p

Opioids in patients with COPD and refractory dyspnea:literature review and design of a multicenter double blind study of low dosed morphine and fentanyl (MoreFoRCOPD)

Abstract Background Refractory dyspnea or breathlessness is a common symptom in patients with advanced chronic obstructive pulmonary disease (COPD), with a high negative impact on quality of life (QoL). Low dosed opioids have been investigated for refractory dyspnea in COPD and other life-limiting conditions, and some positive effects were demonstrated. However, upon first assessment of the literature, the quality of evidence in COPD seemed low or inconclusive, and focused mainly on morphine which may have more side effects than other opioids such as fentanyl. For the current publication we performed a systematic literature search. We searched for placebo-controlled randomized clinical trials investigating opioids for refractory dyspnea caused by COPD. We included trials reporting on dyspnea, health status and/or QoL. Three of fifteen trials demonstrated a significant positive effect of opioids on dyspnea. Only one of four trials reporting on QoL or health status, demonstrated a significant positive effect. Two-thirds of included trials investigated morphine. We found no placebo-controlled RCT on transdermal fentanyl. Subsequently, we hypothesized that both fentanyl and morphine provide a greater reduction of dyspnea than placebo, and that fentanyl has less side effects than morphine. Methods We describe the design of a robust, multi-center, double blind, double-dummy, cross-over, randomized, placebo-controlled clinical trial with three study arms investigating transdermal fentanyl 12 mcg/h and morphine sustained-release 10 mg b.i.d. The primary endpoint is change in daily mean dyspnea sensation measured on a numeric rating scale. Secondary endpoints are change in daily worst dyspnea, QoL, anxiety, sleep quality, hypercapnia, side effects, patient preference, and continued opioid use. Sixty patients with severe stable COPD and refractory dyspnea (FEV1 < 50%, mMRC ≥ 3, on optimal standard therapy) will be included. Discussion Evidence for opioids for refractory dyspnea in COPD is not as robust as usually appreciated. We designed a study comparing both the more commonly used opioid morphine, and transdermal fentanyl to placebo. The cross-over design will help to get a better impression of patient preferences. We believe our study design to investigate both sustained-release morphine and transdermal fentanyl for refractory dyspnea will provide valuable information for better treatment of refractory dyspnea in COPD. Trial registration NCT03834363 (ClinicalTrials.gov), registred at 7 Feb 2019, https://clinicaltrials.gov/ct2/show/NCT03834363

Is the Clinical Risk Score for Patients with Colorectal Liver Metastases Still Useable in the Era of Effective Neoadjuvant Chemotherapy?

Background: Several clinical risk scores (CRSs) for the outcome of patients with colorectal liver metastases have been validated, but not in patients undergoing neoadjuvant chemotherapy. Therefore, this study evaluates the predictive value of these CRSs in this specific group. Methods: Between January 2000 and December 2008, all patients undergoing a metastasectomy were analyzed and divided into two groups: 193 patients did not receive neoadjuvant chemotherapy (group A), and 159 patients received neoadjuvant chemotherapy (group B). In group B, the CRSs were calculated before and after administration of neoadjuvant chemotherapy. Results were evaluated by using the CRSs proposed by Nordlinger et al., Fong et al., Nagashima et al., and Konopke et al. Results: In groups A and B, the overall median survival was 43 and 47 months, respectively (P = 0.648). In group A, all CRSs used were of statistically significant predictive value. Before administration of neoadjuvant chemotherapy, only the Nordlinger score was of predictive value. After administration of neoadjuvant chemotherapy, all CRSs were of predictive value again, except for the Konopke score. Conclusions: Traditional CRSs are not a reliable prognostic tool when used in patients before treatment with neoadjuvant chemotherapy. However, CRSs assessed after the administration of neoadjuvant chemotherapy are useful to predict prognosis

Anatomical Versus Nonanatomical Resection of Colorectal Liver Metastases: Is There a Difference in Surgical and Oncological Outcome?

Background: The increased use of neoadjuvant chemotherapy and minimally invasive therapies for recurrence in patients with colorectal liver metastases (CLM) makes a surgical strategy

Urinary amine and organic acid metabolites evaluated as markers for childhood aggression : the ACTION biomarker study

Biomarkers are of interest as potential diagnostic and predictive instruments in personalized medicine. We present the first urinary metabolomics biomarker study of childhood aggression. We aim to examine the association of urinary metabolites and neurotransmitter ratios involved in key metabolic and neurotransmitter pathways in a large cohort of twins (N = 1,347) and clinic-referred children (N = 183) with an average age of 9.7 years. This study is part of ACTION (Aggression in Children: Unraveling gene-environment interplay to inform Treatment and InterventiON strategies), in which we developed a standardized protocol for large-scale collection of urine samples in children. Our analytical design consisted of three phases: a discovery phase in twins scoring low or high on aggression (N = 783); a replication phase in twin pairs discordant for aggression (N = 378); and a validation phase in clinical cases and matched twin controls (N = 367). In the discovery phase, 6 biomarkers were significantly associated with childhood aggression, of which the association of O-phosphoserine (beta = 0.36; SE = 0.09; p = 0.004), and gamma-L-glutamyl-L-alanine (beta = 0.32; SE = 0.09; p = 0.01) remained significant after multiple testing. Although non-significant, the directions of effect were congruent between the discovery and replication analyses for six biomarkers and two neurotransmitter ratios and the concentrations of 6 amines differed between low and high aggressive twins. In the validation analyses, the top biomarkers and neurotransmitter ratios, with congruent directions of effect, showed no significant associations with childhood aggression. We find suggestive evidence for associations of childhood aggression with metabolic dysregulation of neurotransmission, oxidative stress, and energy metabolism. Although replication is required, our findings provide starting points to investigate causal and pleiotropic effects of these dysregulations on childhood aggression