Sudden gains in routine clinical care: application of a permutation test for trauma-focused cognitive behavioural therapy.

Background: Sudden gains, defined as large and stable improvements of psychopathological symptoms, are a ubiquitous phenomenon in psychotherapy. They have been shown to occur across several clinical contexts and to be associated with better short-term and long-term treatment outcome. However, the approach of sudden gains has been criticized for its tautological character: sudden gains are included in the computation of treatment outcomes, ultimately resulting in a circular conclusion. Furthermore, some authors criticize sudden gains as merely being random fluctuations.Objective: Use of efficient methods to evaluate whether the amount of sudden gains in a given sample lies above chance level.Method: We used permutation tests in a sample of 85 patients with posttraumatic stress disorder (PTSD) treated with trauma-focused cognitive behaviour therapy in routine clinical care. Scores of self-reported PTSD symptom severity were permuted 10.000 times within sessions and between participants to receive a random distribution.Results: Altogether, 18 participants showed a total of 24 sudden gains within the first 20 sessions. The permutation test yielded that the frequency of sudden gains was not beyond chance level. No significant predictors of sudden gains were identified and sudden gains in general were not predictive of treatment outcome. However, subjects with early sudden gains had a significantly lower symptom severity after treatment.Conclusions: Our data suggest that a significant proportion of sudden gains are due to chance. Further research is needed on the differential effects of early and late sudden gains.

Treatment-related sudden gains exhibit clinical significance when their manifestation is above chance level.We used permutation tests to examine their occurrence in trauma-focused cognitive behaviour therapy as applied in a naturalistic treatment setting.The occurrence of sudden gains in general was not significantly higher than chance, yet early sudden gains were associated with improved treatment outcome.

Frequencies of CYP2C19 and CYP2D6 gene variants in a German inpatient sample with mood and anxiety disorders.

OBJECTIVES: Previous results demonstrated that CYP2D6 and CYP2C19 gene variants affect serum concentrations of antidepressants. We implemented a PGx service determining gene variants in CYP2D6 and CYP2C19 in our clinical routine care and report on our first patient cohort. METHODS: We analysed CYP2D6 and CYP2C19 allele, genotype, and phenotype frequencies, and actionable pharmacogenetic variants in this German psychiatric inpatient cohort. Two-tailed z-test was used to investigate for differences in CYP2D6 and CYP2C19 phenotypes and actionable/non-actionable genetic variant frequencies between our cohort and reference cohorts. RESULTS: Out of the 154 patients included, 44.8% of patients were classified as CYP2D6 normal metabolizer, 38.3% as intermediate metabolizers, 8.4% as poor metabolizers, and 2.6% as ultrarapid metabolizers. As for CYP2C19, 40.9% of patients were classified as normal metabolizers, 19.5% as intermediate metabolizers, 2.6% as poor metabolizers, 31.2% as rapid metabolizers, and 5.8% as ultrarapid metabolizers. Approximately, 80% of patients had at least one actionable PGx variant. CONCLUSION: There is a high prevalence of actionable PGx variants in psychiatric inpatients which may affect treatment response. Physicians should refer to PGx-informed dosing guidelines in carriers of these variants. Pre-emptive PGx testing in general may facilitate precision medicine also for other drugs metabolised by CYP2D6 and/or CYP2C19.

Scaling up and implementing the digital Survivorship Passport tool in routine clinical care - The European multidisciplinary PanCareSurPass project.

BACKGROUND: Childhood cancer survivors (CCS), of whom there are about 500,000 living in Europe, are at an increased risk of developing health problems [1-6] and require lifelong Survivorship Care. There are information and knowledge gaps among CCS and healthcare providers (HCPs) about requirements for Survivorship Care [7-9] that can be addressed by the Survivorship Passport (SurPass), a digital tool providing CCS and HCPs with a comprehensive summary of past treatment and tailored recommendations for Survivorship Care. The potential of the SurPass to improve person-centred Survivorship Care has been demonstrated previously [10,11]. METHODS: The EU-funded PanCareSurPass project will develop an updated version (v2.0) of the SurPass allowing for semi-automated data entry and implement it in six European countries (Austria, Belgium, Germany, Italy, Lithuania and Spain), representative of three infrastructure healthcare scenarios typically found in Europe. The implementation study will investigate the impact on person-centred care, as well as costs and processes of scaling up the SurPass. Interoperability between electronic health record systems and SurPass v2.0 will be addressed using the Health Level Seven (HL7) International interoperability standards. RESULTS: PanCareSurPass will deliver an interoperable digital SurPass with comprehensive evidence on person-centred outcomes, technical feasibility and health economics impacts. An Implementation Toolkit will be developed and freely shared to promote and support the future implementation of SurPass across Europe. CONCLUSIONS: PanCareSurPass is a novel European collaboration that will improve person-centred Survivorship Care for CCS across Europe through a robust assessment of the implementation of SurPass v2.0 in different healthcare settings.

Self-rated personality disorder symptoms do not predict treatment outcome for posttraumatic stress disorder in routine clinical care.

OBJECTIVE: To test the hypothesis that self-rated personality disorder (PD) symptoms are a significant and clinically relevant predictor of treatment outcomes in a naturalistic treatment setting specialized in trauma-focused treatment using a single-group pretest-posttest design. METHOD: Treatment-seeking patients reporting clinical levels of posttraumatic stress disorder (PTSD) symptoms filled out questionnaires at intake and after treatment. The primary outcome was change in PTSD severity after treatment, measured by the PTSD Checklist for DSM-5 (PCL-5). PD symptoms were measured with the Structured Clinical Interview for DSM-5 Screening Personality Questionnaire (SCID-5-SPQ). Secondary outcomes were general mental health problems, treatment response, number of sessions and dropout. RESULTS: N = 1174 patients (59% female, baseline PCL-5 score M [SD] = 53.0 [10.8]) were included for the primary analysis. Regression analysis revealed that PD symptoms explained 0.4% of variance in PTSD symptom change (p = .066). After controlling for baseline PTSD symptoms, PD symptoms explained 0.0% of variance (p = .311). The fully adjusted model including baseline PTSD symptom severity, age, gender, cumulative exposure to potentially traumatic experiences, PD symptoms, and number of sessions together explained 5% of the observed variance in PTSD symptom change. Baseline PTSD severity was the only significant predictor and negatively predicted outcome. Sensitivity analyses with imputed data from N = 2694 cases yielded comparable results. Finally, secondary analyses showed that PD symptoms did not predict significant or clinically relevant changes in treatment response status, general mental health problems, dropout rates or number of sessions. CONCLUSION: The findings provide no evidence that self-rated PD symptoms predict treatment outcomes for patients suffering from clinical levels of PTSD symptoms in a naturalistic treatment setting specializing in trauma-focused treatment. Self-report screening for these symptoms to inform clinicians about expected effects of PTSD treatment is not supported by the evidence.

Triglycerides and risk of cardiovascular events in statin-treated patients with newly diagnosed type 2 diabetes: a Danish cohort study.

BACKGROUND: Elevated triglyceride levels are a clinically useful marker of remnant cholesterol. It is unknown whether triglycerides are associated with residual cardiovascular risk in CVD-naïve patients with newly diagnosed type 2 diabetes mellitus (T2DM), who are already on statin therapy. We aimed to assess the association between triglyceride levels and risk of major cardiovascular events (MACE) in statin-treated patients with newly diagnosed T2DM managed in routine clinical care. METHODS: This cohort study included newly diagnosed T2DM patients without a previous diagnosis of cardiovascular disease in Northern Denmark during 2005-2017. Individual triglyceride levels while on statin treatment were assessed within 1 year after T2DM diagnosis. The primary outcome was a composite of myocardial infarction, ischemic stroke, or cardiac death (MACE). Patients were followed from one year after T2DM diagnosis until 30 April 2021, MACE, emigration, or death. We used Cox regression to compute hazard ratios (HRs) controlling for confounding factors. RESULTS: Among 27,080 statin-treated patients with T2DM (median age 63 years; 53% males), triglyceride levels were < 1.0 mmol/L in 17%, 1.0-1.9 mmol/L in 52%, 2.0-2.9 mmol/L in 20%, and ≥ 3.0 mmol/L in 11%. During follow-up, 1,957 incident MACE events occurred (11.0 per 1000 person-years). Compared with triglyceride levels < 1.0 mmol/L, confounder-adjusted HRs for incident MACE were 1.14 (95% CI 1.00-1.29) for levels between 1.0 and 1.9 mmol/L, 1.30 (95% CI 1.12-1.51) for levels between 2.0 and 2.9 mmol/L, and 1.44 (95% CI 1.20-1.73) for levels ≥ 3.0 mmol/L. This association was primarily driven by higher rates of myocardial infarction and cardiac death and attenuated only slightly after additional adjustment for LDL cholesterol. Spline analyses confirmed a linearly increasing risk of MACE with higher triglyceride levels. Stratified analyses showed that the associations between triglyceride levels and MACE were stronger among women. CONCLUSIONS: In statin-treated patients with newly diagnosed T2DM, triglyceride levels are associated with MACE already from 1.0 mmol/L. This suggests that high triglyceride levels are a predictor of residual cardiovascular risk in early T2DM and could be used to guide allocation of additional lipid-lowering therapies for CVD prevention.

Comparison of real-world treatment outcomes of systemic immunomodulating therapy in atopic dermatitis patients with dark and light skin types.

Background: Few data exist on differences in treatment effectiveness and safety in atopic dermatitis patients of different skin types. Objective: To investigate treatment outcomes of dupilumab, methotrexate, and ciclosporin, and morphological phenotypes in atopic dermatitis patients, stratified by Fitzpatrick skin type. Methods: In an observational prospective cohort study, pooling data from the Dutch TREAT (TREatment of ATopic eczema) NL (treatregister.nl) and UK-Irish A-STAR (Atopic eczema Systemic TherApy Register; astar-register.org) registries, data on morphological phenotypes and treatment outcomes were investigated. Results: A total of 235 patients were included (light skin types [LST]: Fitzpatrick skin type 1-3, n = 156 [Ethnicity, White: 94.2%]; dark skin types [DST]: skin type 4-6, n = 68 [Black African/Afro-Caribbean: 25%, South-Asian: 26.5%, and Hispanics: 0%]). DST were younger (19.5 vs 29.0 years; P < .001), more often had follicular eczema (22.1% vs 2.6%; P < .001), higher baseline Eczema Area and Severity Index (EASI) scores (20.1 vs 14.9; P = .009), less allergic contact dermatitis (30.9% vs 47.4%; P = .03), and less previous phototherapy use (39.7% vs 59.0%; P = .008). When comparing DST and LST corrected for covariates including baseline EASI, DST showed greater mean EASI reduction between baseline and 6 months with only dupilumab (16.7 vs 9.7; adjusted P = .032). No differences were found for adverse events for any treatments (P > .05). Limitations: Unblinded, non-randomized. Conclusion: Atopic dermatitis differs in several characteristics between LST and DST. Skin type may influence treatment effectiveness of dupilumab.

Adding an App-Based Intervention to the Cognitive Behavioral Analysis System of Psychotherapy in Routine Outpatient Psychotherapy Treatment: Proof-of-Concept Study.

BACKGROUND: The Cognitive Behavioral Analysis System of Psychotherapy (CBASP) is an empirically supported psychotherapeutic treatment developed specifically for persistent depressive disorder. However, given the high rates of nonresponse and relapse, there is a need for optimization. Studies suggest that outcomes can be improved by increasing the treatment dose via, for example, the continuous web-based application of therapy strategies between sessions. The strong emphasis in CBASP on the therapeutic relationship, combined with limited therapeutic availabilities, encourages the addition of web-based interventions to face-to-face therapy in terms of blended therapy. OBJECTIVE: The aim of this study was to test an app-based intervention called CBASPath, which was designed to be used as a blended therapy tool. CBASPath offers 8 sequential modules with app-based exercises to facilitate additional engagement with the therapy content and a separate exercise to conduct situational analyses within the app at any time. METHODS: CBASPath was tested in an open pilot study as part of routine outpatient CBASP treatment. Participating patients were asked to report their use patterns and blended use (integrated use of the app as part of therapy sessions) at 3 assessment points over the 6-month test period and rate the usability and quality of and their satisfaction with CBASPath. RESULTS: The results of the pilot trial showed that 93% (12/13) of participants used CBASPath as a blended tool during their therapy and maintained this throughout the study period. Overall, they reported good usability and quality ratings along with high user satisfaction. All participants showed favorable engagement with CBASPath; however, the frequency of use differed widely among the participants and assessment points. Situational analysis was used by all participants, and the number of completed modules ranged from 1 to 7. All participants reported blended use, although the frequency of integration in the face-to-face sessions varied widely. CONCLUSIONS: Our findings suggest that the digital augmentation of complex and highly interactive CBASP therapy in the form of blended therapy with CBASPath is feasible in routine outpatient care. Therapeutic guidance might contribute to high adherence and increase patient self-management. A few adjustments, such as saving entries directly in the app, could facilitate higher user engagement. A randomized controlled trial is now needed to investigate the efficacy and added value of this blended approach. In the long term, CBASPath could help optimize persistent depressive disorder treatment and reduce relapse by intensifying therapy and providing long-term patient support through the app.

Inpatient psychotherapy for depression in a large routine clinical care sample: A Bayesian approach to examining clinical outcomes and predictors of change.

BACKGROUND: A routinely collected dataset was analyzed (1) to determine the naturalistic effectiveness of inpatient psychotherapy for depression in routine psychotherapeutic care, and (2) to identify potential predictors of change. METHODS: In a sample of 22,681 inpatients with depression, pre-post and pre-follow-up effect sizes were computed for various outcome variables. To build a probabilistic model of predictors of change, an independent component analysis generated components from demographic and clinical data, and Bayesian EFA extracted factors from the available pre-test, post-test and follow-up questionnaires in a subsample (N = 6377). To select the best-fitted model, the BIC of different path models were compared. A Bayesian path analysis was performed to identify the most important factors to predict changes. RESULTS: Effect sizes were large for the primary outcome and moderate for various secondary outcomes. Almost all pretreatment factors exerted significant influences on different baseline factors. Several factors were found to be resistant to change during treatment: suicidality, agoraphobia, life dissatisfaction, physical disability and pain. The strongest cross-loadings were observed from suicidality on negative cognitions, from agoraphobia on anxiety, and from physical disability on perceived disability. LIMITATIONS: No causal conclusions can be drawn directly from our results as we only used cross-lagged panel data without control group. CONCLUSIONS: The results indicate large effects of inpatient psychotherapy for depression in routine clinical care. The direct influence of pretreatment factors decreased over the course of treatment. However, some factors appeared stable and difficult to treat, which might hinder treatment outcome. Findings of different predictors of change are discussed.

Effectiveness of Parenting Training on Emotional and Behavioral Problems in First through Fourth Grade Thai Children with ADHD: A Randomized Controlled Study.

OBJECTIVE: To evaluate the effectiveness of parenting training on emotional and behavioral problems of first through fourth grade Thai children with ADHD compared with routine clinical care in a university hospital in southern Thailand. MATERIAL AND METHODS: Caregivers of the children were invited and assessed for eligibility. Eighty children with ADHD were randomly assigned to either a parenting training group or a routine clinical care group. The primary caregivers of the parenting training group participated in 6 120-minute weekly sessions in addition to routine clinical care. Caregiver and teacher ADHD ratings and oppositional-defiant disorder ratings were collected at the time of enrollment and after the 6 weeks of training in both groups. The differences in scores in both groups were analyzed using a mixed model ANOVA. RESULTS: Each arm had 40 participants. The mean (SD) age of the children was 8.3 (1.1) years and their mean (SD) age at the first diagnosis of ADHD was 6.8 (1.3) years. Most of them were receiving methylphenidate for treatment of their ADHD. The mother was the primary caregiver for 83.5% of the children. The ADHD symptoms and oppositional-defiant symptoms showed significant improvement after receiving the treatment in both groups; however, no significant differences were found between groups. CONCLUSION: Adding parenting training to the routine clinical care for children with uncomplicated ADHD who are being medicated was not more effective than the routine clinical care alone. However, the power of this study is limited, and follow-up is needed to evaluate the long-term effectiveness.

Work ability and quality of working life in atopic dermatitis patients treated with dupilumab.

Atopic dermatitis is associated with work productivity loss. Little is known about how patients perceive their work ability and quality of working life, and how this is affected by treatment. Our primary objective was to investigate work ability and quality of working life at baseline and during treatment in the long term. A registry-embedded prospective observational cohort study was conducted consisting of patients with atopic dermatitis starting dupilumab in routine clinical care. The instruments used were the Work Ability Index (WAI; questions 1, 2, and 3) and the Quality of Working Life Questionnaire (QWLQ). Ninety-three patients were included of whom 72 were (self-)employed (77%). From baseline to 48 weeks, the mean WAI-1 score (general work ability, range 0-10) improved from 6.8 (±2.0) to 7.9 (±1.3), WAI-2 (physical work ability, range 1-5) from 3.7 (±0.9) to 4.3 (±0.7), and WAI-3 (mental/emotional work ability, range 1-5) from 3.4 (±0.9) to 3.9 (±0.8) (p = 0.001, p = 0.005, p < 0.001, respectively). The mean QWLQ total score improved from 74.0 (±9.1) to 77.5 (±9.6) and subscale "Problems due to health situation" improved from 37.4 (±22.3) to 61.5 (±23.1) (range 0-100; p = 0.032, p < 0.001, respectively). In conclusion, patients with moderate-to-severe atopic dermatitis starting dupilumab report decreased work ability and quality of working life, mainly due to health-related problems. Significant improvement of work ability and quality of working life is observed with dupilumab treatment.

Use of Patient-Reported Experience Measures in Pediatric Care: A Systematic Review.

Introduction: Patient-reported Experience Measures (PREMs) are validated questionnaires, that gather patients' and families' views of their experience receiving care and are commonly used to measure the quality of care, with the goal to make care more patient and family-centered. PREMs are increasingly being adopted in pediatric population, however knowledge gaps exist around understanding the use of PREMs in pediatrics. Objective: To identify and synthesize evidence on the use of PREMs in pediatric healthcare settings and their characteristics. Evidence Review: Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines governed the conduct and reporting of this review. An exhaustive search strategy was applied to MEDLINE, EMBASE, PsycINFO, Cochrane Library, and CINAHL databases to identify relevant peer-reviewed articles from high-income countries. Additionally, gray literature was searched to capture real-world implementation of PREMs. All the articles were screened independently by two reviewers in two steps. Data was extracted independently, synthesized, and tabulated. Findings from gray literature was synthesized and reported separately. Risk of bias for the studies identified through scientific databases was assessed independently by two reviewers using the National Institutes of Health Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies. Results: The initial search identified 15,457 articles. After removing duplicates, the title and abstracts of 11,543 articles were screened. Seven hundred ten articles were eligible for full-text review. Finally, 83 articles met the criteria and were included in the analyses. Of the 83 includes studies conducted in 14 countries, 48 were conducted in USA, 25 in European countries and 10 in other countries. These 83 studies reported on the use of 39 different PREMs in pediatric healthcare settings. The gray literature retrieved 10 additional PREMs. The number of items in these PREMs ranged from 7 to 89. Twenty-three PREMs were designed to be completed by proxy, 10 by either pediatric patients or family caregivers, and 6 by pediatric patients themselves. Conclusion and Relevance: This comprehensive review is the first to systematically search evidence around the use of PREMs in pediatrics. The findings of this review can guide health administrators and researchers to use appropriate PREMs to implement patient and family-centered care in pediatrics.

Patient-Reported Outcome Measures in Routine Pediatric Clinical Care: A Systematic Review.

Introduction: Integration of patient-reported outcome measures (PROMs) in routine clinical care is growing but lacks consolidated evidence around its impact on pediatric care. This systematic review aims to evaluate the impact of integrating PROMs in routine pediatric clinical care on various outcomes in pediatric clinical care. Data Sources: MEDLINE, Embase, CINAHL, PsycINFO, and Cochrane Library. Web of Science database was searched selectively to ensure extended coverage. Study Selection: We included longitudinal studies reporting on the integration of PROMs in routine pediatric clinical care of chronic diseases. Studies in languages other than English, published prior to the year 2000, and reporting on secondary data were excluded. Data Extraction: Two reviewers independently extracted data from included studies. Extracted data included citation of each study, type of healthcare setting, location of the study, characteristics of patient population, type of chronic disease, name and type of PROM, mode of administration, and reported outcomes. Results: Out of 6,869 articles, titles and abstracts of 5,416 articles and full text of 23 articles were screened in duplicate. Seven articles reporting results from six studies met eligibility criteria. Integration of PROMs increased the identification and discussion around health-related quality of life (HRQOL), especially in psychosocial and emotional domains, but showed mixed results with the impact on quality of care. No studies assessed the impact of integrating PROMs on healthcare utilization. Limitations: Due to significant heterogeneity in the studies, a meta-analysis was not conducted. Conclusions: Integrating PROMs could have a positive impact on HRQOL; however, further studies are required to determine the impact of PROMs in routine pediatric clinical care.

Long-term effectiveness and safety of treatment with dupilumab in patients with atopic dermatitis: Results of the TREAT NL (TREatment of ATopic eczema, the Netherlands) registry.

BACKGROUND: Evidence on long-term dupilumab treatment for atopic dermatitis in daily practice is lacking. OBJECTIVE: To investigate patient characteristics, treatment aspects, effectiveness, and safety of up to 84 weeks of dupilumab treatment. METHODS: An observational prospective cohort study was conducted of patients with atopic dermatitis starting dupilumab in routine clinical care. RESULTS: Of the 221 included patients, 103 used systemic therapy at baseline. At 84 weeks, we found a change of -15.2 (SE, 1.7) for the Eczema Area and Severity Index, -16.9 (SE, 1.4) for the Patient-Oriented Eczema Measure, and -17.2 (SE, 1.6) for the Dermatology Life Quality Index. We found a trend for improvement over time for the Investigator Global Assessment and Numerical Rating Scale for pruritus. Severe (n = 79) including serious (n = 11) adverse events were observed in 69 patients. Eye complaints were most frequently reported (n = 46). Twenty-one patients adjusted the regular dosing schedule, and 14 patients discontinued treatment, mainly due to ineffectiveness (n = 7). LIMITATIONS: Only adverse events of severe and serious nature were registered for feasibility reasons. CONCLUSION: Daily practice dupilumab treatment of up to 84 weeks is generally well-tolerated, apart from the reporting of eye complaints. It can be considered a long-term effective treatment for atopic dermatitis in combination with topical and initial concomitant systemic treatment, showing a sustained improvement of signs, symptoms, and quality of life.

Adding Social Determinants in the Electronic Health Record in Clinical Care in Hawai'i: Supporting Community-Clinical Linkages in Patient Care.

Social and behavioral determinants of health, such as poverty, homelessness, and limited social support, account for an estimated 40% of health burdens and predict critical health outcomes. Many clinical-community linkages specifically focus on addressing such challenges. Given its distinctive history, culture, and location, Hawai'i has unique social factors impacting population health. Local health systems are striving to address these issues to meet their patients' health needs. Yet the evidence on precisely how health care systems and communities may work together to achieve these goals are limited both generally and specifically in the Hawai'i context. This article describes real-world efforts by 3 local health care delivery systems that integrate the identification of social needs into clinical care using the electronic health record (EHR). One health care system collects and assesses social challenges and interpersonal needs to improve the care for its frail seniors (aged 65 and older). Another system added key data fields around social support and inpatient mobility in the EHR to identify whether patients needed additional help during hospitalization and post-discharge. A third added a social needs screening tool (eg, housing instability, food insecurity, transportation needs) to its EHR to ensure that patient-specific needs can be appropriately addressed by the care team. Successful integration of this information into the EHR can identify, direct, and support clinical-community linkages and integrate such relationships into the care team. Many lessons can be learned from the implementation of these programs, including the importance of clinical relevance and ensuring capacity for social work liaisons trained for this work to address identified needs.

Determination of plasma concentration reference ranges for oral aripiprazole, olanzapine, and quetiapine.

BACKGROUND: Schizophrenia is a common disease which is commonly managed using antipsychotic medications (APS). Inadequate response and lack of adherence often prevent optimal therapeutic effectiveness. Monitoring APS concentrations can be useful to help improve outcomes for the patient. AIMS: The aim of this study was to develop "reference ranges" for oral aripiprazole, olanzapine, and quetiapine to allow clinicians to understand expected variability in patients treated with APS. The reference ranges were constructed to account for different oral doses, sampling times, and variability both between, and within, subjects. METHODS: Population pharmacokinetic models were used to simulate plasma concentrations over time under different doses and population demographics. The references were validated against external data both numerically and graphically. RESULTS: Reference ranges for oral aripiprazole, olanzapine, and quetiapine were derived and successfully validated against the external data. The 80% reference range for aripiprazole following a 2-mg oral dose was 14.7-41.6 ng/mL 0-4 h post dose and 10.6-37.1 ng/mL 20-24 h post dose. These ranges increased to 221-624 ng/mL 0-4 h post dose following administration of a 30-mg dose, and 159-557 ng/mL 20-24 h post dose. The 80% reference range 0-4 h post dose was 22.5-67.1 ng/mL following a 15-mg dose once daily of oral olanzapine, and 179-768 ng/mL following a 150-mg dose once daily of oral quetiapine. CONCLUSIONS: Comparing individual patients' APS levels with reference ranges, along with a full clinical assessment, could provide important insights to help a clinician optimize APS therapy.

The proposed role of ultrasound in the management of giant cell arteritis in routine clinical practice.

Objective: To develop and explore a protocol for using colour duplex sonography (CDS) in the routine care of GCA. Methods: We tested CDS of temporal arteries and axillary arteries (AXs) on consecutive patients with suspected or established GCA, between July 2014 and September 2016. Results: We assessed 293 patients [age 72 (10), female/male 196/97], of whom 118 had clinically confirmed GCA. Seventy-three percent of patients had already received high-dose glucocorticoids (GCs) for 17 (33) days. Among new referrals with <7 days of GC treatment (n = 55), the sensitivity of CDS was 63.3% (95% CI: 44%, 80%), specificity 100% (95% CI: 83%, 100%), positive predictive value 100% and negative predictive value 64.5% (95% CI: 53%, 74%). Sensitivity rose to 81.8% in patients with jaw claudication and high inflammatory markers. During the observation period, the rate of temporal artery biopsies decreased from 72 (42%) to 36 (25%) (P = 0.002). CDS was positive in 21% of 89 follow-up scans in asymptomatic individuals, compared with 37% in patients experiencing clinical flares. Over time, the number of halos reduced; only new or flaring patients showed a halo in four or more sites. The diameter of axillary halos reduced from referral [1.6 (0.4) mm] to follow-up [1.4 (0.2) mm, P = 0.01] or flares [1.4 (0.2) mm, P = 0.02]. Conclusion: CDS provides high positive predictive value for diagnosing GCA and allows for a significant reduction in temporal artery biopsies. We explored the role of CDS in detecting flares and demonstrated a relationship to the extent of the distribution of halos, but not to their size.

Editorial: Evidence-guided interventions and optimising outcomes in routine clinical care of children and young people's mental health.

This Editorial reflects on several articles in this issue of the journal that focus on evidence-based interventions in routine clinical care. In particular, it highlights the approaches advocated in the review by Bearman & Weisz into overcoming barriers to the implementation of research findings into routine clinical care: conceptually unified treatments that acknowledge the overlap and comorbidity between presenting problems; modular approaches to co-ordinate and combine treatment approaches to improve the fit for young people presenting with multiple problems; and approaches to monitoring and feedback of progress and outcomes to aid clinical review and decision-making. Issues of access, stigma and measurement of meaningful outcomes in routine clinical practice are also considered.

Providing patient progress feedback and clinical support tools to therapists: is the therapeutic process of patients on-track to recovery enhanced in psychosomatic in-patient therapy under the conditions of routine practice?

OBJECTIVES: In previous studies of patients on-track to recovery (OT) involving therapists receiving only patient progress feedback without clinical support tools (CST) inconsistent results were found. Possible effects of combining patient progress feedback with CST on OT patients remain unclear. METHODS: At intake (t1), 252 patients of two in-patient psychosomatic clinics were randomized either into the experimental group (EG) or the treatment-as-usual control group (CG). Both groups were monitored weekly using the self-report instruments "Outcome Questionnaire" (OQ-45) and "Assessment of Signal Cases" (ASC). Therapists received weekly patient progress feedback (OQ-45) and CST feedback (ASC) only for EG patients starting at the week following intake (t2). Patients who did not deviate negatively from expected recovery curves by at least one standard deviation were considered OT patients (N=209; NEG=111; NCG=98). Since therapists received feedback at t2 for the first time, different patterns of change (OQ-45 scales) between the groups from t1 to t2, t2 to t3 (intake+two weeks), t2 to t4 (intake+three weeks), and t2 to t5 (last available OQ-45 score) were evaluated by multilevel models. RESULTS: Merely from t2 to t3, the EG improved significantly more on the OQ-45 symptom distress scale than the CG (p<0.05; g=0.12). CONCLUSION: Providing patient progress feedback and CST to therapists did not substantially surpass treatment-as-usual for OT patients in this explorative study except for a very small time-limited enhancement of symptom change.

Feedback on patient progress and clinical support tools for therapists: improved outcome for patients at risk of treatment failure in psychosomatic in-patient therapy under the conditions of routine practice.

OBJECTIVES: Although psychosomatic in-patient treatment is effective, 5-10% of the patients deteriorate. Providing patient progress feedback and clinical support tools to therapists improves the outcome for patients at risk of deterioration in counseling, outpatient psychotherapy, and substance abuse treatment. This study investigated the effects of feedback on psychosomatically treated in-patients at risk of treatment failure. METHODS: At intake, all patients of two psychosomatic clinics were randomized either into the experimental group or the treatment-as-usual control group. Both groups were tracked weekly with the "Outcome Questionnaire" (OQ-45) measuring patient progress and with the clinical support tool "Assessment of Signal Cases" (ASC). Therapists received feedback from both instruments for all their experimental group patients. "Patients at risk" were defined as patients who deviated from expected recovery curves by at least one standard deviation. Of 252 patients, 43 patients were at risk: 23 belonged to the experimental group, 20 to the control group. The feedback effect was analyzed using a level-2-model for discontinuous change, effect size (d), reliable change index (RCI), and odds ratio for reliable deterioration. RESULTS: For patients at risk, the experimental group showed an improved outcome on the OQ-45 total scale compared to the control group (p<0.05, d=0.54). By providing feedback, the rate of reliably deteriorated patients at risk was reduced from 25.0% (control group) to 8.7% (experimental group) - odds ratio=0.29. All reliably improved patients at risk belonged to the experimental group. CONCLUSION: Feedback improves the outcome of patients at risk undergoing psychosomatic in-patient treatment.