Guideline-based stepped and collaborative care for patients with depression in a cluster-randomised trial

Guidelines recommend stepped and collaborative care models (SCM) for depression. We aimed to evaluate the effectiveness of a complex guideline-based SCM for depressed patients. German primary care units were cluster-randomised into intervention (IG) or control group (CG) (3:1 ratio). Adult routine care patients with PHQ-9 ≥ 5 points could participate and received SCM in IG and treatment as usual (TAU) in CG. Primary outcome was change in PHQ-9 from baseline to 12 months (hypothesis: greater reduction in IG). A linear mixed model was calculated with group as fixed effect and practice as random effect, controlling for baseline PHQ-9 (intention-to-treat). 36 primary care units were randomised to IG and 13 to CG. 36 psychotherapists, 6 psychiatrists and 7 clinics participated in SCM. 737 patients were included (IG: n = 569 vs. CG: n = 168); data were available for 60% (IG) and 64% (CG) after 12 months. IG showed 2.4 points greater reduction [95% confidence interval (CI): -3.4 to -1.5, p < 0.001; Cohen's d = 0.45] (adjusted PHQ-9 mean change). Odds of response [odds ratio: 2.8; 95% CI: 1.6 to 4.7] and remission [odds ratio: 3.2; 95% CI: 1.58 to 6.26] were higher in IG. Guideline-based SCM can improve depression care

Metalloprotease Meprinβ in Rat Kidney: Glomerular Localization and Differential Expression in Glomerulonephritis

Meprin (EC 3.4.24.18) is an oligomeric metalloendopeptidase found in microvillar membranes of kidney proximal tubular epithelial cells. Here, we present the first report on the expression of meprinβ in rat glomerular epithelial cells and suggest a potential involvement in experimental glomerular disease. We detected meprinβ in glomeruli of immunostained rat kidney sections on the protein level and by quantitative RT-PCR of laser-capture microdissected glomeruli on the mRNA level. Using immuno-gold staining we identified the membrane of podocyte foot processes as the main site of meprinβ expression. The glomerular meprinβ expression pattern was altered in anti-Thy 1.1 and passive Heymann nephritis (PHN). In addition, the meprinβ staining pattern in the latter was reminiscent of immunostaining with the sheep anti-Fx1A antiserum, commonly used in PHN induction. Using Western blot and immunoprecipitation assays we demonstrated that meprinβ is recognized by Fx1A antiserum and may therefore represent an auto-antigen in PHN. In anti-Thy 1.1 glomerulonephritis we observed a striking redistribution of meprinβ in tubular epithelial cells from the apical to the basolateral side and the cytosol. This might point to an involvement of meprinβ in this form of glomerulonephritis

Does symptom severity matter in stepped and collaborative care for depression?

BACKGROUND: We investigated the differential effectiveness of a stepped and collaborative care model (SCM) vs. treatment as usual (TAU) for primary care patients with various depression severity degrees and explored whether subgroups received distinct evidence-based treatments. METHODS: Subgroup analyses of a RCT were calculated applying a multiple linear mixed model with the factors 1. group (SCM; TAU), 2. severity ((mild-moderate (MMD); severe depression (SD)) and their interaction, with PHQ-9 as primary outcome. Utilization of treatments was analyzed descriptively. RESULTS: For the 737 participating patients (SCM: n = 569; TAU: n = 168), availability of data substantially varies between subgroups at 12-month follow-up ranging between 37% and 70%. ITT-analysis (Last-observation-carried-forward) revealed a significant interaction for group x severity [p = 0.036] and a significant difference between groups in symptom reduction for MMD (-3.9; [95% CI: -5.1 to -2.6, p < 0.001; d = 0.64] but not for SD (-1.6; [95% CI: -3.4 to 0.2, p = 0.093; d = 0.27]. Sensitivity analyses (multiple imputation, completer analysis, pattern mixture model) didn`t confirm the interaction effect and showed significant effects for both severity groups with slightly higher effect sizes for MMD. Differences between SCM and TAU in the percentage of patients utilizing depression-specific treatments are larger for MMD. LIMITATIONS: There was a high proportion of missing values among severely depressed patients, especially in SCM. CONCLUSION: SCM is effective for both MMD and SD. Utilization patterns might help explain the higher effects for MMD. Various strategies of replacement of missing values lead to slightly divergent results due to selective drop out between severity groups

Cost-effectiveness of guideline-based stepped and collaborative care versus treatment as usual for patients with depression - a cluster-randomized trial

BACKGROUND: Depression is associated with major patient burden. Its treatment requires complex and collaborative approaches. A stepped care model based on the German National Clinical Practice Guideline "Unipolar Depression" has been shown to be effective. In this study we assess the cost-effectiveness of this guideline based stepped care model versus treatment as usual in depression. METHODS: This prospective cluster-randomized controlled trial included 737 depressive adult patients. Primary care practices were randomized to an intervention (IG) or a control group (CG). The intervention consisted of a four-level stepped care model. The CG received treatment as usual. A cost-utility analysis from the societal perspective with a time horizon of 12 months was performed. We used quality-adjusted life years (QALY) based on the EQ-5D-3L as effect measure. Resource utilization was assessed by patient questionnaires. Missing values were imputed by 'multiple imputation using chained equations' based on predictive mean matching. We calculated adjusted group differences in costs and effects as well as incremental cost-effectiveness ratios. To describe the statistical and decision uncertainty cost-effectiveness acceptability curves were constructed based on net-benefit regressions with bootstrapped standard errors (1000 replications). The complete sample and subgroups based on depression severity were considered. RESULTS: We found no statically significant differences in costs and effects between IG and CG. The incremental total societal costs (+€5016; 95%-CI: [-€259;€10,290) and effects (+ 0.008 QALY; 95%-CI: [- 0.030; 0.046]) were higher in the IG in comparison to the CG. Significantly higher costs were found in the IG for outpatient physician services and psychiatrist services in comparison to the CG. Significantly higher total costs and productivity losses in the IG in comparison to the CG were found in the group with severe depression. Incremental cost-effectiveness ratios for the IG in comparison to the CG were unfavourable (complete sample: €627.000/QALY gained; mild depression: dominated; moderately severe depression: €645.154/QALY gained; severe depression: €2082,714/QALY gained) and the probability of cost-effectiveness of the intervention was low, except for the group with moderate depression (ICER: dominance; 70% for willingness-to-pay threshold of €50,000/QALY gained). CONCLUSIONS We found no evidence for cost-effectiveness of the intervention in comparison to treatment as usual. TRIAL REGISTRATION NCT, NCT01731717 . Registered 22 November 2012 - Retrospectively registered

Effectiveness and cost-effectiveness of telephone-based cognitive-behavioural therapy in primary care: study protocol of TIDe - telephone intervention for depression

Abstract Background Despite the availability of evidence-based treatments for depression, a large proportion of patients remains untreated or adequate treatment is initiated with delay. This situation is particularly critical in primary care, where not only most individuals first seek help for their mental health problems, but also depressive disorders – particularly mild to moderate levels of severity – are highly prevalent given the high comorbidity of chronic somatic conditions and depression. Improving the access for evidence-based treatment, especially in primary care, is hence a priority challenge in the mental health care agenda. Telephone usage is widespread and has the potential of overcoming many barriers that individuals suffering from mental health problems are facing: Its implementation for treatment delivery presents an option for optimisation of treatment pathways and outcomes. Methods/design This paper details the study protocol for a randomised controlled trial (RCT) evaluating the effectiveness of a telephone-administered short-term cognitive-behavioural therapy (T-CBT) for depression as compared to treatment as usual (TAU) in the Swiss primary care setting. The study aims at randomising a total of 216 mildly to moderately depressed patients, which are either identified by their General Practitioners (GPs) or who self-refer to the study programme in consultation with their GP. The trial will examine whether telephone-delivered, manualised treatment leads to clinically significant reduction in depression at follow-up. It will further investigate the cost-effectiveness and acceptability of the intervention in the primary care setting. Discussion Conducting a low-intensity treatment on the telephone allows for greater flexibility for both patient and therapist, can grant more anonymity and can thus lead to less hesitation in the patient about whether to attempt treatment or not. In order to benefit from this approach, large-scale studies need to prove superior effectiveness and cost-effectiveness of telephone-delivered therapy over routine care for patients with mild to moderate depression. Trial registration ClinicalTrials.gov NCT02667366 . Registered on 3 December 2015

Figure S14

FIG. S14. Ancestral state reconstruction for the character: “Zigzag steams”, on the phylogenetic hypothesis based on psbA-trnH. Circles denote the state and circles in the nodes show the proportional likelihood visually