Second international collaborative study evaluating performance characteristics of methods measuring the von Willebrand factor cleaving protease (ADAMTS-13)

BACKGROUND: Over the last 4 years ADAMTS-13 measurement underwent dramatic progress with newer and simpler methods. AIMS: Blind evaluation of newer methods for their performance characteristics. DESIGN: The literature was searched for new methods and the authors invited to join the evaluation. Participants were provided with a set of 60 coded frozen plasmas that were prepared centrally by dilutions of one ADAMTS-13-deficient plasma (arbitrarily set at 0%) into one normal-pooled plasma (set at 100%). There were six different test plasmas ranging from 100% to 0%. Each plasma was tested 'blind' 10 times by each method and results expressed as percentage vs. the local and the common standard provided by the organizer. RESULTS: There were eight functional and three antigen assays. Linearity of observed-vs.-expected ADAMTS-13 levels assessed as r2 ranged from 0.931 to 0.998. Between-run reproducibility expressed as the (mean) CV for repeated measurements was below 10% for three methods, 10-15% for five methods and up to 20% for the remaining three. F-values (analysis of variance) calculated to assess the capacity to distinguish between ADAMTS-13 levels (the higher the F-value, the better the capacity) ranged from 3965 to 137. Between-method variability (CV) amounted to 24.8% when calculated vs. the local and to 20.5% when calculated vs. the common standard. Comparative analysis showed that functional assays employing modified von Willebrand factor peptides as substrate for ADAMTS-13 offer the best performance characteristics. CONCLUSIONS: New assays for ADAMTS-13 have the potential to make the investigation/management of patients with thrombotic microangiopathies much easier than in the past.

Comparison of two non-bronchoscopic methods for evaluating inflammation in patients with acute hypoxaemic respiratory failure

INTRODUCTION: The simple bedside method for sampling undiluted distal pulmonary edema fluid through a normal suction catheter (s-Cath) has been experimentally and clinically validated. However, there are no data comparing non-bronchoscopic bronchoalveolar lavage (mini-BAL) and s-Cath for assessing lung inflammation in acute hypoxaemic respiratory failure. We designed a prospective study in two groups of patients, those with acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) and those with acute cardiogenic lung edema (ACLE), designed to investigate the clinical feasibility of these techniques and to evaluate inflammation in both groups using undiluted sampling obtained by s-Cath. To test the interchangeability of the two methods in the same patient for studying the inflammation response, we further compared mini-BAL and s-Cath for agreement of protein concentration and percentage of polymorphonuclear cells (PMNs). METHODS: Mini-BAL and s-Cath sampling was assessed in 30 mechanically ventilated patients, 21 with ALI/ARDS and 9 with ACLE. To analyse agreement between the two sampling techniques, we considered only simultaneously collected mini-BAL and s-Cath paired samples. The protein concentration and polymorphonuclear cell (PMN) count comparisons were performed using undiluted sampling. Bland-Altman plots were used for assessing the mean bias and the limits of agreement between the two sampling techniques; comparison between groups was performed by using the non-parametric Mann-Whitney-U test; continuous variables were compared by using the Student t-test, Wilcoxon signed rank test, analysis of variance or Student-Newman-Keuls test; and categorical variables were compared by using chi-square analysis or Fisher exact test. RESULTS: Using protein content and PMN percentage as parameters, we identified substantial variations between the two sampling techniques. When the protein concentration in the lung was high, the s-Cath was a more sensitive method; by contrast, as inflammation increased, both methods provided similar estimates of neutrophil percentages in the lung. The patients with ACLE showed an increased PMN count, suggesting that hydrostatic lung edema can be associated with a concomitant inflammatory process. CONCLUSIONS: There are significant differences between the s-Cath and mini-BAL sampling techniques, indicating that these procedures cannot be used interchangeably for studying the lung inflammatory response in patients with acute hypoxaemic lung injury.

Prospective clinical study evaluating the long-time adjunctive use of chlorhexidine after one-stage full-mouth SRP

OBJECTIVES: Scaling and root planing are the causal procedure in the treatment of periodontitis. Many attempts have been made to improve the outcome. The aim of this study was to verify the influence of the extended use of chlorhexidine after one-stage full-mouth (FM) SRP in patients with chronic periodontitis on the clinical outcome after 3 months. METHODS: Eighty-one patients with pockets > or =5 mm were treated by FM. All patients rinsed additionally with 0.2% chlorhexidine (CHX) twice daily over 3 months. Plaque index, bleeding on probing, probing depth (PD) and clinical attachment level (CAL) were recorded at baseline and after 1 and 3 months. RESULTS: In the test group, all variables were significantly improved after 1 and 3 months. Mean reduction of PD and CAL gain was 2.25 +/- 1.08 and 1.67 +/- 1.08 after 1 and 2.99 +/- 1.11 and 2.33 +/- 1.31 after 3 months respectively. CONCLUSIONS: Over 3 months of extended use of CHX mouth rinse after SRP showed slightly but statistically significant better results.

CO2 and diode laser for excisional biopsies of oral mucosal lesions. A pilot study evaluating clinical and histopathological parameters

PURPOSE: The present pilot study evaluates the histopathological characteristics and suitability of CO2 and diode lasers for performing excisional biopsies in the buccal mucosa with special emphasis on the extent of the thermal damage zone created. PATIENTS AND METHODS: 15 patients agreed to undergo surgical removal of their fibrous hyperplasias with a laser. These patients were randomly assigned to one diode or two CO2 laser groups. The CO2 laser was used in a continuous wave mode (cw) with a power of 5 W (Watts), and in a pulsed char-free mode (cf). Power settings for the diode laser were 5.12 W in a pulsed mode. The thermal damage zone of the three lasers and intraoperative and postoperative complications were assessed and compared. RESULTS: The collateral thermal damage zone on the borders of the excisional biopsies was significantly smaller with the CO, laser for both settings tested compared to the diode laser regarding values in pm or histopathological index scores. The only intraoperative complication encountered was bleeding, which had to be controlled with electrocauterization. No postoperative complications occurred in any of the three groups. CONCLUSIONS: The CO2 laser seems to be appropriate for excisional biopsies of benign oral mucosal lesions. The CO2 laser offers clear advantages in terms of smaller thermal damage zones over the diode laser. More study participants are needed to demonstrate potential differences between the two different CO2 laser settings tested.

Early reperfusion hemodynamics predict recovery in rat hearts: a potential approach towards evaluating cardiac grafts from non-heart-beating donors

Aims Cardiac grafts from non-heartbeating donors (NHBDs) could significantly increase organ availability and reduce waiting-list mortality. Reluctance to exploit hearts from NHBDs arises from obligatory delays in procurement leading to periods of warm ischemia and possible subsequent contractile dysfunction. Means for early prediction of graft suitability prior to transplantation are thus required for development of heart transplantation programs with NHBDs. Methods and Results Hearts (n = 31) isolated from male Wistar rats were perfused with modified Krebs-Henseleit buffer aerobically for 20 min, followed by global, no-flow ischemia (32°C) for 30, 50, 55 or 60 min. Reperfusion was unloaded for 20 min, and then loaded, in working-mode, for 40 min. Left ventricular (LV) pressure was monitored using a micro-tip pressure catheter introduced via the mitral valve. Several hemodynamic parameters measured during early, unloaded reperfusion correlated significantly with LV work after 60 min reperfusion (p<0.001). Coronary flow and the production of lactate and lactate dehydrogenase (LDH) also correlated significantly with outcomes after 60 min reperfusion (p<0.05). Based on early reperfusion hemodynamic measures, a composite, weighted predictive parameter, incorporating heart rate (HR), developed pressure (DP) and end-diastolic pressure, was generated and evaluated against the HR-DP product after 60 min of reperfusion. Effective discriminating ability for this novel parameter was observed for four HR*DP cut-off values, particularly for ≥20 *103 mmHg*beats*min−1 (p<0.01). Conclusion Upon reperfusion of a NHBD heart, early evaluation, at the time of organ procurement, of cardiac hemodynamic parameters, as well as easily accessible markers of metabolism and necrosis seem to accurately predict subsequent contractile recovery and could thus potentially be of use in guiding the decision of accepting the ischemic heart for transplantation.

Re-evaluating adjuvant breast cancer trials: assessing hormone receptor status by immunohistochemical versus extraction assays

BACKGROUND: Tumor levels of steroid hormone receptors, a factor used to select adjuvant treatment for early-stage breast cancer, are currently determined with immunohistochemical assays. These assays have a discordance of 10%-30% with previously used extraction assays. We assessed the concordance and predictive value of hormone receptor status as determined by immunohistochemical and extraction assays on specimens from International Breast Cancer Study Group Trials VIII and IX. These trials predominantly used extraction assays and compared adjuvant chemoendocrine therapy with endocrine therapy alone among pre- and postmenopausal patients with lymph node-negative breast cancer. Trial conclusions were that combination therapy provided a benefit to pre- and postmenopausal patients with estrogen receptor (ER)-negative tumors but not to ER-positive postmenopausal patients. ER-positive premenopausal patients required further study. METHODS: Tumor specimens from 571 premenopausal and 976 postmenopausal patients on which extraction assays had determined ER and progesterone receptor (PgR) levels before randomization from October 1, 1988, through October 1, 1999, were re-evaluated with an immunohistochemical assay in a central pathology laboratory. The endpoint was disease-free survival. Hazard ratios of recurrence or death for treatment comparisons were estimated with Cox proportional hazards regression models, and discriminatory ability was evaluated with the c index. All statistical tests were two-sided. RESULTS: Concordance of hormone receptor status determined by both assays ranged from 74% (kappa = 0.48) for PgR among postmenopausal patients to 88% (kappa = 0.66) for ER in postmenopausal patients. Hazard ratio estimates were similar for the association between disease-free survival and ER status (among all patients) or PgR status (among postmenopausal patients) as determined by the two methods. However, among premenopausal patients treated with endocrine therapy alone, the discriminatory ability of PgR status as determined by immunohistochemical assay was statistically significantly better (c index = 0.60 versus 0.51; P = .003) than that determined by extraction assay, and so immunohistochemically determined PgR status could predict disease-free survival. CONCLUSIONS: Trial conclusions in which ER status (for all patients) or PgR status (for postmenopausal patients) was determined by immunohistochemical assay supported those determined by extraction assays. However, among premenopausal patients, trial conclusions drawn from PgR status differed--immunohistochemically determined PgR status could predict response to endocrine therapy, unlike that determined by the extraction assay.

Progress on BIG 1-02/IBCSG 27-02/NSABP B-37, a prospective randomized trial evaluating chemotherapy after local therapy for isolated locoregional recurrences of breast cancer

BACKGROUND: The utility of chemotherapy for women who experience a locoregional recurrence after primary treatment of early breast cancer remains an open question. An international collaborative trial is being conducted by the Breast International Group (BIG), the International Breast Cancer Study Group (IBCSG), and the National Surgical Adjuvant Breast and Bowel Project (NSABP) to determine the effectiveness of cytotoxic therapy for these patients, either alone or in addition to selective use of hormonal therapy and trastuzumab. METHODS: The trial population includes women who have had a previous diagnosis of invasive breast cancer treated by mastectomy or breast-conserving surgery, but subsequently develop an isolated local and/or regional ipsilateral invasive recurrence. Excision of all macroscopic tumor without evidence of systemic disease is required for study entry. Patients are randomized to receive chemotherapy or no chemotherapy; type of chemotherapy is not protocol-specified. Radiation, hormonal therapy, and trastuzumab are given as appropriate. The primary endpoint is disease-free survival (DFS). Quality-of-life measurements are collected at baseline, and then at 9 and 12 months. The accrual goal is 977 patients. RESULTS: This report describes the characteristics of the first 99 patients. Sites of recurrence at study entry were: breast (56%), mastectomy scar/chest wall (35%), and regional lymph nodes (9%). Two-thirds of patients have estrogen-receptor-positive recurrences. CONCLUSION: This is the only trial actively investigating the question of "adjuvant" chemotherapy in locally recurrent breast cancer. The case mix of accrual to date indicates a broad representation of this patient population.

A feasibility study evaluating an in situ formed synthetic biodegradable membrane for guided bone regeneration in dogs

PURPOSE: The aim was (1) to evaluate the soft-tissue reaction of a synthetic polyethylene glycol (PEG) hydrogel used as a barrier membrane for guided bone regeneration (GBR) compared with a collagen membrane and (2) to test whether or not the application of this in situ formed membrane will result in a similar amount of bone regeneration as the use of a collagen membrane. MATERIAL AND METHODS: Tooth extraction and preparation of osseous defects were performed in the mandibles of 11 beagle dogs. After 3 months, 44 cylindrical implants were placed within healed dehiscence-type bone defects resulting in approximately 6 mm exposed implant surface. The following four treatment modalities were randomly allocated: PEG+autogenous bone chips, PEG+hydroxyapatite (HA)/tricalcium phosphate (TCP) granules, bioresorbable collagen membrane+autogenous bone chips and autogenous bone chips without a membrane. After 2 and 6 months, six and five dogs were sacrificed, respectively. A semi-quantitative evaluation of the local tolerance and a histomorphometric analysis were performed. For statistical analysis, repeated measures analysis of variance (ANOVA) and subsequent pairwise Student's t-test were applied (P<0.05). RESULTS: No local adverse effects in association with the PEG compared with the collagen membrane was observed clinically and histologically at any time-point. Healing was uneventful and all implants were histologically integrated. Four out of 22 PEG membrane sites revealed a soft-tissue dehiscence after 1-2 weeks that subsequently healed uneventful. Histomorphometric measurement of the vertical bone gain showed after 2 months values between 31% and 45% and after 6 months between 31% and 38%. Bone-to-implant contact (BIC) within the former defect area was similarly high in all groups ranging from 71% to 82% after 2 months and 49% to 91% after 6 months. However, with regard to all evaluated parameters, the PEG and the collagen membranes did not show any statistically significant difference compared with sites treated with autogenous bone without a membrane. CONCLUSION: The in situ forming synthetic membrane made of PEG was safely used in the present study, revealing no biologically significant abnormal soft-tissue reaction and demonstrated similar amounts of newly formed bone for defects treated with the PEG membrane compared with defects treated with a standard collagen membrane.

Evaluating Integration. Research contributions for a gender sensitive migration policy: Research contributions for a gender sensitive migration policy

The integration of academic and non-academic knowledge is a key concern for researchers who aim at bridging the gap between research and policy. Researchers involved in the sustainability-oriented NCCR North-South programme have made the experience that linking different types of knowledge requires time and effort, and that methodologies are still lacking. One programme component was created at the inception of this transdisciplinary research programme to support exchange between researchers, development practitioners and policymakers. After 8 years of research, the programme is assessing whether research has indeed enabled a continuous communication across and beyond academic boundaries and has effected changes in the public policies of poor countries. In a first review of the data, we selected two case studies explicitly addressing the lives of women. In both cases – one in Pakistan, the other in Nepal – the dialogue between researchers and development practitioners contributed to important policy changes for female migration. In both countries, outmigration has become an increasingly important livelihood strategy. National migration policies are gendered, limiting the international migration of women. In Nepal, women were not allowed to migrate to specific countries such as the Gulf States or Malaysia. This was done in the name of positive discrimination, to protect women from potential exploitation and harassment in domestic work. However, women continued to migrate in many other and often illegal and more risky ways, increasing their vulnerability. In Pakistan, female labour migration was not allowed at all and male migration increased the vulnerability of the families remaining back home. Researchers and development practitioners in Nepal and Pakistan brought women’s shared experience of and exposure to the mechanisms of male domination into the public debate, and addressed the discriminating laws. Now, for the first time in Pakistan, the new draft policy currently under discussion would enable broadly-based female labour migration. What can we learn from the two case studies with regard to ways of relating experience- and research-based knowledge? The paper offers insights into the sequence of interactions between researchers, local people, development practitioners, and policy-makers, which eventually contributed to the formulation of a rights-based migration policy. The reflection aims at exploring the gendered dimension of ways to co-produce and share knowledge for development across boundaries. Above all, it should help researchers to better tighten the links between the spheres of research and policy in future.

Five-year results evaluating the effects of platelet-rich plasma on the healing of intrabony defects treated with enamel matrix derivative and natural bone mineral

BACKGROUND Regenerative periodontal surgery using the combination of enamel matrix derivative (EMD) and natural bone mineral (NBM) with and without addition of platelet-rich plasma (PRP) has been shown to result in substantial clinical improvements, but the long-term effects of this combination are unknown. METHODS The goal of this study was to evaluate the long-term (5-year) outcomes after regenerative surgery of deep intrabony defects with either EMD + NBM + PRP or EMD + NBM. Twenty-four patients were included. In each patient, one intrabony defect was randomly treated with either EMD + NBM + PRP or EMD + NBM. Clinical parameters were evaluated at baseline and 1 and 5 years after treatment. The primary outcome variable was clinical attachment level (CAL). RESULTS The sites treated with EMD + NBM + PRP demonstrated a mean CAL change from 10.5 ± 1.6 to 6.0 ± 1.7 mm (P <0.001) at 1 year and 6.2 ± 1.5 mm (P <0.001) at 5 years. EMD + NBM-treated defects showed a mean CAL change from 10.6 ± 1.7 to 6.1 ± 1.5 mm (P <0.001) at 1 year and 6.3 ± 1.4 mm (P <0.001) at 5 years. At 1 year, a CAL gain of ≥4 mm was measured in 83% (10 of 12) of the defects treated with EMD + NBM + PRP and in 100% (all 12) of the defects treated with EMD + NBM. Compared to baseline, in both groups at 5 years, a CAL gain of ≥4 mm was measured in 75% (nine of 12 in each group) of the defects. Four sites in the EMD + PRP + NBM group lost 1 mm of the CAL gained at 1 year. In the EMD + NBM group, one defect lost 2 mm and four other defects lost 1 mm of the CAL gained at 1 year. No statistically significant differences in any of the investigated parameters were observed between the two groups. CONCLUSIONS Within their limits, the present results indicate that: 1) the clinical outcomes obtained with both treatments can be maintained up to a period of 5 years; and 2) the use of PRP does not appear to improve the results obtained with EMD + NBM.

Standard methods for Nosema research

Methods are described for working with Nosema apis and Nosema ceranae in the field and in the laboratory. For fieldwork, different sampling methods are described to determine colony level infections at a given point in time, but also for following the temporal infection dynamics. Suggestions are made for how to standardise field trials for evaluating treatments and disease impact. The laboratory methods described include different means for determining colony level and individual bee infection levels and methods for species determination, including light microscopy, electron microscopy, and molecular methods (PCR). Suggestions are made for how to standardise cage trials, and different inoculation methods for infecting bees are described, including control methods for spore viability. A cell culture system for in vitro rearing of Nosema spp. is described. Finally, how to conduct different types of experiments are described, including infectious dose, dose effects, course of infection and longevity tests

The International ADHD in Substance Use Disorders Prevalence (IASP) study: background, methods and study population

Attention deficit/hyperactivity disorder (ADHD) is an increasingly recognized comorbid condition in subjects with substance use disorders (SUDs). This paper describes the methods and study population of the International ADHD in Substance Use Disorders Prevalence (IASP) study. Objectives of the IASP are to determine the prevalence of ADHD in adult treatment seeking patients with SUD in different countries and SUD populations, determine the reliability and validity of the Adult ADHD Self-report Scale V 1.1 (ASRS) as ADHD screening instrument in SUD populations, investigate the comorbidity profile of SUD patients with and without ADHD, compare risk factors and protective factors in SUD patients with and without a comorbid diagnosis of ADHD, and increase our knowledge about the relationship between ADHD and the onset and course of SUD. In this cross-sectional, multi-centre two stage study, subjects were screened for ADHD with the ASRS, diagnosed with the Conner's Adult ADHD Diagnostic Interview for DSM-IV (CAADID), and evaluated for SUD, major depression, bipolar disorder, anti social personality disorder and borderline personality disorder. Three thousand five hundred and fifty-eight subjects from 10 countries were included. Of these 40.9% screened positive for ADHD. This is the largest international study on this population evaluating ADHD and comorbid disorders.

Evaluating the optimal timing of surgical antimicrobial prophylaxis: study protocol for a randomized controlled trial

BACKGROUND Surgical site infections are the most common hospital-acquired infections among surgical patients. The administration of surgical antimicrobial prophylaxis reduces the risk of surgical site infections . The optimal timing of this procedure is still a matter of debate. While most studies suggest that it should be given as close to the incision time as possible, others conclude that this may be too late for optimal prevention of surgical site infections. A large observational study suggests that surgical antimicrobial prophylaxis should be administered 74 to 30 minutes before surgery. The aim of this article is to report the design and protocol of a randomized controlled trial investigating the optimal timing of surgical antimicrobial prophylaxis.Methods/design: In this bi-center randomized controlled trial conducted at two tertiary referral centers in Switzerland, we plan to include 5,000 patients undergoing general, oncologic, vascular and orthopedic trauma procedures. Patients are randomized in a 1:1 ratio into two groups: one receiving surgical antimicrobial prophylaxis in the anesthesia room (75 to 30 minutes before incision) and the other receiving surgical antimicrobial prophylaxis in the operating room (less than 30 minutes before incision). We expect a significantly lower rate of surgical site infections with surgical antimicrobial prophylaxis administered more than 30 minutes before the scheduled incision. The primary outcome is the occurrence of surgical site infections during a 30-day follow-up period (one year with an implant in place). When assuming a 5 surgical site infection risk with administration of surgical antimicrobial prophylaxis in the operating room, the planned sample size has an 80% power to detect a relative risk reduction for surgical site infections of 33% when administering surgical antimicrobial prophylaxis in the anesthesia room (with a two-sided type I error of 5%). We expect the study to be completed within three years. DISCUSSION The results of this randomized controlled trial will have an important impact on current international guidelines for infection control strategies in the hospital. Moreover, the results of this randomized controlled trial are of significant interest for patient safety and healthcare economics.Trial registration: This trial is registered on ClinicalTrials.gov under the identifier NCT01790529.

Three-dimensional imaging methods for quantitative analysis of facial soft tissues and skeletal morphology in patients with orofacial clefts: a systematic review.

BACKGROUND Current guidelines for evaluating cleft palate treatments are mostly based on two-dimensional (2D) evaluation, but three-dimensional (3D) imaging methods to assess treatment outcome are steadily rising. OBJECTIVE To identify 3D imaging methods for quantitative assessment of soft tissue and skeletal morphology in patients with cleft lip and palate. DATA SOURCES Literature was searched using PubMed (1948-2012), EMBASE (1980-2012), Scopus (2004-2012), Web of Science (1945-2012), and the Cochrane Library. The last search was performed September 30, 2012. Reference lists were hand searched for potentially eligible studies. There was no language restriction. STUDY SELECTION We included publications using 3D imaging techniques to assess facial soft tissue or skeletal morphology in patients older than 5 years with a cleft lip with/or without cleft palate. We reviewed studies involving the facial region when at least 10 subjects in the sample size had at least one cleft type. Only primary publications were included. DATA EXTRACTION Independent extraction of data and quality assessments were performed by two observers. RESULTS Five hundred full text publications were retrieved, 144 met the inclusion criteria, with 63 high quality studies. There were differences in study designs, topics studied, patient characteristics, and success measurements; therefore, only a systematic review could be conducted. Main 3D-techniques that are used in cleft lip and palate patients are CT, CBCT, MRI, stereophotogrammetry, and laser surface scanning. These techniques are mainly used for soft tissue analysis, evaluation of bone grafting, and changes in the craniofacial skeleton. Digital dental casts are used to evaluate treatment and changes over time. CONCLUSION Available evidence implies that 3D imaging methods can be used for documentation of CLP patients. No data are available yet showing that 3D methods are more informative than conventional 2D methods. Further research is warranted to elucidate it.

Evaluating an e-mental health program (“deprexis”) as adjunctive treatment tool in psychotherapy for depression: design of a pragmatic randomized controlled trial

Background Major depressive disorder (MDD) places a significant disease burden on individuals as well as on societies. Several web-based interventions for MDD have shown to be effective in reducing depressive symptoms. However, it is not known whether web-based interventions, when used as adjunctive treatment tools to regular psychotherapy, have an additional effect compared to regular psychotherapy for depression. Methods/design This study is a currently recruiting pragmatic randomized controlled trial (RCT) that compares regular psychotherapy plus a web-based depression program (¿deprexis¿) with a control condition exclusively receiving regular psychotherapy. Adults with a depressive disorder (N?=?800) will be recruited in routine secondary care from therapists over the course of their initial sessions and will then be randomized within therapists to one of the two conditions. The primary outcome is depressive symptoms measured with the Beck Depression Inventory (BDI-II) at three months post randomization. Secondary outcomes include changes on various indicators such as anxiety, somatic symptoms and quality of life. All outcomes are again assessed at the secondary endpoint six months post randomization. In addition, the working alliance and feasibility/acceptability of the treatment condition will be explored. Discussion This is the first randomized controlled trial to examine the feasibility/acceptability and the effectiveness of a combination of traditional face-to-face psychotherapy and web-based depression program compared to regular psychotherapeutic treatment in depressed outpatients in routine care.