Prognostic Risk Factors in Randomized Clinical Trials of Face-to-Face and Internet-Based Psychotherapy for Depression

Importance Variables such as severe symptoms, comorbidity, and sociodemographic characteristics (eg, low educational attainment or unemployment) are associated with a poorer prognosis in adults treated for depressive symptoms. The exclusion of patients with a poor prognosis from RCTs is negatively associated with the generalizability of research findings. Objective To compare the prognostic risk factors (PRFs) in patient samples of RCTs of face-to-face therapy (FTF) and internet-based therapy (IBT) for depression. Data Sources PsycINFO, Cochrane CENTRAL, and reference lists of published meta-analyses were searched from January 1, 2000, to December 31, 2021.Study SelectionRCTs that compared FTF (individual or group therapy) and IBT (guided or self-guided interventions) against a control (waitlist or treatment as usual) in adults with symptoms of depression were included. Data Extraction and Synthesis Data were extracted by 2 independent observers. The Cochrane revised risk-of-bias tool was used to assess the risk of bias. The study was preregistered with OSF Registries and followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline. Main Outcomes and Measures The primary outcome was the standardized mean difference (Hedges g effect size) in depressive symptoms at treatment termination (assessed with standard patient self-report questionnaires), with a positive standardized mean difference indicating larger improvements in the intervention compared with those in the control group. Meta-regression analyses were adjusted for the type of control group. Three preregistered and 2 exploratory sensitivity analyses were conducted. A prognostic risk index (PROG) was created that calculated the sum of 12 predefined individual indicators, with scores ranging from 0 to 12 and higher scores indicating that a sample comprised patients with poorer prognoses. Results This systematic review and meta-regression analysis identified 105 eligible RCTs that comprised 18 363 patients. In total, 48 studies (46%) examined FTF, and 57 studies (54%) examined IBT. The PROG was significantly higher in the RCTs of FTF than in the RCTs of IBT (FTF: mean [SD], 3.55 [1.75]; median [IQR], 3.5 [2.0-4.5]; IBT: mean [SD], 2.27 [1.66]; median [IQR], 2.0 [1.0-3.5]; z = −3.68, P < .001; Hedges g = 0.75; 95% CI, 0.36-1.15). A random-effects meta-regression analysis found no association of the PROG with the effect size. Sensitivity analyses with outliers excluded and accounting for risk of bias or small-study effects yielded mixed results on the association between the PROG and effect size. Conclusions and Relevance The findings of this systematic review and meta-regression analysis suggest that samples of RCTs of FTF vs IBT differ with regard to PRFs. These findings have implications for the generalizability of the current evidence on IBT for depression. More RCTs of internet-based interventions with clinically representative samples are needed, and the reporting of PRFs must be improved

Human contact in internet-based interventions for depression: A pre-registered replication and meta-analysis of randomized trials

Introduction Internet-based self-help interventions have shown to be effective in the treatment of depression. Several meta-analyses indicated that human contact has a crucial impact on adherence and outcome. While most research focused on the role of guidance during interventions, a review by Andersson and Johansson (2012) suggested that contact before the intervention too may play an important role. Objective We investigated the impact of the degree of contact in internet-based interventions (IBIs) for depression on outcome in adults suffering from elevated symptoms of depression. Methods We conducted a preregistered meta-analysis (www.osf.io/4mzyd) and included trials comparing IBIs for depression against control conditions (treatment as usual [TAU] or waiting list [WL]) in patients with symptoms of unipolar depression searching the databases PsycINFO and Cochrane's Central Register of Controlled Trials (CENTRAL) limited to entries from EMBASE and PubMed. Following Andersson and Johansson (2012), contact before an intervention was defined as having had a diagnostic interview before the IBI, and contact during intervention was defined as having received guidance during the IBI. IBIs were grouped as providing (0) no contact, (1) contact before the IBI, (2) contact during the IBI, or (3) contact both before and during the IBI. The primary outcome was standardized mean difference (SMD) of the IBI and control in depressive symptoms at treatment termination. Secondary outcomes were study dropout and adherence to the IBI. Results We included 56 eligible trials that randomized 13,335 patients to 75 internet-based intervention conditions and control groups (TAU in 23 trials, WL in 33 trials). In total, 44 trials (78.57 %) were judged to show some concerns or a high risk of bias. Overall heterogeneity was high regarding the primary outcome (I2s < 66 %) and even higher for secondary outcomes (I2s < 91 %). Degree of contact was a robust predictor of outcome and adherence in all pre-registered and exploratory analyses. We found the effect of the IBI to increase with higher degree of contact. However, in pair-wise contrasts, only IBIs offering both contact before and during the intervention (SMD = 0.573, 95 % CI: 0.437, 0.709) significantly outperformed interventions offering no contact (SMD = 0.224, 95 % CI: 0.090, 0.340). Conclusions The results suggest that contact before and during an intervention increases the effects of IBIs. The combination of contact before and during the intervention seems to a pivotal role regarding adherence as well as treatment outcome for patients suffering from depression

Lay Perspectives on Empathy in Patient-Physician Communication: An Online Experimental Study

Research indicates that patients consider empathy as a key factor contributing to the quality-of-care. However, ambiguities in the definition of this multidimensional construct complicate definite conclusions to-date. Addressing the challenges in the literature, and using a hypothetical physician-patient interaction which explored patient-perceived differences between expressions of affective empathy, cognitive empathy, compassion and no empathy, this study aimed to test whether lay participants' evaluations of the quality-of-care depend on the type of empathic physician behavior, and on the physician's gender. We conducted a randomized web-based experiment using a 4 (type of empathy) by 2 (physician gender) between-subjects design. Empathy was subdivided into three concepts: first, affective empathy (i.e. feeling with someone); second, cognitive empathy (i.e. understanding); and third, compassion (i.e. feeling for someone and offering support). Perceived quality-of-care was the primary outcome. Compared with non-empathic interactions, quality-of-care was rated higher when physicians reacted cognitively empathic or compassionate (d = 0.71; 0.43 to 1.00 and d = 0.68; 0.38 to 0.98). No significant difference was found between affective empathy and no empathy (d = 0.13; -0.14 to 0.42). The physician's gender was not related with quality-of-care. Aspects of participants' personality but not their age, gender or the number of physician visits were associated with quality-of-care. No interactions were observed. In showing that patients rated quality-of-care higher when physician reactions were described as cognitively empathic and compassionate, as compared with affectively empathic or non-empathic, our findings refine views about the kinds of empathy that are important in patient care with implications for clinical practice, education and communication trainings

Intensity of Treatment as Usual and Its Impact on the Effects of Face-to-Face and Internet-Based Psychotherapy for Depression: A Preregistered Meta-Analysis of Randomized Controlled Trials

Introduction: Treatment as usual (TAU) is the most frequently used control group in randomized trials of psychotherapy for depression. Concerns have been raised that the heterogeneity of treatments in TAU leads to biased estimates of psychotherapy efficacy and to an unclear difference between TAU and control groups like waiting list (WL). Objective: We investigated the impact of control group intensity (i.e., amount and degree to which elements of common depression treatments are provided) on the effects of face-to-face and internet-based psychotherapy for depression. Methods: We conducted a preregistered meta-analysis (www.osf.io/4mzyd). We included trials comparing psychotherapy with TAU or WL in patients with symptoms of unipolar depression. Six indicators were used to assess control group intensity. Primary outcome: Standardized mean difference (SMD) of psychotherapy and control in depressive symptoms at treatment termination. Results: We included 89 trials randomizing 14,474 patients to 113 psychotherapy conditions and 89 control groups (TAU in 42 trials, WL in 47 trials). Control group intensity predicted trial results in preregistered (one-sided ps < 0.042) and exploratory analyses. Psychotherapy effects were significantly smaller (one-sided p = 0.002) in trials with higher intensity TAU (SMD = 0.324, CI 0.209 to 0.439) than in trials with lower intensity TAU (SMD = 0.628, CI 0.455 to 0.801). Psychotherapy effects against lower intensity TAU did not differ from effects against WL (two-sided p = 0.663). Conclusions: Our results suggest that variation in TAU intensity impacts the outcome of trials. More scrutiny in the design of control groups for clinical trials is recommended

Speech comprehension across multiple CI processor generations: Scene dependent signal processing

Objectives In clinical practice, characterization of speech comprehension for cochlear implant (CI) patients is typically administered by a set of suprathreshold measurements in quiet and in noise. This study investigates speech comprehension of the three most recent cochlear implant sound processors; CP810, CP910, and CP1000 (Cochlear Limited). To compare sound processor performance across generations and input dynamic range changes, the state-of-the art signal processing technologies available in each sound processor were enabled. Outcomes will be assessed across a range of stimulation intensities, and finally analyzed with respect to normal hearing listeners. Methods In a prospective study, 20 experienced postlingually deafened CI patients who received a Nucleus CI in the ENT department of the University Hospital of SH in Kiel were recruited. Speech comprehension was measured in quiet at 40, 50, and 65 dBSPL with monosyllabic words as well as by speech reception threshold for two-digit numbers. In noise, speech reception thresholds were measured with the adaptive German matrix test with speech and noise in front. Results We found that high levels of open-set speech comprehension are achieved at suprathreshold presentation levels in quiet. However, results at lower test levels have remained mostly unchanged for tested sound processors with default dynamic range. Expanding the lower limit of the acoustic input dynamic range yields better speech comprehension at lower presentation levels. In noise the application of ForwardFocus improves the speech reception. Overall, a continuous improvement for speech perception across three generations of CI sound processors was found. Conclusions Findings motivate further development of signal pre-processing, an additional focus of clinical work on lower stimulation levels, and automation of ForwardFocus. Level of evidence 2

The RIPI-f (Reporting Integrity of Psychological Interventions delivered face-to-face) checklist was developed to guide reporting of treatment integrity in face-to-face psychological interventions.

Objectives: Intervention integrity is the degree to which the study intervention is delivered as intended. This article presents the RIPI-f checklist (Reporting Integrity of Psychological Interventions delivered face-to-face) and summarizes its development methods. RIPI-f proposes guidance for reporting intervention integrity in evaluative studies of face-to-face psychological interventions. Study Design and Setting: We followed established procedures for developing reporting guidelines. We examined 56 documents (reporting guidelines, bias tools, and methodological guidance) for relevant aspects of face-to-face psychological intervention integrity. Eighty four items were identified and grouped as per the template for intervention description and replication (TIDieR) domains. Twenty nine experts from psychology and medicine and other scholars rated the relevance of each item in a single-round Delphi survey.Amultidisciplinary panel of 11 experts discussed the survey results in three online consensus meetings and drafted the final version of the checklist. Results: We propose RIPI-f, a checklist with 50 items. Our checklist enhances TIDieR with important extensions, such as therapeutic alliance, provider’s allegiance, and the adherence of providers and participants. Conclusion: RIPI-f can improve the reporting of face-to-face psychological interventions. The tool can help authors, researchers, systematic reviewers, and guideline developers. We suggest using RIPI-f alongside other reporting guidelines.post-print504 K

The RIPI-f (Reporting Integrity of Psychological Interventions delivered face-to-face) checklist was developed to guide reporting of treatment integrity in face-to-face psychological interventions

Objective: Intervention integrity is the degree to which the study intervention is delivered as intended. This article presents the RIPI-f checklist (Reporting Integrity of Psychological Interventions delivered face-to-face) and summarizes its development methods. RIPI-f proposes guidance for reporting intervention integrity in evaluative studies of face-to-face psychological interventions. Study design and setting: We followed established procedures for developing reporting guidelines. We examined 56 documents (reporting guidelines, bias tools, and methodological guidance) for relevant aspects of face-to-face psychological intervention integrity. Eighty-four items were identified and grouped according to the template for intervention description and replication (TIDieR) domains. Twenty-nine experts from psychology and medicine and other scholars rated the relevance of each item in a single-round Delphi survey. A multidisciplinary panel of 11 experts discussed the survey results in three online consensus meetings and drafted the final version of the checklist. Results: We propose RIPI-f, a checklist with 50 items. Our checklist enhances TIDieR with important extensions, such as therapeutic alliance, provider's allegiance, and the adherence of providers and participants. Conclusion: RIPI-f can improve the reporting of face-to-face psychological interventions. The tool can help authors, researchers, systematic reviewers, and guideline developers. We suggest using RIPI-f alongside other reporting guidelines

Comparative efficacy of seven psychotherapeutic interventions for patients with depression: a network meta-analysis

BACKGROUND Previous meta-analyses comparing the efficacy of psychotherapeutic interventions for depression were clouded by a limited number of within-study treatment comparisons. This study used network meta-analysis, a novel methodological approach that integrates direct and indirect evidence from randomised controlled studies, to re-examine the comparative efficacy of seven psychotherapeutic interventions for adult depression. METHODS AND FINDINGS We conducted systematic literature searches in PubMed, PsycINFO, and Embase up to November 2012, and identified additional studies through earlier meta-analyses and the references of included studies. We identified 198 studies, including 15,118 adult patients with depression, and coded moderator variables. Each of the seven psychotherapeutic interventions was superior to a waitlist control condition with moderate to large effects (range d = -0.62 to d = -0.92). Relative effects of different psychotherapeutic interventions on depressive symptoms were absent to small (range d = 0.01 to d = -0.30). Interpersonal therapy was significantly more effective than supportive therapy (d = -0.30, 95% credibility interval [CrI] [-0.54 to -0.05]). Moderator analysis showed that patient characteristics had no influence on treatment effects, but identified aspects of study quality and sample size as effect modifiers. Smaller effects were found in studies of at least moderate (Δd = 0.29 [-0.01 to 0.58]; p = 0.063) and large size (Δd = 0.33 [0.08 to 0.61]; p = 0.012) and those that had adequate outcome assessment (Δd = 0.38 [-0.06 to 0.87]; p = 0.100). Stepwise restriction of analyses by sample size showed robust effects for cognitive-behavioural therapy, interpersonal therapy, and problem-solving therapy (all d>0.46) compared to waitlist. Empirical evidence from large studies was unavailable or limited for other psychotherapeutic interventions. CONCLUSIONS Overall our results are consistent with the notion that different psychotherapeutic interventions for depression have comparable benefits. However, the robustness of the evidence varies considerably between different psychotherapeutic treatments

Comparison of clinically relevant oncolytic virus platforms for enhancing T-cell therapy of solid tumors

Despite some promising results, the majority of patients do not benefit from T-cell therapies, as tumors prevent T-cells from entering the tumor, shut down their activity, or downregulate key antigens. Due to their nature and mechanism of action, oncolytic viruses have features that can help overcome many of the barriers currently facing T-cell therapies of solid tumors. This study aims to understand how four different oncolytic viruses (adenovirus, vaccinia virus, herpes simplex virus and reovirus) perform in that task. For that purpose, an immunocompetent in vivo tumor model featuring adoptive tumor-infiltrating lymphocyte (TIL) therapy was used. Tumor growth control (pPeer reviewe