In the 1950s, Eysenck suggested that psychotherapies may not be effective at all. Twenty-five years later, the first meta-analysis of randomised controlled trials showed that the effects of ...psychotherapies were considerable and that Eysenck was wrong. However, since that time methods have become available to assess biases in meta-analyses.
We examined the influence of these biases on the effects of psychotherapies for adult depression, including risk of bias, publication bias and the exclusion of waiting list control groups.
The unadjusted effect size of psychotherapies compared with control groups was g = 0.70 (limited to Western countries: g = 0.63), which corresponds to a number-needed-to-treat of 4.18. Only 23% of the studies could be considered as a low risk of bias. When adjusting for several sources of bias, the effect size across all types of therapies dropped to g = 0.31.
These results suggest that the effects of psychotherapy for depression are small, above the threshold that has been suggested as the minimal important difference in the treatment of depression, and Eysenck was probably wrong. However, this is still not certain because we could not adjust for all types of bias. Unadjusted meta-analyses of psychotherapies overestimate the effects considerably, and for several types of psychotherapy for adult depression, insufficient evidence is available that they are effective because too few low-risk studies were available, including problem-solving therapy, interpersonal psychotherapy and behavioural activation.
Objective: In the past decades, many different types of psychotherapy for adult depression have been developed. Method: In this meta-analysis we examined the effects of 15 different types of ...psychotherapy using 385 comparisons between a therapy and a control condition: Acceptance and commitment therapy, mindfulness-based cognitive behavior therapy (CBT), guided self-help using a self-help book from David Burns, Beck's CBT, the "Coping with Depression" course, two subtypes of behavioral activation, extended and brief problem-solving therapy, self-examination therapy, brief psychodynamic therapy, non-directive counseling, full and brief interpersonal psychotherapy, and life review therapy. Results: The effect sizes ranged from g = 0.38 for the "Coping with Depression" course to g = 1.10 for life review therapy. There was significant publication bias for most therapies. In 70% of the trials there was at least some risk of bias. After adjusting studies with low risk of bias for publication bias, only two types of therapy remained significant (the "Coping with Depression" course, and self-examination therapy). Conclusions: We conclude that the 15 types of psychotherapy may be effective in the treatment of depression. However, the evidence is not conclusive because of high levels of heterogeneity, publication bias, and the risk of bias in the majority of studies.
Abstract Background Internet-based interventions (IBI) are effective in treating depression. However, uptake rates in routine care are still limited. Hence, this study aimed to (1) assess the ...acceptance of IBIs in primary care patients with depressive symptoms and to (2) examine the effects of a brief acceptance facilitating intervention in the form of an informational video on patients׳ acceptance of IBIs. Methods Primary care patients ( N =128) with Minor or Major Depression were randomly assigned to an intervention (IG) or control group (CG). Patients in the IG were shown a brief informational video about IBIs before receiving a questionnaire that assessed their acceptance of IBIs and other secondary outcomes. Patients of the CG filled out the questionnaire immediately. Results Baseline acceptance of IBIs in the CG was high for 6.3%, moderate for 53.1% and low for 40.6% of patients. Acceptance of IBIs was significantly higher in the IG when compared to the CG ( d =.71, 95%–CI:.09–2.91). Except for social influence and the general attitude towards psychological treatment , all secondary outcomes were also significantly improved (e.g. effort- ( d= .40) and performance-expectancy: d =.65; knowledge about Internet interventions d= .35). Limitations Depression of the participants was only assessed using a self-report measure (PHQ-9). Conclusion Primary care patients׳ acceptance of IBIs for depressive symptoms was low but could be increased significantly using a brief acceptance facilitating intervention on the basis of an informational video. Future studies should further examine the potential of acceptance facilitating interventions for patients and health care providers to exploit the public health impact of IBIs.
Heterogeneity of major depressive disorder (MDD) illness course complicates clinical decision-making. Although efforts to use symptom profiles or biomarkers to develop clinically useful prognostic ...subtypes have had limited success, a recent report showed that machine-learning (ML) models developed from self-reports about incident episode characteristics and comorbidities among respondents with lifetime MDD in the World Health Organization World Mental Health (WMH) Surveys predicted MDD persistence, chronicity and severity with good accuracy. We report results of model validation in an independent prospective national household sample of 1056 respondents with lifetime MDD at baseline. The WMH ML models were applied to these baseline data to generate predicted outcome scores that were compared with observed scores assessed 10-12 years after baseline. ML model prediction accuracy was also compared with that of conventional logistic regression models. Area under the receiver operating characteristic curve based on ML (0.63 for high chronicity and 0.71-0.76 for the other prospective outcomes) was consistently higher than for the logistic models (0.62-0.70) despite the latter models including more predictors. A total of 34.6-38.1% of respondents with subsequent high persistence chronicity and 40.8-55.8% with the severity indicators were in the top 20% of the baseline ML-predicted risk distribution, while only 0.9% of respondents with subsequent hospitalizations and 1.5% with suicide attempts were in the lowest 20% of the ML-predicted risk distribution. These results confirm that clinically useful MDD risk-stratification models can be generated from baseline patient self-reports and that ML methods improve on conventional methods in developing such models.
Existing methods for human induced pluripotent stem cell (hiPSC) cardiac differentiation are efficient but require complex, undefined medium constituents that hinder further elucidation of the ...molecular mechanisms of cardiomyogenesis. Using hiPSCs derived under chemically defined conditions on synthetic matrices, we systematically developed an optimized cardiac differentiation strategy, using a chemically defined medium consisting of just three components: the basal medium RPMI 1640, L-ascorbic acid 2-phosphate and rice-derived recombinant human albumin. Along with small molecule-based induction of differentiation, this protocol produced contractile sheets of up to 95% TNNT2(+) cardiomyocytes at a yield of up to 100 cardiomyocytes for every input pluripotent cell and was effective in 11 hiPSC lines tested. This chemically defined platform for cardiac specification of hiPSCs will allow the elucidation of cardiomyocyte macromolecular and metabolic requirements and will provide a minimal system for the study of maturation and subtype specification.
A large field experiment of the Saharan Mineral Dust Experiment (SAMUM) was performed in Praia, Cape Verde, in January and February 2008. The aerosol at Praia is a superposition of mineral dust, ...sea-salt, sulphates and soot. Particles smaller than 500 nm are mainly mineral dust, mineral dust-sulphate mixtures, sulphates and soot-sulphate mixtures. Particles larger then 2.5μm consist of mineral dust, sea-salt and few mineral dust-sulphate mixtures. A transition range exists in between. The major internal mixtures are mineral dust-sulphate and soot-sulphate. Mineral dust-sea-salt mixtures occur occasionally, mineral dust-soot mixtures were not observed. The aspect ratio was 1.3-1.4 for dry particles smaller than 500 nm and 1.6-1.7 for larger ones. Parameterizations are given for dry and humid state. Although the real part of the refractive index showed low variation (1.55-1.58 at 532 nm), a multi-modal imaginary part was detected as function of particle size, reflecting the complex composition. Soot mainly influences the absorption for wavelengths longer than the haematite absorption edge, whereas for shorter wavelengths dust is dominating. The refractive index of the aerosol depends on the source region of the mineral dust and on the presence/absence of a marine component.
The masses of the ground, orbitally and radially excited states of heavy-light mesons are calculated within the framework of the QCD-motivated relativistic quark model based on the quasipotential ...approach. Both light (
q
=
u
,
d
,
s
) and heavy (
Q
=
c
,
b
) quarks are treated fully relativistically without application of the heavy-quark 1/
m
Q
expansion. The Regge trajectories in the (
M
2
,
J
) and (
M
2
,
n
r
) planes are investigated and their parameters are obtained. The results are in good agreement with available experimental data except for the masses of the anomalous
,
D
s
1
(2460) and
states.
Abstract Background Brugada syndrome (BrS), a disorder associated with characteristic electrocardiogram precordial ST-segment elevation, predisposes afflicted patients to ventricular fibrillation and ...sudden cardiac death. Despite marked achievements in outlining the organ level pathophysiology of the disorder, the understanding of human cellular phenotype has lagged due to a lack of adequate human cellular models of the disorder. Objectives The objective of this study was to examine single cell mechanism of Brugada syndrome using induced pluripotent stem cell–derived cardiomyocytes (iPSC-CMs). Methods This study recruited 2 patients with type 1 BrS carrying 2 different sodium voltage-gated channel alpha subunit 5 variants as well as 2 healthy control subjects. We generated iPSCs from their skin fibroblasts by using integration-free Sendai virus. We used directed differentiation to create purified populations of iPSC-CMs. Results BrS iPSC-CMs showed reductions in inward sodium current density and reduced maximal upstroke velocity of action potential compared with healthy control iPSC-CMs. Furthermore, BrS iPSC-CMs demonstrated increased burden of triggered activity, abnormal calcium (Ca2+ ) transients, and beating interval variation. Correction of the causative variant by genome editing was performed, and resultant iPSC-CMs showed resolution of triggered activity and abnormal Ca2+ transients. Gene expression profiling of iPSC-CMs showed clustering of BrS compared with control subjects. Furthermore, BrS iPSC-CM gene expression correlated with gene expression from BrS human cardiac tissue gene expression. Conclusions Patient-specific iPSC-CMs were able to recapitulate single-cell phenotype features of BrS, including blunted inward sodium current, increased triggered activity, and abnormal Ca2+ handling. This novel human cellular model creates future opportunities to further elucidate the cellular disease mechanism and identify novel therapeutic targets.
Familial hypertrophic cardiomyopathy (HCM) is a prevalent hereditary cardiac disorder linked to arrhythmia and sudden cardiac death. While the causes of HCM have been identified as genetic mutations ...in the cardiac sarcomere, the pathways by which sarcomeric mutations engender myocyte hypertrophy and electrophysiological abnormalities are not understood. To elucidate the mechanisms underlying HCM development, we generated patient-specific induced pluripotent stem cell cardiomyocytes (iPSC-CMs) from a ten-member family cohort carrying a hereditary HCM missense mutation (Arg663His) in the MYH7 gene. Diseased iPSC-CMs recapitulated numerous aspects of the HCM phenotype including cellular enlargement and contractile arrhythmia at the single-cell level. Calcium (Ca2+) imaging indicated dysregulation of Ca2+ cycling and elevation in intracellular Ca2+ (Ca2+i) are central mechanisms for disease pathogenesis. Pharmacological restoration of Ca2+ homeostasis prevented development of hypertrophy and electrophysiological irregularities. We anticipate that these findings will help elucidate the mechanisms underlying HCM development and identify novel therapies for the disease.
► Patient-specific iPSC-CMs recapitulate the HCM phenotype at the single-cell level ► iPSC-CMs with the HCM Arg663His mutation have irregular Ca2+ handling properties ► Elevation in Ca2+i induces both hypertrophy and arrhythmia in iPSC-CMs ► Pharmacological treatment of Ca2+ imbalance prevents HCM phenotype development
Modeling of familial hypertrophic cardiomyopathy using human iPSCs highlights a role for Ca2+ dysregulation in disease pathology.
PDF
