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Background: Internet cognitive behavioural therapy (iCBT) is a viable delivery format of CBT for depression. However, iCBT programmes include training in a wide array of cognitive and behavioural skills via different delivery methods, and it remains unclear which of these components are more efficacious and for whom., Methods: We did a systematic review and individual participant data component network meta-analysis (cNMA) of iCBT trials for depression. We searched PubMed, PsycINFO, Embase, and the Cochrane Library for randomised controlled trials (RCTs) published from database inception to Jan 1, 2019, that compared any form of iCBT against another or a control condition in the acute treatment of adults (aged ≥18 years) with depression. Studies with inpatients or patients with bipolar depression were excluded. We sought individual participant data from the original authors. When these data were unavailable, we used aggregate data. Two independent researchers identified the included components. The primary outcome was depression severity, expressed as incremental mean difference (iMD) in the Patient Health Questionnaire-9 (PHQ-9) scores when a component is added to a treatment. We developed a web app that estimates relative efficacies between any two combinations of components, given baseline patient characteristics. This study is registered in PROSPERO, CRD42018104683., Findings: We identified 76 RCTs, including 48 trials contributing individual participant data (11 704 participants) and 28 trials with aggregate data (6474 participants). The participants' weighted mean age was 42·0 years and 12 406 (71%) of 17 521 reported were women. There was suggestive evidence that behavioural activation might be beneficial (iMD -1·83 [95% credible interval (CrI) -2·90 to -0·80]) and that relaxation might be harmful (1·20 [95% CrI 0·17 to 2·27]). Baseline severity emerged as the strongest prognostic factor for endpoint depression. Combining human and automated encouragement reduced dropouts from treatment (incremental odds ratio, 0·32 [95% CrI 0·13 to 0·93]). The risk of bias was low for the randomisation process, missing outcome data, or selection of reported results in most of the included studies, uncertain for deviation from intended interventions, and high for measurement of outcomes. There was moderate to high heterogeneity among the studies and their components., Interpretation: The individual patient data cNMA revealed potentially helpful, less helpful, or harmful components and delivery formats for iCBT packages. iCBT packages aiming to be effective and efficient might choose to include beneficial components and exclude ones that are potentially detrimental. Our web app can facilitate shared decision making by therapist and patient in choosing their preferred iCBT package., Funding: Japan Society for the Promotion of Science., Competing Interests: Declaration of interests TAF reports grants from Japan Society for Promotion of Science, during the conduct of the study; grants and personal fees from Mitsubishi-Tanabe, personal fees from MSD, grants and personal fees from Shionogi, outside the submitted work; a patent 2018-177688 concerning smartphone CBT apps pending; and an intellectual properties for Kokoro-app licensed to Tanabe-Mitsubishi. AC reports personal fees from Italian Network for Paediatric Trials and CARIPLO Foundation; and grants and personal fees from Angelini Pharma, outside the submitted work. EGO reports personal fees from Angelini Pharma, outside the submitted work. PCa reports personal fees from Osmond Foundation and Sandoz, outside the submitted work. JD is co-owner of Behavioral Activation Tech LLC, a small business that develops and evaluates mobile app-based treatments for depression and co-occurring disorders. DDE has served as a consultant to or on the scientific advisory boards of Sanofi, Novartis, Minddistrict, Lantern, Schoen Kliniken, Ideamed, German health insurance companies (BARMER, Techniker Krankenkasse), and a number of federal chambers for psychotherapy; is a stakeholder of the Institute for health training online (GET.ON), which aims to implement scientific findings related to digital health interventions into routine care. NRF is an employee of AbleTo. JPK reports grants and personal fees from Servier; personal fees from Beltz, Elsevier, Hogrefe, and Springer, outside the submitted work; funding for clinical trials (German Federal Ministry of Health and Servier); payments for presentations on internet interventions (Servier); and payments for workshops and books (Beltz, Elsevier, Hogrefe, and Springer) on psychotherapy for chronic depression and on psychiatric emergencies. BM is an employee of GAIA AG. DCM reports personal fees from Apple, Pear Therapeutics, and Otsuka Pharmaceuticals and has an equity interest in Adaptive Health, outside the submitted work. JMM is supported by a Wellcome Trust Grant (104908/Z/14/Z). SN is an employee of GET.ON Institut. DR is an employee of SilverCloud Health. LBS is an employee of Influents Innovations. PZ reports grants and non-financial support from Techniker Krankenkasse (German public health insurance company), outside the submitted work. CK reports personal fees from Oberbergklinik and Servier; and grants and non-financial support from Techniker Krankenkasse, outside the submitted work. MH reports grants and non-financial support from Techniker Krankenkasse, outside the submitted work. All other authors declare no competing interests., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Dedicated units for the care of acute coronary syndrome (ACS) have been submitted to economic evaluations; however, the results have not been systematically presented., Objective: To identify and summarize economic outcomes of studies on hospital units dedicated to the initial care of patients with suspected or confirmed ACS., Methods: A systematic review of literature to identify economic evaluations of chest pain unit (CPU), coronary care unit (CCU), or equivalent units was done. Two search strategies were used: the first one to identify economic evaluations irrespective of study design, and the second one to identify randomized clinical trials that reported economic outcomes. The following databases were searched: MEDLINE, EMBASE, CENTRAL, and National Health Service (NHS)Economic Evaluation Database. Data extraction was performed by two independent reviewers. Costs were inflated to 2012 values., Results: Search strategies retrieved five partial economic evaluations based on observational studies, six randomized clinical trials that reported economic outcomes, and five model-based economic evaluations. Overall, cost estimates based on observational studies and randomized clinical trials reported statistically significant cost savings of more than 50% with the adoption of CPU care instead of routine hospitalization or CCU care for suspected low-to-intermediate risk patients with ACS (median per-patient cost US $1,969.89; range US $1,002.12-13,799.15). Model-based economic evaluations reported incremental cost-effectiveness ratios below US $ 50,000/quality-adjusted life-year for all comparisons between intermediate care unit, CPU, or CCU with routine hospital admissions. This finding was sensible to myocardial infarction probability., Conclusions: Published economic evaluations indicate that more intensive care is likely to be cost-effective in comparison to routine hospital admission for patients with suspected ACS., (Copyright © 2016. Published by Elsevier Inc.)

Protocols were defined that enable patch-clamp studies of the approximately 107 pS voltage dependent channel and a class of activity we refer to as MCC (multiconductance channel) which is characterized by multiple levels and transitions as high as 1 to 1.5 nS. If free calcium was kept at 10(-7) M or lower during mitochondrial isolation, no activity was observed at low voltage (+/- 60 mV). If free calcium levels were higher, MCC activity was observed in about 96% of the patches. The observation of approximately 107 pS channel was enhanced from 2% to 68% of patches by washing isolated mitoplasts (mitochondria stripped of outer membrane) with EGTA. Increasing matrix calcium from 10(-9) to 10(-5) M decreased the probability of opening for the MCC and approximately 107 pS activities.

It has been previously demonstrated that spontaneously hypertensive adult rats (SHR) develop severe hypertension and cerebrovascular lesions on drinking 1% NaCl from weaning and that the phospholipid metabolism in the whole brain is actively altered in these lesioned animals (SHR-NaCl) as compared to SHRs which drink only water and show only sporadic cerebrovascular lesions. We have now assayed the incorporation of labelled choline, ethanolamine, glycerol and arachidonic acid into the phospholipids from the cortex and hippocampus of SHR-water and SHR-NaCl at different time intervals from injection into the lateral ventricle of the brain. A noticeable decrease of both choline and arachidonate specific activity (SA) in the phospholipids was found in the cortex and hippocampus (where the effect is most evident) from SHR-NaCl. Based on the literature and the data obtained, we suggest that in SHR-NaCl brain areas a release of choline and fatty acid also occurs from choline glycerophospholipids as a consequence of the cerebrovascular lesions caused by NaCl treatment. Even if a relatively minor loss of the amount of the lipids studied is evident from our results as compared to their entire pool, this change may be quite important if it causes a modification of the lipidic bilayer in excitable membranes. In a parallel group of SHR-NaCl animals, treated with the nootropic drug oxiracetam, we observed that the metabolic utilization of the precursors was completely restored. These experimental data favour the hypothesis that oxiracetam is effective in stimulating the phospholipid metabolism rate at levels even higher than those of the SHR-water animals.