Computational Modelling of Water Transport in Hydrocolloid Wound Dressing, DuoDERMⓇ CGF, and Design Recommendations

Hydrocolloids, and further hydrogels, have arisen as attractive next-generation wound dressings because of their modularity and ability to retain moisture. Hydrocolloids, like DuoDERM Ⓡ CGF, are intended for partial and full thickness wounds. They may be used for minor burns, cuts, tears, abrasions, as well as lacerations, ulcers, and some traumatic or surgical wounds. A computational simulation of water transport in wounds with hydrocolloid dressings was implemented in order to understand the mechanisms of hydrocolloid wound dressings as they relate to water transport. The ideal dressing will maintain the wounded tissue at physiological water content levels while also retaining moisture within the dressing itself to promote re-epithelialization of tissue. This study aims to determine the effectiveness of current wound dressings with respect to retaining moisture and maintaining the skin at physiological levels of water content. This study further seeks to optimize current wound dressing design parameters in order to improve water retention above the wound bed and maintenance of physiological skin water content. To study the transfer of liquid water in skin and an example hydrocolloid wound dressing, a computational model was built in COMSOL Multiphysics Ⓡ Modeling Software using a multifrontal direct solver (MUMPS). This model primarily detailed water transport processes in the skin (stratum corneum, epidermis, and dermis) with an example hydrocolloid dressing DuoDERM Ⓡ CGF (hydrocolloid and polymeric barrier layer). The use of the model can be extended to larger or smaller wound areas as well as different types of hydrocolloid dressings. The parameters of the materials can be easily altered to fit new materials being simulated, however the model is only valid up to the time right before the hydrocolloid would start to degrade. The model considered the skin layers, wound surface, hydrocolloid, and polymeric barrier layer to be a 2D, axisymmetric cylinder. Water (mass) transport was considered diffusion in porous media in the skin and diffusion in the hydrocolloid and polymeric layers. The swelling effect, typical of hydrocolloids, was modeled using deforming geometry. After validating the model, an objective function was created in order to quantify the performance of the model based on its ability to maintain physiological water content in the skin as well as its ability to retain moisture in the hydrocolloid domain above the wound bed. Using this objective function, the material properties of the hydrocolloid dressing were altered in order to obtain an optimal solution, where the dressing would maintain an ideally moist environment. The results confirmed that the hydrocolloid wound dressing retains moisture but does not satisfactorily maintain wounded tissue near physiological levels of water content. The optimization suggested the variation of two hydrocolloid parameters, the diffusivity and the partitioning coefficient between the skin and hydrocolloid, in order to improve its performance. Lowering the diffusivity of the hydrocolloid resulted in a higher water concentration above the wound bed. Decreasing the partition coefficient (an effect observed by increasing the hydrophobicity of the hydrocolloid) reduced the flux of water from the wound to the dressing. The combined effect of a reduced diffusivity and partition coefficient allowed greater regions of the wound to retain physiological water content levels and improved water retention near the wound bed. These results will inform the design of future generations of wound dressings and elucidate difficulties in the use of hydrophilic wound dressings like hydrocolloids and hydrogels

Identification of intraneuronal amyloid beta oligomers in locus coeruleus neurons of Alzheimer's patients and their potential impact on inhibitory neurotransmitter receptors and neuronal excitability

The author's final peer reviewed version can be found by following the URI link. The Publisher's final version can be found by following the DOI link.Aims Amyloid β oligomers (AβO) are potent modulators of Alzheimer’s pathology, yet their impact on one of the earliest brain regions to exhibit signs of the condition, the locus coeruleus (LC), remains to be determined. Of particular importance is whether AβO impact the spontaneous excitability of LC neurons. This parameter determines brain‐wide noradrenaline (NA) release, and thus NA‐mediated brain functions, including cognition, emotion and immune function, which are all compromised in Alzheimer’s. Therefore, the aim of the study was to determine the expression profile of AβO in the LC of Alzheimer’s patients and to probe their potential impact on the molecular and functional correlates of LC excitability, using a mouse model of increased Aβ production (APP‐PSEN1). Methods and Results Immunohistochemistry and confocal microscopy, using AβO‐specific antibodies, confirmed LC AβO expression both intraneuronally and extracellularly in both Alzheimer’s and APP‐PSEN1 samples. Patch clamp electrophysiology recordings revealed that APP‐PSEN1 LC neuronal hyperexcitability accompanied this AβO expression profile, arising from a diminished inhibitory effect of GABA, due to impaired expression and function of the GABA‐A receptor (GABAAR) α3 subunit. This altered LC α3‐GABAAR expression profile overlapped with AβO expression in samples from both APP‐PSEN1 mice and Alzheimer’s patients. Finally, strychnine‐sensitive glycine receptors (GlyRs) remained resilient to Aβ‐induced changes and their activation reversed LC hyperexcitability. Conclusions The data suggest a close association between AβO and α3‐GABAARs in the LC of Alzheimer’s patients, and their potential to dysregulate LC activity, thereby contributing to the spectrum of pathology of the LC‐NA system in this condition

Paradigmatic Approach to Support Personalized Counseling With Digital Health (iKNOW)

iKNOW is the first evidence-based digital tool to support personalized counseling for women in Germany with a hereditary cancer risk. The counseling tool is designed for carriers of pathogenic gBRCA (germline breast cancer gene) variants that increase the lifetime risk of breast and ovarian cancer. Carriers of pathogenic variants are confronted with complex, individualized risk information, and physicians must be able to convey this information in a comprehensible way to enable preference-sensitive health decisions. In this paper, we elaborate on the clinical, regulatory, and practical premises of personalized counseling in Germany. By operationalizing these premises, we formulate 5 design principles that, we suggest, are specific enough to develop a digital tool (eg, iKNOW), yet wide-ranging enough to inform the development of counseling tools for personalized medicine more generally: (1) digital counseling tools should implement the current standard of care (eg, based on guidelines); (2) digital counseling tools should help to both standardize and personalize the counseling process (eg, by enabling the preference-sensitive selection of counseling contents from a common information base); (3) digital counseling tools should make complex information easy to access both cognitively (eg, by using evidenced-based risk communication formats) and technically (eg, by means of responsive design for various devices); (4) digital counseling tools should respect the counselee's data privacy rights (eg, through strict pseudonymization and opt-in consent); and (5) digital counseling tools should be systematically and iteratively evaluated with the users in mind (eg, using formative prototype testing to ensure a user-centric design and a summative multicenter, randomized controlled trial). On the basis of these paradigmatic design principles, we hope that iKNOW can serve as a blueprint for the development of more digital innovations to support personalized counseling approaches in cancer medicine

Is self-guided internet-based cognitive behavioural therapy (iCBT) harmful? : An individual participant data meta-analysis

BACKGROUND: Little is known about potential harmful effects as a consequence of self-guided internet-based cognitive behaviour therapy (iCBT), such as symptom deterioration rates. Thus, safety concerns remain and hamper the implementation of self-guided iCBT into clinical practice. We aimed to conduct an individual participant data (IPD) meta-analysis to determine the prevalence of clinically significant deterioration (symptom worsening) in adults with depressive symptoms who received self-guided iCBT compared with control conditions. Several socio-demographic, clinical and study-level variables were tested as potential moderators of deterioration. METHODS: Randomised controlled trials that reported results of self-guided iCBT compared with control conditions in adults with symptoms of depression were selected. Mixed effects models with participants nested within studies were used to examine possible clinically significant deterioration rates. RESULTS: Thirteen out of 16 eligible trials were included in the present IPD meta-analysis. Of the 3805 participants analysed, 7.2% showed clinically significant deterioration (5.8% and 9.1% of participants in the intervention and control groups, respectively). Participants in self-guided iCBT were less likely to deteriorate (OR 0.62, p < 0.001) compared with control conditions. None of the examined participant- and study-level moderators were significantly associated with deterioration rates. CONCLUSIONS: Self-guided iCBT has a lower rate of negative outcomes on symptoms than control conditions and could be a first step treatment approach for adult depression as well as an alternative to watchful waiting in general practice

Health economic evaluation of a web-based intervention for depression: the EVIDENT-trial, a randomized controlled study.

Gräfe V, Berger T, Hautzinger M, et al. Health economic evaluation of a web-based intervention for depression: the EVIDENT-trial, a randomized controlled study. Health economics review. 2019;9(1): 16.BACKGROUND: Depression often remains undiagnosed or treated inadequately. Web-based interventions for depression may improve accessibility of treatment and reduce disease-related costs. This study aimed to examine the potential of the web-based cognitive behavioral intervention "deprexis" in reducing disease-related costs.; METHODS: Participants with mild to moderate depressive symptoms were recruited and randomized to either a 12-week web-based intervention (deprexis) in addition to care as usual (intervention group) or care as usual (control group). Outcome measures were health-related resource use, use of medication and incapacity to work as well as relating direct health care costs. Outcomes were assessed on patients' self-report at baseline, three months and six months.; RESULTS: A total of 1013 participants were randomized. In both groups total direct health care costs decreased during the study period, but changes from baseline did not significantly differ between study groups. Numeric differences between study groups existed in outpatient treatment costs. They could be attributed to differences in changes of costs for psychotherapeutic treatment from baseline. Whereas costs for psychotherapeutic treatment decreased in the intervention group, costs increased in the control group (-16.8% (80) vs. +14.7% (60)) (tdf=685=2.57; p=0.008).; CONCLUSION: The study indicates the health economic potential of innovative e-mental-health programs. There is evidence to suggest that the use of deprexis over a period of 12weeks leads to a decrease in outpatient treatment cost, especially in those related to different types of psychotherapeutic treatment

Efficacy of Self-guided Internet-Based Cognitive Behavioral Therapy in the Treatment of Depressive Symptoms : A Meta-analysis of Individual Participant Data

IMPORTANCE Self-guided internet-based cognitive behavioral therapy (iCBT) has the potential to increase access and availability of evidence-based therapy and reduce the cost of depression treatment. OBJECTIVES To estimate the effect of self-guided iCBT in treating adults with depressive symptoms compared with controls and evaluate the moderating effects of treatment outcome and response. DATA SOURCES A total of 13 384 abstracts were retrieved through a systematic literature search in PubMed, Embase, PsycINFO, and Cochrane Library from database inception to January 1, 2016. STUDY SELECTION Randomized clinical trials in which self-guided iCBT was compared with a control (usual care, waiting list, or attention control) in individuals with symptoms of depression. DATA EXTRACTION AND SYNTHESIS Primary authors provided individual participant data from 3876 participants from 13 of 16 eligible studies. Missing data were handled using multiple imputations. Mixed-effects models with participants nested within studies were used to examine treatment outcomes and moderators. MAIN OUTCOMES AND MEASURES Outcomes included the Beck Depression Inventory, Center for Epidemiological Studies-Depression Scale, and 9-item Patient Health Questionnaire scores. Scales were standardized across the pool of the included studies. RESULTS Of the 3876 study participants, the mean (SD) age was 42.0 (11.7) years, 2531 (66.0%) of 3832 were female, 1368 (53.1%) of 2574 completed secondary education, and 2262 (71.9%) of 3146 were employed. Self-guided iCBT was significantly more effective than controls on depressive symptoms severity (ß =-0.21; Hedges g = 0.27) and treatment response (ß = 0.53; odds ratio, 1.95; 95% CI, 1.52-2.50; number needed to treat, 8). Adherence to treatment was associated with lower depressive symptoms (ß =-0.19; P =.001) and greater response to treatment (ß = 0.90; P <.001). None of the examined participant and study-level variables moderated treatment outcomes. CONCLUSIONS AND RELEVANCE Self-guided iCBT is effective in treating depressive symptoms. The use of meta-analyses of individual participant data provides substantial evidence for clinical and policy decision making because self-guided iCBT can be considered as an evidence-based first-step approach in treating symptoms of depression. Several limitations of the iCBT should be addressed before it can be disseminated into routine care