Selim Cellek

Background: Previous research has shown that mobile health (mHealth) interventions are effective in reminding older adults with chronic conditions about health care appointments and promoting adherence to medication schedules. However, the evidence is limited by the short duration and poor quality of the interventions. Objective: We evaluated the effectiveness of the Support, Monitoring and Reminder Technology for Mild Dementia (SMART4MD) tablet app in improving the quality of life (QoL) of people with mild cognitive impairment (PwMCI) and their caregivers through medication reminders and health care appointment alerts. Methods: An 18-month pragmatic randomized controlled trial was conducted in Spain and Sweden from December 2017 to September 2020 and included 1078 PwMCI and their informal caregivers. Results: For PwMCI, the intervention improved the primary outcome, composite Quality of Life in Alzheimer’s Disease (QoL-AD) scale, at 18 months (mean difference 0.75, 95% CI 0.07-1.42; P=.03), and a similar effect was observed at 6 months (mean difference 0.73, 95% CI 0.09-1.36; P=.02). Confirmatory secondary outcomes for PwMCI, including medication adherence (P=.12) and Mini-Mental State Examination (MMSE) score (P=.45), did not differ significantly between groups at the 18-month follow-up. Exploratory analyses showed higher total accumulated quality-adjusted life years (QALYs) at 6 months for PwMCI (mean difference 0.035, 95% CI 0.02-0.05; nominal P<.001), informal caregivers (mean difference 0.050, 95% CI 0.04-0.07; nominal P<.001), and dyads (mean difference 0.085, 95% CI 0.06-0.11; nominal P<.001). A dropout rate of approximately 40% (429/1083, 39.61%) was observed in both the intervention and control groups. Conclusions: The SMART4MD intervention was associated with a modest improvement in PwMCI’s QoL as measured by the composite QoL-AD score. Evidence for benefits among informal caregivers and dyads was less consistent and should be interpreted as exploratory. Nominally significant findings for exploratory outcomes should be interpreted with caution, as they were not adjusted for multiplicity. Trial Registration: ClinicalTrials.gov NCT03325699; https://clinicaltrials.gov/ct2/show/NCT03325699 International Registered Report Identifier (IRRID): RR2-10.2196/13711

Background: Support, Monitoring, and Reminder Technology for Mild Dementia (SMART4MD), a customized tablet app, was developed to improve or maintain the quality of life of people with mild cognitive impairment (MCI) and their informal caregivers. Objective: This study conducts an 18-month economic evaluation of the SMART4MD app, in addition to standard care, compared with standard care alone in Sweden and Spain, from a health care provider perspective. Methods: In a pragmatic randomized controlled trial, people with MCI and their informal caregivers were randomized to the intervention and control groups. Health care costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs) were measured in 345 Swedish people with MCI and their informal caregivers, and in 347 Spanish people with MCI. Results: The analysis showed higher incremental costs and lower QALYs for Swedish people with MCI than for controls, whereas higher incremental costs and higher QALYs were observed for Spanish people with MCI. The intervention was not found to be cost-effective for Swedish informal caregivers, with an ICER of €78,000/QALY (€1=US $1.16). Conclusions: The differing findings regarding cost-effectiveness for people with MCI in Sweden and Spain highlight the need for further research with extended follow-up, ideally involving a larger sample size and conducted across different national contexts. Trial Registration: ClinicalTrials.gov NCT03325699; https://clinicaltrials.gov/ct2/show/NCT03325699

Background: Although workshops facilitated by a sexual health professional and a priest to support gay Christian men who struggle with accepting their sexuality and religious identity have been organized, the experience of attending such workshops has not been studied. Aim: To understand the experience of gay Christian men who attended collaborative workshops. Methods: Six collaborative workshops were conducted between a sexual health clinic and a church in central London from January to September 2018. Purposive sampling was used to recruit 11 gay Christian men who participated in the workshops. Data on their experiences were collected through semistructured interviews, images, and the innovative method of haiku poetry, which was used to reflect on their experiences during and after the workshops. All the data were analyzed using thematic analysis. Outcome: Gaining insights into the experiences of gay Christian men who participated in collaborative workshops. Results: The collaborative workshops had a significant impact on gay Christian men in two key areas: self-perception and relationships. The contributing factors to this influence were either environmental or personal. Three themes emerged: motivation, self-development, and the influence of the environment. Some participants embraced the workshops, while others experienced a sense of urgency. The workshops were experienced as fostering their self-growth. In contrast, others were reminded of their destructive behaviors, which left them feeling hopeless. For some participants, the workshop’s environment highlighted their minority status as a strength, whereas for others, it highlighted their loneliness. Clinical Implication: This study showed the importance of understanding motivation for attending the collaborative workshops. Strengths and Limitations: Although the findings cannot be generalized to all religious and sexual minorities, they can inform future collaborations. Although a small sample was recruited, it provided an in-depth understanding of the experiences of these men. Limited funding restricted the workshops’ accessibility to hard-to-reach communities. The data were analyzed from a psychological perspective. Conclusion: This study introduces a novel model for integrating religion and sexuality. It adapts Maslow’s hierarchy of needs for gay Christian men to include freedom from shame as an essential requirement, subsequently fostering belongingness, connection, and love.

Background: Peyronie’s disease (PD) is defined as a fibrotic disease of the penis resulting in plaque formation and abnormal penile curvature. The incidence of PD has been suggested to increase after radical prostatectomy (RP). Hypoxia in the corpus cavernosum secondary to nerve injury has been suggested to be one of the causative factors for development of erectile dysfunction following RP. It is also known that hypoxia can cause fibrosis in vitro and in animal models. We therefore hypothesized that men who develop PD after RP do so due to hypoxia. Aim: To investigate if hypoxia and fibrotic changes can be detected in men undergoing RP. Methods: Erectile function and PD were assessed before, 3 and 6 months after RP using International Index of Erectile Function (IIEF) and PD questionnaires, stretched penile length and nocturnal penile tumescence. Fibrosis was investigated by ultrasonography (USG) and tissue oxygen levels were measured using oximetry. Outcomes: The primary outcome was a significant decrease in flaccid penile oxygen levels in men as measured before and after RP. Results: All 24 men completing the study developed fibrotic changes and calcification confirmed by USG and showed significant decrease in penile oxygen levels after RP. The patients’ IIEF scores and Peyronie’s disease questionnaire also showed a significant decrease in erectile function without any patient-reported curvatures. Stretched penile length was also reduced significantly. There was a significant correlation between calcification and oxygen levels between post-op 3 months and 6 months. Clinical Implications: RP can cause penile fibrosis which may be due RP-associated hypoxia in the penis. Prostate surgeons should consider discussing this risk with their patients before the operation. Strengths and Limitations: USG and oximetry readings before and after the RP allowed us to observe the effect of the surgery within individual patients. A larger study with a longer follow up would be needed to confirm these findings and to investigate a correlation between plaque formation and oxygen levels. Conclusion: In this study, all the patients developed fibrotic changes, calcification and a decrease in penile oxygen levels following RP. This is the first demonstration of a significant decrease in penile oxygen levels following RP. A correlation between calcification and low oxygen levels suggests that hypoxia-induced fibrosis may be the cause of calcification during the progression of PD.

BACKGROUND Previous research has shown that mobile health (mHealth) interventions are effective in reminding older adults with chronic conditions about health care appointments and promoting adherence to medication schedules. However, the evidence is limited by the short duration and poor quality of the interventions. OBJECTIVE We evaluated the effectiveness of the Support, Monitoring and Reminder Technology for Mild Dementia (SMART4MD) tablet app in improving the quality of life (QoL) of people with mild cognitive impairment (PwMCI) and their caregivers through medication reminders and health care appointment alerts. METHODS An 18-month pragmatic randomized controlled trial was conducted in Spain and Sweden from December 2017 to September 2020 and included 1078 PwMCI and their informal caregivers. RESULTS For PwMCI, the intervention improved the primary outcome, composite Quality of Life in Alzheimer’s Disease (QoL-AD) scale, at 18 months (mean difference 0.75, 95% CI 0.07-1.42; P=.03), and a similar effect was observed at 6 months (mean difference 0.73, 95% CI 0.09-1.36; P=.02). Confirmatory secondary outcomes for PwMCI, including medication adherence (P=.12) and Mini-Mental State Examination (MMSE) score (P=.45), did not differ significantly between groups at the 18-month follow-up. Exploratory analyses showed higher total accumulated quality-adjusted life years (QALYs) at 6 months for PwMCI (mean difference 0.035, 95% CI 0.02-0.05; nominal P<.001), informal caregivers (mean difference 0.050, 95% CI 0.04-0.07; nominal P<.001), and dyads (mean difference 0.085, 95% CI 0.06-0.11; nominal P<.001). A dropout rate of approximately 40% (429/1083, 39.61%) was observed in both the intervention and control groups. CONCLUSIONS The SMART4MD intervention was associated with a modest improvement in PwMCI’s QoL as measured by the composite QoL-AD score. Evidence for benefits among informal caregivers and dyads was less consistent and should be interpreted as exploratory. Nominally significant findings for exploratory outcomes should be interpreted with caution, as they were not adjusted for multiplicity. CLINICALTRIAL ClinicalTrials.gov NCT03325699; https://clinicaltrials.gov/ct2/show/NCT03325699 INTERNATIONAL REGISTERED REPORT RR2-10.2196/13711

BACKGROUND Support, Monitoring, and Reminder Technology for Mild Dementia (SMART4MD), a customized tablet app, was developed to improve or maintain the quality of life of people with mild cognitive impairment (MCI) and their informal caregivers. OBJECTIVE This study conducts an 18-month economic evaluation of the SMART4MD app, in addition to standard care, compared with standard care alone in Sweden and Spain, from a health care provider perspective. METHODS In a pragmatic randomized controlled trial, people with MCI and their informal caregivers were randomized to the intervention and control groups. Health care costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs) were measured in 345 Swedish people with MCI and their informal caregivers, and in 347 Spanish people with MCI. RESULTS The analysis showed higher incremental costs and lower QALYs for Swedish people with MCI than for controls, whereas higher incremental costs and higher QALYs were observed for Spanish people with MCI. The intervention was not found to be cost-effective for Swedish informal caregivers, with an ICER of €78,000/QALY (€1=US $1.16). CONCLUSIONS The differing findings regarding cost-effectiveness for people with MCI in Sweden and Spain highlight the need for further research with extended follow-up, ideally involving a larger sample size and conducted across different national contexts. CLINICALTRIAL ClinicalTrials.gov NCT03325699; https://clinicaltrials.gov/ct2/show/NCT03325699

Background: In cancer metastasis, tumor cells condition distant tissues to create a supportive environment, or metastatic niche, by driving the activation of cancer-associated fibroblasts (CAFs). These CAFs remodel the extracellular matrix, creating a microenvironment that supports tumor growth and compromises immune cell function, enabling cancer cells to evade immune detection. Consequently, targeting the activation of CAFs has been proposed as a therapeutic strategy to hinder metastatic spread. Our objective was to develop the first in vitro phenotypic screening assay capable of assessing this activation process.Methods: Human primary lung fibroblasts were co-cultured with highly invasive breast cancer cells (MDA-MB-231) to identify changes in the expression of selected genes using RT-qPCR. An In-Cell ELISA (ICE)-based assay using human lung fibroblasts, MDA-MB-231 cells and human monocytes (THP-1 cells) was developed to measure the activation of CAFs. Another ELISA assay was used to measure released osteopontin.Results: When lung fibroblast were co-cultured with MDA-MB-231 cells, among the 10 selected genes, the genes for osteopontin (SPP1), insulin like growth factor 1 (IGF1), periostin (POSTN) and α-smooth muscle actin (α-SMA, ACTA2) elicited the greatest fold change (55-, 37-, 8- and 5-fold respectively). Since osteopontin, IGF-1 and periostin are secreted proteins and α-SMA is an intracellular cytoskeleton protein, α-SMA was chosen to be the readout biomarker for the ICE assay. When fibroblasts were co-cultured with MDA-MB-231 cells and monocytes in the 96 well ICE assay, α-SMA expression was increased 2.3-fold yielding a robust Z′ of 0.56. A secondary, low throughput assay was developed by measuring the release of osteopontin which showed a 6-fold increase when fibroblasts were co-cultured with MDA-MB-231 cells and monocytes.Discussion: This phenotypic assay is the first to measure the activation of CAFs in a 96-well format, making it suitable for medium-to high-throughput screening of potential therapeutic compounds. By focusing on observable cellular phenotypic changes rather than targeting specific molecular pathways, this assay allows for a broader and unbiased identification of compounds capable of modulating CAF activation.

Hypertrophic scars (HTS) are a common complication of burn injuries and are characterized by excessive dermal fibrosis driven by the transformation of resident dermal fibroblasts to profibrotic myofibroblasts. Although single cell and bulk RNA transcriptomics analysis of HTS and normal skin tissue samples were performed previously, transcriptomics of the transformation of fibroblasts to myofibroblasts has not been studied. Here, we report the data obtained from RNA sequencing of fibroblasts before and after exposure to transforming growth factor beta 1 (TGF-β1) and highlight the pathways that are up-and down-regulated during myofibroblast transformation. Our results suggest increased cellular signalling and rewiring, proliferative surge, immune-like and metabolic reprogramming, and delayed structural remodelling as four groups of events during the transformation of human primary dermal fibroblasts to myofibroblasts.