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| 3. |
- Tabiri, S, et al.
(author)
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- 2021
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| 4. |
- Bravo, L, et al.
(author)
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- 2021
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| 5. |
- Glasbey, JC, et al.
(author)
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- 2021
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| 9. |
- Gregson, J., et al.
(author)
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Cardiovascular Risk Factors Associated With Venous Thromboembolism
- 2019
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In: JAMA Cardiology. - : American Medical Association (AMA). - 0965-2590 .- 2380-6583 .- 2380-6591. ; 4:2, s. 163-173
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Journal article (peer-reviewed)abstract
- IMPORTANCE It is uncertain to what extent established cardiovascular risk factors are associated with venous thromboembolism (VTE). OBJECTIVE To estimate the associations of major cardiovascular risk factors with VTE, ie, deep vein thrombosis and pulmonary embolism. DESIGN, SETTING, AND PARTICIPANTS This study included individual participant data mostly from essentially population-based cohort studies from the Emerging Risk Factors Collaboration (ERFC; 731728 participants; 75 cohorts; years of baseline surveys, February 1960 to June 2008; latest date of follow-up, December 2015) and the UK Biobank (421537 participants; years of baseline surveys, March 2006 to September 2010; latest date of follow-up, February 2016). Participants without cardiovascular disease at baseline were included. Data were analyzed from June 2017 to September 2018. MAIN OUTCOMES AND MEASURES Hazard ratios (HRs) per 1-SD higher usual risk factor levels (or presence/absence). Incident fatal outcomes in ERFC (VTE, 1041; coronary heart disease [CND], 25131) and incident fatal/nonfatal outcomes in UK Biobank (VTE, 2321; CHD, 3385). Hazard ratios were adjusted for age, sex, smoking status, diabetes, and body mass index (BMI). RESULTS Of the 731728 participants from the ERFC. 403 396 (55.1%) were female, and the mean (SD) age at the time of the survey was 51.9 (9.0) years; of the 421537 participants from the UK Biobank, 233 699 (55.4%) were female, and the mean (SD) age at the time of the survey was 56.4 (8.1) years. Risk factors for VTE included older age (ERFC: HR per decade, 2.67; 95% CI, 2.45-2.91; UK Biobank: HR, 1.81; 95% CI, 1.71-1.92), current smoking (ERFC: HR, 1.38; 95% CI, 1.20-1.58; UK Biobank: HR, 1.23; 95% CI, 1.08-1.40), and BMI (ERFC: HR per 1-SD higher BMI, 1.43; 95% CI, 1.35-1.50; UK Biobank: HR, 1.37; 95% CI, 1.32-1.41). For these factors, there were similar HRs for pulmonary embolism and deep vein thrombosis in UK Biobank (except adiposity was more strongly associated with pulmonary embolism) and similar HRs for unprovoked vs provoked VTE. Apart from adiposity, these risk factors were less strongly associated with VTE than CHD. There were inconsistent associations of VTEs with diabetes and blood pressure across ERFC and UK Biobank, and there was limited ability to study lipid and inflammation markers. CONCLUSIONS AND RELEVANCE Older age, smoking, and adiposity were consistently associated with higher VTE risk.
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| 11. |
- Battisti, Umberto Maria, et al.
(author)
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Ellagic Acid and Its Metabolites as Potent and Selective Allosteric Inhibitors of Liver Pyruvate Kinase
- 2023
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In: Nutrients. - : MDPI AG. - 2072-6643. ; 15:3
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Journal article (peer-reviewed)abstract
- Liver pyruvate kinase (PKL) has recently emerged as a new target for non-alcoholic fatty liver disease (NAFLD), and inhibitors of this enzyme could represent a new therapeutic option. However, this breakthrough is complicated by selectivity issues since pyruvate kinase exists in four different isoforms. In this work, we report that ellagic acid (EA) and its derivatives, present in numerous fruits and vegetables, can inhibit PKL potently and selectively. Several polyphenolic analogues of EA were synthesized and tested to identify the chemical features responsible for the desired activity. Molecular modelling studies suggested that this inhibition is related to the stabilization of the PKL inactive state. This unique inhibition mechanism could potentially herald the development of new therapeutics for NAFLD.
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| 12. |
- Hoever, P., et al.
(author)
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Orexin Receptor Antagonism, a New Sleep-Enabling Paradigm: A Proof-of-Concept Clinical Trial
- 2012
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In: Clinical pharmacology and therapeutics. - : Springer Science and Business Media LLC. - 1532-6535 .- 0009-9236. ; 91:6, s. 975-985
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Journal article (peer-reviewed)abstract
- The orexin system is a key regulator of sleep and wakefulness. In a multicenter, double-blind, randomized, placebo-controlled, two-way crossover study, 161 primary insomnia patients received either the dual orexin receptor antagonist almorexant, at 400, 200, 100, or 50 mg in consecutive stages, or placebo on treatment nights at 1-week intervals. The primary end point was sleep efficiency (SE) measured by polysomnography; secondary end points were objective latency to persistent sleep (LPS), wake after sleep onset (WASO), safety, and tolerability. Dose-dependent almorexant effects were observed on SE, LPS, and WASO. SE improved significantly after almorexant 400 mg vs. placebo (mean treatment effect 14.4%; P < 0.001). LPS (-18 min (P = 0.02)) and WASO (-54 min (P < 0.001)) decreased significantly at 400 mg vs. placebo. Adverse-event incidence was dose-related. Almorexant consistently and dose-dependently improved sleep variables. The orexin system may offer a new treatment approach for primary insomnia.
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| 14. |
- Sarac, S., et al.
(author)
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Impact of Patient Education on Compliance with Positive Airway Pressure Treatment in Obstructive Sleep Apnea
- 2017
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In: Medical Science Monitor. - 1643-3750. ; 23, s. 1792-1799
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Journal article (peer-reviewed)abstract
- Background: We addressed the impact of patient education followed by frequent visits on compliance with positive airway pressure (PAP) treatment in patients with obstructive sleep apnea (OSA) in a Turkish sleep clinic cohort. Material/Methods: This single-center, randomized, controlled study was conducted in Istanbul, Turkey between June 2014 and April 2015. Among 115 eligible OSA patients (mean age 51.0 +/- 9.3 years; 75.5% men), 63 were randomized to standard support (SS) group (general information about OSA and PAP treatment at baseline), and 52 to educational support (ES) group (additional polysomnography chart viewing from both diagnostic and titration nights). All patients were scheduled to five PAP control visits between two weeks and six months after the PAP prescription. Primary outcome was the PAP compliance (4 hours/night for 70% of all the nights) at the last visit. Results: Average PAP usage was 4.2 +/- 2.5 hours/night in the SS group, and 5.2 +/- 2.1 hours/night in the ES group (p=0.027). PAP compliance was achieved among 68.3% in the SS group, and 86.5% in the ES group (p=0.021). In a multivariate analysis, ES strategy followed by frequent visits predicted PAP compliance (odds ratio [OR] 3.6, 95% confidence interval [CI] 1.2-10.6; p=0.020). Other predictors were obesity (OR 3.4, 95% CI 1.2-9.7; p=0.019) and severe OSA (apnea-hypopnea index >= 30/hour) at baseline (OR 4.7, 95% CI 1.2-17.6; p=0.023). Primary school education level was inversely related with PAP compliance (OR 0.3, 95% CI 0.1-0.9; p=0.036). Conclusions: Patient education with polysomnography chart view followed by frequent visits increased long-term compliance with PAP treatment.
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| 15. |
- Cinar, C., et al.
(author)
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Determinants of Severe Nocturnal Hypoxemia in Adults with Chronic Thromboembolic Pulmonary Hypertension and Sleep-Related Breathing Disorders
- 2023
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In: Journal of Clinical Medicine. - 2077-0383. ; 12:14
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Journal article (peer-reviewed)abstract
- Objectives: We aimed to investigate the occurrence of sleep-related breathing disorders (SRBDs) in patients with chronic thromboembolic pulmonary hypertension (CTEPH) and addressed the effect of pulmonary hemodynamics and SRBD indices on the severity of nocturnal hypoxemia (NH). Methods: An overnight polysomnography (PSG) was conducted in patients with CTEPH, who were eligible for pulmonary endarterectomy. Pulmonary hemodynamics (mean pulmonary arterial pressure (mPAP), pulmonary arterial wedge pressure (PAWP), pulmonary vascular resistance (PVR) measured with right heart catheterization (RHC)), PSG variables (apnea-hypopnea index (AHI)), lung function and carbon monoxide diffusion capacity (DLCO) values, as well as demographics and comorbidities were entered into a logistic regression model to address the determinants of severe NH (nocturnal oxyhemoglobin saturation (SpO(2)) < 90% under >20% of total sleep time (TST)). SRBDs were defined as obstructive sleep apnea (OSA; as an AHI & GE; 15 events/h), central sleep apnea with Cheyne-Stokes respiration (CSA-CSR; CSR pattern & GE; 50% of TST), obesity hypoventilation syndrome (OHS), and isolated sleep-related hypoxemia (ISRH; SpO(2) < 88% under >5 min without OSA, CSA, or OHS). Results: In all, 50 consecutive patients (34 men and 16 women; mean age 54.0 (SD 15.1) years) were included. The average mPAP was 43.8 (SD 16.8) mmHg. SRBD was observed in 40 (80%) patients, of whom 27 had OSA, 2 CSA-CSR, and 11 ISRH. None had OHS. Severe NH was observed in 31 (62%) patients. Among the variables tested, age (odds ratio (OR) 1.08, 95% confidence interval [CI] 1.01-1.15; p = 0.031), mPAP (OR 1.11 [95% CI 1.02-1.12; p = 0.012]), and AHI (OR 1.17 [95% CI 1.02-1.35; p = 0.031]) were independent determinants of severe NH. Conclusions: Severe NH is highly prevalent in patients with CTEPH. Early screening for SRBDs and intervention with nocturnal supplemental oxygen and/or positive airway pressure as well as pulmonary endarterectomy may reduce adverse outcomes in patients with CTEPH.
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| 16. |
- Despotou, George, et al.
(author)
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Localisation, Personalisation and Delivery of Best Practice Guidelines on an Integrated Care and Cure Cloud Architecture : The C3-Cloud Approach to Managing Multimorbidity
- 2020
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In: Digital Personalized Health and Medicine. - : IOS Press. - 9781643680835 - 9781643680828 ; , s. 623-627
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Conference paper (peer-reviewed)abstract
- BACKGROUND: C3-Cloud is an integrated care ICT infrastructure offering seamless patient-centered approach to managing multimorbidity, deployed in three European pilot sites. Challenge: The digital delivery of best practice guidelines unified for multimorbidity, customized to local practice, offering the capability to improve patient personalization and benefit.METHOD: C3-Cloud has adopted a co-production approach to developing unified multimorbidity guidelines, by collating and reconciling best practice guidelines for each condition. Clinical and technical teams at pilot sites and the C3-Cloud consortium worked in tandem to create the specification and technical implementation.RESULTS: C3-Cloud offers CDSS for diabetes, renal failure, depression and congenital heart failure, with over 300 rules and checks that deliver four best practice guidelines in parallel, customized for each pilot site.CONCLUSIONS: The process provided a traceable, maintainable and audited digitally delivered collated and reconciled guidelines.
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| 19. |
- Erturkmen, Gokce B. Laleci, et al.
(author)
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A Collaborative Platform for Management of Chronic Diseases via Guideline-Driven Individualized Care Plans
- 2019
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In: Computational and Structural Biotechnology Journal. - : Elsevier. - 2001-0370. ; 17, s. 869-885
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Journal article (peer-reviewed)abstract
- Older center dot age is associated with an increased accumulation of multiple chronic conditions. The clinical management of patients suffering from multiple chronic conditions is very complex, disconnected and time-consuming with the traditional care settings. Integrated care is a means to address the growing demand for improved patient experience and health outcomes of multimorbid and long-term care patients. Care planning is a prevalent approach of integrated care, where the aim is to deliver more personalized and targeted care creating shared care plans by dearly articulating the role of each provider and patient in the care process. In this paper, we present a method and corresponding implementation of a semi-automatic care plan management tool, integrated with clinical decision support services which can seamlessly access and assess the electronic health records (EHRs) of the patient in comparison with evidence based clinical guidelines to suggest personalized recommendations for goals and interventions to be added to the individualized care plans. We also report the results of usability studies carried out in four pilot sites by patients and clinicians.
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| 20. |
- Goodman, Matthew O., et al.
(author)
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Causal Association Between Subtypes of Excessive Daytime Sleepiness and Risk of Cardiovascular Diseases
- 2023
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In: Journal of the American Heart Association. - 2047-9980. ; 12:24
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Journal article (peer-reviewed)abstract
- BACKGROUND: Excessive daytime sleepiness (EDS), experienced in 10% to 20% of the population, has been associated with cardiovascular disease and death. However, the condition is heterogeneous and is prevalent in individuals having short and long sleep duration. We sought to clarify the relationship between sleep duration subtypes of EDS with cardiovascular outcomes, accounting for these subtypes. METHODS AND RESULTS: We defined 3 sleep duration subtypes of excessive daytime sleepiness: normal (6-9hours), short (<6hours), and long (>9hours), and compared these with a nonsleepy, normal-sleep-duration reference group. We analyzed their associations with incident myocardial infarction (MI) and stroke using medical records of 355901 UK Biobank participants and performed 2-sample Mendelian randomization for each outcome. Compared with healthy sleep, long-sleep EDS was associated with an 83% increased rate of MI (hazard ratio, 1.83 [95% CI, 1.21-2.77]) during 8.2-year median follow-up, adjusting for multiple health and sociodemographic factors. Mendelian randomization analysis provided supporting evidence of a causal role for a genetic long-sleep EDS subtype in MI (inverse-variance weighted β=1.995, P=0.001). In contrast, we did not find evidence that other subtypes of EDS were associated with incident MI or any associations with stroke (P>0.05). CONCLUSIONS: Our study suggests the previous evidence linking EDS with increased cardiovascular disease risk may be primarily driven by the effect of its long-sleep subtype on higher risk of MI. Underlying mechanisms remain to be investigated but may involve sleep irregularity and circadian disruption, suggesting a need for novel interventions in this population.
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| 21. |
- Laleci Erturkmen, Gokce Banu, et al.
(author)
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Management of personalised guideline-driven care plans addressing the needs of multi-morbidity via clinical decision support services
- 2018
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In: International Journal of Integrated Care. - : University of Utrecht. - 1568-4156. ; 18:132, s. A132-A132
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Journal article (peer-reviewed)abstract
- Introduction: The clinical management of patients suffering from multiple chronic conditions is very complex, disconnected and time-consuming with the traditional care settings. C3-Cloud project aims to build an integrated care platform for addressing the growing demand for improved health outcomes of multimorbid and long-term care patients. Theory/Methods: C3-Cloud has established an ICT infrastructure enabling continuous coordination of patient-centred care activities by a multidisciplinary care team MDT and patients/informal care givers. The Coordinated Care and Cure Delivery Platform C3DP allows, collaborative creation and execution of personalised care plans for multi-morbid patients through systematic and semi-automatic reconciliation of clinical guidelines. Clinical decision support CDS systems implementing flowcharts from evidence based clinical guidelines are integrated to present suggestions for treatment goal and activities e.g. medications, follow-up appointments, diet, exercise, lab tests. Pilot site local care systems are integrated with the C3DP via the technical and semantic interoperability platform to facilitate informed decision making. Active patient involvement is realized through a Patient Empowerment Platform presenting personalized care plan to the patient and establishing a continuous bi-way communication with the patient to collect patient observations, questionnaire responses, symptoms and feedback about care plan goals and activities.Results: The following research results have been achieved to enable guideline enabled personalised care plan management for addressing the needs of multi-morbidity:43 logical flowcharts were designed out of 4 disease guidelines Type 2 Diabetes, Heart Failure, Renal Failure and Depression.181 CDS rules assessing 166 patient criteria and recommending 154 goal/activity suggestions were implemented as CDS services in GDL covering T2D and RF.52 reconciliation rules were designed for eliminating contradicting guideline recommendations due to multi-morbidity.23 HL7 FHIR profiles were defined for representing care plan and patient data.C3DP has been integrated with these CDS services via CDS-Hooks specification to recommend personalised care plan goals and activities.Discussions: In this research, we have successfully implemented an ICT infrastructure enabling guideline-driven integrated care for multi-morbid patients. Although our ICT solution covers all the technical requirements identified by clinical partners, effective implementation of integrated care in real-life care setting requires major changes in organisational responsibilities and care pathways.Conclusions: User-centred design and usability testing have successfully been completed. C3-Cloud pilot application will now be operated in 3 European pilot sites with the participation of 62 MDT members and 1200 multi-morbid patients for 15 months. Lessons learned: There are two main research lines for reconciliation of contradicting guideline recommendations: 1 fully-automated reconciliation via ontology reasoning, 2 manually-crafted reconciliation rules by clinical expert groups. Although first approach is more dynamic, research results are still for very primitive cases and not clinically validated. As we are targeting an industry-ready solution after piloting in real-life settings, we have opted for the second option.Limitations: When a new chronic disease is to be addressed within our platform, reconciliation rules covering all disease combinations have to be re-assessed by the clinical expert group.Suggestions for future research: Fully-automated reconciliation approaches need to be further studied and validated in real-life settings.
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| 22. |
- Markt, Sarah C., et al.
(author)
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ABO Blood Group Alleles and Prostate Cancer Risk : results from the Breast and Prostate Cancer Cohort Consortium (BPC3)
- 2015
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In: The Prostate. - : John Wiley & Sons. - 0270-4137 .- 1097-0045. ; 75:15, s. 1677-1681
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Journal article (peer-reviewed)abstract
- BACKGROUND. ABO blood group has been associated with risk of cancers of the pancreas, stomach, ovary, kidney, and skin, but has not been evaluated in relation to risk of aggressive prostate cancer. METHODS. We used three single nucleotide polymorphisms (SNPs) (rs8176746, rs505922, and rs8176704) to determine ABO genotype in 2,774 aggressive prostate cancer cases and 4,443 controls from the Breast and Prostate Cancer Cohort Consortium (BPC3). Unconditional logistic regression was used to calculate age and study-adjusted odds ratios and 95% confidence intervals for the association between blood type, genotype, and risk of aggressive prostate cancer (Gleason score >= 8 or locally advanced/metastatic disease (stage T3/T4/N1/M1). RESULTS. We found no association between ABO blood type and risk of aggressive prostate cancer (Type A: OR = 0.97, 95% CI = 0.87-1.08; Type B: OR = 0.92, 95% CI = n0.77-1.09; Type AB: OR = 1.25, 95% CI = 0.98-1.59, compared to Type O, respectively). Similarly, there was no association between "dose" of A or B alleles and aggressive prostate cancer risk. CONCLUSIONS. ABO blood type was not associated with risk of aggressive prostate cancer. Prostate 75: 1677-1681, 2015. (C) 2015 Wiley Periodicals, Inc.
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| 23. |
- Saygin, M., et al.
(author)
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The impact of sleep deprivation on hippocampal-mediated learning and memory in rats
- 2017
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In: Bratislava Medical Journal-Bratislavske Lekarske Listy. - : AEPress, s.r.o.. - 0006-9248. ; 118:7, s. 408-416
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Journal article (peer-reviewed)abstract
- BACKGROUND: To examine the impact of different types of sleep deprivation on hippocampal-mediatedlearning and memory in rats. METHODS: Forty-eight Sprague-Dawley male rats were randomly assigned to 1 of 4 equal-size groups: (1) 12 hours of sleep per day (control). (2) total sleep deprivation (TSD), (3) rapid eye movement (REM) deprivation (RD), and (4) sleep restricted to 4 hours per day (SR). All rats were subjected to swimming training in the Morris water maze (MWM). At the end of the experiments, the rats were decapitated, and hippocampus tissue was analyzed for several neurotransmitters and receptors. RESULTS: The time spent at the target quadrant increased from 20.2 to 30.0 seconds in the control group on the third day of the experiment, whereas corresponding values increased from 20.2 to 21.8 seconds in the TSD group, 22.1 to 25.4 seconds in the RD group, and 21.2 to 32.0 sec in the SR group (p = 0.026). On the seventh day of the experiment, the values decreased to 25.0 seconds in controls, 22.5 in the RD group, and 23.6 in the SR group (p = 0.045). The TSD group demonstrated significant decreases in glutamate and serotonin levels compared with the control group. There was a significant increase in 5-HT2(a) receptor expression in all intervention groups compared with the controls. CONCLUSIONS: Our results of glutamate levels and 5-HT2a receptor expression in the hippocampus seem to be primarily involved in sleep and memory regulation (Tab. 2, Fig. 4, Ref. 59).
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| 24. |
- Traore, Lamine, et al.
(author)
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User-Centered Design of the C3-Cloud Platform for Elderly with Multiple Diseases : Functional Requirements and Application Testing
- 2019
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In: Studies in Health Technology and Informatics. - : IOS Press. - 0926-9630 .- 1879-8365. - 9781643680026 - 9781643680033 ; 264, s. 843-847
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Journal article (peer-reviewed)abstract
- The number of patients with multimorbidity has been steadily increasing in the modern aging societies. The European C3-Cloud project provides a multidisciplinary and patient-centered “Collaborative Care and Cure-system” in the management of elderly with multimorbidity, enabling continous coordination of care activities between multidisciplinary care teams (MDTs), patients and informal care givers (ICG). In this paper, we report how various components of the infrastructure were tested to fulfill the functional requirements and how the entire system was subjected to an early application testing involving different groups of end-users. MDTs from participating European regions were involved in requirement elicitation and test formulation, resulting in 57 questions, distributed via an internet platform, to 48 test participants (22 MDTs, 26 patients) from three pilot sites. The results indicate an overall high level of satisfaction for all Information and Communication Technologie (ICT) components among the users. The early testing also provided user feedback important to consider for technical improvement of the entire system.
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| 25. |
- von Tottleben, Malte, et al.
(author)
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An Integrated Care Platform System (C3-Cloud) for Care Planning, Decision Support, and Empowerment of Patients With Multimorbidity: Protocol for a Technology Trial
- 2022
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In: JMIR Research Protocols. - : JMIR Publications. - 1929-0748. ; 11:7
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Journal article (peer-reviewed)abstract
- Background: There is an increasing need to organize the care around the patient and not the disease, while considering the complex realities of multiple physical and psychosocial conditions, and polypharmacy. Integrated patient-centered care delivery platforms have been developed for both patients and clinicians. These platforms could provide a promising way to achieve a collaborative environment that improves the provision of integrated care for patients via enhanced information and communication technology solutions for semiautomated clinical decision support.Objective: The Collaborative Care and Cure Cloud project (C3-Cloud) has developed 2 collaborative computer platforms for patients and members of the multidisciplinary team (MDT) and deployed these in 3 different European settings. The objective of this study is to pilot test the platforms and evaluate their impact on patients with 2 or more chronic conditions (diabetes mellitus type 2, heart failure, kidney failure, depression), their informal caregivers, health care professionals, and, to some extent, health care systems.Methods: This paper describes the protocol for conducting an evaluation of user experience, acceptability, and usefulness of the platforms. For this, 2 “testing and evaluation” phases have been defined, involving multiple qualitative methods (focus groups and surveys) and advanced impact modeling (predictive modeling and cost-benefit analysis). Patients and health care professionals were identified and recruited from 3 partnering regions in Spain, Sweden, and the United Kingdom via electronic health record screening.Results: The technology trial in this 4-year funded project (2016-2020) concluded in April 2020. The pilot technology trial for evaluation phases 3 and 4 was launched in November 2019 and carried out until April 2020. Data collection for these phases is completed with promising results on platform acceptance and socioeconomic impact. We believe that the phased, iterative approach taken is useful as it involves relevant stakeholders at crucial stages in the platform development and allows for a sound user acceptance assessment of the final product.Conclusions: Patients with multiple chronic conditions often experience shortcomings in the care they receive. It is hoped that personalized care plan platforms for patients and collaboration platforms for members of MDTs can help tackle the specific challenges of clinical guideline reconciliation for patients with multimorbidity and improve the management of polypharmacy. The initial evaluative phases have indicated promising results of platform usability. Results of phases 3 and 4 were methodologically useful, yet limited due to the COVID-19 pandemic.
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