Professional quality of life, psychological well-being, and work engagement of healthcare professionals in two Greek hospitals during COVID-19: A cross-sectional study.

BACKGROUND: During the COVID-19 pandemic, the mental health of healthcare professionals has emerged as an issue of great concern. OBJECTIVE: To investigate the levels of professional quality of life, psychological well-being, and work engagement among healthcare professionals in two Greek hospitals during the COVID-19 pandemic. METHODS: A cross-sectional study was conducted in December 2021 in two public hospitals in Greece. To assess the levels of professional quality of life, psychological well-being, and work engagement, respondents completed the Professional Quality of Life Scale Version 5 (ProQOL-V), the Psychological Well-being (PWB) scale, and the Utrecht Work Engagement Scale (UWES-17). RESULTS: A total of 150 questionnaires were distributed, and 102 were returned (response rate: 68%). It was found that as burnout levels increased, the levels of work engagement decreased (rho = -0.36, p-value <  0.01). Higher levels of compassion satisfaction were associated with higher work engagement (rho = 0.48, p-value <  0.01). Multivariable analysis revealed that healthcare personnel's contact with patients or service users exposed to or who have experienced traumatic events was associated with less positive relationships with others (and, consequently, lower levels of psychological well-being) (p-value = 0.035). CONCLUSIONS: Healthcare professionals in the two public hospitals in Greece, experienced moderate levels of compassion satisfaction, burnout, and secondary traumatic stress during the COVID-19 pandemic. Their psychological well-being was also found to be moderate, and their levels of work engagement were moderate to high. Supporting the physical and psychological well-being of healthcare professionals is essential for their ability to provide high-quality care in times of crisis, such as during the COVID-19 pandemic.

SARS-CoV-2-specific T cell therapy for severe COVID-19: a randomized phase 1/2 trial.

Despite advances, few therapeutics have shown efficacy in severe coronavirus disease 2019 (COVID-19). In a different context, virus-specific T cells have proven safe and effective. We conducted a randomized (2:1), open-label, phase 1/2 trial to evaluate the safety and efficacy of off-the-shelf, partially human leukocyte antigen (HLA)-matched, convalescent donor-derived severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific T cells (CoV-2-STs) in combination with standard of care (SoC) in patients with severe COVID-19 compared to SoC during Delta variant predominance. After a dose-escalated phase 1 safety study, 90 participants were randomized to receive CoV-2-ST+SoC (n = 60) or SoC only (n = 30). The co-primary objectives of the study were the composite of time to recovery and 30-d recovery rate and the in vivo expansion of CoV-2-STs in patients receiving CoV-2-ST+SoC over SoC. The key secondary objective was survival on day 60. CoV-2-ST+SoC treatment was safe and well tolerated. The study met the primary composite endpoint (CoV-2-ST+SoC versus SoC: recovery rate 65% versus 38%, P = 0.017; median recovery time 11 d versus not reached, P = 0.052, respectively; rate ratio for recovery 1.71 (95% confidence interval 1.03-2.83, P = 0.036)) and the co-primary objective of significant CoV-2-ST expansion compared to SοC (CoV-2-ST+SoC versus SoC, P = 0.047). Overall, in hospitalized patients with severe COVID-19, adoptive immunotherapy with CoV-2-STs was feasible and safe. Larger trials are needed to strengthen the preliminary evidence of clinical benefit in severe COVID-19. EudraCT identifier: 2021-001022-22 .

The Role of EMT-Related lncRNAs in Ovarian Cancer.

Ovarian cancer (OC) is one of the deadliest cancers worldwide; late diagnosis and drug resistance are two major factors often responsible for high morbidity and treatment failure. Epithelial-to-mesenchymal transition (EMT) is a dynamic process that has been closely linked with cancer. Long non-coding RNAs (lncRNAs) have been also associated with several cancer-related mechanisms, including EMT. We conducted a literature search in the PubMed database in order to sum up and discuss the role of lncRNAs in regulating OC-related EMT and their underlying mechanisms. Seventy (70) original research articles were identified, as of 23 April 2023. Our review concluded that the dysregulation of lncRNAs is highly associated with EMT-mediated OC progression. A comprehensive understanding of lncRNAs' mechanisms in OC will help in identifying novel and sensitive biomarkers and therapeutic targets for this malignancy.

Pre- and Postoperative Exercise Effectiveness in Mobility, Hemostatic Balance, and Prognostic Biomarkers in Hip Fracture Patients: A Study Protocol for a Randomized Controlled Trial.

Hip fractures are a major health concern, particularly for older adults, as they can reduce life quality, mobility loss, and even death. Current evidence reveals that early intervention is recommended for endurance in patients with hip fractures. To our knowledge, preoperative exercise intervention in patients with hip fractures remains poorly researched, and no study has yet applied aerobic exercise preoperatively. This study aims to investigate the short-term benefits of a supervised preoperative aerobic moderate-intensity interval training (MIIT) program and the added effect of an 8-week postoperative MIIT aerobic exercise program with a portable upper extremity cycle ergometer. The work-to-recovery ratio will be 1-to-1, consisting of 120 s for each bout and four and eight rounds for the pre- and postoperative programs, respectively. The preoperative program will be delivered twice a day. A parallel group, single-blinded, randomized controlled trial (RCT) was planned to be conducted with 58 patients each in the intervention and control groups. This study has two primary purposes. First, to study the effect of a preoperative aerobic exercise program with a portable upper extremity cycle ergometer on immediate postoperative mobility. Second, to investigate the additional effect of an 8-week postoperative aerobic exercise program with a portable upper extremity cycle ergometer on the walking distance at eight weeks after surgery. This study also has several secondary objectives, such as ameliorating surgical and keeping hemostatic balance throughout exercise. This study may expand our knowledge of preoperative exercise effectiveness in hip fracture patients and enhance the current literature about early intervention benefits.

Time From Marketing Authorization to Reimbursement of Medicines in Greece After the Introduction of the Health Technology Assessment Process From July 2018 to April 2022.

OBJECTIVES: This study aimed to quantify the median time from marketing authorization (MA) to the inclusion of medicines in the reimbursement list after the introduction of the health technology assessment process in Greece. METHODS: From July 2018 to April 2022, the Ministerial Decisions (MDs) and reimbursement lists, posted on the website of the Ministry of Health, were reviewed. The following information was collected for the medicines: the date that MDs and positive reimbursement lists were issued, the MA date, the date of the official price publication, and the type of the health technology assessment application. The time from MA to listing was calculated as the difference between the MA date and the date that the relevant reimbursement list was issued. RESULTS: During the study period, 93 MDs were issued, from which 79 (85%) were positive and 14 (15%) were negative. Focusing on medicines included in the positive list for the first time, the median time from MA to listing for the new molecules was found to be 34.8 (interquartile range 25.7-41.3) months. This time was statistically significantly shortened for fixed dose combinations (20.9 [15.3-45.4] months, P = .008), and biosimilars (23 [16.6-28.2] months, P = .001). For generics was 17.6 (interquartile range 10-30) months, statistically significantly lower than that of new molecules (P < .001). CONCLUSIONS: The time from MA to the inclusion of medicines in the reimbursement list in Greece is significantly long, especially for innovative medicines. Thus, policy makers should consider this point to optimize and improve patients' subsidized access.

Impact of biologic therapies on risk of adverse cardiovascular events in patients with Ankylosing Spondylitis or Psoriatic Arthritis: A systematic literature review.

BACKGROUND: Recent evidence highlights increased mortality and morbidity due to cardiovascular disease (CVD), especially within the two major forms of Spondyloarthropathies (SpAs), Ankylosing Spondylitis (AS) and Psoriatic Arthritis (PsA). Healthcare professionals and patients in these populations should be alerted regarding the high risk of cardiovascular (CV) events and thus, customize the treatment strategy accordingly. OBJECTIVE: This systematic literature review aimed to determine the effects of biological therapies on serious CV events in AS and PsA. METHODS: Screening for the study was carried out using PubMed and Scopus databases from the database's inception to the 17th of July 2021. The literature search strategy for this review is based on the Population, Intervention, Comparator, Outcomes (PICOs) framework. Randomized controlled trials (RCTs) of biologic therapies for the treatment of AS and/or PsA were included. The primary outcome measure was the number of serious CV events reported during the placebo-controlled phase. RESULTS: 4,422 articles were generated from keywords, eligibility criteria, and databases. Following the screening, we retained 13 studies for analysis: 3 in AS and 10 in PsA. Meta-analysis of results was not feasible due to the small number of the identified studies, the heterogeneity of the biologic treatment and the included populations, as well as the infrequently reported requested endpoint. According to our review, biologic treatments are safe options as for CV risk in patients with PsA or AS. CONCLUSION: Further and more extensive trials in AS/PsA patients at high risk of CV events are needed before firm conclusions can be drawn.

Practices and educational needs of Hellenic Police Officers in providing first aid/cardiopulmonary resuscitation: A cross-sectional survey.

BACKGROUND: It is well known that police officers (POs) are expected to be the first responders in emergency cases requiring First Aid (FA) such as cardiac arrest. OBJECTIVE: Description of practices and educational needs of Hellenic POs in providing FA/Cardiopulmonary Resuscitation (CPR) in case of medical emergencies and description of the equipment of professional FA kit. METHODS: An anonymous cross-sectional survey was conducted from January 1, 2016, to December 31, 2017, using a self-administered questionnaire designed to serve the purposes of this particular survey. The instrument consisted of 53 questions (multiple choice and open-ended questions) administered in a convenience sample of 700 POs of the Attica prefecture. RESULTS: A sample of 520 POs (constables and lieutenants) completed the questionnaire (response rate = 74.28%). Among the participants, 248 (47.7 %) declared that they had provided FA/CPR in the past, while among those declaring that they had never provided FA/PCR (n = 248), 153 (61.7%) said that they had experienced FA/CPR needs, but did not know what they had to do. Moreover, only 18.1% (94/520) of the POs answered that they have FA equipment in their professional equipment, which mainly includes bandages (54/94, 57.4%), while 29.7% of POs provided answers about their educational needs (313 in total) declared that they would like to be educated in bleeding control. CONCLUSION: There is a need to educate and train Greek POs in first aid and CPR in an organized and mandatory way in order to meet emergency needs.

Prevalence of adult self-reported atopic dermatitis in Greece: results from a nationwide survey

Background: Atopic dermatitis (AD) is a common chronic inflammatory skin disorder. In Greece, there is a lack of data on AD epidemiology. Objectives: The objective of the present study was to estimate the self-reported prevalence of AD and the prevalence of moderate/severe AD in the adult population in Greece. Materials & Methods: A nationwide cross-sectional survey with a structured questionnaire was conducted, between June 17th, 2021 and July 12th, 2021, using Computer Assisted Telephone Interviewing (CATI) and Computer Assisted web Interviewing (CAWI) data collection methods. Several different self-reported AD definitions, as extracted from the literature, were used. Self-reported moderate/severe atopic dermatitis was estimated using the Patient Oriented Eczema Measure (POEM). Results: More than 30,500 persons were invited to participate; among them, 3,001 were recruited for the survey. The 12-month self-reported AD prevalence in Greece ranged from 1.7% to 6.4%, while lifetime prevalence reached 11.4%. At least half of the responders who identified with AD during the last 12 months had moderate to very severe eczema. The multivariate analysis confirmed that age, atopy-related comorbidities (asthma, allergies, and rhinitis), a family history of AD, rhinitis, and asthma were factors that are independently associated with AD, irrespective of the definition used. Conclusion: The 12-month and lifetime prevalence of AD in adults in Greece ranges from 1.7% to 6.4% and 3.7% to 11.4%, respectively. At least half of the adults with AD suffer from moderate-to-severe disease. Our study is a first step in understanding AD epidemiology in Greece and may provide useful insights for healthcare decision makers.

Cost-Utility Analysis of Pegaspargase for the Treatment of Acute Lymphoblastic Leukemia in Greece.

BACKGROUND AND OBJECTIVE: Acute lymphoblastic leukemia (ALL) is an acute, rapidly progressing and life-threatening form of cancer involving immature lymphocytes called lymphoblasts. ALL is the most common subtype of leukemia in children and adolescents. The aim of the present study was to assess the cost-utility of pegaspargase versus L-asparaginase, both followed by Erwinase in the therapy sequence, as a treatment option for pediatric, adolescent, and adult patients with ALL in Greece. METHODS: A published cost-utility model comprising a decision tree and a state-transition Markov model was adapted from a public payer perspective to compare a pegaspargase treatment sequence with an L-asparaginase sequence. Efficacy and safety data, as well as utility values, were extracted from the published literature. Direct costs pertaining to drug acquisition, administration, and management of hypersensitivity were considered in the analysis (€2020). Model-extrapolated outcomes included quality-adjusted life-years (QALYs), costs, and incremental cost-effectiveness ratios (ICER). All future outcomes were discounted at 3.5% per annum. Sensitivity analyses were used to explore the impact of changing input data. RESULTS: The analysis showed that the pegaspargase sequence was estimated to produce 0.05 additional QALYs (18.12 vs. 18.07) and lower cost of - €1698 compared with L-asparaginase, indicating that the pegaspargase sequence was a dominant treatment strategy (improved outcomes with reduced costs) compared with L-asparaginase. Deterministic sensitivity analysis confirmed the cost-effective profile of pegaspargase. At the defined willingness-to-pay threshold of €54,000/QALY gained, probabilistic sensitivity analysis showed that pegaspargase had a 100% probability of being cost effective relative to the L-asparaginase sequence. CONCLUSION: The pegaspargase sequence was found to be less costly and more effective (in terms of QALYs) in relation to the L-asparaginase sequence, representing a dominant strategic option for Greek public payers in ALL.

Burden of Atopic Dermatitis in Adults in Greece: Results from a Nationwide Survey.

The objective was to describe the AD burden in terms of quality of life (QoL), sleep, social life, work productivity, and resource utilization in Greece and assess the impact of disease severity. A nationwide cross-sectional survey was conducted. The questionnaire consisted of socioeconomic factors, medical history, AD screening, AD severity, QoL, sleep difficulties, social activities, and work productivity questions. AD was defined using the UK Working Party criteria (UKWP cohort) and a patient-reported AD diagnosis from a physician (Expert Diagnosis cohort). Self-reported moderate/severe AD was estimated using the Patient-Oriented Eczema Measure (POEM). In the UKWP cohort, the AD effect on QoL was moderate/extremely large in 84.3% of moderate/severe AD (vs. 55.7% in mild; p = 0.016), while in the Expert Diagnosis cohort, it was 72.2% (vs. 22.8%; p < 0.001). Disease severity was associated with a higher impact on sleep and social activities. Overall work impairment was high in both mild (32.7%) and moderate/severe (48.5%) AD of the UKWP cohort, while among the Expert Diagnosis cohort, it was significantly higher among those with moderate/severe (31.2%) versus mild AD (11.9%; p < 0.001). The AD burden in Greece is significant, especially for those in moderate/severe AD stages. Acknowledging this burden is the first step toward applying healthcare decisions that will benefit patients and the community.

Patients' satisfaction, unmet needs, and treatment benefits in moderate to severe psoriasis in Greece: results from a cross-sectional survey.

BACKGROUND: Data regarding patients' satisfaction, individuals' therapeutic needs and their perception regarding the treatment benefit might provide useful insights for the unmet medical need from patients' perspective. To the best of our knowledge, no data are available in Greece investigating in depth moderate to severe psoriasis while there is a scarcity of studies in the international literature. The objective of this study was to capture patients' satisfaction and perception about treatment benefits in patients with moderate to severe psoriasis in Greece. METHODS: A cross-sectional survey was conducted in March-April 2021. Eligible to participate were adults with moderate to severe psoriasis, members of the Greek patient association EPIDERMIA. A structured questionnaire including socio-demographic factors, history of disease, comorbidities, current treatment, severity self-assessment and impact in daily activities, treatment adherence, treatment satisfaction, and Patient Benefit Index (PBI), was developed. Univariate parametric and non-parametric tests along with generalized linear models were applied. RESULTS: A total of 314 adults with moderate to severe psoriasis responded. The 97.5% of the participants reported that they were under treatment, while 41.1% of them mentioned none or little/quite satisfaction by their current treatment, with the most frequently reported reason of dissatisfaction to be the "no satisfactory improvement since treatment onset." The most important therapeutic goals from patient perspective were to "be healed of all skin defects," and to "get better skin quickly." The therapeutic benefit for these goals was found to be moderate (55% and 67%, respectively). Multivariate analysis confirmed that treatment type and psoriasis severity were factors independently associated with treatment satisfaction, and PBI Score. CONCLUSIONS: The results of this survey reveal the unmet medical need for moderate to severe psoriasis from patient perspective, since 2/5 patients stated that they are not much or very much satisfied with their current treatment, and more than half patients stated that the most important therapeutic goals (i.e., clean skin, early onset) for them are not achieved.

Cost-effectiveness Analysis of Lorlatinib in Patients Previously Treated with Anaplastic Lymphoma Kinase Inhibitors for Non-small Cell Lung Cancer in Greece.

Background: Non-small cell lung cancer (NSCLC), which accounts for about 80%-85% of lungcancer cases, is a leading cause of cancer-related death worldwide. Lorlatinib is a potent third-generation anaplastic lymphoma kinase (ALK) inhibitor approved for the treatment of patients with advanced, ALK-positive NSCLC previously treated with at least one second-generation ALK tyrosine kinase inhibitor. Objective: The present study assessed the cost-effectiveness of lorlatinib vs pemetrexed with platinum combination of carboplatin or cisplatin (P-ChT) in Greece. Methods: A partitioned survival model with three health states, referring to pre-progression, progressed disease, and death, was locally adapted from a Greek payer perspective over a lifetime horizon. Clinical and safety data and utility values applied in the model were extracted from the literature. A matching-adjusted indirect comparison of lorlatinib and P-ChT was performed. Only direct medical costs (€) from 2020 were included in the analysis. Primary outcomes were patient life years (LYs), quality-adjusted life years (QALYs), total costs, and incremental cost-effectiveness ratios per QALY and LY gained. All future outcomes were discounted at 3.5% per annum. A probabilistic sensitivity analysis was conducted to account for model uncertainty. Results: The analysis showed that, over a lifetime horizon, the estimated total costs of lorlatinib and P-ChT were €81 754 and €12 343, respectively. Lorlatinib was more effective than P-ChT with 2.4 and 1.5 more LYs and QALYs gained, respectively. The generated incremental cost-effectiveness ratios of lorlatinib compared with P-ChT were €28 613 per LY gained and €46 102 per QALY gained. Probabilistic sensitivity analysis confirmed the deterministic results. Conclusion: The present analysis suggests that lorlatinib may be considered as a cost-effective option compared with P-ChT in Greece for the treatment of patients with advanced, ALK-positive NSCLC whose disease has progressed after at least one second-generation ALK tyrosine kinase inhibitor. In addition, this option addresses a significant unmet medical need.

Cost-effectiveness of trifluridine/tipiracil as a third-line treatment of metastatic gastric cancer, including adenocarcinoma of the gastrohesophageal junction, among patients previously treated in Greece.

OBJECTIVE: To evaluate the cost-effectiveness of trifluridine/tipiracil (FTD/TPI) compared with best supportive care (BSC) for the treatment of patients with metastatic gastric cancer(mGC), including gastroesophageal junction adenocarcinoma(GEJ), who have received at least two prior therapies for metastatic disease and are eligible for third-line treatment, in Greece. METHODS: A partitioned survival model was locally adapted from a public payer perspective over a 10-year time horizon. Clinical, safety and utility data were extracted from literature. Resource consumption data obtained from a panel of local experts using a questionnaire developed for the study was combined with unit costs obtained from official sources. All costs reflect the year 2020 (€). Outcomes of the model were patients' life years (LYs) and quality-adjusted life years (QALYs), total costs and incremental cost-effectiveness ratio (ICER) per QALY and LY gained. RESULTS: The total cost per patient was estimated to be €6,965 for FTD/TPI and €1,906 for BSC, while FTD/TPI was associated with 0.180 and 0.107 increments in LYs and QALYs, respectively, compared with BSC, resulting in an ICER of €47,144 per QALY gained and €28,112 per LY gained. CONCLUSION: FTD/TPI was estimated to be a cost-effective treatment option for eligible third line mGC patients, including GEJ in Greece.

Application of Multicriteria Decision Analysis to Determine the Value of Prophylaxis Relative to On-Demand Treatment in Hemophilia A and Emicizumab versus Replacement Therapy in the Greek Healthcare Setting.

BACKGROUND AND OBJECTIVE: Hemophilia A (HA) is a rare disease that is characterized by congenital underproduction or dysfunction of the endogenous coagulation factor VIII (FVIII). The aim of the present study was to determine the value of prophylaxis versus on-demand treatment strategies for moderate to severe HA (MtSHA) patients and the value of emicizumab in the prophylaxis of MtSHA in Greece, compared with short half-life (SHL) FVIII and extended half-life (EHL) FVIII through multicriteria decision analysis (MCDA). METHODS: A literature review was performed to identify a set of criteria relevant to the therapeutic approaches and therapies under investigation. A performance matrix was populated by two literature reviews and meta-analyses. The criteria selected were hierarchically classified by allocating weights on a 0-100 scale. The performances of therapies were scored at the 100-point scale. The value judgments utilized for weighing and scoring were sourced via a survey among independent multidisciplinary system stakeholders. A linear additive value function was used for the calculation of total value estimates. RESULTS: The participants ranked 'annual number of bleedings per patient' and 'percentage of target joint bleeds' as the most important criteria, while the least important criterion was the 'annual treatment cost' for both assessments. Based on the weights elicited and the performance in each criterion, the overall value score was higher for prophylaxis treatment (58.27) compared with on-demand treatment (40.13). In the other comparison, the most valued treatment was emicizumab (77.05) followed by EHL FVIII (71.52) and SHL FVIII (19.88). According to the participants, the most important factors for managing MtSHA patients are those related to successful management of bleeding events given their contribution to improved quality of life (QoL) and reduced morbidity. CONCLUSIONS: This MCDA has shown that the prophylaxis strategy was perceived as a more valuable option for managing MtSHA patients when compared with the on-demand strategy. Moreover, emicizumab adds higher value and improves patient QoL compared with replacement therapy for MtSHA in Greece. Emicizumab addresses important unmet needs due to its improved efficacy and mode of administration.

Evaluation of Pupils' Knowledge about Kidney Health.

The purpose of this study was to investigate the level of renal function knowledge of primary school pupils in Greece. We conducted a cross-sectional study with a convenience sample of 220 pupils, coming from the 5th and 6th grades of general education schools. A questionnaire consisting of 11 questions was developed from scratch. However, based on an analysis of Cronbach's alpha values obtained when individual questions were deleted, two questions were removed from the analysis, and only nine remained for analysis and participated in the calculation of the knowledge score. Moreover, the gender and daily habits of pupils regarding water consumption and frequency of urination were recorded. Pupils had a high percentage of correct knowledge about the number of kidneys (95.2%), whether a child may have problems with the kidneys (85.5%) and whether a person can survive with one kidney (68.5%). Low levels of knowledge were observed in the function and role of the kidneys (36.4%), as well as the part of the body where the kidneys are located (30.9%). The median (interquartile range (IQR)) total knowledge score was 6 (5-7), with no difference detected between genders (p = 0.135). A statistically significant difference between pupils of 5th and 6th grades was found but the difference did not seem to be clinically significant (p = 0.035). The present research demonstrates that pupils' knowledge of renal function and the protection of their kidneys needs improvement.

Effect of prophylactic administration of antipyretics on the immune response to pneumococcal conjugate vaccines in children: a systematic review.

BACKGROUND: Prophylactic administration of antipyretics at the time of immunization seems to decrease some side effects, however reduced immune responses have been reported in some studies. This systematic review aimed to investigate the effect of prophylactic use of antipyretics on the immune response following administration of pneumococcal conjugate vaccines (PCVs). METHODS: A systematic review of randomized controlled trials and observational studies concerning the immune response to PCVs after antipyretic administration was performed up to November 2020 in the electronic databases of Pubmed and Scopus. RESULTS: Of the 3956 citations retrieved, a total of 5 randomized control trials including 2775 children were included in the review. Included studies were referred to PCV10 (3 studies), PCV7 and PCV13 (one study each). The prophylactic administration of paracetamol decreased the immune response to certain pneumococcal serotypes in all included studies. The effect was more evident following primary vaccination and with immediate administration of paracetamol. Despite the reductions in antibody geometric mean concentrations, a robust memory response was observed following the booster dose. Besides, antibody titers remained above protective levels in 88-100% of participants. The use of ibuprofen, that was evaluated in two studies, did not seem to affect the immunogenicity of PCVs . CONCLUSION: Although the reviewed studies had significant heterogeneity in design, paracetamol administration seems to affect the immune response for certain serotypes. The clinical significance of reduced immunogenicity especially before booster dose needs further investigation.

The Effect of a Life-Style Intervention Program of Diet and Exercise on Irisin and FGF-21 Concentrations in Children and Adolescents with Overweight and Obesity.

Overweight and obesity in childhood and adolescence represent major public health problems of our century, and account for increased morbidity and mortality in adult life. Irisin and Fibroblast Growth Factor 21 (FGF-21) have been proposed as prognostic and/or diagnostic biomarkers in subjects with obesity and metabolic syndrome, because they increase earlier than other traditional biomarkers. We determined the concentrations of Irisin and FGF-21 in children and adolescents with overweight and obesity before and after one year of a life-style intervention program of diet and physical exercise and explored the impact of body mass index (BMI) reduction on the concentrations of Irisin, FGF-21 and other cardiometabolic risk factors. Three hundred and ten (n = 310) children and adolescents (mean age ± SD: 10.5 ± 2.9 years) were studied prospectively. Following one year of the life-style intervention program, there was a significant decrease in BMI (p = 0.001), waist-to-hip ratio (p = 0.024), waist-to-height ratio (p = 0.024), and Irisin concentrations (p = 0.001), and an improvement in cardiometabolic risk factors. There was no alteration in FGF-21 concentrations. These findings indicate that Irisin concentrations decreased significantly as a result of BMI reduction in children and adolescents with overweight and obesity. Further studies are required to investigate the potential role of Irisin as a biomarker for monitoring the response to lifestyle interventions and for predicting the development of cardiometabolic risk factors.

Reducing Duration of Antibiotic Use for Presumed Neonatal Early-Onset Sepsis in Greek NICUs. A "Low-Hanging Fruit" Approach.

Antibiotics are commonly prescribed in Neonatal Intensive Care Units (NICU), where stewardship interventions are challenging. Lowering antibiotic consumption is desperately needed in Greece, a country with high antibiotic resistance rates. We sought to assess the effectiveness of a low-cost and -resource intervention to reduce antibiotic use in Greek NICUs implementing a "low-hanging fruit" approach. A prospective quasi-experimental study was conducted in 15/17 public NICUs in Greece (9/2016-06/2019). The intervention selected was discontinuation of antibiotics within 5 days for neonates with gestational age ≥ 37 weeks, no documented signs or symptoms of sepsis, CRP ≤ 10 mg/L and negative cultures within 3 days of antibiotic initiation. Impact was evaluated by the percentage of discontinued regimens by day 5, length of therapy (LOT) and stay. Trends of antibiotic consumption were assessed with days of therapy (DOT) per 1000 patient-days. Overall, there was a 9% increase (p = 0.003) of antibiotic discontinuation in ≤5 days. In total, 7/13 (53.8%) units showed a ≥10% increase. Overall, 615 days on antibiotics per 1000 patients were saved. Interrupted time-series analysis established a declining trend in DOT/1000 patient-days relative to the pre-intervention trend (p = 0.002); a monthly decrease rate of 28.96 DOT/1000 patient-days (p = 0.001, 95%CI [-45.33, -12.60]). The intervention had no impact on antibiotic choice. Antibiotic use was successfully reduced in Greek NICUs using a "low-hanging fruit" approach. In resource-limited settings, similar targeted stewardship interventions can be applied.

Cost-effectiveness of Empagliflozin Compared with Dapagliflozin for the Treatment of Patients with Type 2 Diabetes Mellitus and Established Cardiovascular Disease in Greece.

BACKGROUND AND OBJECTIVE: Type 2 diabetes mellitus (T2DM) accounts for approximately 95% of all diabetes cases and is associated with a substantially elevated risk for cardiovascular disease (CVD) that is 2- to 4-times higher in patients with T2DM compared to those without. The aim of present study was to evaluate the cost effectiveness of empagliflozin compared to dapagliflozin for the treatment of patients with T2DM and established CVD in Greece. METHODS: A published health economic model was used to project clinical and economic outcomes of T2DM patients receiving empagliflozin compared to those receiving dapagliflozin. Individual patient-level discrete-event simulation was conducted to predict time-to-event for CV, renal, and adverse events over patients' lifetimes. Hazard ratios for dapagliflozin versus empagliflozin on each clinical event was estimated from DECLARE-TIMI 58 and EMPA-REG OUTCOME trials' data using an indirect treatment comparison. Following a public payer perspective, only direct medical costs related to drug acquisition, fatal/non-fatal diabetes-related complications and adverse events were considered (€2020). Model extrapolated outcomes included life years (LY), quality-adjusted life years (QALYs), costs as well as incremental cost-effectiveness ratio (ICER). Sensitivity analyses explored the impact of changes in input data. RESULTS: Over a patient's lifetime, empagliflozin was associated with longer mean survival (17.23 LY with empagliflozin vs 16.07 LY with dapagliflozin) and reduced rate of CV mortality resulting in 0.48 more QALYs (9.27 vs 8.79), at additional costs of €462. The generated ICER of empagliflozin was €965 per QALY gained. Deterministic sensitivity analysis confirmed empagliflozin's cost-effective profile. Probabilistic sensitivity analysis revealed that the probability of empagliflozin being cost effective over dapagliflozin was 100%, at the defined threshold of €36,000 per QALY gained. CONCLUSION: Empagliflozin was estimated to be a highly cost-effective treatment option compared to dapagliflozin for the treatment of T2DM patients with established CVD in Greece.