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 .

Cardiorenal multimorbidity in hospitalized cardiology patients: The Hellenic Cardiorenal Morbidity Snapshot (HECMOS) study.

PURPOSE: Cardiovascular disease is commonly accompanied by renal dysfunction. Multimorbidity in hospitalized patients impacts unfavorably on prognosis and hospital stay. We aimed to illustrate the contemporary burden of cardiorenal morbidity across inpatient cardiology care in Greece. METHODS: The Hellenic Cardiorenal Morbidity Snapshot (HECMOS) used an electronic platform to collect demographic and clinically relevant information about all patients hospitalized on March 3, 2022, in Greece. The participating institutions covered all levels of inpatient cardiology care and most of the country's territories to collect a real-world, nation representative sample. RESULTS: A total of 923 patients (men 68.4%, median age 73 ± 14.8 years) were admitted to 55 different cardiology departments. 57.7% of the participants were aged >70 years. Hypertension was highly prevalent and present in 66% of the cases. History of chronic HF, diabetes mellitus, atrial fibrillation, and chronic kidney disease was present in 38%, 31.8%, 30%, and 26%, respectively. Furthermore, 64.1% of the sample exhibited at least one of these 4 entities. Accordingly, a combination of ≥2 of these morbid conditions was recorded in 38.7%, of ≥3 in 18.2%, whereas 4.3% of the sample combined all 4 in their medical history. The most common combination was the coexistence of heart failure-atrial fibrillation accounting for 20.6% of the sample. Nine of 10 nonelectively admitted patients were hospitalized due to acute HF (39.9%), acute coronary syndrome (33.5%), or tachyarrhythmias (13.2%). CONCLUSION: HECMOS participants carried a remarkable burden of cardio-reno-metabolic disease. HF in conjunction with atrial fibrillation was found to be the most prevalent combination among the studied cardiorenal nexus of morbidities in the whole study population.

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.

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.

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.

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.

End-of-life cost for lung cancer patients in Greece: a hospital-based retrospective study.

Objective: The aim of the present study was to estimate the cost of treating patients with lung cancer at their end-of-life (EOL) phase of care in Greece. Materials & methods: A hospital-based retrospective study was conducted in the Oncology Unit of 'Sotiria' Hospital, in Athens, Greece. All lung cancer patients who died between 1 January 2015 and 31 December 2018 with at least 6 months follow-up were enrolled in the study. Healthcare resource utilization data, including inpatient and outpatient ones, during the last 6 months before death was extracted from a registry kept in the unit. This data were combined with the corresponding local unit costs to calculate the 6, 3 and 1-month EOL cost in €2019 values. Results: A total of 122 patients met the inclusion criteria. The mean (standard deviation) age at diagnosis was 67.8 (8.9) years with 78.7% of patients being male and 55.0% diagnosed at stage IV. About 52.5% of patients had been diagnosed with adenocarcinoma, 28.7% with squamous non-small-cell lung cancer types and 18.9% with small-cell-lung cancer. The median overall survival of these patients was 10.8 months. During the EOL periods, the mean cost/patient in the last 6, 3 and 1 month were €7665, €3351 and €1009, respectively. Pharmaceutical cost was the key driver of the total cost (75% of the total 6-month) followed by radiation therapy (16.2%). The median EOL 6-month cost was marginally statistically significantly higher among patients with adenocarcinoma (€9031) compared with squamous (€6606) and to small-cell-lung cancer (€5474). Conclusion: The findings of the present study indicate that lung cancer treatment incurs high costs in Greece, mainly attributed to pharmaceutical expenses, even at the EOL phase.

Cost-effectiveness of tofacitinib for the treatment of moderate to severe active ulcerative colitis in Greece.

OBJECTIVE: To evaluate the cost-effectiveness of tofacitinib versus other treatment options currently available for the management of adult patients with moderate-to-severe ulcerative colitis, who have had an inadequate response, loss of response, or were intolerant to conventional therapy or a biologic agent, in Greece. METHODS: A Markov model was adapted for projecting lifetime costs and outcomes, for a cohort of patients with moderate-to-severe ulcerative colitis from a Greek payer perspective. Patients entered the model in the active ulcerative colitis state and transitioned to a remission or response state or they underwent colectomy. Following an initial 8-week induction treatment period, patients received maintenance therapy until loss of response. Nonresponders could switch to up to two subsequent biologic lines. Clinical efficacy, adverse event rates and utilities derived from OCTAVE trials and a network-meta-analysis (NMA), while adverse event-related disutilities were obtained from the literature. Information on treatment pathways and resource use was provided by an advisory board due to a lack of local data. Unit costs derived from official national sources (€, 2018). RESULTS: Over a life-time horizon, treating moderate-to-severe active ulcerative colitis with tofacitinib resulted in additional quality-adjusted life-years (QALYs) and lower total costs compared to vedolizumab (0.018; €6408), infliximab (biosimilar) (0.009; €3031), golimumab (0.042; €1988) and infliximab (originator) (0.009; €6724). Hence, tofacitinib was estimated to be dominant over all comparators. CONCLUSION: The results of the analysis suggest that in the Greek setting, tofacitinib could be considered a cost-effective (dominant) treatment option for the treatment of patients with moderate-to-severe active ulcerative colitis.

Incidence and cost of bleeding events requiring hospitalization in patients with atrial fibrillation treated with acenocoumarol in Greece.

BACKGROUND: To estimate the incidence of hemorrhagic events in patients with atrial fibrillation (AF) treated with acenocoumarol, and the management cost of those requiring hospitalization in Greece. METHODS: A nationwide telephone survey was conducted between December 2017 and January 2018, to identify cardiologists who treat AF patients with acenocoumarol. A total of 300 cardiologists were selected and reported the number of AF acenocoumarol-treated patients during the past 12 months and the number of those who experienced a hemorrhagic event. The hospital charges to sickness fund and the cost of resource utilization of AF patients hospitalized between January 2013 and June 2017 at a tertiary hospital in Athens due to acenocoumarol-related bleedings were retrieved. RESULTS: Out of 48,255 AF patients, 12,633 (26.2%) were treated with acenocoumarol. In all, 5.1% of patients experienced a hemorrhagic event with the incidence of bleeding requiring hospitalization being 1.7%. The most common bleeding site was the gastrointestinal system (51.5%). The mean (95% CI) management cost per bleeding event requiring hospitalization was €1,202 (€1,058-€1,420). The higher cost was that of intracranial bleeding €3,887 (€2,700-€5,046). The expected annual economic burden for the management of bleedings related to acenocoumarol and requiring hospitalization was estimated at €1,463,955. CONCLUSIONS: The incidence of bleeding events in AF acenocoumarol-treated patients in Greece as well as the estimated annual economic burden for the management of bleeding events requiring hospitalization, emphasize the need to comply with the current guidelines and to optimize therapeutic strategies for the management of AF side effects with oral anticoagulants, particularly in patients with high bleeding risk.

Unravelling the history of hepatitis B virus genotypes A and D infection using a full-genome phylogenetic and phylogeographic approach.

Hepatitis B virus (HBV) infection constitutes a global public health problem. In order to establish how HBV was disseminated across different geographic regions, we estimated the levels of regional clustering for genotypes D and A. We used 916 HBV-D and 493 HBV-A full-length sequences to reconstruct their global phylogeny. Phylogeographic analysis was conducted by the reconstruction of ancestral states using the criterion of parsimony. The putative origin of genotype D was in North Africa/Middle East. HBV-D sequences form low levels of regional clustering for the Middle East and Southern Europe. In contrast, HBV-A sequences form two major clusters, the first including sequences mostly from sub-Saharan Africa, and the second including sequences mostly from Western and Central Europe. Conclusion: We observed considerable differences in the global dissemination patterns of HBV-D and HBV-A and different levels of monophyletic clustering in relation to the regions of prevalence of each genotype.