Lung cancer patients' journey from first symptom to treatment: Results from a Greek registry.

BACKGROUND: To map the patients' journey from symptoms onset to treatment initiation for the most frequent histological types of lung cancer in Greece and describe the initial treatment that patients receive. METHODS: The primary data source was a Greek hospital-based registry. Demographic, anthropometric, lifestyle, and diagnostic-related characteristics as well as treatment-related data were extracted from the registry for patients diagnosed with Adenocarcinoma, Squamous and Small Cell Lung Cancer (SCLC). The time intervals from symptoms onset to diagnosis (StD), diagnosis to treatment initiation (DtT), symptoms onset to treatment initiation (StT) and surgery to post-surgery treatment (SRGtT) were estimated. RESULTS: 231, 120 and 122 patients were diagnosed with Adenocarcinoma, SCLC and Squamous, respectively. The percentage of patients diagnosed at stage III/IV ranged from 75% in Adenocarcinoma to 97.5% in SCLC (p < 0.001). The median (IQR) StD was 52 (28-104) days and no difference was detected across the three histological types (p = 0.301). Cough as first symptom was the only determinant of StD (p = 0.001). The median (IQR) DtT was 23 (13-36) days, with this time interval being shorter among patients with SCLC compared to patients with Adenocarcinoma and Squamous (p < 0.001). The median (IQR) StT was 81 (51-139) days. Almost one third of patients with Adenocarcinoma and Squamous were subjected first to surgery and the median (IQR) SRGtT was 42 (34-55) days. CONCLUSIONS: Our results indicate that time interval from symptoms onset to treatment initiation in Greece is substantially prolonged, highlighting the need for strategies to expedite lung cancer diagnosis and access to evidence-based treatment.

Establishing nationally representative central line-associated bloodstream infection surveillance data for paediatric patients in Greece.

BACKGROUND: Healthcare-associated infections (HCAIs) are associated with increased morbidity and mortality and with excess costs. Central line-associated bloodstream infections (CLABSIs) are the most common HCAIs in neonates and children. AIM: To establish national benchmark data for rates of CLABSI in neonatal and paediatric intensive care units (NICUs and PICUs) and paediatric oncology units (ONCs). METHODS: Active surveillance for CLABSI was conducted from June 2016 to February 2017. A collaborative of 14 NICUs, four PICUs, and six ONCs participated in the programme. Surveillance definitions of central line (CL), central line utilization (CLU) ratio, CLABSI event, and CLABSI rate were based on the Centers for Disease Control and Prevention's 2014 National Healthcare Safety Network criteria. Medical records were assessed daily for calculating CL-days, patient-days, and susceptibility of isolated organisms. FINDINGS: A total of 111 CLABSI episodes were recorded. The overall mean CLABSI rate was 4.41 infections per 1000 CL-days, and the CLU ratio was 0.31. CLABSI rates were 6.02 in NICUs, 6.09 in PICUs, and 2.78 per 1000 CL-days in ONCs. A total of 123 pathogens were isolated. The most common pathogens were Enterobacteriaceae (36%), followed by Gram-positive cocci (29%), non-fermenting Gram-negative bacteria (16%), and fungi (16%). Overall, 37% of Gram-negative pathogens were resistant to third-generation cephalosporins and 37% to carbapenems. CONCLUSION: Nationally representative CLABSI rates were determined for paediatric patients. These data could be used to benchmark and serve as baseline data for the design and evaluation of infection control and antimicrobial stewardship interventions.

The clinical utility of PGD with HLA matching: a collaborative multi-centre ESHRE study.

STUDY QUESTION: Has PGD-HLA been successful relative to diagnostic and clinical efficacy? SUMMARY ANSWER: The diagnostic efficacy of PGD-HLA protocols was found lower in this study in comparison to published PGD-HLA protocols and to that reported for general PGD by ESHRE (78.5 vs 94.1% and vs 92.6%, respectively), while the clinical efficacy has proven very difficult to assess due to inadequate follow-up of both the ART/PGD and HSCT procedure outcomes. WHAT IS KNOWN ALREADY: The first clinical cases for PGD-HLA were reported in 2001. It is now a well-established procedure, with an increasing number of cycles performed every year. However, PGD-HLA is still offered by relatively few PGD centres, the currently available data is fragmented and most reports on PGD-HLA applications are limited in number and scope. Published systematic details on methodology, diagnostic results, overall ART success and haematopoietic stem cell transplantation (HSCT) outcomes are limited, precluding an evaluation of the true clinical utility of PGD-HLA cycles. STUDY DESIGN, SIZE, DURATION: This retrospective multi-centre cohort study aimed to investigate the diagnostic and clinical efficacy of the PGD-HLA procedure and the aspects of PGD-HLA cycles influencing positive outcomes: birth of genetically suitable donor-baby (or babies) and HSCT. In April 2014, 32 PGD centres (Consortium members and non-members) with published/known PGD-HLA activity were invited to participate. Between February and September 2015, 14 centres submitted their data, through a custom-designed secure database, with unique login access for each centre. Data parameters covered all aspects of PGD-HLA cycles (ART, embryology and genetic diagnosis), donor-babies born and HSCT. PARTICIPANTS/MATERIALS, SETTING, METHODS: From 716 cycles submitted by 14 centres (performed between August 2001 and September 2015), the quality evaluation excluded 12 cycles, leaving 704, from 364 couples. The online database, based on REDCap, a free, secure, web-based data-capture application, was customized by Centre for Clinical Epidemiology and Outcomes Research (CLEO), Athens. Continuous variables are presented using mean, standard deviation, median and interquartile range, and categorical variables are presented as absolute and relative frequencies. MAIN RESULTS AND THE ROLE OF CHANCE: The data included 704 HLA-PGD cycles. Mean maternal age was 33.5 years. Most couples (81.3%) requested HLA-typing with concurrent exclusion of a single monogenic disease (58.6% for beta-thalassaemia). In 92.5% couples, both partners were fertile, with an average 1.93 HLA-PGD cycles/couple. Overall, 9751 oocytes were retrieved (13.9/cycle) and 5532 embryos were analysed (7.9/cycle). Most cycles involved fresh oocytes (94.9%) and Day 3 embryo biopsy (85.3%). In 97.5% of cycles, the genotyping method involved PCR only. Of 4343 embryos diagnosed (78.5% of analysed embryos), 677 were genetically suitable (15.4% of those analysed for HLA alone, 11.6% of those analysed for HLA with exclusion of monogenic disease). Of the 364 couples, 56.6% achieved an embryo transfer (ET) and 598 embryos were transferred in 382 cycles, leading to 164 HCG-positive pregnancies (pregnancy rate/ET 41.3%, pregnancy rate/initiated cycle 23.3%) and 136 babies born (live birth rate/ET 34.3%, live birth rate/initiated cycle 19.3%) to 113 couples. Data analysis identified the following limitations to the overall success of the HLA-PGD procedure: the age of the mother undergoing the treatment cycle, the number of oocytes collected per cycle and genetic chance. HSCT was reported for 57 cases, of which 64.9% involved combined umbilical cord-blood and bone marrow transplantation from the HLA-identical sibling donor; 77.3% of transplants reported no complications. LIMITATIONS REASONS FOR CAUTION: The findings of the study may be limited as not all PGD centres with PGD-HLA experience participated. Reporting bias on completion of the online database may be another potential limitation. Furthermore, the study is based on retrospective data collection from centres with variable practices and strategies for ART, embryology and genetic diagnosis. WIDER IMPLICATIONS OF THE FINDINGS: This is the first multi-centre study evaluating the clinical utility of PGD-HLA, indicating variations in practice and outcomes throughout 15 years and between centres. The study highlights parameters important for positive outcomes and provides important information for both scientists and couples interested in initiating a cycle. Above all, the study underlines the need for better collaboration between all specialists involved in the ART-PGD/HLA procedure, as well as the need for comprehensive and prospective long-term data collection, and encourages all specialists to aim to properly evaluate and follow-up all procedures, with the ultimate aim to promote best practice and encourage patient informed decision making. STUDY FUNDING/COMPETING INTEREST(S): The study wishes to acknowledge ESHRE for funding the customization of the REDCap database. There are no competing interests. TRIAL REGISTRATION NUMBER: N/A.

Cost-utility analysis of certolizumab pegol in combination with methotrexate in patients with moderate-to-severe active rheumatoid arthritis in Greece.

We aimed to evaluate the cost-effectiveness of certolizumab pegol (CZP), a pegylated fc-free anti-TNF, as add-on therapy to methotrexate (MTX) versus etanercept, adalimumab, or golimumab in patients with moderate-to-severe active rheumatoid arthritis (RA) not responding to the conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs). A Markov model (6-month cycle length) assessed health and cost outcomes of CZP versus other anti-TNFs recommended for RA in Greece over a patient's lifetime. Following discontinuation of first-line anti-TNF, patients switched to second anti-TNF and then to a biologic with another mode of action. Sequential use of csDMARDs followed third biologic. Clinical data and utilities were extracted from published literature. Analysis was conducted from third-party payer perspective in Greece. Costs (drug acquisition, administration, monitoring, and patient management) were considered for 2014. Results presented are incremental cost-effectiveness ratios (ICERs) per quality-adjusted life year (QALY). Probabilistic sensitivity analysis (PSA) ascertained robustness of base-case findings. Base-case analysis indicated that CZP+MTX was more costly and more effective compared with Etanercept+MTX (base-case ICER: €3,177 per QALY), whilst versus adalimumab/golimumab, CZP was dominant (less costly, more effective). For all comparisons, CZP treatment resulted in greater improvements in life expectancy and QALYs. PSA indicated that at the willingness-to-pay threshold of €34,000/QALY, CZP+MTX was associated with a 71.6, 97.9, or 99.2% probability of being cost-effective versus etanercept, golimumab, or adalimumab, respectively, in combination with MTX. This analysis demonstrates CZP+MTX to be a cost-effective alternative over Etanercept+MTX and a dominant option over Adalimumab+MTX and Golimumab+MTX for management of RA in Greece.

Comprehensive taxonomy and worldwide trends in pharmaceutical policies in relation to country income status.

BACKGROUND: Rapidly evolving socioeconomic and technological trends make it challenging to improve access, effectiveness and efficiency in the use of pharmaceuticals. This paper identifies and systematically classifies the prevailing pharmaceutical policies worldwide in relation to a country's income status. METHODS: A literature search was undertaken to identify and taxonomize prevailing policies worldwide. Countries that apply those policies and those that do not were then grouped by income status. RESULTS: Pharmaceutical policies are linked to a country's socioeconomics. Developed countries have universal coverage and control pharmaceuticals with external and internal price referencing systems, and indirect price-cost controls; they carry out health technology assessments and demand utilization controls. Price-volume and risk-sharing agreements are also evolving. Developing countries are underperforming in terms of coverage and they rely mostly on restrictive state controls to regulate prices and expenditure. CONCLUSIONS: There are significant disparities worldwide in the access to pharmaceuticals, their use, and the reimbursement of costs. The challenge in high-income countries is to maintain access to care whilst dealing with trends in technology and aging. Essential drugs should be available to all; however, many low- and middle-income countries still provide most of their population with only poor access to medicines. As economies grow, there should be greater investment in pharmaceutical care, looking to the policies of high-income countries to increase efficiency. Pharmaceutical companies could also develop special access schemes with low prices to facilitate coverage in low-income countries.

The heart failure pandemic: The clinical and economic burden in Greece.

BACKGROUND: The objective of this study was to identify the epidemiological and clinical characteristics of heart failure (HF) patients in Greece as well as the economic burden and the distribution of costs for the management of the disease. METHODS: Eight Greek secondary and tertiary cardiology centres from different cities have participated in a prospective, observational survey, the ESC HF Pilot Survey. 307 patients with HF, 177 hospitalised and 130 outpatients, have been recruited and monitored for 12months. Clinical and epidemiological data, along with data on mortality, hospitalisations and health care resources used have been collected. The economic evaluation was conducted from the social security system perspective. RESULTS: The annual mortality rate was 24.3% for the hospitalised patients vs 7.7% for the outpatients (P<0.001) and the annual rehospitalisation rate was 42.9% vs 19.2% respectively (P<0.001). Kaplan-Meier analyses revealed that patients with kidney dysfunction, S3 gallop and higher NYHA class have a significantly worse survival. The mean annual economic burden of the social security system per HF patient was estimated at €4411±4764. About two thirds of this cost is due to in-patient care. CONCLUSIONS: Despite the progress in the management of the disease, about one in four hospitalised patients dies and four in ten are rehospitalised in less than one year. Moreover, the disease imposes a significant economic burden for the social security system and national economy. Their findings suggest that there is still need of more effective drug treatment and efficient disease management programs focused in the reduction of the hospital admissions.

A literature review to evaluate the clinical and economic value of olmesartan for the treatment of hypertensive patients.

The objective of the present study was to systematically review the clinical and economic outcomes of olmesartan as monotherapy or in combination with other antihypertensive agents in the treatment of hypertension. A literature search was performed using PubMed and the Cochrane library until December 2015, with no limit on publication date. Eligible studies were selected using predetermined inclusion and exclusion criteria, limiting articles to those published in the English language. Background information of the study, participants' characteristics and study outcomes were collected. Meta-analysis of data was not performed. Fifty-five studies were included, of which fifty investigated the clinical efficacy of olmesartan and five the cost-effectiveness of olmesartan. In general results from clinical trials evaluating the efficacy of olmesartan as monotherapy and as combination therapy demonstrated that olmesartan provided better antihypertensive blood pressure-lowering efficacy and was generally well tolerated compared with other antihypertensive agents. Results from economic evaluations indicated that olmesartan may be more cost-effective than other ARBs such as losartan, valsartan, irbesartan and candesartan, having the potential of decreasing the overall medical costs of care for patients with hypertension. Evidence from the present systematic review confirms the antihypertensive efficacy and good safety profile of olmesartan both as monotherapy and as combination therapy. Olmesartan was also found to be cost-effective compared with other ARBs, though this area has yet relatively poor evidence and needs to further be explored.

Variation in paediatric hospital antibiotic guidelines in Europe.

OBJECTIVE: To assess the availability and source of guidelines for common infections in European paediatric hospitals and determine their content and characteristics. DESIGN: Participating hospitals completed an online questionnaire on the availability and characteristics of antibiotic prescribing guidelines and on empirical antibiotic treatment including duration of therapy for 5 common infection syndromes: respiratory tract, urinary tract, skin and soft tissue, osteoarticular and sepsis in neonates and children. RESULTS: 84 hospitals from 19 European countries participated in the survey of which 74 confirmed the existence of guidelines. Complete guidelines (existing guidelines for all requested infection syndromes) were reported by 20% of hospitals and the majority (71%) used a range of different sources. Guidelines most commonly available were those for urinary tract infection (UTI) (74%), neonatal sepsis (71%) and sepsis in children (65%). Penicillin and amoxicillin were the antibiotics most commonly recommended for respiratory tract infections (RTIs) (up to 76%), cephalosporin for UTI (up to 50%) and for skin and soft tissue infection (SSTI) and bone infection (20% and 30%, respectively). Antistaphylococcal penicillins were recommended for SSTIs and bone infections in 43% and 36%, respectively. Recommendations for neonatal sepsis included 20 different antibiotic combinations. Duration of therapy guidelines was mostly available for RTI and UTI (82%). A third of hospitals with guidelines for sepsis provided recommendations for length of therapy. CONCLUSIONS: Comprehensive antibiotic guideline recommendations are generally lacking from European paediatric hospitals. We documented multiple antibiotics and combinations for most infections. Considerable improvement in the quality of guidelines and their evidence base is required, linking empirical therapy to resistance rates.