BackgroundPrimary health care (PHC) systems are typically organized using uniform administrative models that assume functional similarity across facilities. In practice, however, PHC units differ substantially in how services are delivered. In Greece, despite ongoing reforms, empirical evidence on the functional heterogeneity of public PHC units remains limited. This study aims to classify PHC units based on observed service utilization patterns and to identify the organizational and geographical determinants shaping these functional typologies.MethodsThis cross-sectional study analyzed administrative data from 649 public PHC units in Greece (2024). Visit compositions (regular, emergency, prescription, and other) were analyzed using compositional data analysis with centered log-ratio transformation. K-means clustering was applied to identify utilization-based functional typologies. Associations between cluster membership and unit characteristics (size, organizational type, and geography) were examined using ANOVA and chi-square tests.ResultsThree distinct functional typologies emerged. Cluster 1 (“balanced, generalist units”, n = 308) exhibited a mixed service profile across visit types. Cluster 2 (“routine care–focused units”, n = 66) was dominated by regular visits (82.4%) and minimal prescription activity, but showed substantial within-cluster variability in emergency care. Cluster 3 (“mixed, higher-intensity units”, n = 275) displayed a heterogeneous case-mix and a greater share of complex or administrative activity. Cluster membership was significantly associated with unit size, organizational type, and geographical location (p < 0.001). Cluster 1 units were significantly larger, followed by Cluster 3, while Cluster 2 units were the smallest. Organizationally, Cluster 1 was dominated by Rural Health Centers and Local Health Units, Cluster 2 by Local Medical Practices and Urban Health Centers, and Cluster 3 by Multipurpose Regional Medical Practices and Local Health Units. Spatially, higher-intensity units (Cluster 3) were predominantly located in major urban centers.ConclusionPHC is functionally heterogeneous, with distinct utilization profiles that are not captured by existing administrative classifications. These findings reveal a structural misalignment between formal organizational labels and actual service delivery. A utilization-based typology provides a practical tool for health policy and management, supporting more targeted approaches to resource allocation, workforce planning, and regional service design. Incorporating functional differentiation into PHC governance can enhance efficiency, equity, and system responsiveness.

Greece records the highest level of private health expenditure in the European Union, driven largely by out-of-pocket payments that undermine financial protection and exacerbate inequities. Despite universal coverage, benefit gaps, cost-sharing arrangements, and limits in publicly financed service availability shift a substantial financial burden onto households. Within a dual insurance system, voluntary private health insurance frequently overlaps with public benefits and does little to reduce excessive out-of-pocket spending. A regulated complementary health insurance framework, embedded within a three-tier financing structure, could convert part of private spending into pooled and prepaid contributions while preserving the primacy of public coverage. Targeted regulatory, institutional, and design reforms are therefore proposed to ensure that complementary insurance supports equity-oriented health financing rather than reinforcing disparities.

Effective communication skills are a critical yet often neglected bridge between individual-focused medical education and population-oriented public health goals. Using the Greek medical system as a case study, this paper highlights a significant gap in formal training, finding that only three of the seven medical schools offer dedicated communication modules, with just two being core courses and representing less than 1% of the total ECTS credits. The study contends that this lack of prioritization undermines patient-centered care and broader public health education. Effective provider-patient communication is shown to foster trust, improve treatment adherence, and enhance health literacy, which empowers individuals and communities to make informed health decisions. The study concludes by calling for systematic curricular reform, advocating for the integration of communication and health literacy as core, longitudinal components throughout medical education. It recommends employing simulation-based learning, continuous assessment, and faculty development to ensure that future physicians are equipped to simultaneously improve individual patient outcomes while advancing broader population health goals.

BackgroundDecentralization in health systems enhances responsiveness and equity but is often accompanied by uneven implementation and resource disparities. Greece' health system has undergone successive phases of decentralization, culminating in a transformation in 2015 when regional health authorities (RHAs) assumed operational responsibility for public primary healthcare (PHC). This study presents the first comprehensive assessment of this transition, examining funding adequacy and resource allocation across RHAs.MethodsFinancial and operational analyses were performed to assess disparities among RHAs and between RHAs and hospitals. Data were drawn from publicly available sources, including financial statements, reports from the Ministry of Health, and national statistics. The analysis examined patient visits, staffing levels, infrastructure, funding, labor productivity, and efficiency across health regions.ResultsBetween 2018 and 2023, patient visits declined at most RHAs. Staffing composition shifted toward nursing personnel, while medical staff numbers declined. Substantial intraregional and interregional disparities were observed in service utilization, staffing, infrastructure, funding, labor productivity, and efficiency. Hospitals continued to absorb a large share of PHC demand and funding, whereas RHA units held markedly fewer assets and received lower financial support. Funding imbalances among RHAs were evident, and the overall negative return on assets indicated systemic underfunding of public PHC.ConclusionThe ongoing decentralization of Greece's health system faces structural challenges, including overlapping territorial jurisdictions and uneven, occasionally insufficient, resource allocation. These challenges hinder progress toward health equity. Policy interventions should prioritize evidence-based resource allocation, standardized financing frameworks, and strengthened PHC integration to promote equitable and sustainable healthcare delivery under decentralized governance.

AIMS:This study aimed to analyze the patterns and trends of antidiabetic medication prescriptions in Greece using data from the National Electronic Prescription Database. METHODS:This retrospective observational study used real-world data from the Greek electronic prescription database from 2015 to 2021. The study population included all patients with a confirmed diagnosis of diabetes mellitus. Data on medication details, prescribing patterns, and costs were extracted and analyzed using descriptive statistical methods. RESULTS:The study revealed that blood glucose-lowering drugs, excluding insulins (A10B), accounted for 86.1 % of the total quantity prescribed, while insulins (A10A) contributed significantly to the total cost (28.3 %). Newer drug classes like DPP-4 inhibitors and GLP-1 analogues showed increasing trends, while some older medications declined in use. Prescribing patterns varied among medical specialties, with internal medicine and general practice physicians being the primary prescribers of these drugs. CONCLUSIONS:This study highlights significant shifts in antidiabetic medication prescribing patterns in Greece, with a trend towards newer drug classes. These findings have important implications for healthcare policy, including the need to promote the cost-effective use of newer medications, manage patient transitions between drug classes, and address insulin affordability and access.

Objective: To evaluate the ability of an Artificial Intelligence (AI) algorithm to identify optimal trigger days with significantly higher predicted number of MII oocytes. Design: A retrospective cohort study Materials and Methods: A pre-trained AI algorithm was applied to ovarian stimulation cycles from centers across three regions—Asia, Europe and America. Only cycles in which all retrieved oocytes were fertilized using the ICSI method were analyzed, enabling analysis of both the number of MII oocytes and the number of blastocysts. The algorithm was developed to identify optimal trigger days (today, tomorrow or in two days) with a significantly higher predicted MII oocyte yield, based on a trigger day prediction model. The cycles in the study were not part of the dataset used to develop the AI algorithm. The cycles included were then divided into two groups: “Concordant” - cycles in which the actual trigger day (performed by the physician) was one of the algorithm’s optimal days, and “Discordant” - cycles with no agreement between the algorithm and the physician regarding optimal trigger day. Cycles’ outcomes including number of MII and usable blastocysts were compared between the two groups. Results: A total of 5,357 ovarian stimulation cycles were included. Comparison of cycle outcomes of the “concordant” and “discordant” groups are presented. The number of MII oocytes and usable blastocysts was significantly higher in the concordant group. Conclusions: The use of an AI algorithm to optimize trigger timing may improve MII oocyte and blastocysts yield in ovarian stimulation cycle.

Objective: To evaluate the need for individualized, center specific models for predicting MII oocyte yield by comparing the performance of one generalized multicenter (MC) model trained on a combined dataset of three centers to the performance of three models, each trained on the dataset of its single-center (SC) separately. Design: A retrospective cohort study Materials and Methods: Data consisted of 38,957 IVF retrieval cycles, from centers across three different continents, Asia, Europe (EU), and America (USA). Machine Learning models were developed using XGBoost, integrating patient-specific characteristics and treatment measurements. Separate models for oocyte number prediction were trained for three different possible trigger days: same-day, next-day, and two-days following a patient’s visit. The dataset was randomly split into train (60%), validation (20%) and test (20%) sets. Four models were developed. The MC model was developed using the entire train and validation datasets from all three centers combined. The three SC-specific models were developed using only their respective center-specific cycles from the training and validation datasets. Both the MC and SC models were evaluated on the same test set for each center separately. Results: This analysis compares the performance of each center’s test set when using the multi-center model (MC) versus the corresponding SC specific model. The generalized MC model’s performance was nearly identical to the performance of the center-specific models when tested on the same test sets. Conclusions: The generalized model for predicting MII oocyte yield on different trigger days performs comparably to center-specific models, obviating the need to retrain and individualize the model per center. Support: Study was funded by FertilAI

Aim: Electronic prescribing has allowed for the collection of prescription data in real time in Greece for the first time. Hence, the aim of the current study was to present the characteristics of prescriptions for the Greek population during the period from 2015 to 2021. Methods: This retrospective study was based on data extracted from the nationwide Greek electronic prescription database between January 2015 and December 2021. Descriptive statistics methods were used for the needs of the study. As the basic figures examined depend on the size of the population, in order for the results to be comparable, we estimated the corresponding measures per inhabitant, using population data from the Greek Statistical Authority. Appropriate indicators for the comparison of consumption and expenditure over time were estimated. A study of the trend was also carried out using time series and linear regression models. In order to facilitate the design and implementation of specialized policies, it is useful to identify the drug categories with the highest consumption and expenditure, as well as the geographical areas that present similar characteristics. For the first, ABC analysis was used, which helps to identify the most popular categories of drugs, while for the second, cluster analysis was carried out. Agglomerative clustering was used to divide the regions into similar groups. This hierarchical clustering algorithm classifies the population into several clusters, with areas in the same cluster being more similar, and areas in different clusters being dissimilar. The Ward linkage method with Euclidean distance was used. Results: The analysis of prescription drug consumption and expenditure from 2015 to 2021 revealed significant fluctuations and trends across various drug categories, age groups, and geographical areas. Notably, the quantity of prescriptions increased by 20% since 2015, while expenditure surged by over 30%, with significant spikes following the end of the MoU in 2019 and the onset of the pandemic in 2020. In terms of expenditure, antineoplastic and immunomodulation agents (category L) held the largest share, driven by the introduction of new, costly drugs. The expenditure per inhabitant revealed gender and age disparities, with older populations, particularly women, incurring higher costs. Geographically, drug expenditure, and consumption varied significantly, with distinct regional clusters identified. These clusters, while showing some overlap in consumption and expenditure patterns, also highlighted unique regional characteristics. Conclusions: The insights into prescription drug consumption and expenditure trends offer a valuable basis for developing targeted interventions aimed at optimizing healthcare resource allocation. Moreover, the findings underscore the importance of addressing regional and demographic disparities in pharmaceutical use, thereby contributing to more equitable and cost-effective healthcare strategies. More specifically, the age distribution of prescriptions shows the increase in younger ages, which, as a result, anticipates the overall increase in prescriptions. The knowledge of the most convex categories of medicine, as well as the percentages of the use of generic drugs, shows where interventions should be made, with financial incentives and information through new information channels. The geographic disparities recorded should lead to policies that help the residents of hard-to-reach areas to access prescriptions. In addition, the present study provides a strategic framework for policymakers and healthcare managers to guide future studies and inform decision-making processes.

Purpose This study aims to enrich the debate on whether women should continue to be under-represented in the upper echelons of organisations. Evidence arrives from the health-care battlefield and, more specifically, the Greek public hospitals assessed in terms of financial performance. Design/methodology/approach The whole set of Greek public hospitals operating in 2022 were included in a quantitative approach, whereby financial ratios reflect financial performance, while the Chief Executive Officer (CEO) – Chief Financial Officer (CFO) gender reflects the female representation. Descriptive statistics analysis, t-tests and correlation analysis were performed. Findings The findings of this study suggest that female CEOs significantly outperformed their male counterparts on liquidity and accounts payable turnover, while female CFOs surpassed males concerning inventory turnover. Contrarily, hospitals with male CFOs achieved higher profitability, but income statements seem self-manipulated thanks to state subsidies and cash accounting techniques. Women appear to focus on those components of financial performance which are better aligned to the social role of public entities, while their contribution to non-financial performance is also underpinned by previous research. Practical implications Women’s under-representation in management positions was partially confirmed, as less than 1 / 4 of hospitals appoint a female CEO but circa 7 / 10 of them appoint a female CFO. This could be attributed to stereotypes combined with policy and governance factors. The latter were discussed well in this paper shaping a roadmap towards better gender equality in health-care settings. Originality/value To the best of the authors’ knowledge, this was the first effort to investigate the association between managers’ gender and financial performance in Greek health care.

Ovarian stimulation for assisted reproductive technology is traditionally started in the early follicular phase. The essential rationale is to allow timely follicle growth and oocyte retrieval to ensure synchronization of the in-vitro cultured embryos with the receptive period of the endometrium in a fresh transfer cycle. In addition, conventional thought suggested that follicle recruitment happened only once, around menstruation. A deeper understanding of folliculogenesis, advances in cryobiology and an increasing proportion of freeze-all cycles provide a unique opportunity here. Experience from oncofertility patients as well as infertile women and oocyte donors who underwent ovarian stimulation in different phases of the menstrual cycle, dubbed 'random start' cycles, suggests that the number of oocytes collected and their reproductive potential do not depend on the time of starting ovarian stimulation, although the duration of stimulation and gonadotrophin consumption can vary slightly. It may be time to free both patients and clinics from the obsession with starting ovarian stimulation in the early follicular phase in planned freeze-all cycles. The flexibility provided by random start cycles is one aspect of individualizing treatment to patients' needs.

(1) Background: The presence of adenomyosis among pregnant patients has been associated with a higher incidence of miscarriage and pregnancy complications. Although the role of adenomyosis in women undergoing in vitro fertilization (IVF) was investigated in several studies and demonstrated a potentially detrimental effect on live birth rates following IVF, most of them were small studies in which the adenomyosis diagnosis was not confirmed based on solid ultrasonographic criteria. (2) Methods: 3503 patients undergoing their first blastocyst frozen transfer through a hormonal replacement (HRT) FET cycle. Among them, 140 women had a confirmed diagnosis of adenomyosis based on the MUSA criteria. (3) Results: Adenomyosis patients were more likely to proceed with deferred FET compared with no-adenomyosis women (p = 0.002) and were significantly more likely to be treated with GnRH agonist pre-treatment (2 months) (p < 0.001). The presence of adenomyosis significantly decreased the clinical pregnancy rates (aOR 0.62, 95% CI: 0.39–0.98, p = 0.040) and live birth rates (aOR 0.46, 95% CI: 0.27–0.75, p = 0.003) and significantly increased the miscarriage rates (aOR 2.13, 95% CI: 0.98–4.37, p = 0.045). Multivariable logistic regression adjusting for age, autologous or donor oocytes, PGT-A, deferred FET, serum progesterone levels the day before FET, GnRH agonist pre-treatment, number of embryos transferred, and adenomyosis demonstrated that the use of the GnRH agonist protocol did not decrease or increase the miscarriage rate, clinical pregnancy rate, or live birth rate. (4) Conclusions: The presence of adenomyosis had a significant negative impact on the clinical outcomes of patients undergoing FET and was associated with higher miscarriage, lower clinical pregnancy, and live birth rates. GnRH agonist pre-treatment does not appear to improve clinical outcomes.

Abstract Objective: To assess the cost-effectiveness of two ovarian stimulation procedures comparing the use of FSH antagonists with the use of FSH primed progesterone protocol in a oocyte donor program. Design: Calculation of cost-effectiveness ratios (costs per outcome achieved) from clinical practices using a retrospective cohort single university center study carried out from 2012 to 2021. Main Outcome Measure(s): Cost-effectiveness ratios as cost per mature oocyte and cost per treatment. Result(s): According to the economic analysis, ovarian stimulation with FSH antagonist protocol increased the overall cost of the treatment as well as the cost per retrieved and effective oocyte. The cost of gonadotrophins per mature oocyte retrieved was 49.27 ± 17.94 € and the cost of medication per mature oocyte retrieved was 59.26± 28.01 € . In the FSH primed progesterone group, the cost of gonadotrophins per mature oocyte retrieved was 44.67 ± 16.65€ and the cost of medication per mature oocyte retrieved was 44.91 ± 20.86€ Conclusion(s): Cost-effectiveness is a compelling reason for an egg donation program. Progestins can present an effective and less expensive option for egg donation programs in terms of cost.

Several European administrations have applied various mechanisms promoting cost containment to stabilise their budgets for pharmaceutical expenditure. Since 2016, Greece has adopted the clawback as a policy to contain the NHS hospitals' pharmaceutical expenditure, which increased significantly in the 2016-2020 period. The present study reviews the impact of this policy on the operation of NHS hospitals, the uninterrupted supply and rational use of their medicines, along with the sustainability of their finances. The trend of pharmaceutical expenditure for the period 2016-2020 is combined with further analysis of detailed drug consumption data of 15 sampled NHS hospitals. The data is classified by Anatomical Therapeutic Category (ATC) and the percentage of clawback distributed to each ATC and pharmaceutical company is calculated. It was found that a large proportion of the clawback is allocated to a few therapeutic categories (ATCs) and consequently, few pharmaceutical companies are particularly burdened. The increased burden on pharmaceutical companies, due to the continuous increase in the excessive pharmaceutical expenditure of the NHS hospitals and their limited budget, endangers the uninterrupted supply of medicines to hospitals and the viability of pharmaceutical companies. This issue was discussed in a scientific consensus group*, in which participants proposed ways to keep the level of pharmaceutical expenditure in line with patients' needs, the country's economic potential, and the sustainability of pharmaceutical companies.

The economic crisis in Greece, which began in 2010 and lasted for 10 years, highlighted the serious problems and challenges of the Greek Social Health Insurance system. The reforms that mainly took place during the crisis provided a temporary solution. They focused on establishing a new National Organization for Healthcare Services (named EOPYY) and merging all the old insurance funds. This paper aims to examine whether this social health insurance fund has been sustainable in the long run. An actuarial model was created to project future expenses and revenues. Demographic and economic trends were considered, while it was assumed that medical technology remains unaltered. The assessment of the system solvency was based on the ratio (Revenue/Liabilities) calculated for each year, from 2020 to 2050. The results led to deficits, the amount and the time point in which they appear depends on how optimistic or pessimistic demographic and economic assumptions were. A new financial flow model was proposed to address the deficits. The results show that under the new model, the system remains solvent until 2050. The state subsidy amount on the employees’ health insurance premium was estimated as a percentage of the employees’ wage.

STUDY QUESTION: What is the recommended management of ovarian stimulation, based on the best available evidence in the literature? SUMMARY ANSWER: The guideline development group formulated 84 recommendations answering 18 key questions on ovarian stimulation. WHAT IS KNOWN ALREADY: Ovarian stimulation for IVF/ICSI has been discussed briefly in the National Institute for Health and Care Excellence guideline on fertility problems, and the Royal Australian and New Zealand College of Obstetricians and Gynaecologist has published a statement on ovarian stimulation in assisted reproduction. There are, to our knowledge, no evidence-based guidelines dedicated to the process of ovarian stimulation. STUDY DESIGN, SIZE, DURATION: The guideline was developed according to the structured methodology for development of ESHRE guidelines. After formulation of key questions by a group of experts, literature searches and assessments were performed. Papers published up to 8 November 2018 and written in English were included. The critical outcomes for this guideline were efficacy in terms of cumulative live birth rate per started cycle or live birth rate per started cycle, as well as safety in terms of the rate of occurrence of moderate and/or severe ovarian hyperstimulation syndrome (OHSS). PARTICIPANTS/MATERIALS, SETTING, METHODS: Based on the collected evidence, recommendations were formulated and discussed until consensus was reached within the guideline group. A stakeholder review was organized after finalization of the draft. The final version was approved by the guideline group and the ESHRE Executive Committee. MAIN RESULTS AND THE ROLE OF CHANCE: The guideline provides 84 recommendations: 7 recommendations on pre-stimulation management, 40 recommendations on LH suppression and gonadotrophin stimulation, 11 recommendations on monitoring during ovarian stimulation, 18 recommendations on triggering of final oocyte maturation and luteal support and 8 recommendations on the prevention of OHSS. These include 61 evidence-based recommendations-of which only 21 were formulated as strong recommendations-and 19 good practice points and 4 research-only recommendations. The guideline includes a strong recommendation for the use of either antral follicle count or anti-Mtillerian hormone (instead of other ovarian reserve tests) to predict high and poor response to ovarian stimulation. The guideline also includes a strong recommendation for the use of the GnRH antagonist protocol over the GnRH agonist protocols in the general IVF/ICSI population, based on the comparable efficacy and higher safety. For predicted poor responders, GnRH antagonists and GnRH agonists are equally recommended. With regards to hormone pre-treatment and other adjuvant treatments (metformin, growth hormone (GH), testosterone, dehydroepiandrosterone, aspirin and sildenafil), the guideline group concluded that none are recommended for increasing efficacy or safety. LIMITATIONS, REASON FOR CAUTION: Several newer interventions are not well studied yet. For most of these interventions, a recommendation against the intervention or a research-only recommendation was formulated based on insufficient evidence. Future studies may require these recommendations to be revised. WIDER IMPLICATIONS OF THE FINDINGS: The guideline provides clinicians with clear advice on best practice in ovarian stimulation, based on the best evidence available. In addition, a list of research recommendations is provided to promote further studies in ovarian stimulation.

Objectives: Understanding the process of new drug adoption can inform the development of policies to promote appropriate diffusion of new drugs that result in improved outcomes and are cost-effective. The present study aims to explore factors influencing adoption of new antidiabetic drugs for T2DM in the Greek setting. Methods: The study employs a qualitative descriptive approach. Semi-structured interviews were performed with physicians involved in management of T2DM in adults. Eligible participants were identified using generic purposive sampling. Interviews were audio-recorded, transcribed verbatim and analyzed using framework analysis. Rogers' Diffusion of Innovations theory informed the development of the interview guide and the coding scheme. Results: 10 physicians were interviewed. The mean interview duration was 44 min. Three main themes were derived: (1) Factors influencing prescribing of new medicines for T2DM, (2) Perceptions on pharmaceutical innovation, (3) Use of information sources during the new drug adoption process. The attributes of the new drug, patient-related factors, external influences and prescriber needs and characteristics affected the adoption decision. Physicians reported utilizing information from a variety of sources in the process of adoption. Conclusions: The present study brought forward the importance of relative advantage and compatibility in the adoption of new antidiabetic agents and also highlighted that adoption is a process during which new drug attributes are continuously re-evaluated. (C) 2020 Fellowship of Postgraduate Medicine. Published by Elsevier Ltd. All rights reserved.

[This corrects the article DOI: 10.1093/hropen/hoaa009.][This corrects the article DOI: 10.1093/hropen/hoaa009.].

Fake internet medical information, parapharmacies and counterfeit drugs constitute a market worth hundreds of billions of dollars per year1.Blackstone E.A. Fuhr J.P. Pociask S. The health and economic effects of counterfeit drugs.http://www.ncbi.nlm.nih.gov/pubmed/25126373Am Health Drug Benefits. 2014; 7: 216-224Google Scholar, 2.Ozawa S. Evans D.R. Bessias S. et al.Prevalence and estimated economic burden of substandard and Falsified medicines in low- and middle-income countries: a systematic review and meta-analysis.http://www.ncbi.nlm.nih.gov/pubmed/30646106JAMA Netw Open. 2018; 1 (e181662)doi:10.1001/jamanetworkopen.2018.1662Google Scholar, 3.Wise J. Global operation tackles Internet trade in fake drugs.http://www.ncbi.nlm.nih.gov/pubmed/23043094BMJ. 2012; 345 (e6724)doi:10.1136/bmj.e6724Google Scholar and pose a serious public health risk at the global level.4.Johnson S.B. Park H.S. Gross C.P. et al.Complementary medicine, refusal of conventional cancer therapy, and survival among patients with curable cancers.http://www.ncbi.nlm.nih.gov/pubmed/30027204JAMA Oncol. 2018; 4: 1375-1381doi:10.1001/jamaoncol.2018.2487Google Scholar Exposure of web visitors to fake and misleading information may decrease patients’ compliance to medically recommended treatments, promote the use of questionable and detrimental practices and jeopardise patient outcomes and survival.4.Johnson S.B. Park H.S. Gross C.P. et al.Complementary medicine, refusal of conventional cancer therapy, and survival among patients with curable cancers.http://www.ncbi.nlm.nih.gov/pubmed/30027204JAMA Oncol. 2018; 4: 1375-1381doi:10.1001/jamaoncol.2018.2487Google Scholar, 5.Vosoughi S. Roy D. Aral S. The spread of true and false news online.http://www.ncbi.nlm.nih.gov/pubmed/29590045Science. 2018; 359: 1146-1151doi:10.1126/science.aap9559Google Scholar, 6.The Lancet Oncology Oncology, "fake" news, and legal liability.http://www.ncbi.nlm.nih.gov/pubmed/30191835Lancet Oncol. 2018; 19: 1135doi:10.1016/S1470-2045(18)30610-7Google Scholar The threat posed by fake internet medical information may be of particular harm to patients where the burden of symptoms from the disease or treatment significantly influence quality of life, mood, daily activities and occupational and financial prospects or activity and family integrity.7.Mauri D. Tsali L. P Polyzos N. et al.Facing Internet fake-medicine and web para-pharmacy in the total absence of official recommendations from medical societies.http://www.ncbi.nlm.nih.gov/pubmed/31646774J Buon. 2019; 24: 1314-1325Google Scholar Across a range of cancers, where treatment toxicities, malnutrition, cachexia and pain can be significant factors the substantial functional and emotional needs and the motivation to find a solution leave patients with cancer and their relatives particularly vulnerable to fake information and treatments on the internet. What are the factors that may result in patients being exposed to, and potentially influenced by, such on-line harm? Clinical areas where there is a lack of a high-quality research base make it easier for misinformation to be seen as fact. In cancer medicine, for example, research into pain, malnutrition and cachexia does not attract significant funding and is not a popular field for oncologists, researchers or pharmaceutical companies. This may be as a result of competition with research seen as more cutting edge, for example, that using genome sequencing or translational molecular medicine or advanced radiotherapy techniques. It may also be a consequence of more difficult to define end points for clinical trials in these areas. Despite a slow observed improvement in symptom management in these areas over time, there remains an unmet need to adequately address patients’ nutritional and analgesic needs.8.Greco M.T. Roberto A. Corli O. et al.Quality of cancer pain management: an update of a systematic review of undertreatment of patients with cancer.http://www.ncbi.nlm.nih.gov/pubmed/25403222J Clin Oncol. 2014; 32: 4149-4154doi:10.1200/JCO.2014.56.0383Google Scholar, 9.Breivik H. Cherny N. Collett B. et al.Cancer-related pain: a pan-European survey of prevalence, treatment, and patient attitudes.http://www.ncbi.nlm.nih.gov/pubmed/19244085Ann Oncol. 2009; 20: 1420-1433doi:10.1093/annonc/mdp001Google Scholar, 10.Muscaritoli M. Rossi Fanelli F. Molfino A. Perspectives of health care professionals on cancer cachexia: results from three global surveys.http://www.ncbi.nlm.nih.gov/pubmed/28007753Ann Oncol. 2016; 27: 2230-2236doi:10.1093/annonc/mdw420Google Scholar, 11.Strasser F. Nutritional support in cancer – more formal recommendations are required, 25–29 September, Poster Session, Hall C, Vienna, Austria2019: 377Google Scholar Supportive service availability beyond that provided by oncologists varies among different health systems. However, only a few countries have structured supportive pain, dietetic, psychooncology and palliative care teams. A US survey documented that one-third of oncology patients do not receive pain medications proportional to their pain intensity levels, and concordantly, a European survey indicated that half of the European oncology patients believe that their quality of life is not considered a priority in their overall care by healthcare professionals.8.Greco M.T. Roberto A. Corli O. et al.Quality of cancer pain management: an update of a systematic review of undertreatment of patients with cancer.http://www.ncbi.nlm.nih.gov/pubmed/25403222J Clin Oncol. 2014; 32: 4149-4154doi:10.1200/JCO.2014.56.0383Google Scholar, 9.Breivik H. Cherny N. Collett B. et al.Cancer-related pain: a pan-European survey of prevalence, treatment, and patient attitudes.http://www.ncbi.nlm.nih.gov/pubmed/19244085Ann Oncol. 2009; 20: 1420-1433doi:10.1093/annonc/mdp001Google Scholar, 10.Muscaritoli M. Rossi Fanelli F. Molfino A. Perspectives of health care professionals on cancer cachexia: results from three global surveys.http://www.ncbi.nlm.nih.gov/pubmed/28007753Ann Oncol. 2016; 27: 2230-2236doi:10.1093/annonc/mdw420Google Scholar Consequently, the dissatisfaction of patients and their relatives is very high and, inevitably, they are prone to visit the internet and social media (Instagram, Twitter, Facebook, etc) which may be felt as unique sources to find solutions to their problems and disabilities. Exposure on the web to potentially misleading data, fake information and the counterfeit drug market is therefore maximised. Globally use of the internet has grown exponentially over the last 20 years.12.Internet growth statistics. Available: https://www.internetworld-stats.com/emarketing.htmGoogle Scholar In the real world, the internet is a complex open-access phenomenon with few controls or regulations regarding factual accuracy or sanctions against fraudulent activity. One of the instruments that may be best suited to counteract the detrimental effects of misleading web information and unrestricted access to potentially harmful medicines is through official web recommendations by medical authorities (official medical societies/health policy-maker providers) both for healthcare providers and for patients and their family members. Acknowledging that most oncologists are not trained, have restricted or no time or they do not have established tools to support or protect cancer patients from internet hazards, who should really support and ‘e-protect’ patients with cancer? It could be argued that recognised ‘approved’ medical organisations should provide patients protection by imparting recommendations directly via the internet. Unfortunately, this is not the case. In 2018, only a minority of official medical societies provided updated and structured recommendations to patients and family members on their websites.7.Mauri D. Tsali L. P Polyzos N. et al.Facing Internet fake-medicine and web para-pharmacy in the total absence of official recommendations from medical societies.http://www.ncbi.nlm.nih.gov/pubmed/31646774J Buon. 2019; 24: 1314-1325Google Scholar In a web survey of 370 oncology/anesthesiology societies, the scope and content of recommendations for physicians regarding cancer-related pain and cachexia were remarkably inconsistent. The proportion of societies providing up-to-date on-line evidence-based recommendations to physicians for cancer cachexia was only 2.96% (8 of 270)13.Mauri D. Zafeiri G. Yerolatsite M. et al.Global coverage and consistency of guideline recommendations for cancer cachexia on the web in 2011 and 2018.http://www.ncbi.nlm.nih.gov/pubmed/31316293Contemp Oncol. 2019; 23: 100-109doi:10.5114/wo.2019.85882Google Scholar and for cancer pain only 4.7% (17 of 370).14.Mauri D. Kalopita K.T.L. Cancer pain… who cares? International and national patterns of evidence-based global guidelines recommendations for physicians on the Web (2011 vs. 2018).2020Google Scholar Surprisingly, the web guidelines provision for physicians was not found to be dependent on human development index, geographical region or oncology specialisation. Surprisingly, the paucity of recommendations was evident even among the societies of specialties whose core purpose is the management of patients with cancer. The plethora of medical societies, organisations and health policy-makers that have developed over time offer a landscape of flourishing professional activity which does not seem to translate into adequate provision of practical on-line information for patients and family members. Have we left our patients …‘alone’ in the WEB? Can, in the internet era, medical professionals oversee the overall management and the on-line support of cancer patients? If, for example, we again look at the areas of palliative and supportive cancer medicine and the drivers to seek out on-line information the numbers are impressive. Out of the 18 000 000 new cancer cases diagnosed annually worldwide,15.Bray F. Ferlay J. Soerjomataram I. et al.Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries.http://www.ncbi.nlm.nih.gov/pubmed/30207593CA Cancer J Clin. 2018; 68: 394-424doi:10.3322/caac.21492Google Scholar pain affects more than half of cancer patients, with a prevalence of 55% among patients on anticancer treatment, 66.4% among those with advanced metastatic or terminal phases of the disease, 39.3% following curative treatment and with 38% of all patients reporting moderate to severe pain.16.van den Beuken-van Everdingen M.H.J. Hochstenbach L.M.J. Joosten E.A.J. et al.Update on prevalence of pain in patients with cancer: systematic review and meta-analysis.http://www.ncbi.nlm.nih.gov/pubmed/27112310J Pain Symptom Manage. 2016; 51: 1070-1090doi:10.1016/j.jpainsymman.2015.12.340Google Scholar, 17.Neufeld N.J. Elnahal S.M. Alvarez R.H. Cancer pain: a review of epidemiology, clinical quality and value impact.http://www.ncbi.nlm.nih.gov/pubmed/27875910Future Oncol. 2017; 13: 833-841doi:10.2217/fon-2016-0423Google Scholar Conversely, one-third of patients with malignancy will suffer of cancer cachexia, with this proportion being notably higher among patients affected by solid cancers. Cachexia prevalence in advanced cancer might be as high as 60%–80%.18.Lainscak M. Rosano G.M.C. Cancer cachexia: an orphan with a future.http://www.ncbi.nlm.nih.gov/pubmed/30920780J Cachexia Sarcopenia Muscle. 2019; 10: 3-5doi:10.1002/jcsm.12401Google Scholar Nutritional issues in patients with cancer are so important that the European Cancer Patient Coalition (ECPC) published a Cancer Patient’s Nutritional Bill of Rights, which was presented in the European Parliament in Brussels in November 2017.19.Caccialanza R. De Lorenzo F.G.L. et al.The cancer patients’ charter of rights for appropriate and prompt nutritional support.Nutr Care Cancer. 2017; 25: 3001-3004Crossref PubMed Scopus (39) Google Scholar But, … has the scale of this issue been acknowledged or reflected in provision of adequate support? Strongly motivated, anxious or worried patients and their family members may surf the internet or share their concerns through social media in an attempt to find complementary or alternative treatments, seek for clinical trials as well as to address symptoms and find ways to improve their quality of life.20.Tsuya A. Sugawara Y. Tanaka A. et al.Do cancer patients tweet? Examining the Twitter use of cancer patients in Japan.http://www.ncbi.nlm.nih.gov/pubmed/24867458J Med Internet Res. 2014; 16doi:10.2196/jmir.3298Google Scholar This is especially when they feel that they have been let down by the Health System or their physicians’ behaviour.21.Bell R.A. Hu X. Orrange S.E. et al.Lingering questions and doubts: online information-seeking of support forum members following their medical visits.http://www.ncbi.nlm.nih.gov/pubmed/21315538Patient Educ Couns. 2011; 85: 525-528doi:10.1016/j.pec.2011.01.015Google Scholar Nonetheless, in the absence of web recommendation from official medical societies, the potential risk for patients and family members to be exposed to harmful fake internet information with potentially detrimental effects on patients’ outcome and survival,4.Johnson S.B. Park H.S. Gross C.P. et al.Complementary medicine, refusal of conventional cancer therapy, and survival among patients with curable cancers.http://www.ncbi.nlm.nih.gov/pubmed/30027204JAMA Oncol. 2018; 4: 1375-1381doi:10.1001/jamaoncol.2018.2487Google Scholar is significant. The plethora of available web and social media information (Twitter, Instagram, Facebook etc), makes it difficult for individuals to be able to filter ‘true’ from ‘false’ information. Of note, the use of different social media impacts patients’ communication and information variably. Traditionally, bloggers publish and exchange long texts with the major part of contents being shared not in real time. Nowadays, bloggers are switched from blogs to the more active microblogs (also known as nanoblogs) where instant messaging, direct conversations and the use of microposts in various content formats (including audio, video, images and text) are immediate and super-fasts rendering the risk of uncontrolled e-information much higher, with low threshold of critical thinking. Microblogging is the new form of building connections as users continue to turn to mobile solutions as an immediate source of information. In fact, in 2018, the 52.2% of website traffic worldwide was generated by mobile devices.22.Share of mobile phone website traffic worldwide.2018https://www.statista.com/statistics/241462/global-mobile-phone-website-traffic-share/Google Scholar Real-time sharing, frequent posts, fast-paced environment and the possibility to maintain relationships make microblogs a microenvironment particularly sensitive to e-trade. Here, the potential customers may share time-sensitive information and have a personal interaction with sellers. Actually, we have different microblog platforms with contents designed for quick interactions of different audiences: Facebook (social network site where users share text, live videos and more to connect each other), Twitter (that allow quick and practical way to share short posts, GIFs (Graphics Interchange Format images), article links, videos and more), Pinterest (that links to products, articles and useful information for audiences) LinkedIn (social network site with professional profile); Instagram (visual form of blogging, allowing to share stories and snaps). For those reasons, patients’ exposure to misleading medical information in microblogs’ environment can be maximal. In this setting, it is easy to identify and describe the economic drivers that result in the development formation of a vicious cycle of misinformation and fraud. The potential for enormous profits trigger the paramedical markets to self-perpetuating production of more extensive and persuasive misleading information and availability of counterfeit drugs or quack cures on the internet. The increase in web misinformation is so high that it may reach the dimension of harmful internet fake-data out breaks (figure 1). Apart parapharmacy, black-drug market and counterfeits drug market, another issue that is rapidly arising is how manage the web information on official but particularly expensive drugs, especially when promising treatments are addressed on a very early stage in the absence of a confirmatory study.23.Hwang T.J. Franklin J.M. Chen C.T. et al.Efficacy, safety, and regulatory approval of food and drug Administration-Designated breakthrough and Nonbreakthrough cancer medicines.http://www.ncbi.nlm.nih.gov/pubmed/29688832J Clin Oncol. 2018; 36: 1805-1812doi:10.1200/JCO.2017.77.1592Google Scholar Redundant and extensive web information on a promising but unconfirmed and costly treatment may indeed both expose the patients to futile hopes and threaten the health systems economics. How to inform the media-industry on ‘new, promising but unconfirmed and costly drugs and treatments’ is an emerging issue that needs to be regulated in the next future. In the era of ‘new media, fake e-medicine and counterfeit drug e-market’, medical societies, having been slow to capitalise the role of the internet as a tool to assist and inform patients and families, have left the door open for development of an unregulated and exclusively profit-driven sector. There are convincing data that improved health e-literacy for patients with cancer and their families is an important instrument in understanding and evaluating information provided on the internet.24.Heiman H. Keinki C. Huebner J. et al.EHealth literacy in patients with cancer and their usage of web-based information.http://www.ncbi.nlm.nih.gov/pubmed/30006768J Cancer Res Clin Oncol. 2018; 144: 1843-1850doi:10.1007/s00432-018-2703-8Google Scholar Therefore, the promotion, via the internet, of specific supportive care recommendations by official medical societies working in partnership with patient organisations directed both to physicians (specialists audience) as well as patients and their families (general audience), would likely be of significant value in protecting various internet threats. It will be important to ensure that development of ‘official’ on-line e-recommendations be of a consistently high standard and kept up to date with developments in the field. Of course, e-recommendation production should be notably improved at the global level. Recommendations for the general audience should not be confounded with the recommendations/guidelines for specialists since the information needs may be different and the use of complex, technical language result in confusion. The provision of patient-specific on-line information may be a novel endeavour for official medical societies generally devoted to the specialist education of clinicians and researchers. Thus, we propose the development of a ‘patient corner’ in each society website. This may not require all medical societies to have their own patient-centred recommendations. We believe in the value of both guidelines produced by societies themselves and/or of ‘links’ to recommendations on the web sites of other official medical organisations. To achieve the maximum global reach we believe that this form of patient specific guidance should be provided, in the local language of the target audience. In case of links to international recommendation, usually written in English, the role of national medical societies may be to provide a summary or full translation of such information. Use of web position statements and social media positive ‘influencers’ from official health providers25.Teoh D. The power of social media for HPV Vaccination-Not fake news!.http://www.ncbi.nlm.nih.gov/pubmed/31099637Am Soc Clin Oncol Educ Book. 2019; 39: 75-78doi:10.1200/EDBK_239363Google Scholar may also be important tools to counter-balance fake information from the strong paramedicine market. A step in the right direction has been that the American Cancer Society (ACS), the National Cancer Institute (NCI), the European Society for Medical Oncology (ESMO) and the ECPC have recently provided some updated web recommendations for cancer-related pain and/or cachexia.26.NIH (National Cancer Institute). Cancer Pain (PDQ®)–Patient Version. Available: https://www.cancer.gov/about-cancer/treatment/side-effects/pain/pain-pdqGoogle Scholar, 27.NIH (National Cancer Institute). Nutrition in Cancer Care (PDQ®)–Patient Version. Available: https://www.cancer.gov/about-cancer/treatment/side-effects/appetite-loss/nutrition-pdqGoogle Scholar, 28.ESMO patient guide on cancer pain management.Google Scholar, 29.European Cancer Patient Coalition. Living well during cancer treatment. Draft nutrition consultation document. Available: http://www.ecpc.org/images/updatedDraftConsultationDocument.pdfGoogle Scholar, 30.ACS American Cancer Society. Available: https://www.cancer.org/treatment/treatments-and-side-effects/physical-side-effects/pain/facts-about-cancer-pain.htmlGoogle Scholar Of note, ESMO also provides translation for patient guidelines in multiple languages.31.ESMO. Patient guides. Available: https://www.esmo.org/for-patients/patient-guides/patient-guides-by-language?hit=ehp [Accessed 20 Feb 2020].Google Scholar Form of guidance for patients with cancer and doctor-approved cancer information from the American Sociality of Clinical Oncology (ASCO) had been also supplied in cancer.net web site and in twitter by CancerDotNet.32.ASCO. Patients resources. Available: https://www.asco.org/research-guidelines/clinical-trials/clinical-trial-resources/patient-resources [Accessed 20 Feb 2020].Google Scholar, 33.Cancer.Net. Doctor Approved patient information from ASCO. Available: https://twitter.com/cancerdotnet?lang=en [Accessed 20 Feb 2020].Google Scholar We believe and suggest (in respect of each national society/institution legitimate rights, sovereignty of decision and freedom of expression) each National oncology society (radiation, surgical, medical, nursing oncology) to produce web recommendations for patients either of their own or as a cyber e-link to available official guidelines and translated to each country’s national language(s). The ACS, ASCO, American Society for Radiation Oncology, ESMO, European Society for Radiotherapy and Oncology, European Society of Surgical Oncology, European School of Oncology, European Oncology Nursing Society, ECPC, National Comprehensive Cancer Network, NCI, International Society of Paediatric Oncology, European Society of Paediatric Oncology and all the other major international gatekeeper societies for oncology patients need to closely embrace and further develop this new field of internet education in order to protect patients against fake e-medicine and the counterfeit drug and supplement web market.

Abstract Here are investigated the serum hormones in ovarian stimulation cycles of oocyte donors (OD), under endogenous luteinizing hormone (LH) suppression with GnRH antagonist (antGnRH) vs. desogestrel (DSG) (progesterone-primed [PP]). OD underwent ovarian stimulation with gonadotropins at a private, university-based, infertility center between January 2017 and March 2018. Endogenous LH peak was controlled with either daily injections of antGnRH or with daily oral 75 mcg DSG (PP) until triggering. LH and progesterone were measured at trigger and the following day. A total of 404 OD cycles were included. There were no differences in age (26.7 ± 4.9 vs. 27.1 ± 4.8 years), AMH (3.7 ± 2.1 vs. 4.1 ± 2.7 ng/ml), and body mass index (BMI) (22.4 ± 2.8 vs. 22.1 ± 3.0 kg/m2) between PP and antGnRH groups, respectively. On the day of trigger, progesterone was lower in PP compared to antGnRH (0.9 ± 0.7, vs. 1.5 ± 1.2 ng/ml, p < .001), whereas no significant differences existed in estradiol or LH. On the day after trigger, lower progesterone in PP vs. antGnRH (10.8 ± 6.0 vs. 13.4 ± 7.9 ng/ml, p=.002) was observed. No differences were observed in the number of retrieved oocytes or the clinical pregnancies among recipients. Our study shows that endocrine response to DSG differs significantly as compared to antGnRH use for the control of endogenous LH without apparent impact on number of retrieved oocytes or the clinical pregnancies among recipients.