International Scientific Societies Research Articles

Uric acid in atherosclerosis and cardiovascular diseases: innocent bystander or ruthless killer?

Medical attention to uric acid (UA) has been increasing in recent years, mainly because this molecule has been shown to be associated with increased cardiovascular risk, both in the general population and in the hypertensive patients. A growing body of clinical and experimental data supports this view and prompts reconsideration of the role of UA in the development of atherosclerosis and the genesis of cardiovascular disease. It is known that this substance, in certain plasma concentrations, induces increased oxidative stress, a chronic inflammatory state, and a whole series of other modifications that are potentially deleterious at the cardiovascular level leading to hypertension, atherosclerosis, atrial fibrillation (AF), and other metabolic changes such as diabetes, metabolic syndrome, non-alcoholic fatty liver disease and kidney failure. Despite this epidemiologic and mechanistic evidence, the current guidelines from international cardiology scientific societies do not give precise indications in this regard, and some of them only suggest UA evaluation as part of an initial screening of the hypertensive patient. The purpose of this review is to briefly describe the main clinical and epidemiological evidence supporting the role of hyperuricemia as a possible emerging cardiovascular risk factor and to analyze the potential pathophysiological mechanisms through which elevated UA levels may exert a detrimental effect on the cardiovascular system.

EACVI survey on radiation exposure in interventional echocardiography.

The European Association of Cardiovascular Imaging (EACVI) Scientific Initiatives Committee performed a global survey on radiation exposure in interventional echocardiography. The survey aimed to collect data on local practices for radioprotection in interventional echocardiography and to assess the awareness of echocardiography operators about radiation-related risks. A total of 258 interventional echocardiographers from 52 different countries (48% European) responded to the survey. One hundred twenty-two (47%) participants were women. Two-thirds (76%) of interventional echocardiographers worked in tertiary care/university hospitals. Interventional echocardiography was the main clinical activity for 34% of the survey participants. The median time spent in the cath-lab for the echocardiographic monitoring of structural heart procedures was 10 (5-20) hours/month. Despite this, only 28% of interventional echocardiographers received periodic training and certification in radioprotection and 72% of them did not know their annual radiation dose. The main adopted personal protection devices were lead aprons and thyroid collars (95% and 92% of use, respectively). Dedicated architectural protective shielding was not available for 33% of interventional echocardiographers. Nearly two-thirds of responders thought that the radiation exposure of interventional echocardiographers was higher than that of interventional cardiologists and 72% claimed for an improvement in the radioprotection measures. Radioprotection measures for interventional echocardiographers are widely variable across centres. Radioprotection devices are often underused by interventional echocardiographers, portending an increased radiation-related risk. International scientific societies working in the field should collaborate to endorse radioprotection training, promote reliable radiation dose assessment, and support the adoption of radioprotection shielding dedicated to interventional echocardiographers.

Standardized reporting for systematic global evaluation of axial spondyloarthritis: An evidence-based and consensus-driven initiative

IntroductionNational and international scientific societies advocate for a regular, systematic, and standardized global evaluation of axial spondyloarthritis (axSpA) patients. However, there are no recommendations specifying the content of this global evaluation. This initiative aimed to propose a standardized reporting framework, using evidence-based and consensus approaches, to collect data on all domains of axSpA. MethodsA literature review and consensus process involved a steering committee and an expert panel of 37 rheumatologists and health professionals. The first steering committee took place in March 2022 and identified the main domains for inclusion in the standardized report. A hierarchical literature review was conducted to identify items within these domains and tools for assessment. The items and tools for assessment were discussed and consensus was reached through a vote session during an expert meeting that took place in March 2023. ResultsThe steering committee identified four main domains to include in the standardized reporting framework: disease assessment, comorbidities, lifestyle, and quality of life. Items and tools for assessment were adopted after the expert meeting. Additionally, recommendations regarding digital tools (websites, apps, social media) were provided. ConclusionThis initiative led to a consensus, based on evidence and expertise, on a reporting framework for use during periodic systematic global evaluations of axSpa in daily practice.

Physical activity for muscle rehabilitation in sarcopenia

Background: sarcopenia is a progressive and generalized clinical condition associated with loss of mass, strength, and/or muscle function, impairing physical performance. The definition of sarco-penia is a dilemma, as several studies have been published in the last ten years by different socie-ties. One of the most used definitions is the Guideline created by the European Working Group on Sarcopenia in Older People (EWGSOP) and updated in 2019 (EWGSOP2) to facilitate the under-standing of sarcopenia and improve treatment proposals. This is the only definition supported by several international scientific societies for clinical practice and research in patients with sarcope-nia. Treatment can be divided into non-pharmacological and pharmacological. There are no spe-cific drugs approved for the treatment of sarcopenia. As for non-pharmacological interventions, physical exercise is the most effective intervention, especially resistance exercises. Nutritional in-tervention has a low level of evidence. Objectives: The objective of this article is to review data on the effect of physical exercise in the treatment of sarcopenia. Method: Reviews and systematic re-views were searched in different data sources, including PubMed, between the years 2010 and 2024, with the keywords (sarcopenia and non-pharmacological treatment; sarcopenia and exercise and sarcopenia). Conclusions: Physical exercise is the first-line treatment for sarcopenia. There is no drug released for the specific treatment of sarcopenia, and nutritional interventions have little clinical evidence in improving the quantitative and functional aspects of the muscular system in sarcopenic patients. Among the exercise modalities, resistive exercises alone showed the most sig-nificant benefit in the muscular rehabilitation of sarcopenic patients. Despite this, when evaluated with resistive exercise, aerobic and balance exercises brought additional benefits in some muscular functions. Nutritional intervention also appears to improve muscle strength when associated with resistive exercises. More studies are needed to elucidate the best physical activity program and whether other nutritional interventions could benefit the patient more.

Study rationale and design of the PEOPLHE trial

PurposeLung cancer screening (LCS) by low-dose computed tomography (LDCT) demonstrated a 20–40% reduction in lung cancer mortality. National stakeholders and international scientific societies are increasingly endorsing LCS programs, but translating their benefits into practice is rather challenging. The “Model for Optimized Implementation of Early Lung Cancer Detection: Prospective Evaluation Of Preventive Lung HEalth” (PEOPLHE) is an Italian multicentric LCS program aiming at testing LCS feasibility and implementation within the national healthcare system. PEOPLHE is intended to assess (i) strategies to optimize LCS workflow, (ii) radiological quality assurance, and (iii) the need for dedicated resources, including smoking cessation facilities.MethodsPEOPLHE aims to recruit 1.500 high-risk individuals across three tertiary general hospitals in three different Italian regions that provide comprehensive services to large populations to explore geographic, demographic, and socioeconomic diversities. Screening by LDCT will target current or former (quitting < 10 years) smokers (> 15 cigarettes/day for > 25 years, or > 10 cigarettes/day for > 30 years) aged 50–75 years. Lung nodules will be volumetric measured and classified by a modified PEOPLHE Lung-RADS 1.1 system. Current smokers will be offered smoking cessation support.ConclusionThe PEOPLHE program will provide information on strategies for screening enrollment and smoking cessation interventions; administrative, organizational, and radiological needs for performing a state-of-the-art LCS; collateral and incidental findings (both pulmonary and extrapulmonary), contributing to the LCS implementation within national healthcare systems.

P492 All intestinal ultrasound scores for ulcerative colitis (and IBUS-SAS) strongly correlate with endoscopic activity: a prospective study

Abstract Background Intestinal ultrasound (IUS) is gaining increasing acceptance as a reliable tool for tight monitoring of ulcerative colitis (UC). Although several IUS scores have been proposed, none has been formally implemented into official recommendations of international scientific societies. This study aims to compare the available IUS score for UC, in terms of correlation with endoscopic activity. Methods Patients with UC ≥ 18 years old undergoing partial or full colonoscopy between April and October 2023 were prospectively included. Endoscopic evaluation of at least the sigmoid colon was mandatory for inclusion, and patients with proctitis (Montreal E1) were excluded. Endoscopic activity was scored with both the Mayo Endoscopic Subscore (MES) and the Ulcerative Colitis Endoscopic Index of Severity (UCEIS), and defined by MES ≥ 1 and UCEIS ≥ 2. IUS was performed within 4 weeks of endoscopy. The Milan Ultrasound Criteria (MUC, Allocca et al.), the UC-IUS score (Bots et al.), the US Score from Parente et al., and the score from Hata et al. were included in the analysis. Applicability of the US Score from Civitelli et al, an IUS score developed for paediatric patients, and the IBUS-SAS, an IUS score validated for Crohn’s disease, was also evaluated. The Spearman’s rank coefficient (rho = ρ) was used to perform correlations, while receiver operating characteristic (ROC) curves were compared with the Hanley &amp; McNeil method. Results Fifty-nine patients were included, of which 59.3% and 50.8% showed any endoscopic activity using the MES and the UCEIS, respectively. Detailed information about the population is reported in Table. All the evaluated IUS scores showed a significant positive correlation with endoscopic activity (p &amp;lt; 0.001), with the UC-IUS score and the US Score from Civitelli et al. outperforming the others both with MES (ρ = 0.745, ρ = 0.762) and UCEIS (ρ = 0.751, ρ = 0.769). The same scores showed the highest Areas Under the Curve (AUC) for detecting a MES ≥ 2 (UC-IUS: 0.841, 95%CI 0.722-0.923, p &amp;lt; 0.001; Civitelli et al.: 0.842, 95%CI 0.724-0.924, p &amp;lt; 0.001) [Figure]. The optimal cut-offs for detecting a MES ≥ 2 with both the MUC and the Civitelli score were similar to that proposed by the Authors (&amp;gt; 5.04 vs &amp;gt; 6.20 and &amp;gt; 2 vs &amp;gt; 1, respectively). Conclusion All the included IUS scores showed good correlation with endoscopic activity. The UC-IUS and the US Score from Civitelli et al. performed better than the others in detecting a MES ≥ 2 and might be suggested to monitor disease activity of UC and intervene early during disease relapse.

Traitement guidé des infections à Helicobacter pylori : évolutions des pratiques pour un diagnostic moderne et remboursé ?

AbstractDespite unanimous recommendations from international and national scientific societies and the HAS in 2017 to favor treatment of Helicobacter pylori infections guided by a sensitivity test carried out from gastric biopsies, almost all of the treated patients still receive empirical treatment poorly tolerated and source of the continuous development over forty years of the resistance of this bacteria to antibiotics. It is time for General Practitioners, Gastroenterologists and Biologists to coordinate and mobilize to promote the guided treatment of the most common chronic bacterial infection and thus enter into a process of proper use of antibiotics. The recent reimbursement of PCR detecting H. pylori and the mutations responsible for resistance to clarithromycin should remove one of the obstacles to this guided treatment strategy. We propose a new management algorithm for these infections taking into account the reimbursements recently obtained. Recent technological advances already make it possible to imagine a future integrating sensitivity tests from a non-invasive sample: stools, saving numerous unnecessary fiberoscopies at a time when recourse to a gastroenterologist is difficult. For this near future we propose a new algorithm of what will be the coordinated work of general practitioners, gastroenterologists and biologists.

L’analisi pedagogica come oggetto. Spunti di riflessione della comunità scientifica fra teoria e prassi

The essay discusses the reasons behind the decision to hold a conference at the Collegio Ghisleri, Pavia, on 27 May 2023 and to publish in this journal the dossier that originated from this event, which was an occasion for exchange and discussion. The underlying idea was to gather together representatives (Presidents or their delegates) of national and international scientific societies, especially Italian and French, as well as researchers from different European countries (especially Italy, France and Germany) and from different scientific-disciplinary fields in order to put pedagogical analysis at the center of the debate as a subject of study, along with its impossible and hypercomplex objects, which are the result of constant transactions that necessarily take us beyond the institutional scientific-disciplinary boundaries. A problematization of the epistemic territory between theory and practice thus emerges, also starting from the dossier’s red threads and key themes.

Do the clinical practice guidelines for paediatric dentistry meet the quality standards? A meta-research and quality appraisal using the AGREE II tool.

Clinical practice guidelines (CPGs) enhance health care and aid clinicians' decisions. To evaluate the quality of clinical guidelines in paediatric dentistry using the AGREE II tool. PubMed, EMBASE, Scopus, LIVIVO, Lilacs, international guidelines websites, scientific societies, and gray literature were searched until September 2021. We included paediatric dental clinical guidelines and excluded drafts or guidelines for patients with special needs. Two independent reviewers performed quality assessment using the APPRAISAL OF GUIDELINES FOR RESEARCH & EVALUATION II (AGREE II) instrument. We calculated the mean overall domain scores (95% confidence interval) for each guideline. We used regression analysis to correlate the score of overall assessment and the six domains of AGREE II with guideline characteristics. Forty-four guidelines were included in this study. Highest mean score was for Domain 4 (Clarity of Presentation; 58%, 95% CI: 50.8-64.9), whereas the lowest was for Domain 5 (Applicability; 16%, 95% CI: 10.8-21.4). The reporting quality was improved in Domains 1-5 with reporting checklists (p < .001), whereas that of Domain 6 was improved by decreasing years since publication (p = .047). Paediatric dental guidelines do not comply with the methodological quality standard, especially in Domain 5 (Applicability). The AGREE reporting checklist should be implemented with a system to evaluate the certainty of evidence for future guidelines.

Andrés Posada Arango. The scientist, the naturalist, the doctor, the historian

A hundred years after Andres Posada Arango’s departure, his life is recognized, which, in some way, is part of that of all the doctors graduated from the Antioquia Medical Schools; He was one of the pioneers in the creation of the first School of Medicine in this region and one of its first professors. Through his writings you can discover his great interest in medicine, natural sciences, anthropology and history. His scientific spirit allowed him to recognize in hookworm the etiology of a disease known in the region as the Tun-tun; identify the origin and characteristics of the poison used by the Indians in the Choco; study the aborigines that inhabited the Antioquia territories and deserve that a plant bear its name Posadaea Sphaerocarpa, to transcend time as part of the characters who left their mark on universal history. The 148 publications in national and international journals and being a member of 18 national and international scientific Academies and Societies are the best presentation of the legacy left by this doctor and naturalist from Antioquia.

What Evidence-based Medicine (EBM) Doesn't Say About Allergen-specific Immunotherapy (AIT).

Evidence-based allergology for the treatment of allergic rhinitis with allergen-specific immunotherapy (AIT) has been used in publications by the companies manufacturing AIT. The purpose of randomized controlled trials (RCTs) is to provide physicians, health authorities, patients, and their families with the best evidence upon which to base treatment decisions. However, some RCT results may do more harm than good because they serve the commercial interests of the companies producing and marketing AIT more than the interests of patients. Allergic rhinitis is a trivial disease that is not life-threatening and is easily controlled by drugs. In this paper, we analyze some of the more controversial points underlying the EBM supporting the use of AIT. The paradox behind RCT-based practice is that AIT is based on the results of incorrectly interpreted RCTs. International scientific societies and drug regulatory bodies should analyze trials more carefully, considering potential conflicts of interest.

Clinical practice guideline recommendations for diagnosis and management of anxiety and depression in hospitalized adults with delirium: a systematic review

BackgroundDelirium commonly occurs in hospitalized adults. Psychiatric disorders such as anxiety, depression, and post-traumatic stress disorder (PTSD) can co-occur with delirium, and can be recognized and managed by clinicians using recommendations found in methodological guiding statements called Clinical Practice Guidelines (CPGs). The specific aims of this review were to: [1] synthesize CPG recommendations for the diagnosis and management of anxiety, depression, and PTSD in adults with delirium in acute care; and [2] identify recent published literature in addition to those identified and reported in a 2017 review on delirium CPG recommendations and quality.MethodsMEDLINE, EMBASE, CINAHL, PsycINFO, and 21 sites on the Canadian Agency for Drugs and Technologies listed in the Health Grey Matters Lite tool were searched from inception to February 12, 2021. Selected CPGs focused on delirium in acute care, were endorsed by an international scientific society or governmental organization, and contained at least one recommendation for the diagnosis or management of delirium. Two reviewers independently extracted data in duplicate and independently assessed CPG quality using the AGREE-II tool. Narrative synthesis of CPG recommendations was conducted.ResultsTitle and abstract screening was completed on 7611 records. Full-text review was performed on 197 CPGs. The final review included 27 CPGs of which 7 (26%) provided recommendations for anxiety (4/7, 57%), depression (5/7, 71%), and PTSD (1/7, 14%) in delirium. Twenty CPGs provided recommendations for delirium only (e.g., assess patient regularly, avoid use of benzodiazepines). Recommendations for the diagnosis of psychiatric disorders with delirium included using evidence-based diagnostic criteria and standardized screening tools. Recommendations for the management of psychiatric disorders with delirium included pharmacological (e.g., anxiolytics, antidepressants) and non-pharmacological interventions (e.g., promoting patient orientation using clocks). Guideline quality varied: the lowest was Applicability (mean = 36%); the highest Clarity of Presentation (mean = 76%).ConclusionsThere are few available evidence-based CPGs to facilitate appropriate diagnosis and management of anxiety, depression, and PTSD in patients with delirium in acute care. Future guideline developers should incorporate evidence-based recommendations on the diagnosis and management of these psychiatric disorders in delirium.Systematic review registrationRegistration number: PROSPERO (CRD42021237056)

The international spinal cord injury pain basic data set (version 3.0).

Expert opinion, feedback, revisions, and final consensus. To update the International Spinal Cord Injury Pain Basic Data Set (ISCIPBDS version 2.0) and incorporate suggestions from the SCI pain clinical and research community with respect to overall utility. International. The ISCIPBDS working group evaluated these suggestions and made modifications. The revised ISCIPBDS (Version 3.0) was then reviewed by members of the International SCI Data Sets Committee, the American Spinal Injury Association (ASIA) Board, the International Spinal Cord Society (ISCoS) Executive and Scientific Committees, individual reviewers and societies, and posted on the ASIA and ISCoS websites for 1 month to elicit comments before final approval by ASIA and ISCoS. The ISCIPBDS (Version 3.0) was updated to make the dataset more flexible and useful: 1. The assessment can be based on the patient's perception of several of his/her "worst" pain(s) or based on the International SCI Pain (ISCIP) Classification-defined or other pain types, depending on the specific research questions or clinical needs. 2. Pain interference should usually be rated for overall pain but may also be used for specific pain problems if needed. 3. An optional pain drawing was added to complement the check box documentation of pain location. 4. Data categories consistent with the Extended Pain Dataset list of current treatments were added. 5. Several new training cases were added.

Engaging with the Nagoya Protocol on Access and Benefit-Sharing: recommendations for noncommercial biodiversity researchers

Abstract The Convention on Biological Diversity and the Nagoya Protocol on Access and Benefit-Sharing provide an international legal framework that aims to prevent misappropriation of the genetic resources of a country and ensure the fair and equitable sharing of benefits arising from their use. The legislation was negotiated at the behest of lower-income, biodiverse countries to ensure that benefits derived from research and development of genetic resources from within their jurisdictions were equitably returned and could thereby incentivize conservation and sustainable use of biodiversity. Despite good intentions, however, rapid adoption of access and benefit-sharing measures at the national level, often without participatory strategic planning, has hampered noncommercial, international collaborative genetic research with counterproductive consequences for biodiversity conservation and sustainable use. We outline how current implementation of the Convention of Biological Diversity and the Nagoya Protocol affect noncommercial research, such as that conducted in many disciplines in biology, including mammalogy. We use a case study from Brazil, an early adopter, to illustrate some current challenges and highlight downstream consequences for emerging pathogen research and public health. Most emerging pathogens colonize or jump to humans from nonhuman mammals, but noncommercial research in zoonotic diseases is complicated by potential commercial applications. Last, we identify proactive ways for the mammalogical community to engage with the Convention on Biological Diversity and the Nagoya Protocol, through sharing of nonmonetary benefits and working with local natural history collections. Leveraging international scientific societies to collectively communicate the needs of biodiversity science to policy makers will be critical to ensuring that appropriate accommodations are negotiated for noncommercial research.

Challenges in intensive medicine: Diversity, equity and inclusion. Gender statement of the Spanish Society of Intensive and Critical Medicine and Coronary Units (SEMICYUC)

Gender is a social determinant that impacts health and generates inequalities at all levels. It has impacts patients and critical conditions, health professionals and professional career development, and scientific societies from a perspective of social justice. All the International scientific societies of Intensive Care Medicine committed to contributing a gender perspective agree on the institutional need for achieving a formal positioning standpoint. The Spanish Society of Intensive and Critical Medicine and Coronary Units (SEMICYUC) is committed to ensuring the equality, inclusion and representativeness of its health professionals to fight the existing gender gap in the field of Intensive Medicine.

Publishing industry–sponsored studies

The debate around the role of pharmaceutical industries (hereinafter “pharma”) in the field of sexual medicine over the course of my (A.S.) nearly 30 years of clinical and translational research on this amazing topic has been harsh and sometimes unproductive. This is a welcome opportunity to exchange some observations and thoughts and open an interesting debate for younger colleagues who, for chronologic reasons, missed a flourishing moment of initiatives and studies in this beloved field. Indeed, on one hand, long-term experience helps; on the other, fresh ideas corroborate the experience and open extraordinary new horizons. Historically, pharma have provided valuable support to medical research in terms of funding and intellectual contributions, resulting in several advancements and developments in patient care. That’s all folks: pharma have supported great scientifically rigorous research in the field. Or perhaps it may be better to say—this could be all, dear folks. In the specific and relatively narrow context of sexual medicine, pharma have played a primary role throughout the last 50 years, with an incredible peak in the late 1990s and early 21st century in (1) the discovery, development, and implementation of drugs for the treatment of erectile dysfunction (ED) that have drastically revolutionized the field; (2) the way that we treat patients; (3) our way of approaching medicine; and (4) the way in which research, at least clinical research, has been conducted from 1998 onward. Here, whatever the mythologic origin of sildenafil was—the iconic progenitor of all phosphodiesterase type 5 inhibitors (PDE5is)1,2—and whatever the intention with which sildenafil was initially under investigation,3 it is clear that the quality of life of patients struggling with ED would not have been as dramatically improved as it is now without the financial and managing support of pharma. Second, it is also very clear that, as the physicians and research experts in the field of sexual medicine, we would have never had the opportunity to conduct so many well-designed studies or get to know one another and exchange ideas and projects without the existence of sildenafil and, thereafter, all other PDE5Is that were conceived,4 produced, and launched on the market in the following years. This has been the case not only regarding ED but also surrounding other male sexual dysfunctions (eg, premature ejaculation5) and women’s sexual health.6-8 Last but not least, pharma have played a major role in supporting national and international scientific societies in the area of sexual medicine. This aspect is certainly no less relevant. In fact, the financial support of pharma has been paramount to the execution of research studies and the public presentation of results in the contexts of dedicated experts—opportunities that otherwise would have been difficult to come by. A striking example is the “birth” of the European Society for Sexual Medicine (formally ESIR) in 1995, with the first congress being held in Porto Carras, Greece. This has been the case for many other affiliated societies of the International Society for Sexual Medicine. Likewise, funds from pharma have provided seeds and starting grants to many research centers, by means of which they were able to develop independent lines of research and have the subsequent opportunity to apply for more competitive grants. Again, what an incredible cultural exchange it has been to meet and discuss—sometimes even to vigorously clash on—some of the many themes that the field of sexual medicine proposes. All of this has been thanks to the sponsorship of pharma, who have been able to promote their belief and support in the development of a healthy and correct scientific culture while supporting their own business objectives.

Current diagnostic algorithms for chronic heart failure with preserved left ventricular ejection fraction

Chronic heart failure remains one of the main causes of mortality and reduced life quality both in Ukraine and around the world. More than 50 % of all patients with chronic heart failure are those with preserved left ventricular ejection fraction. In current guidelines, the criteria for evaluating heart failure with reduced left ventricular ejection fraction are described properly, but the issue of timely diagnosing chronic heart failure with preserved ejection fraction still remains unsolved. This review presents four diagnostic algorithms for this condition, which were presented by international scientific societies in recent years: 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure; H2FPEF Score for Heart Failure with Preserved Ejection Fraction (Mayo, 2018); HFA-PEFF diagnostic algorithm: a consensus recommendation from the Heart Failure Association (HFA) of the European Society of Cardiology (ESC) (2019); Multimodality imaging in patients with heart failure and preserved ejection fraction: an expert consensus document of the European Association of Cardiovascular Imaging (2021). The main advantages, limitations and disadvantages of each one are analyzed. All steps of diagnostic evaluation are described in detail. The review is illustrated with patterns of the latest diagnostic approaches.

Determination of vitamin D3 conjugated metabolites: a complementary view on hydroxylated metabolites.

Experts typically define vitamin D deficiency levels by the determination of a circulating 25-hydroxyvitamin D3-calcifediol prohormone. A large part of the population is characterized by deficient vitamin D levels (calcifediol < 20 ng mL-1) despite individuals not being affected by any disorder. Cholecalciferol (vitamin D3) and/or calcifediol supplementation is a common practice for vitamin D-deficient individuals as recommended by international scientific societies and official agencies. In the last few years, several studies have reported the presence of conjugated vitamin D3 metabolites, mainly glucuronidation and sulfation derivatives, although simultaneous quantitative measurements involving phase I and II vitamin D metabolites have not been carried out. A quantitative method based on tandem mass spectrometry detection is proposed here for the combined determination of phase I and phase II vitamin D3 metabolites in human serum. As phase I and phase II metabolites are preferentially ionized in different modes, a switching polarity mode was adopted to determine both groups of compounds in serum at high sensitivity levels (pg mL-1). The validation of this proposal was successfully accomplished by following the Center for Drug Evaluation and Research (CDER) guidelines. Its applicability was tested in a cohort of volunteers with mostly deficient baseline levels. Considering the sulfated form of calcifediol, the sum of its concentrations showed sufficient baseline vitamin D levels in all individuals, suggesting that this could be a novel strategy for vitamin D deficiency definition. Therefore, phase II metabolites are proposed to be included when evaluating the vitamin D status since they provide more information about the overall status of the vitamin D endocrine system. Nevertheless, further studies are required to confirm the biological activity of these conjugated metabolites and the suitability of this strategy for the description of vitamin D deficiency.

Management of Heart Failure with Reduced Ejection Fraction Globally and in Lebanon: Where Do SGLT-2is Stand?

Heart failure (HF) is a clinical syndrome due to structural and/or functional cardiac anomalies, accompanied by elevated natriuretic peptide levels and/or cardiogenic pulmonary or systemic congestion; severely compromising patients’ health, performance and quality of life. The advancement of novel treatment and their endorsement by international medical and scientific societies have shifted the treatment of HF with reduced ejection fraction (HFrEF) towards quadruple therapy: an angiotensin receptor-neprilysin inhibitor or an angiotensin-converting enzyme inhibitor, a beta-blocker, a mineralocorticoid receptor antagonist and a sodium/glucose co-transporter-2 inhibitor (SGLT2i). This paper reviews the available literature on state-of-the-art diagnostic and therapeutic advances in HFrEF, discusses landmark trials that shifted the paradigm towards quadruple therapy in HFrEF, visits the potential challenges in Lebanon and globally, proposes an algorithm for treatment introduction and sequencing in HFrEF and highlights clinical considerations for HFrEF management and patient education and follow-up. This practical guidance could serve cardiologists and other medical specialists in identifying clinical signs of HFrEF, diagnosing patients, referring them or prescribing the components of quadruple therapy, and offering medical advice and follow-up. We highlight the role of SGLT2is in HF management and their effectiveness in reducing rates of hospitalization for HF as well as cardiovascular deaths, with satisfactory safety profile.

Cost-effectiveness analysis and budgetary impact of anidulafungin treatment for patients with candidemia and other forms of invasive candidiasis in Brazil.

Candidemia and other forms of invasive candidiasis (C/IC) are serious conditions, especially for immunosuppressed individuals with prolonged hospitalization in intensive care units (ICU). This study analyzed the incremental cost-effectiveness and budgetary impact (BI) of treatment for IC with anidulafungin compared to amphotericin B lipid complex (ABLC) and amphotericin B deoxycholate (ABD) or conventional amphotericin B (CAB), in the Brazilian Unified Health System (SUS). A decision model was conducted with a time horizon of two weeks from the perspective of SUS. The primary effectiveness endpoints were survival and treatment response rate. All patients were followed up until successful therapy or death. BI analysis was performed based on the measured demand method. A five-year time horizon was adopted based on the number of hospitalizations (per 1,000 hospitalizations). For effectiveness measured in the successful response rate (SRR), anidulafungin dominated the ABLC and ABD formulations. In the results of the analysis with the effectiveness measured according to survival, anidulafungin had a better cost-effectiveness ratio (R$988.26/survival) compared to ABD (R$16,359.50/survival). The BI estimate related to the incorporation of anidulafungin suggests savings of approximately 148 million reais in 5 years when comparing it to ABD. The economic evaluation of anidulafungin and its comparators found it to be cost-effective. The consensus of international scientific societies recommends it as a first-line drug for IC, and its incorporation by SUS would be important.