Main International Guidelines Research Articles

Identification of Psychological Treatment Dropout Predictors Using Machine Learning Models on Italian Patients Living with Overweight and Obesity Ineligible for Bariatric Surgery.

According to the main international guidelines, patients with obesity and psychiatric/psychological disorders who cannot be addressed to surgery are recommended to follow a nutritional approach and a psychological treatment. A total of 94 patients (T0) completed a battery of self-report measures: Symptom Checklist-90-Revised (SCL-90-R), Barratt Impulsiveness Scale-11 (BIS-11), Binge-Eating Scale (BES), Obesity-Related Well-Being Questionnaire-97 (ORWELL-97), and Minnesota Multiphasic Personality Inventory-2 (MMPI-2). Then, twelve sessions of a brief psychodynamic psychotherapy were delivered, which was followed by the participants completing the follow-up evaluation (T1). Two groups of patients were identified: Group 1 (n = 65), who fully completed the assessment in both T0 and T1; and Group 2-dropout (n = 29), who fulfilled the assessment only at T0 and not at T1. Machine learning models were implemented to investigate which variables were most associated with treatment failure. The classification tree model identified patients who were dropping out of treatment with an accuracy of about 80% by considering two variables: the MMPI-2 Correction (K) scale and the SCL-90-R Phobic Anxiety (PHOB) scale. Given the limited number of studies on this topic, the present results highlight the importance of considering the patient's level of adaptation and the social context in which they are integrated in treatment planning. Cautionary notes, implications, and future directions are discussed.

Predictive parameters of the efficacy of varicocele repair: a review.

Varicocele has a prevalence of 15% in the population and represents a primary cause of infertility in 40% of cases and a secondary cause in approximately 80% of cases. It is considered the major correctable cause of male infertility. Despite its high prevalence in the infertile population, a large number of patients with varicocele do not experience reproductive difficulties. For this reason, it is still highly debated which parameters could be used to predict which patients with varicocele will be most likely to benefit from its repair. The main international and European guidelines state that treatment should only be considered in infertile patients with abnormal sperm quality. However, these guidelines do not help physicians to identify which of these patients may benefit from the treatment. Therefore, this narrative review collects the evidence in the literature on the usefulness of some factors as predictors of improvement, highlighting how some of them may be effective in an initial selection of patients to be treated, while others are promising but further studies are needed. Finally, a brief consideration on the possible role of artificial intelligence is proposed.

There are those who would like zero LDL cholesterol.

The overwhelming evidence that the reduction of LDL cholesterol (LDLc) levels is associated with a parallel reduction in cardiovascular (CV) risk has led the scientific community to progressively and constantly reduce the optimal therapeutic targets of LDLc, both in patients with known CV disease and in patients undergoing primary prevention. The recent introduction of proprotein convertase subtilisin/kexin type 9 inhibitors has allowed clinicians to observe reductions in LDLc levels that go well beyond the limits set by the main international guidelines; following the 'the lower the better' paradigm, it is natural to ask how low LDLc can be reduced, whether this intervention is associated with a further reduction in CV risk and, above all, whether there are no issues related to safety in the use of polypharmacotherapies that determine an extreme reduction in LDLc levels. The purpose of this article is to summarize the main scientific evidence on the topic, trying to provide an answer to all clinicians who 'would like their LDLc to be-almost-zero'.

Efficacy of cryoablation in atrial fibrillation: comparison with antiarrhythmic therapy.

Atrial fibrillation (AF) represents the most common arrhythmia in clinical practice, characterized by irregular atrial electrical activity originating mainly in and around the pulmonary veins. This condition can manifest itself symptomatically or silently but still dangerously. Complications associated with AF include stroke, heart failure, worst clinical outcome in patients with underlying conditions, increased emergency room visits, hospitalizations, and cardiovascular mortality. Currently, according to the main international guidelines, antiarrhythmic therapy is considered the first choice for rhythm control in patients with AF despite modest efficacy and non-negligible side effects. In recent decades, radiofrequency catheter ablation has emerged as an alternative to antiarrhythmic drugs for rhythm control. Cryoablation was developed with the aim of reducing procedural times and reducing complications related to the ablative procedure with radiofrequency without losing efficacy. Recent studies conducted with rigour and scientific solidity have demonstrated on the one hand that the results of this technique are not inferior compare with radiofrequency. This study aims to compare data on the safety and efficacy of cryoablation with those obtained from antiarrhythmic drugs through a review of the most recent scientific evidence.

Sentinel Lymph Node Staging in Early-Stage Cervical Cancer: A Comprehensive Review.

Cervical cancer (CC) continues to be a significant global public health concern, even with preventive measures in place. In women with early-stage CC, the status of lymph nodes is of paramount importance, not only for the final prognosis but also for determining the best therapeutic strategy. According to main international guidelines, pelvic full lymphadenectomy (PLND) is recommended for lymph node staging. However, in these early stages of CC, sentinel lymph node biopsy (SLNB) has emerged as a precise technique for evaluating lymph node involvement, improving its morbidity profile. We performed a literature review through PubMed articles about progress on the application of SLNB in women with early-stage CC focusing on the comparison with PET/CT and PLND in terms of oncological outcomes and diagnostic accuracy. While the superiority of SLNB is clear compared to radiologic modalities, it demonstrates no clear oncologic inferiority over PLND, given the higher detection rate of positive lymph nodes and predominance of no lymph node recurrences. However, due to a lack of prospective evidence, particularly concerning long-term oncological safety, SLNB is not the current gold standard. With careful patient selection and adherence to straightforward protocols, a low false-negative rate can be ensured. The aim of the ongoing prospective trials is to address these issues.

A guiding framework for new eco-industrial park

ABSTRACT Industrial activities and waste are the main sources of air, water, soil pollution, depletion of natural resources, global warming and climatic changes, acid rain, biodiversity degradation worldwide. Egypt is suffering from industrial pollution and moving towards zero pollution goal represents a great challenge. Recently, Egypt is committed to achieving the Sustainable Development Goals (SDGs) by 2030. The notion of eco-industrial park (EIP) has been revitalized recently to reduce waste and pollution, efficiently share resources, and help to achieve sustainable development in the industrial sector. The objective of this research is to suggest a framework to guide the development of eco-industrial parks in Egypt. The research applies the inductive method to deduce the suggested framework. The main international and national eco-industrial park guidelines as well as international case studies are used to conclude the main categories and criteria as well as the relationship between criteria. In order to investigate the proposed guiding framework, a local case study was chosen to be studied as a sample of Egyptian eco-industrial park. In conclusion, the application of the suggested framework helped highlighting the covered and uncovered areas in the sample local case study as a step to build on in the Egyptian context.

Main Treatment Choices in the 2 First Lines of Therapy for Multiple Myeloma in Patients with High Risk Cytogenetics: Lesson from the Real World in the EU5 Countries and the USA

Background Typical approach to initial therapy in multiple myeloma (MM) includes more aggressive combinations early on with triplets. To further improve response rates and survival, quadruplets are moving to frontline, in both stem cell transplant (SCT) eligible and ineligible patients (pts). Defining high risk features is crucial; current international NCCN and IMWG clinical practice guidelines stratify pts based on those criteria proposing more aggressive therapy in this setting. Definitions of high risk are: cytogenetic abnormalities incl. del(17p), some laboratory factors with ISS III and increased LDH, some clinical features including plasma cell leukaemia, extramedullary involvement or age and functional assessment with primary refractory disease and rapid progression within 18 months of diagnosis. Aims Identify in real world setting the main regimens used in first line SCT eligible and ineligible pts as well as in 2nd line high risk pts with MM in EU5 countries (France, Germany, Italy, Spain, UK) and in the USA. Methods Anonymous patient charts were analysed based on data reported by onco-haematologists treating MM pts in EU5 countries and USA. A total of 1,575 unique patient charts in 1st line (530 SCT eligible and 1,045 SCT ineligible pts) and 1,665 unique pts in 2nd line were included in the analysis, from Oct. to Dec. 2022. The analysis focused on pts with high risk cytogenetic features and regimens used in accordance with international clinical practice guidelines. D= daratumumab; V=bortezomib; T=thalidomide; d= dexamethasone; R=lenalidomide; M= melphalan; p= prednisone; K=carfilzomib; Isa=isatuximab Results Mean age in 1st line SCT eligible pts was 59.0 years (n=441) in EU5 and 60.9 years (n=89) in the USA. In 1st line SCT ineligible pts, mean age was 74.0 years (n=838) in EU5 and 65.9 years (n=207) in the USA. Among all 1st line SCT eligible pts, 34% in EU5 and 29% in US had high risk cytogenetic features, with del17p identified in 12% of EU5 cases and 16% of US cases. In 1st line SCT ineligible pts in the EU5 and in the US 14% and 17% respectively were high risk, including 9% and 13% del17p. In the 2nd line setting, 1,208 unique pts were included in the EU5 and 457 in the US with 17% and 14% classified at high risk, respectively, del17p was identified in 9% and 11% of pts. The most frequently used regimens in 1st line SCT eligible pts in EU5 are D-VRd (n=56), VRd (n=69) and D-VTd (n=136) with 41% and 39% of high-risk pts. In the US, the most frequent regimens used in this subset were D-VRd (n=17) and VRd (n=33) with 35% and 39% of pts belonging to the high-risk group. For 1st line SCT ineligible pts in EU5, 40% of patients were high risk, with the most common regimen being VRd (n=67). Pts with del17p were also overrepresented in this subgroup with 15% of total population receiving VRd. Other frequently used regimens were D-VMP (n=95), DRd (n=188), Rd (n=148) and VMP (n=80) but none was preferred in high-risk pts. In the US, the most frequently-used regimen in 1st line SCT ineligible population was VRd (n=73) with 27% of pts with high-risk features (vs. 17% in the overall population). For 2nd line treatment in the EU5, carfilzomib-based combinations are more frequently used in high-risk pts, particularly DKd (n=42) and KRd (n=118), both associated with 35% of pts with high-risk features. Kd was also regularly used in this subset (n=76) with 32% of high-risk pts. Despite a small number of pts (n=29), Isa-Kd triplet is more regularly used in pts with del17p (21% of all pts). In 2nd line setting in the USA, the most frequently used regimen was DKd (n=37) with 30% high-risk pts. In pts with del17p, Kd was regularly used (n=14) with 21% of pts presenting this abnormality. Among other regimens, such as DPd (n=38), Dd (n=30), DRd (n=35) and KRd (n=21), none was preferred in high-risk pts. Conclusion This real-world study reveals quite heterogeneous treatment choices in 1st and 2nd line pts with high-risk cytogenetic features with no large consensus, especially between EU5 and the US. Some trends can be identified between different pts subsets: quadruplets with D-VRd and D-VTd in EU5 and D-VRd in the US are preferred as induction treatment prior to SCT. VRd is regularly used in 1st line SCT ineligible pts in the EU5, particularly in case of del17p. Carfilzomib-based regimens are more common in 2nd line pts in both EU5 and US, especially DKd, KRd and Kd. Those are in line with the main international guidelines and expert recommendations for high-risk pts.

Experimental Tests and Numerical Analyses for the Dynamic Characterization of a Steel and Wooden Cable-Stayed Footbridge

Vibrations are an issue of increasing importance in current footbridge design practice. More sophisticated footbridges with increasing spans and more effective construction materials result in lightweight structures and a high ratio of live load to dead load. As a result of this trend, many footbridges have become more susceptible to vibrations when subjected to dynamic loads. The most common dynamic loads on footbridges, other than wind loading, are pedestrian-induced footfall forces due to the movement of people. This paper concerns the experimental and numerical dynamic characterization of a newly built steel and wooden cable-stayed footbridge. The footbridge was dynamically tested in situ under ambient vibration, and the results allowed the real dynamic behavior of the footbridge to be captured. The dynamic response under pedestrian dynamic loads was also investigated and compared with the limitations provided by the main international codes and guidelines for footbridge serviceability assessment. A numerical model of the footbridge was also developed and updated based on the experimental outcomes. Then, the calibrated model was used to numerically assess the footbridge’s serviceability following the guideline prescriptions for pedestrian load simulation, and the design accuracy was also validated. This paper aims to increase the state-of-the-art knowledge about footbridge dynamic testing so as to support the design of new and futuristic structures as well as prove the effectiveness of using the requirements of codes and guidelines for footbridge serviceability assessment by adopting a calibrated numerical model.

The Experience of Ethics Committees in Portuguese Speaking Countries

In recent decades we have seen an increase in scientific research, including in Portuguese Speaking Countries (PALOP). This growth highlighted the concern for compliance with the principles of bioethics in research involving human beings. Lack of resources, scarce legislation, poor training of members of bioethics committees, limited knowledge of the main international guidelines, limited training on ethics and bioethics in research, are some of the characteristics common to the PALOPs. On the other hand, language constitutes a barrier considering that most of the literature is available in English. As an example, between 2005-2016 the EDCTP partnership funded 74 ethics projects in Africa with only two for the PALOP. The creation of bioethics committees in these countries dates back to the year 2000 in Angola, Cape Verde and Mozambique and from 2010 in Guinea-Bissau and São Tomé and Príncipe, all with Portuguese and Brazilian influence. In 2011, the National Committee on Bioethics in Health in Mozambique registered an increase in research, triggering the creation process of Institutional Bioethics Committees, with regulations and norms for the creation, functioning and hierarchy. In 2016, during the International Conference on “Ethics in Scientific Research: the first step towards south-south cooperation”, Angola, Mozambique, Brazil and Cuba signed the Malange Declaration. It expresses the commitment of the health ethics committees to work as a network in south-south collaboration, recognizing the need to boost training in bioethics. Mozambique's declaration reinforces this commitment. However, only in Mozambique is there a boost in the formation and regulation of bioethics committees. Currently, it is the PALOP country with the highest number of research projects evaluated. Between 2017-2021, two projects financed by EDCTP were implemented, in the perspective of North-South collaboration between Portugal and the PALOP. LusoAfro-BioEthics, aimed at Strengthening Bioethics Committees in Mozambique, Angola and Cape Verde. Highlights include online courses in Portuguese, the availability of a website in Portuguese and the implementation of the online research protocol submission process for Mozambique. BERC-luso, an Ethical and Regulatory Capacity Building project in the five PALOP countries, with the aim of developing and strengthening national drug regulation systems and capacities for the ethical review of clinical research. In September 2022, representatives of the Ethics Councils, Bioethics Associations and Clinical Research Committees of Portugal and the PALOP, gathered at the Lusophone Bioethics Meeting, signed the Lisbon Declaration with the commitment to Bioethical Cooperation and One Health in Lusophone countries between 2022-2026. The challenges for the PALOP continue to be training in ethics and bioethics in undergraduate and postgraduate courses as well as in intensive courses for the preparation and evaluation of research projects and the legislation for the creation, organization and hierarchy of Bioethics Committees and define norms and procedures in research using living beings, including clinical trials.

Metacognition, emotional dysregulation, psychosocial functioning and subjective well-being after 6 months of CBT treatment in pharmacologically stabilized schizophrenic patients

IntroductionPsychoses represent serious psychiatric disorders in which an individual perceptions, thoughts, mood and behavior are significantly altered. Each person who develops a psychosis lives a unique set of symptoms and experiences that may widely vary depending on life circumstances. Although cognitive behavioral psychotherapy (CBT) for psychosis is recommended by main international guidelines, its effectiveness in real-world is still a subject of controversy.ObjectivesThe aim of this study was to evaluate, in an Italian outpatient clinical setting, eventual improvements induced by a 6 months intensive CBT specific programme focused on metacognition and emotional regulation and its consequences on psychosocial functioning and subjective well-being in pharmacologically stabilized psychotic patients.MethodsEight patients with schizophrenia spectrum disorders (DSM-V), clinically and pharmacologically stabilized, were included in a 6-month program of weekly CBT sessions with focus on metacognition, emotional dysregulation, social functioning and subjective well-being. Patients were assessed with the Metacognitions Questionnaire-30, Difficulties in Emotion Regulation Scale, Heinrichs Quality of Life Scale, The Psychological General Well-Being Index, Brief Psychiatric Rating Scale, Hamilton Depression Rating Scale at baseline and at 3 and 6 months, to verify any improvement on these specific domains and, possibly, on general psychopathology.ResultsIn this study CBT showed to be effective on all domains evaluated, most notably for younger patients with a short history of disease (<5 years). Metacognitive capacity was the dimension with most evident improvements, followed by the ability to modulate emotions and the consequent improvement in psychosocial functioning and perceived subjective well-being. During the 6 months follow-up none of the enrolled patients experienced symptoms exacerbation or psychotic relapses.ConclusionsIn conclusion, the 6-month CBT treatment showed to be effective for stabilized psychotic patients, improving metacognitive functions, emotional regulation, psychosocial functioning, and subjective well-being. In addition, insight, adherence and the therapeutic alliance improved. The absence of psychotic relapses is not attributable with certainty to the effect of CBT since, for this purpose, longer duration studies on larger case series and with RCT methods are required. However, it is plausible that the improvement obtained in disease awareness and adherence may be a facilitating factor in relapse reduction.Disclosure of InterestNone Declared

Hospital at home treatment with remdesivir for patients with COVID-19: real-life experience

ObjectivesAccess and appropriateness of therapeutics for COVID-19 vary because of access or regulatory barriers, the severity of the disease, and for some therapies, the stage of the pandemic and circulating variants. Remdesivir has shown benefits in clinical recovery and is the treatment of choice for selected patients, both hospitalized and nonhospitalized, in main international guidelines. The use of remdesivir in alternatives to conventional hospitalization such as hospital at home (HaH) units remains incompletely explored. In this study, we aim to describe the real-life experience of outpatient remdesivir infusion for COVID-19 in a HaH unit. MethodsWe selected all the consecutive patients receiving remdesivir from a prospective cohort of 507 COVID-19 patients admitted at a HaH unit. Admission criteria included COVID-19 with a fraction of inspired oxygen requirement under 0.35 and respiratory rate under 22 rpm. Patients were daily assessed in person by a nurse and a physician. ResultsA total of 236 patients admitted at the HaH unit received remdesivir, 172 of whom were treated at home. Only 2% presented any adverse event related to the infusion, all of them mild. HaH saved 1416 day-beds, with only 5% of the patients requiring transfer back to the hospital. ConclusionRemdesivir infusion in HaH units seems to be a safe and efficient alternative to conventional hospitalization for treating patients with nonsevere COVID-19.

Liver magnetic resonance imaging for evaluation of response to treatment after stereotactic body radiation therapy of hepatocellular carcinoma.

BACKGROUNDAlthough stereotactic body radiation therapy (SBRT) is increasingly used, its application has not yet been regulated by the main international guidelines, leaving the decision to multidisciplinary teams.AIMTo assess magnetic resonance imaging (MRI) features of hepatocellular carcinoma (HCC) treated with SBRT, highlighting the efficacy of the treatment and the main aspects of the lesion before and after the procedure.METHODSAs part of a retrospective study, 49 patients who underwent SBRT for HCC between January 2013 and November 2019 were recruited. Each patient underwent a pre-treatment MRI examination with a hepatospecific contrast agent and a similar follow-up examination within 6 mo of therapy. In addition, 22 patients underwent a second follow-up examination after the first 6 mo. The following characteristics were analysed: Features analysed compared to pre-treatment MRI examination, presence or absence of infield and outfield progression, ring-like enhancement, signal hyperintensity in T2-weighted sequences in the perilesional parenchyma, capsular retraction, and "band" signal hypointensity in T1-weighted gradient echo fat saturated sequences obtained during hepatobiliary excretion.RESULTSSignal hyperintensity in the T2-weighted sequences showed a statistically significant reduction in the number of lesions at the post-SBRT first control (P = 0.0006). Signal hyperintensity in diffusion-weighted imaging-weighted sequences was decreased at MRI first control (P < 0.0001). A statistically significant increase of apparent diffusion coefficient values from a median of 1.01 to 1.38 at the first post-control was found (P < 0.0001). Capsular retraction was increased at the late evaluation (P = 0.006). Band-like signal hypointensity in the hepatobiliary phase was present in 94% at the late control (P = 0.006). The study of the risk of outfield progression vs infield progression revealed a hazard ratio of 9.CONCLUSIONThe efficacy of SBRT should be evaluated not in the first 6 mo, but at least 9 mo post-SBRT, when infield progression persists at very low rates while the risk of outfield progression increases significantly.

Nutraceuticals for Dyslipidaemia and Glucometabolic Diseases: What the Guidelines Tell Us (and Do Not Tell, Yet).

Background: The use of nutraceutical products and functional foods in the cardiovascular and metabolic field is rising in several countries. Preparation and implementation of guidelines are pivotal for translating research-derived knowledge and evidence-based medicine to the clinical practice. Based on these considerations, the aim of this paper is to explore if and how nutraceutical products are discussed by the most recent international guidelines related to cardio-metabolic diseases (dyslipidaemia, obesity, type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD) prevention). Some, but not all, guidelines for dyslipidaemia mention nutraceutical products as potential useful options for the treatment of mild dyslipidaemia, but also indicate the low level of evidence associated to their effects on hard endpoints (myocardial infarction, stroke, CVD-related death). In the most recent guidelines on obesity, it is mentioned that no safe and effective dietary supplement nor nutraceutical product is available for the management of weight loss in this condition, and more high-quality studies are necessary in this field. The examined guidelines for T2DM do not mention any specific nutraceutical approach to this disease, nor to milder forms, such as insulin resistance and pre-diabetes. Conclusions: The focus on nutraceutical products in the main international guidelines for cardio-metabolic disease management remains limited. Since robust scientific evidence is the background of useful and effective guidelines, the implementation of high-quality clinical research is strongly needed in the field of nutraceutical products for cardio-metabolic diseases.

Mixed Depression: A Mini-Review to Guide Clinical Practice and Future Research Developments.

The debate on mixed states (MS) has been intense for decades. However, several points remain controversial from a nosographic, diagnostic, and therapeutic point of view. The different perspectives that have emerged over the years have turned into a large, but heterogeneous, literature body. The present review aims to summarize the evidence on MS, with a particular focus on mixed depression (MxD), in order to provide a guide for clinicians and encourage the development of future research on the topic. First, we review the history of MS, focusing on their different interpretations and categorizations over the centuries. In this section, we also report alternative models to traditional nosography. Second, we describe the main clinical features of MxD and list the most reliable assessment tools. Finally, we summarize the recommendations provided by the main international guidelines for the treatment of MxD. Our review highlights that the different conceptualizations of MS and MxD, the variability of clinical pictures, and the heterogeneous response to pharmacological treatment make MxD a real challenge for clinicians. Further studies are needed to better characterize the phenotypes of patients with MxD to help clinicians in the management of this delicate condition.

Chronic use of the unfixed combination of ACE-inhibitors and beta-blockers in Italy from 2013 to 2019 through the healthcare administrative data.

The association between an ACE-inhibitor and a beta-blocker is recommended in case of complicated arterial hypertension and heart failure with reduced ejection fraction. This retrospective drug-utilization study has described its chronic use from the Italian National Healthcare Service perspective. From the ReS (Ricerca e Salute) database, collecting Italian healthcare administrative data, patients receiving an ACE-inhibitor or a beta-blocker from 2013 to 2019 were selected. The prevalence of use (patients treated/1000 inhabitants) and of continuous treatment (patients treated for ≥80% period from the supply to the end of the same year - by means of dosage units - per 1000 inhabitants) of each single active substance were assessed. Among patients continuously treated, those supplied with an ACE-inhibitor and a beta-blocker (unfixed and fixed combinations) were analyzed in terms of prevalence of continuous treatment. Subjects treated with the unfixed combination ramipril-bisoprolol in 2019 were characterized by gender and age. The prevalence of ACE-inhibitors' use increased from 49.7/1000 inhab. in 2013 to 50.2 in 2019: ramipril was the most supplied each year (28.9 to 31.6/1000 inhab.). The prevalence of continuous treatment increased from 27.4 to 28.3/1000 inhab.: ramipril the most continuously dispensed (16 to 18/1000 inhab.). The prevalence of beta-blockers' use increased from 61.0 to 90.4/1000 inhab.: bisoprolol the most supplied and with the highest increase (27.1 to 52.2/1000 inhab.). The prevalence of continuous treatment increased from 33.1 to 55.8/1000 inhab.: bisoprolol the most continuously dispensed (18 to 37/1000 inhab.). Among patients with continuous supplies, from 49,843 a 51,496 were treated with associations between an ACE-inhibitor and a beta-blocker on an ongoing basis. Half of them were continuously treated with the unfixed combination ramipril-bisoprolol (4.3 to 4.8/1000 inhab.). In 2019, subjects with continuous supplies of ramipril-bisoprolol were mainly males (63.4%) and elderly (mean age 71±12), and the prevalence of use increased with age. These findings, together with recommendations from the main international guidelines encourage to make available also ramipril and bisoprolol as fixed dose combination, in order to simplify the therapy administration and improve the adherence, especially among elderly and patients with multimorbidity.

Procedure for Reviewing Pharmaceutical Inspections in the Eurasian Economic Union (Review)

Introduction. The article discusses significant changes in the procedure for pharmaceutical inspection of drug manufacturers for compliance with the requirements of the rules of good manufacturing practice (GMP) of the Eurasian Economic Union (EAEU), related to restrictions due to the COVID-19 pandemic.Text. The article presents the main international guidelines describing the remote conduct of pharmaceutical inspections, which is the basis for further updating the relevant procedures in the law of the EAEU. An overview of the foreign practice of pharmaceutical inspection during the pandemic is given. In addition, the changes in the Russian regulatory approaches to control and supervision in the Russian legislation are presented.Conclusion. These data give an idea that, with considering the above, there is a need for further convergence of the requirements, the practice of conducting pharmaceutical inspections for compliance with the requirements of GMP Rules in order to harmonize the norms between Russian regulatory documents, the norms of the EAEU law and international standards. This requires the development of a dialogue with the participation of stakeholders.

Multigene tests for breast cancer: the physician's perspective.

Breast cancer is the most common tumour in women and the first cause of death for cancer in the female population. Preserving the quality of life has therefore become an important objective in the management of the disease. The benefits of adjuvant chemotherapy in patients with HR+ HER2- early breast cancer should always be balanced against its potential short and long-term adverse effects, and identifying the appropriate patients for whom chemotherapy can offer the highest clinical benefit is critical. Besides clinical and pathological factors, today four multigene tests able to guide the choice of the adjuvant therapy early breast cancer are available in Italy: Oncotype DX®, EndoPredict®, MammaPrint® e Prosigna®. This review evaluates the main characteristics of these diagnostic tests, the studies on clinical utility, their economic impact and their inclusion in international and national guidelines. The Oncotype DX Breast Recurrence Score® test is the only multigene test validated, with level IA evidence, to guide the adjuvant therapy decisions: hormone therapy alone for most patients with RS results 0–25, and chemotherapy for patients with RS results 26–100. Clinical data demonstrate that the Oncotype DX test is able to significantly impact therapeutic decisions, reducing chemotherapy use up to 49% and supporting the use of chemotherapy (up to 12%) in potentially under-treated patients. Based on the level of clinical evidence and established clinical utility, several multigene tests have been included in the main international guidelines, with recommendations ranging from “strong” to “moderate”.

Sentinel lymph node in cervical cancer: time to move forward.

In early-stage cervical cancer, lymph node status is of paramount importance to determine the best therapeutic strategy and is one of the most important prognostic factors of survival. According to main international guidelines, pelvic full lymphadenectomy is recommended for lymph node staging. Sentinel lymph node (SLN) biopsy is an accurate method for the assessment of lymph nodal involvement and has been suggested instead of systematic pelvic lymph node dissection (PLND). The SLN technique requires a learning-curve to be well performed. Combined detection with technetium-99 and blue dye has been widely used but the recent introduction of indocyanine green (ICG) is of growing interest since it could improve SLN detection. SLN biopsy offers a more accurate anatomical staging by finding potential metastatic nodes outside of usual lymphadenectomy areas. SLN biopsy improves the diagnostic value of lymph node staging with ultrastaging and detection of low-volume nodal metastases [isolated tumor cells (ITCs) and micrometastases]. Appropriate selection of patient and minimal training combined with some simple rules may guarantee a low false negative rate. Several studies have shown that SLN mapping in these patients is feasible, with excellent detection rates and sensitivity. Less-radical lymph node dissection decreases the associated morbidity of PLND, especially the risk of lower-limb lymphoedema, which severely affects patient quality of life. Some points are still subject to debate such as the low accuracy of intraoperative SLN status assessment by frozen section and the impact of micrometastasis on prognosis. Although international guidelines consider SLN biopsy as an alternative to PLND, SLN biopsy alone is not the gold-standard yet due to lack of prospective evidence on long-term oncological safety. The 3 ongoing prospective trials SENTIX, PHENIX and SENTICOL III will most probably give an answer to these issues.

Overview of lithium's use: a nationwide survey

BackgroundLithium is considered the gold standard treatment for bipolar disorder (BD). Current clinical guidelines and scientific evidence support its use as a first-line treatment in BD. However, over the last two decades, there has been a downward tendency in lithium's use in several developed countries. Based on a nationwide survey, this study's objective is to analyze in a large sample of psychiatrists relevant issues of the use of lithium salts in BD.MethodsData were collected through an anonymous survey sent by email among 500 psychiatrists who belong to a National Society of Psychiatry (Spanish Society of Biological Psychiatry). The survey is a self-administered questionnaire consisting of 21 items on the most key aspects of lithium's use (indication, dosage, monitoring, and information for patients).Results212 psychiatrists completed the survey. 70% of psychiatrists prescribe lithium to more than 50% of patients diagnosed with BD. Adverse effects are the main reason not to use lithium salts. Over 75% of the participants consider lithium salts the treatment of choice for the maintenance phase of BD, both in women and men. Most of the participants (> 50%) start lithium after the first affective episode, use conservative plasma concentrations (0.6–0.8 mmol/L), and generally prescribe it twice a day. 57% of psychiatrists who treat patients under 18 do not use lithium in this population. About 70% of the survey respondents use official protocols to inform and monitor patients on lithium treatment.ConclusionsFrom the results of the present study, it can be concluded that the use of lithium in Spain is in line with the recommendations of the main international clinical guidelines and current scientific literature. The first reason not to prescribe lithium in our country is the perception of its adverse effects and not the aspects related to its practical use or its effectiveness. Considering that BD is a chronic disease with a typical onset in adolescence, the low rate of prescription of lithium salts in patients under 18 must be thoroughly studied.

Enteral versus Parenteral Nutrition as Nutritional Support after Allogeneic Hematopoietic Stem Cell Transplantation: a Systematic Review and Meta-Analysis

Nutritional support for patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) has been widely debated. Enteral nutrition (EN) is recommended as first-line nutritional support by the main international guidelines. However, these recommendations are based on weak evidence, and there is wide variability in the types of nutritional support among transplantation centers, with the majority providing parenteral nutrition (PN) instead of EN. Here we provide an up-to-date systematic review and meta-analysis of studies comparing EN and PN for nutritional support during the neutropenic period after allo-HSCT. The literature search strategy identified 13 papers, of which 10 compared clinical transplantation outcomes, 2 compared gut microbiota (GM) compositions, and 1 compared systemic metabolic profiles. For the meta-analysis, among the 10 clinical studies, 8 studies in which 2 groups were compared were selected: in 1 group, EN was provided as primary nutritional support in the neutropenic phase after allo-HSCT with or without the addition of PN (EN group), whereas in the other group, only PN was provided as nutritional support. The incidence rates of acute graft-versus-host disease (aGVHD) (relative risk [RR], 0.69; 95% confidence interval [CI], 0.56 to 0.86; P=.0007), aGVHD grade III-IV (RR, 0.44; 95% CI, 0.30 to 0.64; P < .0001), and gut aGVHD (RR, 0.44; 95% CI, 0.30 to 0.66; P < .0001) were lower in the EN group than in the PN group. No differences were found between the 2 groups with regard to the incidence of severe oral mucositis (RR, 0.95; 95% CI, 0.83 to 1.09; P=.46) or overall survival at day +100 (RR, 1.07; 95% CI, 0.95 to 1.21; P=.29). Other variables were too heterogeneous to perform quantitative analyses. The results of the meta-analysis showed that EN reduced the incidence of aGVHD, specifically grade III-IV and gut aGVHD. This result should prompt improved efforts to implement EN as first-line nutritional support in patients undergoing allo-HSCT. Considering the emerging evidence regarding the association between GM dysbiosis and aGVHD onset, we speculate that this protective effect could be attributed to the improved gut eubiosis observed in enterally fed patients. Further studies are warranted to better address the relationship between the GM composition, aGVHD, and the nutritional administration route during HSCT.