Innovative Drug Modalities for the Treatment of Advanced Prostate Cancer.

Prostate cancer, a prevalent malignancy affecting the prostate gland, is a significant global health concern. Androgen-deprivation therapy (ADT) has proven effective in controlling advanced disease, with over 50% of patients surviving at the 10-year mark. However, a diverse spectrum of responses exists, and resistance to ADT may emerge over time. This underscores the need to explore innovative treatment strategies for effectively managing prostate cancer progression. Ongoing research endeavors persist in unraveling the complexity of prostate cancer and fostering the development of biologic and innovative approaches, including immunotherapies and targeted therapies. This review aims to provide a valuable synthesis of the dynamic landscape of emerging drug modalities in this context. Interestingly, the complexities posed by prostate cancer not only present a formidable challenge but also serve as a model and an opportunity for translational research and innovative therapies in the field of oncology.

The use of new antibacterial drugs against infections caused by multidrug-resistant Gram-negative bacteria: an Italian real-world evidence study in a Lombardy hospital.

Infections caused by multidrug-resistant (MDR) bacteria are typically associated with high morbidity and mortality, especially in vulnerable individuals such as patients with prolonged hospitalizations, immunocompromised individuals, and the elderly. This study aimed to provide post-marketing surveillance results concerning the prevalence of antibiotic resistance against Gram-negative bacteria through the collaboration of a multidisciplinary team. Patients involved have been treated with new antibacterial drugs, in particular ceftazidime/avibactam (C/A), meropenem/vaborbactam (M/V), cefiderocol, and ceftolozane/tazobactam (C/T). The most resistant bacterial species were Klebsiella spp., Pseudomonas aeruginosa, and Acinetobacter baumannii. Italian Drug Agency (AIFA) monitoring records for inpatients have been collected and analyzed, assessing the characteristics of the patients involved. Adverse drug reactions (ADRs) and drugs involved have been reported using a descriptive analytical approach. All data have been collected retrospectively from patient's medical records and entered into an electronic case report form (CRF). Among the 104 treated patients, Klebsiella spp. accounted for 50.1% of infections, Pseudomonas aeruginosa for 32.7%, Acinetobacter baumannii for 3%, and other bacterial species for 1.92% configuring polymicrobial infections. Regarding treatment outcomes, healing was achieved in 61 (58.6%) patients, 23 (22.1%) patients died, 8 (7.7%) patients discontinued empirical therapy, and 3 (2.9%) patients were lost to follow-up. Despite the introduction of new antibacterial drugs active against Gram-negative bacteria is improving the clinical scenario, it is crucial that the use of new antibacterial drugs be implemented by appropriate antimicrobial stewardship, surveillance programs, and monitoring efforts to prevent further spread of resistance. This study showed that the new antibiotics have good efficacy against MDR bacteria and cause negligible side effects.

Antimicrobial Resistance in Gonorrhea.

Antimicrobial resistance is a global public health emergency. The World Health Organization recently highlighted the growing number of new sexually transmitted infections such as gonorrhea, syphilis, and Chlamydia, which are resistant to common antibiotics. The phenomenon is also on the rise due to increasing intercontinental travel. Emerging antibiotic-resistant strains of gonorrhea are particularly associated with international spread from Southeast Asian travelers. Infection with Neisseria gonorrhoeae can cause a wide spectrum of associated diseases such as dermatitis, arthritis and septic arthritis, and pelvic inflammatory disease, and can even lead to serious health consequences for the individual. Natural infection confers no immunity, and vaccination is not available currently, although in several countries, it has been reported that the antimeningococcal vaccine may protect against gonorrhea. Implementing all necessary preventive measures is crucial, as well as appropriate and timely diagnostic methods and effective antimicrobial therapeutic treatments in the correct modalities to avoid the increase of forms of gonorrhea that are resistant to common antibiotics and difficult to eradicate.

Four-year follow-up of psychiatric and psychosomatic profile in patients with Inflammatory Bowel Disease (IBD).

Psychological characterization of patients affected by Inflammatory Bowel Disease (IBD) focuses on comorbidity with psychiatric disorders, somatization or alexithymia. Whereas IBD patients had higher risk of stable anxiety and depression for many years after the diagnosis of the disease, there is a lack of studies reporting a comprehensive psychosomatic assessment addressing factors of disease vulnerability, also in the long-term. The objective of this investigation is to fill this gap in the current literature. The aims were thus to assess: a) changes between baseline and a 4-year follow-up in psychiatric diagnoses (SCID), psychosomatic syndromes (DCPR), psychological well-being (PWB-I), lifestyle, gastrointestinal symptoms related to IBD and Irritable Bowel Syndrome (IBS)-like symptoms b) stability of psychiatric and psychosomatic syndromes at 4-year follow-up. A total of 111 IBD outpatients were enrolled; 59.5% of them participated at the follow-up. A comprehensive assessment, including both interviews and self-report questionnaires, was provided at baseline and follow-up. Results showed increased psychiatric diagnoses, physical activity, consumption of vegetables and IBS-like symptoms at follow-up. Additionally, whereas psychiatric diagnoses were no longer present and new psychopathological pictures ensued at follow-up, more than half of the sample maintained psychosomatic syndromes (particularly allostatic overload, type A behavior, demoralization) from baseline to follow-up. Long-term presence/persistence of such psychosocial burden indicates the need for integrating a comprehensive psychosomatic evaluation beyond traditional psychiatric nosography in IBD patients. Moreover, since psychosomatic syndromes represent vulnerability factors of diseases, further studies should target subgroups of patients presenting with persistent psychosomatic syndromes and worse course of the disease.

Covid-19 psychological distress: Analysis of antipsychotic drugs' use in an Italian population sample.

BACKGROUND: The current pandemic, in addition to putting a strain on healthcare systems and global economies, has exacerbated psychiatric problems and undermined the mental health of many individuals. In an Italian cohort, this phenomenon has been assessed through a retrospective study aimed at evaluating the consumption and costs of antipsychotic drugs between 2020 and 2022. METHODS: All dispensations made in local pharmacies accessible to the public have been extracted from a database called 'Sistema Tessera Sanitaria', which covers a population of approximately one million people residents in the ASL Napoli 3 Sud. Consumption data expressed in defined daily dose (DDD) and expenditure data expressed in Euro have been extrapolated. RESULTS: The results in the years 2020-2021 were relatively consistent, with consumption and expenditure decreasing slightly from 2020 to 2021. In 2022, the results showed a decrease in consumption and expenditure (2,706,951.07 DDD and €1,700,897.47) representing the reduced accessibility of patients to the healthcare facilities due to the pandemic. However, it should be noted that the antipsychotic drug aripiprazole showed an upward trend, registering an increase in consumption. CONCLUSION: Despite expectations of increased consumption of antipsychotic medications, real-world evidence indicated a different phenomenon, with the pandemic seemingly not affecting the consumption of these drugs. The difficulty in accessing care and medical appointments has probably influenced this data, masking the therapeutic needs of citizens. It will be necessary to assess in the coming years, as normal clinical activity resumes, whether there will be a growing consumption of these medications, which represent one of the main expenditure categories for the National Healthcare System.

Two-year Opioid Prescription Trends in Local Sanitary Agency Naples 3 South, Campania Region, Italy. Descriptive Analyses and AI-based Translational Perspectives.

Aims: This study delves into the two-year opioid prescription trends in the Local Sanitary Agency Naples 3 South, Campania Region, Italy. The research aims to elucidate prescribing patterns, demographics, and dosage categories within a population representing 1.7% of the national total. Perspectives on artificial intelligence research are discussed. Methods: From the original dataset, spanning from January 2022 to October 2023, we processed multiple variables including demographic data, medications, dosages, drug consumption, and administration routes. The dispensing quantity was calculated as defined daily doses (DDD). Results: The analysis reveals a conservative approach to opioid therapy. In subjects under the age of 20, prescriptions accounted for 2.1% in 2022 and declined to 1.4% in 2023. The drug combination paracetamol/codeine was the most frequently prescribed, followed by tapentadol. Approximately two-thirds of the consumption pertains to oral formulations. Transdermal formulations were 15% (fentanyl 9.8%, buprenorphine 5.1%) in 2022; and 16.6% (fentanyl 10%, buprenorphine 6.6%) in 2023. These data were confirmed by the DDD analysis. The trend analysis demonstrated a significant reduction ( p < 0.001) in the number of prescribed opioids from 2022 to 2023 in adults (40-69 years). The study of rapid-onset opioids (ROOs), drugs specifically used for breakthrough cancer pain, showed higher dosage (>267 mcg) consumption among women, whereas a lower dosage (<133 mcg) was calculated for men. Fentanyl pectin nasal spray accounted for approximately one-fifth of all ROOs. Conclusion: Despite limitations, the study provides valuable insights into prescribing practices involving an important study population. The findings underscore the need for tailored approaches to prescribing practices, recognizing the complexities of pain management in different contexts. This research can contribute to the ongoing discourse on opioid use, advocating for innovative strategies that optimize therapeutic outcomes while mitigating potential risks.

Atopic dermatitis: treatment and innovations in immunotherapy.

Atopic dermatitis (AD) is a common inflammatory skin disease characterized by itching and skin barrier dysfunction. Moderate to severe AD is often refractory to first-line topical treatments, and systemic immunosuppressants have been shown to be effective but have significant adverse effects. The paucity of basic treatments has contributed to the development of targeted topical and systemic immunotherapies based on the use of small molecules and biologic drugs which can directly interact with AD pathogenetic pathways. They represent a new era of therapeutic innovation. Additional new treatments are desirable since AD is a heterogeneous disease marked by different immunological phenotypes. This manuscript will review the mechanism of action, safety profile, and efficacy of promising new systemic immunological treatments for AD. Since moderate to severe AD can result in poor quality of life, the development of targeted and well-tolerated immunomodulators is a crucial purpose. The introduction of new pharmacological agents may offer new therapeutic options. However, there is the need to evaluate how "narrow-acting" agents, such as individual interleukin inhibitors, will perform under the safety and efficacy profiles compared with "broad-acting" agents, such as JAK inhibitors.

Anti-CGRP mAbs for the Preventive Treatment of Migraine: An Overview Review and a Cost Saving Analysis in the Global Scenario.

Objectives: Migraine is a neurological disease with a high frequency of incidence. The new monoclonal antibodies selective for the calcitonin gene-related peptide and its ligand (anti-CGRP mAbs) have been marketed both in the USA and EU based on the positive efficacy results in the prevention of migraine. This search has been carried out with the aim of collecting real-world evidence on the effectiveness of anti-CGRP mAbs, performing a cost-savings analysis, and comparing performances among anti-CGRP mAbs medicines marketed in the American and European market. Methods: The literature review has been performed in PubMed database on 31 December 2022; the cost of the unitary dose of anti-CGRP mAbs has been extracted consulting an American national database. Results: The results confirm efficacy and good tolerability of anti-CGRP mAbs, determining a difference in the purchase price. In fact, all extracted studies showed a protective risk factor exposure in monthly migraine days reduction for all the anti-CGRP mAbs, whereas the cost analysis showed that using eptinezumab, in a quarter there is a cost saving of at least $425 per patient, compared with the other anti-CGRP mAbs. Conclusions: With equal efficacy and equal safety, anti-CGRP mAbs should be prescribed also regard to the cost established at the negotiation, making sure to guarantee the best treatment to the patients, but at the same time impacting as little as possible to the healthcare services resources.

Healthcare Systems and Artificial Intelligence: Focus on Challenges and the International Regulatory Framework.

BACKGROUND: Nowadays, healthcare systems are coping with the challenge of countering the exponential growth of healthcare costs worldwide, to support sustainability and to guarantee access to treatment for all patients. METHODS: Artificial Intelligence (AI) is the technology able to perform human cognitive functions through the creation of algorithms. The value of AI in healthcare and its ability to address healthcare delivery issues has been a subject of discussion within the scientific community for several years. RESULTS: The aim of this work is to provide an overview of the primary uses of AI in the healthcare system, to discuss its desirable future uses while shedding light on the major issues related to implications within international regulatory processes. In this manuscript, it will be described the main applications of AI in various aspects of health care, from clinical studies to ethical implications, focusing on the international regulatory framework in countries in which AI is used, to discuss and compare strengthens and weaknesses. CONCLUSIONS: The challenges in regulatory processes to facilitate the integration of AI in healthcare are significant. However, overcoming them is essential to ensure that AI-based technologies are adopted safely and effectively.

Advancing amyotrophic lateral sclerosis disease diagnosis: A lab-on-chip electrochemical immunosensor for ultra-sensitive TDP-43 protein detection and monitoring in serum patients'.

The global increase in population aging has led to a rise in neurodegenerative diseases (NDs), posing significant challenges to public health. Developing selective and specific biomarkers for early diagnosis and drug development is crucial addressing the growing burden of NDs. In this context, the RNA-binding protein TDP-43 has emerged as a promising biomarker for amyotrophic lateral sclerosis (ALS), frontotemporal lobar degeneration (FTLD), and TDP-43-associated proteinopathies. However, existing detection methods suffer from limitations such as cost, complexity, and operator dependence. Here, we present a novel electrochemical biosensor integrated into a lab-on-chip (LoC) platform to detect TDP-43. The sensor utilizes electrosynthesized polypyrrole derivatives with carboxylic groups for transducer functionalization, enabling targeted immobilization of TDP-43 antibodies. Differential pulsed voltammetry (DPV) is used for the indirect detection and quantification of TDP-43. The chip exhibits rapid response, good reproducibility, a linear detection range, and sensitivity from 0.01 ng/mL to 25 ng/mL of TDP-43 protein concentration with a LOD = 10 pg/mL. Furthermore, successful TDP-43 detection in complex matrices like serum of ALS patients and healthy individuals demonstrates its potential as a point-of-care diagnostic device. This electrochemical biosensor integrated into a chip offers good sensitivity, rapid response, and robust performance, providing a promising avenue for advancing neurodegenerative disease diagnostics and therapeutic development.

The use of the biosimilar drug can lead to large health care savings that can be reinvested for continued innovation: Analysis of consumption of an Italian health care company.

BACKGROUND: Biosimilar drugs offer an opportunity for all global healthcare systems because they provide significant cost savings while ensuring equal efficacy and safety in the treatment of chronic diseases. These savings can be allocated to support ongoing innovation. METHODS: An analysis of the usage of major biosimilar drugs across various therapeutic areas has been conducted within an Italian healthcare company serving a population of over one million. Data on consumption, expenditure, and the number of treated patients has been extracted from the company's databases. Finally, a comparison with the year 2021 has been performed to determine if biosimilar drug usage increased in 2022. RESULTS: In 2022, the data reveals that a substantial portion of the analysed active ingredients are being used as biosimilar drugs, except in a few residual cases. However, among the most consumed drugs, resistance still exists in the case of Adalimumab and Etanercept, for which expenditure on originator drugs exceeds 2 million euros. CONCLUSION: The 2022-2021 comparison highlights the increasing use of biosimilar drugs. This data is encouraging and suggests that in the coming months, we may achieve total utilization, which would be to the benefit of the National Health System (NHS) and the citizens who can rely on an efficient and sustainable healthcare policy that is continually improving.

Comparison and Analysis of Antibiotic Consumption in Two Italian Hospital Settings in Relation to the Fight of Antimicrobial Resistance.

Introduction: The emergence and spread of drug-resistant pathogens due to the improper use of antibiotics have become increasingly apparent in recent years. Objective: This retrospective comparative analysis aimed to assess and compare antibiotic prescription trends in Italy across two different regions based on geographic area and healthcare structure. One region represents a large hospital institution, while the other represents a populous local Italian health agency. The study also examined the impact of documented antibiotic stewardship programs and efforts to promote responsible antibiotic use at all levels, in alignment with international goals. Antibiotic consumption data were collected from the Umberto I Polyclinic Hospital and the ASL Napoli 3 South Local Health Agency. Methods: To compare consumption between regions, a standardized comparison using the Defined Daily Dose (DDD) was employed. The internal management system of each healthcare facility records all prescriptions and drug dispensations, and these data were extrapolated for this retrospective study. Results: A comparative assessment between the first half of 2022 and 2023 (January-June) highlighted a significant increase in beta-lactam antibiotic consumption, showing a twofold rise compared to the previous year's term. Regarding prescription averages, there was a noticeable increase of +29.00% in hospitalizations and +28.00% in hospital discharges within the ASL Napoli 3 South. Conversely, at Policlinico Umberto I, there was a marginal increase of +1.60% in hospitalizations and a decrease of -7.40% in hospital discharges. Conclusions: The study offers valuable insights into expenditure patterns and antibiotic consumption, underscoring the need for enhanced prescribing practices and awareness campaigns to address the issue of antibiotic resistance. The findings stress the importance of implementing international guidelines to combat the growing threat of antibiotic resistance and ensure the effective management of infectious diseases.

Antibacterial agents and the fight against antibiotic resistance: A real-world evidence analysis of consumption and spending by an Italian healthcare company.

INTRODUCTION: The escalating bacterial resistance stands as an increasingly pertinent concern, particularly in the post-pandemic era where the use of antibiotics appears to be relentlessly surging, giving rise to profound apprehensions. The substantial utilization of last-generation penicillins and cephalosporins is anticipated to imminently result in the emergence of superbugs for which therapeutic solutions will be scarce. METHODS: An analysis of antibiotic consumption in the hospital setting has been conducted in an Italian healthcare organization. Querying the internal management system facilitated the calculation of indicators and assessment of prescription trends. RESULTS: A comparison has been made between the first half of 2023 and the first half of 2022, to highlight the exponential growth in the consumption of beta-lactam antibiotics, with consumption doubling compared to the previous year's semester. Overall, considering the prescription averages, there is a prescribing growth of +29% concerning hospitalization and +28% concerning hospital discharge. However, it should be noted that the consumption of certain antibiotics such as sulphonamides and trimethoprim (-103.00%), tetracyclines (-54.00%), macrolides, lincosamides and streptogramins (-50.00%) and colistin (-13.00%) decreased. CONCLUSION: This real-world evidence analysis aimed to support the justified and comprehensible global concerns regarding bacterial resistance. The extensive consumption of antibiotics will inevitably lead to the development of increasingly drug-resistant bacteria for which no antibiotic may be efficacious. National programs addressing antibiotic resistance and the awareness of all healthcare personnel must be accorded the utmost priority to enhance consumption data and, consequently, safeguard future human survival.

Trend analysis of proton pump inhibitor consumption and expenditure: The real-world evidence.

INTRODUCTION: Proton pump inhibitors (PPIs) constitute a widely utilized pharmaceutical class, frequently associated with notable instances of therapeutic inappropriateness. Such patterns of misuse not only contribute to elevated healthcare expenditure, but may also exacerbate clinical conditions in certain patients. METHODS: A comprehensive analysis was conducted between 2019 and 2023 to assess all prescriptions dispensed using the Anatomical, Therapeutic and Chemical (ATC) classification system, which allowed trends among primary PPIs to be visualized. This was achieved by calculating the defined daily dose (DDD) and then defining the total expenditure incurred on these drugs. RESULTS: With regard to the prescription of PPIs, an upward trend in consumption was observed with a decreasing expenditure, due to the phenomena of drug generics and increased competition between pharmaceutical companies, ranging from €9,512,481.22 in the first six months of 2019 to €8,509,820.80 in the first six months of 2023. From 2019 to 2023, consumption increased by approximately 3 million DDDs for a total ranging from 18,483,167.59 DDDs to 21,480,871.00 DDDs. Pantoprazole and esomeprazole, the most expensive drugs compared to omeprazole, rabeprazole and lansoprazole, accounted for 61.4% of therapies in the first six months of 2023, up from 2019, where these two drugs were prescribed 54.9%. CONCLUSION: Within this analysis, we provide an illustrative representation of the prescribing trends for PPIs within a European context. Omeprazole, rabeprazole and lansoprazole appear to be the cheapest drugs compared to pantoprazole and esomeprazole. However, the results show that the most widely used PPIs, despite their therapeutic equivalence, are precisely the high-cost ones, thus generating higher expenditure for central governments.

Analysis of biosimilars consumption in an Italian Local Health Authority.

Biosimilar drugs offer an opportunity for all global healthcare systems because they provide significant cost savings while ensuring equal efficacy and safety in the treatment of chronic diseases. These savings can be allocated to support ongoing innovation. An analysis of the usage of major biosimilar drugs across various therapeutic areas has been conducted within an Italian healthcare company serving a population of over one million. Data on consumption, expenditure, and the number of treated patients has been extracted from the company's databases. Finally, a comparison with the year 2021 has been performed to determine if biosimilar drug usage increased in 2022. In 2022, the data reveals that a substantial portion of the analysed active ingredients are being used as biosimilar drugs, except in a few residual cases. However, among the most consumed drugs, resistance still exists in the case of Adalimumab and Etanercept, for which expenditure on originator drugs exceeds 2 million euros. The 2022-2021 comparison highlights the increasing use of biosimilar drugs. This data is encouraging and suggests that in the coming months, we may achieve total utilization, which would be to the benefit of the National Healthcare System (NHS) and the citizens who can rely on an efficient and sustainable healthcare policy that is continually improving.

Intrahepatic cholangiocarcinoma biomarkers: Towards early detection and personalized pharmacological treatments.

Cholangiocarcinoma (CCA) is a rare malignancy originating from the biliary tree and is anatomically categorized as intrahepatic (iCCA), perihilar, and extrahepatic or distal. iCCA, the second most prevalent hepatobiliary cancer following hepatocellular carcinoma (HCC), constitutes 5-20 % of all liver malignancies, with an increasing incidence. The challenging nature of iCCA, combined with nonspecific symptoms, often leads to late diagnoses, resulting in unfavorable outcomes. The advanced phase of this neoplasm is difficult to treat with dismal results. Early diagnosis could significantly reduce mortality attributed to iCCA but remains an elusive goal. The identification of biomarkers specific to iCCA and their translation into clinical practice could facilitate diagnosis, monitor therapy response, and potentially reveal novel interventions and personalized medicine. In this review, we present the current landscape of biomarkers in each of these contexts. In addition to CA19.9, a widely recognized biomarker for iCCA, others such as A1BG, CYFRA 21-1, FAM19A5, MMP-7, RBAK, SSP411, TuM2-PK, WFA, etc., as well as circulating tumor DNA, RNA, cells, and exosomes, are under investigation. Advancing our knowledge and monitoring of biomarkers may enable us to improve diagnosis, prognostication, and apply treatments dynamically and in a more personalized manner.