Current therapeutic overview and future perspectives regarding the treatment of psoriasis.

Psoriasis is a chronic inflammatory skin disease affecting millions of people worldwide, characterized by rapid proliferation of keratinocytes, immune cell infiltration, and systemic inflammation. Over time, treatment strategies have evolved significantly from traditional topical therapies and phototherapy to advanced systemic options such as biologics and, more recently, oral small molecule drugs. This review aims to provide an in-depth examination of current psoriasis therapies, with a focus on biologics, oral small molecules, and new and emerging treatments. Several classes of biologic therapies have received regulatory approval for psoriasis, including inhibitors of TNF-α, IL-12/23, IL-17, and IL-23. Biologics have transformed psoriasis care, offering improved disease management and quality of life for patients, with generally favorable safety profiles. However, challenges such as high cost, potential immunogenicity and complexity of administration have sparked interest in alternative treatment options. Oral small molecules, particularly Janus kinase (JAK) inhibitors, have gained attention for their efficacy and ease of use, being orally administered drugs. These drugs mark a shift in therapeutic paradigms by providing an oral option that precisely targets specific signaling pathways. In addition to existing therapies, this review also highlights emerging treatments that could shape the future of psoriasis care, including new small-molecule inhibitors. Early clinical trials suggest that these agents could improve treatment outcomes for psoriasis patients. Current research is increasingly focused on understanding disease recurrence, particularly the influence of tissue-resident memory T cells (TRMs). Avoiding the proliferation of these cells may be crucial in attenuating recurrence. In particular, interleukin-23 (IL-23), produced by CD301b+ cells, has been linked to stimulation of TRM cell proliferation in the skin. This finding highlights that IL-23 inhibitors and treatments targeting CD301b+ cells are promising strategies for maintaining remission and preventing relapse. In summary, the landscape of psoriasis treatments is advancing rapidly, with an increasing focus on personalized, patient-specific therapies. Research is expected to continue to refine and improve therapeutic approaches for this complex disease.

Analysis of prescriptive monitoring regarding the current therapeutic landscape of rheumatoid arthritis: the experience of an Italian local health authority.

INTRODUCTION: Rheumatoid Arthritis (RA) is among the most prevalent chronic inflammatory diseases affecting millions of people with a significant expenditure of resources by National Healthcare Systems. This study aimed to analyze all available treatments exclusively for RA to highlight the costs of each treatment type and raise awareness of the use of biosimilar drugs. METHODS: In an Italian healthcare authority, all prescriptions made for the diagnosis of RA were extracted to verify consumption expressed in Defined Daily Dose (DDD) and the expenditure incurred expressed in euros. Consequently, a grouping into three major drug categories has been performed: anti - tumor necrosis factor alpha agents (TNFα), other injectable formulations, and novel oral formulations. RESULTS: Prescriptions for the second half-year 2022 and 2023 have been analyzed, with a total cost of almost 7 million euros in the sample considered. All pharmaceutical categories showed an increase in consumption, but only anti- TNFα recorded a decrease in costs from 25% in 2022 to 22% in 2023, thanks to the lower cost of the biosimilar drug. CONCLUSION: The costs of RA may represent a significant spending commitment for central governments. As a result, actions are needed to encourage the preferential use of biosimilar drugs.

Food Supplements Marketed Worldwide: A Comparative Analysis Between the European and the U.S. Regulatory Frameworks.

In recent decades, a new health paradigm emerged which increasingly places diet and nutrition at the center of citizens' healthcare. The resulting evolution of the food market has prompted country governments to adapt their regulatory frameworks to ensure product safety and preserve the health of citizens. Dietary supplements (DS) are products which are increasingly occupying a significant market share in Western countries, contributing to meeting the nutritional and physiological needs of a large portion of the global population. Food supplements must be safe for use by the final consumer who has access to the global market, but currently they are framed by a different legislation worldwide. This search aimed of comparing the legislative frameworks currently in force in the European Union (EU) and in the United States (USA), the two main markets in which DS are purchased, to focus on the strengths, similarities and possible shortcomings, against the backdrop of a global market which often transcends the regulatory barriers of individual countries. Both in the EU and the USA, food supplements are governed by specific regulations to ensure their safety and quality. However, the regulatory approaches differ sharply in some cases. It is expected that more and more operators will launch new DS in Western markets. As a result, it is crucial for competent authorities in food safety to deepen and develop additional regulatory tools aimed to control and safeguard the DS market.

The resulting evolution of the food market has prompted country governments to adapt their regulatory frameworks to ensure food safety and safeguard the health of citizensFood supplements must be safe for use by the final consumer who has access to the global market, but currently they are framed by a different legislation worldwideBoth in the EU and the USA, the two main markets in which DS are purchased, food supplements are governed by specific regulations to ensure their safetyNevertheless, the regulatory approaches differ sharply in some casesAs a result, it is crucial for competent authorities to develop additional regulatory tools aimed to control and safeguard the DS market.

Myocarditis Induced by Immune Checkpoint Inhibitors: An Exploratory Review.

Checkpoints are essential proteins in the immune system that regulate the intensity and duration of immune responses, preventing damage to healthy tissues during the fight against pathogens and abnormal cells. While these mechanisms are crucial in cancer defense, this disease can alter the functionality of these proteins. This is why checkpoint inhibitors have emerged as an important class of drugs to potentiate the antitumor immune response. However, it has been observed that these drugs can trigger adverse effects, among which myocarditis is one of the most prevalent. This article explores the signaling pathways associated with checkpoint inhibitors, their adverse effects, and their impact on the development of myocarditis, as well as potential therapeutic strategies.

Therapeutic Advances in Psoriasis: From Biologics to Emerging Oral Small Molecules.

Psoriasis is a persistent, inflammatory condition affecting millions globally, marked by excessive keratinocyte proliferation, immune cell infiltration, and widespread inflammation. Over the years, therapeutic approaches have developed significantly, shifting from conventional topical treatments and phototherapy to more sophisticated systemic interventions such as biologics and, recently, oral small-molecule drugs. This review seeks to present a comprehensive investigation of the existing psoriasis treatment options, focusing on biologic agents, oral small molecules, and emerging treatments. Several categories of biologic treatments have received regulatory approval for psoriasis, including TNF-α, IL-17, IL-12/23, and IL-23 inhibitors. Biologics have revolutionized the treatment of psoriasis. These targeted therapies offer significant improvement in disease control and quality of life, with acceptable safety profiles. However, limitations such as cost, potential immunogenicity, and administration challenges have driven the exploration of alternative treatment modalities. Oral small molecules, particularly inhibitors of Janus kinase (JAK), have emerged as options due to their convenience and efficacy. These agents represent a paradigm shift in the management of the condition, offering oral administration and targeted action on specific signaling pathways. In addition to existing therapies, the review explores emerging treatments that hold promise for the future of psoriasis care. These include innovative small-molecule inhibitors. Early-stage clinical trials suggest these agents may enhance outcomes for psoriasis patients. In conclusion, the therapeutic landscape of psoriasis is rapidly evolving, emphasizing targeted, patient-centered treatments. Ongoing research and development are expected to lead to more personalized and effective management strategies for this complex condition.

Therapeutic Strategies to Combat Increasing Rates of Multidrug Resistant Pathogens.

The emergence of antimicrobic-resistant infectious pathogens and the consequent rising in the incidence and prevalence of demises caused by or associated to infections which are not sensitive to drug treatments is one of today's major global health challenges. Antimicrobial resistance (AMR) can bring to therapeutic failure, infection's persistence and risk of serious illness, in particular in vulnerable populations such as the elderly, patients with neoplastic diseases or the immunocompromised. It is assessed that AMR will induce until 10 million deaths per year by 2050, becoming the leading cause of disease-related deaths. The World Health Organisation (WHO) and the United Nations General Assembly urgently call for new measures to combat the phenomenon. Research and development of new antimicrobial agents has decreased due to market failure. However, promising results are coming from new alternative therapeutic strategies such as monoclonal antibodies, microbiome modulators, nanomaterial-based therapeutics, vaccines, and phages. This narrative review aimed to analyse the benefits and weaknesses of alternative therapeutic strategies to antibiotics which treat multidrug-resistant bacterial infections.

Dietary management and access to treatment for patients with glucose deficiency syndrome type 1: an overview review with focus on the European regulatory framework.

BACKGROUND: Glut-1 deficiency Syndrome (GLUT-1 DS) is a rare disease caused by a mutation in the SLC2A1 gene that codes for the glucose transporter protein GLUT-1 DS. Currently, there is no indicated drug therapy for this condition and ketogenic diet (KD) is the most effective remedy to treat it. OBJECTIVE: The objective of this study was to review the published literature that evaluated the effectiveness of KD in the dietary management of GLUT-1 DS syndrome, describing the state-of-the-art the treatment pathway for patients with GLUT-1 DS syndrome in light of the current European regulatory framework within the National Health Services. METHODS: The literature search was carried out on September 10, 2023, and all studies conducted in humans diagnosed with GLUT-1 deficiency syndrome and treated with KD were included. RESULTS: A total of 156 scientific papers have been extracted. Applying the exclusion criteria, 38 articles have been considered eligible. In 29 out of 38 studies, the main outcome for determining the efficacy of KD was the measurement of the number of epileptic seizures, demonstrating that patients treated with KD experienced improvements with a clear reduction in the number of epileptic attacks. Currently, in the European Union, only one country provides full reimbursement by the national health system for KD. DISCUSSION: Although they are crucial for the treatment of GLUT-1 DS, according with current food regulations, KD are not evaluated on the basis of an unambiguous efficacy result, but only on the basis of safety. As a result, it is desirable to carry out clinical studies in the coming years based on the determination of efficacy in target populations, also in view of the marketing of these products on the European market.

The challenge of antimicrobial resistance (AMR): current status and future prospects.

Antimicrobial resistance (AMR) represents a critical global threat, compromising the effectiveness of antibacterial drugs as bacteria adapt and survive exposure to many classes of these drugs. This phenomenon is primarily fueled by the widespread overuse and misuse of antibacterial drugs, exerting selective pressure on bacteria and promoting the emergence of multi-resistant strains. AMR poses a top-priority challenge to public health due to its widespread epidemiological and economic implications, exacerbated not only by the diminishing effectiveness of currently available antimicrobial agents but also by the limited development of genuinely effective new molecules. In addressing this issue, our research aimed to examine the scientific literature narrating the Italian situation in the common European context of combating AMR. We sought to delineate the current state of AMR and explore future prospects through an analysis of strategies to counter antibacterial drug resistance. Adopting the "One Health" model, our objective was to comprehensively engage diverse sectors, integrate various disciplines, and propose programs, policies, and regulations. This narrative review, based on PubMed research related to antibiotic resistance, emphasizes the urgent need for a coordinated and proactive approach at both national and European levels to mitigate the impact of AMR and pave the way for effective strategies to counter this global health challenge.

The importance of antibiotic treatment duration in antimicrobial resistance.

Antimicrobial resistance (AMR) poses a significant threat to global health, leading to increased deaths from drug-resistant infections and escalates healthcare costs. Often termed a "silent pandemic," AMR occurs when pathogens become resistant to antimicrobial drugs, enabling their proliferation and spread. Inappropriate antibiotic usage is a major contributor to this phenomenon, which also extends to fungal infections. In particular, the duration of antibiotic therapy is a crucial aspect, with evidence suggesting that prolonged use can heighten bacterial resistance and harm the human microbiota. In fact, studies comparing short-term versus long-term antibiotic therapies show no significant difference in traditional treatments. In addition, therapeutic drug monitoring allows personalized antibiotic regimens, optimizing dosage and duration to minimize resistance and adverse effects. As a result, clinicians should regularly reassess treatment effectiveness, utilizing techniques like antibiotic timeout and de-escalation therapy to avoid prolonged antibiotic use and mitigate resistance. All these strategies are crucial to prevent and counter the phenomenon of antimicrobial resistance.

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.

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.

Tracking progress on antimicrobial resistance by the quadripartite country self-assessment survey (TrACSS) in G7 countries, 2017-2023: opportunities and gaps.

Antimicrobial resistance (AMR) poses serious challenges to the healthcare systems worldwide. Multiple factors and activities contribute to the development and spread of antimicrobial-resistant microorganisms. Monitoring progress in combating AMR is fundamental at both global and national levels to drive multisectoral actions, identify priorities, and coordinate strategies. Since 2017, the World Health Organization (WHO) has collected data through the Tracking AMR Country Self-Assessment Survey (TrACSS). TrACSS data are published in a publicly-available database. In 2023, 71 (59.9%) out of 177 responding countries reported the existence of a monitoring and evaluation plan for their National Action Plan (NAP) on AMR, and just 20 countries (11.3%) the allocation of funding to support NAP implementation. Countries reported challenges including limited financial and human resources, lack of technical capacity, and variable political commitment. Even across the Group of Seven (G7) countries, which represent some of the world's most advanced economies, many areas still need improvement, such as full implementation of infection prevention and control measures, adoption of WHO access/watch/reserve (AWaRe) classification of antibiotics, effective integration of laboratories in AMR surveillance in the animal health and food safety sectors, training and education, good manufacturing and hygiene practices in food processing, optimising pesticides use and environmental residues of antimicrobial drugs. Continuous and coordinated efforts are needed to strengthen multisectoral engagement to fight AMR.

Advances in Therapeutic Strategies for the Management of Clostridioides difficile Infection.

The infection caused by Clostridioides difficile represents one of the bacterial infections with the greatest increase in incidence among nosocomial infections in recent years. C. difficile is a Gram-positive bacterium able to produce toxins and spores. In some cases, infection results in severe diarrhoea and fulminant colitis, which cause prolonged hospitalisation and can be fatal, with repercussions also in terms of health economics. C. difficile is the most common cause of antibiotic-associated diarrhoea in the healthcare setting. The problem of bacterial forms that are increasingly resistant to common antibiotic treatments is also reflected in C. difficile infection (CDI). One of the causes of CDI is intestinal dysmicrobialism induced by prolonged antibiotic therapy. Moreover, in recent years, the emergence of increasingly virulent strains resistant to antibiotic treatment has made the picture even more complex. Evidence on preventive treatments to avoid recurrence is unclear. Current guidelines indicate the following antibiotics for the treatment of CDI: metronidazole, vancomycin, and fidaxomycin. This short narrative review provides an overview of CDI, antibiotic resistance, and emerging treatments.

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.

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.

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.

A Short Update on the Use of Monoclonal Antibodies in COVID-19.

Monoclonal antibodies in the prophylaxis and treatment of COVID-19 have been crucial in reducing severe infections when vaccines were unavailable. However, as the virus and its variants have changed over time, the effectiveness of monoclonal antibodies has been questioned. This technical note highlights the need to assess the antiviral activity of these antibodies against new variants and adapt treatment strategies accordingly. On the one hand, in vitro studies have suggested reduced susceptibility of the latest variants to monoclonal antibodies, whereas clinical data still show benefits in reducing severe illness and mortality, indicating that laboratory results do not always mirror real-world outcomes. As a result, although resistance to monoclonal antibodies can develop over time, they could still have an important role in COVID-19 treatment, especially when used in combination, and ongoing research aims to identify effective antibodies against new variants.

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.

The Impact of Antimicrobial Resistance in Cystic Fibrosis.

The phenomenon of antimicrobial resistance (AMR) is a critical global health challenge, with prospects indicating its potential to become the leading cause of death worldwide in the coming years. Individuals with pre-existing conditions, such as neoplastic disease undergoing chemotherapy, those on immunosuppressive therapy, and individuals with rare diseases like cystic fibrosis (CF), face heightened challenges due to AMR. CF is a rare disease caused by a deficiency in the synthesis of the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) channel protein, resulting in multi-organ clinical symptoms, particularly in the respiratory system. PwCF experience recurrent pulmonary exacerbations triggered by bacterial or viral infections, making them particularly vulnerable to the impact of AMR. This review delves into the complex relationship between AMR and climate dynamics, focusing on the unique challenges faced by individuals with CF. It discusses the methods employed to measure AMR, its global impact on antibiotic resistance, and the specific microbial communities present in the CF airway. The review also explores the intricacies of antimicrobial resistance within the context of cystic fibrosis, emphasizing the urgent need for research in this field.

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.