Valutazione Della Politica di Pricing Dei Farmaci Oncologici Innovativi: Correlazione Tra Costi e Sopravvivenza in 15 Paesi Europei:

Evaluating national pricing policies of innovative anti-cancer drugs: correlation analysis between costs and survival in 15 European countriesIntroductionIn recent years, public health systems in Europe have faced the challenge of sustainability in different ways. The aim of this study is to analyse the pricing policies of 15 European countries by studying the correlation between cost and survival of a series of anti-cancer drugs.MethodsOur study assessed nine anti-cancer drugs licensed by EMA in the last decade. Clinical benefits, measured as overall survival (OS) and progression free survival (PFS), were obtained from EPAR or randomized controlled trials, while nominal and real prices in the 15 different countries (including discounts) were derived from a published study. We performed a correlation analysis between cost and OS for each indication of any given drug.ResultsOnly two countries (Hungary and Lithuania) demonstrated a strong correlation coefficient in the OS analysis. The PFS analysis has shown better results with 12 countries, with R values higher than 0.20.DiscussionTo the best of our knowledge, this is the first study in which the correlation between costs and outcomes has been studied in a large number of countries. Our results showed that, in these countries, prices had generally a poor correlation with OS and a better correlation with PFS

Off-Label Use of Dalbavancin for Sequential Treatment of Spondylodiscitis by Methicillin-Resistant Staphylococcus aureus: A Retrospective Single-Centre Experience

Background: Our aim was to describe the clinical outcome and safety of the sequential treatment with off-label dalbavancin in patients with spondylodiscitis that is caused by methicillin-resistant Staphylococcus aureus (MRSA). Methods: We retrospectively included all patients >18 years of age with spondylodiscitis that is caused by MRSA that was treated with dalbavancin from January 2018-January 2021, recording the instances of clinical cure/failure, adverse events, and the need to be re-hospitalized after the initiation of dalbavancin. In 2/15 patients, we performed therapeutic drug monitoring (TDM) for dalbavancin. Results: We included 15 patients, 53.3% of them were females, with a median age of 67.9 years (57.4-78.5); 100% patients reported back pain, while a fever was present only in 2/15 cases. The spondylodiscitis was localized in 86.6% cases at the lumbar level. A median of a 2-week in-hospital intravenous vancomycin was followed by dalbavancin with a median duration of 12 weeks (12-16). All patients reported a clinical cure, except for a woman who is still on a suppressive treatment. No patient needed to be re-hospitalized, access to emergency department, or experienced adverse events. The TDM for dalbavancin showed that more than 90% of the determinations were above the pharmacodynamic target against staphylococci. Conclusions: The results from our unique, even if it was small, cohort demonstrated that dalbavancin can be a safe/effective option as a sequential treatment in patients with serious infections requiring prolonged antibiotic therapy, such as spondylodiscitis

Progression-Free and Overall Survival of First-Line Treatments for Advanced Renal Cell Carcinoma: Indirect Comparison of Six Combination Regimens

Background: Recently, numerous combination therapies based on immune checkpoint inhibitors (ICI) and vascular endothelial growth factor (VEGF) inhibitors have been proposed as first-line treatments for advanced renal cell carcinoma (aRCC). Our study aimed to compare the efficacy of these combination regimens by the application of an innovative method that reconstructs individual patient data. Methods: Six phase III studies describing different combination regimens for aRCC were selected. Individual patient data were reconstructed from Kaplan–Meier (KM) curves through the “Shiny method”. Overall survival (OS) and progression-free survival (PFS) were compared among combination treatments and sunitinib. Results were summarized as multi-treatment KM curves. Standard statistical testing was used, including hazard ratio and likelihood ratio tests for heterogeneity. Results: In the overall population of aRCC patients, pembrolizumab + lenvatinib showed the longest median PFS and was expected to determine the longest OS. Pembrolizumab + axitinib, nivolumab + cabozantinib and nivolumab + ipilimumab were similar in terms of PFS, but pembrolizumab + axitinib also demonstrated a better OS. Our subgroup analysis showed that sunitinib is still a valuable option, whereas, in intermediate-poor risk patients, pembrolizumab + axitinib and nivolumab + ipilimumab significantly improve OS compared to sunitinib. Conclusion: The Shiny method allowed us to perform all head-to-head indirect comparisons between these agents in a context in which “real” comparative trials have not been performed

Psychiatric Disorders after Switching to Dolutegravir: A Case Report of a 59-Year-Old Virosuppressed HIV-1 Positive Woman

We report a case of a woman who experienced psychiatric disorders after switching her antiretroviral therapy (c-ART) to dolutegravir (DTG). She is a 59-year-old HIV-1 positive woman with a recent story of cardiovascular disorders treated with beta-blockers, clopidogrel, and rosuvastatin. She underwent a c-ART switch from darunavir/cobicistat and maraviroc to emtricitabine/tenofovir alafenamide fumarate in association with dolutegravir due to drug-drug interactions. One week later, she started to show psychiatric symptoms that required admission to the psychiatric unit. These disorders resolved within a couple of days after DTG discontinuation to allow a regular discharge. With this case-report, we would like to analyse the possible correlation between integrase inhibitor and severe psychiatric disorders in order to confirm the evidences already published in literature

Early Use of Sotrovimab in Children: A Case Report of an 11-Year-Old Kidney Transplant Recipient Infected with SARS-CoV-2

Background: The use of virus-neutralizing monoclonal antibodies has been approved in fragile populations, including kidney transplant recipients, who are at risk of developing severe COVID-19. Sotrovimab is the only currently available anti-SARS-CoV-2 neutralizing monoclonal antibody with activity against the new Omicron variant of concern. While sotrovimab has been approved in adolescents and adults, studies regarding its efficacy and safety in children aged less than 12 years old and weighing less than 40 kg are still lacking. Here, we report a first case of a child, who was treated early with sotrovimab after a kidney transplant. Case Report: At the end of January 2022, a 11-year-old male child underwent a deceased-donor kidney transplant and became infected with SARS-CoV-2 during the first day after surgery. Due to the increased risk of developing severe COVID-19, based on the predominance of Omicron and the patient’s renal function, the child was treated with sotrovimab. The clinical course was successful and no adverse reactions were reported. Conclusions: For the first time, we report the well-tolerated use of sotrovimab in children under 12 years old. As the pandemic affects children across the globe, urgent data on sotrovimab dosing in children with a higher risk of developing severe COVID-19 are needed

Alternative Antimicrobial Irrigation Strategies for the Treatment of Infections in Children: A Review of the Existing Literature

As a synergistic treatment approach with systemic antimicrobial therapy or a systemic antibiotic-sparing strategy, the local administration of antimicrobial agents has been proposed as an alternative route for complicated infections. With the rationale of concentrating the active principle in the desired target site, avoiding potentially toxic systemic levels and bypassing anatomical and physiological barriers, local irrigation or infusion of antibiotics may effectively shorten the antimicrobial therapy course and reduce both infection-related and systemic therapy-related complications. Although evidence from the adult population supports its use in selected patients with an acceptable safety profile, data specifically focused on the pediatric population are limited. To provide a rapid and easily accessible tool for clinical practice, we synthesized the most relevant evidence on the use of local antimicrobial agents in common severe infections in children: meningitis, mediastinitis, pleural infections, recurrent urinary infections, and peritonitis. A literature search was performed using predefined combined keywords through an electronic research database (PubMed). Described molecules, dosages, routes, treated age groups, and related efficacy have been summarized for prompt application to clinical practice. It should, however, be noted that the evidence for the pediatric population remains limited, and the local administration of several molecules remains off-label. A careful multidisciplinary and patient-tailored evaluation, as well as a rational use of available guidelines, should always be the basis of clinical decision making in settings where local administration of antibiotics may be considered

Early Use of Sotrovimab in Children: A Case Report of an 11-Year-Old Kidney Transplant Recipient Infected with SARS-CoV-2

Background: The use of virus-neutralizing monoclonal antibodies has been approved in fragile populations, including kidney transplant recipients, who are at risk of developing severe COVID-19. Sotrovimab is the only currently available anti-SARS-CoV-2 neutralizing monoclonal antibody with activity against the new Omicron variant of concern. While sotrovimab has been approved in adolescents and adults, studies regarding its efficacy and safety in children aged less than 12 years old and weighing less than 40 kg are still lacking. Here, we report a first case of a child, who was treated early with sotrovimab after a kidney transplant. Case Report: At the end of January 2022, a 11-year-old male child underwent a deceased-donor kidney transplant and became infected with SARS-CoV-2 during the first day after surgery. Due to the increased risk of developing severe COVID-19, based on the predominance of Omicron and the patient’s renal function, the child was treated with sotrovimab. The clinical course was successful and no adverse reactions were reported. Conclusions: For the first time, we report the well-tolerated use of sotrovimab in children under 12 years old. As the pandemic affects children across the globe, urgent data on sotrovimab dosing in children with a higher risk of developing severe COVID-19 are needed

Therapeutic Options and Outcomes for the Treatment of Children with Gram-Positive Bacteria with Resistances of Concern: A Systematic Review

Background: Methicillin-resistant Staphylococcus aureus (MRSA), methicillin-resistant coagulase-negative Staphylococci (MR-CoNS), and vancomycin-resistant Enterococci (VRE) are increasing worldwide and represent a threat for the limited treatment options in pediatric patients and neonates compared to adults. Recommendations in pediatrics are mainly extrapolated from adults’ studies. Methods: A literature search for the treatment of these pathogens in children (<18 years old) was conducted in Embase, MEDLINE, and Cochrane Library. Studies reporting data on single-patient-level outcomes related to a specific antibiotic treatment for multidrug resistant (MDR) Gram-positive bacterial infection in children were included. Studies reporting data from adults and children were included if single-pediatric-level information could be identified (PROSPERO registration: CRD42022383867). Results: The search identified 11,740 studies (since January 2000), of which 48 fulfilled both the inclusion and the exclusion criteria and were included in the analysis: 29 for MRSA, 20 for VRE, and seven for MR-CoNS. Most studies were retrospective studies. Vancomycin was mainly used as a comparator, while linezolid and daptomycin were the most studied antimicrobials showing good efficacy. Conclusions: Linezolid showed a safety and efficacy profile in a neonatal setting; daptomycin is increasingly used for MRSA, but the evidence is scarce for VRE