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Background: Eosinophilic esophagitis (EoE) is a rare, chronic immune-mediated disorder with limited treatment options. Despite the U.S. Food and Drug Administration (FDA) approval of dupilumab for EoE, other monoclonal antibodies remain unapproved and are used off-label with limited evidence on their efficacy and safety. This systematic review rigorously and comprehensively evaluates the evidence for monoclonal antibody therapies used off-label to treat EoE. Methods: We conducted a systematic review across PubMed, EMBASE, Cochrane Central, and ClinicalTrials.gov, assessing the efficacy and safety of off-label monoclonal antibodies in EoE through clinical outcomes and the FDA Adverse Event Reporting System (FAERS) data. Results: Among ten monoclonal antibodies reviewed, mepolizumab that targets IL-5 showed the most promise with a moderate recommendation based on Level 2 evidence. Others like omalizumab (anti-IgE), dectrekumab (anti-IL-13), and reslizumab (anti-IL-5) showed limited utility. Safety evaluations via the FAERS database revealed significant adverse drug reactions, including serious events like asthmatic crises, pneumonia, and adrenal insufficiency for mepolizumab and reslizumab, as well as chronic obstructive pulmonary disease and gastroenteritis for omalizumab. Dectrekumab’s safety profile remains unclear due to a lack of data. Conclusions: While mepolizumab demonstrates potential as an off-label treatment, none of the antibodies reviewed have FDA approval for EoE. Clinicians should consider the balance between local and systemic effects and exercise caution, closely monitoring for adverse effects, particularly in patients with respiratory comorbidities. Continued research is crucial to establish a more robust evidence base for these therapies.

Abrocitinib, an oral small-molecule Janus Kinase 1 (JAK1) inhibitor, is primarily approved for treating moderate-to-severe atopic dermatitis (AD) in adults and adolescents aged 12 and older. This review examines the emerging off-label uses of Abrocitinib. We identified 37 papers reporting on the use of Abrocitinib in various conditions other than AD. The most commonly reported uses were for vitiligo, prurigo nodularis, and hand eczema, with 12 cases each. There were also 10 cases of lichen sclerosus and chronic pruritus of unknown origin and 5 cases each of pityriasis rubra pilaris alopecia areata. Additionally, erythematotelangiectatic rosacea and steroid-induced rosacea were reported in four cases each. Other conditions treated with Abrocitinib were noted, but these mostly had only one or two reported cases. Interestingly, out of the 103 patients reviewed, all studies reported favorable clinical outcomes and satisfactory results, with the exception of one isolated case where Abrocitinib was used to treat erythematotelangiectatic rosacea.

There are few data on yellow fever (YF) and hepatitis A (HA) off-label vaccination. Given the rising trend of travel to endemic countries, there is a growing necessity to broaden vaccination coverage among the pediatric population. For this reason, we aim to assess the adverse effects associated with off-label vaccination, with the ultimate purpose of expanding the vaccine spectrum. We analyzed ambispectively ninety-four children under 12 months of age who received YF or HA off-label vaccines. The YF vaccine was administered to children aged 6–9 months and those allergic to eggs (with a prior negative prick test and no history of anaphylaxis), while the HA vaccine was given to children aged 6–12 months. Overall, 71 (75%) were vaccinated against YF, and 57 (60%) against HA; 34 against both. All of them fulfilled off-label vaccination criteria. No immediate adverse effects (AEs) were reported. Mild common AEs (diarrhea, fever, or malaise) were experienced by 10.8% of patients within 10 days after vaccination. The rate of AEs associated with off-label vaccination for HA and YF is low, suggesting that the vaccines could be considered safe.

Background: Information regarding off-label and unlicensed medicine use among South African children is limited. This is a concern as the prescribing of off-label and unlicensed medicines can lead to issues of effectiveness and safety as well as raise liability issues in the event of adverse events. This potentially exposes physicians to legal penalties. Consequently, we sought to determine the prevalence of off-label and unlicensed medicine use among paediatric patients in South Africa to provide future direction. Methods: This study retrospectively examined the use of medicine in a point-prevalence survey study (PPS) involving paediatric patients aged (0–2 years) admitted to selected public hospitals in Gauteng Province, South Africa. Data were collected per hospital over two days between February 2022 and July 2022. Demographics, duration of treatment, diagnosis, and medicines prescribed were collected from patient medical records using a mobile application. Prescribed medicines were reviewed against the medicine formularies and other databases to assess their appropriateness. Results: From three academic hospitals, 184 patient records were reviewed. A total of 592 medicines were dispensed, of which 379 (64.0%) were licensed and 213 (36.0%) were used off-label/unlicensed for paediatric patients 0–2 years of age. The most prevalent off-label and unlicensed medicines were multivitamins (n = 32, 15.0%) and ampicillin injections (n = 15, 7.0%). Conclusion: The frequency of unlicensed and off-label medicine prescribing shown in this study is consistent with the literature and can be considered high. This practice can pose a risk because it adversely affects patients if not properly regulated. Attention is needed to ensure future high-quality, safe, and effective use of medicines.

Abrocitinib, an oral small-molecule Janus Kinase 1 (JAK1) inhibitor, is primarily approved for treating moderate-to-severe atopic dermatitis (AD) in adults and adolescents aged 12 and older. This review examines the emerging off-label uses of Abrocitinib. We identified 37 papers reporting on the use of Abrocitinib in various conditions other than AD. The most commonly reported uses were for vitiligo, prurigo nodularis, and hand eczema, with 12 cases each. There were also 10 cases of lichen sclerosus and chronic pruritus of unknown origin and 5 cases each of pityriasis rubra pilaris alopecia areata. Additionally, erythematotelangiectatic rosacea and steroid-induced rosacea were reported in four cases each. Other conditions treated with Abrocitinib were noted, but these mostly had only one or two reported cases. Interestingly, out of the 103 patients reviewed, all studies reported favorable clinical outcomes and satisfactory results, with the exception of one isolated case where Abrocitinib was used to treat erythematotelangiectatic rosacea.

(1) Background: SARS-CoV-2 infection is notably mild in children, though comorbidities may increase the risk of hospitalization and may represent a risk for increased disease severity. There is an urgent need for targeted therapies with an acceptable efficacy and safety profile. To date, most of the medicines for COVID-19-specific treatment are prescribed off-label for children due to a lack of clinical trials and consequent evidence in this population. (2) Methods: This was a retrospective, observational study investigating the safety of treatments for the prevention of severe COVID-19 in fragile pediatric patients who received monoclonal antibodies and antivirals for mild-to-moderate symptoms between December 2021 and July 2022. (3) Results: Thirty-two patients were included. Monoclonal antibodies were prescribed to 62%, intravenous antivirals to 22%, and oral antivirals to 16% of children. Sotrovimab was the most frequently prescribed drug among monoclonal antibodies and overall (59%). The second most prescribed drug was remdesivir (22%). No severe adverse drug reaction was reported. There was no progression to severe disease and no death cases due to COVID-19 or drug administration. At drug-type stratification, resolution of symptoms and swab positivity time showed no difference between the two groups at 7 and 28 days. Off-label prescriptions were 84% overall, and in similar proportions between the two groups. (4) Conclusions: in this small sample, antivirals seemed safe and showed no differences in efficacy as compared to MAbs for the early treatment of COVID-19 in fragile children, thus representing a valuable choice, even when administered off-label.

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.

Randomized controlled trials have demonstrated that noninsulin medications used to treat type 2 diabetes can improve health outcomes among patients with type 1 diabetes (T1D). This study assessed the effects of adjuvant diabetes medications on glycated hemoglobin (A1C), body mass index (BMI), or total daily insulin (TDI) among patients with T1D in a real-world setting. This was an analysis of the T1D Exchange Clinic Registry, using the study periods of 2010–2012, 2015–2016, and 2016–2017, to assess differences in A1C, BMI, and TDI between patients with and without adjuvant medications. The relationships between characteristics and A1C in 2015–2016 and 2016–2017 were determined. Analysis included 517 patients in the adjuvant medication cohort and 4968 in the insulin-only cohort. No significant improvement in A1C was observed. A significant difference in BMI and TDI between the insulin-only (median BMI: 25.5, 26.2, 26.4 and median TDI: 45, 44 units) and adjuvant medication cohorts (median BMI: 29.8, 30.5, 30.5 and median TDI: 51, 52 units) (p < 0.001) was observed. Patients with a continuous glucose monitor (CGM), higher education level, higher annual income, and older age were associated with lower A1C (p ≤ 0.001). Higher BMI and self-description as African American/Black were associated with higher A1C (p ≤ 0.01). Insulin pump use was associated with lower A1C (p < 0.01) in 2015–2016. Patients who used adjuvant medications did not demonstrate significant improvement in disease control. These data suggest that findings from well-designed research studies may not be consistently reproducible in real-world settings, due to patient-specific factors.

(1) Background: The incidence of thromboembolic events is relatively low in the general population, but it increases in hospitalized children and those who underwent thrombogenic procedures. Although the evidence regarding direct oral anticoagulants (DOACs) in children with venous thromboembolism (VTE) is growing, DOACs were excluded from existing guidelines due to the lack of reliable data at that moment. Therefore, current evidence on VTE management in children needs to be critically reviewed. (2) Methods: We have conducted a literature search in the Scopus, EMBASE, and MEDLINE databases using prespecified keywords to retrieve studies published between 2010 and 2022. (3) Results: Clinical trials highlighted that rivaroxaban and dabigatran had predictable pharmacokinetic and pharmacodynamic profiles in children, similar to those observed in adults. Dabigatran and rivaroxaban had a similar safety profile to standard therapy but improved thrombotic burden and resolution during follow-up. Most studies involving apixaban and edoxaban are ongoing, and results are awaited. (4) Conclusions: Dabigatran and rivaroxaban could be valid therapeutic options for VTE management in children. In the case of apixaban and edoxaban, results from ongoing clinical studies are required before using them in pediatric VTE.

In recent years, off-label and unlicensed drug use has extensively developed in the paediatric population. For a long time, clinical trials in the paediatric population were considered complicated to perform because of ethical problems, causing frequent off-label use. Off-label drug use remains an important public health issue, especially for children with rare conditions or with diseases not responsive to conventional treatments. The present paper is a narrative review of the literature of off-label drug use in children. The aim of our study is to summarize the main works dealing with the off-label use of biological drugs in paediatrics. Further studies analyzing their efficacy, safety, and cost–benefit ratios are needed to extend the use of biological therapies to the paediatric population.

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.

There are few data on yellow fever (YF) and hepatitis A (HA) off-label vaccination. Given the rising trend of travel to endemic countries, there is a growing necessity to broaden vaccination coverage among the pediatric population. For this reason, we aim to assess the adverse effects associated with off-label vaccination, with the ultimate purpose of expanding the vaccine spectrum. We analyzed ambispectively ninety-four children under 12 months of age who received YF or HA off-label vaccines. The YF vaccine was administered to children aged 6-9 months and those allergic to eggs (with a prior negative prick test and no history of anaphylaxis), while the HA vaccine was given to children aged 6-12 months. Overall, 71 (75%) were vaccinated against YF, and 57 (60%) against HA; 34 against both. All of them fulfilled off-label vaccination criteria. No immediate adverse effects (AEs) were reported. Mild common AEs (diarrhea, fever, or malaise) were experienced by 10.8% of patients within 10 days after vaccination. The rate of AEs associated with off-label vaccination for HA and YF is low, suggesting that the vaccines could be considered safe.

While mental health services for children are increasing, few psychiatric drugs have been approved for such use. We analyzed claim data from 19,557 South Korean pediatric and adolescent patients (

The availability of liquid oral preparations compounded by pharmacists is essential to meet paediatric needs which remain unanswered by the pharmaceutical industry. Unfortunately, compendial monographs are often not available and, in many cases, pre-formulation studies (e.g., compatibility with other excipients and solubility evaluations) are not performed in-depth, leading, in some rare cases, to the inadvertent administration of a toxic dose. In this study, the preparation of an oral liquid formulation for paediatric use, containing flecainide acetate at different strengths, was considered, taking into account the possible effects of conventionally used excipients. First, the optimal vehicle was selected based on a solubility study, evidencing some unexpected formations of precipitates. As a matter of fact, the buffers commonly used for oral solutions significantly reduced flecainide solubility, and the concomitant presence of citrate buffer and methylparaben even caused the formation of non-resuspendable crystals. Then, chemical, physical, and microbiological stability were assessed. Solutions at strengths of 10 and 20 mg/mL flecainide acetate were stable up to 8 weeks when compounded by using a 40% sucrose solution as a vehicle. Microbiological data showed that the use of methylparaben was not necessary over this time period.

Background: Unlicensed and off-label (UL/OL) prescriptions have been associated with an increased risk of drug-related problems. Data of their prevalence at hospital discharge remain insufficient. We aimed to describe the prevalence of UL/OL drugs in outpatient prescriptions at discharge in children., Methods: We conducted a retrospective study using the routinely collected health data of children at discharge from 2014 to 2016. The primary reference source for determining licensed labelling was the summaries of product characteristics (SPCs) in a French industry-independent formulary named Thériaque. We described the characteristics of UL/OL prescriptions at discharge and looked for predictors of UL/OL prescriptions., Results: We included 2536 prescriptions of 479 children. Licensed, OL, and UL prescriptions accounted for 58.6% (95% CI: 56.7-60.5), 39.2% (95% CI: 37.3-41.1), and 2.3% (95% CI: 1.7-2.9), respectively. A total of 323 (74%) children received at least one UL/OL drug. Among the licensed drugs, bronchodilators (8.8%) and analgesics (8.6%), and among the OL drugs, antibiotics (2.8%), were the most prescribed. The younger age of the children and higher number of drugs they received increased the probability of UL/OL prescriptions (unadjusted p -value of ≤0.05)., Conclusion: The prevalence of UL/OL prescriptions is about 40% at discharge from a pediatric university hospital in France.

Tablets containing prescribed doses are not always available, and this is of particular importance in paediatric care where suitable age-appropriate formulations are generally lacking. To obtain a child-adjusted dose, tablets are manipulated in several ways; e.g., they may be dispersed in water before a fraction is extracted, or they may be split before the resulting fragment is dispersed. In this study, the accuracy attained through these manipulation methods was investigated for two generic tablets containing the anticoagulant warfarin. Tablets were dispersed in water (10 mL) before a fraction (10%) was withdrawn, alternatively tablets were split in half or quarter fragments before the fragments were dispersed in water. To investigate the contribution of variability from the different steps in the manipulation processes, the amount of warfarin recovered from the various dispersions was determined, as was the accuracy of the splitting. A validated UHPLC-method was used for quantitative determination of warfarin. Splitting of the tablets could result in deviation >30% from the ideal, theoretical weight. The amount of drug substance extracted as a fraction from the dispersed tablets deviated no more than 10% from the intended amount. To obtain the most accurate child-adjusted fraction dose of warfarin, the tablets investigated in this study should be dispersed and the desired proportion extracted. Practices that involve splitting tablets are likely to increase the variation, and should be avoided.

Children need a distinct medicines-use system designed explicitly for them since their continued inclusion in a system of prescription processing developed for adults generates insoluble risk points and workarounds. The American Academy of Pediatrics (AAP), in its policy statement released by the AAP Committee on Drugs in early 2014 about off-label use in children, posits that federal legislation on increased drug testing in children has been effective, as “there have been over 500 pediatric-specific labeling changes.” However, the AAP’s position has not changed materially since the original 2002 policy statement. Indeed, other health professionals, their organizations, or affiliated practice-based research network (PBRNs) mechanisms continue to be excluded from consideration, collaboration, or even honorable mention. It is noteworthy that most of the 500 labeling changes made since 1997 have addressed the scientific validity of indications for medication use in pediatric population without regard to pharmacotherapy formulation or monitoring. Medication use in children continues to be associated with an unacceptably high rate of adverse events, morbidity, and death. Children should no longer be “shoehorned” into the adult medication-use system, which faces challenges in addressing even the adult population’s needs. The time is now to design a multi-phasic, systematic approach to the pharmacotherapy of children. This paper will argue for the establishment of a distinct medication use system for children, a trans-disciplinary system designed thoughtfully and intentionally, not by convention, consensus, or imitation.

Background: Information regarding off-label and unlicensed medicine use among South African children is limited. This is a concern as the prescribing of off-label and unlicensed medicines can lead to issues of effectiveness and safety as well as raise liability issues in the event of adverse events. This potentially exposes physicians to legal penalties. Consequently, we sought to determine the prevalence of off-label and unlicensed medicine use among paediatric patients in South Africa to provide future direction., Methods: This study retrospectively examined the use of medicine in a point-prevalence survey study (PPS) involving paediatric patients aged (0-2 years) admitted to selected public hospitals in Gauteng Province, South Africa. Data were collected per hospital over two days between February 2022 and July 2022. Demographics, duration of treatment, diagnosis, and medicines prescribed were collected from patient medical records using a mobile application. Prescribed medicines were reviewed against the medicine formularies and other databases to assess their appropriateness., Results: From three academic hospitals, 184 patient records were reviewed. A total of 592 medicines were dispensed, of which 379 (64.0%) were licensed and 213 (36.0%) were used off-label/unlicensed for paediatric patients 0-2 years of age. The most prevalent off-label and unlicensed medicines were multivitamins (n = 32, 15.0%) and ampicillin injections (n = 15, 7.0%)., Conclusion: The frequency of unlicensed and off-label medicine prescribing shown in this study is consistent with the literature and can be considered high. This practice can pose a risk because it adversely affects patients if not properly regulated. Attention is needed to ensure future high-quality, safe, and effective use of medicines.

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.

Randomized controlled trials have demonstrated that noninsulin medications used to treat type 2 diabetes can improve health outcomes among patients with type 1 diabetes (T1D). This study assessed the effects of adjuvant diabetes medications on glycated hemoglobin (A1C), body mass index (BMI), or total daily insulin (TDI) among patients with T1D in a real-world setting. This was an analysis of the T1D Exchange Clinic Registry, using the study periods of 2010−2012, 2015−2016, and 2016−2017, to assess differences in A1C, BMI, and TDI between patients with and without adjuvant medications. The relationships between characteristics and A1C in 2015−2016 and 2016−2017 were determined. Analysis included 517 patients in the adjuvant medication cohort and 4968 in the insulin-only cohort. No significant improvement in A1C was observed. A significant difference in BMI and TDI between the insulin-only (median BMI: 25.5, 26.2, 26.4 and median TDI: 45, 44 units) and adjuvant medication cohorts (median BMI: 29.8, 30.5, 30.5 and median TDI: 51, 52 units) (p < 0.001) was observed. Patients with a continuous glucose monitor (CGM), higher education level, higher annual income, and older age were associated with lower A1C (p ≤ 0.001). Higher BMI and self-description as African American/Black were associated with higher A1C (p ≤ 0.01). Insulin pump use was associated with lower A1C (p < 0.01) in 2015−2016. Patients who used adjuvant medications did not demonstrate significant improvement in disease control. These data suggest that findings from well-designed research studies may not be consistently reproducible in real-world settings, due to patient-specific factors.

(1) Background: The incidence of thromboembolic events is relatively low in the general population, but it increases in hospitalized children and those who underwent thrombogenic procedures. Although the evidence regarding direct oral anticoagulants (DOACs) in children with venous thromboembolism (VTE) is growing, DOACs were excluded from existing guidelines due to the lack of reliable data at that moment. Therefore, current evidence on VTE management in children needs to be critically reviewed. (2) Methods: We have conducted a literature search in the Scopus, EMBASE, and MEDLINE databases using prespecified keywords to retrieve studies published between 2010 and 2022. (3) Results: Clinical trials highlighted that rivaroxaban and dabigatran had predictable pharmacokinetic and pharmacodynamic profiles in children, similar to those observed in adults. Dabigatran and rivaroxaban had a similar safety profile to standard therapy but improved thrombotic burden and resolution during follow-up. Most studies involving apixaban and edoxaban are ongoing, and results are awaited. (4) Conclusions: Dabigatran and rivaroxaban could be valid therapeutic options for VTE management in children. In the case of apixaban and edoxaban, results from ongoing clinical studies are required before using them in pediatric VTE.

The lack of appropriate medicines for children has a significant impact on health care practices in various countries around the world, including Thailand. The unavailability of pediatric medicines in hospital formularies causes issues regarding off-label use and extemporaneous preparation, resulting in safety and quality risks relating to the use of medicines among children. This research aimed to identify missing pediatric formulations based on the experience of healthcare professionals in a teaching hospital in northern Thailand. A cross-sectional survey was conducted to collect data on missing pediatric formulations, the reasons for their inaccessibility, their off-label uses, their reactions to the situation, and suggestions to improve access to these identified medications. The survey was distributed to all physicians, nurses, and pharmacists involved in prescribing, preparing, dispensing, and administering pediatric medicines. A total of 218 subjects responded to the survey. Omeprazole, sildenafil, and spironolactone suspension were most often identified as missing formulations for children by physicians and pharmacists. They are unavailable on the Thai market or in any hospital formulary. For nurses, sodium bicarbonate, potassium chloride, and chloral hydrate were the most problematic formulations in terms of preparation, acceptability, and administration. These medicines were difficult to swallow because of their taste or texture.

Major advances in sequencing technologies and targeted therapies have accelerated the incorporation of oncology into the era of precision medicine and "biomarker-driven" treatments. However, the impact of this approach on the everyday clinic has yet to be determined. Most precision oncology reports are based on developed countries and usually involve metastatic, hard-to-treat or incurable cancer patients. Moreover, in many cases race and ethnicity in these studies is commonly unreported and real-world evidence in this topic is scarce. Herein, we report data from a total of 202 Chilean advanced stage refractory cancer patients. Retrospectively, we collected patient data from NGS tests and IHC in order to determine the proportion of patients that would benefit from targeted treatments. Overall >20 tumor types were included in our cohort and 37% of patients ( n = 74) displayed potentially actionable alterations, including on-label, off-label and immune checkpoint inhibitor recommendations. Our findings were in-line with previous reports such as the cancer genome atlas (TCGA). To our knowledge, this is the first report of its kind in Latin America delivering real-world evidence to estimate the percentage of refractory tumor patients that might benefit from precision oncology. Although this approach is still in its infancy in Chile, we strongly encourage the implementation of mutational tumor boards in our country in order to provide more therapeutic options for advanced stage refractory patients., Competing Interests: The authors declare no conflicts of interest.

While mental health services for children are increasing, few psychiatric drugs have been approved for such use. We analyzed claim data from 19,557 South Korean pediatric and adolescent patients (<20 years) who were diagnosed with schizophrenia, bipolar disorder, major depressive disorder, anxiety disorder, attention deficit-hyperactivity disorder (ADHD), or a tic disorder. Among these diseases, depressive episodes were the most common, followed by an anxiety disorder, ADHD, bipolar disorder, tic disorder, and schizophrenia. For each disease, prescriptions were categorized as full-label (approved indication with pediatric dosing in the package insert (PI)), partial-label (approved indication without pediatric dosing in the PI), and contraindication (contraindicated for the specific pediatric age in the PI). For schizophrenia, major depressive disorder, and anxiety disorder, more than 50% of the patients were prescribed partial-labeled medications. Additionally, more than 5% of patients with major depressive disorder were prescribed medications that were contraindicated for their age group. Our findings reveal that children with full-labeled psychiatric conditions are commonly administered drugs that are not explicitly approved for either their disease state or age, including off-label and unlicensed drugs. To use pharmaceuticals more safely, expanding drug indications using real-world data are needed.

Off-label use of rituximab is commonly requested for patients with resistant nephropathies. The outcomes and tolerability of rituximab in adult patients with nephropathy treated at our hospital (from 2013 to 2018) were described. Data were retrieved from electronic medical records. Response was classified as complete remission (CR), partial remission (PR), or no response (NR) according to the KDIGO criteria. A total of 89 requests were received for 61 patients. Median age was 58 years (45.9% female). Idiopathic membranous nephropathy (MN) ( n = 30) was the most frequent indication, followed by minimal change disease (MCD) ( n = 15) and secondary membranoproliferative glomerulonephritis (MPGN) ( n = 12). Three patients with focal segmental glomerulosclerosis (FSGS) were included. After most treatment cycles in MN, a CR or PR was observed; median proteinuria levels significantly decreased for these patients (6000 mg/24h (IQR 3584-10,300) vs. 1468.8 (IQR 500-4604.25), p < 0.01). In MPGN, no response was documented after 46.7% of rituximab cycles. A CR or PR was described with the majority of rituximab cycles in MCD, with a significant decrease in proteinuria (6000 mg/24 h (IQR 4007-11,426) vs. 196.8 (IQR 100-1300), p = 0.013). No cycles produced a response in FSGS. Mean CD19+ B-cell decreased in all types of nephropathy (10.44% vs. 0.29%, p < 0.0001). Eleven patients presented infusion-related reactions, and 17 presented infectious complications. The majority of patients with MN and MCD had complete or partial responses; however, neither MPGN nor FSGS had encouraging results.

Chorea-acanthocytosis (ChAc) is a neurodegenerative disease caused by mutations in the VPS13A gene. It is characterized by several neurological symptoms and the appearance of acanthocytes. Elevated tyrosine kinase Lyn activity has been recently identified as one of the key pathophysiological mechanisms in this disease, and therefore represents a promising drug target. Methods: We evaluated an individual off-label treatment with the tyrosine kinase inhibitor dasatinib (100 mg/d, 25.8-50.4 weeks) of three ChAc patients. Alongside thorough safety monitoring, we assessed motor and non-motor scales (e.g., MDS-UPDRS, UHDRS, quality of life) as well as routine and experimental laboratory parameters (e.g., serum neurofilament, Lyn kinase activity, actin cytoskeleton in red blood cells). Results: Dasatinib appeared to be reasonably safe. The clinical parameters remained stable without significant improvement or deterioration. Regain of deep tendon reflexes was observed in one patient. Creatine kinase, serum neurofilament levels, and acanthocyte count did not reveal consistent effects. However, a reduction of initially elevated Lyn kinase activity and accumulated autophagy markers, as well as a partial restoration of the actin cytoskeleton, was found in red blood cells. Conclusions: We report on the first treatment approach with disease-modifying intention in ChAc. The experimental parameters indicate target engagement in red blood cells, while clinical effects on the central nervous system could not be proven within a rather short treatment time. Limited knowledge on the natural history of ChAc and the lack of appropriate biomarkers remain major barriers for "clinical trial readiness". We suggest a panel of outcome parameters for future clinical trials in ChAc.

Children need a distinct medicines-use system designed explicitly for them since their continued inclusion in a system of prescription processing developed for adults generates insoluble risk points and workarounds. The American Academy of Pediatrics (AAP), in its policy statement released by the AAP Committee on Drugs in early 2014 about off-label use in children, posits that federal legislation on increased drug testing in children has been effective, as "there have been over 500 pediatric-specific labeling changes." However, the AAP's position has not changed materially since the original 2002 policy statement. Indeed, other health professionals, their organizations, or affiliated practice-based research network (PBRNs) mechanisms continue to be excluded from consideration, collaboration, or even honorable mention. It is noteworthy that most of the 500 labeling changes made since 1997 have addressed the scientific validity of indications for medication use in pediatric population without regard to pharmacotherapy formulation or monitoring. Medication use in children continues to be associated with an unacceptably high rate of adverse events, morbidity, and death. Children should no longer be "shoehorned" into the adult medication-use system, which faces challenges in addressing even the adult population's needs. The time is now to design a multi-phasic, systematic approach to the pharmacotherapy of children. This paper will argue for the establishment of a distinct medication use system for children, a trans-disciplinary system designed thoughtfully and intentionally, not by convention, consensus, or imitation.