Package Insert Research Articles

1998 Advance care planning on the Same Day Emergency Care Older People's Unit - a quality improvement initiative

Abstract Introduction Same Day Emergency Care (SDEC) at St James’ Hospital, Leeds provides urgent care at the interface between primary and secondary care, offering comprehensive geriatric assessment (CGA) to those living with frailty, aiming to prevent hospitalisation and delay frailty progression. Advance care planning (ACP) is a vital component of prioritising care preferences including at end-of-life, but timing often falls short in practice. This quality improvement (QI) initiative aims to proactively open ACP discussions, allowing patients to consider their care goals, ensuring our care is aligned with their priorities. Method Between July 2022 and April 2023, the project involved 1039 patients. Led by Advanced Clinical Practitioners with support from consultant geriatricians and a palliative care specialist nurse, ACP discussions were encouraged through prompts in daily staff huddles and drop-in teaching sessions. Results ACP uptake increased from 7.8 % to 19.3%. Insights from a perception survey involving 83 healthcare professionals revealed key barriers including clinical workload, limited space, lack of experience and confidence as well as prognostic uncertainty and patient factors. Education and training, clinical supervision, patient information leaflets and a conducive environment were positively associated with ACP. Conclusion There has been a cultural shift in the department as the practitioners now routinely prompt staff to undertake ACP in safety huddles. Key catalysts for ACP initiation were found to be progression of frailty, terminal diagnoses, dementia, and recurrent hospital admissions. As a new SDEC unit is scheduled to open in the coming months, with provision of space and privacy, our aim is to improve the quality and quantity of ACP discussions with the patient at the centre of all decision-making. In line with these endeavours, parallel support within the community through our home (virtual) ward will further enhance proactive care planning in older people living with frailty.

Real-world reporting rates of administration-site reactions with on-demand treatment of hereditary angioedema attacks.

Background: Hereditary angioedema (HAE) is characterized by recurrent and unpredictable episodes of subcutaneous and/or submucosal swelling. Objective: To characterize the real-world treatment burden associated with existing on-demand therapies, we analyzed administration-site adverse drug reactions (ADR) associated with approved on-demand HAE therapies reported in the U.S. Food and Drug Administration's (FDA) Adverse Event Reporting System (FAERS). Methods: We searched the FAERS database from October 1, 2009, to March 31, 2022, for reports of all FDA-approved on-demand therapies for HAE: plasma-derived C1-inhibitor (pdC1-INH), ecallantide, icatibant, and recombinant C1-inhibitor (rhC1-INH). ADRs in which the drug was listed as the "primary suspect" were recorded for each drug. ADR preferred terms were grouped into 18 ADR domains based on semantic and/or clinical similarity, and the number of reports for each drug was calculated per year from the time of approval through March 2022, and descriptive results were presented. Preferred terms associated with administration-site ADRs identified from clinical trials and denoted on approved HAE drug U.S. package inserts were examined in a complementary analysis. Results: The highest reported rates of administration-site ADRs per year were site pain (17.9 reports per year), site erythema (7.4 per year), and site swelling (6.7 per year). RhC1-INH was the only drug for which access-site complications and/or malfunctions were reported (9.5 per year). PdC1-INH had the highest rate of incorrect route of product administration (3.7 per year). PdC1-INH showed statistically significant elevated reporting rate of injection-site reactions (reporting odds ratio [ROR] 3.59 [2.36-5.46]; empirical Bayesian geometric mean [EBGM] 1.97 [1.39]). Icatibant and rhC1-INH showed a statistical trend toward an increased reporting rate of administration-site reactions. Conclusion: Real-world data from FAERS were generally consistent with adverse events reported in clinical trials and suggest that patients experience substantial treatment burden associated with FDA-approved parenteral on-demand therapies for HAE attacks. It should be noted that ADR rates are not exposure adjusted and are based on spontaneous reporting.

Development of Pharmaceutical Equivalent Montelukast Sodium Immediate-Release, Film-Coated Tablets

Montelukast tablets are sold under the brand name Singulair and are used to control and prevent asthma symptoms. In this study, 10 mg film-coated montelukast tablets were developed as a generic drug in order to evaluate the pharmaceutical equivalent of the innovator’s products. The primary formulation ingredients used in all developed formulations (F1-F5) were the same as those described in the Singulair tablet package insert, except for formulations F3, F4, and F5, to which solubilizing enhancers were added to increase montelukast solubility. The core tablets were produced using the wet granulation method before being coated with HPMC polymer. FT-IR and DSC were used to determine drug and excipient compatibility. The micromeritic properties of the granules were assessed. The physicochemical properties of generated montelukast tablets and Singulair tablets were also investigated. The dissolution profiles of the tested drug and the innovator were assessed in a variety of pH mediums (pH 1.2, 4.5, 6.8, and water). The similarity (f2) and difference (f1) factors were computed. The accelerated and long-term stability of the tested drug in hot and humid climate zones was evaluated. The analytical method validation used in this study was ICH-acceptable for 8 parameters including specificity, range, linearity, accuracy, precision, limit of detection, limit of quantitation, and robustness. F1-F5 granules had similar properties, such as a pale-yellow color and excellent flow properties. There were no chemical interactions between montelukast and the excipients according to FT-IR and DSC analyses. The physical properties of all developed montelukast film-coated tablets were similar (average weight 212-218 mg; thickness 3.02-3.07 mm; assay 101-102% LA; disintegration time 3-4 min), except that the disintegration time of F3 was 8.10 min and that of F5 was 5.90 min, which was caused by the addition of poloxamer 188 to the formulation. In all mediums, only the F1 formula produced acceptable comparison dissolution profiles to Singulair. After 6 months of storage under accelerated and long-term conditions, the results showed the F1 formulation remained physically and chemically stable.

Impact of Fine-Tuned Machine Translation on Medical Documentation Translation and Client Satisfaction

Aim: The aim of this study was to assess the impact of Fine-Tuned Machine Translation (FTMT) models, followed by Machine Translation Post-Editing (MTPE), on the translation quality and client satisfaction in medical documentation. Materials and Methods: The research analyzed 733,632 words across 317 projects completed in 2023 by Lingrowth, a medical and life science translation service provider. These projects involved translations from 16 source languages to 34 target languages. Document types included Instructions for Use (IFU), Investigator Brochures (IB), Summary of Product Characteristics (SmPC), Clinical Study Reports (CSR), and Informed Consent Forms (ICF). The projects were categorized into two groups for comparison: translations performed by human translators using Translation Memory (TM) and those processed by FTMT followed by MTPE. The primary metrics for evaluation were the number of post-project finalization requests and instances of severe negative feedback from clients. Results: It was observed that human-translated projects had a higher frequency of post-project finalization requests, whereas MTPE projects after FTMT exhibited a marginally higher rate of severe negative feedback. However, statistical analysis indicated that these differences were not significant, suggesting that the introduction of FTMT models with subsequent MTPE does not adversely affect the overall quality of medical document translations. Conclusion: The study concludes that FTMT models, when supplemented by MTPE, are com-parable in effectiveness to traditional human translations in the context of medical documentation. This highlights the potential of integrating FTMT in translation workflows without compromising translation quality or client satisfaction.

Use of Patient Information Leaflets in the Algerian Context. Current Situation and Regulatory Framework

This paper aims to present the marketing and translation process of patient information leaflets (PILs) into Arabic and their accessibility to the public, taking the Algerian market as a case study. PILs are the main source of information related to medication and are required to be lay-friendly as part of the process of marketing authorization. Lay-friendliness in the Algerian context means that the information contained in the PILS, (1) is conveyed through the receiver language, i.e., Arabic, and (2) is written in a language that is understandable by the receiver. To test these hypotheses, an assessment of the regulatory framework of PILS in the Algerian context was carried out. Furthermore, a study was conducted based on 1) a questionnaire targeting 56 participants to assess the readability of PILS, and 2) a field survey in pharmaceutical laboratories to document the translation stage in the marketing process. The assessment showed that the use of Arabic is mandatory in addition to a foreign language. The questionnaire showed that participants tend to read the Arabic content of the PIL. The survey’s results reported that the translation task is delegated to a sworn translator’s office though the examination of 16 randomly-selected (out of 72 PILs) revealed some linguistic discrepancies.

Family Therapy as a Dynamic Balance of Action and Inaction. To Act or Not to Act – Dilemmas in Family Therapy

Four principles of ethical questioning in family therapy dilemmas are the basis for ethical questions in family therapy as a guideline for to act, how to act, or not to act. An example of an ethical dilemma from the practice of family therapy is described. A “package insert” for family and couples therapy as information about family therapy is comparable to information on the effects of medication: Why not apply the same standard when it comes to effective procedures? Methods of family therapy and individual therapy have been developed side by side and one after the other, for which a clear differential indication and systematization of application still needs to be developed. An experience- and outcome-based family therapy (EBF) could be the goal. The therapeutic position and a guideline for families in therapy are discussed. The application of a five step process model to find out and to solve the ethical questions is developed and presented. We dare to present the thesis that a differential family therapy based on effect and side effect studies with informed consent of the patients or family members can be the basis for a critical classification of the methods to a general “Evidence Based Family Therapy” (experience based family therapy).

Trends in Anti-Influenza Drug Prescription and Adverse Drug Reaction Reporting After the Lifting of Oseltamivir Prescribing Restrictions in Pediatric Outpatients: An Ecological Study Using the MDV Analyzer® And the Japanese Adverse Drug Event Report Database.

Abnormal behavior after oseltamivir administration has been reported in the media; in 2007, the package insert for oseltamivir phosphate was revised to restrict its administration to individuals aged over 10 years. However, in 2018, the age limitation specified in the package insert was removed. Here, we evaluated the trends in anti-influenza drug prescription and adverse drug reactions (ADRs) reported in pediatric outpatients after revising the oseltamivir package insert as an ecological study. Anti-influenza drug prescriptions for pediatric outpatients with influenza aged 0-19 years were downloaded from the acute Diagnosis Procedure Combination hospital databases using the MDV analyzer®. ADR reports on anti-influenza drug prescription among patients aged 0-20 years in the Japanese Adverse Drug Event Report database were downloaded from the Pharmaceutical and Medical Devices Agency website. Data were collected during the 2016/2017 and 2019/2020 influenza seasons. During the influenza epidemic season (January-March), the percentage of oseltamivir prescriptions for patients with influenza aged 10-19 years tripled after the revision of the oseltamivir package insert (9.3% during the 2016/2017 season and 29.2% during the 2019/2020 season); however, reports of abnormal behavior did not increase (two during the 2016/2017 season and none during the 2019/2020 season). The number of oseltamivir-related ADR reports among minors over 10 years of age did not increase although the proportion of oseltamivir prescriptions increased after the revision of the oseltamivir package insert.

Drug-induced depressive symptoms: An update through the WHO pharmacovigilance database

BackgroundDepression is a highly incident condition and some drugs have been described as inducing or worsening depression. However, literature on this topic is rare and possibly outdated. MethodsWe performed disproportionality analyses using VigiBase®, the largest pharmacovigilance database worldwide to identify drugs associated with depression. Then we excluded drugs already known as depressogenic according to American Summary of Product Characteristics (SPC). We then reviewed drug mechanism of action, scientific literature and European SPC for each drug identified to assess a level of plausibility. We measured Reporting Odds Ratio (ROR) statistically significant and superior to 1, suggesting a significant association between a drug and the reporting of depressive symptoms. ResultsOut of the 5237 drugs extracted on VigiBase®, we have retained 89 new drugs associated with depression. More than half of drugs of interest are from nervous system. Opicapone (ROR: 20.66 95 %CI: 15.62–27.33), and gadoversetamide (ROR 18.62, 95 %CI 9.63–35.95) were the drugs with the highest ROR. Among the 89 drugs, 38 were considered already described such as suvorexant or ivacaftor, 20 likely associated such as anti-migraines drugs or new antipsychotic drugs and 31 potentially associated. LimitationsPharmacovigilance studies have many inherent limitations, such as under-reporting bias, notoriety effect and protopathic bias. These results are not intended to establish a causal link, only a statistical association. ConclusionWe found a strong statistical signal and pharmacological plausibility for 58 new depressogenic drugs. This update list of suspected drugs may prove useful for doctors faced with potential cases of drug-induced depression or to stay aware in case. Other studies are needed to confirm the list.

Potentially Harmful Excipients: State of the Art for Oral Liquid Forms Used in Neonatology and Pediatrics Units.

The pediatric population exhibits an important age-dependent heterogeneity in pharmacokinetics and pharmacodynamics parameters, resulting in differences in drug efficacy and toxicity compared to the adult population, particularly for neonates. Toxicity and efficacy divergences have been studied for active molecules, but the impact on the pharmacological parameters of excipients remains less well known. To fill this lack of knowledge, several initiatives have been started to gather information on the specific toxicity of excipients, such as the KIDS list or the STEP database. In order to contribute to this much-needed action, in this work, a compilation of the 219 formulations of oral liquid forms prescribed in pediatrics and neonatology units was established based on the summary of product characteristics. Then, for excipients found in more than 10% of the analyzed formulations, a review of their toxicity data was carried out using the STEP database. Finally, for a selection of 10 frequently used liquid forms, the amounts of excipients administered daily were calculated based on the recommended posology in the Summary of Product Characteristics (SPC) and compared with the recommended daily limits proposed by the European Medicine Agency. Pediatrics-adapted formulations are still rare, and it is not always possible to find safe alternatives to drugs containing excipients of interest.

Pharmacogenomic biomarker information on drug labels of the Spanish Agency of Medicines and Sanitary products: evaluation and comparison with other regulatory agencies.

This work aimed to analyse the pharmacogenetic information in the Spanish Drug Regulatory Agency (AEMPS) Summary of Products Characteristics (SmPC), evaluating the presence of pharmacogenetic biomarkers, as well as the associated recommendations. A total of 55.4% of the 1891 drug labels reviewed included information on pharmacogenetic biomarker(s). Pharmacogenomic information appears most frequently in the "antineoplastic and immunomodulating agents", "nervous system", and "cardiovascular system" Anatomical Therapeutic Chemical groups. A total of 509 different pharmacogenetic biomarkers were found, of which CYP450 enzymes accounted for almost 34% of the total drug-biomarker associations evaluated. A total of 3679 drug-biomarker pairs were identified, 102 of which were at the 1A level (PharmGKB® classification system), and 33.33% of these drug-pharmacogenetic biomarker pairs were assigned to "actionable PGx", 12.75% to "informative PGx", 4.9% to "testing recommended", and 4.9% to "testing required". The rate of coincidence in the assigned PGx level of recommendation between the AEMPS and regulatory agencies included in the PharmGKB® Drug Label Annotations database (i.e., the FDA, EMA, SWISS Medic, PMDA, and HCSC) ranged from 45% to 65%, being 'actionable level' the most frequent. On the other hand, discrepancies between agencies did not exceed 35%. This study highlights the presence of relevant pharmacogenetic information on Spanish drug labels, which would help avoid interactions, toxicity, or lack of treatment efficacy.

Review on Toxicity, Mechanisms and Health Effects of Herbicides and Prevention Mechanisms

In agricultural crop production, herbicides are typically used to prevent or control weeds and other plant pathogens by reducing crop losses and maintaining high product quality. This brief overview sheds light on the level of toxicity, mechanisms of toxicity, health effects and prevention strategies. Three main levels of toxicity have been identified in herbicides: acute (short-term exposure), sub-chronic (medium-term exposure), and chronic (long-term exposure). These levels of toxicity have detrimental effects on humans, animals, and the environment. Herbicides must be handled and administered appropriately to minimize or completely prevent their negative side effects. It is recommended to manage herbicide to its minimum residue level while using them in agriculture. On the hand, certain mechanisms of action must be followed including contact, absorption, movement, toxicity, and death in order to be effective in management of weed by herbicides. This mechanism of actions of herbicides are also applied to humans and animals too. Improper usage of herbicides has adverse health effects on humans such as carcinogenic, cardiovascular, respiratory, hormonal, metabolic, cellular and neurological effects. In order to eliminate or minimize their effect the preventive safety mechanisms/strategies such as employing alternative and less herbicide-dependent cropping systems, properly using all certified personal protective equipment (PPE), proper packaging and package leaflet, proper labeling and giving general awareness about the use or handle of herbicide for farmers or any others who are not familiar with the use of herbicides must applied before or after handling of herbicides. In order to minimize or totally avoid the negative impacts of herbicides on humans, animals, and the environment, it is not just the responsibility of farmers but also of other stakeholders (agricultural experts, policymakers, etc.).

Factors affecting the medication literacy of older adults and targeted initiatives for improvement: a cross-sectional study in central China.

This study explored the state of rational drug use among older adults in central China, aiming to unveil factors influencing their medication literacy and proposing targeted improvement measures. A cross-sectional study involving 454 participants aged 60 and above was conducted in Hubei province between February 1 and May 30, 2023, with data collected through face-to-face interviews by pharmacists. Multiple logistic regression analysis was conducted to determine factors that affected medication literacy. Of the 412 valid questionnaires, findings revealed inadequate knowledge of rational drug use among older adults in central China. Those who fully understood (105, 25.49%, OR = 9.349, p < 0.001, 95%CI = 3.884-22.502) or partially understood (228, 55.34%, OR = 3.295, p = 0.002, 95%CI = 1.548-7.013) drug instructions exhibited significantly higher medication literacy than those who did not understand (79, 19.17%). Subsequent research revealed a lack of awareness in reading drug instructions or difficulty in understanding them. Most older adults seldom heard of but exhibited high acceptance of medication guidance services. In conclusion, the ability to comprehend drug instructions significantly influenced the medication literacy of older adults. Initiatives such as revising age-appropriate drug instructions could effectively enhance rational drug use among this demographic.

Unlicensed/Off-Label Drug Prescriptions at Hospital Discharge in Children: An Observational Study Using Routinely Collected Health Data.

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. 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. 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). The prevalence of UL/OL prescriptions is about 40% at discharge from a pediatric university hospital in France.

Should we depend on reference intervals from manufacturer package inserts? Comparing TSH and FT4 reference intervals from four manufacturers with results from modern indirect methods and the direct method.

Correct interpretation of thyroid function tests relies on correct reference intervals (RIs) for thyroid-stimulating hormone (TSH) and free thyroxine (FT4). ISO15189 mandates periodic verification of RIs, but laboratories struggle with cost-effective approaches. We investigated whether indirect methods (utilizing historical laboratory data) could replace the direct approach (utilizing healthy reference individuals) and compared results with manufacturer-provided RIs for TSH and FT4. We collected historical data (2008-2022) from 13 Dutch laboratories to re-establish RIs by employing indirect methods, TMC (for TSH) and refineR (for FT4). Laboratories used common automated platforms (Roche, Abbott, Beckman or Siemens). Indirect RIs (IRIs) were determined perlaboratory per year and clustered per manufacturer (>1.000.000 data points per manufacturer). Direct RIs (DRIs) were established in 125 healthy individuals per platform. TSH IRIs remained robust over the years for all manufacturers. FT4 IRIs proved robust for three manufacturers (Roche, Beckman and Siemens), but the IRI upper reference limit (URL) of Abbott showed a decrease of 2 pmol/L from 2015. Comparison of the IRIs and DRIs for TSH and FT4 showed close agreement using adequate age-stratification. Manufacturer-provided RIs, notably Abbott, Roche and Beckman exhibited inappropriate URLs (overall difference of 0.5-1.0 µIU/mL) for TSH. For FT4, the URLs provided by Roche, Abbott and Siemens were overestimated by 1.5-3.5 pmol/L. These results underscore the importance of RI verification as manufacturer-provided RIs are often incorrect and RIs may not be robust. Indirect methods offercost-effective alternatives for laboratory-specific or platform-specific verification of RIs.

Exploratory study on the relationship between urinary sodium/potassium ratio, salt intake, and the antihypertensive effect of esaxerenone: the ENaK Study

Excessive salt intake is one of the causes of hypertension, and reducing salt intake is important for managing the risk of hypertension and subsequent cardiovascular events. Esaxerenone, a mineralocorticoid receptor blocker, has the potential to exert an antihypertensive effect in hypertensive patients with excessive salt intake, but evidence is still lacking, especially in clinical settings. We aimed to determine if baseline sodium/potassium ratio and baseline estimated 24-h urinary sodium excretion can predict the antihypertensive effect of esaxerenone in patients with essential hypertension inadequately controlled with an angiotensin receptor blocker (ARB) or a calcium channel blocker (CCB). This was an exploratory, open-label, interventional study with a 4-week observation period and a 12-week treatment period. Esaxerenone was orally administered once daily in accordance with the Japanese package insert. In total, 126 patients met the eligibility criteria and were enrolled (ARB subcohort, 67; CCB subcohort, 59); all were included in the full analysis set (FAS) and safety analysis. In the FAS, morning home systolic blood pressure (SBP)/diastolic blood pressure (DBP) significantly decreased from baseline to end of treatment (primary efficacy endpoint) (−11.9 ± 10.9/ − 6.4 ± 6.8 mmHg, both p < 0.001); a similar trend was observed in both subcohorts. Significant reductions were also shown in bedtime home and office SBP/DBP (all p < 0.001). Each BP change was consistent regardless of the urinary sodium/potassium ratio or estimated 24-h urinary sodium excretion at baseline. The urinary albumin-creatinine ratio (UACR) and N-terminal pro-brain natriuretic peptide (NT-proBNP) significantly decreased from baseline to Week 12 in the total population and both subcohorts. No new safety concerns were raised. Esaxerenone significantly decreased morning home, bedtime home, and office BP; UACR; and NT-proBNP in this patient population, regardless of concomitant ARB or CCB use. The antihypertensive effect of esaxerenone was independent of the urinary sodium/potassium ratio and estimated 24-h urinary sodium excretion at baseline.

Threshold size of Tablet and Capsule : Prospective Study

Background: Medical tablets and capsules are the most commonly used dose form due to their portability. However, their enormous size frequently causes difficulties during swallowing, which might lead to decreased drug adherence. The authors examined postmarketing surveillance data to assess the size of medical tablets and capsules that patients consider too large to swallow. Aim: This study aims to learn the law behind keeping the shape or size of capsules/ tablets in higher dimensions. Method: A dataset was created from the package inserts of the reported medications based on reports from patients saying that the pill or capsule was too large for consumption. Two analyses were performed: size distribution histogram analysis and geometric analysis utilizing linear approximation. Conclusion: The size of tablets/capsules that patients consider too large to consume. As a result, while creating or modifying tablets/capsules, the drug should be scored, divided into smaller dosages, or redesigned as an orally disintegrating formulation.

Artificial intelligence-generated patient information leaflets: a comparison of contents according to British Association of Dermatologists standards.

Patient information leaflets (PILs) can supplement a clinical consultation and provide additional information for a patient to read in their own time. A wide range of PILs are available for distribution by the British Association of Dermatologists (BAD) and undergo rigorous review ahead of publication. In the UK, 7.1 million adults are estimated to have the reading age of a 9-year-old child and 43% are unable to comprehend written health information. To determine whether artificial intelligence (AI) can produce PILs that include a similar degree of content to current BAD PILs. Using the AI tool ChatGPT, 10 PILs were generated, and their contents compared with those of existing BAD PILs using an author-generated list of commonly included themes. Omissions were noted and a repeat series of PILs generated using targeted request phrasing. The readability of AI-generated PILs was also analysed. AI-generated PILs were found to include similar factual content to BAD PILs but excluded information that was felt to be more pertinent to patient concerns such as curability and heritability. Targeted request phrasing saw AI generate PILs including this content. The readability of AI-generated PILs was beyond that of a large number of UK adults. Where a condition-specific PIL is not readily available, an AI-generated PIL can provide relevant information of lesser quality than existing BAD PILs, which may be inaccessible to some patients. Specific caution is advised regarding AI-generated medication-specific PILs.

Five paediatric patients with mycosis fungoides and our approach to provide age-appropriate information and psychological support.

Cutaneous lymphoproliferative diseases in childhood are rare and they are clinically and pathologically heterogeneous, which makes their diagnosis challenging. Although there is limited long-term data and guidance on management, evidence suggests these to be different conditions from cutaneous lymphoma in adults, highlighting the need for age-appropriate patient information. We present clinical outcomes for our paediatric cohort of five patients with mycosis fungoides, emphasizing that despite diagnostic delays, mycosis fungoides in this age group tends to yield a good prognosis. It remains uncommon to provide clinical expertise together with psychological support in a dermatology paediatric service. Here, we provide our experience in offering this combined service. In conjunction with these patients, we have co-produced an accessible patient information leaflet targeted at a younger audience for support and to clarify potential misconceptions from a diagnosis of cutaneous lymphoma.

Safety and Real-World Dosing of OnabotulinumtoxinA for the Treatment of Adult Spasticity: Post Hoc Analysis of the Adult Spasticity International Registry Study.

The aim of the study is to evaluate the safety of onabotulinumtoxinA treatment for spasticity across dose ranges in real-world practice. Adult Spasticity International Registry was a multicenter, prospective, observational study (NCT01930786) of onabotulinumtoxinA treatment for adult spasticity over 2 yrs. Adverse events, serious adverse events, treatment-related adverse events, and serious treatment-related adverse events were sorted into five categories (≤200, 201-400, 401-600, 601-800, ≥801 U) based on cumulative dose per session. In 3103 treatment sessions ( T ), 730 patients received ≥1 dose of onabotulinumtoxinA. Dose categories included the following: ≤200 U ( n = 312, T = 811), 201-400 U ( n = 446, T = 1366), 401-600 U ( n = 244, T = 716), 601-800 U ( n = 69, T = 149), and ≥801 U ( n = 29, T = 61). Of these patients, 261 reported 827 adverse events, 94 reported 195 serious adverse events, 20 reported 23 treatment-related adverse events, and 2 patients treated with 201-400 U onabotulinumtoxinA reported 3 serious treatment-related adverse events. Treatment-related adverse events reported included ≤200 U (8/811, 0.9%), 201-400 U (7/1366, 0.5%), 401-600 U (6/716, 0.8%), 601-800 U (1/149, 0.7%), and ≥801 U (1/61, 1.6%). In this post hoc analysis, most treatment sessions were performed with 201-400 U onabotulinumtoxinA. Patients treated with 201-400 U onabotulinumtoxinA had an adverse event profile consistent with onabotulinumtoxinA package inserts globally (e.g., United States, European Union, United Kingdom, Canada). No new safety signals were identified.

Pharmacovigilance of esketamine nasal spray: an analysis of the FDA adverse event reporting system database.

Esketamine nasal spray (ESK-NS) is a new drug for treatment-resistant depression, and we aimed to detect and characterize the adverse events (AEs) of ESK-NS using the Food and Drug Administration (FDA) adverse event reporting system (FAERS) database between 2019 Q1 and 2023 Q4. Reporting odds ratio (ROR), proportional reporting ratio (PRR), and multi-item gamma Poisson shrinker (MGPS) were performed to detect risk signals from the FAERS data to identify potential ESK-NS-AEs associations. A total of 14,606 reports on AEs with ESK-NS as the primary suspected drug were analyzed. A total of 518 preferred terms signals and 25 system organ classes mainly concentrated in psychiatric disorders (33.20%), nervous system disorders (16.67%), general disorders and administration site conditions (14.21%), and others were obtained. Notably, dissociation (n = 1,093, ROR 2,257.80, PRR 899.64, EBGM 876.86) exhibited highest occurrence rates and signal intensity. Moreover, uncommon but significantly strong AEs signals, such as hand-eye coordination impaired, feeling guilty, and feelings of worthlessness, were observed. Additionally, dissociative disorder (n = 57, ROR 510.92, PRR 506.70, EBGM 386.60) and sedation (n = 688, ROR 172.68, PRR 155.53, and EBGM 142.05) both presented strong AE signals, and the former is not recorded in the Summary of Product Characteristics (SmPC). In clinical applications, close attention should be paid to the psychiatric disorders and nervous system disorders, especially dissociation. Meanwhile, clinical professionals should be alert for the occurrence of AEs signals not mentioned in the SmPC and take preventive measures to ensure the safety of clinical use.