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Immunosuppressants, rheumatic and gastrointestinal topics
Published in Evelyne Jacqz-Aigrain, Imti Choonara, Paediatric Clinical Pharmacology, 2021
Evelyne Jacqz-Aigrain, Imti Choonara
Since Bradley’s publication in 1937 [5], reporting behavioural improvement in children treated with benzedrine, studies have increased in number and, over the last 60 years, confirmed the benefit of stimulant medication in the treatment of this disorder. Drugs most often studied in the international community are: methylphenidate (MPH), dextro-amphetamine (DEX), mixed-salts amphetamine (AMP), and pemoline (PEM). These drugs are the most widely prescribed psychotropic medications for children.
Pigmented epithelioid melanocytoma
Published in Longo Caterina, Diagnosing the Less Common Skin Tumors, 2019
Eugenia Veronica Di Brizzi, Gerardo Ferrara, Giuseppe Argenziano, Elvira Moscarella
Histopathologically, it is characterized by dark pigment in deep derma with frequent involvement of subcutis and extension along the adnexal structures. It often presents hyperplasia of the epidermis above the tumor, and in some cases a grenz zone can be seen. PEMs are composed of several cell types. The first are spindled cells, some with pseudodendrites, small epithelioid cells with heavily pigmented cytoplasm and big epithelioid cells with big vesicles, eosinophilic macronuclei, light perinuclear cytoplasm and peripherally pigmented ring. Melanophages can be observed, constituting less than 10% of the cells in the tumor. Moreover, PEM shows prominent nuclear membrane and low mitotic activity.3
Pharmacovigilance
Published in Christine Bond, Ann Lewis, Using Medicines Information, 2018
The technique of PEM has been described in detail elsewhere.25 When a new drug is licensed and selected by the DSRU, the NHS Business Services Authority (NHSBSA) in England is notified (Figure 9.3). Exposure data for the study drug is obtained from data collected on dispensed NHS prescriptions issued by GPs immediately after the date of marketing until a sufficiently large cohort of eligible patients (>30 000) has been identified. The NHSBSA makes available a limited set of data under an agreed protocol to the DSRU. The protocol complies with the requirements of the Data Protection Act (registration No. B0077065). The NHSBSA data is sent to the DSRU in confidence to be downloaded onto the PEM database. Demographic and outcome data (event reports) for each patient are obtained by sending simple questionnaires (Green Forms) to the prescribing GP at least six months after the date of the first prescription for each eligible individual patient, until a cohort size of at least 10 000 patients (for whom a Green Form is returned) is achieved. This interim period before the Green Form is sent allows for the newly licensed drug to penetrate the market; prescribing patterns to establish; and collection of NHS prescription data, longitudinal follow-up and sufficient time to achieve anticipated cohort sizes. PEM studies aim to recruit at least 10 000 patients, since this allows one to be 95% certain that any events not observed occur less often than 1 in 3333 cases.26
A guiding process to culturally adapt assessments for participation-focused pediatric practice: the case of the Participation and Environment Measures (PEM)
Published in Disability and Rehabilitation, 2022
Vanessa Tomas, Roopa Srinivasan, Vrushali Kulkarni, Rachel Teplicky, Dana Anaby, Mary Khetani
Additionally, through cognitive interviews with the end user of the measure, early insights about the adapted measure can be addressed, such as the measure’s feasibility and utility. For example, in the aforementioned India case study, caregivers also mentioned that the adapted tool was easy to understand and recommended that it would be both useful and suitable for clinical practice in the Indian context. While Singaporean service providers expressed concerns related to the accessibility and length of the measure, caregivers did not express these concerns and, thus, no modifications to measure length were made. By interviewing the Singaporean caregivers, a decision was made to not expend the effort to shorten the measure without necessity. An additional point is that although Indian caregivers stated that the adapted tool was easy to understand, the measure was administered through assistance with research assistants. In low- and middle-income countries like India, self-administered tools pose challenges because of low levels of literacy. As such, the PEM-CY may require provider and self-administered options in such contexts for widespread use.
Difference in home participation patterns and environmental factors between Korean children with and without disabilities
Published in Disability and Rehabilitation, 2022
The original version of the PEM-CY is a parent-reported survey measure, which examines the participation patterns of children aged 5 to 17 years and the influence of environmental factors on their participation in three settings (i.e., home, school, and community) [12]. The PEM-CY consists of two different sections (i.e., participation and environment). Its participation section is composed of activities typically performed by children in specific settings and is scored by three measurement dimensions: (1) frequency (8-point scale ranging from “never” = 0 to “daily” = 7), (2) level of involvement (5-point scale ranging from “minimally involved” = 1 to “very involved” = 5), and (3) desire for change (“no or yes”; if “yes”, select one of the response options based on the type of change desired). The environment section consists of environmental features (e.g., functional demands of activities, equipment, and information), which are grouped into two categories: (1) environmental supports or barriers (4-point scale ranging from “not an issue” to “usually makes harder”) and (2) perceived adequacy of resources (4-point scale ranging from “not needed” to “usually no”). PEM-CY provides examples of each item in the participation and environment section to help parents better understand the concept of participation and environmental factors.
Systematic review and meta-analysis of the predictive power of MTHFR polymorphisms for pemetrexed drug efficacy and toxicity in non-small cell lung cancer patients
Published in Journal of Chemotherapy, 2022
The primary mechanism of action of PEM is inhibition of TS, which is a 5,10-MTHF-dependent enzyme that catalyzes the reductive methylation of deoxyuridylate (dUMP) to deoxythymidylate (dTMP) [44]. MTHFR is an essential enzyme in folic acid metabolism that converts 5,10-MTHF to 5-MTHF. MTHFR polymorphisms, especially MTHFR 677 C > T, reduce enzyme activity, which can elevate 5,10-MTHF levels and influence therapeutic efficacy [44,45]. While the specific interconnected mechanisms underlying PEM and MTHFR are unknown, we hypothesize that a mutation in the MTHFR gene increases the level of 5,10-MTHF that competes with PEM for thymidylate synthase (TS) enzyme, leading to a decrease in TS inhibition [13,46]. Indeed, a meta-analysis showed that patients with higher TS expression had a worse response to PEM [47]. Therefore, MTHFR variants decrease the efficiency of the MTHFR enzyme, resulting in a decrease in TS inhibition that might be responsible for the reduction in the PEM efficacy observed in patients with MTHFR gene mutations.