4 research outputs found
Hepatotoxicity during 6-thioguanine treatment in inflammatory bowel disease and childhood acute lymphoblastic leukaemia:A systematic review
<div><p>Background</p><p>The recently established association between higher levels of DNA-incorporated thioguanine nucleotides and lower relapse risk in childhood acute lymphoblastic leukaemia (ALL) calls for reassessment of prolonged 6-thioguanine (6TG) treatment, while avoiding the risk of hepatotoxicity.</p><p>Objectives</p><p>To assess the incidence of hepatotoxicity in patients treated with 6TG, and to explore if a safe dose of continuous 6TG can be established.</p><p>Data sources</p><p>Databases, conference proceedings, and reference lists of included studies were systematically searched for 6TG and synonyms from 1998â2018.</p><p>Methods</p><p>We included studies of patients with ALL or inflammatory bowel disorder (IBD) treated with 6TG, excluding studies with 6TG as part of an intensive chemotherapy regimen. We uploaded a protocol to PROSPERO (registration number CRD42018089424). Database and manual searches yielded 1823 unique records. Of these, 395 full-texts were screened for eligibility. Finally, 134 reports representing 42 studies were included.</p><p>Results and conclusions</p><p>We included data from 42 studies of ALL and IBD patients; four randomised controlled trials (RCTs) including 3,993 patients, 20 observational studies including 796 patients, and 18 case reports including 60 patients. Hepatotoxicity in the form of sinusoidal obstruction syndrome (SOS) occurred in 9â25% of the ALL patients in two of the four included RCTs using 6TG doses of 40â60 mg/m<sup>2</sup>/day, and long-term hepatotoxicity in the form of nodular regenerative hyperplasia (NRH) was reported in 2.5%. In IBD patients treated with 6TG doses of approximately 23 mg/m<sup>2</sup>/day, NRH occurred in 14% of patients. At a 6TG dose of approximately 12 mg/m<sup>2</sup>/day, NRH was reported in 6% of IBD patients, which is similar to the background incidence. According to this review, doses at or below 12 mg/m<sup>2</sup>/day are rarely associated with notable hepatotoxicity and can probably be considered safe.</p></div
Outcome of osteoporosis evaluation, treatment, and follow-up in patients referred to a specialized outpatient clinic compared to patients in care of general practitioners
Vulnerable newborn types: analysis of subnational, populationâbased birth cohorts for 541 285 live births in 23 countries, 2000â2021
Objective: To examine prevalence of novel newborn types among 541â285 live births in 23 countries from 2000 to 2021. Design: Descriptive multi-country secondary data analysis. Setting: Subnational, population-based birth cohort studies (nâ=â45) in 23 low- and middle-income countries (LMICs) spanning 2000â2021. Population: Liveborn infants. Methods: Subnational, population-based studies with high-quality birth outcome data from LMICs were invited to join the Vulnerable Newborn Measurement Collaboration. We defined distinct newborn types using gestational age (preterm [PT], term [T]), birthweight for gestational age using INTERGROWTH-21st standards (small for gestational age [SGA], appropriate for gestational age [AGA] or large for gestational age [LGA]), and birthweight (low birthweight, LBW [<2500âg], nonLBW) as ten types (using all three outcomes), six types (by excluding the birthweight categorisation), and four types (by collapsing the AGA and LGA categories). We defined small types as those with at least one classification of LBW, PT or SGA. We presented study characteristics, participant characteristics, data missingness, and prevalence of newborn types by region and study. Results: Among 541â285 live births, 476â939 (88.1%) had non-missing and plausible values for gestational age, birthweight and sex required to construct the newborn types. The median prevalences of ten types across studies were T+AGA+nonLBW (58.0%), T+LGA+nonLBW (3.3%), T+AGA+LBW (0.5%), T+SGA+nonLBW (14.2%), T+SGA+LBW (7.1%), PT+LGA+nonLBW (1.6%), PT+LGA+LBW (0.2%), PT+AGA+nonLBW (3.7%), PT+AGA+LBW (3.6%) and PT+SGA+LBW (1.0%). The median prevalence of small types (six types, 37.6%) varied across studies and within regions and was higher in Southern Asia (52.4%) than in Sub-Saharan Africa (34.9%). Conclusions: Further investigation is needed to describe the mortality risks associated with newborn types and understand the implications of this framework for local targeting of interventions to prevent adverse pregnancy outcomes in LMICs
Vulnerable newborn types: analysis of subnational, populationâbased birth cohorts for 541 285 live births in 23 countries, 2000â2021
Setting: Subnational, population-based
birth cohort studies (n = 45) in 23 low-and
middle-income
countries (LMICs) spanning 2000â2021.
Population: Liveborn infants.
Methods: Subnational, population-based
studies with high-quality
birth outcome
data from LMICs were invited to join the Vulnerable Newborn Measurement
Collaboration. We defined distinct newborn types using gestational age (preterm
[PT], term [T]), birthweight for gestational age using INTERGROWTH-21st
standards
(small for gestational age [SGA], appropriate for gestational age [AGA] or large
for gestational age [LGA]), and birthweight (low birthweight, LBW [<2500 g], non-
LBW) as ten types (using all three outcomes), six types (by excluding the birthweight
categorisation), and four types (by collapsing the AGA and LGA categories). We defined
small types as those with at least one classification of LBW, PT or SGA. We
presented study characteristics, participant characteristics, data missingness, and
prevalence of newborn types by region and study.
Results: Among 541 285 live births, 476 939 (88.1%) had non-missing
and plausible
values for gestational age, birthweight and sex required to construct the newborn
types. The median prevalences of ten types across studies were T+AGA+nonLBW
(58.0%), T+LGA+nonLBW (3.3%), T+AGA+LBW (0.5%), T+SGA+nonLBW
(14.2%), T+SGA+LBW (7.1%), PT+LGA+nonLBW (1.6%), PT+LGA+LBW (0.2%),
PT+AGA+nonLBW (3.7%), PT+AGA+LBW (3.6%) and PT+SGA+LBW (1.0%). The
median prevalence of small types (six types, 37.6%) varied across studies and within
regions and was higher in Southern Asia (52.4%) than in Sub-Saharan
Africa (34.9%).
Conclusions: Further investigation is needed to describe the mortality risks associated
with newborn types and understand the implications of this framework for local
targeting of interventions to prevent adverse pregnancy outcomes in LMICs