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Biomedical subjects

Richard Adams

Publications and source records attributed to Richard Adams.

9 recordsLinked to original sources
PubMed2026

UGT1A1 genotype testing for irinotecan: A guideline developed by the UK Centre of Excellence in Regulatory Science and Innovation in Pharmacogenomics (CERSI-PGx).

Irinotecan, a topoisomerase I inhibitor, is available as both non-pegylated and pegylated formulations. The non-pegylated formulation is licensed for use in advanced colorectal cancer either in combination with other agents or as monotherapy. However, it is also used off-label across a range of gastrointestinal malignancies and in rare malignancies such as glioblastoma and sarcomas. The pegylated formulation is licensed for use as combination therapy in adult patients with metastatic pancreatic adenocarcinoma. Irinotecan is hydrolysed to its active metabolite, SN-38, which is predominantly inactivated by the enzyme uridine diphosphate glucuronosyltransferase UGT1A1. UGT1A1 is encoded by the gene UGT1A1, which is polymorphically expressed, with allele frequencies varying across populations. Poor metabolizers carry two variants that reduce UGT1A1 enzyme expression or activity, leading to increased risk of irinotecan toxicity. Any patient who is about to be prescribed irinotecan for an epithelial malignancy should have pharmacogenetic testing, to identify clinically relevant UGT1A1 variants, where testing is available. Irinotecan dose should be reduced by 30% at Cycle 1 treatment in poor metabolizers for all indications, with doses titrated thereafter based on tolerability and neutrophil counts. The lack of evidence precludes us from making any recommendation for rare malignancies such as sarcomas. Our guideline is consistent with other international pharmacogenetics prescribing guidelines. This guideline is grounded in the latest evidence but cannot account for all individual factors relevant to patient care. Therefore, prescribers must conduct a thorough assessment of each patient's risk-benefit profile, ensuring that therapy is optimized to maximize benefits while minimizing potential harms.

Humans↗
PubMed2005

Performance on the NEPSY among children with spina bifida.

Usefulness of the NEPSY: A Developmental Neuropsychological Assessment (NEPSY) to assess attention/executive function skills was examined in a sample of 30 children with spina bifida and shunted hydrocephalus (SBSH; 20 females/10 males; age range: 6-12 years). Statistically significant moderate-to-strong correlations between the NEPSY and other measures of executive functioning were obtained. The strength of these associations decreased when controlling for intelligence as measured by the WISC-III. The Attention and Executive Function domain appeared more closely associated with tests requiring focused attention and an ability to shift set than those emphasizing more abstract reasoning, memory, or non-verbal problem-solving skills. The NEPSY appears useful in the assessment of specific executive function abilities in young individuals with SBSH. More research into the NEPSY and particularly its Attention and Executive Function domain is needed among individuals with SBSH before its use as a stand-alone tool apart from adjunctive cognitive assessment instruments.

Attention↗
PubMed2005

Tobacco use in adolescence: longitudinal links to later problem behavior among African American and Puerto Rican urban young adults.

In this study, the authors assessed the relationship between adolescent tobacco smoking and measures of inner control, deviant behavior, and associating with deviant peers, which are indicators of problem behavior. African American (N = 333) and Puerto Rican (N = 329) early adolescents completed questionnaires in their classrooms in 1990 at Time 1 (T1) and were individually interviewed thereafter when they were late adolescents in 1995 at Time 2 (T2) and as young adults in 2000 at Time 3 (T3). The authors used ordinary least squares regression analysis to assess the comparative association of adolescent smoking patterns at T1 and T2 and the young adult outcomes at T3; they controlled for demographic variables, level of the outcome measure at T2, and marijuana use at T2. The analyses suggested that experimental tobacco smokers demonstrated more problem behaviors than did nonsmokers, and late and continuous smokers demonstrated more problem behaviors as young adults than did experimental smokers and nonusers. These findings may provide a useful guide to a next step that involves translational research.

Adolescent↗
PubMed2004

Myelomeningocele, temperament patterns, and parental perceptions.

OBJECTIVE: Description of temperament profiles of children has largely been reported in typically developing populations. Children undergo individualized assessments of achievement (developmental/academic) and receive individualized interventions. In contrast, their individual behavioral styles are not evaluated as completely, if at all. For children with developmental disabilities, description of temperament characteristics can provide better understanding of the already complex child. This study describes temperament characteristics in a group of children with myelomeningocele and shunted hydrocephalus (MM/SH). METHODS: A consecutive cohort study with historical control group measuring temperament characteristics was conducted at a tertiary-level, university affiliated, interdisciplinary spina bifida program. Analysis includes group comparisons. Primary caregivers of 46 children (age range: 5-12 years) with MM/SH completed age-appropriate Carey Temperament Scales questionnaires as a component of a larger developmental study. The Carey Temperament Scales comprise a series of behavioral rating instruments that assess 9 temperament characteristics: activity, adaptability, approach-withdrawal, mood, intensity, attention/persistence, distractibility, sensory threshold, and rhythmicity/predictability. The Carey questionnaires used in this study were (1) the Behavioral Style Questionnaire for children aged 5 to 7 years and (2) the Middle Childhood Temperament Questionnaire for those aged 8 to 12 years. Both questionnaires assess the same temperament characteristics; the contexts within which items were rated were designed to better reflect developmental levels. Children were excluded when there were comorbid diagnoses of attention-deficit/hyperactivity disorder or mental retardation. RESULTS: One-sample normal tests (Bonferroni corrected) revealed that children within the MM/SH group differed significantly from the standardized population in 5 dimensions: (1) adaptability (less adaptable), (2) approach/withdrawal (poor first approach/greater withdrawal), (3) distractibility (more distractible), (4) attention/persistence (less attentive/persistent), and (5) predictability/rhythm (less predictable). Caregiver perceptions of having a difficult-to-manage child were significantly correlated with negative mood, more intensity of response, and less adaptability. CONCLUSIONS: Temperament profiles previously described in typically developing populations (eg, "easy" or "difficult child") were not prominent profiles in this group of children with MM/SH. A constellation of temperament characteristics not commonly recognized may place these children at risk for being contributors to and recipients of misunderstandings of social cues and have implications for successful learning within academic, home/community, and medical settings.

Case-Control Studies↗
PubMed2004

Initial urologic management of myelomeningocele.

Disordered innervation of the detrusor musculature and external sphincter in patients with myelomeningocele adversely affects bladder function and potentially threatens the upper urinary tracts. Children with this condition can be categorized into high and low- risk groups for secondary damage from a neurogenic bladder based on intravesical pressure. Those with elevated pressure are at risk for hydronephrosis or reflux,and evidence suggests that early management of high pressure protects the bladder from additional damage, reducing the need for augmentation. Management decisions made during infancy potentially impact long-term outcomes for preserving renal function and achieving urinary continence. This discussion focuses on the initial urologic care of infants with myelomeningocele, emphasizing the controversy regarding urodynamic versus radiologic-based management of the neurogenic bladder.

Humans↗
PubMed2003

Bone mineral density in children with myelomeningocele: effect of hydrochlorothiazide.

Children with myelomeningocele experience difficulty with ambulation, which leads to immobilization and secondary loss of bone mineral density (BMD). In addition, non-ambulatory myelomeningocele patients have higher urinary calcium losses than their ambulatory counterparts. Hydrochlorothiazide (HCTZ) is known to reduce urinary calcium loss and increase BMD in non-myelomeningocele patients with hypercalciuria. This study examines the effect of HCTZ on urinary calcium and BMD in non-ambulatory children with myelomeningocele. Thirteen of 20 non-ambulatory patients with myelomeningocele completed the year-long randomized double-blinded study (placebo = 7 and HCTZ = 6). Evaluation included electrolytes, PTH, osteocalcin, 1, 25-OH vitamin D, urinary pyridinolines/deoxypyridinolines (U(pyr/dpyr)), urinary calcium/creatinine (U(Ca/Cr)), and forearm BMD (dual X-ray absorptiometry). Follow-up electrolytes were obtained at 1-2, 6, and 12 months and U(Ca/Cr) and BMD was obtained again at 12 months. There were no initial differences between the placebo and HCTZ groups. U(Ca/Cr) decreased in the HCTZ group after treatment (0.20+/-0.09 vs. 0.04+/-0.02, p<0.05). However, forearm BMD ( z-scores) after 1 year remained unchanged in both the HCTZ (-5.95+/-0.98 to -5.86+/-0.92) and placebo (-7.19+/-0.69 to -6.67+/-0.63) groups. While use of HCTZ for 1 year did not affect BMD, it reduced urinary calcium excretion in non-ambulatory children with myelomeningocele.

Adolescent↗
PubMed2003

Language differences in young children with myelomeningocele and shunted hydrocephalus.

OBJECTIVE: This comparative cohort study examined language differences in young children (preschool to first grade) with myelomeningocele and shunted hydrocephalus (MM/SH). METHOD: A well-validated, standardized language test was administered to 17 children with MM/SH (age range 4-6 years) and 16 age-matched, nonaffected children. RESULTS: Standard scores were obtained within lexical/semantic, syntactic, and pragmatic domains. An analysis of performance on individual subtests within the lexical/semantic domain was striking. Children with MM/SH performed significantly worse (p<0.01) on a test measuring the comprehension of words representing important early learning concepts and on pragmatic tasks that measured their ability to use language functionally in social situations. CONCLUSIONS: Words representing basic precepts and concepts are commonly used in instructions to children in early childhood. Difficulty with functional pragmatic language results in suboptimal communication skills. Academic and community implications are discussed.

Age Factors↗