Fenella Kirkham - Academia.edu (original) (raw)

Papers by Fenella Kirkham

Children (Basel), Sep 21, 2023

Trials, 2021

Background Young children with sickle cell anaemia (SCA) often have slowed processing speed assoc... more Background Young children with sickle cell anaemia (SCA) often have slowed processing speed associated with reduced brain white matter integrity, low oxygen saturation, and sleep-disordered breathing (SDB), related in part to enlarged adenoids and tonsils. Common treatments for SDB include adenotonsillectomy and nocturnal continuous positive airway pressure (CPAP), but adenotonsillectomy is an invasive surgical procedure, and CPAP is rarely well-tolerated. Further, there is no current consensus on the ability of these treatments to improve cognitive function. Several double-blind, randomised controlled trials (RCTs) have demonstrated the efficacy of montelukast, a safe, well-tolerated anti-inflammatory agent, as a treatment for airway obstruction and reducing adenoid size for children who do not have SCA. However, we do not yet know whether montelukast reduces adenoid size and improves cognition function in young children with SCA. Methods The Study of Montelukast In Children with S...

Children

Sickle cell disease (SCD) is the most common inherited single-gene disease. Complications include... more Sickle cell disease (SCD) is the most common inherited single-gene disease. Complications include chronic anaemia, reduced oxygen-carrying capability, and cerebral vasculopathy, resulting in silent cerebral infarction, stroke, and cognitive dysfunction with impairments in measures of executive function, attention, reasoning, language, memory, and IQ. This systematic review aims to investigate the association between neuroimaging findings and cognition in children with SCD. Searches of PubMed and Embase were conducted in March 2022. Studies were included if participants were <18 years, if original data were published in English between 1960 and 2022, if any genotype of SCD was included, and if the relationship between cognition and neuroimaging was examined. Exclusion criteria included case studies, editorials, and reviews. Quality was assessed using the Critical Appraisal Skills Programme Case Control Checklist. A total of 303 articles were retrieved; 33 met the eligibility crite...

Drugs of Today, 2020

L-Glutamine is a conditionally essential amino acid required for synthesis of the pyridines for n... more L-Glutamine is a conditionally essential amino acid required for synthesis of the pyridines for nucleotides, including nicotinamide adenine dinucleotide (NAD) and glutathione, as well as glutamate, and becomes essential during oxidative stress exposure. The NADH:[NAD⁺ + NADH] (redox) ratio in sickle red blood cells (RBCs) is lower than in normal RBCs, consistent with oxidative stress, therefore glutamine availability is important in sickle cell disease (SCD). RBC glutamine levels vary between SCD studies but the ratio glutamine:glutamate was inversely related to tricuspid regurgitant jet velocity in one. Oral L-glutamine was associated with an increase in NADH and reduction in RBC endothelium adhesion in small studies of SCD patients. In a sickle mouse model, glutamine levels were directly related to cerebral blood flow. Phase II and III randomized, double-blind, controlled trials of L-glutamine 0.6 g/kg/day compared with placebo in children and adults with SCD and = 2 episodes of pain in the previous year provide evidence that L-glutamine is safe and associated with a reduction in painful episodes and in hospitalizations. However, L-glutamine was only tolerated in two-thirds of patients, anemia and hemolysis did not improve and there are few data on mortality and organ complications. Future studies should investigate the effect of other amino acids and total protein intake.

NMR in Biomedicine, Mar 30, 2018

The Journal of Thoracic and Cardiovascular Surgery, Oct 1, 1997

British Journal of Haematology, Jul 27, 2013

Sickle cell anaemia (SCA) is associated with silent cerebral infarction (SCI), affecting white an... more Sickle cell anaemia (SCA) is associated with silent cerebral infarction (SCI), affecting white and cortical grey matter, but there are few data on subcortical volumes. We analysed retrospective magnetic resonance imaging (MRI) data in 26 SCA patients and 20 controls, comparing mean subcortical volumes between three groups: controls, SCA with SCI (n = 13) and SCA without visible abnormality (n = 13). Specific volumetric differences were found in the hippocampus, amygdala, pallidum, caudate, putamen, thalamus, and cerebellum. This is the first study to demonstrate subcortical volume change in SCA, with the most severe volumetric deficits occurring in children with SCI seen on MRI.

Journal of Child Neurology, May 1, 2000

Two magnetic resonance imaging techniques, diffusion and perfusion imaging, are being used increa... more Two magnetic resonance imaging techniques, diffusion and perfusion imaging, are being used increasingly for evaluation of pathophysiology of stroke. This article introduces these techniques and reports some initial studies using these approaches, together with conventional T2-weighted magnetic resonance imaging, for investigation of childhood stroke. It is shown that the combination of T2-weighted and diffusion images can provide information about the timing of stroke events in childhood, and perfusion imaging can detect abnormalities not visible by other magnetic resonance imaging techniques. These magnetic resonance methods therefore should play an important role in investigation of children with stroke and could be of particular value in studies of at-risk populations of children such as those with sickle cell disease. (J Child Neurol 2000;15:279-283).

Archives of Disease in Childhood, Oct 1, 1999

Acta Neurologica Scandinavica, Mar 1, 1994

The Lancet Haematology, 2022

JMIR Mental Health, 2021

Background Behavioral mitigation strategies to slow the spread of COVID-19 have resulted in sweep... more Background Behavioral mitigation strategies to slow the spread of COVID-19 have resulted in sweeping lifestyle changes, with short- and long-term psychological, well-being, and quality of life implications. The Attitudes About COVID-19 and Health (ATTACH) study focuses on understanding attitudes and beliefs while considering the impact on mental and physical health and the influence of broader demographic and geographic factors on attitudes, beliefs, and mental health burden. Objective In this assessment of our first wave of data collection, we provide baseline cohort description of the ATTACH study participants in the United Kingdom, the United States, and Mexico. Additionally, we assess responses to daily poll questions related to COVID-19 and conduct a cross-sectional analysis of baseline assessments collected in the UK between June 26 and October 31, 2020. Methods The ATTACH study uses smartphone app technology and online survey data collection. Participants completed poll quest...

American Journal of Hematology, 2020

REFERENCES 1. Swerdlow SH, Campo E, Pileri SA, et al. The 2016 revision of the World Health Organ... more REFERENCES 1. Swerdlow SH, Campo E, Pileri SA, et al. The 2016 revision of the World Health Organization classification of lymphoid neoplasms. Blood. 2016;127:2375-2390. 2. Fielding AK, Richards SM, Chopra R, et al. Outcome of 609 adults after relapse of acute lymphoblastic leukemia (ALL); an MRC UKALL12/ECOG 2993 study. Blood. 2007;109:944-950. 3. Jain N, Stevenson KE, Winer ES, et al. A Multicenter Phase I Study Combining Venetoclax with Mini-Hyper-CVD in Older Adults with Untreated and Relapsed/Refractory Acute Lymphoblastic Leukemia. Blood. 2019;134:3867-3867. 4. Lacayo NJ, Pullarkat VA, Stock W, et al. Safety and Efficacy of Venetoclax in Combination with Navitoclax in Adult and Pediatric Relapsed/Refractory Acute Lymphoblastic Leukemia and Lymphoblastic Lymphoma. Blood. 2019;134:285. 5. Bride KL, Vincent TL, Im SY, et al. Preclinical efficacy of daratumumab in T-cell acute lymphoblastic leukemia. Blood. 2018;131:995-999. 6. Wang SL X, Gao L, Yuan Z, Wu K, Liu L, Luo L, et al. Clinical safety and efficacy study of TruUCARTM GC027: The first-in-human, universal CAR-T therapy for adult relapsed/refractory T-cell acute lymphoblastic leukemia (r/r T-ALL). American Association for Cancer Research (AACR), Virtual Annual Meeting I 2020. SUPPORTING INFORMATION Additional supporting information may be found online in the Supporting Information section at the end of this article.

Blood Advances, 2020

Background:Red cell transfusions remain a mainstay of therapy for patients with sickle cell disea... more Background:Red cell transfusions remain a mainstay of therapy for patients with sickle cell disease (SCD), but pose significant clinical challenges. Guidance for specific indications and administration of transfusion, as well as screening, prevention, and management of alloimmunization, delayed hemolytic transfusion reactions (DHTRs), and iron overload may improve outcomes.Objective:Our objective was to develop evidence-based guidelines to support patients, clinicians, and other healthcare professionals in their decisions about transfusion support for SCD and the management of transfusion-related complications.Methods:The American Society of Hematology formed a multidisciplinary panel that was balanced to minimize bias from conflicts of interest and that included a patient representative. The panel prioritized clinical questions and outcomes. The Mayo Clinic Evidence-Based Practice Research Program supported the guideline development process. The Grading of Recommendations Assessmen...

Blood Advances, 2019

To address the global burden of sickle cell disease and the need for novel therapies, the America... more To address the global burden of sickle cell disease and the need for novel therapies, the American Society of Hematology partnered with the US Food and Drug Administration to engage the work of 7 panels of clinicians, investigators, and patients to develop consensus recommendations for clinical trial end points. The panels conducted their work through literature reviews, assessment of available evidence, and expert judgment focusing on end points related to patient-reported outcome, pain (non–patient-reported outcomes), the brain, end-organ considerations, biomarkers, measurement of cure, and low-resource settings. This article presents the findings and recommendations of the end-organ considerations, measurement of cure, and low-resource settings panels as well as relevant findings and recommendations from the biomarkers panel.