Publications by authors named "Phoebe Williams"

57 Publications

IV and oral fosfomycin pharmacokinetics in neonates with suspected clinical sepsis.

J Antimicrob Chemother 2021 06;76(7):1855-1864

Infection, Immunity and Inflammation, Great Ormond Street Institute of Child Health, University College London, London, UK.

Background: Fosfomycin has the potential to be re-purposed as part of a combination therapy to treat neonatal sepsis where resistance to current standard of care (SOC) is common. Limited data exist on neonatal fosfomycin pharmacokinetics and estimates of bioavailability and CSF/plasma ratio in this vulnerable population are lacking.

Objectives: To generate data informing the appropriate dosing of IV and oral fosfomycin in neonates using a population pharmacokinetic analysis of plasma and CSF data.

Methods: The NeoFosfo study (NCT03453177) was a randomized trial that examined the safety and pharmacokinetics of fosfomycin comparing SOC versus SOC plus fosfomycin. Sixty-one neonates received fosfomycin (100 mg/kg IV q12h for 48 h) and then they converted to oral therapy at the same dose. Two plasma pharmacokinetic samples were taken following the first IV and oral doses, sample times were randomized to cover the whole pharmacokinetic profile and opportunistic CSF pharmacokinetic samples were collected. A population pharmacokinetic model was developed in NONMEM and simulations were performed.

Results: In total, 238 plasma and 15 CSF concentrations were collected. A two-compartment disposition model, with an additional CSF compartment and first-order absorption, best described the data. Bioavailability was estimated as 0.48 (95% CI = 0.347-0.775) and the CSF/plasma ratio as 0.32 (95% CI = 0.272-0.409). Allometric weight and postmenstrual age (PMA) scaling was applied; additional covariates included postnatal age (PNA) on clearance and CSF protein on CSF/plasma ratio.

Conclusions: Through this analysis a population pharmacokinetic model has been developed that can be used alongside currently available pharmacodynamic targets to select a neonatal fosfomycin dose based on an infant's PMA, PNA and weight.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/jac/dkab083DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8212774PMC
June 2021

Harmonising regulatory approval for antibiotics in children.

Lancet Child Adolesc Health 2021 02;5(2):96-98

Paediatric Infectious Diseases Research Group, Institute of Infection and Immunity, St George's University London, London, UK.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/S2352-4642(20)30365-5DOI Listing
February 2021

State of the Mind: Growing up with HIV.

Paediatr Drugs 2020 Oct;22(5):511-524

HIV-NAT, Thai Red Cross AIDS Research Centre, Bangkok, Thailand.

Human immunodeficiency virus (HIV) is a neurotropic virus that has a detrimental impact on the developing central nervous system (CNS) of children growing up with perinatal HIV (PHIV) due to a combination of pathophysiological processes related to direct viral cytopathic effects and immune activation. This leads to a spectrum of neurocognitive impairment ranging from severe encephalopathy to subtle domain-specific cognitive impairments, as well as psychological disorders that are compounded by HIV-related stigma and sociodemographic factors that disproportionately affect PHIV children. Early commencement and consistent use of combination antiretroviral therapy (cART) has resulted in a dramatic improvement in neuropsychological outcomes for PHIV children; however, they remain vulnerable to cognitive impairment and psychological disorders, as evidenced by imaging findings, randomised clinical trials and observational studies. An optimal neuroprotective cART regimen remains elusive in children, but systemic viral suppression, regular neurocognitive and psychological screening and ready access to neuropsychological management strategies are key components for optimising neuropsychological outcomes. However, a lack of standardised and validated screening tools, particularly in resource-limited settings, hinders a precise understanding of the nature, prevalence and associations between neuropsychological symptomatology and HIV health. This article reviews the natural history, cellular pathophysiology and structural and functional imaging findings for children growing up with HIV, as well as summarising management strategies related to antiretroviral therapy, screening tools and specific interventions for neurocognitive impairments and psychological disorders.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s40272-020-00415-1DOI Listing
October 2020

SARS-CoV-2 in children: spectrum of disease, transmission and immunopathological underpinnings.

Pathology 2020 Dec 19;52(7):801-808. Epub 2020 Aug 19.

Department of Immunology and Infectious Diseases, Sydney Children's Hospital, Randwick, NSW, Australia; School of Women's and Children's Health, UNSW Sydney, NSW, Australia. Electronic address:

As the SARS-CoV-2 pandemic unfolds across the globe, consistent themes are emerging with regard to aspects of SARS-CoV-2 infection and its associated disease entities in children. Overall, children appear to be less frequently infected by, and affected by, SARS-CoV-2 virus and the clinical disease COVID-19. Large epidemiological studies have revealed children represent less than 2% of the total confirmed COVID-19 cases, of whom the majority experience minimal or mild disease that do not require hospitalisation. Children do not appear to be major drivers of SARS-CoV-2 transmission, with minimal secondary virus transmission demonstrated within families, schools and community settings. There are several postulated theories regarding the relatively low SARS-CoV-2 morbidity and mortality seen in children, which largely relate to differences in immune responses compared to adults, as well as differences in angiotensin converting enzyme 2 distribution that potentially limits viral entry and subsequent inflammation, hypoxia and tissue injury. The recent emergence of a multisystem inflammatory syndrome bearing temporal and serological plausibility for an immune-mediated SARS-CoV-2-related disease entity is currently under investigation. This article summarises the current available data regarding SARS-CoV-2 and the paediatric population, including the spectrum of disease in children, the role of children in virus transmission, and host-virus factors that underpin the unique aspects of SARS-CoV-2 pathogenicity in children.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.pathol.2020.08.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7437539PMC
December 2020

Successful treatment of invasive carbapenemase-producing Enterobacteriaceae infections in children using carbapenem-aminoglycoside combination therapy: A case series.

Infect Dis Health 2020 11 19;25(4):314-318. Epub 2020 Jul 19.

Department of Immunology and Infectious Diseases, The Sydney Children's Hospital Network, Randwick Australia; School of Women and Children's Health, The University of NSW, Sydney Australia.

Multidrug-resistant infections present a treatment challenge for pediatric clinicians and these infections have been associated with increased morbidity and mortality. There are very limited published data to support safe and effective treatment regimens for carbapenemase-producing Enterobacteriaceae (CPE) infections, particularly in children. We report the successful treatment of three children with invasive CPE infections using a combination of extended-infusion meropenem and amikacin.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.idh.2020.06.002DOI Listing
November 2020

Potential of fosfomycin in treating multidrug-resistant infections in children.

J Paediatr Child Health 2020 Jun 15;56(6):864-872. Epub 2020 Apr 15.

Department of Infectious Diseases and Immunology, Sydney Children's Hospital, Sydney, New South Wales, Australia.

In an era of increasing antimicrobial resistance, there are limited treatment options available to treat multidrug-resistant organisms in paediatric patients. Fosfomycin is an antibiotic defined as 'critically important' by The World Health Organization due to its potential efficacy against multidrug-resistant bacteria and is increasingly cited in the international literature as a promising antimicrobial for combating sepsis in an era of increasing antimicrobial resistance. With broad-spectrum cover that includes both Gram-positive and Gram-negative organisms and both parenteral and oral formulations available, fosfomycin provides a promising treatment option for paediatric patients. This review summarises fosfomycin's spectrum of activity, published efficacy in paediatric patients, safety considerations and pharmacokinetic data, as well as identifying current clinical trials delineating pharmacokinetic parameters and safety parameters in neonatal sepsis which will provide further information regarding the use of fosfomycin in neonatal and paediatric infections. Limitations regarding the current standards for fosfomycin susceptibility definitions, variations in dosing regimens and the potential mechanisms for resistance are also discussed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/jpc.14883DOI Listing
June 2020

The potential of fosfomycin for multi-drug resistant sepsis: an analysis of in vitro activity against invasive paediatric Gram-negative bacteria.

J Med Microbiol 2019 May 17;68(5):711-719. Epub 2019 Apr 17.

The University of Oxford, Nuffield Department of Clinical Medicine, Headington, Oxford, UK.

Purpose: Antimicrobial resistance (AMR) is of increasing global concern, threatening to undermine recent progress in reducing child and neonatal mortality. Repurposing older antimicrobials is a prominent strategy to combat multidrug-resistant sepsis. A potential agent is fosfomycin, however, there is scarce data regarding its in vitro activity and pharmacokinetics in the paediatric population.

Methodology: We analysed a contemporary, systematically collected archive of community-acquired (CA) and hospital-acquired (HA) paediatric Gram-negative bacteraemia isolates for their susceptibility to fosfomcyin. MICs were determined using agar serial dilution methods and validated by disk diffusion testing where breakpoints are available. Disk diffusion antimicrobial susceptibility testing was also conducted for current empirical therapies (ampicillin, gentamicin, ceftriaxone) and amikacin (proposed in the literature as a new combination empirical therapeutic option).

Results: Fosfomycin was highly active against invasive Gram-negative isolates, including 90  % (202/224) of Enterobacteriaceae and 96  % (22/23) of Pseudomonas spp. Fosfomycin showed high sensitivity against both CA isolates (94 %, 142/151) and HA isolates (81 %, 78/96; P =0.0015). CA isolates were significantly more likely to be susceptible to fosfomycin than the current first-line empirical therapy (96  % vs 59  %, P <0.0001). Extended spectrum β-lactamases (ESBL) production was detected in 34  % (85/247) of isolates with no significant difference in fosfomycin susceptibility between ESBL-positive or -negative isolates [73/85 (86  %) vs 147/162 (91  %) respectively, P =0.245]. All isolates were susceptible to a fosfomycin-amikacin combination.

Conclusion: Gram-negative paediatric bacteraemia isolates are highly susceptible to fosfomycin, which could be combined with aminoglycosides as a new, carbapenem-sparing regimen to achieve excellent coverage to treat antimicrobial-resistant neonatal and paediatric sepsis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1099/jmm.0.000973DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7116424PMC
May 2019

Grading antimicrobial susceptibility data quality: room for improvement - Authors' reply.

Lancet Infect Dis 2018 06;18(6):604-605

Kenya Medical Research Institute (KEMRI)/Wellcome Trust Research Programme, Kilifi, Kenya; The Childhood Acute Illness & Nutrition (CHAIN) Network, Kilifi, Kenya; Centre for Tropical Medicine & Global Health, Nuffield Department of Medicine, The University of Oxford, Oxford, UK.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/S1473-3099(18)30295-0DOI Listing
June 2018

Guidelines for the treatment of dysentery (shigellosis): a systematic review of the evidence.

Paediatr Int Child Health 2018 11;38(sup1):S50-S65

b Kenya Medical Research Institute (KEMRI)/Wellcome Trust Research Programme , Kilifi , Kenya.

Background: Shigella remains the primary cause of diarrhoea in paediatric patients worldwide and accounts for up to 40,000 deaths per year. Current guidelines for the treatment of shigellosis are based on data which are over a decade old. In an era of increasing antimicrobial resistance, an updated review of the appropriate empirical therapy for shigellosis in children is necessary, taking into account susceptibility patterns, cost and the risk of adverse events.

Methods: A systematic review of the current published literature on the treatment of shigella dysentery was undertaken in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA).

Results: The initial search produced 131 results, of which nine studies met the inclusion criteria. The quality of the studies was assessed as per the Grading of Recommendations Assessment, Development and Evaluation (GRADE) guidelines. International guidelines were also reviewed. There is a lack of current research regarding the clinical treatment of shigellosis in paediatric and adult patients, despite rising antimicrobial resistance worldwide. In particular, there is a lack of studies assessing the non-susceptibility of community-acquired strains, with almost all published research pertaining to microbiological data from hospital-based settings.

Discussion: Current WHO guidelines support the use of fluoroquinolones (first-line), β-lactams (second-line) and cephalosporins (second-line) which accords with currently available evidence and other international guidelines, and there is no strong evidence for changing this guidance. Azithromycin is appropriate as a second-line therapy in regions where the rate of non-susceptibility of ciprofloxacin is known to be high, and research suggests that, from a cardiac point of view, azithromycin is safer than other macrolide antibiotics. Cefixime is also a reasonable alternative, although its use must be weighed against the risk of dissemination of extended-spectrum β-lactamase-producing organisms.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/20469047.2017.1409454DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6021764PMC
November 2018

Guidelines for the management of paediatric cholera infection: a systematic review of the evidence.

Paediatr Int Child Health 2018 11;38(sup1):S16-S31

b Kenya Medical Research Institute (KEMRI)/Wellcome Trust Research Programme , Kilifi , Kenya.

Background Vibrio cholerae is a highly motile Gram-negative bacterium which is responsible for 3 million cases of diarrhoeal illness and up to 100,000 deaths per year, with an increasing burden documented over the past decade. Current WHO guidelines for the treatment of paediatric cholera infection (tetracycline 12.5 mg/kg four times daily for 3 days) are based on data which are over a decade old. In an era of increasing antimicrobial resistance, updated review of the appropriate empirical therapy for cholera infection in children (taking account of susceptibility patterns, cost and the risk of adverse events) is necessary. Methods A systematic review of the current published literature on the treatment of cholera infection in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) was undertaken. International clinical guidelines and studies pertaining to adverse effects associated with treatments available for cholera infection were also reviewed. Results The initial search produced 256 results, of which eight studies met the inclusion criteria. Quality assessment of the studies was performed as per the Grading of Recommendations Assessment, Development and Evaluation guidelines. Conclusions In view of the changing non-susceptibility rates worldwide, empirical therapy for cholera infection in paediatric patients should be changed to single-dose azithromycin (20 mg/kg), a safe and effective medication with ease of administration. Erythromycin (12.5 mg/kg four times daily for 3 days) exhibits similar bacteriological and clinical success and should be listed as a second-line therapy. Fluid resuscitation remains the cornerstone of management of paediatric cholera infection, and prevention of infection by promoting access to clean water and sanitation is paramount.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/20469047.2017.1409452DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5972638PMC
November 2018

Guidelines for the treatment of severe acute malnutrition: a systematic review of the evidence for antimicrobial therapy.

Paediatr Int Child Health 2018 11;38(sup1):S32-S49

b Kenya Medical Research Institute (KEMRI)/Wellcome Trust Research Programme , Kilifi , Kenya.

Background Severe acute malnutrition (SAM) affects nearly 20 million children worldwide and is responsible for up to 1 million deaths per year in children under the age of 5 years. Current WHO guidelines recommend oral amoxicillin for children with uncomplicated malnutrition and parenteral benzylpenicillin and gentamicin for those with complicated malnutrition. Because of cost pressures and increasing antimicrobial resistance, the administration of empirical antibiotics for children with SAM has recently been debated. Methods A systematic review of the current published literature was undertaken to assess the efficacy, safety, cost-effectiveness and pharmacokinetics of antimicrobial treatment of children with SAM in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Results The initial search found 712 papers, eight of which met the inclusion criteria. Quality assessment of the studies was performed as per the Grading of Recommendations Assessment, Development and Evaluation guidelines. International guidelines and clinical data registries were also reviewed which identified inconsistencies in current first- and second-line therapies and dosing regimens. Conclusion Current evidence supports the continued use of broad-spectrum oral amoxicillin for treating children with uncomplicated SAM as outpatients. There is no strong evidence to justify changing the current parenteral therapy guidelines for children admitted with complicated SAM, although they should be clarified to harmonise the dosage regimen of amoxicillin for the treatment of SAM to 40 mg/kg twice daily, and to continue parenteral antimicrobials beyond 2 days if indicated by the clinical condition.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/20469047.2017.1409453DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5972636PMC
November 2018

Tuberculin skin test versus interferon-gamma release assay in refugee children: A retrospective cohort study.

J Paediatr Child Health 2018 08 14;54(8):834-839. Epub 2018 Feb 14.

Department of Community Child Health, Sydney Children's Hospitals Network, Sydney, New South Wales, Australia.

Aim: The aim of this study was to assist clinicians evaluating refugee children for latent tuberculosis infection (LTBI) by comparing paired tuberculin skin test (TST) and Quantiferon Gold In-Tube (QGIT) test results with clinical management decisions and follow-up data in a large cohort of newly arrived refugee children.

Methods: This was a retrospective analysis of all refugee children (<15 years of age) evaluated for LTBI with both TST and interferon-γ release assay between 2007 and 2010 in the Illawarra-Shoalhaven region of New South Wales, Australia. Demographics, country of origin, bacille Calmette-Guerin (BCG) vaccination status, chest X-ray results, TST and QGIT test results, clinical management and outcome on long-term follow-up were assessed.

Results: Of 272 children evaluated, complete results were available for 212 (78%). The vast majority (207; 98%) were from Africa or Southeast Asia. Overall, 33 (16%) children were treated for LTBI; 13 (39%) had concordant TST and QGIT results and 20 (61%) discordant results. Of 63 (30%) TST-positive (≥10 mm) children, 46 (73%) were QGIT assay-negative, 44 (70%) had a BCG scar, 3 (5%) were younger than 2 years and 6 (10%) were treated for LTBI. Of 32 QGIT assay-positive children, 15 (47%) were TST negative, 31 (97%) had a BCG scar, all were older than 2 years and 14 (44%) were treated for LTBI.

Conclusions: Discordant TST and QGIT results were found in a high percentage of refugee children. QGIT is convenient and more specific than TST to diagnose LTBI in BCG-vaccinated children, although a careful tuberculosis exposure history and clinical assessment to rule out active disease remain important.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/jpc.13865DOI Listing
August 2018

Arabidopsis Phospholipase C3 is Involved in Lateral Root Initiation and ABA Responses in Seed Germination and Stomatal Closure.

Plant Cell Physiol 2018 Mar;59(3):469-486

Swammerdam Institute for Life Sciences, section Plant Physiology, University of Amsterdam, Science Park 904, Amsterdam, 1098 XH, The Netherlands.

Phospholipase C (PLC) is well known for its role in animal signaling, where it generates the second messengers, inositol 1,4,5-trisphosphate (IP3) and diacylglycerol (DAG), by hydrolyzing the minor phospholipid, phosphatidylinositol 4,5-bisphosphate (PIP2), upon receptor stimulation. In plants, PLC's role is still unclear, especially because the primary targets of both second messengers are lacking, i.e. the ligand-gated Ca2+ channel and protein kinase C, and because PIP2 levels are extremely low. Nonetheless, the Arabidopsis genome encodes nine PLCs. We used a reversed-genetic approach to explore PLC's function in Arabidopsis, and report here that PLC3 is required for proper root development, seed germination and stomatal opening. Two independent knock-down mutants, plc3-2 and plc3-3, were found to exhibit reduced lateral root densities by 10-20%. Mutant seeds germinated more slowly but were less sensitive to ABA to prevent germination. Guard cells of plc3 were also compromised in ABA-dependent stomatal closure. Promoter-β-glucuronidase (GUS) analyses confirmed PLC3 expression in guard cells and germinating seeds, and revealed that the majority is expressed in vascular tissue, most probably phloem companion cells, in roots, leaves and flowers. In vivo 32Pi labeling revealed that ABA stimulated the formation of PIP2 in germinating seeds and guard cell-enriched leaf peels, which was significantly reduced in plc3 mutants. Overexpression of PLC3 had no effect on root system architecture or seed germination, but increased the plant's tolerance to drought. Our results provide genetic evidence for PLC's involvement in plant development and ABA signaling, and confirm earlier observations that overexpression increases drought tolerance. Potential molecular mechanisms for the above observations are discussed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/pcp/pcx194DOI Listing
March 2018

Antimicrobial resistance among children in sub-Saharan Africa.

Lancet Infect Dis 2018 02 9;18(2):e33-e44. Epub 2017 Oct 9.

Kenya Medical Research Institute (KEMRI)/Wellcome Trust Research Programme, Kilifi, Kenya; The Childhood Acute Illness & Nutrition (CHAIN) Network, Kilifi, Kenya; Centre for Tropical Medicine & Global Health, Nuffield Department of Medicine, The University of Oxford, Oxford, UK.

Antimicrobial resistance is an important threat to international health. Therapeutic guidelines for empirical treatment of common life-threatening infections depend on available information regarding microbial aetiology and antimicrobial susceptibility, but sub-Saharan Africa lacks diagnostic capacity and antimicrobial resistance surveillance. We systematically reviewed studies of antimicrobial resistance among children in sub-Saharan Africa since 2005. 18 of 1075 articles reviewed met inclusion criteria, providing data from 67 451 invasive bacterial isolates from inconsistently defined populations in predominantly urban tertiary settings. Among neonates, Gram-negative organisms were the predominant cause of early-onset neonatal sepsis, with a high prevalence of extended-spectrum β-lactamase-producing organisms. Gram-positive bacteria were responsible for a high proportion of infections among children beyond the neon atal period, with high reported prevalence of non-susceptibility to treatment advocated by the WHO therapeutic guidelines. There are few up-to-date or representative studies given the magnitude of the problem of antimicrobial resistance, especially regarding community-acquired infections. Research should focus on differentiating resistance in community-acquired versus hospital-acquired infections, implementation of standardised reporting systems, and pragmatic clinical trials to assess the efficacy of alternative treatment regimens.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/S1473-3099(17)30467-XDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5805911PMC
February 2018

The reality of the mortality statistics of the nurses' strike in Kenya.

Lancet 2017 08;390(10094):551

Nuffield Department of Medicine, The University of Oxford, Oxford OX1 2JD, UK. Electronic address:

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/S0140-6736(17)31944-XDOI Listing
August 2017

The symptom experiences of Puerto Rican children undergoing cancer treatments and alleviation practices as reported by their mothers.

Int J Nurs Pract 2017 Feb 19;23(1). Epub 2016 Dec 19.

Pediatric Hematology and Oncology, University of Puerto Rico School of Medicine, San Juan, Puerto Rico.

Although symptoms during cancer treatments are prevalent and are important clinical outcomes of childhood cancer, the symptom experiences of Puerto Rican children along with the symptom alleviation/care practices that parents provide during cancer treatments have received limited attention. To examine the occurrence/severity of symptoms on the Therapy-Related Symptom Checklist-Children (TRSC-C), reported by mothers of Puerto Rican children undergoing cancer treatments and identifying mothers' symptom alleviation/management strategies. Descriptive study conducted between January and May 2012. Mothers of 65 Puerto Rican children/adolescents undergoing cancer treatments responded to the Spanish versions of the TRSC-C, Symptom Alleviation: Self-Care Methods, and a Demographic and Health form. The children/adolescents' mean age was 9.2 (1-17) years; 62% were boys; 56 had chemotherapy; 9 had chemoradiotherapy. Children diagnoses were 35.4% leukemia, 24.6% solid tumors, 24.6% nervous system tumors, and 15.4% other. On the TRSC-C, the symptoms experienced by 70% or more of the children were: irritability (77%), nausea (75%), and hair loss (72%). On the Symptom Alleviation: Self-Care Methods, the most commonly reported symptom alleviation category was "taking prescribed medicines." Puerto Rican mothers reported the use of alleviation practices to treat their children experiencing symptoms during pediatric cancer treatments. Patients and caregivers need to be educated about treatment-induced side effects, and the life-threatening consequences of underreporting and undermanagement. Symptoms should always be addressed at the time of initiation of primary or adjuvant cancer therapy because pretreatment symptoms may persist or get worse across the trajectory of treatment. A continuous assessment and management of symptoms during the childhood cancer trajectory can optimize clinical care and improve quality of life of patients and families.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/ijn.12500DOI Listing
February 2017

Self-reported assessment of symptoms and self-care within a cohort of U.S. veterans during outpatient care for cancer.

Clin J Oncol Nurs 2015 Oct;19(5):595-602

School of Nursing, University of Kansas, Kansas City.

Background: This study was undertaken as part of a feasibility study of the use of a symptom checklist and self-care assessment of veterans receiving oncology outpatient treatment within the U.S. Department of Veterans Affairs system.

Objectives: The study aimed to examine (a) symptom occurrence and severity as self-reported on the Therapy-Related Symptom Checklist (TRSC) by veterans at a cancer clinic, (b) symptom alleviation strategies and use of self-care, and (c) the relationship between symptom occurrence and severity and functional status and quality of life.

Methods: Veterans (N = 100) undergoing chemotherapy and/or radiation therapy participated in a cross-sectional study. Tools used, including TRSC, Symptom Alleviation.

Findings: Thirteen symptoms were reported by more than 35% of patients. Top-ranked symptoms by percentage occurrence and severity were feeling sluggish, taste changes, nausea, pain, constipation, loss of appetite, numbness of fingers and toes, difficulty sleeping, weight loss, hair loss, difficulty concentrating, shortness of breath, and decreased interest in sexual activity. Occurrence and severity of symptoms had significant negative correlations with functional status and with overall quality of life. Self-care (symptom alleviation) strategies that helped were medicines, diet and nutrition, and lifestyle change. Checklist use (TRSC) facilitated patient-report of symptoms during cancer treatments; self-care strategies helped relieve symptoms.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1188/15.CJON.595-602DOI Listing
October 2015

The development and application of an oncology Therapy-Related Symptom Checklist for Adults (TRSC) and Children (TRSC-C) and e-health applications.

Biomed Eng Online 2015 13;14 Suppl 2:S1. Epub 2015 Aug 13.

Background: Studies found that treatment symptoms of concern to oncology/hematology patients were greatly under-identified in medical records. On average, 11.0 symptoms were reported of concern to patients compared to 1.5 symptoms identified in their medical records. A solution to this problem is use of an electronic symptom checklist that can be easily accessed by patients prior to clinical consultations.

Purpose: Describe the oncology Therapy-Related Symptom Checklists for Adults (TRSC) and Children (TRSC-C), which are validated bases for e-Health symptom documentation and management. The TRSC has 25 items/symptoms; the TRSC-C has 30 items/symptoms. These items capture up to 80% of the variance of patient symptoms. Measurement properties and applications with outpatients are presented. E-Health applications are indicated.

Methods: The TRSC was developed for adults (N = 282) then modified for children (N = 385). Statistical analyses have been done using correlational, epidemiologic, and qualitative methods. Extensive validation of measurement properties has been reported.

Results: Research has found high levels of patient/clinician satisfaction, no increase in clinic costs, and strong correlations of TRSC/TRSC-C with medical outcomes. A recently published sequential cohort trial with adult outpatients at a Mayo Clinic community cancer center found TRSC use produced a 7.2% higher patient quality of life, 116% more symptoms identified/managed, and higher functional status.

Discussion, Implications, And Follow-up: An electronic system has been built to collect TRSC symptoms, reassure patients, and enhance patient-clinician communications. This report discusses system design and efforts made to provide an electronic system comfortable to patients. Methods used by clinicians to promote comfort and patient engagement were examined and incorporated into system design. These methods included (a) conversational data collection as opposed to survey style or standardized questionnaires, (b) short response phrases indicating understanding of the reported symptom, (c) use of open-ended questions to reduce long lists of symptoms, (d) directed questions that ask for confirmation of expected symptoms, (e) review of symptoms at designated stages, and (d) alerting patients when the computer has informed clinicians about patient-reported symptoms.

Conclusions: An e-Health symptom checklist (TRSC/TRSC-C) can facilitate identification, monitoring, and management of symptoms; enhance patient-clinician communications; and contribute to improved patient outcomes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/1475-925X-14-S2-S1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4547195PMC
June 2016

Symptom alleviation and self-care among breast cancer survivors after treatment completion.

Clin J Oncol Nurs 2015 Jun;19(3):343-9

School of Nursing, University of Kansas, Kansas City.

Background: This article elucidates the symptom experiences of breast cancer survivors after completion of their treatment. It also provides self reports of the types, frequency of use, and effectiveness of self-care measures to treat the symptoms they are experiencing.

Objectives: The purpose of this article is to describe the self-care strategies used to alleviate symptoms reported by breast cancer survivors recruited from a secure state coalition database.

Methods: The Therapy-Related Symptom Checklist (TRSC) was used to identify the occurrence and severity of ongoing symptoms in breast cancer survivors who were six months or more post-treatment. Two groups were identified for further exploration of self-care.

Findings: The self-care method category most commonly reported was diet/nutrition/lifestyle and the least common category was herbs/vitamins/complementary therapy. With few exceptions, the reported methods were perceived as effective.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1188/15.CJON.343-349DOI Listing
June 2015

Monitoring and Alleviation of Symptom Occurrence and Severity Among Thai Children and Adolescents During Cancer Treatments.

J Pediatr Oncol Nurs 2015 Nov-Dec;32(6):417-28. Epub 2015 Jan 23.

James A. Haley Veterans Affairs Medical Center, Tampa, FL, USA George Mason University, Washington, DC, USA.

Background: Symptom monitoring and alleviation are important during pediatric cancer treatments.

Aims: To examine the use of the Therapy-Related Symptom Checklist for Children (TRSC-C; Thai version) for reported occurrence, severity, and management of treatment-related symptoms within a cohort of Thai pediatric oncology patients/parents

Method: Cross-sectional study; convenience sample: 100 parents of 71 male children/29 females, 63% with leukemia, 37%, other diagnoses; age-groups: <5 years, n = 33; 5 to 11 years, n = 44; 12 to 17 years, n = 25. Parents reported children's symptom occurrence/severity on the TRSC-C; and complementary care methods on the Symptom Alleviation: Self-Care Methods and their symptom alleviation methods. All tools had good psychometric properties.

Results: 18 symptoms on the 30-item TRSC-C occurred in 42% to 95% of children. Mean severity of symptoms was between 1.0 ("a bit") and 2.0 ("quite a bit"); 5-month to 11-year-old children had higher (worse) TRSC-C total scores. Complementary care was used and reported.

Conclusions: Monitoring of multiple symptoms with the TRSC-C and parental symptom alleviation helped children.

Clinical Implications: Thai parents/patients need and accept assistance in monitoring/managing side effects of pediatric cancer therapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/1043454214563754DOI Listing
September 2016

Treatment-related symptom severity and occurrences among oncology adults in Australia.

Asia Pac J Oncol Nurs 2015 Jul-Sep;2(3):144-151

Research Centre for Nursing and Midwifery Practice, Canberra, Australia.

Objective: Cancer treatments cause a range of distressing symptoms that can be well managed with pharmacological and nonpharmacological interventions. Treatment-related symptom screening and management by health care professionals is required to provide appropriate guidance to help patients to complete successfully their treatment regimen and achieve the best possible outcomes for patients. The aims of this study were to explore treatment-related symptom severity and occurrences among oncology adults in Australia and compare the results with the Chinese and Filipino studies.

Methods: A cross-sectional descriptive survey of 84 adult patients over 18 years of age undergoing chemotherapy (CT) and/or radiotherapy (RT) in the Radiation Oncology and Medical Oncology Departments in one public teaching hospital in Canberra, Australia using the 25-item treatment-related symptom checklist (TRSC) was used in this study.

Results: Six symptom clusters emerged from combining the 25 symptoms. Patients receiving CT experienced highest fatigue symptom occurrences (95.8%) and greater symptom severity (mean = 2.59) for fatigue symptom cluster for patients receiving a combination of CT-RT. Australians treatment-related symptom severity and occurrences were higher compared with the Filipino and Chinese adult cancer patients.

Conclusions: Nurses in oncology settings are uniquely placed to assess patients' therapy-related symptoms that will assist them to target education to cancer patients' individual needs. For all types of cancer, it is important to assess treatment-related symptoms and to provide the most appropriate interventions in consideration to the patients' preferences.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4103/2347-5625.160973DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5123468PMC
December 2016

Symptom monitoring, alleviation, and self-care among Mexican Americans during cancer treatment.

Clin J Oncol Nurs 2014 Oct;18(5):547-54

University of Texas at El Paso.

Monitoring the occurrence and severity of symptoms among Mexican American adults undergoing cancer treatments, along with their self-care to alleviate symptoms, are understudied; the current study aimed to fill this gap in the literature. A total of 67 Mexican Americans receiving outpatient oncology treatments in the southwestern United States participated. Instruments included a patient-report checklist, the Therapy-Related Symptom Checklist (TRSC), the Symptom Alleviation: Self-Care Methods tool, and a demographic and health information form. At least 40% of participants reported the occurrence of 12 symptoms: hair loss, feeling sluggish, nausea, taste change, loss of appetite, depression, difficulty sleeping, weight loss, difficulty concentrating, constipation, skin changes, and numb fingers and toes. More than a third also reported pain, vomiting, decreased interest in sexual activity, cough, and sore throat. The helpful self-care strategies reported included diet and nutrition changes; lifestyle changes; and mind, body control, and spiritual activities. Patient report of symptoms during cancer treatments was facilitated by the use of the TRSC. Patients use symptom alleviation strategies to help relieve symptoms during their cancer treatment. The ability to perform appropriate, effective self-care methods to alleviate the symptoms may influence adherence to the treatment regimen.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1188/14.CJON.547-554DOI Listing
October 2014

Outcomes in multifocal neuroblastoma as part of the neurocristopathy syndrome.

Pediatrics 2014 Aug;134(2):e611-6

Kids Cancer Centre, Sydney Children's Hospital, Randwick, New South Wales, Australia;School of Women's and Children's Health, Faculty of Medicine, University of New South Wales, Australia; and

The neurocristopathy syndrome occurs because of a germline mutation of the paired-like homeobox 2b (PHOX2B) gene at 4p12, a neurogenesis regulator gene. The result is abnormal neural crest cell development resulting in congenital central hypoventilation syndrome, Hirschsprung disease, and neuroblastoma (NB), which is often multifocal and disseminated in its presentation. Previously, such widespread disease was regarded as highly aggressive and treated either with palliative intent or, conversely, with very intense, high-dose chemotherapy. We now present a patient who had neurocristopathy syndrome who had multifocal NB associated with an underlying germline PHOX2B mutation. He was treated conservatively with surgery and low-dose chemotherapy. After treatment he had extensive residual disease that has continued to mature despite no further treatment. A literature review identified 26 similar patients presenting with multifocal NB as part of the neurocristopathy syndrome. In all cases the NB behaved in an indolent manner with no deaths from tumor reported when patients received appropriate treatment. These provocative findings suggest for the first time that children who have neurocristopathy-associated NB should be treated conservatively, despite the aggressive appearance of their disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1542/peds.2013-3340DOI Listing
August 2014

Parental caregiving of children with cancer and family impact, economic burden: nursing perspectives.

Issues Compr Pediatr Nurs 2014 Mar 21;37(1):39-60. Epub 2013 Nov 21.

University of Kansas School of Nursing, Kansas City , Kansas , USA .

Pediatric cancer diagnoses affect the entire family: parents, well siblings, the ill child, and others. The objective of this study was to review nursing studies on parental caregiving of children with cancer, family impact, and costs. The study used inclusion/exclusion criteria and family systems theory, self/dependent-care, and symptom management (monitoring, alleviation) concepts. Regarding "levels of evidence," 3 studies were Level II; 7 were Level IV; 7 were Level VI; 1 review was Level V and the second was Level I. Of 19 studies: 11 were qualitative; 4, quantitative; 2 were mixed methods. Content analysis themes were: Parental caregiving and family impact, economic burden. Conclusions were that (a) qualitative studies are predominant; findings supported quantitative findings; (b) quantitative nursing studies are less common: found one longitudinal, randomized controlled trial (RCT) focused on outcomes of an intervention for well siblings and parents, implemented by Clinical Nurse Specialists, CNSs; (c) few quantitative studies with large samples were found, especially ones with theoretical models of the family system and measures of illness impact on families; and (d) "mixed methods" longitudinal nursing research is illustrated. There is a need for "evidence-based" practice (EBP) nursing studies of interventions focused on parent education/support/assistance; respite care, and increasing family/well sibling knowledge/other information on the child's illness.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3109/01460862.2013.855843DOI Listing
March 2014

Symptom occurrence and severity on the therapy-related symptom checklist for children among Hispanic pediatric oncology outpatients.

Cancer Nurs 2014 May-Jun;37(3):E12-20

Author Affiliations: School of Nursing, University of Kansas, Kansas City (Dr P. Williams and Ms Robinson); School of Nursing, Washburn University, Topeka, Kansas (Ms Robinson); and Department of Health Policy & Management, College of Public Health, University of South Florida, Tampa (Dr A. Williams).

Background: A calibrated easy-to-use symptom checklist for children who are under treatment for cancer had been developed and reported in Cancer Nursing. The 30-item Therapy-Related Symptom Checklist for Children (TRSC-C) has good measurement and psychometric properties and uses "kid-friendly" terms to monitor symptom occurrence and severity during oncology treatment. A secondary analysis is reported using participants who self-identified as Hispanic.

Objective: The objective of this study was to examine among Hispanic pediatric oncology outpatients (a) occurrence and (b) severity of symptoms reported on the TRSC-C, (c) relationships of symptoms to gender and age (<12 vs ≥12), and (d) differences in summated TRSC-C symptom scores between patients with acute lymphoblastic leukemia (ALL) and other diagnoses.

Method: This was a cross-sectional analysis using secondary data and descriptive statistics.

Sample: The sample was composed of 79 children (55% male) aged 5 to 17 years (mean, 10.3 years) with diagnosis of ALL (52%) or other (48%). Instrument used was TRSC-C by patient/parent report (Cronbach's α = .91).

Results: (a) Symptom occurrence: 15 symptoms on the TRSC-C were reported by 40% or greater. (b) Severity means on 11 symptoms were greater than "a little bit." (c) No gender or age differences were found on mean TRSC-C summated scores. (d) Mean TRSC-C scores (symptom occurrence and severity) were slightly lower but not significantly different (t = 1.71) between ALL (13.71 [SD, 8.06]) and other diagnoses (15.71 [SD, 7.01]).

Conclusion: Symptom occurrence and severity reported on the TRSC-C by this Hispanic subsample are consistent with findings in the calibration study and with those of another Hispanic group and other ethnicities.

Implications For Practice: Use of the TRSC-C is appropriate during pediatric oncology treatment and diagnoses of Hispanic populations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/NCC.0b013e3182948438DOI Listing
August 2015

A case-control study of pediatric falls using electronic medical records.

Rehabil Nurs 2013 Mar-Apr;38(2):73-9

School of Nursing, Miami Dade College, Miami, FL, USA.

The purpose of this study was to retrospectively review Humpty Dumpty Falls Scale (HDFS) scores using electronic medical records (EMR) reports at a pediatric hospital to determine characteristics related to falls, injuries, and performance of the HDFS tool. The specific research question was: Is there a significant difference in HDFS total scores between cases (children who fell) and controls (those who did not fall)? Results from 74 cases and 242 controls revealed the number of falls did not differ significantly between those who obtained high HDFS scores and those who obtained low scores. HDFS sensitivity was 57%, specificity was 39%. The pediatric patients who fell were mostly oriented and ambulating; falls with injury did not exceed 19%. Future case-control studies should use larger sample sizes across multiple institutions with EMR capability.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/rnj.73DOI Listing
July 2013

Repiphysis prosthesis for limb preservation in pediatric patients with bone cancer: a literature review.

Orthop Nurs 2013 Mar-Apr;32(2):81-6; quiz 87-8

Sarcoma Institute of Menorah, Menorah Medical Center, Menorah Medical Center, Overland Park, KS, USA.

Osteosarcoma is the most common bone sarcoma in children and adolescents. It occurs mainly around the knee joint; the distal femur is the most common location. When it occurs in children who are skeletally immature, a significant limb length discrepancy can occur. The Repiphysis prosthesis was developed in the 1980s to assist in reconstruction of the affected limb in these patients. Ten articles were reviewed to identify the challenges and complications that affect the functional outcome on this population. The reports included patients, aged 7-16 years, who were skeletally immature and had bone sarcomas of the lower extremities. Complications reported by the authors were similar and included aseptic loosening, mechanical failure, infection, flexion contracture of the knee, fracture, and neuropraxia.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/NOR.0b013e3182879bbbDOI Listing
December 2013

Confirmatory factor analysis of the Chinese version of the Pediatric Quality-of-Life Inventory Cancer Module.

Cancer Nurs 2013 Nov-Dec;36(6):E66-72

Author Affiliations: School of Nursing, Lee Ka Shing Faculty of Medicine, the University of Hong Kong, China (Dr Li and Ms Chung); School of Nursing, University of Kansas Medical Center, Kansas City (Dr P. D. Williams); College of Public Health, Department of Health Policy and Management, University of South Florida, Tampa (Dr A. R. Williams); Research Centre for Nursing and Midwifery Practice, Nursing and Midwifery Practice, Australian National University, Woden (Dr. Lopez); Paediatric Oncology Unit, Queen Mary Hospital, Hong Kong, China (Ms Chiu).

Background: Before the Chinese version of the Pediatric Quality-of-Life Inventory Cancer Module can be used to assess the multidimensional construct of quality of life among Hong Kong Chinese pediatric patients with cancer, its psychometric properties need to be further empirically tested.

Objective: The objectives of the study were to establish the construct validity, including hypothesis testing and a confirmatory factor analysis of factor structure, of the Chinese version of the Pediatric Quality-of-Life Inventory Cancer Module.

Methods: A cross-sectional study was used; 200 children hospitalized with cancer (9- to 16-year-olds) were recruited. Participants were asked to respond to the Chinese version of the Cancer Module, Therapy-Related Symptom Checklist, and Rosenberg's Self-esteem Scale.

Results: The results showed that there was a strong positive correlation between children's self-esteem and quality of life (r = 0.50) and a strong negative correlation between children's therapy-related symptoms and quality of life (r = -0.65). Confirmatory factor analysis indicated that there were 7 factors underlying the Chinese version of the Cancer Module.

Conclusion: The study added further evidence of the construct validity of the Chinese version of the Cancer Module, patient version.

Implication For Practice: The Cancer Module can be used to assess and evaluate psychological interventions directed toward promoting the quality of life of children hospitalized with cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/NCC.0b013e318276e056DOI Listing
August 2014

Relationships among therapy-related symptoms, depressive symptoms, and quality of life in Chinese children hospitalized with cancer: an exploratory study.

Cancer Nurs 2013 Sep-Oct;36(5):346-54

School of Nursing, University of Hong Kong, China.

Background: Recent advances in cancer screening and treatment have resulted in a decrease in mortality rates in children and adolescents. However, despite the improved prognosis, the course of cancer treatment continues to be a very stressful experience in the life of a child.

Objectives: The objectives of the study were to assess the occurrence and severity of treatment-related symptoms manifested by children and adolescents undergoing active cancer treatment and to examine the relationships between therapy-related symptoms, depressive symptoms, and quality of life of these pediatric patients.

Methods: A cross-sectional study design was used, and 135 Hong Kong Chinese children (9- to 16-year-olds) who were admitted for treatment of cancer in a pediatric oncology unit were invited to participate in the study.

Results: Results indicated that children and adolescents receiving combined cancer treatment generally experienced greater symptom occurrence and severity. In addition, children reporting greater symptom occurrence and severity experienced higher levels of depression and a lower level of quality of life. The study revealed that therapy-related symptoms are a strong predictor of quality of life of children and adolescents hospitalized for cancer treatment.

Conclusions: Cancer and its treatments significantly affect the psychosocial well-being and quality of life of children and adolescent hospitalized for cancer care. Therapy-related symptoms can be a useful indicator for screening those pediatric patients who are likely to exhibit psychosocial distress or are at high risk of depression.

Implications For Practice: It is essential for nurses to be sensitive and knowledgeable about the therapy-related symptoms of cancer treatment and their effects on children and adolescents to promote the psychosocial well-being of these patients and enhance their quality of life.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/NCC.0b013e31824062ecDOI Listing
August 2014

Effect of art making on cancer-related symptoms of blood and marrow transplantation recipients.

Oncol Nurs Forum 2012 Jul;39(4):E353-60

Department of Occupational Therapy Education, University of Kansas Medical Center, USA.

Purpose/objectives: To examine whether a one-hour art-making session during blood and marrow transplantation (BMT) treatment significantly affects therapy-related symptoms, state anxiety, and stress.

Design: A pre- and post-test crossover design.

Setting: An urban outpatient cancer center in the midwestern United States.

Sample: A convenience sample of 20 patients, aged 20-68 years (X = 38.5), receiving treatment at a BMT clinic.

Methods: Participants completed a demographic questionnaire, the Therapy-Related Symptom Checklist, and the Spielberger State-Trait Anxiety Index, and provided salivary cortisol samples. After pretesting, individuals were assigned to either a wait list or intervention. Individuals in the wait-list group received the usual treatment before completing the post-test measures. Individuals in the intervention group participated in a one-hour art-making session, after which they completed post-test measures. Participants then crossed over to the other group.

Main Research Variables: Art making, stress, state anxiety, and therapy-related symptoms.

Findings: Therapy-related symptom concerns for the intervention group at post-test were significantly lower than at pretest; no change ocurred in the control group. The salivary cortisol levels were significantly lower at post-test in the intervention and control groups. No change occurred in the anxiety levels of participants in the intervention and control groups. The study hypothesis was partially supported.

Conclusions: Art making decreased therapy-related symptoms (e.g., feeling sluggish, difficulty concentrating). Use of more physiologic indices to measure stress and replication on a larger sample are suggested.

Implications For Nursing: Individuals receiving BMT may benefit from participation in art-making interventions. Art making is easy to implement in a clinic setting and allows for positive interactions between nurses and patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1188/12.ONF.E353-E360DOI Listing
July 2012
-->