Imperial College London

Dr Jonathan Underwood

Faculty of MedicineDepartment of Infectious Disease

Honorary Clinical Research Fellow
 
 
 
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Contact

 

+44 (0)20 3312 1466jonathan.underwood Website CV

 
 
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Location

 

Winston Churchill WingSt Mary's Campus

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Summary

 

Publications

Publication Type
Year
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47 results found

Yilmaz A, Blennow K, Hagberg L, Nilsson S, Price RW, Schouten J, Spudich S, Underwood J, Zetterberg H, Gisslen Met al., 2017, Neurofilament light chain protein as a marker of neuronal injury: review of its use in HIV-1 infection and reference values for HIV-negative controls, EXPERT REVIEW OF MOLECULAR DIAGNOSTICS, Vol: 17, Pages: 761-770, ISSN: 1473-7159

Journal article

De Francesco D, Underwood J, Post FA, Vera JH, Williams I, Boffito M, Sachikonye M, Anderson J, Mallon PWG, Winston A, Sabin CAet al., 2016, Defining cognitive impairment in people-living-with-HIV: the POPPY study, BMC Infectious Diseases, Vol: 16, ISSN: 1471-2334

BackgroundThe reported prevalence of cognitive impairment (CI) varies widely in cohorts of people living with HIV (PLWH); this may partly be due to the use of different diagnostic criteria. Agreement between diagnostic criteria of CI, the optimal definition to use, and associations with patient-reported cognitive symptoms have not been fully investigated.MethodsTwo hundred ninety PLWH aged >50 years and 97 matched negative controls completed a detailed assessment of cognitive function and three questions regarding cognitive symptoms. Age- and education-adjusted test scores (T-scores) determined if subjects met the following definitions of CI: Frascati, global deficit score (GDS) and the multivariate normative comparison (MNC) method.ResultsPLWH were more likely than controls to meet each definition of CI (ORs were 2.17, 3.12 and 3.64 for Frascati, GDS and MNC, respectively). Agreement of MNC with Frascati and GDS was moderate (Cohen’s k = 0.42 and 0.48, respectively), whereas that between Frascati and GDS was good (k = 0.74). A significant association was found between all the three criteria and reporting of memory loss but not with attention and reasoning problems. The 41 (14 %) PLWH meeting all the three criteria had the lowest median global T-score (36.9) and highest rate of symptom reporting (42 %).ConclusionsDifferent CI criteria show fair diagnostic agreement, likely reflecting their ability to exclude CI in the same group of individuals. Given the lower overall cognitive performance and higher rates of symptom reporting in those meeting all three criteria of CI, further work assessing this as a definition of CI in PLWH is justified.

Journal article

Underwood J, De Francesco D, Post FA, Vera JH, Williams I, Boffito M, Mallon PW, Anderson J, Sachikonye M, Sabin C, Winston A, Pharmacokinetic and Clinical Observations in People Over Fifty POPPY study groupet al., 2016, Associations between cognitive impairment and patient-reported measures of physical/mental functioning in older people living with HIV, HIV Medicine, Vol: 18, Pages: 363-369, ISSN: 1464-2662

OBJECTIVES: While cognitive impairment is frequently reported in HIV-positive individuals and has historically been associated with poorer functional outcomes, the associations between cognitive impairment and patient-reported outcome measures (PROMs) in contemporary cohorts are unclear. METHODS: We tested cognitive function using a computerized battery (CogState(™) ) in 290 HIV-positive and 97 HIV-negative individuals aged ≥ 50 years participating in the Pharmacokinetic and Clinical Observations in People Over Fifty (POPPY) study. Participants completed questionnaires detailing physical and mental health [Short Form Health Survey (SF-36)], cognitive function [European AIDS Clinical Society (EACS) questions], activities of daily living [Lawton Instrumental Activities of Daily Living (IADL)], depression [Patient Depression Questionnaire (PHQ-9) and Centres for Epidemiologic Studies Depression scale (CES-D)], falls and sexual desire. Cognitive impairment was defined using the Frascati criteria, global deficit score (GDS) and multivariate normative comparison (MNC). In the HIV-positive group, the classification performances of the different definitions of cognitive impairment and dichotomized questionnaire results were calculated. RESULTS: The prevalence of cognitive impairment in the HIV-positive group was 34.5% (GDS), 30.0% (Frascati) and 22.1% (MNC), with only 2% diagnosed with HIV-associated dementia. In general, the associations between cognitive impairment and PROMs were weak regardless of the definition used: mean c-statistics were 0.543 (GDS), 0.530 (MNC) and 0.519 (Frascati). Associations were similar using the global T-score to define cognitive impairment. Summary health scores (SF-36) were lower, but only significantly so for those with cognitive impairment identified using MNC, for both mental health (61.4 vs. 75.8; P = 0.03) and physical health (60.9 vs. 75.0; P = 0.03). CONCLUSIONS: The associations between cognitive impairment and PROMs were wea

Journal article

De Francesco D, Underwood J, Boffito M, Post F, Mallon P, Vera J, Williams I, Anderson J, Johnson M, Sabin C, Winston Aet al., 2016, Cognitive function and depression in HIV-positive individuals and matched controls, JOURNAL OF THE INTERNATIONAL AIDS SOCIETY, Vol: 19

Journal article

Underwood J, Winston A, 2016, Guidelines for Evaluation and Management of Cognitive Disorders in HIV-Positive Individuals, Current HIV/AIDS Reports, Vol: 13, Pages: 235-240, ISSN: 1548-3576

Antiretroviral therapy has revolutionised the treatment for people living with HIV (PLWH). Where antiretroviral coverage is high, the treatment paradigm for HIV-disease is now one of managing the long-term consequences of the virus and its treatment rather than the consequences of untreated HIV-disease such as immunosuppression and opportunistic infections. One such long-term consequence is HIV-associated cognitive impairment which is reported to occur in up to 50 % of treated PLWH and has been associated with poorer outcomes. Given the ageing cohort and increased frequency of comorbidities, the prevalence of symptomatic cognitive impairment may increase with time. High quality evidence for management strategies including screening, diagnosis and treatment of HIV-associated cognitive impairment are lacking and in general guidelines are based on best clinical practice. In this article, we assessed recent guidelines concerning the management of HIV-associated cognitive impairment by performing a systematic review of the MEDLINE database using PubMed. We report that, in general, guidelines from around the world regarding the management of HIV-associated cognitive impairment are converging. Screening is generally not recommended in asymptomatic PLWH. Diagnosis of HIV-associated cognitive impairment should be made only after a comprehensive assessment and exclusion of other potential causes. Antiretroviral therapy forms the cornerstone of management of HIV-associated cognitive impairment and should be guided by plasma and cerebrospinal fluid (CSF) genotype(s).

Journal article

Mora-Peris B, Stevens E, Ferretti F, Underwood J, Taylor S, Winston Aet al., 2016, Evolution of changes in cognitive function after the initiation of antiretroviral therapy., AIDS Research and Therapy, Vol: 13, ISSN: 1742-6405

BACKGROUND: Cognitive function is reported to improve after the initiation of combination antiretroviral therapy (cART). Data on the evolution of such changes are limited. We assessed the dynamics of changes in cognitive parameters, in HIV-positive subjects initiating cART. METHODS: Cognitive function in seven domains was evaluated for HIV-infected patients without clinically significant cognitive impairment prior to the initiation of cART, and 24 and 48 weeks after. Cognitive scores were transformed using standardised z-scores according to the pooled baseline standard deviation. Global, speed, and accuracy composite z-scores were calculated with changes calculated using a paired t test. RESULTS: In 14 subjects, change in global cognitive z-scores from baseline was by 0.08 at week 24 (p = 0.59) and 0.15 at week 48 (p = 0.43). Change in composite speed and accuracy z-scores from baseline at weeks 24/48 were 0.07/0.05 (p = 0.45/0.82) and 0.13/0.23 (p = 0.47/0.45), respectively. In two of the cognitive domains assessing speed (learning and monitoring time), a continued improvement from baseline to weeks 24 and 48 was observed (changes of 0.06-0.08 and 0.10-0.19, respectively), whereas in two domains (detection and identification) an initial improvement at week 24 (changes of -0.10 and 0.04 from baseline, respectively) was followed by a deterioration in score at week 48 (changes of -0.12 and -0.08 from baseline, respectively). None of these changes were statistically significant. CONCLUSIONS: A trend for improvement in cognitive function was observed in naïve HIV-positive patients starting cART. The dynamics of this improvement differed both between cognitive domains and the time-points assessed.

Journal article

Thornhill J, Underwood J, Kuldanek K, Mahay K, Fidler S, Frater J, Hopkins E, Meyerowitz J, Fox J, Nwokolo N, Whitlock G, Mackie N, Porter Ket al., 2016, Impact of timing of ART on HIV DNA; findings from HEATHER, an observational cohort study, 22nd Annual Conference of the British HIV Association (BHIVA), Publisher: Wiley, Pages: 11-11, ISSN: 1464-2662

Conference paper

Underwood J, Cole JH, Sharp D, Winston A, Leech R, Majoie C, Caan M, De Francesco D, van Zoest R, Geurtsen G, Schmand B, Wit F, Reiss P, Sabin Cet al., 2016, Brain MRI changes associated with poorer cognitive function despite suppressive antiretroviral therapy, 22nd Annual Conference of the British HIV Association (BHIVA), Publisher: Wiley, Pages: 6-6, ISSN: 1464-2662

Conference paper

Scott J, Underwood J, Garvey LJ, Mora-Peris B, Winston Aet al., 2016, A comparison of two post-processing analysis methods to quantify cerebral metabolites measured via proton magnetic resonance spectroscopy in HIV disease., British Journal of Radiology, Vol: 89, ISSN: 1748-880X

OBJECTIVE: Non-invasive biomarkers to monitor cerebral function in treated human immunodeficiency virus (HIV) disease are required. Cerebral metabolite ratios (CMRs) measured by proton-MR spectroscopy ((1)H-MRS) are a potential biomarker. Here, we compare two post-processing software packages to quantify CMRs. METHODS: Cerebral (1)H-MRS data from 11 HIV-positive subjects before and after antiretroviral therapy intensification with maraviroc were quantified using a java-based version of the MR user interface package (jMRUI) and the totally automatic robust quantitation in nuclear MR (TARQUIN). (1)H-MRS data included N-acetylaspartate (NAA), creatine (Cr), choline (Cho) and myo-inositol (mI) from three cerebral locations. Differences in quantification and clinical associations of CMRs measured by the two packages were evaluated. RESULTS: Mean CMRs were generally lower when measured by TARQUIN than by jMRUI (NAA/Cr, Cho/Cr, mI/Cr ratios of 1.78, 0.83, 0.81 for jMRUI, and 1.27, 0.25, 0.81 for TARQUIN). Longitudinal changes were observed in CMRs in the basal ganglia voxel although these changes were not statistically significant [+7.1% (p = 0.18), +0.0% (p = 0.91) and -6.6% (p = 0.61) and +14.8% (p = 0.18), +17.9% (p = 0.07) and +34.8% (p = 0.17) for NAA/Cr, Cho/Cr and mI/Cr ratios measured by TARQUIN and jMRUI, respectively]. Plasma maraviroc concentration was associated with a decrease in mI/Cr ratio measured via TARQUIN (p = 0.049). CONCLUSION: Although CMRs differed when quantified by jMRUI vs TARQUIN, these differences were consistently observed across three cerebral locations, and clinical associations were evident by both methods. ADVANCES IN KNOWLEDGE: TARQUIN and jMRUI are viable options to use in the post-processing of cerebral MRS data acquired in HIV disease.

Journal article

Winston A, Underwood J, 2016, Plasma Biomarkers of HIV-associated Cognitive Disease., EBioMedicine, Vol: 3, Pages: 12-13

Journal article

Underwood J, 2015, Cognitive deficits persist in the combination antiretroviral era: Preliminary results from the Co-morBidity in Relation to AIDS (COBRA) collaboration London cohort, 12th International Symposium on the Neurobiology and Neuroendocrinology of Aging, Publisher: Elsevier, Pages: 104-104, ISSN: 1873-6815

Background: HIV is a neurotropic virus that if left untreated leads to a frank dementia in a significant proportion of patients. Modern combination antiretroviral therapy (cART) has transformed HIV into a chronic disease with life expectancy approaching normal. The more severe forms of HIV associated neurocognitive dysfunction (HAND) are now rarely seen but there have been many reports of more subtle cognitive deficits occurring in up to 50% of patients in the modern era. Unfortunately many previous studies have had heterogeneous patient groups or lacked appropriate controls making extrapolation to well treated patients, common in current practice, difficult. This study set out to investigate the true prevalence of cognitive dysfunction and the mechanisms underlying it in an older group of HIV positive individuals on effect cART.Methods: To date 46 participants (33 HIV-positive patients and 13 HIV-negative controls) have been recruited into the London cohort of the COBRA observational study. All participants were aged over 50 (mean age 61 ± 7.7 years) and were predominantly male (87%). All HIV positive patients were on fully suppressive stable cART > 12 months. The two groups were well matched in terms of age, gender, sexual orientation, ethnicity and educational attainment. Subjects underwent a full cognitive battery in addition to MRI scanning with a 64-direction diffusion protocol. Mean FA (fractional anisotropy) for the major white matter tracts was calculated using a white matter skeleton created from the centre of tracts common to the group and standard atlases.Results: Poorer performance on trail making tests A and B (p = 0.007 and < 0.001 respectively), the Stroop test (p = 0.006), grooved peg board test (p = 0.004) and the Wisconsin card sort test (p = 0.002) were observed in the HIV-positive group compared to the control group. After adjusting for age the mean white matter skeleton FA was highly significantly correlated (p < 0.01) with all

Conference paper

Winston A, Underwood J, 2015, Emerging concepts on the use of antiretroviral therapy in older adults living with HIV infection, CURRENT OPINION IN INFECTIOUS DISEASES, Vol: 28, Pages: 17-22, ISSN: 0951-7375

Journal article

Underwood J, Robertson KR, Winston A, 2015, Could antiretroviral neurotoxicity play a role in the pathogenesis of cognitive impairment in treated HIV disease?, AIDS, Vol: 29, Pages: 253-261, ISSN: 0269-9370

Journal article

Underwood J, 2014, Bone, joint and soft tissue infections, Oxford Handbook of Tropical Medicine, Editors: Brent, Davidson, Seale, Publisher: Oxford University Press, ISBN: 9780199692569

The new edition of this unique handbook continues to provide an accessible and comprehensive, signs-and-symptoms based source of information on medical problems commonly seen in the tropics.

Book chapter

Underwood J, 2013, RECURRENT UTI IN NON-PREGNANT WOMEN Don't forget the embalming fluid for treating recurrent infections ..., BMJ-BRITISH MEDICAL JOURNAL, Vol: 346, ISSN: 1756-1833

Journal article

Underwood J, Klein JL, Newsholme W, 2011, Escherichia coli bacteraemia: how preventable is it?, Journal of Hospital Infection, Vol: 79, Pages: 364-365, ISSN: 0195-6701

Summary Mandatory bacteraemia reporting was extended to include Escherichia coli from June 2011. The purpose of this study was to investigate whether the success seen in reducing meticillin-resistant Staphylococcus aureus infection rates could be duplicated with E. coli. All cases of E. coli bacteraemia occurring at our Trust in 2010 were reviewed. There were 216 episodes of E. coli bacteraemia, of which 63% were community-acquired. Only 19% had a potentially preventable cause identified, the majority (71%) of whom had urinary catheter-associated bacteraemia. These data must be kept in mind should targets to reduce E. coli bacteraemia be set in the future.

Journal article

Cowie MR, Komajda M, Murray-Thomas T, Underwood J, Ticho Bet al., 2006, Prevalence and impact of worsening renal function in patients hospitalized with decompensated heart failure: results of the prospective outcomes study in heart failure (POSH), EUROPEAN HEART JOURNAL, Vol: 27, Pages: 1216-1222, ISSN: 0195-668X

Journal article

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