113 results on '"Haddow L"'
Search Results
2. Vascular dysfunction and increased cardiovascular risk in hypospadias
- Author
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Lucas-Herald AK, Montezano AC, Alves-Lopes R, Haddow L, Alimussina M, O'Toole S, Flett M, Lee B, Amjad SB, Steven M, Brooksbank K, McCallum L, Delles C, Padmanabhan S, Ahmed SF, and Touyz RM
- Subjects
General Economics, Econometrics and Finance - Published
- 2022
3. Clinical round up
- Author
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Herbert, S and Haddow, L
- Published
- 2017
- Full Text
- View/download PDF
4. CT Guided Thalamotomy for Movement Disorders in Multiple Sclerosis: Problems and Paradoxes
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Whittle, I. R., Haddow, L. J., Meyerson, Björn A., editor, and Ostertag, Christoph, editor
- Published
- 1995
- Full Text
- View/download PDF
5. Clinical round-up
- Author
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Herbert, S and Haddow, L
- Published
- 2016
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- View/download PDF
6. Clinical roundup
- Author
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Herbert, S and Haddow, L
- Published
- 2015
- Full Text
- View/download PDF
7. Abnormalities of the lymphatic system and impaired fluid clearance in patients with heart failure with preserved ejection fraction
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Rossitto, G, primary, Mary, S, additional, McAllister, C, additional, Neves, K.B, additional, Haddow, L, additional, Rocchiccioli, P, additional, Lang, N, additional, Murphy, C, additional, Touyz, R.M, additional, Petrie, M.C, additional, and Delles, C, additional
- Published
- 2020
- Full Text
- View/download PDF
8. Analysis of high voltage impulse generator circuits
- Author
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Haddow, L. Martin
- Subjects
621.31 - Abstract
A study is made of transient or oscillatory voltages which arise in an impulse generator of the two-column Marx type during the firing process (i.e. between the breakdown of the first and the last spark-gap and immediately thereafter). These voltages are liable to appear on the external test and measuring equipment, but this aspect is not dealt with, nor are the spark-gap characteristics investigated systematically. The voltages are shown to be relatively independent of the main circuit elements, but to be set up in the stray capacitative and inductive fields in the generator, structure. These fields are resolved into an equivalent circuit involving measurable parameters. A matrix method is developed to analyze its dynamic properties, the solution being given in terms of eigenvalues. It is particularly suited to numerical treatment on a digital computer. The theory is extended, tentatively, to the evaluation of optimum damping resistances. By a second approach, the generator is represented by a one-dimensional lattice circuit. Although an explicit solution is not obtained, some propagation characteristics are determined, enabling comparison to be made with the one-column type of generator (and with such analogous problems as transformer windings). The gaps cannot in general be assumed to fire simultaneously. The transient voltages are of primary importance in causing their successive breakdown, but the instant of breakdown due to an overvoltage cannot be determined from present data. Again, the firing of the gaps constitutes the excitation to the circuit, but it is doubtful whether they behave as ideal switches. These two factors make a complete solution impracticable. The experimental work made use of a four-stage generator. Voltages calculated from measured parameters are compared with oscillographic measurements. Sources of error in the capacitance-divider circuit are investigated and compensation for the connecting leads shown to be desirable.
- Published
- 1959
9. Discontinuation of non-nucleoside reverse transcriptase inhibitor-based highly active antiretroviral therapy due to nucleoside analogue reverse transcriptase inhibitor-related metabolic toxicity
- Author
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Haddow, L J, Wood, C W, and Ainsworth, J G
- Published
- 2007
10. Increase in rates of herpes simplex virus type 1 as a cause of anogenital herpes in western Sydney, Australia, between 1979 and 2003
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Haddow, L J, Dave, B, Mindel, A, McPhie, K A, Chung, C, Marks, C, and Dwyer, D E
- Published
- 2006
11. A case of a false positive result on a home HIV test kit obtained on the internet
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Haddow, L J and Robinson, A J
- Published
- 2005
12. Polymorph count for predicting non-gonococcal urethral infection: a model using Chlamydia trachomatis diagnosed by ligase chain reaction
- Author
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Haddow, L J, Bunn, A, Copas, A J, Gilson, R, Prince, M, Ridgway, G L, and Sadiq, S T
- Published
- 2004
13. Patients lost to follow up: experience of an HIV clinic
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Haddow, L J, Edwards, S G, Sinka, K, and Mercey, D E
- Published
- 2003
14. Neisseria elongata endocarditis: case report and literature review
- Author
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Haddow, L. J., Mulgrew, C., Ansari, A., Miell, J., Jackson, G., Malnick, H., and Rao, G. Gopal
- Published
- 2003
15. Spontaneous Achilles tendon rupture in patients treated with levofloxacin
- Author
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Haddow, L. J., Sekhar, M. Chandra, Hajela, V., and Rao, G. Gopal
- Published
- 2003
16. Kaposi’s sarcoma infiltrating skeletal muscle
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Haddow, L J, Davies, S, Buckingham, S, and Miller, R F
- Published
- 2002
17. CT Guided Thalamotomy for Movement Disorders in Multiple Sclerosis: Problems and Paradoxes
- Author
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Whittle, I. R., primary and Haddow, L. J., additional
- Published
- 1995
- Full Text
- View/download PDF
18. Acceptability of an open-label wait-listed trial design: Experiences from the PROUD PrEP study
- Author
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Gafos, M., Brodnicki, E., Desai, M., McCormack, S., Nutland, W., Wayal, S., White, E., Wood, G., Barber, T., Bell, G., Clarke, A., Dolling, D., Dunn, D., Fox, J., Haddow, L., Lacey, C., Nardone, A., Quinn, K., Rae, C., Reeves, I., Rayment, M., White, D., Apea, V., Ayap, W., Dewsnap, C., Collaco-Moraes, Y., Schembri, G., Sowunmi, Y., Horne, R., Proud Study Team , ., and Law, M
- Subjects
Science ,Medicine ,humanities - Abstract
Background\ud \ud PROUD participants were randomly assigned to receive pre-exposure prophylaxis (PrEP) immediately or after a deferred period of one-year. We report on the acceptability of this open-label wait-listed trial design.\ud \ud Methods\ud \ud Participants completed an acceptability questionnaire, which included categorical study acceptability data and free-text data on most and least liked aspects of the study. We also conducted in-depth interviews (IDI) with a purposely selected sub-sample of participants.\ud \ud Results\ud \ud Acceptability questionnaires were completed by 76% (415/544) of participants. After controlling for age, immediate-group participants were almost twice as likely as deferred-group participants to complete the questionnaire (AOR:1.86;95%CI:1.24,2.81). In quantitative data, the majority of participants in both groups found the wait-listed design acceptable when measured by satisfaction of joining the study, intention to remain in the study, and interest in joining a subsequent study. However, three-quarters thought that the chance of being in the deferred-group might put other volunteers off joining the study. In free-text responses, data collection tools were the most frequently reported least liked aspect of the study. A fifth of deferred participants reported ‘being deferred’ as the thing they least liked about the study. However, more deferred participants disliked the data collection tools than the fact that they had to wait a year to access PrEP. Participants in the IDIs had a good understanding of the rationale for the open-label wait-listed study design. Most accepted the design but acknowledged they were, or would have been, disappointed to be randomised to the deferred group. Five of the 25 participants interviewed reported some objection to the wait-listed design.\ud \ud Conclusion\ud \ud The quantitative and qualitative findings suggest that in an environment where PrEP was not available, the rationale for the wait-listed trial design was well understood and generally acceptable to most participants in this study.
- Published
- 2017
19. Admissions for antibiotic-resistant infections in cancer patients during first year of cancer diagnosis: a cross-sectional study
- Author
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Slavova-Azmanova, N., Haddow, L., Hohnen, H., Coombs, G.W., Robinson, J.O., Ives, A., Slavova-Azmanova, N., Haddow, L., Hohnen, H., Coombs, G.W., Robinson, J.O., and Ives, A.
- Abstract
In this study, linked Western Australian health data were used to determine presence of an antibiotic-resistant infection (ABRI) for all people diagnosed with a primary invasive cancer in 2009. Of 10 858 cancer cases, 154 (1.42%) had an ABRI. Patients with an ABRI were older (71.5 vs 66 years), and more had died in the year following diagnosis (37.7 vs 20.2%, P < 0.001). The ABRI cohort had a higher proportion of colorectal, genitourinary and haematological cancers (19.5 vs 11.9%; 14.3 vs 9.7% and 16.9 vs 5.8%, respectively). Hospital admissions with an ABRI were longer (22.3 vs 2.9 days, P < 0.001) and had a higher proportion of unplanned admissions (60.3 vs 15.2%), admissions through emergency department (36.8 vs 8.3%) and intensive care admissions (14.9 vs 1.7%, P < 0.001). Patients with solid tumours who developed an ABRI were more likely to have received chemotherapy (35.9 vs 27.8%, P = 0.04). In haematological cancer patients, a greater proportion of the admissions with an ABRI occurred after radiation therapy or chemotherapy (P = 0.01 and P = 0.005, respectively). This study is the first to report population-level data on ABRI in cancer patients. Patients with an ABRI had more hospital admissions and poorer outcomes.
- Published
- 2017
20. CSF/plasma HIV-1 RNA discordance even at low levels is associated with up-regulation of host inflammatory mediators in CSF
- Author
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Nightingale, S, Michael, BD, Fisher, M, Winston, A, Nelson, M, Taylor, S, Ustianowski, A, Ainsworth, J, Gilson, R, Haddow, L, Ong, E, Leen, C, Minton, J, Post, F, Beloukas, A, Borrow, R, Pirmohamed, M, Geretti, AM, Khoo, S, and Solomon, T
- Subjects
Inflammation ,Biochemistry & Molecular Biology ,Science & Technology ,PLASMA ,CENTRAL-NERVOUS-SYSTEM ,BIOMARKERS ,Immunology ,HIV ,Cell Biology ,Hematology ,IMMUNODEFICIENCY-VIRUS INFECTION ,IMPAIRMENT ,Biochemistry ,CSF escape ,ERA ,Cerebrospinal fluid ,CEREBROSPINAL-FLUID ,ANTIRETROVIRAL THERAPY ,MARKERS ,Sanctuary site ,1107 Immunology ,NEUROCOGNITIVE DISORDERS ,Immunology and Allergy ,Life Sciences & Biomedicine ,Molecular Biology - Abstract
INTRODUCTION: HIV-1 RNA can be found at higher levels in cerebrospinal fluid (CSF) than in plasma, termed CSF/plasma discordance. The clinical significance of CSF/plasma discordance is not known and the degree of discordance considered important varies. We aimed to determine whether a panel of CSF cytokines, chemokines and associated mediators were raised in patients with CSF/plasma discordance at different levels.METHODS: A nested case-control study of 40 CSF samples from the PARTITION study. We used a cytometric bead array to measure CSF mediator concentrations in 19 discordant and 21 non-discordant samples matched for plasma HIV-1 RNA. Discordant samples were subdivided into 'high discordance' (>1log10) and 'low discordance' (0.5-1log10, or ultrasensitive discordance). CSF mediators significant in univariate analysis went forward to two-way unsupervised hierarchical clustering based on the patterns of relative mediator concentrations.RESULTS: In univariate analysis 19 of 21 CSF mediators were significantly higher in discordant than non-discordant samples. There were no significant differences between samples with high versus low discordance. The samples grouped into two clusters which corresponded to CSF/plasma discordance (pCONCLUSIONS: CSF/plasma discordance is associated with potentially damaging neuroinflammatory process. Patients with discordance at lower levels (ie. 0.5-1log10) should also be investigated as mediator profiles were similar to those with discordance >1log10. Sensitive testing may have a role to determine whether ultrasensitive discordance is present in those with low level CSF escape.
- Published
- 2016
21. Routine detection and management of neurocognitive impairment in HIV-positive patients in a UK centre
- Author
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Haddow, L J, Accoroni, A, Cartledge, J D, Manji, H, Benn, P, and Gilson, R J C
- Subjects
Adult ,Male ,Psychiatric Status Rating Scales ,HIV-associated dementia ,AIDS Dementia Complex ,HIV-associated neurocognitive disorder ,Anti-HIV Agents ,prevalence ,cross-sectional studies ,HIV Infections ,Middle Aged ,Neuropsychological Tests ,HIV infection ,United Kingdom ,Young Adult ,Original Research Articles ,Humans ,Female ,Cognition Disorders ,asymptomatic neurocognitive impairment ,Aged ,Retrospective Studies - Abstract
Summary We estimated the burden of HIV-associated neurocognitive disorders (HAND) in a UK clinic. From a random sample, and referrals to specialist services over one year (neurology, clinical psychology, hospital admissions), we determined whether patients were diagnosed with HIV-associated dementia (HAD) and whether they reported symptoms suggesting neurocognitive impairment (NCI). In the first sample, 2/150 (prevalence 1.3%; 95% confidence interval [CI] 0.2–4.7%) had documented HAD. Eleven patients (7.3%; CI 3.7–12.7%) reported recent symptoms suggesting NCI; most of these individuals were diagnosed with a psychiatric or substance-use disorder. Among specialist referrals with symptoms suggesting NCI, 11 were diagnosed with HAD from a clinic population of 3129 individuals (annual incidence 0.4%; CI 0.2–0.6%). No patients with mildly symptomatic or asymptomatic HAND were identified in either sample, suggesting that such patients remain undetected in current clinical practice. Evidence-based screening for HAND in HIV clinics may be needed.
- Published
- 2013
22. Clinical round up: June 2015
- Author
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Herbert, S, primary and Haddow, L, additional
- Published
- 2015
- Full Text
- View/download PDF
23. Neurocognitive change observed in the CHARTER HIV cohort could be due to chance, and may be a cause as well as a consequence of detectable viraemia
- Author
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Haddow, L. J., primary, Pierce, K. J., additional, Daskalopoulou, M., additional, Lampe, F., additional, and Rodger, A., additional
- Published
- 2015
- Full Text
- View/download PDF
24. Minimal Cognitive Impairment in UK HIV-Positive Men Who Have Sex With Men: Effect of Case Definitions and Comparison With the General Population and HIV-Negative Men
- Author
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McDonnell, J, Haddow, L, Daskalopoulou, M, Lampe, F, Speakman, A, Gilson, R, Phillips, A, Sherr, L, Wayal, S, Harrison, J, Antinori, A, Maruff, P, Schembri, A, Johnson, M, Collins, S, Rodger, A, McDonnell, J, Haddow, L, Daskalopoulou, M, Lampe, F, Speakman, A, Gilson, R, Phillips, A, Sherr, L, Wayal, S, Harrison, J, Antinori, A, Maruff, P, Schembri, A, Johnson, M, Collins, S, and Rodger, A
- Abstract
BACKGROUND: To determine the prevalence of neurocognitive impairment (NCI) in UK HIV-positive and HIV-negative men who have sex with men (MSM). METHODS: HIV-positive and HIV-negative participants were recruited to a cross-sectional study from 2 London clinics and completed computer-assisted neuropsychological tests and questionnaires of depression, anxiety, and activities of daily living. Published definitions of HIV-associated neurocognitive disorders (HAND) and global deficit scores were used. Age- and education-adjusted neuropsychological test scores were directly compared with reference population data. RESULTS: A total of 248 HIV-positive and 45 HIV-negative MSM participated. In the HIV-positive group, median time since diagnosis was 9.4 years, median CD4 count was 550 cells per cubic millimeter, and 88% were on antiretroviral therapy. Prevalence of HAND was 21.0% in HIV-positive MSM (13.7% asymptomatic neurocognitive impairment, 6.5% mild neurocognitive disorder, and 0.8% HIV-associated dementia). Using a global deficit score threshold of 0.5, the prevalence of NCI was 31.5% (when averaged over 5 neuropsychological domains) and 40.3% (over 10 neuropsychological test scores). These results were not significantly different from the HIV-negative study sample. No consistent pattern of impairment was seen in HIV-positive patients relative to general male population data (n = 380). CONCLUSIONS: We found a prevalence of HAND and degree of impairment on neuropsychological testing of HIV-positive MSM that could represent a normal population distribution. These findings suggest that NCI may be overestimated in HIV-positive MSM, and that the attribution of NCI to HIV infection implied by the term HAND requires revision.
- Published
- 2014
25. Pre-antiretroviral therapy plasma levels of CCL2 may aid in the prediction of tuberculosis-associated immune reconstitution inflammatory syndrome in HIV patients after they commence antiretroviral therapy
- Author
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Oliver, B., Haddow, L., Agarwal, U., Kumar, M., Easterbrook, P., Moosa, M., Singh, S., Price, Patricia, Oliver, B., Haddow, L., Agarwal, U., Kumar, M., Easterbrook, P., Moosa, M., Singh, S., and Price, Patricia
- Published
- 2013
26. Short communication: Plasma levels of vitamin D in HIV patients initiating antiretroviral therapy do not predict immune restoration disease associated with mycobacterium tuberculosis
- Author
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Price, Patricia, Haddow, L., Affandi, J., Agarwal, U., Easterbrook, P., Elliott, J., French, M., Kumar, M., Moosa, M., Oliver, B., Singh, S., Sola, M., Saphonn, V., Vun, M., Price, Patricia, Haddow, L., Affandi, J., Agarwal, U., Easterbrook, P., Elliott, J., French, M., Kumar, M., Moosa, M., Oliver, B., Singh, S., Sola, M., Saphonn, V., and Vun, M.
- Abstract
Immune restoration disease associated with Mycobacterium tuberculosis (TB IRD) is clinically important among HIV patients commencing antiretroviral therapy in countries where tuberculosis is endemic. Vitamin D affects dendritic cell and T cell function and the antimicrobial activity of monocytes. Plasma levels of vitamin D and polymorphisms in the vitamin D receptor may affect tuberculosis, and HIV infection associates with vitamin D deficiency. Here we assess whether plasma vitamin D levels may predict TB IRD. Samples were available from prospective studies of TB IRD in Cambodia (26 cases), India (19 cases), and South Africa (29 cases). IRD cases and controls from each site were similar in age and baseline CD4+ T cell count. Plasma samples were assessed using 25(OH) vitamin D immunoassay plates. DNA samples were available from a subset of patients and were genotyped for the VDR FokI (F/f) [C/T, rs10735810] SNP. When data from each cohort were pooled to assess ethnic/geographic differences, 25(OH)D levels were higher in Cambodian than Indian or South African patients (p<0.0001) and higher in South African than Indian patients (p<0.0001). TB IRD was not associated with differences in levels of 25(OH)D in any cohort (p=0.36-0.82), irrespective of the patients' prior TB diagnoses/treatment. Carriage of the minor allele of VDR FokI (F/f) was marginally associated with TB IRD in Indian patients (p=0.06) with no association in Cambodians. Neither plasma levels of vitamin D nor the vitamin D allele will usefully predict TB IRD in diverse populations from TB endemic regions. © 2012, Mary Ann Liebert, Inc.
- Published
- 2012
27. Including questionnaires with the invitation package appeared to increase the response fraction among women
- Author
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Rogers, P., Haddow, L., Thomson, Allyson, Fritschi, Lin, Girschik, J., Boyle, T., Zaemey, S., Heyworth, J., Rogers, P., Haddow, L., Thomson, Allyson, Fritschi, Lin, Girschik, J., Boyle, T., Zaemey, S., and Heyworth, J.
- Published
- 2012
28. Including questionnaires with the invitation package appeared to increase the response fraction among women.
- Author
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Rogers PA, Haddow L, Thomson AK, Fritschi L, Girschik J, Boyle T, El Zaemey S, and Heyworth JS
- Published
- 2012
29. Minimal cognitive impairment in UK HIV-positive men who have sex with men: Effect of case definitions and comparison with the general population and HIV-negative men
- Author
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Mcdonnell, J., Haddow, L., Marina Daskalopoulou, Lampe, F., Speakman, A., Gilson, R., Phillips, A., Sherr, L., Wayal, S., Harrison, J., Antinori, A., Maruff, P., Schembri, A., Johnson, M., Collins, S., and Rodger, A.
30. Analysis of high voltage impulse generator circuits
- Author
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Haddow, L. Martin and Haddow, L. Martin
- Abstract
A study is made of transient or oscillatory voltages which arise in an impulse generator of the two-column Marx type during the firing process (i.e. between the breakdown of the first and the last spark-gap and immediately thereafter). These voltages are liable to appear on the external test and measuring equipment, but this aspect is not dealt with, nor are the spark-gap characteristics investigated systematically. The voltages are shown to be relatively independent of the main circuit elements, but to be set up in the stray capacitative and inductive fields in the generator, structure. These fields are resolved into an equivalent circuit involving measurable parameters. A matrix method is developed to analyze its dynamic properties, the solution being given in terms of eigenvalues. It is particularly suited to numerical treatment on a digital computer. The theory is extended, tentatively, to the evaluation of optimum damping resistances. By a second approach, the generator is represented by a one-dimensional lattice circuit. Although an explicit solution is not obtained, some propagation characteristics are determined, enabling comparison to be made with the one-column type of generator (and with such analogous problems as transformer windings). The gaps cannot in general be assumed to fire simultaneously. The transient voltages are of primary importance in causing their successive breakdown, but the instant of breakdown due to an overvoltage cannot be determined from present data. Again, the firing of the gaps constitutes the excitation to the circuit, but it is doubtful whether they behave as ideal switches. These two factors make a complete solution impracticable. The experimental work made use of a four-stage generator. Voltages calculated from measured parameters are compared with oscillographic measurements. Sources of error in the capacitance-divider circuit are investigated and compensation for the connecting leads shown to be desirable.
31. TWIN VOLUME APPARATUS FOR MICRODOSIMETRIC STUDIES.
- Author
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Haddow, L
- Published
- 1972
32. Effects of Sex Hormones on Vascular Reactivity in Boys With Hypospadias.
- Author
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Lucas-Herald AK, Montezano AC, Alves-Lopes R, Haddow L, O'Toole S, Flett M, Lee B, Amjad SB, Steven M, McNeilly J, Brooksbank K, Touyz RM, and Ahmed SF
- Subjects
- Male, Humans, Infant, Nitroprusside pharmacology, Testosterone pharmacology, Estradiol pharmacology, Androgens pharmacology, Dihydrotestosterone pharmacology, Acetylcholine, Hypospadias surgery
- Abstract
Background: Arteries from boys with hypospadias demonstrate hypercontractility and impaired vasorelaxation. The role of sex hormones in these responses in unclear., Aims: We compared effects of sex steroids on vascular reactivity in healthy boys and boys with hypospadias., Methods: Excess foreskin tissue was obtained from 11 boys undergoing hypospadias repair (cases) and 12 undergoing routine circumcision (controls) (median age [range], 1.5 [1.2-2.7] years) and small resistance arteries were isolated. Vessels were mounted on wire myographs and vascular reactivity was assessed in the absence/presence of 17β-estradiol, dihydrotestosterone (DHT), and testosterone., Results: In controls, testosterone and 17β-estradiol increased contraction (percent of maximum contraction [Emax]: 83.74 basal vs 125.4 after testosterone, P < .0002; and 83.74 vs 110.2 after estradiol, P = .02). 17β-estradiol reduced vasorelaxation in arteries from controls (Emax: 10.6 vs 15.6 to acetylcholine, P < .0001; and Emax: 14.6 vs 20.5 to sodium nitroprusside, P < .0001). In hypospadias, testosterone (Emax: 137.9 vs 107.2, P = .01) and 17β-estradiol (Emax: 156.9 vs 23.6, P < .0001) reduced contraction. Androgens, but not 17β-estradiol, increased endothelium-dependent and endothelium-independent vasorelaxation in cases (Emax: 77.3 vs 51.7 with testosterone, P = .02; and vs 48.2 with DHT to acetylcholine, P = .0001; Emax: 43.0 vs 39.5 with testosterone, P = .02; and 39.6 vs 37.5 with DHT to sodium nitroprusside, P = .04)., Conclusion: In healthy boys, testosterone and 17β-estradiol promote a vasoconstrictor phenotype, whereas in boys with hypospadias, these sex hormones reduce vasoconstriction, with androgens promoting vasorelaxation. Differences in baseline artery function may therefore be sex hormone-independent and the impact of early-life variations in androgen exposure on vascular function needs further study., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society.)
- Published
- 2024
- Full Text
- View/download PDF
33. Is scabies an increasing problem in the UK, and how should the UK Health Security Agency and sexual health services respond?
- Author
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Morris GC, Haddow L, and Sashidharan P
- Subjects
- Humans, United Kingdom epidemiology, Health Services, Scabies epidemiology, Scabies prevention & control
- Abstract
Competing Interests: Competing interests: None declared.
- Published
- 2024
- Full Text
- View/download PDF
34. Surveillance of Mpox Cases Attending Sexual Health Services in England (SOMASS): design, implementation and initial findings from the SOMASS data collection tool, 2022.
- Author
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Charles H, Prochazka M, Murray J, Sexual Health Liaison Group U, Soni S, Haddow L, Beets K, Pilkington V, Low N, Candfield S, Jones R, Bleiker T, Dewsnap C, Phillips M, and Phillips D
- Subjects
- Male, Humans, Adult, Homosexuality, Male, England epidemiology, Surveys and Questionnaires, Health Services, Mpox (monkeypox), Sexual and Gender Minorities, Sexually Transmitted Diseases diagnosis, Sexually Transmitted Diseases epidemiology, Sexually Transmitted Diseases prevention & control, HIV Infections diagnosis, HIV Infections epidemiology, HIV Infections prevention & control
- Abstract
Objectives: We aimed to design and implement a data collection tool to support the 2022 mpox (monkeypox) outbreak, and to describe clinical and epidemiological data from individuals with mpox attending sexual health services (SHSs) in England., Methods: The UK Health Security Agency and the British Association for Sexual Health and HIV established the Surveillance of Mpox Cases Attending Sexual Health Services in England (SOMASS) system.Descriptive data were collected via a secure web-based data collection tool, completed by SHS clinicians following consultation with individuals with suspected mpox. Data were collected on patient demographics, clinical presentation and severity, exposures and behavioural characteristics., Results: As of 17 November 2022, 276 SOMASS responses were submitted from 31 SHSs in England.Where recorded, most (245 of 261; 94%) individuals identified as gay, bisexual or men who have sex with men (GBMSM), of whom two-thirds were HIV negative (170 of 257; 66%) and taking HIV pre-exposure prophylaxis (87 of 140; 62%), with a median age of 37 years (IQR: 30-43). Where known, thirty-nine per cent (63 of 161) had a concurrent sexually transmitted infection (STI) at the time of their mpox diagnosis.For 46% of individuals (127 of 276), dermatological lesions were the initial symptom. Lesions were mostly asymmetrical and polymorphic, predominately affecting the genital area and perianal areas.Nine per cent (24 of 276) of individuals were hospitalised. We report an association between receptive anal intercourse among GBMSM and proctitis (27 of 115; 24% vs 7 of 130; 5%; p<0.0001), and the presence of perianal lesions as the primary lesion site (46 of 115; 40% vs 25 of 130; 19%; p=0.0003)., Conclusions: We demonstrate multidisciplinary and responsive working to develop a robust data collection tool, which improved surveillance and strengthened the knowledge base. The SOMASS tool will allow data collection if mpox resurges in England. The model for developing the tool can be adapted to facilitate the preparedness and response to future STI outbreaks., Competing Interests: Competing interests: NL is the Deputy Editor at BMJ Sexually Transmitted Infections., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)
- Published
- 2023
- Full Text
- View/download PDF
35. Association between inflammatory biomarker profiles and cardiovascular risk in individuals with and without HIV.
- Author
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Sukumaran L, Kunisaki KM, Bakewell N, Winston A, Mallon PWG, Doyle N, Anderson J, Boffito M, Haddow L, Post FA, Vera JH, Sachikonye M, and Sabin CA
- Subjects
- Humans, Male, Middle Aged, Female, Risk Factors, Risk Assessment, Heart Disease Risk Factors, Inflammation complications, Biomarkers, Cardiovascular Diseases etiology, HIV Infections complications
- Abstract
Background: People with HIV have an increased risk for cardiovascular morbidity and mortality. Inflammation and immune activation may contribute to this excess risk., Methods: We assessed thirty-one biomarkers in a subset of POPPY participants and identified three distinct inflammatory profiles: 'gut/immune activation', 'neurovascular', and 'reference' (relatively low levels of inflammation). Ten-year cardiovascular disease (CVD) risk predictions were calculated using the QRISK, Framingham Risk Score (FRS) and the Data Collection on Adverse effects of anti-HIV Drugs (D:A:D) algorithms. The distributions of CVD risk scores across the different inflammatory profiles, stratified by HIV status, were compared using median quantile regression., Results: Of the 312 participants included [70% living with HIV, median (interquartile range; IQR) age 55 (51-60) years; 82% male; 91% white], 36, 130, and 146 were in the 'gut/immune activation', 'neurovascular', and 'reference' cluster, respectively. The median (IQR) QRISK scores were 9.3% (4.5-14.5) and 10.2% (5.5-16.9) for people with and without HV, respectively, with similar scores obtained with the FRS and D:A:D. We observed statistically significant differences between the distributions of scores in the three clusters among people with HV. In particular, median QRISK [5.8% (1.0-10.7) and 3.1% (0.3-5.8)] scores were higher, respectively, for those in the 'gut/immune activation' and 'neurovascular' clusters compared to those in the reference cluster., Conclusions: People with HIV with increased gut/immune activation have a higher CVD risk compared to those with relatively low inflammation. Our findings highlight that clinically important inflammatory subgroups could be useful to differentiate risk and maximise prediction of CVD among people with HIV., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc.)
- Published
- 2023
- Full Text
- View/download PDF
36. Alcohol, smoking, recreational drug use and association with virological outcomes among people living with HIV: cross-sectional and longitudinal analyses.
- Author
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Jones TPW, Lampe FC, Arenas-Pinto A, Smith C, McDonnell J, Haddow L, Johnson M, Yousef E, Lascar M, Maria Geretti A, Sherr L, Collins S, Phillips AN, and Rodger AJ
- Subjects
- Cross-Sectional Studies, Female, Homosexuality, Male, Humans, Male, Medication Adherence, Recreational Drug Use, Smoking, Viral Load, Anti-HIV Agents therapeutic use, HIV Infections epidemiology, Sexual and Gender Minorities
- Abstract
Objectives: There is increasing evidence to suggest that people living with HIV (PLWH) have significant morbidity from alcohol, recreational drug use and cigarette smoking. Our aim was to report associations of these factors with antiretroviral therapy (ART) non-adherence, viral non-suppression and subsequent viral rebound in PLWH., Methods: The Antiretroviral Sexual Transmission Risk and Attitudes (ASTRA) study recruited PLWH attending eight outpatient clinics in England between February 2011 and December 2012. Data included self-reported excessive drinking (estimated consumption of > 20 units of alcohol/week), alcohol dependency (CAGE score ≥ 2 with current alcohol consumption), recreational drug use (including injection drug use in the past 3 months), and smoking status. Among participants established on ART, cross-sectional associations with ART non-adherence [missing ≥2 consecutive days of ART on ≥2 occasions in the past three months] and viral-non suppression [viral load (VL) > 50 copies/mL] were assessed using logistic regression. In participants from one centre, longitudinal associations with subsequent viral rebound (first VL > 200 copies/mL) in those on ART with VL ≤ 50 copies/mL at baseline were assessed using Cox regression during a 7-year follow-up., Results: Among 3258 PLWH, 2248 (69.0%) were men who have sex with men, 373 (11.4%) were heterosexual men, and 637 (19.6%) were women. A CAGE score ≥ 2 was found in 568 (17.6%) participants, 325 (10.1%) drank > 20 units/week, 1011 (31.5%) currently smoked, 1242 (38.1%) used recreational drugs and 74 (2.3%) reported injection drug use. In each case, prevalence was much more common among men than among women. Among 2459 people on ART who started at least 6 months previously, a CAGE score ≥ 2, drinking > 20 units per week, current smoking, injection and non-injection drug use were all associated with ART non-adherence. After adjusting for demographic and socioeconomic factors, CAGE score ≥ 2 [adjusted odds ratio (aOR) = 1.52, 95% confidence interval (CI): 1.09-2.13], current smoking (aOR = 1.58, 95% CI: 1.10-2.17) and injection drug use (aOR = 2.11, 95% CI: 1.00-4.47) were associated with viral non-suppression. During follow-up of a subset of 592 people virally suppressed at recruitment, a CAGE score ≥ 2 [adjusted hazard ratio (aHR) = 1.66, 95% CI: 1.03-2.74], use of 3 or more non-injection drugs (aHR = 1.82, 95% CI: 1.12-3.57) and injection drug use (aHR = 2.73, 95% CI: 1.08-6.89) were associated with viral rebound., Conclusions: Screening and treatment for alcohol, cigarette and drug use should be integrated into HIV outpatient clinics, while clinicians should be alert to the potential for poorer virological outcomes., (© 2021 The Authors. HIV Medicine published by John Wiley & Sons Ltd on behalf of British HIV Association.)
- Published
- 2022
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37. Osteoprotegerin regulates vascular function through syndecan-1 and NADPH oxidase-derived reactive oxygen species.
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Alves-Lopes R, Neves KB, Strembitska A, Harvey AP, Harvey KY, Yusuf H, Haniford S, Hepburn RT, Dyet J, Beattie W, Haddow L, McAbney J, Graham D, and Montezano AC
- Subjects
- Animals, Cells, Cultured, Male, Mesenteric Arteries drug effects, Mesenteric Arteries enzymology, Mesenteric Arteries physiopathology, Mice, Inbred C57BL, Muscle, Smooth, Vascular enzymology, Muscle, Smooth, Vascular physiopathology, Myocytes, Smooth Muscle enzymology, NADPH Oxidase 1 genetics, NADPH Oxidase 1 metabolism, NADPH Oxidase 4 genetics, NADPH Oxidase 4 metabolism, NADPH Oxidases genetics, Rats, Inbred WKY, Signal Transduction, Mice, Rats, Hemodynamics drug effects, Muscle, Smooth, Vascular drug effects, Myocytes, Smooth Muscle drug effects, NADPH Oxidases metabolism, Osteoprotegerin toxicity, Oxidative Stress, Reactive Oxygen Species metabolism, Syndecan-1 metabolism
- Abstract
Osteogenic factors, such as osteoprotegerin (OPG), are protective against vascular calcification. However, OPG is also positively associated with cardiovascular damage, particularly in pulmonary hypertension, possibly through processes beyond effects on calcification. In the present study, we focused on calcification-independent vascular effects of OPG through activation of syndecan-1 and NADPH oxidases (Noxs) 1 and 4. Isolated resistance arteries from Wistar-Kyoto (WKY) rats, exposed to exogenous OPG, studied by myography exhibited endothelial and smooth muscle dysfunction. OPG decreased nitric oxide (NO) production, eNOS activation and increased reactive oxygen species (ROS) production in endothelial cells. In VSMCs, OPG increased ROS production, H2O2/peroxynitrite levels and activation of Rho kinase and myosin light chain. OPG vascular and redox effects were also inhibited by the syndecan-1 inhibitor synstatin (SSNT). Additionally, heparinase and chondroitinase abolished OPG effects on VSMCs-ROS production, confirming syndecan-1 as OPG molecular partner and suggesting that OPG binds to heparan/chondroitin sulphate chains of syndecan-1. OPG-induced ROS production was abrogated by NoxA1ds (Nox1 inhibitor) and GKT137831 (dual Nox1/Nox4 inhibitor). Tempol (SOD mimetic) inhibited vascular dysfunction induced by OPG. In addition, we studied arteries from Nox1 and Nox4 knockout (KO) mice. Nox1 and Nox4 KO abrogated OPG-induced vascular dysfunction. Vascular dysfunction elicited by OPG is mediated by a complex signalling cascade involving syndecan-1, Nox1 and Nox4. Our data identify novel molecular mechanisms beyond calcification for OPG, which may underlie vascular injurious effects of osteogenic factors in conditions such as hypertension and/or diabetes., (© 2021 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.)
- Published
- 2021
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38. Correlation between computerised and standard cognitive testing in people with HIV and HIV-negative individuals.
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De Francesco D, Underwood J, Anderson J, Boffito M, Post FA, Sachikonye M, Mallon PWG, Haddow L, Vera JH, Kunisaki KM, Sabin CA, and Winston A
- Subjects
- Cognition, Humans, Neuropsychological Tests, Cognition Disorders diagnosis, Cognitive Dysfunction diagnosis, HIV Infections complications
- Abstract
We investigated the correlations and agreement between cognitive assessments made using a computerised (CogState™, six domains) and a standard pen-and-paper battery (five domains) in PWH and lifestyle-similar HIV-negative individuals. Demographically adjusted domain and global T -scores were obtained and used to define cognitive impairment according to the multivariate normative comparison (MNC) criteria. Correlations between T -scores and the agreement between the classifications of cognitive impairment obtained from the two batteries were assessed using the Spearman's rank correlation and Cohen's κ , respectively. The correlation between global T -scores from the two batteries was 0.52 (95% CI 0.44-0.60) in PWH and 0.45 (0.29-0.59) in controls ( p = 0.38 for their difference). Correlations were generally stronger between domains within the same battery than between those from different batteries. The agreement between the two batteries in classifying individuals as cognitively impaired or not impaired was fair in PWH ( κ = 0.24) and poor in HIV-negative individuals ( κ = -0.02). The moderate correlation between overall cognitive function and the modest agreement between binary classifications of cognitive impairment obtained from two different batteries indicate the two batteries may assess slightly different components of cognition.
- Published
- 2021
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39. Sleep health and cognitive function among people with and without HIV: the use of different machine learning approaches.
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De Francesco D, Sabin CA, Winston A, Rueschman MN, Doyle ND, Anderson J, Vera JH, Boffito M, Sachikonye M, Mallon PWG, Haddow L, Post FA, Redline S, and Kunisaki KM
- Subjects
- Actigraphy, Cognition, Female, Humans, Machine Learning, Male, Middle Aged, HIV Infections complications, Sleep
- Abstract
Study Objectives: We investigated associations between actigraphy-assessed sleep measures and cognitive function in people with and without HIV using different analytical approaches to better understand these associations and highlight differences in results obtained by these approaches., Methods: Cognitive and 7-day/night actigraphy data were collected from people with HIV (PWH) and lifestyle-similar HIV-negative individuals from HIV and sexual health clinics in the United Kingdom/Ireland. A global cognitive T-score was obtained averaging the standardized individual cognitive test scores accounting for sociodemographics. Average and SD of 11 sleep measures over 7 days/nights were obtained. Rank regression, partial least-squares (PLS) regression, random forest, sleep dimension construct, and latent class analysis (LCA) were applied to evaluate associations between global T-scores and sleep measures., Results: In 344 PWH (median age 57 years, 86% males), average sleep duration, efficiency, and wake after sleep onset were not associated with global T-scores according to rank regression (p = 0.51, p = 0.09, p = 0.16, respectively). In contrast, global T-scores were associated with average and SD of length of nocturnal awakenings, SD of maintenance efficiency, and average out-of-bed time when analyzed by PLS regression and random forest. No associations were found when using sleep dimensions or LCA. Overall, findings observed in PWH were similar to those seen in HIV-negative individuals (median age 61 years, 67% males)., Conclusions: Using multivariable analytical approaches, measures of sleep continuity, timing, and regularity were associated with cognitive performance in PWH, supporting the utility of newer methods of incorporating multiple standard and novel measures of sleep-wake patterns in the assessment of health and functioning., (© Sleep Research Society 2021. Published by Oxford University Press on behalf of the Sleep Research Society.)
- Published
- 2021
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40. Osteolytic lesions as the sole presenting feature of secondary syphilis.
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Colquhoun M, Kirresh O, Keikha M, and Haddow L
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- Humans, Male, Middle Aged, Penicillin G therapeutic use, Radiography, Osteolysis, Syphilis complications, Syphilis diagnosis, Syphilis drug therapy
- Abstract
We present the case of a 48-year-old man with a background of well-controlled HIV who presented with bony pain in multiple regions and raised inflammatory markers. After an investigative process, the patient was newly diagnosed with secondary syphilis. Bony pain, secondary to osteolytic lesions and demonstrated on plain radiography, CT and nuclear medicine imaging, was the sole presenting feature. The patient was successfully treated with penicillin G and his symptoms improved. Rheumatologists are often tasked with diagnosing the cause of a patient's pain. However, in this case, a multidisciplinary approach was needed and the contribution of a specialist in Genitourinary Medicine/HIV was required to help diagnose this rare cause of bony pain., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2021. No commercial re-use. See rights and permissions. Published by BMJ.)
- Published
- 2021
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41. Agreement between self-reported and objective measures of sleep in people with HIV and lifestyle-similar HIV-negative individuals.
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De Francesco D, Sabin CA, Winston A, Mallon PWG, Anderson J, Boffito M, Doyle ND, Haddow L, Post FA, Vera JH, Sachikonye M, Redline S, and Kunisaki KM
- Subjects
- Cross-Sectional Studies, Humans, Life Style, Male, Self Report, Sleep, HIV Infections complications
- Abstract
Objectives: The aim of this study was to evaluate the agreement between self-reported sleep measures and insomnia with objectively measured sleep parameters in people with HIV (PWH) and HIV-negative individuals., Design: A cross-sectional analysis of PWH and lifestyle-similar HIV-negative individuals., Methods: Self-reported measures included time spent in bed, sleep onset latency and a validated insomnia questionnaire. Objective measures were assessed via 7-days/nights of actigraphy data to determine average and intra-individual variability of several sleep measures (including time spent in bed and onset latency). Spearman's correlation coefficient and Cohen's κ were used to assess the agreement between self-reported and actigraphy-assessed measures. Associations between insomnia and actigraphy-assessed sleep parameters were evaluated using partial least-square discriminant analysis (PLS-DA)., Results: We found fair correlation between self-reported and actigraphy-assessed time spent in bed in 342 PWH (rs = 0.46) and 119 HIV-negative individuals (rs = 0.48). Among PWH, the correlation did not differ by age, education, depressive symptoms and self-reported insomnia (all P > 0.05), but was stronger in men (P = 0.05) and in those with a BMI of at least 25 kg/m2 (P < 0.001). Agreement between self-reported and actigraphy-assessed sleep onset latency was poor in both PWH (κ = 0.002, P = 0.49) and HIV-negative individuals (κ = 0.009, P = 0.65). According to PLS-DA, self-reported insomnia most strongly correlated with intra-individual variability of sleep duration, movement index and efficiency., Conclusion: We report poor-to-fair agreement between self-reported and actigraphy-assessed sleep measures in PWH. Insomnia symptoms correlated with regularity of sleep duration, quality and efficiency. These findings highlight the importance of both patient-reported and objective measures of daily sleep variation, for better understanding sleep disorders in PWH., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)
- Published
- 2021
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42. Reduced Lymphatic Reserve in Heart Failure With Preserved Ejection Fraction.
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Rossitto G, Mary S, McAllister C, Neves KB, Haddow L, Rocchiccioli JP, Lang NN, Murphy CL, Touyz RM, Petrie MC, and Delles C
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- Aged, Case-Control Studies, Female, Heart Failure metabolism, Humans, Male, Middle Aged, Skin blood supply, Skin metabolism, Sodium metabolism, Stroke Volume, Heart Failure physiopathology, Lymphatic Vessels physiopathology, Microvessels physiopathology
- Abstract
Background: Microvascular dysfunction plays an important role in the pathogenesis of heart failure with preserved ejection fraction (HFpEF). However, no mechanistic link between systemic microvasculature and congestion, a central feature of the syndrome, has yet been investigated., Objectives: This study aimed to investigate capillary-interstitium fluid exchange in HFpEF, including lymphatic drainage and the potential osmotic forces exerted by any hypertonic tissue Na
+ excess., Methods: Patients with HFpEF and healthy control subjects of similar age and sex distributions (n = 16 per group) underwent: 1) a skin biopsy for vascular immunohistochemistry, gene expression, and chemical (water, Na+ , and K+ ) analyses; and 2) venous occlusion plethysmography to assess peripheral microvascular filtration coefficient (measuring capillary fluid extravasation) and isovolumetric pressure (above which lymphatic drainage cannot compensate for fluid extravasation)., Results: Skin biopsies in patients with HFpEF showed rarefaction of small blood and lymphatic vessels (p = 0.003 and p = 0.012, respectively); residual skin lymphatics showed a larger diameter (p = 0.007) and lower expression of lymphatic differentiation and function markers (LYVE-1 [lymphatic vessel endothelial hyaluronan receptor 1]: p < 0.05; PROX-1 [prospero homeobox protein 1]: p < 0.001) compared with control subjects. In patients with HFpEF, microvascular filtration coefficient was lower (calf: 3.30 [interquartile range (IQR): 2.33 to 3.88] l × 100 ml of tissue-1 × min-1 × mm Hg-1 vs. 4.66 [IQR: 3.70 to 6.15] μl × 100 ml of tissue-1 × min-1 × mm Hg-1 ; p < 0.01; forearm: 5.16 [IQR: 3.86 to 5.43] l × 100 ml of tissue-1 × min-1 × mm Hg-1 vs. 5.66 [IQR: 4.69 to 8.38] μl × 100 ml of tissue-1 × min-1 × mm Hg-1 ; p > 0.05), in keeping with blood vascular rarefaction and the lack of any observed hypertonic skin Na+ excess, but the lymphatic drainage was impaired (isovolumetric pressure in patients with HFpEF vs. control subjects: calf 16 ± 4 mm Hg vs. 22 ± 4 mm Hg; p < 0.005; forearm 17 ± 4 mm Hg vs. 25 ± 5 mm Hg; p < 0.001)., Conclusions: Peripheral lymphatic vessels in patients with HFpEF exhibit structural and molecular alterations and cannot effectively compensate for fluid extravasation and interstitial accumulation by commensurate drainage. Reduced lymphatic reserve may represent a novel therapeutic target., Competing Interests: Author Disclosures This study was supported by British Heart Foundation Centre of Research Excellence Awards to Drs. Touyz, Delles, Petrie, and Rossitto (RE/13/5/30177 and RE/18/6/34217+). Dr. Touyz is supported by a British Heart Foundation Chair award (CH/12/29762). The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)- Published
- 2020
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43. Sleep Disorders in Human Immunodeficiency Virus: A Substudy of the Pharmacokinetics and Clinical Observations in People Over Fifty (POPPY) Study.
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Kunisaki KM, De Francesco D, Sabin CA, Winston A, Mallon PWG, Anderson J, Bagkeris E, Boffito M, Doyle N, Haddow L, Post FA, Sachikonye M, Vera J, Khalil W, and Redline S
- Abstract
Background: Self-reported sleep quality is poor in persons with human immunodeficiency virus (PWH), but prior studies commonly used nonspecific questionnaires, investigated only single sleep disorders, or lacked human immunodeficiency virus (HIV)-negative controls. We addressed these limitations in the Pharmacokinetics and Clinical Observations in People Over Fifty (POPPY) Sleep Substudy by assessing PWH and HIV-negative controls for insomnia, restless legs syndrome (RLS), and sleep apnea (SA)., Methods: Previously enrolled POPPY participants coenrolled in this substudy without regard to sleep symptoms. Participants completed validated sleep assessments including the Insomnia Severity Index questionnaire, International Restless Legs Syndrome Study Group questionnaire, and in-home, wrist-worn overnight oximetry. They also completed health-related quality of life questionnaires including 36-item Short Form (SF-36) and Patient-Reported Outcomes Measurement Information System (PROMIS) sleep questionnaires., Results: We enrolled 357 PWH (246 >50 years of age; 111 between 18 and 50 years) and 126 HIV-negative controls >50 years of age. Among PWH, criteria were met by 21% for insomnia, 13% for RLS, and 6% for SA. Compared with HIV-negative controls, PWH had a higher risk of insomnia (adjusted odds ratio, 5.3; 95% confidence interval, 2.2-12.9) but not RLS or SA. Compared with PWH without insomnia, those with insomnia reported significantly worse scores on all SF-36 and PROMIS components; fewer than 30% reported previous diagnosis or treatment for insomnia., Conclusions: Insomnia was more common in PWH, associated with worse health-related quality of life, and frequently undiagnosed. Further research should focus on the pathogenesis of insomnia in PWH and the development of effective screening and intervention strategies for this unique population., (Published by Oxford University Press on behalf of Infectious Diseases Society of America 2020.)
- Published
- 2020
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44. Systemic microvascular dysfunction in microvascular and vasospastic angina.
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Ford TJ, Rocchiccioli P, Good R, McEntegart M, Eteiba H, Watkins S, Shaukat A, Lindsay M, Robertson K, Hood S, Yii E, Sidik N, Harvey A, Montezano AC, Beattie E, Haddow L, Oldroyd KG, Touyz RM, and Berry C
- Subjects
- Coronary Vasospasm diagnosis, Coronary Vessels drug effects, Electrocardiography, Female, Follow-Up Studies, Humans, Male, Microcirculation drug effects, Microcirculation physiology, Microvascular Angina diagnosis, Middle Aged, Nitroprusside pharmacology, Prospective Studies, Vasoconstriction drug effects, Vasodilator Agents pharmacology, Coronary Circulation physiology, Coronary Vasospasm physiopathology, Coronary Vessels physiopathology, Endothelium, Vascular physiopathology, Microvascular Angina physiopathology, Vascular Resistance physiology, Vasoconstriction physiology
- Abstract
Aims: Coronary microvascular dysfunction and/or vasospasm are potential causes of ischaemia in patients with no obstructive coronary artery disease (INOCA). We tested the hypothesis that these patients also have functional abnormalities in peripheral small arteries., Methods and Results: Patients were prospectively enrolled and categorised as having microvascular angina (MVA), vasospastic angina (VSA) or normal control based on invasive coronary artery function tests incorporating probes of endothelial and endothelial-independent function (acetylcholine and adenosine). Gluteal biopsies of subcutaneous fat were performed in 81 subjects (62 years, 69% female, 59 MVA, 11 VSA, and 11 controls). Resistance arteries were dissected enabling study using wire myography. Maximum relaxation to ACh (endothelial function) was reduced in MVA vs. controls [median 77.6 vs. 98.7%; 95% confidence interval (CI) of difference 2.3-38%; P = 0.0047]. Endothelium-independent relaxation [sodium nitroprusside (SNP)] was similar between all groups. The maximum contractile response to endothelin-1 (ET-1) was greater in MVA (median 121%) vs. controls (100%; 95% CI of median difference 4.7-45%, P = 0.015). Response to the thromboxane agonist, U46619, was also greater in MVA (143%) vs. controls (109%; 95% CI of difference 13-57%, P = 0.003). Patients with VSA had similar abnormal patterns of peripheral vascular reactivity including reduced maximum relaxation to ACh (median 79.0% vs. 98.7%; P = 0.03) and increased response to constrictor agonists including ET-1 (median 125% vs. 100%; P = 0.02). In all groups, resistance arteries were ≈50-fold more sensitive to the constrictor effects of ET-1 compared with U46619., Conclusions: Systemic microvascular abnormalities are common in patients with MVA and VSA. These mechanisms may involve ET-1 and were characterized by endothelial dysfunction and enhanced vasoconstriction., Clinical Trial Registration: ClinicalTrials.gov registration is NCT03193294.
- Published
- 2018
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45. HIV Cerebrospinal Fluid Escape and Neurocognitive Pathology in the Era of Combined Antiretroviral Therapy: What Lies Beneath the Tip of the Iceberg in Sub-Saharan Africa?
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Collier DA, Haddow L, Brijkumar J, Moosa MS, Benjamin L, and Gupta RK
- Abstract
Neurocognitive impairment remains an important HIV-associated comorbidity despite combination antiretroviral therapy (ART). Since the advent of ART, the spectrum of HIV-associated neurocognitive disorder (HAND) has shifted from the most severe form to milder forms. Independent replication of HIV in the central nervous system despite ART, so-called cerebrospinal fluid (CSF) escape is now recognised in the context of individuals with a reconstituted immune system. This review describes the global prevalence and clinical spectrum of CSF escape, it role in the pathogenesis of HAND and current advances in the diagnosis and management. It highlights gaps in knowledge in sub-Saharan Africa where the HIV burden is greatest and discusses the implications for this region in the context of the global HIV treatment scale up.
- Published
- 2018
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46. Early screening and treatment of gestational diabetes in high-risk women improves maternal and neonatal outcomes: A retrospective clinical audit.
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Ryan DK, Haddow L, Ramaesh A, Kelly R, Johns EC, Denison FC, Dover AR, and Reynolds RM
- Subjects
- Adult, Female, Humans, Infant, Newborn, Pregnancy, Pregnancy Outcome, Prenatal Care, Retrospective Studies, Risk Factors, Diabetes, Gestational diagnosis, Diabetes, Gestational therapy, Fetal Macrosomia prevention & control, Hypoglycemia prevention & control, Infant, Newborn, Diseases prevention & control, Mass Screening methods, Pregnancy Complications prevention & control
- Abstract
Aims: Evidence suggests that screening for gestational diabetes (GDM) occurs too late in pregnancy, when changes in glucose metabolism and fetal growth rates can already be detected. In August 2016 NHS Lothian began screening women with risk factors for GDM during early pregnancy (11-13 weeks). We hypothesised that an earlier identification and treatment of dysglycaemia would improve pregnancy outcomes compared to previous standard care., Methods: We compared management and outcomes for singleton pregnancies with GDM delivering at Royal Infirmary Edinburgh, UK, diagnosed through routine or early screening from 01/01/2015-31/10/2017 (routine screening n = 335, early screening n = 241)., Results: Early screening increased the proportion of women diagnosed before 24 weeks' gestation (n = 59/335, 17.6% vs n = 103/241, 42.7%, p < 0.001) but did not change the average monthly rate of diagnosis. Early screening increased the median duration of GDM during pregnancy (71 vs 93 days of gestation, p < 0.001) with no significant changes in the pharmacological management. Early screening improved the primary composite outcome (emergency caesarean section, neonatal hypoglycaemia and macrosomia; n = 138/335, 41.2% vs n = 73/241, 30.3%, adjusted Odds Ratio [95% confidence interval] 0.62 [0.43-0.91]., Conclusions: There is a role for early screening and management of GDM however it is unclear whether this represents a cost-effective intervention., (Copyright © 2018 Elsevier B.V. All rights reserved.)
- Published
- 2018
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47. Measurement of Retinal Vessels as a Biomarker of Cerebrovascular Aging in Older HIV-Positive Men Compared With Controls.
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Haddow L, Laverick R, Leung I, Post F, Vera J, Gilson R, Williams I, Boffito M, Sabin C, Winston A, and Peto T
- Subjects
- Aged, Cross-Sectional Studies, Fundus Oculi, Humans, Male, Middle Aged, Ophthalmoscopy, White People, Aging pathology, Biomarkers analysis, HIV Infections pathology, Retinal Vessels pathology
- Abstract
Background: To compare retinal vascular measurements, biomarkers of cerebral small vessel disease, in HIV-positive men aged 50 years and older with similarly aged HIV-negative men and younger HIV-positive men., Methods: We recruited white, nondiabetic men into a cross-sectional substudy of a larger cohort including 3 demographically matched groups. Optic disc-centered 45-degree color fundus photographs were used to calculate central retinal arterial and venous caliber and the arterial-venous ratio (AVR). We used univariate and multivariable linear regression to compare retinal vessel measurements in the 3 groups and to identify factors associated with AVR., Results: All HIV-positive men were virologically suppressed. In a multivariable model, study group was not associated with AVR [adjusted β 0.010 for HIV-positive men <50 (n = 39) compared with HIV-positive men aged ≥50 years (n = 120), 95% confidence interval [CI] -0.018 to 0.038, P = 0.47; adjusted β 0.00002 for HIV-negative men ≥50 years (n = 52), 95% CI -0.022 to 0.022, P = 0.99]. Factors associated with lower AVR were systolic blood pressure (adjusted β -0.009 per +10 mm Hg, 95% CI -0.015 to -0.003, P = 0.002), history of stroke or transient ischemic attack (adjusted β -0.070, 95% CI -0.12 to -0.015, P = 0.01), and recent recreational drug use (adjusted β -0.037, 95% CI -0.057 to -0.018, P = 0.0002)., Conclusions: There were no differences in retinal vascular indices between HIV-positive men aged ≥50 years and HIV-negative men aged ≥50 years or HIV-positive men aged <50 years, suggesting that HIV is not associated with an increased burden of cerebral small vessel disease.
- Published
- 2018
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48. Self-Reported Decline in Everyday Function, Cognitive Symptoms, and Cognitive Function in People With HIV.
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Laverick R, Haddow L, Daskalopoulou M, Lampe F, Gilson R, Speakman A, Antinori A, Bruun T, Vassilenko A, Collins S, and Rodger A
- Subjects
- Adult, Female, HIV Infections complications, Humans, Male, Middle Aged, Neuropsychological Tests, Regression Analysis, Risk Factors, Activities of Daily Living, Cognition physiology, Cognition Disorders etiology, HIV Infections physiopathology
- Abstract
Background: We determined factors associated with self-reported decline in activities of daily living (ADLs) and symptoms of cognitive impairment in HIV positive adults in 5 European clinics., Methods: HIV+ adults underwent computerized and pen-and-paper neuropsychological tests and questionnaires of cognitive symptoms and ADLs. We considered cognitive function in 5 domains, psychosocial factors, and clinical parameters as potentially associated with symptoms. Separate regression analyses were used to determine factors associated with a decline in ADL (defined as self-reported decline affecting ≥2 ADLs and attributed to cognitive difficulties) and self-reported frequency of symptoms of cognitive impairment. We also estimated the diagnostic accuracy of both questionnaires as tests for cognitive impairment., Results: Four hundred forty-eight patients completed the assessments [mean age 45.8 years, 84% male, 87% white, median CD4 count 550 cells/mm, median time since HIV diagnosis 9.9 years, 81% virologically suppressed (HIV-1 plasma RNA <50 copies/mL)]. Ninety-six (21.4%) reported decline in ADLs and attributed this to cognitive difficulties. Self-reported decline in ADLs and increased symptoms of cognitive impairment were both associated with worse performance on some cognitive tests. There were also strong associations with financial difficulties, depressive and anxiety symptoms, unemployment, and longer time since HIV diagnosis. Both questionnaires performed poorly as diagnostic tests for cognitive impairment., Conclusions: Patients' own assessments of everyday function and symptoms were associated with objectively measured cognitive function. However, there were strong associations with other psychosocial issues including mood and anxiety disorders and socioeconomic hardship. This should be considered when assessing HIV-associated cognitive impairment in clinical care or research studies.
- Published
- 2017
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49. Admissions for antibiotic-resistant infections in cancer patients during first year of cancer diagnosis: a cross-sectional study.
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Slavova-Azmanova N, Haddow L, Hohnen H, Coombs G, Robinson JO, and Ives A
- Subjects
- Aged, Aged, 80 and over, Anti-Bacterial Agents pharmacology, Anti-Bacterial Agents therapeutic use, Bacterial Infections drug therapy, Cross-Sectional Studies, Drug Resistance, Bacterial physiology, Female, Humans, Male, Middle Aged, Time Factors, Western Australia epidemiology, Bacterial Infections diagnosis, Bacterial Infections epidemiology, Drug Resistance, Bacterial drug effects, Neoplasms diagnosis, Neoplasms epidemiology, Patient Admission trends
- Abstract
In this study, linked Western Australian health data were used to determine presence of an antibiotic-resistant infection (ABRI) for all people diagnosed with a primary invasive cancer in 2009. Of 10 858 cancer cases, 154 (1.42%) had an ABRI. Patients with an ABRI were older (71.5 vs 66 years), and more had died in the year following diagnosis (37.7 vs 20.2%, P < 0.001). The ABRI cohort had a higher proportion of colorectal, genitourinary and haematological cancers (19.5 vs 11.9%; 14.3 vs 9.7% and 16.9 vs 5.8%, respectively). Hospital admissions with an ABRI were longer (22.3 vs 2.9 days, P < 0.001) and had a higher proportion of unplanned admissions (60.3 vs 15.2%), admissions through emergency department (36.8 vs 8.3%) and intensive care admissions (14.9 vs 1.7%, P < 0.001). Patients with solid tumours who developed an ABRI were more likely to have received chemotherapy (35.9 vs 27.8%, P = 0.04). In haematological cancer patients, a greater proportion of the admissions with an ABRI occurred after radiation therapy or chemotherapy (P = 0.01 and P = 0.005, respectively). This study is the first to report population-level data on ABRI in cancer patients. Patients with an ABRI had more hospital admissions and poorer outcomes., (© 2017 Royal Australasian College of Physicians.)
- Published
- 2017
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50. If you needed an organ transplant would you have one? The effect of reciprocity priming and mode of delivery on organ donor registration intentions and behaviour.
- Author
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O'Carroll RE, Haddow L, Foley L, and Quigley J
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- Adolescent, Adult, Aged, Altruism, Female, Humans, Male, Middle Aged, Surveys and Questionnaires, United Kingdom, Young Adult, Cues, Intention, Registries statistics & numerical data, Tissue Donors psychology, Tissue and Organ Procurement statistics & numerical data, Transplants
- Abstract
Objective: There are approximately 6,500 people on the UK national transplant waiting list, around 400 of whom die every year. Only 35% of the UK population are currently on the organ donation register. We report two studies examining whether a reciprocity prime, in which participants were asked whether they would accept a donated organ, increased organ donation intentions and behaviour., Design: Between-participants, randomized controlled design., Methods: In two studies, participants who were not currently registered organ donors took part either face-to-face or online and were randomly allocated to a reciprocity prime or control condition. Following the manipulation, they were asked to indicate, on either a paper or online questionnaire, their intention to join the organ donor register. Study 2 was similar to Study 1 but with the addition that after reporting intention, participants were then offered an organ donation information leaflet or the opportunity to click a link for further information (proxy behavioural measure)., Results: In both studies, reciprocity primed participants reported greater intentions to register than controls. However, in Study 2, no effect on donation behaviour was found., Conclusions: Reciprocal altruism may be a useful tool in increasing intentions to join the organ donor register. Further evaluation is required to determine whether this increase in intention can be translated into organ donation behaviour. Statement of contribution What was already known? Demand for organs in the United Kingdom far outstrips supply, so finding strategies to increase registration on the organ donor register could save hundreds of lives per year. Despite the majority of people in the United Kingdom agreeing that organ donation is a good thing, most people do not register as donors. A limited amount of evidence of the impact of perceived reciprocity suggests that encouraging people to consider themselves as recipients and priming ideas of shared responsibility may increase the likelihood of their subsequent willingness to register. What does this study add? Novel evidence that employing a simple reciprocity prime increases organ donor registration intentions. Replication of findings across two separate studies. Novel examination of the impact of mode of delivery of messages to encourage organ donation. A basis for further research into the translation of intentions into organ donor registration behaviour., (© 2017 The British Psychological Society.)
- Published
- 2017
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