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1. Validation of a Novel Multivariate Method of Defining HIV-Associated Cognitive Impairment

Author

Underwood, Jonathan, De Francesco, Davide, Cole, James H, Caan, Matthan W A, van Zoest, Rosan A, Schmand, Ben A, Sharp, David J, Sabin, Caroline A, Reiss, Peter, Winston, Alan Coolaboratori: Reiss P, Wit FWNM, Schouten J, Kooij KW, van Zoest RA, Elsenga BC, Janssen FR, Heidenrijk M, Zikkenheiner W, van der Valk M, Kootstra NA, Harskamp-Holwerda AM, Maurer I, Mangas Ruiz MM, Girigorie AF, Villaudy J, Frankin E, Pasternak A, Berkhout B, van der Kuyl T, Portegies P, Schmand BA, Geurtsen GJ, Ter Stege JA, Klein Twennaar M, Majoie CBLM, Caan MWA, Su T, Weijer K, Bisschop PHLT, Kalsbeek A, Wezel M, Visser I, Ruhé HG, Franceschi C, Garagnani P, Pirazzini C, Capri M, Dall'Olio F, Chiricolo M, Salvioli S, Hoeijmakers J, Pothof J, Prins M, Martens M, Moll S, Berkel J, Totté M, Kovalev S, Gisslén M, Fuchs D, Zetterberg H, Winston A, Underwood J, McDonald L, Stott M, Legg K, Lovell A, Erlwein O, Doyle N, Kingsley C, Sharp DJ, Leech R, Cole JH, Zaheri S, Hillebregt MMJ, Ruijs YMC, Benschop DP, Burger D, de Graaff-Teulen M, Guaraldi G, Bürkle A, Sindlinger T, Moreno-Villanueva M, Keller A, Sabin C, de Francesco D, Libert C, Dewaele S, Boffito M, Mallon P, Post F, Sachikonye M, Anderson J, Asboe D, Garvey L, Pozniak A, Vera J, Williams I, Campbell L, Yurdakul S, Okumu S, Pollard L, Otiko D, Phillips L, Laverick R, Fisher M, Clarke A, Bexley A, Richardson C, Macken A, Ghavani-Kia B, Maher J, Byrne M, Flaherty A, Mguni S, Clark R, Nevin-Dolan R, Pelluri S, Johnson M, Ngwu N, Hemat N, Jones M, Carroll A, Whitehouse A, Burgess L, Babalis D, Higgs C, Seah E, Fletcher S, Anthonipillai M, Moyes A, Deats K, Syed I, Matthews C., Underwood, Jonathan, De Francesco, Davide, Cole, James H, Caan, Matthan W A, van Zoest, Rosan A, Schmand, Ben A, Sharp, David J, Sabin, Caroline A, Reiss, Peter, Winston, Alan Coolaboratori: Reiss P, Wit FWNM, Schouten J, Kooij KW, van Zoest RA, Elsenga BC, Janssen FR, Heidenrijk M, Zikkenheiner W, van der Valk M, Kootstra NA, Harskamp-Holwerda AM, Maurer I, Mangas Ruiz MM, Girigorie AF, Villaudy J, Frankin E, Pasternak A, Berkhout B, van der Kuyl T, Portegies P, Schmand BA, Geurtsen GJ, Ter Stege JA, Klein Twennaar M, Majoie CBLM, Caan MWA, Su T, Weijer K, Bisschop PHLT, Kalsbeek A, Wezel M, Visser I, Ruhé HG, Franceschi C, Garagnani P, Pirazzini C, Capri M, Dall'Olio F, Chiricolo M, Salvioli S, Hoeijmakers J, Pothof J, Prins M, Martens M, Moll S, Berkel J, Totté M, Kovalev S, Gisslén M, Fuchs D, Zetterberg H, Winston A, Underwood J, McDonald L, Stott M, Legg K, Lovell A, Erlwein O, Doyle N, Kingsley C, Sharp DJ, Leech R, Cole JH, Zaheri S, Hillebregt MMJ, Ruijs YMC, Benschop DP, Burger D, de Graaff-Teulen M, Guaraldi G, Bürkle A, Sindlinger T, Moreno-Villanueva M, Keller A, Sabin C, de Francesco D, Libert C, Dewaele S, Boffito M, Mallon P, Post F, Sabin C, Sachikonye M, Winston A, Anderson J, Asboe D, Boffito M, Garvey L, Mallon P, Post F, Pozniak A, Sabin C, Sachikonye M, Vera J, Williams I, Winston A, Post F, Campbell L, Yurdakul S, Okumu S, Pollard L, Williams I, Otiko D, Phillips L, Laverick R, Fisher M, Clarke A, Vera J, Bexley A, Richardson C, Mallon P, Macken A, Ghavani-Kia B, Maher J, Byrne M, Flaherty A, Anderson J, Mguni S, Clark R, Nevin-Dolan R, Pelluri S, Johnson M, Ngwu N, Hemat N, Jones M, Carroll A, Whitehouse A, Burgess L, Babalis D, Winston A, Garvey L, Underwood J, Stott M, McDonald L, Boffito M, Asboe D, Pozniak A, Higgs C, Seah E, Fletcher S, Anthonipillai M, Moyes A, Deats K, Syed I, Matthews C., Molecular Genetics, Biomedical Engineering and Physics, Radiology and Nuclear Medicine, ACS - Atherosclerosis & ischemic syndromes, ACS - Diabetes & metabolism, ACS - Microcirculation, AMS - Restoration & Development, Amsterdam Neuroscience - Brain Imaging, Amsterdam Neuroscience - Neurovascular Disorders, Graduate School, AII - Infectious diseases, APH - Aging & Later Life, Medical Psychology, Amsterdam Neuroscience - Neurodegeneration, Global Health, Infectious diseases, APH - Mental Health, APH - Methodology, Commission of the European Communities, Imperial College Healthcare NHS Trust- BRC Funding, and National Institute for Health Research

Subjects
Multivariate statistics, medicine.medical_specialty, COmorBidity in Relation to AIDS (COBRA) Collaboration and the Pharmacokinetic and clinical Observations in PePle over fiftY (POPPY) Study Group, Immunology, Human immunodeficiency virus (HIV), Audiology, medicine.disease_cause, Microbiology, 03 medical and health sciences, 0302 clinical medicine, multivariate, SDG 3 - Good Health and Well-being, Neuroimaging, Medicine and Health Sciences, medicine, Major Article, OLDER-PEOPLE, 030212 general & internal medicine, VALIDITY, Cognitive impairment, cognitive impairment, Science & Technology, neuroimaging, SCORES, business.industry, Biology and Life Sciences, HIV, MEN, Cognition, Mental health, White matter microstructure, PREVALENCE, 3. Good health, Infectious Diseases, Oncology, REGISTRATION, business, Life Sciences & Biomedicine, Neurocognitive, 030217 neurology & neurosurgery
Abstract

Background The optimum method of defining cognitive impairment in virally suppressed people living with HIV is unknown. We evaluated the relationships between cognitive impairment, including using a novel multivariate method (NMM), patient– reported outcome measures (PROMs), and neuroimaging markers of brain structure across 3 cohorts. Methods Differences in the prevalence of cognitive impairment, PROMs, and neuroimaging data from the COBRA, CHARTER, and POPPY cohorts (total n = 908) were determined between HIV-positive participants with and without cognitive impairment defined using the HIV-associated neurocognitive disorders (HAND), global deficit score (GDS), and NMM criteria. Results The prevalence of cognitive impairment varied by up to 27% between methods used to define impairment (eg, 48% for HAND vs 21% for NMM in the CHARTER study). Associations between objective cognitive impairment and subjective cognitive complaints generally were weak. Physical and mental health summary scores (SF-36) were lowest for NMM-defined impairment (P < .05). There were no differences in brain volumes or cortical thickness between participants with and without cognitive impairment defined using the HAND and GDS measures. In contrast, those identified with cognitive impairment by the NMM had reduced mean cortical thickness in both hemispheres (P < .05), as well as smaller brain volumes (P < .01). The associations with measures of white matter microstructure and brain-predicted age generally were weaker. Conclusion Different methods of defining cognitive impairment identify different people with varying symptomatology and measures of brain injury. Overall, NMM-defined impairment was associated with most neuroimaging abnormalities and poorer self-reported health status. This may be due to the statistical advantage of using a multivariate approach., We have previously described a novel multivariate method (NMM) with theoretical statistical advantages over existing methods, which we assessed here in 3 cohorts of people living with HIV. Overall, NMM-defined impairment was associated with most neuroimaging abnormalities and poorer self-reported health status.

Published
2019

2. Validation of a Novel Multivariate Method of Defining HIV-Associated Cognitive Impairment

Author

Underwood, J, de Francesco, D, Cole, JH, Caan, MWA, van Zoest, RA, Schmand, BA, Sharp, DJ, Sabin, CA, Reiss, P, Winston, A, Wit, FWNM, Schouten, J, Kooij, KW, Elsenga, BC, Janssen, FR, Heidenrijk, M, Zikkenheiner, W, van der Valk, M, Kootstra, NA, Harskamp-Holwerda, AM, Maurer, I, Ruiz, MMM, Girigorie, AF, Villaudy, J, Frankin, E, Pasternak, A, Berkhout, B, van der Kuyl, T, Portegies, P, Geurtsen, GJ, ter Stege, JA, Twennaar, MK, Majoie, CBLM, Su, T, Weijer, K, Bisschop, PHLT, Kalsbeek, A, Wezel, M, Visser, I, Ruhe, HG, Franceschi, C, Garagnani, P, Pirazzini, C, Capri, M, Dall'Olio, F, Chiricolo, M, Salvioli, S, Hoeijmakers, J, Pothof, J, Prins, M, Martens, M, Moll, S, Berkel, J, Totte, M, Kovalev, S, Gisslen, M, Fuchs, D, Zetterberg, H, McDonald, L, Stott, M, Legg, K, Lovell, A, Erlwein, O, Doyle, N, Kingsley, C, Leech, R, Zaheri, S, Hillebregt, MMJ, Ruijs, YMC, Benschop, DP, Burger, D, de Graaff-Teulen, M, Guaraldi, G, Buerkle, A, Sindlinger, T, Moreno-Villanueva, M, Keller, A, Sabin, C, Libert, C, Dewaele, S, Boffito, M, Mallon, P, Post, F, Sachikonye, M, Anderson, J, Asboe, D, Garvey, L, Pozniak, A, Vera, J, Williams, I, Campbell, L, Yurdakul, S, Okumu, S, Pollard, L, Otiko, D, Phillips, L, Laverick, R, Fisher, M, Clarke, A, Bexley, A, Richardson, C, Macken, A, Ghavani-Kia, B, Maher, J, Byrne, M, Flaherty, A, Mguni, S, Clark, R, Nevin-Dolan, R, Pelluri, S, Johnson, M, Ngwu, N, Hemat, N, Jones, M, Carroll, A, Whitehouse, A, Burgess, L, Babalis, D, Higgs, C, Seah, E, Fletcher, S, Anthonipillai, M, Moyes, A, Deats, K, Syed, I, Matthews, C, Underwood, J, de Francesco, D, Cole, JH, Caan, MWA, van Zoest, RA, Schmand, BA, Sharp, DJ, Sabin, CA, Reiss, P, Winston, A, Wit, FWNM, Schouten, J, Kooij, KW, Elsenga, BC, Janssen, FR, Heidenrijk, M, Zikkenheiner, W, van der Valk, M, Kootstra, NA, Harskamp-Holwerda, AM, Maurer, I, Ruiz, MMM, Girigorie, AF, Villaudy, J, Frankin, E, Pasternak, A, Berkhout, B, van der Kuyl, T, Portegies, P, Geurtsen, GJ, ter Stege, JA, Twennaar, MK, Majoie, CBLM, Su, T, Weijer, K, Bisschop, PHLT, Kalsbeek, A, Wezel, M, Visser, I, Ruhe, HG, Franceschi, C, Garagnani, P, Pirazzini, C, Capri, M, Dall'Olio, F, Chiricolo, M, Salvioli, S, Hoeijmakers, J, Pothof, J, Prins, M, Martens, M, Moll, S, Berkel, J, Totte, M, Kovalev, S, Gisslen, M, Fuchs, D, Zetterberg, H, McDonald, L, Stott, M, Legg, K, Lovell, A, Erlwein, O, Doyle, N, Kingsley, C, Leech, R, Zaheri, S, Hillebregt, MMJ, Ruijs, YMC, Benschop, DP, Burger, D, de Graaff-Teulen, M, Guaraldi, G, Buerkle, A, Sindlinger, T, Moreno-Villanueva, M, Keller, A, Sabin, C, Libert, C, Dewaele, S, Boffito, M, Mallon, P, Post, F, Sachikonye, M, Anderson, J, Asboe, D, Garvey, L, Pozniak, A, Vera, J, Williams, I, Campbell, L, Yurdakul, S, Okumu, S, Pollard, L, Otiko, D, Phillips, L, Laverick, R, Fisher, M, Clarke, A, Bexley, A, Richardson, C, Macken, A, Ghavani-Kia, B, Maher, J, Byrne, M, Flaherty, A, Mguni, S, Clark, R, Nevin-Dolan, R, Pelluri, S, Johnson, M, Ngwu, N, Hemat, N, Jones, M, Carroll, A, Whitehouse, A, Burgess, L, Babalis, D, Higgs, C, Seah, E, Fletcher, S, Anthonipillai, M, Moyes, A, Deats, K, Syed, I, and Matthews, C

Abstract

BACKGROUND: The optimum method of defining cognitive impairment in virally suppressed people living with HIV is unknown. We evaluated the relationships between cognitive impairment, including using a novel multivariate method (NMM), patient- reported outcome measures (PROMs), and neuroimaging markers of brain structure across 3 cohorts. METHODS: Differences in the prevalence of cognitive impairment, PROMs, and neuroimaging data from the COBRA, CHARTER, and POPPY cohorts (total n = 908) were determined between HIV-positive participants with and without cognitive impairment defined using the HIV-associated neurocognitive disorders (HAND), global deficit score (GDS), and NMM criteria. RESULTS: The prevalence of cognitive impairment varied by up to 27% between methods used to define impairment (eg, 48% for HAND vs 21% for NMM in the CHARTER study). Associations between objective cognitive impairment and subjective cognitive complaints generally were weak. Physical and mental health summary scores (SF-36) were lowest for NMM-defined impairment ( P < .05).There were no differences in brain volumes or cortical thickness between participants with and without cognitive impairment defined using the HAND and GDS measures. In contrast, those identified with cognitive impairment by the NMM had reduced mean cortical thickness in both hemispheres ( P < .05), as well as smaller brain volumes ( P < .01). The associations with measures of white matter microstructure and brain-predicted age generally were weaker. CONCLUSION: Different methods of defining cognitive impairment identify different people with varying symptomatology and measures of brain injury. Overall, NMM-defined impairment was associated with most neuroimaging abnormalities and poorer self-reported health status. This may be due to the statistical advantage of using a multivariate approach.

Published
2019

4. The Influence of Land Based Activities on the Phytoplankton Communities of Shimoni-Vanga system, Kenya.

Author

Kiteresi, L. I., Okuku, E. O., Mwangi, S. N., Ohowa, B., Wanjeri, V. O., Okumu, S., and Mkono, M.

Abstract

Phytoplankton communities play a significant role in the oceanic biological pump by forming the base of the trophic structure. Increase in nutrients loading affects spatial and temporal distribution of phytoplankton. This study examined the phytoplankton community structure and ecological indices in relation to nutrients dynamics in both estuarine and oceanic areas of Ramisi-Vanga systems along the Kenyan coast. Surface water samples were collected and analysed for nutrients (PO4 3--P, NO3-N) and phytoplankton abundance and community structure. This study reported very diverse phytoplankton community structure consisting of 88 taxa that were dominated by Chaetoceros sp., Coscinodiscus sp., Nitzschia sp., Pseudo-nitzschia sp., Alexandrium sp., Protoperidium sp. and Prorocentrum sp that are among the potentially harmful algae. Diatoms were the most abundant taxa in Ramisi-Vanga system. Phytoplankton abundance was found to be higher in the estuarine systems (1182.06±149.14 cells/L) as compared to the oceanic systems (551.99±166.70 cells/L) with high abundance observed in May for oceanic and estuarine systems. Shannon Weiner's species diversity index was greater than 2 in both oceanic and estuarine systems. Phytoplankton species' abundance, composition and diversity were found to be influenced by the availability of NH--N and NH4 +-N) and phytoplankton abundance and community structure. This study reported very diverse phytoplankton community structure consisting of 88 taxa that were dominated by Chaetoceros sp., Coscinodiscus sp., Nitzschia sp., Pseudo-nitzschia sp., Alexandrium sp., Protoperidium sp. and Prorocentrum sp that are among the potentially harmful algae. Diatoms were the most abundant taxa in Ramisi-Vanga system. Phytoplankton abundance was found to be higher in the estuarine systems (1182.06±149.14 cells/L) as compared to the oceanic systems (551.99±166.70 cells/L) with high abundance observed in May for oceanic and estuarine systems. Shannon Weiner's species diversity index was greater than 2 in both oceanic and estuarine systems. Phytoplankton species' abundance, composition and diversity were found to be influenced by the availability of NH4 +-N, NO3 --N and PO4 3--P. Phytoplankton cell density was below 4000 cells/ L, thus, this study has classified Ramisi-Vanga system as an oligotrophic system implying that the current level of land based activities are not having significant impacts on the phytoplankton communities. [ABSTRACT FROM AUTHOR]

Published
2012

5. Sewage pollution in the Coastal waters of Mombasa City, Kenya: A norm Rather than an Exception.

Author

Okuku, E.O., Ohowa, B., Mwangi, S. N., Munga, D., Kiteresi, L.I., Wanjeri, V.O., Okumu, S., and Kilonzo, J.

Abstract

This study investigated the effects of sewage discharge on nutrient concentrations and BOD5 levels in the coastal waters and sediments ofthe City of Mombasa. The results indicated that nutrient concentrations in Tudor, Mtwapa and Makupa Creeks were elevated as compared to concentrations in Gazi Creek (mean ranges of 0.022-0.039mg/L, 0.038-0.163mg/L and 0.034-0.118mg/Lphosphates, nitrates and ammonium respectively). Sediments were found to harbour relatively higher concentrations of nutrients than water compartment (mean ranges of 0.217-1.131mg/L, 0.199-0.603mg/L and 9.394-26.73mg/L for phosphates, nitrates and ammonium respectively) thus serving as a reservoir and potential source if sediments are resuspended during heavy storms or dredging. Based on Chl-a levels, Makupa Creek could be classified as eutrophic whereas Mtwapa and Tudor Creeks could be placed at the upper limit of higher mesotrophy while Gazi Creekcould be considered as an oligotrophic system. Of the three impacted Creeks, Tudor was found to be the most polluted. [ABSTRACT FROM AUTHOR]

Published
2011

6. Comparison of intravenous methylprednisolone therapy vs. oral methylprednisolone therapy in patients with Graves’ ophthalmopathy.

Author

Aktaran, Ş., Akarsu, E., Erbağci, İ., Araz, M., Okumu, S., and Kartal, M.

Abstract

A prospective, randomised and single blind clinical trial was designed to compare intravenous methylprednisolone pulse (IVGC) with oral methylprednisolone (OGC) monotherapy in terms of effectiveness and tolerability in Graves’ ophthalmopathy (GO). Fifty-two consecutive patients with untreated, moderately severe and active GO were randomly treated with either IVGC or OGC therapy for 12 weeks. IVGC therapy achieved a more rapid and significant improvement than OGC therapy according to clinical activity score (p < 0.01), proptosis (p < 0.038), lid width (p < 0.0001), extraocular muscle changes (p < 0.02), optic neuropathy. (p < 0.001), intraocular pressure (p < 0.04), visual acuity (p < 0.03), quality of life (p < 0.0001) and treatment response (p < 0.001). Diplopia was significantly improved in two groups but there was no difference between them (p < 0.6). Heavy smokers indicated alteration of ophthalmic signs with increased thyroid stimulating hormone (TSH)-receptor antibody during the therapy. In conclusion, IVGC therapy was more effective and better tolerated than OGC therapy in the management of GO. [ABSTRACT FROM AUTHOR]

Published
2007
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7. Many Cooks in the Kitchen: Iterating a Qualitative Analysis Process Across Multiple Countries, Sites, and Teams.

Author

Suchman L, Gitome S, Nyando M, Kwena ZA, Wekesa P, Okumu S, Ndunyu L, Okoli C, Tijani A, Jegede A, Idiodi I, Nmadu G, Dimowo S, Maluwa A, Atuyambe L, Birabwa C, Alitubeera P, Kaudha B, Kayego A, Jumbe T, Mtalimanja I, Vallin J, Sinha E, Phillips BS, Amongin D, Bukusi E, Holt K, Kamanga M, Liu J, Malata A, Omoluabi E, and Waiswa P

Subjects
Humans, Female, Uganda, Kenya, Malawi, Learning, Research Personnel
Abstract

Establishing and proving methodological rigor has long been a challenge for qualitative researchers where quantitative methods prevail, but much published literature on qualitative analysis assumes a relatively small number of researchers working in relative proximity. This is particularly true for research conducted with a grounded theory approach. Different versions of grounded theory are commonly used, but this methodology was originally developed for a single researcher collecting and analyzing data in isolation. Although grounded theory has evolved since its development, little has been done to reconcile this approach with the changing nature and composition of international research teams. Advances in technology and an increased emphasis on transnational collaboration have facilitated a shift wherein qualitative datasets have been getting larger and the teams collecting and analyzing them more diverse and diffuse. New processes and systems are therefore required to respond to these conditions. Data for this article are drawn from the experiences of the Innovations for Choice and Autonomy (ICAN) Research Consortium. ICAN aims to understand how self-injectable contraceptives can be implemented in ways that best meet women's needs in Kenya, Uganda, Malawi, and Nigeria. We found that taking a structured approach to analysis was important for maintaining consistency and making the process more manageable across countries. However, it was equally important to allow for flexibility within this structured approach so that teams could adapt more easily to local conditions, making data collection and accompanying analysis more feasible. Meaningfully including all interested researchers in the analysis process and providing support for learning also increased rigor. However, competing priorities in a complex study made it difficult to adhere to planned timelines. We conclude with recommendations for both funders and study teams to design and conduct global health studies that ensure more equitable contributions to analysis while remaining logistically feasible and methodologically sound., (© Suchman et al.)

Published
2023
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