13 research outputs found
Lupus anticoagulant in human immunodeficiency virus -infected patients on highly active antiretroviral therapy
Background: Lupus anticoagulant (LA) is a heterogeneous group of antibodies that causes a variety of clinical and laboratory effects; has been described in infections such as human immunodeficiency virus. LA has not been previously described in Nigerians with human immunodeficiency virus infection on highly active antiretroviral therapy (HAART). Aim: To determine the frequency of LA in patients infected with the human immunodeficiency virus on HAART. Methods: Cross sectional study of patients with human immunodeficiency virus infection undergoing HAART at a tertiary hospital in Nigeria. Screening for LA was done using the activated partial thromboplastin time (aPTT) and kaolin clotting time (KCT). Mixing experiments were conducted on samples with prolonged clotting time. KCT ratio was calculated. A positive result was taken as KCT ratio greater than or equal to 1.2. Fisher′s exact test was used to test the association between LA and sex. Association between aPTT and KCT was tested according to Pearson. P-value < 0.05 was considered significant. Results: Fifty-eight patients aged 18- 60 years were studied, comprising of 28 males (mean age 40.50 plus/minus 8.8 years) and 30 females (mean age 35.4 plus/minus 9.02). Frequency of LA among human immunodeficiency infected patients was 5.2%, (frequency in males and females were 3.6 and 6.7 % respectively). This was lower than 46% reported in patients not on HAART. There was no statistically significant difference in LA prevalence between males and females P greater than0.05. A positive correlation was observed between the clotting tests aPTT and KCT (r is equal to 0.9406, p less than 0.0001). Conclusion: HAART may prevent development of LA in HIV-infected patients
Hydroxyurea therapy in adult Nigerian sickle cell disease: a monocentric survey on pattern of use, clinical effects and patient’s compliance
Hydroxyurea therapy in adult Nigerian sickle cell disease: a monocentric survey on pattern of use, clinical effects and patient’s compliance
Background: The clinical prospects of hydroxyurea therapy in the management of sickle cell disease (SCD) require evaluation in the Nigerian setting to develop indigenous guidelines. This survey examines the pattern of hydroxyurea therapy, its clinico-haematologic benefits and safety profile in Nigerian SCD subjects.Methods: A cross sectional pilot survey was carried out among 60 adult SCD subjects over 3 months. Data on clinical phenotypes, relevant haematological parameters and details of hydroxyurea therapy were obtained using a structured questionnaire through an interview process and case file review.Results: The median age was 30 years. Thirty-four (56.7%) of the subjects are aware of hydroxyurea therapy in SCD. Twenty-four (40%) SCD patients had previously used hydroxyurea. Only 4 subjects were fully compliant. Reasons for non-complianceincluded poor knowledge and lack of funds. In particular, hydroxyurea reduced leucocyte count and increased mean red cell volume (MCV) in compliant subjects.Conclusion: Hydroxyurea use is low among Nigerian SCD subjects despite its proven efficacy/clinical prospects in the developed nations. Large scale multicenter studies and clinical trials are needed to form a basis for developing standard local treatment protocol for its use.Keywords: Hydroxyurea therapy, Nigerian sickle cell disease, pattern of use, clinical effects, patient’s complianc
Some Haematological and Haemostatic Indexes in Young Semi-vegetarians in Sub-Sahara Africa
Rh and Kell blood group antigen prevalence in a multi-ethnic cohort in Nigeria: implications for local transfusion service
International Society on Thrombosis and Haemostasis clinical practice guideline for treatment of congenital hemophilia A and B based on the Grading of Recommendations Assessment, Development, and Evaluation methodology
Background: Hemophilia is a rare congenital bleeding disorder that results from complete or partial deficiency of blood coagulation factor (F)VIII (hemophilia A) or FIX (hemophilia B) due to pathogenic variants in their coding genes. Hemophilia requires complex management. To date, there is no evidence-based clinical practice guideline on hemophilia treatment based on the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. Objectives: This evidence-based clinical practice guideline from the International Society on Thrombosis and Haemostasis aims to provide an overview of evidence and support patients, caregivers, hematologists, pediatricians, other clinicians, researchers, and stakeholders in treatment decisions about congenital hemophilia A and B. Methods: The International Society on Thrombosis and Haemostasis formed a multidisciplinary guideline panel of physicians and patients with global representation, balanced to minimize potential bias from conflicts of interest. The panel prioritized a set of clinical questions and outcomes according to their importance for clinicians and patients. A methodological team supported the guideline development process, including searching for evidence and performing systematic reviews. The GRADE approach was used, including GRADE Evidence to Decision frameworks. The recommendations were subject to public comment. Results: The panel selected 13 questions, of which 11 addressed the treatment of hemophilia A and 2 the treatment of hemophilia B. Specifically, the panel addressed questions on prophylactic and episodic treatment with FVIII concentrates, bypassing agents, and nonfactor therapy (emicizumab) for hemophilia A (with and without inhibitors) as well as immune tolerance induction for hemophilia A. For hemophilia B, the panel addressed questions on prophylactic and episodic treatment of bleeding events with FIX concentrates. Agreement was reached for all 13 recommendations, of which 7 (54%) were based on evidence from randomized clinical trials, 3 (23%) on observational studies, and 3 (23%) on indirect comparisons. Conclusion: Strong recommendations were issued for prophylactic over episodic treatment for severe and moderately severe hemophilia A and B. Only conditional recommendations were issued for the remaining questions. Future research should focus on direct treatment comparisons and the treatment of hemophilia B with and without inhibitors. Future updates of this guideline will provide an updated evidence synthesis on the current questions and focus on new FVIII and FIX concentrates, novel nonfactor therapies, and gene therapy for severe and nonsevere hemophilia A and B
A politics of conversion: nihilism and love in Toni Morrison's fiction
Tese (doutorado) - Universidade Federal de Santa Catarina, Centro de Comunicação e Expressão. Programa de Pós-Graduação em Letras.O estudo Uma Política de Conversão: Niilismo e Amor na Ficção de Toni Morrison começa com a idéia de que a Literatura Afro-Americana apresenta um sentido de auto-reflexividade e hibridismo, através do qual autobiografia dialoga com romance, o espiritual se funde com o político. A partir deste traço dialógico a auto-reflexividade é politicamente estabelecida entre niilismo e amor. Na política de conversão, o estudo analisa as formas como mulheres negras, individualmente ou em grupo, fogem da escravidão para a liberdade, avançam da individualidade para a coletividade, ou substituem niilismo por amor. Metodologicamente o estudo apresenta sete capítulos. O primeiro discute os aspectos dialógicos que ilustram as conexões entre narrativas espirituais, de escravos e ficção, entre espiritualidade e política. O segundo examina o diálogo entre a conversão, pregação pública e formação da comunidade em Diário e Experiências Religiosas de Lee. O capítulo sugere que ao afirmar espiritualidade e humanidade a narradora abre profundo espaço para a mulher negra reclamar direitos civis. O terceiro discute o diálogo no interior da política de conversão entre narrativa de escravos e ficção. Este diálogo lida com niilismo e amor em Incidentes de Jacobs e Amada, Sula e O Olho Mais Azul de Morrison. Para a análise de niilismo e amor valores individuais e coletivos são considerados em relação a cinco aspectos: ambiente e agente antagonistas, agente de apoio, propósito da personagem e resultado alcançado. É visível, no estudo, o apoio que certas mulheres recebem de suas comunidades para contra-atacar antagonistas. O apoio nem sempre resulta na superação do niilismo e, por isso, derrota temporária pode ocorrer antes que elas sejam reintegradas à comunidade, como acontece com Linda Brent. O quarto capítulo examina as fraquezas e as energias da política da conversão e a reintegração de Sethe Suggs à comunidade de Bluestone Road. O quinto avalia como a comunidade de Bottom tenta controlar a individualidade de Sula Peace e como um grupo de mulheres lideradas por Nel Wrights consegue resgatar o espírito de independência da heroína. O sexto mostra como a política da conversão das mulheres de Lorain é incapaz de garantir a saúde mental de Pecola Breedlove, mas consegue criar um papel mais consistente para o grupo. No sétimo, a conclusão examina da relação dialética entre niilismo e amor ou auto-amor nas experiências dos indivíduos e dos grupos. O estudo sugere que em Incidentes a busca de Linda Brent por liberdade envolve elementos de autodestruição e de autoempoderamento. Da mesma maneira, o estudo conclui que em Amada o amor que Sethe Suggs tem para as suas crianças mata a própria filha, enfatizando, assim, o desejo de livrá-la da escravidão. Igualmente em Sula, a individualidade de Sula Peace não apenas limita, mas também expande as experiências do grupo, levando-o à emancipação. Finalmente, em O Olho Mais Azul a luta de Pecola Breedlove por amor e beleza reflete auto-ódio ao mesmo tempo em que reconstrói a auto-apreciação de toda a comunidade
Thrombomodulin and Lactate Dehydrogenase as Potential Predictors of Leg Ulcers in Sickle Cell Disease
Background: Endothelial dysfunction, hypercoagulability, hemolysis, and vasculopathy are involved in the pathogenesis of sickle cell leg ulcers (SCLUs). Understanding these processes is crucial for developing effective strategies to manage and prevent SCLU. Objectives: To evaluate the plasma levels of thrombomodulin (TM) in patients with SCLU, determine if TM levels have any association with SCLU and its severity, and determine if TM has any association with markers of hemolysis. Materials and Methods: This was a cross-sectional analytical study carried out among patients with SCLU and their age-matched sickle cell disease (SCD) patients without leg ulcers. Venous blood samples were collected for the determination of TM and lactate dehydrogenase (LDH) levels. Statistical significance across means was determined using independent t tests and the one-way analysis of variance (ANOVA). Pearson’s correlation and linear regression analysis were used to determine the relationship between variables. Results: Of the 82 patients with SCD, 41 had SCLU (test group), and 41 had no SCLU (control group). Their mean age was 33.3 ± 9.0 and 33.0 ± 8.5 (P = 0.30), respectively. There was no significant statistical difference between plasma levels of TM and number (P = 0.191) and severity (P = 0.148) of SCLU. Seventy-three (89%) SCD patients had LDH concentration above the reference limit of normal, and 9 (11%) were within normal limits (P = 0.002). None of the test (SCLU) group patients had normal LDH values. Conclusion: SCLU is associated with higher levels of LDH, whereas plasma TM levels showed no association with the occurrence and severity of SCLU
Neonatal jaundice in Global Majority babies: A Scoping Review of diagnostic and management practices in Western healthcare systems
Rationale for scoping review vs. systematic review
For the chosen research question, a systematic review may be considered inappropriate as the literature is heterogenous and potentially underdeveloped conceptually (Munn et al., 2018). Additionally, as the research question is broad and exploratory, key concepts, especially surrounding how individuals are racialised within society are not clearly established. In contrast to a systematic review, a scoping review allows researchers to examine how a topic has been studied within literature, which populations have been included and also where gaps in literature exist (Arksey and O’Malley, 2005; Peters et. al. 2020).
As the aim of this literature review is not to infer causality of an intervention relative to an outcome, a scoping review is preferred, as opposed to a systematic review where evidence synthesis may be the final output. The heterogeneity of the available evidence base in terms of study design e.g. grey literature, qualitative studies, policy documents and observational research may mean that a scoping review design is preferable. This is also due to the permission of the inclusion of multiple methodologies without requiring formal quality appraisal or meta-analysis processes (Levac, Colquhoun and O’Brien, 2010). What is more, scoping reviews identify research gaps and concepts which could justify a subsequent systematic review, which could then in turn synthesise existing evidence to inform policy changes (Tricco et al., 2018).
As the research question focuses on perceptions and experiences as opposed to objective outcomes alone, a scoping review is preferred and commonplace within health service research in investigating how care is delivered in different population groups (Peters et al., 2020). A systematic review may not describe the nuance of social or institutional factors affecting healthcare delivery and experiences of clinicians.
Research question:
How do UK clinicians approach diagnosis and management of neonatal jaundice in global majority babies? A mixed methods study.
Stage 1: Identification of the research question
The objectives of this scoping review are to:
1. Map the existing evidence on how neonatal jaundice is diagnosed and managed in global majority babies within Western clinical settings.
2. Identify and describe clinical approaches, tools, and guidelines used by clinicians based in Western healthcare settings when assessing and managing neonatal jaundice in global majority infants.
3. Explore clinicians’ experiences, perceptions, and decision-making related to diagnosing and managing neonatal jaundice in global majority babies.
4. Identify reported challenges, uncertainties, and inequities in the diagnosis and management of neonatal jaundice affecting global majority babies.
5. Highlight gaps in the evidence base to inform future research, clinical guidance and policy development aimed at improving equity in neonatal jaundice care.
Informed by the Joanna Briggs Institute (JBI) methodology for scoping reviews, these objectives align closely with the PCC framework to ensure methodological rigour (Peters et. al., 2020).
To explore concepts, contexts, varying evidence and populations, a broad research question is chosen using the PCC (Population, Concept, Context) framework to adhere to methodological consistency (Peters et. al., 2020):
‘Neonatal jaundice in Global Majority babies: A Scoping Review of diagnostic and management practices in Western healthcare systems’
PCC Framework Application
Population (P)
• Global majority babies/neonates
(may also be described in the literature as infants from Black, Asian, and other racially minoritised groups)
Concept (C)
• Diagnosis and management of neonatal jaundice
• Clinical approaches, assessment methods (visual assessment, transcutaneous bilirubinometry, serum bilirubin testing) and management strategies following diagnosis by a health care professional/clinician
Context (C)
• Western healthcare settings
• Clinical settings where neonatal care is provided (e.g. labour wards, birth centres, postnatal wards, neonatal units, transitional care units, community midwifery services)
• Healthcare delivered within healthcare settings in North America, Australia, Western Europe
PCC Inclusion and Exclusion Criteria
Population
Inclusion
• Neonates (≤28 days of age) described as global majority babies, including but not limited to infants identified in the literature as:
o Black, Asian, African, Caribbean, Middle Eastern, Mixed groups or other racially minoritised groups
• Studies involving clinicians (e.g. midwives, neonatal nurses, paediatricians, neonatologists, general practitioners) providing care to global majority neonates
Exclusion
• Studies exclusively involving white infants with no disaggregated data for global majority babies
• Studies focused on older infants or children (>28 days)
Concept
Inclusion
• Clinical diagnosis of neonatal jaundice, including:
o Visual assessment
o Transcutaneous bilirubin measurement
o Serum bilirubin testing
o Use of clinical guidelines or decision-making tools
• Management of neonatal jaundice, including:
o Phototherapy
o Exchange transfusion
o Monitoring, follow-up, and referral pathways
• Clinicians’ knowledge, attitudes, experiences, or decision-making relating to neonatal jaundice in global majority babies
• Identification of barriers, facilitators, or uncertainties in diagnosis and management
Exclusion
• Studies focusing solely on biochemical mechanisms, pathophysiology or genetics without clinical application
• Studies addressing jaundice secondary to non-neonatal conditions (e.g. congenital liver disease beyond the neonatal period)
• Intervention studies unrelated to diagnosis or management (e.g. parental education only)
Context
Inclusion
• Studies conducted in Western healthcare settings
• All Western healthcare settings providing neonatal care, including:
o Neonatal units
o Transitional care units
o Labour wards
o Birth centres
o Postnatal wards
o Community midwifery or health visiting services
o Primary care settings
Exclusion
• Studies conducted outside Western healthcare settings
• Non-clinical settings or care provided by non-clinicians
Types of Sources
Inclusion
• Quantitative, qualitative and mixed methods studies
• Clinical guidelines, audits and service evaluations
• Grey literature (e.g. NHS reports, professional body guidance, theses, NGO reports)
Exclusion
• Opinion pieces without empirical or policy basis
Stage 2: Identification of relevant studies
A comprehensive search strategy will be adopted to capture the full scope of appropriate literature using multiple databases, grey literature sources and secondary references lists (Levac et al., 2010). As researcher familiarity with the existing literature improves, the search strategies may be refined throughout the review process, demonstrating the iterative nature of scoping reviews (Arksey and O’Malley, 2005). Searches will be conducted across databases including; MEDLINE, CINAHL, PsycINFO using terms; ‘neonatal jaundice’, ‘hyperbilirubinaemia’, ‘race’, ‘ethnicity’, ‘disparities’, ‘diagnosis’, ‘diagnostic accuracy’, ‘disparities’, ‘disparity’, ‘clinic decision making’, ‘escalation.’ Inclusion criteria for studies include; qualitative, quantitative, policies, peer-reviewed, published 2000-2025, English language, addressing behaviour of clinicians, race, ethnicity and neonatal care. Exclusion criteria include publications without racial analysis or without clinical context.
Stage 3: Study selection
Against the predefined inclusion and exclusion criteria, titles and abstracts will be screened, followed by a review of the full text. Due to the limitations of the Professional Doctorate, the screening will only be conducted by the primary researcher, which will minimise methodological rigour, however this is due to the small funding capabilities of the research (Peter et. al., 2020). Using the PRISMA-ScR flow diagram, the study selection processes will be clearly documented and reported (Tricco et. al., 2018).
Stage 4: Charting data
Key data and information are extracted systematically by data charting from the studies included within the scoping review. This can include key concepts, population characteristics, author, study design and country where the research was conducted (Arksey and O’Malley, 2005). To improve rigour, transparency and findings credibility, a data extraction form will be piloted for 5 studies from the scoping review study selection and refined iteratively by the reviewer (Levac et. al., 2010).
Stage 5: Collating, summarising and reporting results
Data extracted from stage 4 will be synthesised by thematic analysis to present an overview of the themes within the existing evidence and to identify gaps within the literature, as opposed to assessing methodological quality via critical appraisal tools or synthesise new evidence for example with pooled effect estimates (Arksey and O’Malley, 2005; Peters et. al., 2020). Findings will be reproducible and directly related to the research question.
Stage 6: Consultation with relevant stakeholders
To attempt to ensure that missing evidence is added to the scoping review or to inform the interpretation of the studies, stakeholder consultation can be added as a final optional stage if it is within the scope of a Professional Doctorate (Arksey and O’Malley, 2005). If appropriate, clinicians, patients, policymakers and families of babies racialised as belonging to Global Majority groups can be approached to consult on the scoping review (Levac et. al., 2010)
Ligand-directed covalent labelling of a GPCR with a fluorescent tag in live cells
© 2020, The Author(s). To study the localisation of G protein-coupled receptors (GPCR) in their native cellular environment requires their visualisation through fluorescent labelling. To overcome the requirement for genetic modification of the receptor or the limitations of dissociable fluorescent ligands, here we describe rational design of a compound that covalently and selectively labels a GPCR in living cells with a fluorescent moiety. We designed a fluorescent antagonist, in which the linker incorporated between pharmacophore (ZM241385) and fluorophore (sulfo-cyanine5) is able to facilitate covalent linking of the fluorophore to the adenosine A2A receptor. We pharmacologically and biochemically demonstrate irreversible fluorescent labelling without impeding access to the orthosteric binding site and demonstrate its use in endogenously expressing systems. This offers a non-invasive and selective approach to study function and localisation of native GPCRs
