Browsing by Author "Louw, Vernon"

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    Anaemia in a South African colorectal ERAS programme – identifying the prevalence and predictors of preoperative anaemia and the effect on post-operative complications and length of stay
    (2023) Nieuwenhuis, Kathryn; Gibbs, Matthew; Louw, Vernon; Alphonsus; Warden, C; Boutall, A; Bannister, S
    Background: Anaemia is a widespread public health problem associated with increased mortality and morbidity. In a surgical population, the prevalence of preoperative anaemia often exceeds that of the general population. Elective colorectal patients often have multiple risk factors for preoperative anaemia. The fourth updated ERAS Society guidelines for optimal perioperative care in colorectal surgery include specific recommendations for screening and treatment of preoperative anaemia as well as utilising restrictive blood transfusion practice. Assessing the prevalence and predictors of anaemia and outcomes in this population may allow for improved preoperative assessment and treatment of colorectal patients in a resource limited setting. Objectives: The primary objective of this retrospective study was to determine the prevalence of anaemia in the colorectal surgical population who were part of the enhanced recovery after surgery (ERAS) programme at a tertiary level hospital in the Western Cape, South Africa. Secondary objectives were to determine independent risk factors of preoperative anaemia, and the effect of anaemia on post-operative complications and length of stay after elective colorectal surgery. Methods: We performed a secondary analysis of data collected for the colorectal surgical ERAS programme. Data of 260 patients was reviewed from the initiation of the database 01 September 2016 to 30 September 2019. Three regression analyses were performed as part of the secondary objective to determine the risk factors for preoperative anaemia and predictors for postoperative complications and length of hospital stay. Patients were defined as anaemic if their haemoglobin was less than 13.0 g/dL. Results: The prevalence of preoperative anaemia was 157/260 (60.3%). Female sex (odds ratio (OR) 2.44, 95% confidence interval (CI) 1.43 – 4.18; p=0.001) and the presence of malignancy (OR 2.42, CI 1.26- 4.67; p=0.008) showed a significant association with anaemia. Anaemia was not associated with increased risk of post-operative complications or length of hospital stay. Conclusion: South African colorectal surgical patients in an enhanced recovery after surgery programme have a higher prevalence of preoperative anaemia compared to the general surgical population. Predictors of preoperative anaemia in this population included female sex and the presence of malignancy. Long waiting lists for patients awaiting elective colorectal surgery allow time for evaluation and optimisation of patients at risk for anaemia preoperatively
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    From the marrow to the blood: Optimising the diagnosis of iron deficiency in the setting of inflammation
    (2024) Richardson, David; Opie, Jessica; Louw, Vernon
    Iron deficiency (ID) is a common condition with readily available treatment but can be challenging to diagnose. Traditional biomarkers of ID are acute phase reactants, which complicates diagnosis in patients with co-existent inflammation. This study aimed to establish optimal biomarker diagnostic thresholds for ID diagnosis using bone marrow (BM) iron stores as the gold standard and the Creactive protein (CRP) as an inflammatory marker. A cross-sectional study was carried out in the haematology department of a tertiary academic hospital. Patients undergoing BM biopsies for any reason were recruited for inclusion. Retrospective case finding was used to enrich the data for cases with confirmed BM ID. Laboratory markers including red cell indices, reticulocyte haemoglobin and iron studies were evaluated to establish optimal cut-offs for ID diagnosis. A CRP of >5 mg/L was used as a marker of inflammation. The study included 139 patients. Forty-two patients had BM ID with a median serum ferritin (SF) of 48.5 μg/L. 96/134 (72%) had inflammation with a CRP > 5 mg/L. A SF of < 80 μg/L had optimal sensitivity (69%) and specificity (94%) for ID diagnosis in the whole group (OR 23.5; CI 4.3-129). In patients without inflammation, a SF 80 cut-off had high sensitivity (93%) and specificity (96%). A SF < 200 μg/L indicated ID in those with inflammation (sensitivity 78%, specificity 74%). A transferrin saturation of <13% in those with inflammation increased the diagnostic specificity (92%). The reticulocyte haemoglobin was unhelpful in diagnosing ID in this setting. In this hospital population, SF was the best parameter to diagnose ID, even in the presence of inflammation, albeit at a higher cut-off level. The CRP was useful to identify populations in whom a higher SF threshold could be used together with the transferrin saturation to accurately diagnose ID.
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    Lymphoma: Understanding the diagnostic challenges and improving outcomes in a TBand HIV-endemic area
    (2021) Antel, Katherine Rae; Verburgh, Estelle; Maartens, Gary; Louw, Vernon
    Background and aims Diagnosing lymphoma can be challenging: even in the best-resourced settings, lymphoma diagnosis may be delayed owing to the insidious onset of symptoms and/or difficulties in obtaining lymph node biopsy for diagnosis. In TB-endemic countries the diagnostic challenges in lymphoma may be further compounded by symptoms overlapping with those of TB and by resource limitations that may impede obtaining a diagnostic biopsy. New lymphoma diagnostic modalities, including the use of nextgeneration sequencing, are evolving rapidly and informing both prognosis and therapy in the field of lymphoma. These modalities of testing are likely to mean that less tissue is needed for assessment, or even that diagnosis can be made from peripheral blood. In this thesis we identify and describe local barriers in the diagnosis of lymphoma; and describe methods used to decrease the time-to-diagnosis of lymphoma and to subtype the most common lymphoma, diffuse large B-cell lymphoma (DLBCL). Our four main aims have been to: (i) Describe the pathway to a diagnosis of lymphoma in South Africa, with emphasis on the examination of local barriers to diagnosis (including overlapping symptomatology with TB) by retrospectively studying a cohort of patients with lymphoma. (ii) Investigate the diagnostic utility of the newest TB diagnostic test (the Xpert MTB/RIF Ultra); and apply this test in a diagnostic algorithm for lymphadenopathy of unknown aetiology, both on a fine-needle aspirate (FNA) from a lymph node and on tissue obtained by corebiopsy. (iii) Investigate whether a rapid-access lymph node biopsy clinic that used a core-biopsy method for lymph node biopsy was able to reduce the time-to-diagnosis of lymphoma, and to subtype accurately lymphomas for which subtyping is clinically relevant. (iv) Describe the subtype of DLBCL by HIV status using an immunohistochemical algorithm, in order both to describe the pattern of DLBCL by the most current diagnostic classification and to lay the foundations for further genetic work potentially capable of identifying mutations that could be used for genetic testing in DLBCL locally. Methods Four cohorts were analysed: (i) In the first, a group of 163 patients with lymphoma, the time-to-diagnosis and factors causing a delay in diagnosis were analysed. (ii) In the second, 99 patients with lymphadenopathy of unknown cause were recruited and the sensitivity and specificity of the Ultra were analysed using both fine-needle aspirate (FNA) and a core-biopsy technique. (iii) In the third cohort (n = 130), which included the second cohort of n = 99), outcomes from a rapid-access lymph node biopsy clinic – which used the core-biopsy method for the diagnosis of lymphoma – were analysed. (iv) In the fourth cohort (n = 182), the tissue of patients with DLBCL was analysed based on further immunohistochemical stains using the Hans algorithm in order to determine the molecular subtypes of DLBCL and determine their effect on prognosis. Results (i) In the first cohort ((n = 163), 29% HIV-infected), which was studied retrospectively, it took a median of 7 weeks for the diagnosis of lymphoma to be made from the time the patient sought medical attention. The longest time delay was in the healthcare practitioner interval (time from first healthcare visit to diagnostic biopsy). On multivariable logistic regression analysis, diagnostic delay > 6 weeks was associated with late-stage disease at presentation (odds ratio (OR) 2.3, 95% confidence interval (CI) 1.1–5.2) and a diagnosis of Hodgkin lymphoma (OR 3.0, 95% CI 1.1–8.0). HIV status was not associated with diagnostic delay (OR 0.9, 95% CI 0.3–2.2). The median time to diagnosis for patients on TB treatment was a month longer than for patients not on TB treatment. However, this was not statistically significant owing likely to a small sample size (n = 16, p = 0.28). (ii) In the second cohort, the diagnostic utility of the Ultra on lymph node aspirate and tissue were prospectively evaluated. The Ultra was found to be a sensitive and specific test for diagnosing TB of the lymph node. When compared with culture, the Ultra on aspirate had a sensitivity of 78% (40–97; 7/9) and on tissue 90% (55–100; 9/10). When using a composite reference score that combined both ‘definite TB' (culture positive) and ‘probable TB' (histological and clinical criteria), the Ultra was superior to currently used methods of diagnosing TB of the lymph node, including the detection of AFBs from an aspirate or on tissue biopsy or tissue culture (which had sensitivities of 26%, 33% and 39% respectively). The detection of granulomas on histology had high sensitivity (83%) but the lowest specificity. (iii) In the third cohort, which was studied prospectively, we obtained two important outcomes. Firstly, we showed that a rapid-access lymph node biopsy clinic was able to decrease the time-to-diagnosis of lymphoma when compared with that of cohort one (the historical cohort) to a diagnostic interval of 13.5 days compared with 48 days (p = 0.002). Secondly, the core-biopsy was able to detect lymphoma with a high rate of accuracy. The first-attempt core-biopsy was able to diagnose lymphoma in 84% of cases, and provided sufficient tissue to subtype lymphoma in a high proportion of the lymphoma cases (27/30, 90%). (iv) In the fourth, retrospectively evaluated cohort of patients with DLBCL (n = 181, 51 HIVpositive), there was a similar distribution of germinal centre (GC) and activated B cell (ABC) subtypes in the HIV-infected and HIV-uninfected groups. In contrast to what is reported in HIV-negative DLBCL literature, there were no statistically significant differences in overall survival by DLBCL subtype. Moreover, no significant difference in 5-year overall survival was demonstrated between the GCB and ABC subtypes (HR 1.2, 95% CI 0.8–1.9). Patients with HIV infection with a CD4 count of < 150 CD4 cells/mm3 had significantly poorer survival than those with no HIV infection (HR 2.4, 95% CI 1.3–4.1). Conclusions Making a diagnosis of lymphoma in South Africa is challenging. Two of the greatest challenges are overlapping symptomatology with TB and obtaining an adequate lymph node sample. The Ultra test on lymph node tissue is rapid, sensitive and specific; and can be performed on both FNA and tissue obtained through core-biopsy. Making an accurate diagnosis of TB is of critical importance, as TB is the most common cause for enlarged lymph nodes in TB-endemic areas. A reliable TB test on lymph node tissue will enable both an accurate TB diagnosis and the identification of patients who are negative for TB. The latter will require further investigation with a lymph node biopsy (via core needle or excision). As diagnostic testing and methods evolve in the direction of next-generation platforms, it is important to understand the tumour biology in our local setting, and in HIV-lymphoma, in order to be able to apply these new methods. This thesis describes the subtypes and outcomes seen in HIV DLBCL – knowledge that will be important in developing genetic next-generation sequencing methods that are specific to the type of lymphoma to be found in our context (and which may include genetic mutations induced by the Epstein–Barr virus). A clear diagnostic algorithm for the investigation of lymphadenopathy is presented, pulling together the four aims presented at the start of this section. Considering the prevalence of TB in South Africa, the goal is, in the first instance, to diagnose or exclude TB adenitis. In patients who test negative for TB, the goal then becomes to proceed with a diagnostic biopsy and, from our findings, to support the use of core-biopsy. This method, we have demonstrated, is able to provide sufficient tissue for the diagnosis and subtyping of lymphoma.
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    The intersection of the HIV epidemic and blood donation in South Africa
    (2024) Van Den Berg, Karin; Louw, Vernon; Maartens, Gary; Murphy, Edward; Hughes, Shana
    South Africa's large population of people living with HIV (PLWH) affects the local blood transfusion services (BTS) in multiple ways, including the recruitment of safe donors, the demand for blood and the development of blood safety policies. The latter includes the deferral of persons at risk of recently acquired HIV and sensitive testing for HIV antibodies and RNA. Estimating HIV incidence in blood donors is a key measure of successful prevention strategies. Blood donation by PLWH on antiretroviral therapy (ART) was identified as an emerging risk to blood safety as early ART initiation may result in delayed seroconversion, seroreversion, and prolonged suppression of viral replication which may escape detection by HIV antibody and nucleic acid amplification testing (NAT). My PhD research used epidemiologic, incidence modelling and mixed-method qualitative research techniques to assess the impact of undisclosed ART use among blood donors on the safety of the country's blood supply.