Department of Paediatrics and Child Health

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Browsing Department of Paediatrics and Child Health by Subject "Africa"

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    Exploring mechanisms of excess mortality with early fluid resuscitation: insights from the FEAST trial
    (2013) Maitland, Kathryn; George, Elizabeth C; Evans, Jennifer; Kiguli, Sarah; Olupot-Olupot, Peter; Akech, Samuel O; Opoka, Robert O; Engoru, Charles; Nyeko, Richard; Mtove, George; Reyburn, Hugh; Brent, Bernadette; Nteziyaremye, Julius; Mpoya, Ayub; Prevatt, Natalie; Dambisya, Cornelius M; Semakula, Daniel; Ddungu, Ahmed; Okuuny, Vicent; Wokulira, Ronald; Otii, Benedict; Levin, Michael; Crawley, Jane; Babiker, Abdel G; Gibb, Diana M; FEAST trial group
    Background: Early rapid fluid resuscitation (boluses) in African children with severe febrile illnesses increases the 48-hour mortality by 3.3% compared with controls (no bolus). We explored the effect of boluses on 48-hour allcause mortality by clinical presentation at enrolment, hemodynamic changes over the first hour, and on different modes of death, according to terminal clinical events. We hypothesize that boluses may cause excess deaths from neurological or respiratory events relating to fluid overload. Methods: Pre-defined presentation syndromes (PS; severe acidosis or severe shock, respiratory, neurological) and predominant terminal clinical events (cardiovascular collapse, respiratory, neurological) were described by randomized arm (bolus versus control) in 3,141 severely ill febrile children with shock enrolled in the Fluid Expansion as Supportive Therapy (FEAST) trial. Landmark analyses were used to compare early mortality in treatment groups, conditional on changes in shock and hypoxia parameters. Competing risks methods were used to estimate cumulative incidence curves and sub-hazard ratios to compare treatment groups in terms of terminal clinical events. Results: Of 2,396 out of 3,141 (76%) classifiable participants, 1,647 (69%) had a severe metabolic acidosis or severe shock PS, 625 (26%) had a respiratory PS and 976 (41%) had a neurological PS, either alone or in combination. Mortality was greatest among children fulfilling criteria for all three PS (28% bolus, 21% control) and lowest for lone respiratory (2% bolus, 5% control) or neurological (3% bolus, 0% control) presentations. Excess mortality in bolus arms versus control was apparent for all three PS, including all their component features. By one hour, shock had resolved (responders) more frequently in bolus versus control groups (43% versus 32%, P <0.001), but excess mortality with boluses was evident in responders (relative risk 1.98, 95% confidence interval 0.94 to 4.17, P = 0.06) and ‘nonresponders’ (relative risk 1.67, 95% confidence interval 1.23 to 2.28, P = 0.001), with no evidence of heterogeneity (P = 0.68). The major difference between bolus and control arms was the higher proportion of cardiogenic or shock terminal clinical events in bolus arms (n = 123; 4.6% versus 2.6%, P = 0.008) rather than respiratory (n = 61; 2.2% versus 1.3%, P = 0.09) or neurological (n = 63, 2.1% versus 1.8%, P = 0.6) terminal clinical events. Conclusions: Excess mortality from boluses occurred in all subgroups of children. Contrary to expectation, cardiovascular collapse rather than fluid overload appeared to contribute most to excess deaths with rapid fluid resuscitation. These results should prompt a re-evaluation of evidence on fluid resuscitation for shock and a reappraisal of the rate, composition and volume of resuscitation fluids.
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    Mortality risk over time after early fluid resuscitation in African children
    (Clinical care, 2019) George, Elizabeth C.; Kiguli, Sarah; Olupot Olupot, Peter; Opoka, Robert O.; Engoru, Charles; Akech, Samuel O.; Nyeko, Richard; Mtove, George; Mpoya, Ayub; Thomason, Margaret J.; Crawley, Jane; Evans, Jennifer A.; Gibb, Diana M.; Babiker, Abdel G.; Maitland, Kathryn; Walker, A. Sarah
    Background: African children hospitalised with severe febrile illness have a high risk of mortality. The Fluid Expansion As Supportive Therapy (FEAST) trial (ISCRTN 69856593) demonstrated increased mortality risk associated with fluid boluses, but the temporal relationship to bolus therapy and underlying mechanism remains unclear. Methods: In a post hoc retrospective analysis, flexible parametric models were used to compare change in mortality risk post-randomisation in children allocated to bolus therapy with 20–40 ml/kg 5% albumin or 0.9% saline over 1–2 h or no bolus (control, 4 ml/kg/hour maintenance), overall and for different terminal clinical events (cardiogenic, neurological, respiratory, or unknown/other). Results: Two thousand ninety-seven and 1041 children were randomised to bolus vs no bolus, of whom 254 (12%) and 91 (9%) respectively died within 28 days. Median (IQR) bolus fluid in the bolus groups received by 4 h was 20 (20, 40) ml/kg and was the same at 8 h; total fluids received in bolus groups at 4 h and 8 h were 38 (28, 43) ml/kg and 40 (30, 50) ml/kg, respectively. Total fluid volumes received in the control group by 4 h and 8 h were median (IQR) 10 (6, 15) ml/kg and 10 (10, 26) ml/kg, respectively. Mortality risk was greatest 30 min post-randomisation in both groups, declining sharply to 4 h and then more slowly to 28 days. Maximum mortality risk was similar in bolus and no bolus groups; however, the risk declined more slowly in the bolus group, with significantly higher mortality risk compared to the no bolus group from 1.6 to 101 h (4 days) post-randomisation. The delay in decline in mortality risk in the bolus groups was most pronounced for cardiogenic modes of death. Conclusions: The increased risk from bolus therapy was not due to a mechanism occurring immediately after bolus administration. Excess mortality risk in the bolus group resulted from slower decrease in mortality risk over the ensuing 4 days. Thus, administration of modest bolus volumes appeared to prevent mortality risk declining at the same rate that it would have done without a bolus, rather than harm associated with bolus resulting from a concurrent increased risk of death peri-bolus administration.
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    Pediatric low-grade glioma in Africa: a baseline study before the implementation of Global Initiative for Childhood Cancer strategies.
    (Frontiers in Cancer Control and Society, 2025) van Heerden, Jaques; Esterhuizen, Tonya Marianna; Jbebli, Elhem; Fedhila, Faten; Rhayem, Samar; Chabchoub, Imène; Togo, Boubacar; Van Zyl, Anel; Neethling, Beverley; Thomas, Karla; Charlton, Robyn; Ngcana, Thandeka; Naidu, Gita; du Plessis, Jan; Nyeko, Richard; Balagadde-Kambugu, Joyce; Hessissen, Laila; Zeyad, Abdel Aziz; Gamal, Aya; Amany, Mohamed Ali; Hamdy, Rana; Asfour, Hosam Y.; Elayadi, Moatasem; Geel, Jennifer; Parkes, Jeannette; Davidson, Alan
    Introduction: Pediatric low-grade glioma (LGG) is a World Health Organization (WHO) Global Initiative for Childhood Cancer (GICC) index tumor constituting up to a third of pediatric central nervous system (CNS) tumors. The baseline characteristics, survival, and management resources for pediatric LGG in Africa are unknown. We aimed to evaluate the pediatric neuro- oncology multidisciplinary team resources, epidemiology, and survival outcomes of pediatric LGG in Africa to document baseline information prior to GICC implementation. Methods: The study consisted of two parts: a survey completed by African pediatric oncology units (POU) to evaluate the local resources and a retrospective evaluation of data to determine the 5-year overall survival (OS) for patients under 18 years diagnosed with LGG between 2008 and 2018. Data were described in frequencies and percentages. Survival was expressed with Kaplan–Meier curves. Results: Five-hundred and eighty-eight patients were included from fifteen POUs in six countries: South Africa (45.9%), Egypt (30.8%), Morocco (12.6%), Mali (4.4%), Tunisia (3.6%) and Uganda (2.7%). The median age was 4.4 years (interquartile range 2.4–7.3 years). The most common primary tumor site was the brainstem (n = 125, 21.3%), the most common histology was pilocytic astrocytoma (n = 270, 47.5%), the majority of tumors (n = 292, 93%) were localized, and 40 (6.8%) patients had neurofibromatosis. Complete resection was obtained in 99 (16.8%) cases, incomplete resection in 179 (30.4%), and no surgery or biopsy only was performed in 310 (52.7%) cases. One hundred and forty- seven (25.3%) of the 580 patients with a documented radiotherapy status, were irradiated, and 320 (54.4%) received chemotherapy. Only 259 (15.3%) patients received chemotherapy of which the most common chemotherapy regimen was vincristine-carboplatin (n = 220, 84.9%). The 5-year OS was 90.5% ± 1.6%. The 5- year OS in Tunisia was 95.1% ± 1.1%, 92.4% ± 2.1% in Egypt, 89.0% ± 3.2% in South Africa, 70.7% ± 6.7% in Morocco and 66.7% ± 15.7% in Uganda (p < 0.001). Four of the 41 (9.8%) responding countries reported having pediatric neuro-oncology subspecialists, and four (9.8%) had national pediatric LGG protocols. In Africa there is one radiotherapy center per 2,235,125 children and one neurosurgeon per 304,685 children, with ∼70% of these resources accessible in four countries. Discussion: Due to several resource challenges and developing treatment centers, only fifteen pediatric oncology units from six countries participated. We documented a baseline 5-year OS of 94.9% for LGG in African children. To obtain an accurate estimation of pediatric LGG survival in Africa, increasing participation from a wider range of countries, especially poorly resourced settings, is necessary. KEYWORDS Africa, low-grade glioma, children, outcomes, systems, GICC
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    Predicting mortality in sick African children: the FEAST Paediatric Emergency Triage (PET) Score
    (BMC Medicine, 2015) George, Elizabeth C.; Walker, A. Sarah; Kiguli, Sarah; Olupot-Olupo, Peter; Opoka, Robert O.; Engoru, Charles; Akech, Samuel O.; Nyeko, Richard; Mtove, George; Reyburn, Hugh; Berkley, James A.; Mpoya, Ayub; Levin, Michael; Crawley, Jane; Gibb, Diana M.; Maitland, Kathryn; Babiker, Abdel G.
    Background: Mortality in paediatric emergency care units in Africa often occurs within the first 24 h of admission and remains high. Alongside effective triage systems, a practical clinical bedside risk score to identify those at greatest risk could contribute to reducing mortality. Methods: Data collected during the Fluid As Expansive Supportive Therapy (FEAST) trial, a multi-centre trial involving 3,170 severely ill African children, were analysed to identify clinical and laboratory prognostic factors for mortality. Multivariable Cox regression was used to build a model in this derivation dataset based on clinical parameters that could be quickly and easily assessed at the bedside. A score developed from the model coefficients was externally validated in two admissions datasets from Kilifi District Hospital, Kenya, and compared to published risk scores using Area Under the Receiver Operating Curve (AUROC) and Hosmer-Lemeshow tests. The Net Reclassification Index (NRI) was used to identify additional laboratory prognostic factors. Results: A risk score using 8 clinical variables (temperature, heart rate, capillary refill time, conscious level, severe pallor, respiratory distress, lung crepitations, and weak pulse volume) was developed. The score ranged from 0–10 and had an AUROC of 0.82 (95 % CI, 0.77–0.87) in the FEAST trial derivation set. In the independent validation datasets, the score had an AUROC of 0.77 (95 % CI, 0.72–0.82) amongst admissions to a paediatric high dependency ward and 0.86 (95 % CI, 0.82–0.89) amongst general paediatric admissions. This discriminative ability was similar to, or better than other risk scores in the validation datasets. NRI identified lactate, blood urea nitrogen, and pH to be important prognostic laboratory variables that could add information to the clinical score. Conclusions: Eight clinical prognostic factors that could be rapidly assessed by healthcare staff for triage were combined to create the FEAST Paediatric Emergency Triage (PET) score and externally validated. The score discriminated those at highest risk of fatal outcome at the point of hospital admission and compared well to other published risk scores. Further laboratory tests were also identified as prognostic factors which could be added if resources were available or as indices of severity for comparison between centres in future research studies.