Cardiovascular abnormalities in chest radiographs of children with pneumonia, Uganda.

Objective: To describe chest radiograph findings among children hospitalized with clinically diagnosed severe pneumonia and hypoxaemia at three tertiary facilities in Uganda. Methods: The study involved clinical and radiograph data on a random sample of 375 children aged 28 days to 12 years enrolled in the Children's Oxygen Administration Strategies Trial in 2017. Children were hospitalized with a history of respiratory illness and respiratory distress complicated by hypoxaemia, defined as a peripheral oxygen saturation (SpO2) < 92%. Radiologists blinded to clinical findings interpreted chest radiographs using standardized World Health Organization method for paediatric chest radiograph reporting. We report clinical and chest radiograph findings using descriptive statistics. Findings: Overall, 45.9% (172/375) of children had radiological pneumonia, 36.3% (136/375) had a normal chest radiograph and 32.8% (123/375) had other radiograph abnormalities, with or without pneumonia. In addition, 28.3% (106/375) had a cardiovascular abnormality, including 14.9% (56/375) with both pneumonia and another abnormality. There was no significant difference in the prevalence of radiological pneumonia or of cardiovascular abnormalities or in 28-day mortality between children with severe hypoxaemia (SpO2: < 80%) and those with mild hypoxaemia (SpO2: 80 to < 92%). Conclusion: Cardiovascular abnormalities were relatively common among children hospitalized with severe pneumonia in Uganda. The standard clinical criteria used to identify pneumonia among children in resource-poor settings were sensitive but lacked specificity. Chest radiographs should be performed routinely for all children with clinical signs of severe pneumonia because it provides useful information on both cardiovascular and respiratory systems.

Randomised controlled trial of oxygen therapy and high-flow nasal therapy in African children with pneumonia.

PURPOSE: The life-saving role of oxygen therapy in African children with severe pneumonia is not yet established. METHODS: The open-label fractional-factorial COAST trial randomised eligible Ugandan and Kenyan children aged > 28 days with severe pneumonia and severe hypoxaemia stratum (SpO2 < 80%) to high-flow nasal therapy (HFNT) or low-flow oxygen (LFO: standard care) and hypoxaemia stratum (SpO2 80-91%) to HFNT or LFO (liberal strategies) or permissive hypoxaemia (ratio 1:1:2). Children with cyanotic heart disease, chronic lung disease or > 3 h receipt of oxygen were excluded. The primary endpoint was 48 h mortality; secondary endpoints included mortality or neurocognitive sequelae at 28 days. RESULTS: The trial was stopped early after enrolling 1852/4200 children, including 388 in the severe hypoxaemia stratum (median 7 months; median SpO2 75%) randomised to HFNT (n = 194) or LFO (n = 194) and 1454 in the hypoxaemia stratum (median 9 months; median SpO2 88%) randomised to HFNT (n = 363) vs LFO (n = 364) vs permissive hypoxaemia (n = 727). Per-protocol 15% of patients in the permissive hypoxaemia group received oxygen (when SpO2 < 80%). In the severe hypoxaemia stratum, 48-h mortality was 9.3% for HFNT vs. 13.4% for LFO groups. In the hypoxaemia stratum, 48-h mortality was 1.1% for HFNT vs. 2.5% LFO and 1.4% for permissive hypoxaemia. In the hypoxaemia stratum, adjusted odds ratio for 48-h mortality in liberal vs permissive comparison was 1.16 (0.49-2.74; p = 0.73); HFNT vs LFO comparison was 0.60 (0.33-1.06; p = 0.08). Strata-specific 28 day mortality rates were, respectively: 18.6, 23.4 and 3.3, 4.1, 3.9%. Neurocognitive sequelae were rare. CONCLUSIONS: Respiratory support with HFNT showing potential benefit should prompt further trials.

Development of a feedback framework within a mentorship alliance using activity theory.

Background: Mentorship is useful in enhancing student learning experiences. The provision of feedback by faculty mentors is a central activity within a fruitful mentorship relationship. Therefore, effective feedback delivery by mentors is key to the development of successful mentorship relationships. Mentorship is a social interactive relationship between mentors and mentees. Therefore, activity theory, a sociocultural theory, has been applied in this study to develop a framework for feedback delivery within the mentorship educational alliance between mentors and mentees. Objective: The purpose of the study was to explore experiences of students and faculty mentors regarding feedback in a mentorship relationship, and to develop a feedback delivery framework in a mentorship relationship underpinned by activity theory. Methods: This was a mixed-method sequential study conducted at Makerere University College of Health Sciences using both quantitative and qualitative data collection methods. The study involved undergraduate medical students and faculty mentors. Data were collected through self-administered questionnaires, focus group discussions and interviews. Descriptive statistics were used for quantitative data, while thematic analysis was used for qualitative data. Results: Most students reported negative experiences with feedback received during the mentorship process. Of the total of 150, a significant number of students (n=60) reported receiving no feedback at all from their mentors. One hundred students reported that feedback received from mentors focused on only weaknesses, and 80 reported that the feedback was not timely. A total of 130 students reported that the feedback sessions were a one-way process, with limited involvement of mentees. The feedback also tended to focus on academics, with limited emphasis on psychosocial contextual aspects that may potentially influence student learning. The focus group discussions with students confirmed most of the quantitative findings. The interviews with faculty mentors led to the emergence of two key themes, namely: (i) limited understanding of feedback delivery during mentorship; and (ii) need for feedback guidelines for faculty mentors. Based on the findings of the mixed-method study as well as the theory guiding the study, a feedback framework for mentorship interactions has been suggested. Conclusion: While students generally reported low satisfaction with feedback received from mentors, faculty suggested the need to have feedback guidelines for mentors to frame their feedback during mentorship interactions. A feedback framework to guide mentorship interactions has therefore been suggested as a result of this study, guided by principles of activity theory.

Mentors' and student nurses' experiences of the clinical competence assessment tool.

Background: The assessment tool for registered comprehensive nursing was introduced in nursing education in Uganda in 2005 with the main purpose of facilitating nurse mentors to easily assess the clinical competency of student nurses. The tool contributes to the formative and summative assessment of students. Despite continued use of the assessment tool over the years, no study has been conducted to explore the perceptions of nurse mentors and students regarding its use. Objective: To explore the experiences of nursing students and their mentors regarding the clinical competence assessment tool. Methods: A qualitative exploratory study design was used. The study was conducted at Masaka School of Comprehensive Nursing in Uganda. The participants included 48 final-year nursing students and 5 nurse/midwifery mentors. Purposive sampling was used to select the participants. Data were collected using 6 focus group discussions with students and 5 key informant interviews with mentors, and thematic analysis was used to interpret the data. Results: From the responses, the participants generally had mixed experiences of the tool and suggestions were put forward for improvement. Five major themes emerged from student responses: (i) the orientation process; (ii) using the assessment tool; (iii) strengths of the assessment tool; (iv) challenges with the assessment tool; and (v) suggestions for improvement. The nurse mentors generally corroborated what the students reported, i.e. that the tool had challenges when one assesses student performance and gives feedback. Conclusion: The participants reported satisfaction with the design of the assessment tool. However, some challenges were identified regarding its implementation by students and mentors. Key among these were the failure to have immediate assessment and feedback to students. Findings from the study could offer insights on how the tool could be improved.

Caregivers and community perceptions of blood transfusion for children with severe anaemia in Uganda.

OBJECTIVE: To describe local perceptions of blood transfusion for children with severe anaemia in Uganda. BACKGROUND: Blood transfusion is a common emergency treatment for children with severe anaemia and saves millions of lives of African children. However, the perceptions of transfusion recipients have not been well studied. A better understanding of the perceived risk may improve transfusion care. METHODS: A qualitative study based on 16 in-depth interviews of caregivers of transfused children, and six focus group discussions with community members was conducted in three regions of Uganda between October and November 2017. RESULTS: Caregivers of children and community members held blood transfusion in high regard and valued it as life-saving. However, there were widespread perceived transfusion risks, including: Human immunodeficiency virus (HIV) transmission, too rapid blood infusion and blood incompatibility. Other concerns were: fatality, changes in behaviour, donor blood being 'too strong' and use of animal blood. In contrast, recent transfusion, older age, knowledge of HIV screening of blood for transfusion, faith in God and having a critically ill child were associated with less fear about transfusion. Respondents also emphasised challenges to transfusion services access including distance to hospitals, scarcity of blood and health workers' attitudes. CONCLUSION: Perceptions of the community and caregivers of transfused children in Uganda about blood transfusion were complex: transfusion is considered life-saving but there were strong perceived transfusion risks of HIV transmission and blood incompatibility. Addressing community perceptions and facilitating access to blood transfusion represent important strategies to improve paediatric transfusion care.

Elevated cerebrospinal fluid tumour necrosis factor is associated with acute and long-term neurocognitive impairment in cerebral malaria.

Systemic tumour necrosis factor-α (TNF-α) may contribute to the pathogenesis of cerebral malaria (CM) by promoting endothelial activation and parasite sequestration. However, less is known about the role of central nervous system (CNS) TNF-α in CM. We assessed plasma (n=249) and cerebrospinal fluid (CSF) (n=167) TNF-α levels in Ugandan children with CM, plasma TNF-α in Ugandan community control children (n=198) and CSF TNF-α in North American control children who had recovered from leukaemia (n=13). Plasma and CSF TNF-α were measured by magnetic bead assay. We compared plasma and CSF TNF-α levels in children with CM to mortality, acute and chronic neurologic deficits and long-term neurocognitive impairment. Plasma and CSF TNF-α levels were higher in CM than control children (P<.0001 for both). CSF TNF-α levels were higher in children who had neurologic deficits at discharge or 6-month follow-up (P≤.05 for both). Elevated CSF but not plasma TNF-α was associated with longer coma duration (Spearman's rho .18, P=.02) and deficits in overall cognition in children 5 years and older (ß coefficient -.74, 95% CI -1.35 to -0.13, P=.02). The study findings suggest that CNS TNF-α may be involved in the development of acute and chronic neurologic and cognitive sequelae in children with CM.

Caregiver mental health and HIV-infected child wellness: perspectives from Ugandan caregivers.

Prior studies indicate a substantial link between maternal depression and early child health but give limited consideration to the direction of this relationship or the context in which it occurs. We sought to create a contextually informed conceptual framework of this relationship through semi-structured interviews with women that had lived experience of caring for an HIV-infected child while coping with depression and anxiety symptoms. Caregivers explained their role in raising healthy children as complex and complicated by poverty, stigma, and isolation. Caregivers discussed the effects of their own mental health on child well-being as primarily emotional and behavioral, and explained how looking after a child could bring distress, particularly when unable to provide desired care for sick children. Our findings suggest the need for investigation of the reciprocal effects of child sickness on caregiver wellness and for integrated programs that holistically address the needs of HIV-affected families.

Solar-powered oxygen delivery: proof of concept.

SETTING: A resource-limited paediatric hospital in Uganda. OBJECTIVE: Pneumonia is a leading cause of child mortality worldwide. Access to life-saving oxygen therapy is limited in many areas. We designed and implemented a solar-powered oxygen delivery system for the treatment of paediatric pneumonia. DESIGN: Proof-of-concept pilot study. A solar-powered oxygen delivery system was designed and piloted in a cohort of children with hypoxaemic illness. RESULTS: The system consisted of 25 × 80 W photovoltaic solar panels (daily output 7.5 kWh [range 3.8-9.7kWh]), 8 × 220 Ah batteries and a 300 W oxygen concentrator (output up to 5 l/min oxygen at 88% [±2%] purity). A series of 28 patients with hypoxaemia were treated with solar-powered oxygen. Immediate improvement in peripheral blood oxygen saturation was documented (median change +12% [range 5-15%], P < 0.0001). Tachypnoea, tachycardia and composite illness severity score improved over the first 24 h of hospitalisation (P < 0.01 for all comparisons). The case fatality rate was 6/28 (21%). The median recovery times to sit, eat, wean oxygen and hospital discharge were respectively 7.5 h, 9.8 h, 44 h and 4 days. CONCLUSION: Solar energy can be used to concentrate oxygen from ambient air and oxygenate children with respiratory distress and hypoxaemia in a resource-limited setting.

CD101 inhibits the expansion of colitogenic T cells.

CD101 exerts negative-costimulatory effects in vitro, but its function in vivo remains poorly defined. CD101 is abundantly expressed on lymphoid and myeloid cells in intestinal tissues, but absent from naïve splenic T cells. Here, we assessed the impact of CD101 on the course of inflammatory bowel disease (IBD). Using a T-cell transfer model of chronic colitis, we found that in recipients of naïve T cells from CD101(+/+) donors up to 30% of the recovered lymphocytes expressed CD101, correlating with an increased interleukin (IL)-2-mediated FoxP3 expression. Transfer of CD101(-/-) T cells caused more severe colitis and was associated with an expansion of IL-17-producing T cells and an enhanced expression of IL-2Rα/ß independently of FoxP3. The co-transfer of naïve and regulatory T cells (Treg) protected most effectively from colitis, when both donor and recipient mice expressed CD101. Although the expression of CD101 on T cells was sufficient for Treg-function and the inhibition of T-cell proliferation, sustained IL-10 production required additional CD101 expression by myeloid cells. Finally, in patients with IBD a reduced CD101 expression on peripheral and intestinal monocytes and CD4(+) T cells correlated with enhanced IL-17 production and disease activity. Thus, CD101 deficiency is a novel marker for progressive colitis and potential target for therapeutic intervention.

Executive function and attention-deficit/hyperactivity disorder in Ugandan children with perinatal HIV exposure.

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is among the most commonly diagnosed mental disorders in childhood and is associated with substantial deficits in executive functioning and lost academic and occupational attainment. This study evaluates symptoms of ADHD and their association with neurocognitive deficits in a cohort of rural Ugandan children who were born to HIV-infected mothers. METHODS: We assessed ADHD symptoms and executive function (including memory and attention) in a non-clinical sample of children born to HIV-infected mothers in rural eastern Uganda. Analyses included assessments of the psychometric properties, factor structure, and convergent and discriminant validity of the ADHD measure (ADHD-Rating Scale-IV); and executive function deficits in children meeting symptom criteria for ADHD. RESULTS: 232 children [54% female; mean age 7.8 years (s.d. 2.0)] were assessed for ADHD and executive function deficits. The ADHD measure showed good internal consistency (α = 0.85.) Confirmatory factor analysis showed an acceptable fit for the diagnostic and statistical manual of mental disorders (DSM-5) two-factor model. Subjects meeting DSM-5 symptom criteria for ADHD had worse parent-rated executive function on six out of seven subscales. CONCLUSIONS: Our results demonstrate structural validity of the ADHD measure with this population, strong associations between ADHD symptom severity and poorer executive function, and higher levels of executive function problems in perinatally HIV-exposed Ugandan children with ADHD. These findings suggest that ADHD may be an important neurocognitive disorder associated with executive function problems among children in sub-Saharan African settings where perinatal HIV exposure is common.

Immunological correlates of behavioral problems in school-aged children living with HIV in Kayunga, Uganda.

BACKGROUND: HIV can affect the neuropsychological function of children, including their behavior. We aim to identify immunological correlates of behavioral problems among children living with HIV in Uganda. METHODS: Children participating in a parent randomized control trial in Kayunga, Uganda were assessed with the Behavior Rating Inventory of Executive Function (BRIEF) and the Child Behavior Checklist (CBCL). We constructed simple and multiple linear regression models to identify immunological correlates of behavioral problems. RESULTS: A total of 144 children living with HIV (50% male) with a mean age of 8.9 years [Standard Deviation (s.d.) = 1.9] were included in the analysis. Eighty-two children were on antiretroviral therapy. Mean CD4 cell count % was 35.1 cells/µl (s.d. = 15.0), mean CD4 cell activation 5.7% (s.d. = 5.1), mean CD8 cell activation was 17.5% (s.d. = 11.2) and 60 children (41.7%) had a viral load of <4000 copies/ml. In the adjusted models for the BRIEF, higher scores were associated with higher viral loads (aß = 16.7 × 10-6, 95% CI -5.00 × 10-6 to 28.4 × 10-6), specifically on the behavioral regulation index. Higher mean CD8 activation % was associated with higher scores on the Externalizing Problems  and Total Problems  scales of the CBCL (aß = 0.17, 95% CI 0.04-0.31 and aß = 0.15, 95% CI 0.00-0.28, respectively). CONCLUSIONS: Poorer behavioral outcomes were associated with higher viral loads while higher CD8 activation was associated with poorer emotional and behavioral outcomes. Complete immunological assessments for children living with HIV could include commonly used viral and immunological parameters to identify those at higher risk of having negative behavior outcomes and who would benefit the most from behavioral interventions.

Seizure Activity and Neurological Sequelae in Ugandan Children who have Survived an Episode of Cerebral Malaria

Background: Seizures are a common presenting feature in children with cerebral malaria (CM) and neurologic deficits have been described in survivors of CM. However few prospective studies have described the frequency of seizure activity and neurologic deficits in survivors of CM over time. Methods: Eighty-two children aged 3 to 12 years who survived an episode of CM were followed up and monitored for seizure activity and neurologic deficits at discharge; 3; 6 and 24 months. Seventy six children with uncomplicated malaria (UM) and 105 healthy community controls (CC) age 3 to 12 years were recruited as comparison groups and the frequency of seizures in the 6 to 24 month follow-up period was compared in the 3 groups. Results: Cumulative incidence of seizures increased over time in children with CM; with a total of 2 of 76 children (2.6) reporting seizures at 3 months; 3 of 74 children (4.1) at 6 months and 11 of 68 children (16.2) at 24 months (Chi square for trend = 9.36; P=0.002). In contrast; neurologic deficits almost completely resolved over time; occurring in 19 of 76 children with CM (25) at discharge; 2 of 74 children (2.7) at 6 months; and 1 of 68 (1.5) children at 24 months. Conclusions: During the 24 months following a CM episode; neurologic deficits resolve but the cumulative incidence of seizures increases in children with CM. Neurologic impairment after an episode of CM may not be limited to the neurologic deficits seen at discharge

Social and psychological aspects of onchocercal skin disease in Nebbi district, Uganda.

Onchocerciasis affects 7% of Uganda's population and 1.5 million more people are at risk of infection with Onchocerca volvulus, the nematode that causes the disease. This paper reports the results of part of a multi-centre study whose objective was to determine the prevalence of onchocercal skin disease and its associated psychosocial importance in Uganda. The study employed a standardised clinical dermatological survey method along with the use of structured questionnaires, focus group discussions and key informant interviews. Out of a total of 993 persons examined to determine the prevalence of onchocercal skin lesions 253 persons were interviewed to determine the psychosocial importance of the disease. The results indicate that onchocercal skin disease is associated with a variety of psychosocial, physical and economic effects. The disease also leads to stigmatisation of affected persons and their families. It is suggested that dermatological effects of onchocerciasis should be recognised as an important cause of morbidity in Uganda.