Publications by authors named "Charles R Newton"

308 Publications

Performance of primary health care workers in detection of mental disorders comorbid with epilepsy in rural Ethiopia.

BMC Fam Pract 2021 Oct 14;22(1):204. Epub 2021 Oct 14.

Centre for Innovative Drug Development and Therapeutic Trials for Africa (CDT-Africa), College of Health Sciences, Addis Ababa University, Addis Ababa, Ethiopia.

Background: Timely detection and management of comorbid mental disorders in people with epilepsy is essential to improve outcomes. The objective of this study was to measure the performance of primary health care (PHC) workers in identifying comorbid mental disorders in people with epilepsy against a standardised reference diagnosis and a screening instrument in rural Ethiopia.

Methods: People with active convulsive epilepsy were identified from the community, with confirmatory diagnosis by trained PHC workers. Documented diagnosis of comorbid mental disorders by PHC workers was extracted from clinical records. The standardized reference measure for diagnosing mental disorders was the Operational Criteria for Research (OPCRIT plus) administered by psychiatric nurses. The mental disorder screening scale (Self-Reporting Questionnaire; SRQ-20), was administered by lay data collectors. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of PHC worker diagnosis against the reference standard diagnosis was calculated. Logistic regression was used to examine the factors associated with misdiagnosis of comorbid mental disorder by PHC workers.

Results: A total of 237 people with epilepsy were evaluated. The prevalence of mental disorders with standardised reference diagnosis was 13.9% (95% confidence interval (CI) 9.6, 18.2%) and by PHC workers was 6.3% (95%CI 3.2, 9.4%). The prevalence of common mental disorder using SRQ-20 at optimum cut-off point (9 or above) was 41.5% (95% CI 35.2, 47.8%). The sensitivity and specificity of PHC workers diagnosis was 21.1 and 96.1%, respectively, compared to the standardised reference diagnosis. In those diagnosed with comorbid mental disorders by PHC workers, only 6 (40%) had SRQ-20 score of 9 or above. When a combination of both diagnostic methods (SRQ-20 score ≥ 9 and PHC diagnosis of depression) was compared with the standardised reference diagnosis of depression, sensitivity increased to 78.9% (95% (CI) 73.4, 84.4%) with specificity of 59.7% (95% CI 53.2, 66.2%). Only older age was significantly associated with misdiagnosis of comorbid mental disorders by PHC (adjusted odds ratio, 95% CI = 1.06, 1.02 to 1.11).

Conclusion: Routine detection of co-morbid mental disorder in people with epilepsy was very low. Combining clinical judgement with use of a screening scale holds promise but needs further evaluation.
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http://dx.doi.org/10.1186/s12875-021-01551-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8518249PMC
October 2021

Mental health and well-being of older adults living with HIV in sub-Saharan Africa: a systematic review.

BMJ Open 2021 Sep 22;11(9):e052810. Epub 2021 Sep 22.

Department of Clinical Research (Neurosciences), KEMRI-Wellcome Trust Research Programme, Kilifi, Kenya.

Objective: In this systematic review, we aimed to summarise the empirical evidence on common mental disorders (CMDs), cognitive impairment, frailty and health-related quality of life (HRQoL) among people living with HIV aged ≥50 years (PLWH50 +) residing in sub-Saharan Africa (SSA). Specifically, we document the prevalence and correlates of these outcomes.

Design, Data Sources And Eligibility Criteria: The following online databases were systematically searched: PubMed, CINAHL, PsycINFO, Embase and Scopus up to January 2021. English-language publications on depression, anxiety, cognitive function, frailty and quality of life among PLWH50+ residing in SSA were included.

Data Extraction And Synthesis: We extracted information, including study characteristics and main findings. These were tabulated, and a narrative synthesis approach was adopted, given the substantial heterogeneity among included studies.

Results: A total of 50 studies from fifteen SSA countries met the inclusion criteria. About two-thirds of these studies emanated from Ethiopia, Uganda and South Africa. Studies regarding depression predominated (n=26), followed by cognitive impairment (n=13). Overall, PLWH50+ exhibited varying prevalence of depression (6%-59%), cognitive impairments (4%-61%) and frailty (3%-15%). The correlates of CMDs, cognitive impairment, frailty and HRQoL were rarely investigated, but those reported were sociodemographic variables, many of which were inconsistent.

Conclusions: This review documented an increasing number of published studies on HIV and ageing from SSA. However, the current evidence on the mental and well-being outcomes in PLWH50+ is inadequate to characterise the public health dimension of these impairments in SSA, because of heterogeneous findings, few well-designed studies and substantial methodological limitations in many of the available studies. Future work should have sufficiently large samples of PLWH50+, engage appropriate comparison groups, harmonise the measurement of these outcomes using a standardised methodology to generate more robust prevalence estimates and confirm predictors.

Prospero Registration Number: CRD42020145791.
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http://dx.doi.org/10.1136/bmjopen-2021-052810DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8461287PMC
September 2021

Impact of the COVID-19 pandemic on people with epilepsy: Findings from the Brazilian arm of the COV-E study.

Epilepsy Behav 2021 10 9;123:108261. Epub 2021 Aug 9.

Oxford Epilepsy Research Group, NIHR Biomedical Research Centre, Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital, Oxford OX3 9DU, UK. Electronic address:

The COVID-19 pandemic has had an unprecedented impact on people and healthcare services. The disruption to chronic illnesses, such as epilepsy, may relate to several factors ranging from direct infection to secondary effects from healthcare reorganization and social distancing measures.

Objectives: As part of the COVID-19 and Epilepsy (COV-E) global study, we ascertained the effects of COVID-19 on people with epilepsy in Brazil, based on their perspectives and those of their caregivers. We also evaluated the impact of COVID-19 on the care delivered to people with epilepsy by healthcare workers.

Methods: We designed separate online surveys for people with epilepsy and their caregivers. A further survey for healthcare workers contained additional assessments of changes to working patterns, productivity, and concerns for those with epilepsy under their care. The Brazilian arm of COV-E initially collected data from May to November 2020 during the country's first wave. We also examined national data to identify the Brazilian states with the highest COVID-19 incidence and related mortality. Lastly, we applied this geographic grouping to our data to explore whether local disease burden played a direct role in difficulties faced by people with epilepsy.

Results: Two hundred and forty-one people returned the survey, 20% were individuals with epilepsy (n = 48); 22% were caregivers (n = 53), and 58% were healthcare workers (n = 140). Just under half (43%) of people with epilepsy reported health changes during the pandemic, including worsening seizure control, with specific issues related to stress and impaired mental health. Of respondents prescribed antiseizure medication, 11% reported difficulty taking medication on time due to problems acquiring prescriptions and delayed or canceled medical appointments. Only a small proportion of respondents reported discussing significant epilepsy-related risks in the previous 12 months. Analysis of national COVID-19 data showed a higher disease burden in the states of Sao Paulo and Rio de Janeiro compared to Brazil as a whole. There were, however, no geographic differences observed in survey responses despite variability in the incidence of COVID-19.

Conclusion: Our findings suggest that Brazilians with epilepsy have been adversely affected by COVID-19 by factors beyond infection or mortality. Mental health issues and the importance of optimal communication are critical during these difficult times. Healthcare services need to find nuanced approaches and learn from shared international experiences to provide optimal care for people with epilepsy as the direct burden of COVID-19 improves in some countries. In contrast, others face resurgent waves of the pandemic.
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http://dx.doi.org/10.1016/j.yebeh.2021.108261DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8457887PMC
October 2021

Classifying epilepsy pragmatically: Past, present, and future.

J Neurol Sci 2021 08 29;427:117515. Epub 2021 May 29.

NIHR University College London Hospitals Biomedical Research Centre, UCL Queen Square Institute of Neurology, Queen Square, London WC1N 3BG, UK; Stichting Epilepsie InstelClingen Nederland (SEIN), Heemstede, the Netherlands; Chalfont Centre for Epilepsy, Chalfont St Peter SL9 0RJ, UK. Electronic address:

The classification of epilepsy is essential for people with epilepsy and their families, healthcare providers, physicians and researchers. The International League Against Epilepsy proposed updated seizure and epilepsy classifications in 2017, while another four-dimensional epilepsy classification was updated in 2019. An Integrated Epilepsy Classification system was proposed in 2020. Existing classifications, however, lack consideration of important pragmatic factors relevant to the day-to-day life of people with epilepsy and stakeholders. Despite promising developments, consideration of comorbidities in brain development, genetic causes, and environmental triggers of epilepsy remains largely user-dependent in existing classifications. Demographics of epilepsy have changed over time, while existing classification schemes exhibit caveats. A pragmatic classification scheme should incorporate these factors to provide a nuanced classification. Validation across disparate contexts will ensure widespread applicability and ease of use. A team-based approach may simplify communication between healthcare personnel, while an individual-centred perspective may empower people with epilepsy. Together, incorporating these elements into a modern but pragmatic classification scheme may ensure optimal care for people with epilepsy by emphasising cohesiveness among its myriad users. Technological advancements such as 7T MRI, next-generation sequencing, and artificial intelligence may affect future classification efforts.
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http://dx.doi.org/10.1016/j.jns.2021.117515DOI Listing
August 2021

Epilepsy in Sero-Positive Patients From Northern Uganda-Clinical, EEG and Brain Imaging Features.

Front Neurol 2021 3;12:687281. Epub 2021 Jun 3.

College of Health Sciences, Makerere University, Kampala, Uganda.

Globally, epilepsy is the most common chronic neurological disorder. The incidence in sub-Saharan Africa is 2-3 times higher than that in high income countries. Infection by may be an underlying risk factor for the high burden and based upon epidemiological associations, has been proposed to cause a group of disorders- associated epilepsies (OAE) like nodding syndrome (NS). To improve our understanding of the disease spectrum, we described the clinical, electroencephalographic (EEG) and magnetic resonance imaging (MRI) features of children with epilepsy and sero-positive for (possible OAEs other than nodding syndrome). Twenty-nine children and adolescents with non-nodding syndrome OAE in northern Uganda were enrolled. A diagnosis of OAE was made in patients with epilepsy and seizure onset after age 3 years, no reported exposure to perinatal severe febrile illness or traumatic brain injury, no syndromic epilepsy diagnosis and a positive Ov-16 ELISA test. Detailed clinical evaluation including psychiatric, diagnostic EEG, a diagnostic brain MRI (in 10 patients) and laboratory testing were performed. Twenty participants (69%) were male. The mean age was 15.9 (standard deviation [SD] 1.9) years while the mean age at seizure onset was 9.8 (SD 2.9) years. All reported normal early childhood development. The most common clinical presentation was a tonic-clonic seizure. The median number of seizures was 2 (IQR 1-4) in the previous month. No specific musculoskeletal changes, or cranial nerve palsies were reported, neither were any vision, hearing and speech difficulties observed. The interictal EEG was abnormal in the majority with slow wave background activity in 52% (15/29) while 41% (12/29) had focal epileptiform activity. The brain MRI showed mild to moderate cerebellar atrophy and varying degrees of atrophy of the frontal, parietal and occipital lobes. The clinical spectrum of epilepsies associated with Onchocerca may be broader than previously described. In addition, focal onset tonic-clonic seizures, cortical and cerebellar atrophy may be important brain imaging and clinical features.
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http://dx.doi.org/10.3389/fneur.2021.687281DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8209377PMC
June 2021

Setting the record straight on measuring SDG 4.2.1 - Authors' reply.

Lancet Glob Health 2021 07;9(7):e912

Population Health Science, London School of Economics, London, UK.

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http://dx.doi.org/10.1016/S2214-109X(21)00256-4DOI Listing
July 2021

Global survey on disruption and mitigation of neurological services during COVID-19: the perspective of global international neurological patients and scientific associations.

J Neurol 2021 Jun 11. Epub 2021 Jun 11.

Department of Neurology, Hospital Clínico Universitario de Valladolid, Valladolid, Spain.

Background: The COVID-19 pandemic outbreak has dramatically disrupted healthcare systems. Two rapid WHO pulse surveys studied disruptions in mental health services, but did not particularly focus on neurology. Here, a global survey was conducted and addresses the impact of the pandemic on neurology services.

Methods: A cross-sectional study was carried out in which 34 international neurological associations were asked to distribute the survey to national associations. The responses represented the national situation, in November-December 2020, with regard to the main disrupted neurological services, reasons and the mitigation strategies implemented as well as the disruption on training of residents and on neurological research. A comparison with the situation in February-April 2020, first pandemic wave, was also requested.

Findings: 54 completed surveys came from 43 countries covering all the 6 WHO regions. Overall, neurological services disruption was reported as mild by 26%, moderate by 30%, complete by 13% of associations. The most affected services were cross-sectoral neurological services (57%) and neurorehabilitation (56%). The second wave of the pandemic, however, was associated with the improvement of service provision for diagnostics services (44%) and for neurorehabilitation (41%). Governmental directives were the major cause of services' disruption (56%). Mitigation strategies were mostly established through telemedicine (48%). Almost half of respondents reported a significant impact on neurological research (48%) and educational activities (60%). Most associations (67%) were not involved in decision making for neurological patients' issues by their national government.

Interpretation: The COVID-19 pandemic affects neurological services and raises the universal need for the development of neurological health care at the policy, systems and services levels. A global national plan on mitigation strategies for disruption of neurological services during pandemic situations should be established and neurological scientific and patients associations should get involved in decision making.
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http://dx.doi.org/10.1007/s00415-021-10641-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8195244PMC
June 2021

Clinical features of bacterial meningitis among hospitalised children in Kenya.

BMC Med 2021 06 4;19(1):122. Epub 2021 Jun 4.

Clinical Research Department, KEMRI-Wellcome Trust Research Programme, P.O. Box 230 80108, Kilifi, Kenya.

Background: Diagnosing bacterial meningitis is essential to optimise the type and duration of antimicrobial therapy to limit mortality and sequelae. In sub-Saharan Africa, many public hospitals lack laboratory capacity, relying on clinical features to empirically treat or not treat meningitis. We investigated whether clinical features of bacterial meningitis identified prior to the introduction of conjugate vaccines still discriminate meningitis in children aged ≥60 days.

Methods: We conducted a retrospective cohort study to validate seven clinical features identified in 2002 (KCH-2002): bulging fontanel, neck stiffness, cyanosis, seizures outside the febrile convulsion age range, focal seizures, impaired consciousness, or fever without malaria parasitaemia and Integrated Management of Childhood Illness (IMCI) signs: neck stiffness, lethargy, impaired consciousness or seizures, and assessed at admission in discriminating bacterial meningitis after the introduction of conjugate vaccines. Children aged ≥60 days hospitalised between 2012 and 2016 at Kilifi County Hospital were included in this analysis. Meningitis was defined as positive cerebrospinal fluid (CSF) culture, organism observed on CSF microscopy, positive CSF antigen test, leukocytes ≥50/μL, or CSF to blood glucose ratio <0.1.

Results: Among 12,837 admissions, 98 (0.8%) had meningitis. The presence of KCH-2002 signs had a sensitivity of 86% (95% CI 77-92) and specificity of 38% (95% CI 37-38). Exclusion of 'fever without malaria parasitaemia' reduced sensitivity to 58% (95% CI 48-68) and increased specificity to 80% (95% CI 79-80). IMCI signs had a sensitivity of 80% (95% CI 70-87) and specificity of 62% (95% CI 61-63).

Conclusions: A lower prevalence of bacterial meningitis and less typical signs than in 2002 meant the lower performance of KCH-2002 signs. Clinicians and policymakers should be aware of the number of lumbar punctures (LPs) or empirical treatments needed for each case of meningitis. Establishing basic capacity for CSF analysis is essential to exclude bacterial meningitis in children with potential signs.
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http://dx.doi.org/10.1186/s12916-021-01998-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8176744PMC
June 2021

High Prevalence of Epilepsy in an Onchocerciasis-Endemic Area in Mvolo County, South Sudan: A Door-To-Door Survey.

Pathogens 2021 May 14;10(5). Epub 2021 May 14.

Global Health Institute, University of Antwerp, Kinsbergen Centrum, Doornstraat 331, 2610 Antwerp, Belgium.

In June 2020, a door-to-door household survey was conducted in Mvolo County, an onchocerciasis-endemic area in South Sudan. A total of 2357 households containing 15,699 individuals agreed to participate in the study. Of these, 5046 (32.1%, 95% CI: 31.4-32.9%) had skin itching and 445 (2.8%, 95% CI: 2.6-3.1%) were blind. An epilepsy screening questionnaire identified 813 (5.1%) persons suspected of having epilepsy. Of them, 804 (98.9%) were seen by a medical doctor, and in 798 (98.1%) the diagnosis of epilepsy was confirmed. The overall epilepsy prevalence was 50.8/1000 (95% CI: 47.6-54.4/1000), while the prevalence of nodding syndrome was 22.4/1000 (95% CI: 20.1-24.9/1000). Younger age, being male, skin itching, blindness, and living in a neighbourhood or village close to the Naam River were risk factors for epilepsy. The annual incidence of epilepsy was 82.8/100,000 (95% CI: 44.1-141.6/100,000). Among children 7-9 years old without epilepsy, 34% were Ov16 seropositive, suggesting high ongoing transmission, but only 41.9% of them took ivermectin during the last mass distribution. In conclusion, a high prevalence and incidence of epilepsy was observed in Mvolo, South Sudan. Strengthening of the onchocerciasis elimination programme is urgently needed in order to prevent epilepsy in this region.
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http://dx.doi.org/10.3390/pathogens10050599DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8157079PMC
May 2021

Epidemiology of status epilepticus in children.

Authors:
Charles R Newton

Dev Med Child Neurol 2021 09 27;63(9):1011. Epub 2021 May 27.

Department of Psychiatry, Warneford Hospital, University of Oxford, Oxford, UK.

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http://dx.doi.org/10.1111/dmcn.14946DOI Listing
September 2021

Systemic and cerebrospinal fluid immune and complement activation in Ugandan children and adolescents with long-standing nodding syndrome: A case-control study.

Epilepsia Open 2021 Jun 12;6(2):297-309. Epub 2021 Mar 12.

Makerere University College of Health Sciences, Kampala, Uganda.

Objective: Nodding syndrome is a poorly understood epileptic encephalopathy characterized by a unique seizure type-head nodding-and associated with Onchocerca volvulus infection. We hypothesized that altered immune activation in the cerebrospinal fluid (CSF) and plasma of children with nodding syndrome may yield insights into the pathophysiology and progression of this seizure disorder.

Method: We conducted a case-control study of 154 children (8 years or older) with long-standing nodding syndrome and 154 healthy age-matched community controls in 3 districts of northern Uganda affected by nodding syndrome. Control CSF samples were obtained from Ugandan children in remission from hematological malignancy during routine follow-up. Markers of immune activation and inflammation (cytokines and chemokines) and complement activation (C5a) were measured in plasma and CSF using ELISA or Multiplex Luminex assays. O volvulus infection was assessed by serology for anti-OV-16 IgG levels.

Results: The mean (SD) age of the population was 15.1 (SD: 1.9) years, and the mean duration of nodding syndrome from diagnosis to enrollment was 8.3 (SD: 2.7) years. The majority with nodding syndrome had been exposed to O volvulus (147/154 (95.4%)) compared with community children (86/154 (55.8%)), with an OR of 17.04 (95% CI: 7.33, 45.58), P < .001. C5a was elevated in CSF of children with nodding syndrome compared to controls (P < .0001). The levels of other CSF markers tested were comparable between cases and controls after adjusting for multiple comparisons. Children with nodding syndrome had lower plasma levels of IL-10, APRIL, CCL5 (RANTES), CCL2, CXCL13, and MMP-9 compared with community controls (P < .05 for all; multiple comparisons). Plasma CRP was elevated in children with nodding syndrome compared to community children and correlated with disease severity.

Significance: Nodding syndrome is associated with exposure to O. volvulus. Compared to controls, children with long-standing symptoms of nodding syndrome show evidence of complement activation in CSF and altered immune activation in plasma.
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http://dx.doi.org/10.1002/epi4.12463DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8166803PMC
June 2021

Disruptions of neurological services, its causes and mitigation strategies during COVID-19: a global review.

J Neurol 2021 Nov 22;268(11):3947-3960. Epub 2021 May 22.

Neurology, Public Health, Disability Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy.

Background: The COVID-19 pandemic leads to disruptions of health services worldwide. To evaluate the particular impact on neurological services a rapid review was conducted.

Methods: Studies reporting the provision of neurological services during the pandemic and/or adopted mitigation strategies were included in this review. PubMed and World Health Organization's (WHO) COVID-19 database were searched. Data extraction followed categories used by WHO COVID-19 pulse surveys and operational guidelines on maintaining essential health services during COVID-19.

Findings: The search yielded 1101 articles, of which 369 fulfilled eligibility criteria, describing data from 210,419 participants, being adults (81%), children (11.4%) or both (7.3%). Included articles reported data from 105 countries and territories covering all WHO regions and World Bank income levels (low income: 1.9%, lower middle: 24.7%, upper middle: 29.5% and high income; 44.8%). Cross-sectoral services for neurological disorders were most frequently disrupted (62.9%), followed by emergency/acute care (47.1%). The degree of disruption was at least moderate for 75% of studies. Travel restrictions due to lockdowns (81.7%) and regulatory closure of services (65.4%) were the most commonly reported causes of disruption. Authors most frequently described telemedicine (82.1%) and novel dispensing approaches for medicines (51.8%) as mitigation strategies. Evidence for the effectiveness of these measures is largely missing.

Interpretation: The COVID-19 pandemic affects all aspects of neurological care. Given the worldwide prevalence of neurological disorders and the potential long-term neurological consequences of COVID-19, service disruptions are devastating. Different strategies such as telemedicine might mitigate the negative effects of the pandemic, but their efficacy and acceptability remain to be seen.
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http://dx.doi.org/10.1007/s00415-021-10588-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8140556PMC
November 2021

Premature Mortality, Risk Factors, and Causes of Death Following Childhood-Onset Neurological Impairments: A Systematic Review.

Front Neurol 2021 9;12:627824. Epub 2021 Apr 9.

Kenya Medical Research Institute (KEMRI-Wellcome Trust Research Programme), Clinical Research (Neurosciences), Kilifi, Kenya.

Neurological impairment (NI) and disability are associated with reduced life expectancy, but the risk and magnitude of premature mortality in children vary considerably across study settings. We conducted a systematic review to estimate the magnitude of premature mortality following childhood-onset NI worldwide and to summarize known risk factors and causes of death. We searched various databases for published studies from their inception up to 31st October 2020. We included all cohort studies that assessed the overall risk of mortality in individuals with childhood-onset epilepsy, intellectual disability (ID), and deficits in hearing, vision and motor functions. Comparative measures of mortality such as the standardized mortality ratio (SMR), risk factors and causes were synthesized quantitatively under each domain of impairment. This review is registered on the PROSPERO database (registration number CRD42019119239). The search identified 2,159 studies, of which 24 studies were included in the final synthesis. Twenty-two (91.7%) studies originated from high-income countries (HICs). The median SMR was higher for epilepsy compared with ID (7.1 [range 3.1-22.4] vs. 2.9 [range 2.0-11.6]). In epilepsy, mortality was highest among younger age groups, comorbid neurological disorders, generalized seizures (at univariable levels), untreatable epilepsy, soon after diagnosis and among cases with structural/metabolic types, but there were no differences by sex. Most deaths (87.5%) were caused by non-epilepsy-related causes. For ID, mortality was highest in younger age groups and girls had a higher risk compared to the general population. Important risk factors for premature mortality were severe-to-profound severity, congenital disorders e.g., Down Syndrome, comorbid neurological disorders and adverse pregnancy and perinatal events. Respiratory infections and comorbid neurological disorders were the leading causes of death in ID. Mortality is infrequently examined in impairments of vision, hearing and motor functions. The risk of premature mortality is elevated in individuals with childhood-onset NI, particularly in epilepsy and lower in ID, with a need for more studies for vision, hearing, and motor impairments. Survival in NI could be improved through interventions targeting modifiable risk factors and underlying causes.
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http://dx.doi.org/10.3389/fneur.2021.627824DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8062883PMC
April 2021

Low-coverage sequencing cost-effectively detects known and novel variation in underrepresented populations.

Am J Hum Genet 2021 04 25;108(4):656-668. Epub 2021 Mar 25.

Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA 02114, USA; Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.

Genetic studies in underrepresented populations identify disproportionate numbers of novel associations. However, most genetic studies use genotyping arrays and sequenced reference panels that best capture variation most common in European ancestry populations. To compare data generation strategies best suited for underrepresented populations, we sequenced the whole genomes of 91 individuals to high coverage as part of the Neuropsychiatric Genetics of African Population-Psychosis (NeuroGAP-Psychosis) study with participants from Ethiopia, Kenya, South Africa, and Uganda. We used a downsampling approach to evaluate the quality of two cost-effective data generation strategies, GWAS arrays versus low-coverage sequencing, by calculating the concordance of imputed variants from these technologies with those from deep whole-genome sequencing data. We show that low-coverage sequencing at a depth of ≥4× captures variants of all frequencies more accurately than all commonly used GWAS arrays investigated and at a comparable cost. Lower depths of sequencing (0.5-1×) performed comparably to commonly used low-density GWAS arrays. Low-coverage sequencing is also sensitive to novel variation; 4× sequencing detects 45% of singletons and 95% of common variants identified in high-coverage African whole genomes. Low-coverage sequencing approaches surmount the problems induced by the ascertainment of common genotyping arrays, effectively identify novel variation particularly in underrepresented populations, and present opportunities to enhance variant discovery at a cost similar to traditional approaches.
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http://dx.doi.org/10.1016/j.ajhg.2021.03.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8059370PMC
April 2021

The conundrum of a global tool for early childhood development to monitor SDG indicator 4.2.1.

Lancet Glob Health 2021 05 25;9(5):e586-e587. Epub 2021 Feb 25.

Population Health Science, London School of Economics, London, UK.

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http://dx.doi.org/10.1016/S2214-109X(21)00030-9DOI Listing
May 2021

Prevalence, risk and protective indicators of common mental disorders among young people living with HIV compared to their uninfected peers from the Kenyan coast: a cross-sectional study.

BMC Psychiatry 2021 02 10;21(1):90. Epub 2021 Feb 10.

KEMRI-Wellcome Trust Research Programme, Centre for Geographic Medicine Research (Coast), KEMRI, Box 230, Kilifi, Kenya.

Background: In sub-Saharan Africa, common mental disorders (CMDs) like depression and anxiety are under-investigated amongst young people living with HIV (YLWH). To address the gap, in Kenya we: a) determined the prevalence of CMDs among YLWH compared to their uninfected peers; b) investigated HIV status as an independent predictor of CMDs in young people; c) investigated CMDs risk and protective indicators with more focus on YLWH.

Methods: Between November 2018 and September 2019, 819 young people aged 18-24 years (407 HIV-infected) were recruited from two Counties on the Kenyan coast. Locally adapted pre-existing mental health measures, Patient Health Questionnaire (9-item) and Generalized Anxiety Disorder scale (7-item), were administered among other questionnaires via audio computer-assisted self-interview. Logistic regression was used to determine the correlates of CMDs.

Results: Prevalence of CMDs was significantly elevated among YLWH compared to their uninfected peers i.e. 29% vs. 12%; p < 0.001 for depressive symptoms, 19% vs. 8%; p < 0.001 for anxiety symptoms, and 16% vs. 5%; p < 0.001 for comorbid depressive and anxiety symptoms. HIV status independently predicted depressive symptoms and its co-occurrence with anxiety symptoms. Among YLWH, negative life events, higher perceived HIV-related stigma and low adherence to antiretroviral therapy were the risk indicators for elevated CMDs. Among HIV-uninfected youths, death of both parents was a risk indicator for elevated depressive symptoms. Protective indicators against CMDs among youths with and without HIV included higher social support and health-related quality of life.

Conclusion: At the Kenyan coast, YLWH have significantly higher burden of CMDs compared to their uninfected peers. Being HIV-positive as a youth in this setting is predictive of more depressive symptoms and its comorbidity with anxiety symptoms. YLWH at high risk of CMDs in coastal Kenya can benefit from early detection, referral and treatment if routine screening for CMDs is integrated in their care package. The mental wellbeing of bereaving HIV-unaffected youths could be improved through continued support to help them come to terms with their loss. At the community level, programmes strengthening the social capital or improving the overall quality of life of youths with or without HIV may be beneficial to their mental health.
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http://dx.doi.org/10.1186/s12888-021-03079-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7877112PMC
February 2021

Comorbid mental disorders and quality of life of people with epilepsy attending primary health care clinics in rural Ethiopia.

PLoS One 2021 20;16(1):e0238137. Epub 2021 Jan 20.

Centre for Innovative Drug Development and Therapeutic Trials for Africa (CDT-Africa), College of Health Sciences, Addis Ababa University, Addis Ababa, Ethiopia.

Background: Evidence from high-income countries demonstrates that co-morbid mental disorders in people with epilepsy adversely affect clinical and social outcomes. However, evidence from low-income countries is lacking. The objective of this study was to measure the association between co-morbid mental disorders and quality of life and functioning in people with epilepsy.

Methods: A facility-based, community ascertained cross-sectional survey was carried out in selected districts of the Gurage Zone, Southern Ethiopia. Participants were identified in the community and referred to primary health care (PHC) clinics. Those diagnosed by PHC workers were recruited. Co-morbid mental disorders were measured using a standardised, semi-structured clinical interview administered by mental health professionals. The main outcome, quality of life, was measured using the Quality of Life in Epilepsy questionnaire (QOLIE-10p). The secondary outcome, functional disability, was assessed using the 12-item World Health Organization Disability Assessment Schedule (WHODAS-2).

Results: The prevalence of comorbid mental disorders was 13.9%. Comorbid mental disorders were associated with poorer quality of life (Adjusted (Adj.) β -13.27; 95% CI -23.28 to-3.26) and greater disability (multiplier of WHODAS-2 score 1.62; 95% CI 1.05, 2.50) after adjusting for hypothesised confounding factors. Low or very low relative wealth (Adj. β = -12.57, 95% CI -19.94 to-5.20), higher seizure frequency (Adj.β coef. = -1.92, 95% CI -2.83 to -1.02), and poor to intermediate social support (Adj. β coef. = -9.66, 95% CI -16.51 to -2.81) were associated independently with decreased quality of life. Higher seizure frequency (multiplier of WHODAS-2 score 1.11; 95% CI 1.04, 1.19) was associated independently with functional disability.

Conclusion: Co-morbid mental disorders were associated with poorer quality of life and impairment, independent of level of seizure control. Integrated and comprehensive psychosocial care is required for better health and social outcomes of people with epilepsy.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0238137PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7817054PMC
April 2021

Long-Term Mental Health and Quality of Life Outcomes of Neonatal Insults in Kilifi, Kenya.

Child Psychiatry Hum Dev 2021 Jan 16. Epub 2021 Jan 16.

Centre for Geographic Medicine Research Coast, Kenya Medical Research Institute, Kilifi, Kenya.

We examined the mental health and quality of life (QoL) outcomes and their correlates of school-aged survivors of neonatal jaundice (NNJ), hypoxic-ischemic encephalopathy (HIE), and a comparison group. The Child Behavior Checklist and the Pediatric Quality of Life Inventory were administered to assess the mental health and QoL of 375 children (134 with NNJ, 107 with HIE, and 134 comparison group) aged 6 to 12 years [Median age 9 (interquartile range 7 to 11)]. The results showed that survivors of NNJ and HIE have mental health problems and QoL similar to the comparison group. Maternal mental health was the predominant covariate of mental health and QoL in survivors of NNJ and HIE. This result could indicate that mothers with mental health problems are more likely to have children with mental health issues, but also that caring for children with these adversities may affect mental health well-being of the caregivers. There is a need for early mental health screening and psychosocial intervention for caregivers and their children to enhance both their mental health and QoL.
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http://dx.doi.org/10.1007/s10578-020-01079-1DOI Listing
January 2021

Onchocerca volvulus and epilepsy: A comprehensive review using the Bradford Hill criteria for causation.

PLoS Negl Trop Dis 2021 01 7;15(1):e0008965. Epub 2021 Jan 7.

Global Health Institute, University of Antwerp, Antwerp, Belgium.

Background: The possibility that onchocerciasis may cause epilepsy has been suggested for a long time, but thus far, an etiological link has not been universally accepted. The objective of this review is to critically appraise the relationship between Onchocerca volvulus and epilepsy and subsequently apply the Bradford Hill criteria to further evaluate the likelihood of a causal association.

Methods: PubMed and gray literature published until September 15, 2020, were searched and findings from original research were synthesized. Adherence to the 9 Bradford Hill criteria in the context of onchocerciasis and epilepsy was determined to assess whether the criteria are met to strengthen the evidence base for a causal link between infection with O. volvulus and epilepsy, including the nodding syndrome.

Results: Onchocerciasis as a risk factor for epilepsy meets the following Bradford Hill criteria for causality: strength of the association, consistency, temporality, and biological gradient. There is weaker evidence supporting causality based on the specificity, plausibility, coherence, and analogy criteria. There is little experimental evidence. Considering the Bradford Hill criteria, available data suggest that under certain conditions (high microfilarial load, timing of infection, and perhaps genetic predisposition), onchocerciasis is likely to cause epilepsy including nodding and Nakalanga syndromes.

Conclusion: Applying the Bradford Hill criteria suggests consistent epidemiological evidence that O. volvulus infection is a trigger of epilepsy. However, the pathophysiological mechanisms responsible for seizure induction still need to be elucidated.
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http://dx.doi.org/10.1371/journal.pntd.0008965DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7790236PMC
January 2021

Time-to-death is a potential confounder in observational studies of blood transfusion in severe malaria - Authors' reply.

Lancet Haematol 2021 01 22;8(1):e12-e13. Epub 2020 Dec 22.

ISGlobal, Barcelona, Spain; Hospital Clínic i Provincial de Barcelona, Centro de Diagnóstico Biomédico, Universitat de Barcelona, Barcelona, Spain; Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.

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http://dx.doi.org/10.1016/S2352-3026(20)30412-9DOI Listing
January 2021

Childhood autism spectrum disorder: insights from a tertiary hospital cohort in Kenya.

Afr J Health Sci 2020 Mar-Apr;33(2):12-21. Epub 2020 Sep 17.

School of Public Health, Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, MA, USA.

Introduction: Autism spectrum disorder (ASD) is characterized by impairments in behavior, social communication, and interaction. There is little data on ASD from sub-Saharan Africa (SSA) describing clinical characteristics in large cohorts of patients. Preliminary studies report a high male sex ratio, excess of nonverbal cases, possible infectious etiologies, and comorbidities e.g. epilepsy.

Objective: To describe the clinical characteristics of children diagnosed with ASD in an African context.

Methods: A retrospective medical chart review identified 116 children diagnosed with ASD according to DSM-5 criteria at a pediatric neurology clinic in Nairobi, Kenya.

Results: The male to female ratio was 4.3:1. The median age at presentation was 3 years with speech delay as the most common reason for presentation. Expressive language delay was observed in 90% of the population. Sixty percent who obtained imaging had normal MRI brain findings. Only 44% and 34% of children had access to speech therapy and occupational therapy respectively. Epilepsy and ADHD were the most prevalent comorbidities.

Conclusion: An early median age at presentation and preponderance of male gender is observed. Access to speech therapy and other interventions was low. A prospective study would help determine outcomes for similar children following appropriate interventions.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7746135PMC
September 2020

Evaluating risk to people with epilepsy during the COVID-19 pandemic: Preliminary findings from the COV-E study.

Epilepsy Behav 2021 02 28;115:107658. Epub 2020 Nov 28.

Oxford Epilepsy Research Group, NIHR Biomedical Research Centre, Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital, Oxford OX3 9DU, UK. Electronic address:

The COVID-19 pandemic has caused global anguish unparalleled in recent times. As cases rise, increased pressure on health services, combined with severe disruption to people's everyday lives, can adversely affect individuals living with chronic illnesses, including people with epilepsy. Stressors related to disruption to healthcare, finances, mental well-being, relationships, schooling, physical activity, and increased isolation could increase seizures and impair epilepsy self-management. We aim to understand the impact that COVID-19 has had on the health and well-being of people with epilepsy focusing on exposure to increased risk of seizures, associated comorbidity, and mortality. We designed two online surveys with one addressing people with epilepsy directly and the second for caregivers to report on behalf of a person with epilepsy. The survey is ongoing and has yielded 463 UK-based responses by the end of September 2020. Forty percent of respondents reported health changes during the pandemic (n = 185). Respondents cited a change in seizures (19%, n = 88), mental health difficulties (34%, n = 161), and sleep disruption (26%, n = 121) as the main reasons. Thirteen percent found it difficult to take medication on time. A third had difficulty accessing medical services (n = 154), with 8% having had an appointment canceled (n = 39). Only a small proportion reported having had discussions about epilepsy-related risks, such as safety precautions (16%, n = 74); mental health (29%, n = 134); sleep (30%, n = 140); and Sudden Unexpected Death in Epilepsy (SUDEP; 15%, n = 69) in the previous 12 months. These findings suggest that people with epilepsy are currently experiencing health changes, coupled with inadequate access to services. Also, there seems to be a history of poor risk communication in the months preceding the pandemic. As the UK witnesses a second COVID-19 wave, those involved in healthcare delivery must ensure optimal care is provided for people with chronic conditions, such as epilepsy, to ensure that avoidable morbidity and mortality is prevented during the pandemic, and beyond.
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http://dx.doi.org/10.1016/j.yebeh.2020.107658DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7698680PMC
February 2021

Validation of a Swahili version of the 9-item Patient Health Questionnaire (PHQ-9) among adults living with HIV compared to a community sample from Kilifi, Kenya.

J Affect Disord Rep 2020 Dec;1:100013

Neurosciences Group, KEMRI-Wellcome Trust Research Programme, Centre for Geographic Medicine Research (Coast), Box 230, Kilifi, Kenya.

Background: Depression remains under-investigated in people living with HIV in sub-Saharan Africa due to paucity of adequately validated measures. This study aimed to validate an adapted version of the 9-item Patient Health Questionnaire (PHQ-9) among adults living with HIV compared to those from the community in Kilifi, Kenya.

Methods: Analysis of data from 450 adults living with HIV and 337 adults from the community was conducted examining the reliability, factorial structure, measurement invariance and discriminant validity of interviewer-administered PHQ-9, Swahili version.

Results: Internal consistency of the Swahili PHQ-9 was good overall, in adults living with HIV and those from the community (Macdonald's omega > 0.80). The two-week test-retest reliability was acceptable among adults living with HIV (0.64). A one-factor confirmatory factor analysis (CFA) model indicated the Swahili PHQ-9 was unidimensional in the overall sample, in adults living with HIV and those from the community. Multi-group CFA substantiated measurement invariance of this unidimensional scale across participant group (adults living with HIV vs. community), sex (females vs. males) and age category (young, middle-age and elderly adults). The Swahili PHQ-9 exhibited good discriminant validity between the two participant groups.

Limitations: No diagnostic interview for mental disorders was administered in the original studies limiting analysis of sensitivity and specificity of the Swahili PHQ-9.

Conclusion: The Swahili PHQ-9 is a reliable and valid unidimensional scale. It appears a valuable tool for assessing depressive symptoms that can be generalized across different demographic groups, in primary HIV clinics and the general community within this and similar settings.
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http://dx.doi.org/10.1016/j.jadr.2020.100013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7714257PMC
December 2020

Long-term neurocognitive and educational outcomes of neonatal insults in Kilifi, Kenya.

BMC Psychiatry 2020 12 2;20(1):578. Epub 2020 Dec 2.

Centre for Geographic Medicine Research Coast, Kenya Medical Research Institute, P.O Box 230, Kilifi, Kenya.

Background: There is little data on the long-term neurocognitive and educational outcomes among school-aged survivors of neonatal jaundice (NNJ) and hypoxic-ischemic encephalopathy (HIE) in Africa. This study investigates the long-term neurocognitive and educational outcomes and the correlates of these outcomes in school-aged survivors of NNJ or HIE in Kilifi, Kenya.

Methods: We conducted a cross-sectional study on neurocognitive and educational outcomes among school-aged survivors (6-12 years) of NNJ (n = 134) and HIE (n = 107) and compared them to a community comparison group (n = 134). We assessed nonverbal intelligence, planning, working memory, attention, syntax, pragmatics, word-finding, memory, perceptual-motor, mathematical, and reading abilities. We also collected information on medical history, caregivers' mental health, and family environment.

Results: The survivors of NNJ had lower mean total scores in word-finding [F (1, 250) = 3.89, p = 0.050] and memory [F (1, 248) = 6.74, p = 0.010] than the comparison group. The survivors of HIE had lower mean scores in pragmatics [F (1, 230) = 6.61, p = 0.011] and higher scores higher scores in non-verbal reasoning [F (1, 225) =4.10, p = 0.044] than the comparison group. Stunted growth was associated with almost all the outcomes in HIE.

Conclusion: Survivors of NNJ and HIE present with impairment in the multiple domains, which need to be taken into consideration in the planning of educational and rehabilitative services.
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http://dx.doi.org/10.1186/s12888-020-02939-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7709237PMC
December 2020

Household poverty, schooling, stigma and quality of life in adolescents with epilepsy in rural Uganda.

Epilepsy Behav 2021 01 25;114(Pt A):107584. Epub 2020 Nov 25.

Makerere University College of Health Sciences, Kampala, Uganda; Centre for Tropical Neuroscience, Kampala, Uganda; Kenya Medical Research Institute-Wellcome Trust Collaborative Programme, Kilifi, Kenya; Centre for Tropical Medicine and Global Health, University of Oxford, Oxford, UK. Electronic address:

Background: Epilepsy remains a leading chronic neurological disorder in Low- and Middle-Income Countries. In Uganda, the highest burden is among young rural people. We aimed to; (i) describe socio-economic status (including schooling), and household poverty in adolescents living with epilepsy (ALE) compared to unaffected counterparts in the same communities and (ii) determine the factors associated with the overall quality of life (QoL).

Methods: This was a cross-sectional survey nested within a larger study of ALE compared to age-matched healthy community children in Uganda. Between Sept 2016 to Sept 2017, 154 ALE and 154 healthy community controls were consecutively recruited. Adolescents recruited were frequency and age-matched based on age categories 10-14 and 15-19 years. Clinical history and standardized assessments were conducted. One control participant had incomplete assessment and was excluded. The primary outcome was overall QoL and key variables assessed were schooling status and household poverty. Descriptive and multivariable linear regression analysis were conducted for independent associations with overall QoL.

Results: Mean (SD) age at seizure onset was 8.8 (3.9) years and median (IQR) monthly seizure burden was 2 (1-4). Epilepsy was associated with living in homes with high household poverty; 95/154 (61.7%) ALE lived in the poorest homes compared to 68/153 (44.5%) of the healthy adolescents, p = 0.001. Nearly two-thirds of ALE had dropped out of school and only 48/154 (31.2%) were currently attending school compared to 136/153 (88.9%) of healthy controls, p < 0.001. QoL was lowest among ALE who never attended school (p < 0.001), with primary education (p = 0.006) compared to those with at least secondary education. Stigma scores [mean(SD)] were highest among ALE in the poorest [69.1(34.6)], and wealthy [70.2(32.2)] quintiles compared to their counterparts in poorer [61.8(31.7)], medium [68.0(32.7)] and wealthiest [61.5(33.3)] quintiles, though not statistically significant (p = 0.75). After adjusting for covariates, ALE currently attending school had higher overall QoL compared to their counterparts who never attended school (β = 4.20, 95%CI: 0.90,7.49, p = 0.013). QoL scores were higher among ALE with ≥secondary education than those with no or primary education (β = 10.69, 95%CI: 1.65, 19.72).

Conclusions: ALE in this rural area are from the poorest households, are more likely to drop out of school and have the lowest QoL. Those with poorer seizure control are most affected. ALE should be included among vulnerable population groups and in addition to schooling, strategies for seizure control and addressing the epilepsy treatment gap in affected homes should be specifically targeted in state poverty eradication programs.
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http://dx.doi.org/10.1016/j.yebeh.2020.107584DOI Listing
January 2021

Community health workers to improve adherence to anti-seizure medication in rural South Africa: Is it cost-effective?

Epilepsia 2021 01 25;62(1):98-106. Epub 2020 Nov 25.

Department of Epidemiology and Global Health, Umeå University, Umeå, Sweden.

Objective: Epilepsy is a common, chronic neurological disorder that disproportionately affects individuals living in low- and middle-income countries (LMICs), where the treatment gap remains high and adherence to medication remains low. Community health workers (CHWs) have been shown to be effective at improving adherence to chronic medications, yet no study assessing the costs of CHWs in epilepsy management has been reported.

Methods: Using a Markov model with age- and sex-varying transition probabilities, we determined whether deploying CHWs to improve epilepsy treatment adherence in rural South Africa would be cost-effective. Data were derived using published studies from rural South Africa. Official statistics and international disability weights provided cost and health state values, respectively, and health gains were measured using quality adjusted life years (QALYs).

Results: The intervention was estimated at International Dollars ($) 123 250 per annum per sub-district community and cost $1494 and $1857 per QALY gained for males and females, respectively. Assuming a costlier intervention and lower effectiveness, cost per QALY was still less than South Africa's Gross Domestic Product per capita of $13 215, the cost-effectiveness threshold applied.

Significance: CHWs would be cost-effective and the intervention dominated even when costs and effects of the intervention were unfavorably varied. Health system re-engineering currently underway in South Africa identifies CHWs as vital links in primary health care, thereby ensuring sustainability of the intervention. Further research on understanding local health state utility values and cost-effectiveness thresholds could further inform the current model, and undertaking the proposed intervention would provide better estimates of its efficacy on reducing the epilepsy treatment gap in rural South Africa.
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http://dx.doi.org/10.1111/epi.16756DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7839757PMC
January 2021

Clustering of health risk behaviors among adolescents in Kilifi, Kenya, a rural Sub-Saharan African setting.

PLoS One 2020 12;15(11):e0242186. Epub 2020 Nov 12.

Centre for Geographic Medicine Research Coast, Kenya Medical Research Institute (KEMRI), Kilifi, Kenya.

Background: Adolescents tend to experience heightened vulnerability to risky and reckless behavior. Adolescents living in rural settings may often experience poverty and a host of risk factors which can increase their vulnerability to various forms of health risk behavior (HRB). Understanding HRB clustering and its underlying factors among adolescents is important for intervention planning and health promotion. This study examines the co-occurrence of injury and violence, substance use, hygiene, physical activity, and diet-related risk behaviors among adolescents in a rural setting on the Kenyan coast. Specifically, the study objectives were to identify clusters of HRB; based on five categories of health risk behavior, and to identify the factors associated with HRB clustering.

Methods: A cross-sectional survey was conducted of a random sample of 1060 adolescents aged 13-19 years living within the area covered by the Kilifi Health and Demographic Surveillance System. Participants completed a questionnaire on health behaviors which was administered via an Audio Computer-Assisted Self-Interview. Latent class analysis on 13 behavioral factors (injury and violence, hygiene, alcohol tobacco and drug use, physical activity, and dietary related behavior) was used to identify clustering and stepwise ordinal logistic regression with nonparametric bootstrapping identified the factors associated with clustering. The variables of age, sex, education level, school attendance, mental health, form of residence and level of parental monitoring were included in the initial stepwise regression model.

Results: We identified 3 behavioral clusters (Cluster 1: Low-risk takers (22.9%); Cluster 2: Moderate risk-takers (67.8%); Cluster 3: High risk-takers (9.3%)). Relative to the cluster 1, membership of higher risk clusters (i.e. moderate or high risk-takers) was strongly associated with older age (p<0.001), being male (p<0.001), depressive symptoms (p = 0.005), school non-attendance (p = 0.001) and a low level of parental monitoring (p<0.001).

Conclusion: There is clustering of health risk behaviors that underlies communicable and non-communicable diseases among adolescents in rural coastal Kenya. This suggests the urgent need for targeted multi-component health behavior interventions that simultaneously address all aspects of adolescent health and well-being, including the mental health needs of adolescents.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0242186PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7660520PMC
January 2021

The reliability, validity and factorial structure of the Swahili version of the 7-item generalized anxiety disorder scale (GAD-7) among adults living with HIV from Kilifi, Kenya.

Ann Gen Psychiatry 2020 28;19:62. Epub 2020 Oct 28.

Neuroassessment Group, KEMRI/Wellcome Trust Research Programme, Centre for Geographic Medicine Research (Coast), KEMRI, Box 230, Kilifi, Kenya.

Background: Generalized Anxiety Disorder (GAD) is under-investigated in people living with HIV/AIDS from sub-Saharan Africa. In part, this is due to paucity of culturally appropriate measures for GAD which are psychometrically robust. This study aimed to evaluate the reliability, factorial structure, and validity of Swahili version of the 7-item GAD questionnaire (GAD-7) among adults living with HIV.

Study Design: Descriptive cross-sectional study.

Methods: 450 adults receiving comprehensive care from an HIV specialized clinic in Kilifi County, coastal Kenya, were consecutively recruited. Swahili versions of GAD-7, Patient Health Questionnaire (PHQ-9) and a 12-item HIV stigma scale were administered alongside measures of psychosocial and health-related characteristics. Internal consistency, test-retest reliability, factorial structure, convergent validity, and discriminant validity of Swahili GAD-7 were examined using Cronbach's alpha (), intra-class correlation coefficient (ICC), Confirmatory Factor Analysis (CFA), Pearson's correlation, and analysis of covariance (ANCOVA), respectively.

Results: Internal consistency of Swahili GAD-7 was good,  =  CI . Its test-retest reliability (2 weeks apart) was acceptable, ICC =  CI ). A confirmatory analysis of a one-factor solution indicated an excellent fit to the hypothesized structure (RMSEA = 0.00 [95% confidence interval 0.00, 0.05], CFI = 1.00, TLI = 1.00). Multi-group CFA substantiated factorial invariance for sex and age for the one-factor structure of Swahili GAD-7. Scores of GAD-7, Swahili version, significantly correlated with those of PHQ-9 ( =  <  and the HIV stigma scale ( =  <  suggesting good convergent validity. Statistically significant differences were observed between participants on first-line antiretroviral therapy compared to those on second-line treatment  =  =  indicative of good discriminant validity of Swahili GAD-7

Conclusion: GAD-7 Swahili version retained its original unidimensional latent structure with good psychometric properties among adults living with HIV from Kilifi, Kenya. It can be used to identify symptoms of GAD in similar research settings. However, to confidently identify those in need of mental health treatment or referral services in HIV primary care clinics, more research on the validity of Swahili GAD-7 is needed especially its discriminant validity and diagnostic accuracy at different cut-off scores.
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http://dx.doi.org/10.1186/s12991-020-00312-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7594456PMC
October 2020

The effect of blood transfusion on outcomes among African children admitted to hospital with Plasmodium falciparum malaria: a prospective, multicentre observational study.

Lancet Haematol 2020 Nov;7(11):e789-e797

ISGlobal, Barcelona, Spain; Hospital Clínic i Provincial de Barcelona, Centro de Diagnóstico Biomédico, Universitat de Barcelona, Barcelona, Spain; Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.

Background: Infection with Plasmodium falciparum leads to severe malaria and death in approximately 400 000 children each year in sub-Saharan Africa. Blood transfusion might benefit some patients with malaria but could potentially harm others. The aim of this study was to estimate the association between transfusion and death among children admitted to hospital with P falciparum malaria.

Methods: In this prospective, multicentre observational study, we analysed admissions to six tertiary care hospitals in The Gambia, Malawi, Gabon, Kenya, and Ghana that participated in the Severe Malaria in African Children network. Patients were enrolled if they were younger than 180 months and had a Giemsa-stained thick blood smear that was positive for P falciparum. Blood transfusion (whole blood at a target volume of 20 mL per kg) was administered at the discretion of the responsible physicians who were aware of local and international transfusion guidelines. The primary endpoint was death associated with transfusion, which was estimated using models adjusted for site and disease severity. We also aimed to identify factors associated with the decision to transfuse. The exploratory objective was to estimate optimal haemoglobin transfusion thresholds using generalised additive models.

Findings: Between Dec 19, 2000, and March 8, 2005, 26 106 patients were enrolled in the study, 25 893 of whom had their transfusion status recorded and were included in the primary analysis. 8513 (32·8%) patients received a blood transfusion. Patients were followed-up until discharge from hospital for a median of 2 days (IQR 1-4). 405 (4·8%) of 8513 patients who received a transfusion died compared with 689 (4·0%) of 17 380 patients who did not receive a transfusion. Transfusion was associated with decreased odds of death in site-adjusted analysis (odds ratio [OR] 0·82 [95% CI 0·71-0·94]) and after adjusting for the increased disease severity of patients who received a transfusion (0·50 [0·42-0·60]). Severe anaemia, elevated lactate concentration, respiratory distress, and parasite density were associated with greater odds of receiving a transfusion. Among all study participants, transfusion was associated with improved survival when the admission haemoglobin concentration was up to 77 g/L (95% CI 65-110). Among those with impaired consciousness (Blantyre Coma Score ≤4), transfusion was associated with improved survival at haemoglobin concentrations up to 105 g/L (95% CI 71-115). Among those with hyperlactataemia (blood lactate ≥5·0 mmol/L), transfusion was not significantly associated with harm at any haemoglobin concentration-ie, the OR of death comparing transfused versus not transfused was less than 1 at all haemoglobin concentrations (lower bound of the 95% CI for the haemoglobin concentration at which the OR of death equals 1: 90 g/L; no upper bound).

Interpretation: Our findings suggest that whole blood transfusion was associated with improved survival among children hospitalised with P falciparum malaria. Among those with impaired consciousness or hyperlactataemia, transfusion was associated with improved survival at haemoglobin concentrations above the currently recommended transfusion threshold. These findings highlight the need to do randomised controlled trials to test higher transfusion thresholds among African children with severe malaria complicated by these factors.

Funding: US National Institute of Allergy and Infectious Diseases.
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http://dx.doi.org/10.1016/S2352-3026(20)30288-XDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7611367PMC
November 2020

Contextualizing and pilot testing the Mental Health Gap Action Programme Intervention Guide (mhGAP-IG) to primary healthcare workers in Kilifi, Kenya.

Glob Ment Health (Camb) 2020 18;7:e11. Epub 2020 May 18.

Clinical Research-Neurosciences, KEMRI/Wellcome Trust Research Programme, Centre for Geographic Medicine Research (Coast), Kilifi, Kenya.

Background: Little data exists about the methodology of contextualizing version two of the Mental Health Gap Action Programme Intervention Guide (mhGAP-IG) in resource-poor settings. This paper describes the contextualisation and pilot testing of the guide in Kilifi, Kenya.

Methods: Contextualisation was conducted as a collaboration between the KEMRI-Wellcome Trust Research Programme (KWTRP) and Kilifi County Government's Department of Health (KCGH) between 2016 and 2018. It adapted a mixed-method design and involved a situational analysis, stakeholder engagement, local adaptation and pilot testing of the adapted guide. Qualitative data were analysed using content analysis to identify key facilitators and barriers to the implementation process. Pre- and post-training scores of the adapted guide were compared using the Wilcoxon signed-rank test.

Results: Human resource for mental health in Kilifi is strained with limited infrastructure and outdated legislation. Barriers to implementation included few specialists for referral, unreliable drug supply, difficulty in translating the guide to Kiswahili language, lack of clarity of the roles of KWTRP and KCGH in the implementation process and the unwillingness of the biomedical practitioners to collaborate with traditional health practitioners to enhance referrals to hospital. In the adaptation process, stakeholders recommended the exclusion of child and adolescent mental and behavioural problems, as well as dementia modules from the final version of the guide. Pilot testing of the adapted guide showed a significant improvement in the post-training scores: 66.3% (95% CI 62.4-70.8) 76.6% (95% CI 71.6-79.2) ( < 0.001).

Conclusion: The adapted mhGAP-IG version two can be used across coastal Kenya to train primary healthcare providers. However, successful implementation in Kilifi will require a review of new evidence on the burden of disease, improvements in the mental health system and sustained dialogue among stakeholders.
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http://dx.doi.org/10.1017/gmh.2020.6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7379318PMC
May 2020
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