Enhancing stroke care in Ghana: A systematic review of stroke rehabilitation services.

OBJECTIVE: In Ghana, the shifting demographics of stroke incidence towards young adults have prompted the expansion of stroke care and rehabilitation efforts. Nevertheless, the precise impact of stroke rehabilitation remains unclear. We conducted a systematic review to explore the landscape and effects of stroke rehabilitation in Ghana. METHOD: We identified articles on stroke rehabilitation services in Ghana through searches of PubMed, Scopus, Embase, and Web of Science from inception until February 2024. The Critical Appraisal Skills Programme (CASP) Qualitative Checklist was employed to assess the risk of bias in the included studies, supplemented by qualitative synthesis. RESULTS: Among the 213 articles screened, 8 were deemed suitable for review. These studies primarily focused on two groups: stroke survivors (n = 335) and healthcare professionals (HCPs) (n = 257). Many stroke survivors reported significant benefits from telerehabilitation, with increased participation in rehabilitation activities correlating with improved physical and cognitive outcomes. The findings also underscored a lack of knowledge about stroke rehabilitation among HCPs, alongside variations in the availability of protocols and guidelines for stroke management across different hospital levels. CONCLUSIONS: The review reveals several challenges in stroke rehabilitation in Ghana, including disparities in HCPs' perceptions and utilization of rehabilitation services. The findings emphasize the need for comprehensive, patient-centered approaches, standardized training for HCPs, improved resource allocation, and the integration of telehealth to overcome barriers and enhance stroke rehabilitation in Ghana. These insights hold significance not only for Ghana but also for guiding strategies in similar contexts worldwide, aiming to improve stroke rehabilitation outcomes.

Inflammatory cytokines as potential biomarkers for early diagnosis of severe malaria in children in Ghana.

BACKGROUND: Severe malaria (SM) is a fatal multi-system disease which accounted for an estimated 619,000 deaths in 2021. Less than 30% of children presenting with SM are diagnosed and treated promptly, resulting in increased mortality and neurologic impairments in survivors. Studies have identified cytokine profiles that differentiate the various clinical manifestations of malaria (severe and uncomplicated). However, the diagnostic capability of these cytokines in differentiating between the disease states in terms of cut-off values has not yet been determined. METHODS: The plasma levels of 22 pro-inflammatory cytokines (Eotaxin/CCL 11, interferon-gamma (IFN-γ), interleukin (IL)- 2, IL-6, IL-1ß, IL-12p40/p70, IL-17A, RANTES, MCP-1, IL-15, IL-5, IL-1RA, IL-2R, IFN-α, IP-10, TNF, MIG, MIP-1α, MIP-1ß, IL-7, IL-8 and Granulocyte Macrophage-Colony Stimulating Factor (GM-CSF), and 3 anti-inflammatory cytokines-(IL-4, IL-13 and IL-10) in patients with SM, uncomplicated malaria (UM) and other febrile conditions, were measured and compared using the Human Cytokine Magnetic 25-Plex Panel. The receiver operating characteristic (ROC) curve analysis was used to determine the diagnostic value of these cytokines. RESULTS: The level of the pro-inflammatory cytokine, IL-17A, was significantly higher in the SM group as compared to the UM group. Levels of the anti-inflammatory cytokines however did not differ significantly among the SM and UM groups. Only IL-1ß and IL-17A showed good diagnostic potential after ROC curve analysis. CONCLUSION: The data show that levels of pro-inflammatory cytokines correlate with malaria disease severity. IL-1ß and IL-17A showed good diagnostic potentials and can be considered for use in clinical practice to target treatment.

Population cause of death estimation using verbal autopsy methods in large-scale field trials of maternal and child health: lessons learned from a 20-year research collaboration in Central Ghana.

Low and middle-income countries continue to use Verbal autopsies (VAs) as a World Health Organisation-recommended method to ascertain causes of death in settings where coverage of vital registration systems is not yet comprehensive. Whilst the adoption of VA has resulted in major improvements in estimating cause-specific mortality in many settings, well documented limitations have been identified relating to the standardisation of the processes involved. The WHO has invested significant resources into addressing concerns in some of these areas; there however remains enduring challenges particularly in operationalising VA surveys for deaths amongst women and children, challenges which have measurable impacts on the quality of data collected and on the accuracy of determining the final cause of death. In this paper we describe some of our key experiences and recommendations in conducting VAs from over two decades of evaluating seminal trials of maternal and child health interventions in rural Ghana. We focus on challenges along the entire VA pathway that can impact on the success rates of ascertaining the final cause of death, and lessons we have learned to optimise the procedures. We highlight our experiences of the value of the open history narratives in VAs and the training and skills required to optimise the quality of the information collected. We describe key issues in methods for ascertaining cause of death and argue that both automated and physician-based methods can be valid depending on the setting. We further summarise how increasingly popular information technology methods may be used to facilitate the processes described. Verbal autopsy is a vital means of increasing the coverage of accurate mortality statistics in low- and middle-income settings, however operationalisation remains problematic. The lessons we share here in conducting VAs within a long-term surveillance system in Ghana will be applicable to researchers and policymakers in many similar settings.

Trauma and depressive symptomatology in middle-aged persons at high risk of dementia: the PREVENT Dementia Study.

OBJECTIVE: Depression and trauma are associated with changes in brain regions implicated in Alzheimer's disease. The present study examined associations between childhood trauma, depression, adult cognitive functioning and risk of dementia. METHODS: Data from 378 participants in the PREVENT Dementia Study aged 40-59 years. Linear and logistic models were used to assess associations between childhood trauma, depression, dementia risk, cognitive test scores and hippocampal volume. RESULTS: Childhood trauma was associated with depression and reduced hippocampal volume but not current cognitive function or dementia risk. Poorer performance on a delayed face/name recall task was associated with depression. Childhood trauma was associated with lower hippocampal volume however poorer cognitive performance was mediated by depression rather than structural brain differences. CONCLUSION: Depressive symptomatology may be associated with dementia risk via multiple pathways, and future studies should consider subtypes of depressive symptomatology when examining its relationship to dementia.

Multivariate Data Analysis and Machine Learning for Prediction of MCI-to-AD Conversion.

There has always been a need for discovering efficient and dependable Alzheimer's disease (AD) diagnostic biomarkers. Like the majority of diseases, the earlier the diagnosis, the most effective the treatment. (Semi)-automated structural magnetic resonance imaging (MRI) processing approaches are very popular in AD research. Mild cognitive impairment (MCI) is considered to be a stage between normal cognitive ageing and dementia. MCI can often be the prodromal stage of AD. Around 10-15% of MCI patients convert to AD per year. In this study, we used three supervised machine learning (ML) techniques to differentiate MCI converters (MCIc) from MCI non-converters (MCInc) and predict their conversion rates from baseline MRI data (cortical thickness (CTH) and hippocampal volume (HCV)). A total of 803 participants from the ADNI cohort were included in this study (188 AD, 107 MCIc, 257 MCInc and 156 healthy controls (HC)). We studied the classification abilities of three different WEKA classifiers (support vector machine (SVM), decision trees (J48) and Naive Bayes (NB)). We built six different classification models, three models based on CTH and three based on HCV (CTH-SVM, CTH-J48, CTH-NB, HCV-SVM, HCV-J48 and HCV-NB). For the classification experiments, we obtained up to 71% sensitivity and up to 56% specificity. The prediction of conversion showed accuracy for up to 84%. The value of certain multivariate models derived from the classification experiments has exhibited robust and effective results in MCIc identification. However, there was a limitation in this study since we could not compare the CTH with the HCV models seeing as the data used originated from different subjects. As future direction, we propose the creation of a model that would combine various features with data originating from the same subjects, thus being a far more reliable and accurate prognostic tool.

Provider initiated tuberculosis case finding in outpatient departments of health care facilities in Ghana: yield by screening strategy and target group.

BACKGROUND: Meticulous identification and investigation of patients presenting with tuberculosis (TB) suggestive symptoms rarely happen in crowded outpatient departments (OPDs). Making health providers in OPDs diligently follow screening procedures may help increase TB case detection. From July 2010 to December 2013, two symptom based TB screening approaches of varying cough duration were used to screen and test for TB among general outpatients, PLHIV, diabetics and contacts in Accra, Ghana. METHODS: This study was a retrospective analysis comparing the yield of TB cases using two different screening approaches, allocated to selected public health facilities. In the first approach, the conventional 2 weeks cough duration with or without other TB suggestive symptoms was the criterion to test for TB in attendants of 7 general OPDs. In the second approach the screening criteria cough of >24 hours, as well as a history of at least one of the following symptoms: fever, weight loss and drenching night sweats were used to screen and test for TB among attendants of 3 general OPDs, 7 HIV clinics and 2 diabetes clinics. Contact investigation was initiated for index TB patients. The facilities documented the number of patients verbally screened, with presumptive TB, tested using smear microscopy and those diagnosed with TB in order to calculate the yield and number needed to screen (NNS) to find one TB case. Case notification trends in Accra were compared to those of a control area. RESULTS: In the approach using >24-hour cough, significantly more presumptive TB cases were identified among outpatients (0.82% versus 0.63%), more were tested (90.1% versus 86.7%), but less smear positive patients were identified among those tested (8.0% versus 9.4%). Overall, all forms of TB cases identified per 100,000 screened were significantly higher in the >24-hour cough approach at OPD (92.7 for cough >24 hour versus 82.7 for cough >2 weeks ), and even higher in diabetics (364), among contacts (693) and PLHIV (995). NNS (95% Confidence Interval) varied from 100 (93-109) for PLHIV, 144 (112-202) for contacts, 275 (197-451) for diabetics and 1144 (1101-1190) for OPD attendants. About 80% of the TB cases were detected in general OPDs. Despite the intervention, notifications trends were similar in the intervention and control areas. CONCLUSION: The >24-hour cough approach yielded more TB cases though required TB testing for a larger number of patients. The yield of TB cases per 100,000 population screened was highest among PLHIV, contacts, and diabetics, but the majority of cases were detected in general OPDs. The intervention had no discernible impact on general case notification.

Determinants of postnatal depression in rural ghana: findings from the don population based cohort study.

BACKGROUND: Risk factors for postnatal depression (PND), one of the most pervasive complications of child bearing, are poorly understood in Africa. A recent systematic review of 31 studies found that the strongest predictors are social and economic disadvantage and gender-based factors; only six of these studies were community based, and almost all were in South Asia. METHODS: Cohort study nested within 4 weekly surveillance of all women of reproductive age to identify pregnancies and collect data on births and deaths in the Kintampo Health Research Centre study area of Ghana. Women were screened for depression during pregnancy and after birth using the Patient Health Questionnaire to ascertain DSM-IV major or minor depression. Information was collected on determinants relating to the mother, birth, and baby, which were examined using logistic regression; effect sizes reported as relative risks with 95% confidence intervals. RESULTS: Thirteen thousand nine hundred and twenty nine women were screened both during pregnancy and after birth, of whom 13,360 (95.9%) had complete data on potential determinants. Two hundred and fifty five (3.8%, 95% CI: 3.5%, 4.1%) had PND. Antenatal depression (AND) was the strongest determinant accounting for 34.4% of PND cases. Other determinants were season of delivery, peripartum/postpartum complications, newborn ill health, still birth, or neonatal death. Common determinants were observed for onset and persistent depression. CONCLUSIONS: Although most AND resolves in this setting, more than a third of women with PND also had AND. Adverse birth- and baby-related outcomes are the other main determinants. We recommend that programs detect and treat depression during pregnancy and provide support to women with adverse birth outcomes.

Effect of the Newhints home-visits intervention on neonatal mortality rate and care practices in Ghana: a cluster randomised controlled trial.

BACKGROUND: In 2009, on the basis of promising evidence from trials in south Asia, WHO and UNICEF issued a joint statement about home visits as a strategy to improve newborn survival. In the Newhints trial, we aimed to test this home-visits strategy in sub-Saharan Africa by assessing the effect on all-cause neonatal mortality rate (NMR) and essential newborn-care practices. METHODS: The Newhints cluster randomised trial was undertaken in 98 zones in seven districts in the Brong Ahafo Region, Ghana. 49 zones were randomly assigned to the Newhints intervention and 49 to the control intervention by use of restricted randomisation with stratification to ensure comparability between interventions. Community-based surveillance volunteers (CBSVs) in Newhints zones were trained to identify pregnant women in their community and to make two home visits during pregnancy and three in the first week of life to promote essential newborn-care practices, weigh and assess babies for danger signs, and refer as necessary. Primary outcomes were NMR and coverage of key essential newborn-care practices. Analyses were by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00623337. FINDINGS: 16,168 (99%) of 16,329 deliveries between November, 2008, and December, 2009, were livebirths; the status at 1 month was known for 15,619 (97%) livebirths. 482 neonatal deaths were recorded. Coverage data were available from 6029 women in Newhints zones; of these 4358 (72%) reported having CBSV visits during pregnancy and 3815 (63%) reported having postnatal visits. This coverage increased substantially from June, 2009, after the introduction of new implementation strategies and reached almost 90% for pregnancy visits by the end of the trial and 75% for postnatal visits. The Newhints intervention significantly increased coverage of key essential newborn-care behaviours, except for four or more antenatal-care visits (5975 [76%] of 7859 vs 5988 [74%] of 8121, respectively; relative risk 1·02, 95% CI 0·96-1·09; p=0·52) and baby delivered in a facility (5373 [68%] vs 5539 [68%], respectively; 0·97, 0·81-1·14; p=0·69). The largest increase was for care-seeking, with 102 (77%) of 132 sick babies in Newhints zones taken to a hospital or clinic compared with 77 (55%) of 139 in control zones (1·43, 1·17-1·76; p=0·001). Increases were also noted in bednet use during pregnancy (5398 [69%] of 7859 vs 5135 [63%] of 8121, respectively; 1·12, 1·03-1·21; p=0·005), money saved for delivery or emergency (5730 [86%] of 6681 vs 5525 [80%] of 6941, respectively; 1·09, 1·05-1·12; p<0·0001), transport arranged in advance for facility (2496 [37%] vs 2061 [30%], respectively; 1·30, 1·12-1·49; p=0·0004), birth assistant for home delivery washed hands with soap (1853 [93%] of 1992 vs 1817 [87%] of 2091, respectively; 1·05, 1·02-1·09; p=0·001), initiation of breastfeeding in less than 1 h of birth (3743 [49%] of 7673 vs 3280 [41%] of 7921, respectively; 1·22, 1·07-1·40; p=0·004), skin to skin contact (3355 [44%] vs 1931 [24%], respectively; 2·30, 1·85-2·87; p=0·0002), first bath delayed for longer than 6 h (3131 [41%] vs 2269 [29%], respectively; 1·65, 1·27-2·13; p<0·0001), exclusive breastfeeding for 26-32 days (1217 [86%] of 1414 vs 1091 [80%] of 1371; 1·10, 1·04-1·16; p=0·001), and baby sleeping under bednet for 8-56 days (4548 [79%] of 5756 vs 4291 [73%] of 5846; 1·09, 1·03-1·15; p=0·002). There were 230 neonatal deaths in the Newhints zones compared with 252 in the control zones. The overall NMRs per 1000 livebirths were 29·8 and 31·9, respectively (0·92, 0·75-1·12; p=0·405). INTERPRETATION: The reduction in NMR with Newhints is consistent with the reductions achieved in three trials undertaken in programme settings in south Asia. Because there is no suggestion of any heterogeneity (p=0·850) between these trials and Newhints, the meta-analysis summary estimate of a reduction of 12% (95% CI 5-18) provides the best evidence for the likely effect of the home-visits strategy delivered within programmes in sub-Saharan Africa and in south Asia. Improvements in the quality of delivery and neonatal care in health facilities and development of innovative, effective strategies to increase coverage of home visits on the day of birth could lead to the achievement of more substantial reductions. FUNDING: WHO, Bill & Melinda Gates Foundation, and UK Department for International Development.

Socio-economic determinants and inequities in coverage and timeliness of early childhood immunisation in rural Ghana.

OBJECTIVES: To assess the extent of socio-economic inequity in coverage and timeliness of key childhood immunisations in Ghana. METHODS: Secondary analysis of vaccination card data collected from babies born between January 2008 and January 2010 who were registered in the surveillance system supporting the ObaapaVita and Newhints Trials was carried out. 20 251 babies had 6 weeks' follow-up, 16 652 had 26 weeks' follow-up, and 5568 had 1 year's follow-up. We performed a descriptive analysis of coverage and timeliness of vaccinations by indicators for urban/rural status, wealth and educational attainment. The association of coverage with socio-economic indicators was tested using a chi-square-test and the association with timeliness using Cox regression. RESULTS: Overall coverage at 1 year of age was high (>95%) for Bacillus Calmette-Guérin (BCG), all three pentavalent diphtheria-pertussis-tetanus-haemophilus influenzae B-hepatitis B (DPTHH) doses and all polio doses except polio at birth (63%). Coverage against measles and yellow fever was 85%. Median delay for BCG was 1.7 weeks. For polio at birth, the median delay was 5 days; all other vaccine doses had median delays of 2-4 weeks. We found substantial health inequity across all socio-economic indicators for all vaccines in terms of timeliness, but not coverage at 1 year. For example, for the last DPTHH dose, the proportion of children delayed more than 8 weeks were 27% for urban children and 31% for rural children (P < 0.001), 21% in the wealthiest quintile and 41% in the poorest quintile (P < 0.001), and 9% in the most educated group and 39% in the least educated group (P < 0.001). However, 1-year coverage of the same dose remained above 90% for all levels of all socio-economic indicators. CONCLUSIONS: Ghana has substantial health inequity across urban/rural, socio-economic and educational divides. While overall coverage was high, most vaccines suffered from poor timeliness. We suggest that countries achieving high coverage should include timeliness indicators in their surveillance systems.

The PREVENT dementia programme: baseline demographic, lifestyle, imaging and cognitive data from a midlife cohort study investigating risk factors for dementia.

PREVENT is a multi-centre prospective cohort study in the UK and Ireland that aims to examine midlife risk factors for dementia and identify and describe the earliest indices of disease development. The PREVENT dementia programme is one of the original epidemiological initiatives targeting midlife as a critical window for intervention in neurodegenerative conditions. This paper provides an overview of the study protocol and presents the first summary results from the initial baseline data to describe the cohort. Participants in the PREVENT cohort provide demographic data, biological samples (blood, saliva, urine and optional cerebrospinal fluid), lifestyle and psychological questionnaires, undergo a comprehensive cognitive test battery and are imaged using multi-modal 3-T MRI scanning, with both structural and functional sequences. The PREVENT cohort governance structure is described, which includes a steering committee, a scientific advisory board and core patient and public involvement groups. A number of sub-studies that supplement the main PREVENT cohort are also described. The PREVENT cohort baseline data include 700 participants recruited between 2014 and 2020 across five sites in the UK and Ireland (Cambridge, Dublin, Edinburgh, London and Oxford). At baseline, participants had a mean age of 51.2 years (range 40-59, SD ± 5.47), with the majority female (n = 433, 61.9%). There was a near equal distribution of participants with and without a parental history of dementia (51.4% versus 48.6%) and a relatively high prevalence of APOEɛ4 carriers (n = 264, 38.0%). Participants were highly educated (16.7 ± 3.44 years of education), were mainly of European Ancestry (n = 672, 95.9%) and were cognitively healthy as measured by the Addenbrookes Cognitive Examination-III (total score 95.6 ± 4.06). Mean white matter hyperintensity volume at recruitment was 2.26 ± 2.77 ml (median = 1.39 ml), with hippocampal volume being 8.15 ± 0.79 ml. There was good representation of known dementia risk factors in the cohort. The PREVENT cohort offers a novel data set to explore midlife risk factors and early signs of neurodegenerative disease. Data are available open access at no cost via the Alzheimer's Disease Data Initiative platform and Dementia Platforms UK platform pending approval of the data access request from the PREVENT steering group committee.

Effect of vitamin A supplementation on cause-specific mortality in women of reproductive age in Ghana: a secondary analysis from the ObaapaVitA trial.

OBJECTIVE: To determine the effect of weekly low-dose vitamin A supplementation on cause-specific mortality in women of reproductive age in Ghana. METHODS: A cluster-randomized, triple-blind, placebo-controlled trial was conducted in seven districts of the Brong Ahafo region of Ghana. Women aged 15-45 years who were capable of giving informed consent and intended to live in the trial area for at least 3 months were enrolled and randomly assigned, according to their cluster of residence, to receive oral vitamin A (7500 µg) or placebo once a week. Randomization was blocked, with two clusters in each fieldwork area allocated to vitamin A and two to placebo. Every 4 weeks, fieldworkers distributed capsules and collected data during home visits. Verbal autopsies were conducted by field supervisors and reviewed by physicians, who assigned a cause of death. Cause-specific mortality rates in both arms were compared by means of random-effects Poisson regression models to allow for the cluster randomization. Analysis was by intention-to-treat, based on cluster of residence, with women eligible for inclusion once they had consistently received the supplement or placebo capsules for 6 months. FINDINGS: The analysis was based on 581 870 woman-years and 2624 deaths. Cause-specific mortality rates were found to be similar in the two study arms. CONCLUSION: Low-dose vitamin A supplements administered weekly are of no benefit in programmes to reduce mortality in women of childbearing age.

Résumé OBJECTIF: Déterminer l'effet de la supplémentation hebdomadaire en vitamine A à faible dose sur la mortalité spécifique des femmes en âge de procréer au Ghana. MÉTHODES: Une étude randomisée, en triple aveugle, contrôlée contre placebo, a été menée dans sept districts de la région de Brong Ahafo au Ghana. Les femmes âgées de 15 à 45 ans, capables de donner un consentement éclairé et amenées à vivre dans la région de l'étude pendant au moins 3 mois, ont été incluses et il a été déterminé qu'elles recevraient une fois par semaine, au hasard selon leur groupe de résidence, de la vitamine A par voie orale (7 500 µg) ou un placebo. La randomisation a été fixée par deux groupes dans chaque zone recevant la vitamine A et deux groupes recevant le placebo. Toutes les 4 semaines, les agents de terrain distribuaient les capsules et recueillaient les données lors de visites à domicile. Des autopsies orales ont été effectuées par les superviseurs sur le terrain et analysées par des médecins, qui déterminaient la cause du décès. Les taux de mortalité spécifique dans les deux groupes ont été comparés à l'aide d'une régression de Poisson pour valider la randomisation des groupes. L'analyse, basée sur l'intention de traiter, était basée sur le groupe de résidence, pour des femmes éligibles à l'étude ayant reçu les capsules de supplément ou de placebo de manière constante pendant 6 mois. RÉSULTATS: L'analyse s'est basée sur 581 870 années-femmes et 2624 décès. Les taux de mortalité spécifique ont été jugés similaires dans les deux groupes de l'étude. CONCLUSION: Les suppléments en vitamine A à faible dose administrés hebdomadairement ne sont d'aucune utilité dans les programmes visant à réduire la mortalité chez les femmes en âge de procréer.

Resumen OBJETIVO: Determinar el efecto de la administración semanal de dosis bajas de vitamina A en la mortalidad por causas específicas de mujeres en edad reproductiva en Ghana. MÉTODOS: Se realizó un ensayo aleatorio de grupos, triple ciego y controlado por placebo en siete distritos de la región de Brong Ahafo, en Ghana. Se inscribieron mujeres de entre 15 y 45 años de edad capaces de dar su consentimiento informado y que tuvieran previsto vivir en el área de ensayo durante al menos tres meses. De acuerdo con el grupo de residencia al que habían sido asignadas de forma aleatoria, recibieron semanalmente vitamina A por vía oral (7500 µg) o placebo. La distribución aleatoria se limitó en cada área de trabajo a dos grupos a los que se les administró vitamina A y dos grupos que recibieron placebo. Cada cuatro semanas, los investigadores de campo distribuyeron cápsulas y recogieron datos durante las visitas a los hogares. Las autopsias verbales realizadas por los supervisores de campo fueron revisadas por médicos, quienes determinaron la causa de la muerte. Se compararon las tasas de mortalidad por causas específicas de ambos brazos mediante los modelos de regresión de Poisson con efectos aleatorios para facilitar la distribución aleatoria de los grupos. El análisis fue por intención de tratar, según el grupo de residencia y con mujeres que cumplieron las condiciones de inclusión una vez habían recibido de forma constante las cápsulas de suplemento o placebo durante seis meses. RESULTADOS: El análisis se basó en 581 870 años-mujer y 2624 muertes. Se descubrió que las tasas de mortalidad por causas específicas fueron similares en ambos brazos del estudio. CONCLUSIÓN: Los suplementos de dosis bajas de vitamina A administrados semanalmente no presentan ninguna ventaja en los programas para reducir la mortalidad de las mujeres en edad reproductiva.

Knowledge, attitudes, and practices of caregivers on childhood immunization in Okaikoi sub-metro of Accra, Ghana.

Background: Immunization remains one of the most cost-effective health interventions. However, there are still issues of vaccine hesitancy especially in caregivers who are required to protect their children from vaccine-preventable diseases. This thwarts the overall vaccine coverage in disease-endemic areas such as sub-Saharan Africa. Therefore, to determine the factors that promote vaccine hesitancy in caregivers, this study sought to assess the knowledge, attitude, and practices of caregivers on childhood immunization in Okaikoi, a sub-metro of Accra in Ghana. Methods: A cross-sectional study on childhood immunization was conducted to determine the knowledge, attitudes, and practices of caregivers. A total of 120 caregivers with infants aged 12 months to 23 months were interviewed with a structured questionnaire containing open-ended and closed-ended queries. Results: From the community, infants whose caregivers had adhered completely to immunization constituted 53.3% while the rest were partially immunized. The two main deterrents to complete immunization were time constraints (25.8%) and forgetfulness (17.5%). It was observed that vaccination uptake and maternal level of education, as well as vaccination adverse reaction, did not impact the completion of the EPI program by these caregivers. Unfortunately, it was noted that caregivers with higher education levels were unable to complete their vaccination schedules due to their busy work schedules. Nonetheless, the main deterrent to adhering to complete childhood immunization was poor maternal knowledge (58%). Conclusion: The study revealed that, the caregivers in the community had poor knowledge on vaccination and its benefits, and therefore, with no strict adherence to vaccination schedules. This promoted the incomplete immunization of children in the community by their caregivers. Also, since the main source of information with regard to immunization in the sub-metro was through the antenatal and postnatal child welfare clinics and the media, we recommend that the health workers collaborate with media personnel to ensure that standardized information is disseminated.

Development and validation of a machine learning-supported strategy of patient selection for osteoarthritis clinical trials: the IMI-APPROACH study.

Objectives: To efficiently assess the disease-modifying potential of new osteoarthritis treatments, clinical trials need progression-enriched patient populations. To assess whether the application of machine learning results in patient selection enrichment, we developed a machine learning recruitment strategy targeting progressive patients and validated it in the IMI-APPROACH knee osteoarthritis prospective study. Design: We designed a two-stage recruitment process supported by machine learning models trained to rank candidates by the likelihood of progression. First stage models used data from pre-existing cohorts to select patients for a screening visit. The second stage model used screening data to inform the final inclusion. The effectiveness of this process was evaluated using the actual 24-month progression. Results: From 3500 candidate patients, 433 with knee osteoarthritis were screened, 297 were enrolled, and 247 completed the 2-year follow-up visit. We observed progression related to pain (P, 30%), structure (S, 13%), and combined pain and structure (P â€‹+ â€‹S, 5%), and a proportion of non-progressors (N, 52%) ∼15% lower vs an unenriched population. Our model predicted these outcomes with AUC of 0.86 [95% CI, 0.81-0.90] for pain-related progression and AUC of 0.61 [95% CI, 0.52-0.70] for structure-related progression. Progressors were ranked higher than non-progressors for P â€‹+ â€‹S (median rank 65 vs 143, AUC = 0.75), P (median rank 77 vs 143, AUC = 0.71), and S patients (median rank 107 vs 143, AUC = 0.57). Conclusions: The machine learning-supported recruitment resulted in enriched selection of progressive patients. Further research is needed to improve structural progression prediction and assess this strategy in an interventional trial.

COVID-19 and future pandemics: A blockchain-based privacy-aware secure borderless travel solution from electronic health records.

COVID-19 pandemic undoubtedly lingers on and has brought unprecedented changes globally including travel arrangements. Blockchain-based solutions have been proposed to aid travel amid the pandemic hap. Presently, extant solutions are country or regional-based, downplay privacy, non-responsive, often impractical, and come with blockchain-related complexities presenting technological hurdle for travelers. We therefore propose a solution namely, Borderless to foster global travel allowing travelers and countries collaboratively engage in a secure adaptive proof protocol dubbed Proof-of-COVID-19 status a number of arbitrary statements to ascertain the fact that the traveler poses no danger irrespective of the country located. As far as we know, this is first of its kind. Borderless is implemented as a decentralized application leveraging blockchain as a trust anchor and decentralized storage technology. Security analysis and evaluation are performed proving security, privacy-preservation, and cost-effectiveness along with implementation envisioning it as a blueprint to facilitate cross-border travel during the present and future pandemics. Our experimental results show it takes less than 60 and 3 s to onboard users and perform proof verification respectively attesting to real usability scenarios along with the traits of arbitrary proofs to aid responsiveness to the dynamics of pandemics and blockchain abstraction from travelers.

Rational design of potent ultrashort antimicrobial peptides with programmable assembly into nanostructured hydrogels.

Microbial resistance to common antibiotics is threatening to cause the next pandemic crisis. In this context, antimicrobial peptides (AMPs) are receiving increased attention as an alternative approach to the traditional small molecule antibiotics. Here, we report the bi-functional rational design of Fmoc-peptides as both antimicrobial and hydrogelator substances. The tetrapeptide Fmoc-WWRR-NH2-termed Priscilicidin-was rationally designed for antimicrobial activity and molecular self-assembly into nanostructured hydrogels. Molecular dynamics simulations predicted Priscilicidin to assemble in water into small oligomers and nanofibrils, through a balance of aromatic stacking, amphiphilicity and electrostatic repulsion. Antimicrobial activity prediction databases supported a strong antimicrobial motif via sequence analogy. Experimentally, this ultrashort sequence showed a remarkable hydrogel forming capacity, combined to a potent antibacterial and antifungal activity, including against multidrug resistant strains. Using a set of biophysical and microbiology techniques, the peptide was shown to self-assemble into viscoelastic hydrogels, as a result of assembly into nanostructured hexagonal mesophases. To further test the molecular design approach, the Priscilicidin sequence was modified to include a proline turn-Fmoc-WPWRR-NH2, termed P-Priscilicidin-expected to disrupt the supramolecular assembly into nanofibrils, while predicted to retain antimicrobial activity. Experiments showed P-Priscilicidin self-assembly to be effectively hindered by the presence of a proline turn, resulting in liquid samples of low viscosity. However, assembly into small oligomers and nanofibril precursors were evidenced. Our results augur well for fast, adaptable, and cost-efficient antimicrobial peptide design with programmable physicochemical properties.

Effect of vitamin A supplementation in women of reproductive age on maternal survival in Ghana (ObaapaVitA): a cluster-randomised, placebo-controlled trial.

BACKGROUND: A previous trial in Nepal showed that supplementation with vitamin A or its precursor (betacarotene) in women of reproductive age reduced pregnancy-related mortality by 44% (95% CI 16-63). We assessed the effect of vitamin A supplementation in women in Ghana. METHODS: ObaapaVitA was a cluster-randomised, double-blind, placebo-controlled trial undertaken in seven districts in Brong Ahafo Region in Ghana. The trial area was divided into 1086 small geographical clusters of compounds with fieldwork areas consisting of four contiguous clusters. All women of reproductive age (15-45 years) who gave informed consent and who planned to remain in the area for at least 3 months were recruited. Participants were randomly assigned by cluster of residence to receive a vitamin A supplement (25 000 IU retinol equivalents) or placebo capsule orally once every week. Randomisation was blocked and based on an independent, computer-generated list of numbers, with two clusters in each fieldwork area allocated to vitamin A supplementation and two to placebo. Capsules were distributed during home visits undertaken every 4 weeks, when data were gathered on pregnancies, births, and deaths. Primary outcomes were pregnancy-related mortality and all-cause female mortality. Cause of death was established by verbal post mortems. Analysis was by intention to treat (ITT) with random-effects regression to account for the cluster-randomised design. Adverse events were synonymous with the trial outcomes. This trial is registered with ClinicalTrials.gov, number NCT00211341. FINDINGS: 544 clusters (104 484 women) were randomly assigned to vitamin A supplementation and 542 clusters (103 297 women) were assigned to placebo. The main reason for participant drop out was migration out of the study area. In the ITT analysis, there were 39 601 pregnancies and 138 pregnancy-related deaths in the vitamin A supplementation group (348 deaths per 100 000 pregnancies) compared with 39 234 pregnancies and 148 pregnancy-related deaths in the placebo group (377 per 100 000 pregnancies); adjusted odds ratio 0.92, 95% CI 0.73-1.17; p=0.51. 1326 women died in 292 560 woman-years in the vitamin A supplementation group (453 deaths per 100 000 years) compared with 1298 deaths in 289 310 woman-years in the placebo group (449 per 100 000 years); adjusted rate ratio 1.01, 0.93-1.09; p=0.85. INTERPRETATION: The body of evidence, although limited, does not support inclusion of vitamin A supplementation for women in either safe motherhood or child survival strategies. FUNDING: UK Department for International Development, and USAID.

Developing an Explainable Machine Learning-Based Personalised Dementia Risk Prediction Model: A Transfer Learning Approach With Ensemble Learning Algorithms.

Alzheimer's disease (AD) has its onset many decades before dementia develops, and work is ongoing to characterise individuals at risk of decline on the basis of early detection through biomarker and cognitive testing as well as the presence/absence of identified risk factors. Risk prediction models for AD based on various computational approaches, including machine learning, are being developed with promising results. However, these approaches have been criticised as they are unable to generalise due to over-reliance on one data source, poor internal and external validations, and lack of understanding of prediction models, thereby limiting the clinical utility of these prediction models. We propose a framework that employs a transfer-learning paradigm with ensemble learning algorithms to develop explainable personalised risk prediction models for dementia. Our prediction models, known as source models, are initially trained and tested using a publicly available dataset (n = 84,856, mean age = 69 years) with 14 years of follow-up samples to predict the individual risk of developing dementia. The decision boundaries of the best source model are further updated by using an alternative dataset from a different and much younger population (n = 473, mean age = 52 years) to obtain an additional prediction model known as the target model. We further apply the SHapely Additive exPlanation (SHAP) algorithm to visualise the risk factors responsible for the prediction at both population and individual levels. The best source model achieves a geometric accuracy of 87%, specificity of 99%, and sensitivity of 76%. In comparison to a baseline model, our target model achieves better performance across several performance metrics, within an increase in geometric accuracy of 16.9%, specificity of 2.7%, and sensitivity of 19.1%, an area under the receiver operating curve (AUROC) of 11% and a transfer learning efficacy rate of 20.6%. The strength of our approach is the large sample size used in training the source model, transferring and applying the "knowledge" to another dataset from a different and undiagnosed population for the early detection and prediction of dementia risk, and the ability to visualise the interaction of the risk factors that drive the prediction. This approach has direct clinical utility.

Resting-state brain connectivity in healthy young and middle-aged adults at risk of progressive Alzheimer's disease.

Functional brain connectivity of the resting-state networks has gained recent attention as a possible biomarker of Alzheimer's Disease (AD). In this paper, we review the literature of functional connectivity differences in young adults and middle-aged cognitively intact individuals with non-modifiable risk factors of AD (n = 17). We focus on three main intrinsic resting-state networks: The Default Mode network, Executive network, and the Salience network. Overall, the evidence from the literature indicated early vulnerability of functional connectivity across different at-risk groups, particularly in the Default Mode Network. While there was little consensus on the interpretation on directionality, the topography of the findings showed frequent overlap across studies, especially in regions that are characteristic of AD (i.e., precuneus, posterior cingulate cortex, and medial prefrontal cortex areas). We conclude that while resting-state functional connectivity markers have great potential to identify at-risk individuals, implementing more data-driven approaches, further longitudinal and cross-validation studies, and the analysis of greater sample sizes are likely to be necessary to fully establish the effectivity and utility of resting-state network-based analyses.

Human neuropeptide substance P self-assembles into semi-flexible nanotubes that can be manipulated for nanotechnology.

Substance P neuropeptide is here reported to self-assemble into well-defined semi-flexible nanotubes. Using a blend of synchrotron small angle X-ray scattering, atomic force microscopy and other biophysical techniques, the natural peptide is shown to self-assemble into monodisperse 6 nm wide nanotubes, which can closely associate into nano-arrays with nematic properties. Using simple protocols, the nanotubes could be precipitated or mineralised while conserving their dimensions and core-shell morphology. Our discovery expands the small number of available monodisperse peptide nanotube systems for nanotechnology, beyond direct relevance to biologically functional peptide nanostructures since the substance P nanotubes are fundamentally different from typical amyloid fibrils.

Statistical methods for dementia risk prediction and recommendations for future work: A systematic review.

INTRODUCTION: Numerous dementia risk prediction models have been developed in the past decade. However, methodological limitations of the analytical tools used may hamper their ability to generate reliable dementia risk scores. We aim to review the used methodologies. METHODS: We systematically reviewed the literature from March 2014 to September 2018 for publications presenting a dementia risk prediction model. We critically discuss the analytical techniques used in the literature. RESULTS: In total 137 publications were included in the qualitative synthesis. Three techniques were identified as the most commonly used methodologies: machine learning, logistic regression, and Cox regression. DISCUSSION: We identified three major methodological weaknesses: (1) over-reliance on one data source, (2) poor verification of statistical assumptions of Cox and logistic regression, and (3) lack of validation. The use of larger and more diverse data sets is recommended. Assumptions should be tested thoroughly, and actions should be taken if deviations are detected.