Understanding lived experiences and perceptions of resilience in black and South Asian Muslim children living in East London: a qualitative study protocol.

INTRODUCTION: It is important to promote resilience in preadolescence; however, there is limited research on children's understandings and experiences of resilience. Quantitative approaches may not capture dynamic and context-specific aspects of resilience. Resilience research has historically focused on white, middle-class Western adults and adolescents, creating an evidence gap regarding diverse experiences of resilience in middle childhood which could inform interventions. East London's Muslim community represents a diverse, growing population. Despite being disproportionately affected by deprivation and racial and cultural discrimination, this population is under-represented in resilience research. Using participatory and arts-based methods, this study aims to explore lived experiences and perceptions of resilience in black and South Asian Muslim children living in East London. METHODS AND ANALYSIS: We propose a qualitative study, grounded in embodied inquiry, consisting of a participatory workshop with 6-12 children and their parents/carers to explore lived experiences and perceptions of resilience. Participants will be identified and recruited from community settings in East London. Eligible participants will be English-speaking Muslims who identify as being black or South Asian, have a child aged 8-12 years and live in East London. The workshop (approx. 3.5 hours) will take place at an Islamic community centre and will include body mapping with children and a focus group discussion with parents/carers to explore resilience perspectives and meanings. Participants will also complete a demographic survey. Workshop audio recordings will be transcribed verbatim and body maps and other paper-based activities will be photographed. Data will be analysed using systematic visuo-textual analysis which affords equal importance to visual and textual data. ETHICS AND DISSEMINATION: The Queen Mary Ethics of Research Committee at Queen Mary University of London has approved this study (approval date: 9 October 2023; ref: QME23.0042). The researchers plan to publish the results in peer-reviewed journals and present findings at academic conferences

A simple cost-effective high performance liquid chromatographic assay of sulphadoxine in whole blood spotted on filter paper for field studies

<p>Abstract</p> <p>Background</p> <p>Artesunate plus sulphadoxine-pyrimethamine is one of the four artemisinin-based combination therapies currently recommended by WHO as first-line treatment for falciparum malaria. Sulphadoxine-pyrimethamine is also used for intermittent preventive treatment for malaria in pregnancy. Drug use patterns and drug pharmacokinetics are important factors impacting the spread of drug resistant parasites hence it is imperative to monitor the effect of pharmacokinetic variability on therapeutic efficacy. Unfortunately, information on the pharmacokinetics of sulphadoxine in children and pregnant women with malaria is very limited. Methods for the assay of sulphadoxine-pyrimethamine have been previously reported, but they are not cost-effective and practicable in analytical laboratories in low resource areas where malaria is endemic. Efforts in this study were thus devoted to development and evaluation of a simple, cost-effective and sensitive method for quantification of sulphadoxine in small capillary samples of whole blood dried on filter paper.</p> <p>Methods</p> <p>Sulphadoxine was determined in whole blood by reversed-phase high performance liquid chromatography with UV detection at 340 nm. Sulisoxazole (SLX) was used as internal standard. Chromatographic separation was achieved using a Beckman Coulter ODS C₁₈and a mobile phase consisting of 0.05 M phosphate buffer-methanol-acetonitrile (70:17:13 V/V/V) containing 1% triethylamine solution.</p> <p>Results</p> <p>Standard curves from sulphadoxine-spiked blood added to filter paper were linear over the concentration range studied. Linear regression analysis yielded correlation coefficient r²> 0.99 (n = 6). Extraction recoveries were about 82-85%. The limit of quantification was 120 ng/ml while the within and between assay coefficient of variations were < 10%. The inter-day precision was < 5.8% and inter-day accuracy ranged from 4.1 to 5.3%. There was no interference from endogenous compounds or any of the commonly used anti-malarial, analgesic and anti-infective drugs with the peaks of SDX or the internal standard.</p> <p>Conclusion</p> <p>The recovery and accuracy of determination of SDX from whole blood filter paper samples using the method described in this study is satisfactory, thus making the method a valuable tool in epidemiological studies and therapeutic drug monitoring in developing endemic countries. Furthermore, the applicability of the method in studying the pharmacokinetic disposition of SDX in a patient suggests that the method is suitable in malaria endemic areas.</p

Understanding lived experiences and perceptions of resilience in black and South Asian Muslim children living in East London: a qualitative study protocol

Supplementary materials: Supplementary Data are available online at: https://bmjopen.bmj.com/content/14/4/e082346.info .ProtocolIntroduction: It is important to promote resilience in preadolescence; however, there is limited research on children’s understandings and experiences of resilience. Quantitative approaches may not capture dynamic and context-specific aspects of resilience. Resilience research has historically focused on white, middle-class Western adults and adolescents, creating an evidence gap regarding diverse experiences of resilience in middle childhood which could inform interventions. East London’s Muslim community represents a diverse, growing population. Despite being disproportionately affected by deprivation and racial and cultural discrimination, this population is under-represented in resilience research. Using participatory and arts-based methods, this study aims to explore lived experiences and perceptions of resilience in black and South Asian Muslim children living in East London. Methods and analysis: We propose a qualitative study, grounded in embodied inquiry, consisting of a participatory workshop with 6–12 children and their parents/carers to explore lived experiences and perceptions of resilience. Participants will be identified and recruited from community settings in East London. Eligible participants will be English-speaking Muslims who identify as being black or South Asian, have a child aged 8–12 years and live in East London. The workshop (approx. 3.5 hours) will take place at an Islamic community centre and will include body mapping with children and a focus group discussion with parents/carers to explore resilience perspectives and meanings. Participants will also complete a demographic survey. Workshop audio recordings will be transcribed verbatim and body maps and other paper-based activities will be photographed. Data will be analysed using systematic visuo-textual analysis which affords equal importance to visual and textual data.Barts Charity, UK (charity number: 212563, project code: MRC&U0042)

Hypoglycaemia in severe malaria, clinical associations and relationship to quinine dosage

<p>Abstract</p> <p>Background</p> <p>Hypoglycaemia is an independent risk factor for death in severe malaria and a recognized adverse treatment effect of parenteral quinine. In 2006 our hospital changed quinine treatment policy from 15 mg/kg loading (plus 10 mg/kg 12-hourly) to 20 mg/kg loading (plus 10 mg/kg 8-hourly) to comply with new WHO guidelines. This presented us with the opportunity to examine whether there was any dose relationship of quinine and hypoglycaemia occurrence.</p> <p>Methods</p> <p>Retrospective case notes review of all children admitted to hospital with severe falciparum malaria between April 2002 - July 2009, before and after the introduction of the new WHO quinine regimen. Four-hourly bedside glucose levels were measured until intravenous quinine was discontinued. Clinical events immediately preceding or concurrent with each episode of hypoglycaemia (glucose < = 3.0 mmol/l) were recorded.</p> <p>Results</p> <p>954 children received the old quinine regime and 283 received the new regime. We found no evidence of an increased prevalence of hypoglycaemia (< = 3.0 mmol/L) on the new regime compared to former (15% vs. 15%); similar findings were noted for profound hypoglycaemia (< 2.2 mmols/L) 8% v 5%, P = 0.07. Episodes were co-incident with disease severity markers: coma (57%), circulatory failure (38%) and respiratory distress (21%) but less commonly with seizures (10%). Disruption of maintenance fluids and/or blood transfusion concurred with 42% of the hypoglycaemia episodes. Post admission hypoglycaemia increased odds of fatal outcome (24%) compared to euglycaemic counterparts (8%), odds ratio = 3.45 (95% confidence interval = 2.30-5.16) P < 0.01.</p> <p>Conclusion</p> <p>There was no evidence to indicate a dose relationship between quinine and occurrence of hypoglycaemia. Hypoglycaemia concurred with severity features, disruption of glucose infusion and transfusion. Careful glucose monitoring should be targeted to these complications where resources are limited.</p

Comparative genomics of isolates of a pseudomonas aeruginosa epidemic strain associated with chronic lung infections of cystic fibrosis patients

Pseudomonas aeruginosa is the main cause of fatal chronic lung infections among individuals suffering from cystic fibrosis (CF). During the past 15 years, particularly aggressive strains transmitted among CF patients have been identified, initially in Europe and more recently in Canada. The aim of this study was to generate high-quality genome sequences for 7 isolates of the Liverpool epidemic strain (LES) from the United Kingdom and Canada representing different virulence characteristics in order to: (1) associate comparative genomics results with virulence factor variability and (2) identify genomic and/or phenotypic divergence between the two geographical locations. We performed phenotypic characterization of pyoverdine, pyocyanin, motility, biofilm formation, and proteolytic activity. We also assessed the degree of virulence using the Dictyostelium discoideum amoeba model. Comparative genomics analysis revealed at least one large deletion (40-50 kb) in 6 out of the 7 isolates compared to the reference genome of LESB58. These deletions correspond to prophages, which are known to increase the competitiveness of LESB58 in chronic lung infection. We also identified 308 non-synonymous polymorphisms, of which 28 were associated with virulence determinants and 52 with regulatory proteins. At the phenotypic level, isolates showed extensive variability in production of pyocyanin, pyoverdine, proteases and biofilm as well as in swimming motility, while being predominantly avirulent in the amoeba model. Isolates from the two continents were phylogenetically and phenotypically undistinguishable. Most regulatory mutations were isolate-specific and 29% of them were predicted to have high functional impact. Therefore, polymorphism in regulatory genes is likely to be an important basis for phenotypic diversity among LES isolates, which in turn might contribute to this strain's adaptability to varying conditions in the CF lung

Field-adapted sampling of whole blood to determine the levels of amodiaquine and its metabolite in children with uncomplicated malaria treated with amodiaquine plus artesunate combination

<p>Abstract</p> <p>Background</p> <p>Artemisinin combination therapy (ACT) has been widely adopted as first-line treatment for uncomplicated falciparum malaria. In Uganda, amodiaquine plus artesunate (AQ+AS), is the alternative first-line regimen to Coartem^®(artemether + lumefantrine) for the treatment of uncomplicated falciparum malaria. Currently, there are few field-adapted analytical techniques for monitoring amodiaquine utilization in patients. This study evaluates the field applicability of a new method to determine amodiaquine and its metabolite concentrations in whole blood dried on filter paper.</p> <p>Methods</p> <p>Twelve patients aged between 1.5 to 8 years with uncomplicated malaria received three standard oral doses of AQ+AS. Filter paper blood samples were collected before drug intake and at six different time points over 28 days period. A new field-adapted sampling procedure and liquid chromatographic method was used for quantitative determination of amodiaquine and its metabolite in whole blood.</p> <p>Results</p> <p>The sampling procedure was successively applied in the field. Amodiaquine could be quantified for at least three days and the metabolite up to 28 days. All parasites in all the 12 patients cleared within the first three days of treatment and no adverse drug effects were observed.</p> <p>Conclusion</p> <p>The methodology is suitable for field studies. The possibility to determine the concentration of the active metabolite of amodiaquine up to 28 days suggested that the method is sensitive enough to monitor amodiaquine utilization in patients. Amodiaquine plus artesunate seems effective for treatment of falciparum malaria.</p

Population pharmacokinetics of artesunate and amodiaquine in African children

<p>Abstract</p> <p>Background</p> <p>Pharmacokinetic (PK) data on amodiaquine (AQ) and artesunate (AS) are limited in children, an important risk group for malaria. The aim of this study was to evaluate the PK properties of a newly developed and registered fixed dose combination (FDC) of artesunate and amodiaquine.</p> <p>Methods</p> <p>A prospective population pharmacokinetic study of AS and AQ was conducted in children aged six months to five years. Participants were randomized to receive the new artesunate and amodiaquine FDC or the same drugs given in separate tablets. Children were divided into two groups of 70 (35 in each treatment arm) to evaluate the pharmacokinetic properties of AS and AQ, respectively. Population pharmacokinetic models for dihydroartemisinin (DHA) and desethylamodiaquine (DeAq), the principal pharmacologically active metabolites of AS and AQ, respectively, and total artemisinin anti-malarial activity, defined as the sum of the molar equivalent plasma concentrations of DHA and artesunate, were constructed using the non-linear mixed effects approach. Relative bioavailability between products was compared by estimating the ratios (and 95% CI) between the areas under the plasma concentration-time curves (AUC).</p> <p>Results</p> <p>The two regimens had similar PK properties in young children with acute malaria. The ratio of loose formulation to fixed co-formulation AUCs, was estimated as 1.043 (95% CI: 0.956 to 1.138) for DeAq. For DHA and total anti-malarial activity AUCs were estimated to be the same. Artesunate was rapidly absorbed, hydrolysed to DHA, and eliminated. Plasma concentrations were significantly higher following the first dose, when patients were acutely ill, than after subsequent doses when patients were usually afebrile and clinically improved. Amodiaquine was converted rapidly to DeAq, which was then eliminated with an estimated median (range) elimination half-life of 9 (7 to 12) days. Efficacy was similar in the two treatments groups, with cure rates of 0.946 (95% CI: 0.840–0.982) in the AS+AQ group and 0.892 (95% CI: 0.787 – 0.947) in the AS/AQ group. Four out of five patients with PCR confirmed recrudescences received AQ doses < 10 mg/kg. Both regimens were well tolerated. No child developed severe, post treatment neutropaenia (<1,000/μL). There was no evidence of AQ dose related hepatotoxicity, but one patient developed an asymptomatic rise in liver enzymes that was resolving by Day-28.</p> <p>Conclusion</p> <p>The bioavailability of the co-formulated AS-AQ FDC was similar to that of the separate tablets for desethylamodiaquine, DHA and the total anti-malarial activity. These data support the use this new AS-AQ FDC in children with acute uncomplicated falciparum malaria.</p

Pentoxifylline as an adjunct therapy in children with cerebral malaria

<p>Abstract</p> <p>Background</p> <p>Pentoxifylline (PTX) affects many processes that may contribute to the pathogenesis of severe malaria and it has been shown to reduce the duration of coma in children with cerebral malaria. This pilot study was performed to assess pharmacokinetics, safety and efficacy of PTX in African children with cerebral malaria.</p> <p>Methods</p> <p>Ten children admitted to the high dependency unit of the Kilifi District Hospital in Kenya with cerebral malaria (Blantyre coma score of 2 or less) received quinine plus a continuous infusion of 10 mg/kg/24 hours PTX for 72 hours. Five children were recruited as controls and received normal saline instead of PTX. Plasma samples were taken for PTX and tumour necrosis factor (TNF) levels. Blantyre Coma Score, parasitemia, hematology and vital signs were assessed 4 hourly.</p> <p>Results</p> <p>One child (20%) in the control group died, compared to four children (40%) in the PTX group. This difference was not significant (p = 0.60). Laboratory parameters and clinical data were comparable between groups. TNF levels were lower in children receiving PTX.</p> <p>Conclusions</p> <p>The small sample size does not permit definitive conclusions, but the mortality rate was unexpectedly high in the PTX group.</p