Multidisciplinary approach to genomics research in Africa:the AfriCRAN model

This article is an outcome of the African Craniofacial Anomalies Research Network (AfriCRAN) Human Hereditary and Health (H3A) grant planning meeting in 2012 in Lagos, Nigeria. It describes the strengths of a multidisciplinary team approach to solving complex genetic traits in the craniofacial region. It also highlights the different components and argues for the composition of similar teams to fast track the discovery of disease genes, diagnostic tools, improved clinical treatment and ultimately prevention of disease

Readmissions after general surgery: a prospective multicenter audit

Background: Readmission rates after surgical procedures are viewed as a marker of quality of care and as a driver to improve outcomes in the United Kingdom, they are not remunerated. However, readmissions are not wholly avoidable. The aim of this study was to develop a regional overview of readmissions to determine the proportion that might be avoidable and to examine predictors of readmissions at a unit level. Methods: We undertook a prospective multicenter audit of readmissions following National Health Service funded general surgical procedures in five National Health Service hospitals and three independent sector providers over a 2-wk period. Basic demographic and procedure data were captured. Readmissions to hospitals were identified through acute admissions lists. Reason for readmission was identified, and the readmission data assessed by a senior surgical doctor as to whether it was avoidable. Results: We identified 752 operations in the study period with all followed up to 30 d. The overall rate of readmissions was 4.7%, with 40% of these judged as being potentially avoidable. Pain and wound problems accounted for the vast majority of avoidable readmissions. The number of unavoidable readmissions was correlated with the workload of each center (r ¼ 0.63, P ¼ 0.06) and as with the higher (British United Provident Association) complexity of surgery (r ¼ 0.90, P ¼ 0.01). Patient and demographic factors were not associated with readmissions. Conclusions: This prospective audit describes readmission rates after general surgery. Volume and complexity of work are associated with readmission rates. A large proportion of readmissions could be reduced by attention to analgesia and outpatient arrangements for wound management

Community engagement and compliance monitoring of COVID-19 safety protocols: innovative approach combining indigenous practice and GIS technology in Oyo State, Nigeria

Background: One of the major challenges that has driven the spread of Coronavirus Disease 2019 (COVID-19) worldwide is the burden of enforcing the preventive measures required to contain the pandemic. Enforcement of COVID-19 precautionary behaviour should not be homogenous; every country needs to be creative to ensure that humane considerations guide all decisions during the extraordinary experience that COVID-19 pandemic portends. The model of self-policing is acceptable and maintained principally because the citizens of any communities operate, recognize, and accept them as preferred alternatives to the official models of policing for enforcement. Hence the approach presented in this paper, which deployed existing indigenous alternative systems in ensuring compliance with COVID-19 precautionary behaviour. This article therefore documents the unique approach deployed for the containment of COVID-19 in Oyo State, Nigeria. Objective: This intervention was designed to explore established indigenous alternative systems and models of control, justice, law, security, and enforcement in Nigeria. Additionally, geographic information system (GIS) technology and investigative journalism was used to monitor and evaluate the effectiveness of the intervention. Method: The method employed was community conversation; a method of increasing inclusive, community-based engagement harnessing the expertise and motivation of key stakeholders. The community conversations were convened after the pattern of a traditional Town-hall meeting. Community conversations were organized as a qualitative framework focusing on deploying the indigenous practice of self-policing associated with Nigerias trade unions and aims to inform COVID-19 preventive behaviour at the community level. Geographical information system technology was used to develop COVID-19 Containment Compliance Citizens Reporter App. The App was developed using ESRI ArcGIS online platform to crowd source public feedback on compliance or contravention of COVID-19 protocols. Social media platforms were also deployed for monitoring and evaluation of the intervention post townhall meeting. Results: The establishment of a State-wide Containment response network provided the required inroad for advocacy and deployment of state-wide community conversation framework in the different communities comprising diverse ethnic groups, religious leaders, market leaders, National Union of Road Transport Workers (NURTW), and so on. Testimonials from the various communities showed that the people have embraced the self-policing strategy and the network system was effective with good outcomes in terms of response to decontamination, containment, and advocacy. The COVID-19 Containment Compliance Citizens Reporter App, investigative reporting by mass media were highly effective tools for monitoring and evaluation of the outcome of the intervention as well as possible evidence for melting out incentive and disincentive measures as necessary. This approach is a template, which could be adapted and replicated in other parts of Nigeria and other African societies with similar structures, demographics, and indigenous practices

Intravenous versus oral iron for iron deficiency anaemia in pregnant Nigerian women (IVON): study protocol for a randomised hybrid effectiveness-implementation trial

Background Anaemia in pregnancy is highly prevalent in African countries. High-dose oral iron is the current recommended treatment for pregnancy-related iron deficiency anaemia (IDA) in Nigeria and other African countries. This oral regimen is often poorly tolerated and has several side effects. Parenteral iron preparations are now available for the treatment of IDA in pregnancy but not widely used in Africa. The IVON trial is investigating the comparative effectiveness and safety of intravenous ferric carboxymaltose versus oral ferrous sulphate standard-of-care for pregnancy-related IDA in Nigeria. We will also measure the implementation outcomes of acceptability, feasibility, fidelity, and cost-effectiveness for intravenous ferric carboxymaltose. Methods This is an open-label randomised controlled trial with a hybrid type 1 effectiveness-implementation design, conducted at 10 health facilities in Kano (Northern) and Lagos (Southern) states in Nigeria. A total of 1056 pregnant women at 20–32 weeks’ gestational age with moderate or severe anaemia (Hb < 10g/dl) will be randomised 1:1 into two groups. The interventional treatment is one 1000-mg dose of intravenous ferric carboxymaltose at enrolment; the control treatment is thrice daily oral ferrous sulphate (195 mg elemental iron daily), from enrolment till 6 weeks postpartum. Primary outcome measures are (1) the prevalence of maternal anaemia at 36 weeks and (2) infant preterm birth (<37 weeks’ gestation) and will be analysed by intention-to-treat. Maternal full blood count and iron panel will be assayed at 4 weeks post-enrolment, 36 weeks’ gestation, delivery, and 6 weeks postpartum. Implementation outcomes of acceptability, feasibility, fidelity, and cost will be assessed with structured questionnaires, key informant interviews, and focus group discussions. Discussion The IVON trial could provide both effectiveness and implementation evidence to guide policy for integration and uptake of intravenous iron for treating anaemia in pregnancy in Nigeria and similar resource-limited, high-burden settings. If found effective, further studies exploring different intravenous iron doses are planned. Trial registration ISRCTN registry ISRCTN63484804. Registered on 10 December 2020. Clinicaltrials.govNCT04976179. Registered on 26 July 2021 The current protocol version is version 2.1 (080/080/2021)

Intravenous versus oral iron for iron deficiency anaemia in pregnant Nigerian women (IVON): study protocol for a randomised hybrid effectiveness-implementation trial.

BACKGROUND: Anaemia in pregnancy is highly prevalent in African countries. High-dose oral iron is the current recommended treatment for pregnancy-related iron deficiency anaemia (IDA) in Nigeria and other African countries. This oral regimen is often poorly tolerated and has several side effects. Parenteral iron preparations are now available for the treatment of IDA in pregnancy but not widely used in Africa. The IVON trial is investigating the comparative effectiveness and safety of intravenous ferric carboxymaltose versus oral ferrous sulphate standard-of-care for pregnancy-related IDA in Nigeria. We will also measure the implementation outcomes of acceptability, feasibility, fidelity, and cost-effectiveness for intravenous ferric carboxymaltose. METHODS: This is an open-label randomised controlled trial with a hybrid type 1 effectiveness-implementation design, conducted at 10 health facilities in Kano (Northern) and Lagos (Southern) states in Nigeria. A total of 1056 pregnant women at 20-32 weeks' gestational age with moderate or severe anaemia (Hb < 10g/dl) will be randomised 1:1 into two groups. The interventional treatment is one 1000-mg dose of intravenous ferric carboxymaltose at enrolment; the control treatment is thrice daily oral ferrous sulphate (195 mg elemental iron daily), from enrolment till 6 weeks postpartum. Primary outcome measures are (1) the prevalence of maternal anaemia at 36 weeks and (2) infant preterm birth (<37 weeks' gestation) and will be analysed by intention-to-treat. Maternal full blood count and iron panel will be assayed at 4 weeks post-enrolment, 36 weeks' gestation, delivery, and 6 weeks postpartum. Implementation outcomes of acceptability, feasibility, fidelity, and cost will be assessed with structured questionnaires, key informant interviews, and focus group discussions. DISCUSSION: The IVON trial could provide both effectiveness and implementation evidence to guide policy for integration and uptake of intravenous iron for treating anaemia in pregnancy in Nigeria and similar resource-limited, high-burden settings. If found effective, further studies exploring different intravenous iron doses are planned. TRIAL REGISTRATION: ISRCTN registry ISRCTN63484804 . Registered on 10 December 2020 Clinicaltrials.gov NCT04976179 . Registered on 26 July 2021 The current protocol version is version 2.1 (080/080/2021)

Intravenous versus oral iron for anaemia among pregnant women in Nigeria (IVON): an open-label, randomised controlled trial.

BACKGROUND: Oral iron for anaemia in pregnancy is often not well tolerated, with poor adherence. Iron administered intravenously might address these tolerance and adherence issues. We investigated the effectiveness and safety of intravenous ferric carboxymaltose versus oral ferrous sulphate on anaemia and iron deficiency among pregnant women in Nigeria. METHODS: We did a multicentre, open-label, parallel, randomised controlled trial of pregnant women (aged 15-49 years) with haemoglobin (Hb) concentrations of less than 10 g/dL at 20-32 weeks' gestation from 11 primary, secondary, or tertiary health facilities in Nigeria (five in Lagos and six in Kano). Exclusion criteria included vaginal bleeding, blood transfusion or major surgery within the past 3 months, symptomatic anaemia, anaemia known to be unrelated to iron deficiency, clinically confirmed malabsorption syndrome, previous hypersensitivity to any form of iron, pre-existing maternal depression or other major psychiatric illness, immune-related diseases, such as systemic lupus erythematosus or rheumatoid arthritis, or severe allergic reactions. Participants were randomly assigned (1:1) by nurses and doctors using a web-based randomisation service to either receive a single dose of intravenous ferric carboxymaltose (20 mg/kg to a maximum of 1000 mg) or oral ferrous sulphate (200 mg; 65 mg elemental iron) three times daily until 6 weeks postpartum. The study was primarily unmasked. Primary outcomes were maternal anaemia (Hb <11 g/dL) at 36 weeks' gestation and preterm birth at before 37 weeks' gestation, with analysis by intention to treat in participants with available data. This study was registered at the ISRCTN registry on Dec 10, 2020 (ISRCTN63484804) and on ClinicalTrials.gov (NCT04976179) on April 7, 2021. FINDINGS: Between Aug 10, 2021, and Dec 15, 2022, 13 724 pregnant women were screened for eligibility. 12 668 were excluded due to ineligibility for inclusion, and 1056 provided consent to participate and were randomly assigned to either the intravenous or oral administration groups. 527 were assigned to the intravenous ferric carboxymaltose group and 529 were assigned to the oral ferrous sulphate group. 518 in the intravenous group were assessed at 36 weeks' gestational age and after 518 deliveries, and 511 completed the 6 weeks postpartum visit. 513 in the oral ferrous sulphate group were assessed at 36 weeks' gestational age and after 512 deliveries, and 501 completed the 6 weeks postpartum visit. No significant difference was found in anaemia at 36 weeks (299 [58%] of 517 in the intravenous group vs 305 [61%] of 503 in the oral group; risk ratio 0·95, 95% CI 0·85-1·06; p=0·36), nor in preterm birth (73 [14%] of 518 vs 77 [15%] of 513; 0·94, 0·70-1·26; p=0·66). There were no significant differences in adverse events. The most common adverse events were diarrhoea (in six participants) and vomiting (in three participants) in the oral group and fatigue (in two participants) and headache (in two participants) in the intravenous group. INTERPRETATION: Although the effect on overall anaemia did not differ, intravenous iron reduced the prevalence of iron deficiency to a greater extent than oral iron and was considered to be safe. We recommend that intravenous iron be considered for anaemic pregnant women in Nigeria and similar settings. FUNDING: Bill & Melinda Gates Foundation

Epigenome-wide association study of serum urate reveals insights into urate co-regulation and the SLC2A9 locus

Elevated serum urate levels, a complex trait and major risk factor for incident gout, are correlated with cardiometabolic traits via incompletely understood mechanisms. DNA methylation in whole blood captures genetic and environmental influences and is assessed in transethnic meta-analysis of epigenome-wide association studies (EWAS) of serum urate (discovery, n = 12,474, replication, n = 5522). The 100 replicated, epigenome-wide significant (p &lt; 1.1E–7) CpGs explain 11.6% of the serum urate variance. At SLC2A9, the serum urate locus with the largest effect in genome-wide association studies (GWAS), five CpGs are associated with SLC2A9 gene expression. Four CpGs at SLC2A9 have significant causal effects on serum urate levels and/or gout, and two of these partly mediate the effects of urate-associated GWAS variants. In other genes, including SLC7A11 and PHGDH, 17 urate-associated CpGs are associated with conditions defining metabolic syndrome, suggesting that these CpGs may represent a blood DNA methylation signature of cardiometabolic risk factors. This study demonstrates that EWAS can provide new insights into GWAS loci and the correlation of serum urate with other complex traits

Discovery and fine-mapping of adiposity loci using high density imputation of genome-wide association studies in individuals of African ancestry: African Ancestry Anthropometry Genetics Consortium

Genome-wide association studies (GWAS) have identified >300 loci associated with measures of adiposity including body mass index (BMI) and waist-to-hip ratio (adjusted for BMI, WHRadjBMI), but few have been identified through screening of the African ancestry genomes. We performed large scale meta-analyses and replications in up to 52,895 individuals for BMI and up to 23,095 individuals for WHRadjBMI from the African Ancestry Anthropometry Genetics Consortium (AAAGC) using 1000 Genomes phase 1 imputed GWAS to improve coverage of both common and low frequency variants in the low linkage disequilibrium African ancestry genomes. In the sex-combined analyses, we identified one novel locus (TCF7L2/HABP2) for WHRadjBMI and eight previously established loci at P < 5×10−8: seven for BMI, and one for WHRadjBMI in African ancestry individuals. An additional novel locus (SPRYD7/DLEU2) was identified for WHRadjBMI when combined with European GWAS. In the sex-stratified analyses, we identified three novel loci for BMI (INTS10/LPL and MLC1 in men, IRX4/IRX2 in women) and four for WHRadjBMI (SSX2IP, CASC8, PDE3B and ZDHHC1/HSD11B2 in women) in individuals of African ancestry or both African and European ancestry. For four of the novel variants, the minor allele frequency was low (<5%). In the trans-ethnic fine mapping of 47 BMI loci and 27 WHRadjBMI loci that were locus-wide significant (P < 0.05 adjusted for effective number of variants per locus) from the African ancestry sex-combined and sex-stratified analyses, 26 BMI loci and 17 WHRadjBMI loci contained ≤ 20 variants in the credible sets that jointly account for 99% posterior probability of driving the associations. The lead variants in 13 of these loci had a high probability of being causal. As compared to our previous HapMap imputed GWAS for BMI and WHRadjBMI including up to 71,412 and 27,350 African ancestry individuals, respectively, our results suggest that 1000 Genomes imputation showed modest improvement in identifying GWAS loci including low frequency variants. Trans-ethnic meta-analyses further improved fine mapping of putative causal variants in loci shared between the African and European ancestry populations

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P &lt; 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely