Effect of Perioperative Tranexamic Acid on Blood Loss following Open Simple Prostatectomy: A Prospective Review in Nigerian Men.

BACKGROUND: Haemorrhage is a common complication following open simple prostatectomy and patients may sometimes require a blood transfusion. Tranexamic acid has been shown to reduce blood loss following transurethral resection of the prostate and open radical prostatectomy. This study evaluated the effect of perioperative intravenous administration of tranexamic acid on blood loss and blood transfusion rates in patients who had OSP for benign prostatic enlargement. METHODOLOGY: This was a comparative study of patients with documented prostate glands 60g and above scheduled for OSP. Initial hematocrit was done a day before surgery. The patients were randomized into a tranexamic acid group, which received perioperative intravenous tranexamic acid and the no-TXA group which received placebo (0.9% saline). All patients had open simple retropubic prostatectomy. Final post-operative hematocrit was assessed 72 hours after surgery, and blood loss was calculated using the modified Gross formula (actual blood loss = estimated blood volume x change in hematocrit / mean hematocrit). The transfusion rate was documented. RESULTS: Fifty-six patients participated in this study and were randomized into a tranexamic acid group and no-tranexamic acid group. The mean age of patients in the tranexamic acid group was 66.07 ±7.08 years and was comparable to the no- tranexamic acid group which was 66.50 ± 8.80 years (P = 0.842). The median total blood loss was lower in the tranexamic acid group (502mls, IQR 613) compared to the no-tranexamic acid group (801mls, IQR 1069). The difference in the median blood loss between the two groups was 299mls (U 275, P 0.055). The rate of blood transfusion was lower in the tranexamic acid group (6 patients, 21%) compared to the no tranexamic acid group (11 patients, 39%), (P = 0.146). There was no difference in complication rates between the two groups. CONCLUSION: The use of tranexamic acid in patients undergoing open simple prostatectomy showed a trend towards reduced intraoperative blood loss and less need no tranexamic for blood transfusion. This is of clinical significance, especially in elderly patients with low cardiovascular reserve.

CONTEXTE: L'hémorragie est une complication courante après une prostatectomie simple ouverte et les patients doivent parfois recevoir une transfusion sanguine. Il a été démontré que l'acide tranexamique réduit la perte de sang après une résection transurétrale de la prostate et une prostatectomie radicale ouverte. Cette étude a évalué l'effet de l'administration intraveineuse périopératoire d'acide tranexamique sur les pertes sanguines et les taux de transfusion sanguine chez des patients ayant subi une PSO pour hypertrophie bénigne de la prostate. MÉTHODOLOGIE: Il s'agissait d'une étude comparative de patients dont la prostate de 60 g et plus était documentée et qui devaient subir une PSO. L'hématocrite de base a été effectué un jour avant la chirurgie. Les patients ont été répartis aléatoirement dans le groupe acide tranexamique, qui a reçu de l'acide tranexamique periopératoire par voie intraveineuse, et dans le groupe sans TXA, qui a reçu un placebo. Tous les patients ont subi une prostatectomie rétropubienne simple ouverte. L'hématocrite postopératoire a été évalué, et la perte de sang calculée à l'aide de la formule de Gross modifiée. Le taux de transfusion a été documenté. RÉSULTATS: Cinquante-six patients ont participé à cette étude et ont été randomisés entre le groupe avec acide tranexamique et le groupe sans acide tranexamique. L'âge moyen des patients du groupe acide tranexamique était de 66,07 ±7,08 ans et était comparable à celui du groupe sans acide tranexamique qui était de 66,50 ± 8,80 ans (P =0,842). La perte sanguine totale médiane était plus faible dans le groupe avec acide tranexamique (502 ml, IQR 613) que dans le groupe sans acide tranexamique (801 ml, IQR 1069). La différence de la perte de sang médiane entre les deux groupes était de 299 ml (U 275, P 0,055). Le taux de transfusion sanguine était inférieur dans le groupe acide tranexamique (6 patients, 21%) par rapport au groupe sans acide tranexamique (11 patients, 39%), (P =0,146). Il n'y avait pas de différence dans les taux de complication entre les deux groupes. CONCLUSION: L'utilisation de l'acide tranexamique chez les patients subissant une prostatectomie simple ouverte a montré une tendance à la réduction de la perte de sang peropératoire et un besoin moindre de transfusion sanguine. Mots clés: Hypertrophie bénigne de la prostate, Prostatectomie simple ouverte, Hémorragie, Acide tranexamique.

Outcome of Combined Trabeculotomy-Trabeculectomy in Eyes of Nigerian Children with Primary Congenital Glaucoma.

PURPOSE: To report the outcome of combined trabeculotomy-trabeculectomy among children with primary congenital glaucoma at a child eye health tertiary facility in southwest Nigeria. METHODS: A retrospective review of children who underwent combined trabeculotomy-trabeculectomy (CTT) surgery on account of primary congenital glaucoma between 2016 and 2020 at the University College Hospital, Ibadan, Nigeria. All surgeries were performed by paediatric ophthalmologists. The main outcome measures were postoperative intraocular pressure, corneal clarity, and complications. RESULTS: A total of 21 eyes of 13 patients were included. Ten (76.9%) of the patients were males and 8 (61.5%) had bilateral disease. The mean age at presentation was 4.8 (± 3.6) months, while the mean age at surgery was 8.1 (± 5.9) months. The average waiting time between noticing symptoms and presenting to the clinic was 3.2 (±4.9) months. The mean horizontal corneal diameter was 13.2 (± 1.4) mm, while the mean pre-operative intraocular pressure (IOP) was 25.7 (± 8.6) mmHg. The surgical success (IOP<21 mmHg) rates at 3, 6, and 12 months were 86.7%, 64.3%, and 92.9% respectively. The Kaplan-Meier estimates of the probability that IOP remained below 21 mmHg up till 3, 6, and 12 months were 74%, 53%, and 53% respectively. Postoperatively, 85.7% of the eyes had complete resolution of corneal oedema. One eye had an intraoperative complication of vitreous loss. The post-operative clinic follow-up rate reduced to 52.4% by 1 year. CONCLUSION: Combined trabeculotomy-trabeculectomy is a relatively safe procedure that is associated with favorable success in Nigerian children with primary congenital glaucoma.

OBJECTIF: Présenter le résultat de la combinaison de la trabeculotomie et la trabeculectomie chez les enfants atteints de glaucome congénital primitif dans un hôpital tertiaire du sud-ouest du Nigéria. METHODES: Une revue rétrospective des enfants qui avaient subi une combinaison de trabeculotomie et trabeculectomie pour le traitement de glaucome congénital primitif entre 2016 et 2020 à l'University College Hospital,Ibadan, Nigeria. Toutes les chirurgies avaient été effectuées par des ophtalmologistes pédiatres. Les principaux résultats étaient la pression intraoculaire postopératoire, la clarté cornéenne et les complications. RESULTATS: Au total 21 yeux de 13 patients étaient étudiés. Dix (76,9%) patients étaient des garçons et 8 (61,5%) avaient une atteinte bilatérale. La moyenne d'age à la présentation était de 4,8 (± 3,6) mois, tandis que la moyenne d'age au moment de la chirurgie était de 8,1 (± 5,9) mois. Le temps d'attente moyen entre l'observation des symptômes et la présentation à la consultation était de 3,2 (± 4,9) mois. Le diamètre cornéen horizontal moyen était de 13,2 (± 1,4) mm, tandis que la pression intraoculaire (PIO) préopératoire moyen était de 25,7 (± 8,6) mmHg. Les taux de succès chirurgical (PIO <21 mmHg) à 3, 6 et 12 mois étaient respectivement de 86,7%, 64,3% et 92,9% . Les estimations de Kaplan-Meier de la probabilité que la PIO restait en dessous de 21 mmHg jusqu'à 3, 6 et 12 mois était respectivement 74%, 53% et 53%. Après l'opération, 85,7% des yeux avaient une résolution complète de l'œdème cornéen. Un œil avait une complication peropératoire de perte de vitré. Le taux de visites médicales en postopératoire était réduit à 52,4% en 1 an. CONCLUSION: La combinaison de la trabeculotomie et de la trabeculectomie est une procedure chirurgicale relativement sûre associée à un succès favorable chez les enfants Nigérians atteints de glaucome congénital primitif. Mots clés: Glaucome congenital, Trabeculotomie et Trabeculectomie, Résultat chirurgical, Pression intraoculaire.

Addressing Unmet Surgical Needs in an Underserved Nigerian Community: Report of a 'Town and Gown' Initiative.

BACKGROUND: Access to quality and timely care prevents unnecessary deaths and morbidity from potentially curable surgical diseases. This study describes the magnitude of unmet surgical needs in a Nigerian community and describes the experiences garnered during a surgical outreach organized by a tertiary institution in an underserved community. METHODS: This is a descriptive study highlighting details of a surgical outreach to a community in south-Western part of Nigeria. The project was based on a collaboration between a University Teaching Hospital (gown) and the community (town). Details of the patients' demographic and disease characteristics as well as barriers to seeking medical care were obtained. The operational workflow, treatment offered, and outcomes are highlighted. Results are presented as descriptive statistics. RESULTS: Over a two-day period, 83 out of 3,056 patients who were screened had surgically treatable conditions (2.7%), predominantly hernias (37, 46.6%), goitres (13, 15.7%) and soft tissue swellings (9, 10.8%). The majority were adults (56, 67.5%) while 27 (32.5%) were in the paediatric age group. The mean duration of symptoms was 8.64 months ± 9.5 months. About half of the patients (46.9%) had never visited a medical facility on account of their index illnesses. Lack of funds was cited by many patients as the main reason for having not presented at a hospital. Sixty-three surgical operations were performed with no peri-operative adverse events. CONCLUSION: Lack of financial access was the major barrier to surgical care in the sampled community. Moving from 'gown to town' helped address a significant proportion of the unmet needs over a relatively short period. Tertiary hospitals can provide surgical oversight to communities within their jurisdiction using this approach.

CONTEXTE: L'accès à des soins de qualité et en temps opportun permet d'éiter les décès et la morbidité inutiles dus à des maladies chirurgicales potentiellement curables. Cette étude décrit l'ampleur des besoins chirurgicaux non satisfaits dans une communauté nigériane et décrit les expériences recueillies au cours d'une action chirurgicale organisée par une institution tertiaire dans une communauté mal desservie. MÉTHODES: Il s'agit d'une étude descriptive mettant en évidence les détails d'une action chirurgicale dans une communauté du sud-ouest du Nigeria. Le projet était basé sur une collaboration entre un hôpital universitaire (ville) et la communauté (ville). Les détails des caractéristiques démographiques et pathologiques des patients ainsi que les obstacles à la recherche de soins médicaux ont été obtenus. Le déroulement des opérations, le traitement proposé et les résultats sont mis en évidence. Les résultats sont présentés sous forme de statistiques descriptives. RÉSULTATS: Sur une période de deux jours, 83 des 3056 patients examinés présentaient des affections pouvant être traitées chirurgicalement (2,7 %), principalement des hernies (37, 46,6 %), des goitres (13, 15,7 %) et des tuméfactions des tissus mous (9, 10,8 %). La majorité des patients étaient des adultes (56, 67,5 %), tandis que 27 (32,5 %) appartenaient au groupe d'âge pédiatrique. La durée moyenne des symptômes était de 8,64 mois ±9,5 mois. Environ la moitié des patients (46,9 %) ne s'étaient jamais rendus dans un établissement médical en raison de leurs maladies index. Le manque de moyens financiers a été cité par de nombreux patients comme la principale raison pour laquelle ils ne s'étaient pas présentés à l'hôpital. Soixante-trois opérations chirurgicales ont été réalisées sans aucun événement indésirable périopératoire. CONCLUSION: Le manque d'accès financier était le principal obstacle aux soins chirurgicaux dans la communauté échantillonnée. Le passage de la ville à l'hôpital a permis de répondre à une proportion importante des besoins non satisfaits sur une période relativement courte. Les hôpitaux tertiaires peuvent fournir une supervision chirurgicale aux communautés de leur juridiction en utilisant cette approche. Mots clés: Chirurgie, Besoins non satisfaits, Nigeria, Communauté mal desservie.

Paediatric paranasal sinus fibrous dysplasia.

Fibrous dysplasia in the bony walls of a paranasal sinus is a developmental tumour that is associated with a marked facial deformity. Delay in hospital presentation contributes to the destructive resection techniques employed and the management outcome. Our study looks at the factors for delay in hospital presentation and the management outcome by a retrospective review between January 1997 and December 2018. Of 43 children (M: F 1:1.2) with a mean age of 12 ± 1.75 years, the maxillary bones were mostly affected. All underwent surgical resection with good management outcomes except for maxillectomy. Tumour recurrence was noted in five and there was no mitotic cell at histology. The clinical symptoms of fibrous dysplasia vary in severity and age of onset, often with late hospital presentation already with complications. Health education is needed to reverse this trend.

ASYMPTOMATIC BACTERIURIA AS A PREDICTOR OF PRE-ECLAMPSIA: A CASECONTROLLED STUDY.

Background: Pre-eclampsia, an important cause of maternal and perinatal morbidity and mortality world-wide has been linked to subclinical infections, with maternal infection and inflammation postulated in its aetio-pathogenesis including asymptomatic bacteriuria which is common in pregnancy. The Obejctive of the study is to determine the relationship of asymptomatic bacteriuria as a risk factor for pre-eclampsia. Methodology: A hospital-based case-control study among 28 pre-eclamptic pregnant women (cases) and 56 healthy pregnant women (controls) at gestational age of at least 28 weeks at the University College Hospital, Ibadan, between January 2019 and August 2019. Controls were matched with cases in age, parity and gestational age. Asymptomatic bacteriuria was determined with mid-stream urine analysis for microscopy and culture and data collected using an interviewer administered questionnaire with other details from medical records extracts. Chi- square, and multivariate regression analysis were used to assess statistical significance, odds ratio and adjusted odds ratio respectively, with P-value <0.05 and 95% confidence interval (CI). Results: There was a significant association between asymptomatic bacteriuria and pre-eclampsia. The rate of asymptomatic bacteriuria was about three times higher in women with pre-eclampsia compared to those without pre-eclampsia and 1.23 times higher after adjusting for confounders (OR: 2.9, AOR:1.23). There was no significant relationship between sterile pyuria and pre-eclampsia (p-value: 0.92). Conclusion: This study supports the proposition that asymptomatic bacteriuria is a risk factor for pre-eclampsia. It has not however shown whether the association is causal or casual. Further studies will be needed to explain this.

Genome-wide Gene-by-Sex Interaction Studies Identify Novel Nonsyndromic Orofacial Clefts Risk Locus.

Risk loci identified through genome-wide association studies have explained about 25% of the phenotypic variations in nonsyndromic orofacial clefts (nsOFCs) on the liability scale. Despite the notable sex differences in the incidences of the different cleft types, investigation of loci for sex-specific effects has been understudied. To explore the sex-specific effects in genetic etiology of nsOFCs, we conducted a genome-wide gene × sex (GxSex) interaction study in a sub-Saharan African orofacial cleft cohort. The sample included 1,019 nonsyndromic orofacial cleft cases (814 cleft lip with or without cleft palate and 205 cleft palate only) and 2,159 controls recruited from 3 sites (Ethiopia, Ghana, and Nigeria). An additive logistic model was used to examine the joint effects of the genotype and GxSex interaction. Furthermore, we examined loci with suggestive significance (P < 1E-5) in the additive model for the effect of the GxSex interaction only. We identified a novel risk locus on chromosome 8p22 with genome-wide significant joint and GxSex interaction effects (rs2720555, p2df = 1.16E-08, pGxSex = 1.49E-09, odds ratio [OR] = 0.44, 95% CI = 0.34 to 0.57). For males, the risk of cleft lip with or without cleft palate at this locus decreases with additional copies of the minor allele (p < 0.0001, OR = 0.60, 95% CI = 0.48 to 0.74), but the effect is reversed for females (p = 0.0004, OR = 1.36, 95% CI = 1.15 to 1.60). We replicated the female-specific effect of this locus in an independent cohort (p = 0.037, OR = 1.30, 95% CI = 1.02 to 1.65), but no significant effect was found for the males (p = 0.29, OR = 0.86, 95% CI = 0.65 to 1.14). This locus is in topologically associating domain with craniofacially expressed and enriched genes during embryonic development. Rare coding mutations of some of these genes were identified in nsOFC cohorts through whole exome sequencing analysis. Our study is additional proof that genome-wide GxSex interaction analysis provides an opportunity for novel findings of loci and genes that contribute to the risk of nsOFCs.

Clinical neglect of aspergillosis in pulmonary tuberculosis co-infection: a case report of avoidable mortality in a resource-constrained setting

Background: Pulmonary aspergillosis (PA) is common among patients with tuberculosis (TB). With both infections presenting with similar clinical and radiologic features, diagnosis of PA is often made too late or missed completely due to lack of clinical suspicion and poor diagnostic laboratory capacity for mycotic infections prevalent in our settings. We present a case of preventable mortality caused by delayed diagnosis and treatment of PA in a patient with pulmonary TB (PTB). Case presentation: A 13-year-old female was diagnosed and treated for PTB, having received anti-TB regimen for 8 months in a mission hospital from where she was referred due to worsening cough, chest pain and progressive breathlessness. The patient was re-assessed and investigated, with GeneXpert detecting Mycobacterium tuberculosis, susceptible to rifampicin. Diagnosis of pulmonary tuberculosis complicated by right pneumothorax was made indicating an emergency thoracotomy and chest tube insertion and continuation of the first line anti-TB regimen. At about 2 weeks into admission, patients had features of superimposed acute bacterial sepsis with fever becoming high grade, marked neutrophilia with toxic granulation and elevated sepsis biomarker, and this necessitated empiric antibiotic treatment with parenteral meropenem and vancomycin. However, the patient only had mild clinical improvement following which there was progressively worsening respiratory symptoms and massive haemoptysis. Result of sputum fungal study was available on admission day 20 and revealed a growth of Aspergillus flavus. Treatment with intravenous voriconazole was however commenced rather late when the fungal respiratory disease could no longer be remedied. The patient died on admission day 23. Conclusion: Diagnosis of PA in patients with background TB is often made too late to guarantee timely and effective antifungal treatment with negative consequences on patients' outcomes. Improving clinical and laboratory capacities is essential to reducing mortality from PA in healthcare facilities.

EVOLVING TELEMEDICINE PRACTICE: EXPERIENCES OF HEALTH CARE WORKERS DURING COVID-19 PANDEMIC.

BACKGROUND: Telemedicine is employed in patient care when direct physical contact is not possible or discouraged, as was seen during the COVID-19 pandemic. The use of smartphone technology could make telemedicine affordable and available in low and medium-income countries (LMICs). However, the evolution of telemedicine care depends on multiple factors. AIM: To explore the practice of telemedicine by Nigerian health care workers (HCWs) during the COVID-19 pandemic. METHODS: A cross-sectional study of the Nigerian HCWs on telemedicine practice in patient care during the COVID-19 pandemic period. Recruitment of respondents was done through dedicated WhatsApp and Telegram social media platforms for HCWs over a period of 40 days (May 1st and June 10th, 2020). RESULTS: A total of 481 HCWs participated in the study consisting of 153(31.8%) doctors, 150(31.2%) nurses and 178(37%) other HCWs. Though 89.2% of the HCWs agreed that telemedicine is important, it was only 266 (55.3%) that practiced telemedicine, phone consultation was the form of telemedicine used in all the health institutions. Telemedicine was practiced more by doctors 91(18.9%), nurses 79(16.4%) and pharmacists 35(7.3%) than other groups of health care workers. Inadequate COVID-19 screening test and lack of personal protective equipment were strong motivators for the attending HCWs to practice telemedicine. CONCLUSION: There was widespread use of phone consultation by all cadres of health care workers during the pandemic. Hence there should be a health policy that will encourage greater use and acceptance of telemedicine in clinical practice and in the patients care beyond the pandemic period.

DENTURE IMPACTION IN THE OESOPHAGUS: CORRELATION OF SITE AND DURATION OF IMPACTION WITH SEQUELAE.

BACKGROUND: Denture restores aesthesis and function of missing teeth. Accidentally swallowed denture is an otorhinolaryngology emergency. The types of denture base and oesophageal anatomy infuluence the site of impaction. OBJECTIVE: To review site of denture impaction and factors associated with site of impaction. To correlate site and duration of denture impaction before removal with associated sequelae. METHOD: A retrospective study of 27 patients managed in Otorhinolaryngology Department of University College Hospital Ibadan, Nigeria for oesophageal partial denture impaction, between August 2006 and September 2016. The demographic and clinical data of the patients were extracted from the hospital records, and statistical tables were used to illustrate the data. RESULTS: A total of 27 patients; 14(51.9%) males and 13(48.1%) females, (M: F, 1.1:1) were studied. The age ranged from 24 to 77 years (mean age 49.0 ± 14.2years). Dentures were worn for 3 to 30 years (mean 3.8 ± 2.3years) without follow-up visit to dentist and 85.2% were upper dentures. All patients had history of accidental ingestion of denture, and the mean site of impaction was 18.2 ± 3.2cm from upper incisor, typically at upper cervical oesophagus in elderly patients and in lower oesophagus in females. There was no association between site of denture impaction, duration of denture impaction and operative findings. CONCLUSION: Advanced age and female gender are associated with site of denture impaction. Late hospital presentation significantly promotes sequelae associated with management of impacted dentures. It is recommended that fundamental changes in denture designs, education on regular follow-ups and avoidance of ill-fitting dentures would reduce the prevalence of denture impaction.

Novel GREM1 Variations in Sub-Saharan African Patients With Cleft Lip and/or Cleft Palate.

OBJECTIVE: Cleft lip and/or cleft palate (CL/P) are congenital anomalies of the face and have multifactorial etiology, with both environmental and genetic risk factors playing crucial roles. Though at least 40 loci have attained genomewide significant association with nonsyndromic CL/P, these loci largely reside in noncoding regions of the human genome, and subsequent resequencing studies of neighboring candidate genes have revealed only a limited number of etiologic coding variants. The present study was conducted to identify etiologic coding variants in GREM1, a locus that has been shown to be largely associated with cleft of both lip and soft palate. PATIENTS AND METHOD: We resequenced DNA from 397 sub-Saharan Africans with CL/P and 192 controls using Sanger sequencing. Following analyses of the sequence data, we observed 2 novel coding variants in GREM1. These variants were not found in the 192 African controls and have never been previously reported in any public genetic variant database that includes more than 5000 combined African and African American controls or from the CL/P literature. RESULTS: The novel variants include p.Pro164Ser in an individual with soft palate cleft only and p.Gly61Asp in an individual with bilateral cleft lip and palate. The proband with the p.Gly61Asp GREM1 variant is a van der Woude (VWS) case who also has an etiologic variant in IRF6 gene. CONCLUSION: Our study demonstrated that there is low number of etiologic coding variants in GREM1, confirming earlier suggestions that variants in regulatory elements may largely account for the association between this locus and CL/P.

Cardiac diastolic function after recovery from pre-eclampsia.

BACKGROUND: Pre-eclampsia is associated with significant changes to the cardiovascular system during pregnancy. Eccentric and concentric remodelling of the left ventricle occurs, resulting in impaired contractility and diastolic dysfunction. It is unclear whether these structural and functional changes resolve completely after delivery. AIMS: The objective of the study was to determine cardiac diastolic function at delivery and one year post-partum in women with severe pre-eclampsia, and to determine possible future cardiovascular risk. METHODS: This was a descriptive study performed at Steve Biko Academic Hospital, a tertiary referral hospital in Pretoria, South Africa. Ninety-six women with severe preeclampsia and 45 normotensive women with uncomplicated pregnancies were recruited during the delivery admission. Seventy-four (77.1%) women in the pre-eclamptic group were classified as a maternal near miss. Transthoracic Doppler echocardiography was performed at delivery and one year post-partum. RESULTS: At one year post-partum, women with pre-eclampsia had a higher diastolic blood pressure (p = 0.001) and body mass index (p = 0.02) than women in the normotensive control group. Women with early onset pre-eclampsia requiring delivery prior to 34 weeks' gestation had an increased risk of diastolic dysfunction at one year post-partum (RR 3.41, 95% CI: 1.11-10.5, p = 0.04) and this was irrespective of whether the patient had chronic hypertension or not. CONCLUSION: Women who develop early-onset pre-eclampsia requiring delivery before 34 weeks are at a significant risk of developing cardiac diastolic dysfunction one year after delivery compared to normotensive women with a history of a low-risk pregnancy.

Loss-of-Function GRHL3 Variants Detected in African Patients with Isolated Cleft Palate.

In contrast to the progress that has been made toward understanding the genetic etiology of cleft lip with or without cleft palate, relatively little is known about the genetic etiology for cleft palate only (CPO). A common coding variant of grainyhead like transcription factor 3 ( GRHL3) was recently shown to be associated with risk for CPO in Europeans. Mutations in this gene were also reported in families with Van der Woude syndrome. To identify rare mutations in GRHL3 that might explain the missing heritability for CPO, we sequenced GRHL3 in cases of CPO from Africa. We recruited participants from Ghana, Ethiopia, and Nigeria. This cohort included case-parent trios, cases and other family members, as well as controls. We sequenced exons of this gene in DNA from a total of 134 nonsyndromic cases. When possible, we sequenced them in parents to identify de novo mutations. Five novel mutations were identified: 2 missense (c.497C>A; p.Pro166His and c.1229A>G; p.Asp410Gly), 1 splice site (c.1282A>C p.Ser428Arg), 1 frameshift (c.470delC; p.Gly158Alafster55), and 1 nonsense (c.1677C>A; p.Tyr559Ter). These mutations were absent from 270 sequenced controls and from all public exome and whole genome databases, including the 1000 Genomes database (which includes data from Africa). However, 4 of the 5 mutations were present in unaffected mothers, indicating that their penetrance is incomplete. Interestingly, 1 mutation damaged a predicted sumoylation site, and another disrupted a predicted CK1 phosphorylation site. Overexpression assays in zebrafish and reporter assays in vitro indicated that 4 variants were functionally null or hypomorphic, while 1 was dominant negative. This study provides evidence that, as in Caucasian populations, mutations in GRHL3 contribute to the risk of nonsyndromic CPO in the African population.

Association Studies and Direct DNA Sequencing Implicate Genetic Susceptibility Loci in the Etiology of Nonsyndromic Orofacial Clefts in Sub-Saharan African Populations.

Orofacial clefts (OFCs) are congenital dysmorphologies of the human face and oral cavity, with a global incidence of 1 per 700 live births. These anomalies exhibit a multifactorial pattern of inheritance, with genetic and environmental factors both playing crucial roles. Many loci have been implicated in the etiology of nonsyndromic cleft lip with or without cleft palate (NSCL/P) in populations of Asian and European ancestries, through genome-wide association studies and candidate gene studies. However, few populations of African descent have been studied to date. Here, the authors show evidence of an association of some loci with NSCL/P and nonsyndromic cleft palate only (NSCPO) in cohorts from Africa (Ghana, Ethiopia, and Nigeria). The authors genotyped 48 single-nucleotide polymorphisms that were selected from previous genome-wide association studies and candidate gene studies. These markers were successfully genotyped on 701 NSCL/P and 163 NSCPO cases, 1,070 unaffected relatives, and 1,078 unrelated controls. The authors also directly sequenced 7 genes in 184 nonsyndromic OFC (NSOFC) cases and 96 controls from Ghana. Population-specific associations were observed in the case-control analyses of the subpopulations, with West African subpopulations (Ghana and Nigeria) showing a similar pattern of associations. In meta-analyses of the case-control cohort, PAX7 (rs742071, P = 5.10 × 10(-3)), 8q24 (rs987525, P = 1.22 × 10(-3)), and VAX1 (rs7078160, P = 0.04) were nominally associated with NSCL/P, and MSX1 (rs115200552, P = 0.01), TULP4 (rs651333, P = 0.04), CRISPLD2 (rs4783099, P = 0.02), and NOG1 (rs17760296, P = 0.04) were nominally associated with NSCPO. Moreover, 7 loci exhibited evidence of threshold overtransmission in NSOFC cases through the transmission disequilibrium test and through analyses of the family-based association for disease traits. Through DNA sequencing, the authors also identified 2 novel, rare, potentially pathogenic variants (p.Asn323Asp and p.Lys426IlefsTer6) in ARHGAP29 In conclusion, the authors have shown evidence for the association of many loci with NSCL/P and NSCPO. To the best of this knowledge, this study is the first to demonstrate any of these association signals in any African population.

Effects of Community Health Nurse-Led Intervention on Childhood Routine Immunization Completion in Primary Health Care Centers in Ibadan, Nigeria.

Immunization coverage of vulnerable children is often sub-optimal in many low- and middle-income countries. The use of a reminder/recall (R/R) system has been one of the strategies shown to be effective in improving immunization rates. In the resent study, we evaluated the effect of R/R and Primary Health Care Immunization Providers' Training (PHCIPT) intervention on routine immunization completion among 595 infants in Ibadan, Nigeria. The design was a group randomized controlled trial with Local Government Area (LGA) being the unit of randomization. Four randomly selected LGAs were randomized to receive a cellphone R/R only (A), a PHCIPT only (B); combined R/R and PHCIPT (C) intervention or serve as a control group (D). Children aged 0-12 weeks were consecutively recruited into each group and followed up for 12 months. The primary outcome measure was routine immunization completion at 12 months of age. At the study endpoint, immunization completion rates were: group A, 98.6 %; group B, 70 %; group C, 97.3 %; and group D, 57.3 %. Compared to the control group, the cellphone R/R group was 72 % (RR 1.72, 95 % CI 1.50-1.98) and the combined RR/PHCIPT group 70 % (RR 1.70, 95 % CI 1.47-1.95) more likely to complete immunization. In contrast, immunization completion in the PHCIPT group was marginally different from the control group (RR 1.22, 95 % CI 1.03-1.45). These findings remained robust to adjustment for potential predictors of immunization completion as covariates. In conclusion, cellphone reminder/recall was effective in improving immunization completion in this Nigerian setting. Its use is recommended for large scale implementation.

Takayasu arteritis in pregnancy.

Takayasu arteritis is a chronic, granulomatous arteritis affecting large and medium-sized arteries. During pregnancy, maternal and foetal complications are largely as a consequence of maternal arterial hypertension. We present a case of a 35-year-old para one gravida two patient with Takayasu arteritis (group III disease) complicated by chronic hypertension and a severely dilated ascending aorta. Good blood pressure control during pregnancy is an important measure in reducing obstetric morbidity.

Pharmacogenomics, ancestry and clinical decision making for global populations.

Pharmacogenomically relevant markers of drug response and adverse drug reactions are known to vary in frequency across populations. We examined minor allele frequencies (MAFs), genetic diversity (FST) and population structure of 1156 genetic variants (including 42 clinically actionable variants) in 212 genes involved in drug absorption, distribution, metabolism and excretion (ADME) in 19 populations (n=1478). There was wide population differentiation in these ADME variants, reflected in the range of mean MAF (ΔMAF) and FST. The largest mean ΔMAF was observed in African ancestry populations (0.10) and the smallest mean ΔMAF in East Asian ancestry populations (0.04). MAFs ranged widely, for example, from 0.93 for single-nucleotide polymorphism (SNP) rs9923231, which influences warfarin dosing to 0.01 for SNP rs3918290 associated with capecitabine metabolism. ADME genetic variants show marked variation between and within continental groupings of populations. Enlarging the scope of pharmacogenomics research to include multiple global populations can improve the evidence base for clinical translation to benefit all peoples.

Multidrug-resistant human mycobacterium tuberculosis strain resisted inactivation by 10% formalin.

Multidrug-resistant strain of Mycobacterium tuberculosis (MDR-Tb) and Multidrug-sensitive Mycobacterium tuberculosis (MDS-Tb) isolated from humans were injected subcutaneously into the guinea pigs. One set of infected lungs of animals was fixed in 10% formalin pH7.2, while the other set was treated with 75% ethanol 2 hours prior to fixation in 10% formalin. After six months of fixation, MDS-Tb strains were completely inactivated by both methods of fixation. MDR-Tb strains resisted inactivation by 10% formalin, but were inactivated by the treatment with 75% ethanol 2 hours prior to 10% formalin fixation. MDR-Tb was still viable after six months in tissue preserved in 10% formalin only. Pretreatment of tissue with 75% ethanol prior to preservation in 10% formalin gave a better safety precaution against MDR-Tb in tissue. Of the 50 infected patients studied during the period, 4 (8%) haboured MDR-Tb, while 46 (92%) carried MDS-Tb.

Achieving rapid reduction of HIV-1 viral load in HIV-positive pregnant women close to term - an obstetric/medical emergency: a review of three cases.

Mother-to-child transmission (MTCT) of HIV infection is now uncommon in the UK and the management of HIV-positive pregnant women is usually relatively straightforward. However, HIV viral load suppression may be difficult to achieve peripartum for women who book very late in pregnancy and those with a poor adherence to antiretroviral therapy (ART). These pregnancies are at a higher risk of MTCT due to high viral load (VL). Therefore, the development of interventions to achieve a rapid reduction of HIV VL is essential. We describe three relevant cases that presented to our unit over a 12-month period and discuss the strategies employed to manage these challenging cases. All babies were born healthy and were HIV proviral DNA-negative at 12 weeks postpartum. No serious adverse events were reported for the mothers or their babies.

Kaposi's sarcoma in pregnancy after initiation of highly active antiretroviral therapy: a manifestation of immune reconstitution syndrome.

A case of Kaposi's sarcoma (KS) presenting as an immune reconstitution inflammatory syndrome in pregnancy with conservative management is reported. Successful outcomes for mother and baby were achieved. HIV was diagnosed at antenatal booking and highly active antiretroviral therapy commenced at 20 weeks. Multiple lymphadenopathies developed two months later. Excision biopsy of a node confirmed KS. In the absence of advanced disease, she was managed conservatively until delivery. The placenta showed no evidence of KS or human herpes virus 8 (HHV-8). The baby had negative HIV and HHV-8 polymerase chain reaction tests at zero, six and 12 weeks of life. Six months postpartum, the KS had regressed and HHV-8 viral load was undetectable.