Determinants of hydroxyurea use among doctors, nurses and sickle cell disease patients in Nigeria.

BACKGROUND: Hydroxyurea (HU) is an evidence-based therapy that is currently the most effective drug for sickle cell disease (SCD). HU is widely used in high-income countries with consequent reduction of morbidity and mortality. In Nigeria, HU is prescribed by physicians while nurses are mainly involved in counseling the patients to ensure adherence. The extent of utilization and the determinant factors have not been sufficiently evaluated in Nigeria. OBJECTIVE: To assess the frequency of use of HU and factors affecting utilization among healthcare providers, patients, and caregivers for SCD. METHODS: A questionnaire was administered online and in- person to assess the frequency of HU use and the factors that promote and limit its use. The data were analyzed by descriptive statistics using IBM SPSS software version 23 and the result was presented in frequency tables and percentages. RESULT: A total of 137 physicians, 137 nurses, and 237 patients/caregivers responded to the survey. The rate of prescription of HU by doctors in the past 6 months was 64 (46.7%), 43 (31.4%) nurses provided counseling and 36 (15.6%) patients were on HU. Among doctors, adequate knowledge (91.3%), clinical benefits and safety (94.8%), and inclusion of HU in management guidelines (86.9%) were motivators for prescribing it while inadequate knowledge (60.9%) and unawareness of treatment guidelines (68.6%) constituted barriers. Among nurses, reduction of crisis (91.6%) and safety (64.8%) were the major motivators while barriers were high cost (79.1%) and intensive monitoring (63.1%) of HU treatment. Among the patients, the major motivator was the reduction of crises (80.3%) while poor knowledge (93.2%), high cost of the drug (92.2%) while monitoring (91.2%), non-availability (87.7%) and side effects (83.9%) were the major barriers for the utilization of HU. CONCLUSION: HU prescription and utilization are still poor among healthcare providers and patients. Inadequate knowledge, non-availability and high cost of HU as well as unawareness of treatment guidelines constitute major barriers to prescription and utilization.

Testing the generalizability of ancestry-specific polygenic risk scores to predict prostate cancer in sub-Saharan Africa.

BACKGROUND: Genome-wide association studies do not always replicate well across populations, limiting the generalizability of polygenic risk scores (PRS). Despite higher incidence and mortality rates of prostate cancer in men of African descent, much of what is known about cancer genetics comes from populations of European descent. To understand how well genetic predictions perform in different populations, we evaluated test characteristics of PRS from three previous studies using data from the UK Biobank and a novel dataset of 1298 prostate cancer cases and 1333 controls from Ghana, Nigeria, Senegal, and South Africa. RESULTS: Allele frequency differences cause predicted risks of prostate cancer to vary across populations. However, natural selection is not the primary driver of these differences. Comparing continental datasets, we find that polygenic predictions of case vs. control status are more effective for European individuals (AUC 0.608-0.707, OR 2.37-5.71) than for African individuals (AUC 0.502-0.585, OR 0.95-2.01). Furthermore, PRS that leverage information from African Americans yield modest AUC and odds ratio improvements for sub-Saharan African individuals. These improvements were larger for West Africans than for South Africans. Finally, we find that existing PRS are largely unable to predict whether African individuals develop aggressive forms of prostate cancer, as specified by higher tumor stages or Gleason scores. CONCLUSIONS: Genetic predictions of prostate cancer perform poorly if the study sample does not match the ancestry of the original GWAS. PRS built from European GWAS may be inadequate for application in non-European populations and perpetuate existing health disparities.

Determination of Serum Prostate Specific Antigen Levels Amongst Apparently Healthy Nigerian Males in a University and University Hospital Community in the Federal Capital Territory.

BACKGROUND: Prostate cancer is the commonest cancer among men worldwide and serum prostate specific antigen (PSA) has remained the most commonly applied screening test for the disease till date. Current PSA test results guidelines in our population are informed by reference intervals derived from studies from Caucasians and other racial groups. With scanty data on PSA reference values from our local population, this study evaluated the serum PSA levels of apparently healthy Nigerian male subjects in whom prostate cancer and urinary tract infection have been excluded. METHOD: This study had participants aged 40 to 70 years, with no lower urinary tract symptoms or other symptoms suggestive of prostate disease recruited from the male staff population of the University of Abuja and University of Abuja Teaching Hospital and the adjoining local community. They were physically examined, had prostate ultrasonography, urine analysis, and blood sample collected for PSA testing. Data collected was analyzed using Statistical Package for Social Science (SPSS) version 24. RESULT: Of a total of 210 men who participated in the study, 191 eventually met the inclusion criteria. The average age was 52.9 years, ninety seven percent of them had heard of prostate cancer before now. The mean total PSA was 1.46 ng/mL (SD +/-1.55), while the reference interval was .23-5.60 ng/mL. The average prostate size was 41.8 mL (SD+/-20.11), and there was a positive correlation between the PSA and the prostate size (.418) as well as the age of the subjects (.446). There was no significant difference in the mean PSA value for those with or without family history of prostate cancer (P=.979). CONCLUSION: The reference range of PSA in Nigeria is higher than in other races, hence utilizing a local value in decision making would help to reduce unnecessary invasive procedures.

Hyperhomocysteinemia and its relations to conventional risk factors for cardiovascular diseases in adult Nigerians: the REMAH study.

BACKGROUND: Evidence linking homocysteine (Hcy) with cardiovascular diseases (CVD) or its risk factors are limited in a sub-Saharan black population. OBJECTIVE: We set out to evaluate the association between Hcy and hypertension and other CVD risk factors in a population of adult Nigerians. METHODS: Data of 156 adults aged 18-70 years was accessed from the North Central study site of the REmoving the MAsk on Hypertension (REMAH) study. Homocysteine, blood glucose and lipid profile in whole blood/serum were measured using standard laboratory methods. Hypertension was diagnosed if average of 5 consecutive blood pressure (BP) measurements obtained using a mercury sphygmomanometer was equal to or higher than 140 systolic and/or 90 mmHg diastolic or the individual is on antihypertensive medication. Hyperhomocysteinemia (HHcy) was defined as Hcy > 10 µmol/L. RESULTS: Of the 156 participants, 72 (43.5%) were hypertensive, of whom 18 had HHcy. Subjects with HHcy were significantly (p < 0.05) older (41.5 vs. 40.6yrs), had lower HDL-cholesterol (0.6 vs. 0.8 mmol/L) and higher systolic (145.5 vs. 126.0 mmHg) and diastolic BP (92.9 vs. 79.6 mmHg), compared to those without HHcy. Intake of alcohol and a 1 yr increase in age were respectively and significantly (p < 0.05) associated with a 1.54 and 0.10 µmol/L increase in Hcy. In a multivariable model adjusted for age, sex and body mass index, a 1 µmol/L increase in Hcy, was associated with a 1.69 mmHg and 1.34 mmHg increase in systolic and diastolic pressure (p < 0.0001) respectively; and a 0.01 mmol/L decrease in HDL-cholesterol (p < 0.05). CONCLUSION: HHcy occurs among hypertensive Nigerians and it is independently associated with age, HDL-cholesterol, systolic and diastolic BP.

Prevalence and Determinants of Masked Hypertension in Nigeria: The REMAH Study.

BACKGROUND: Estimating the burden of hypertension in Nigeria hitherto relied on clinic blood pressure (BP) measurement alone. This excludes individuals with masked hypertension (MH), i.e., normotensive clinic but hypertensive out-of-clinic BP. METHODS: In a nationally representative sample of adult Nigerians, we obtained clinic BP using auscultatory method and out-of-clinic BP by self-measured home BP with semi-automated oscillometric device. Clinic BP was average of 5 consecutive measurements and home BP was average of 3 days duplicate morning and evening readings. MH was clinic BP <140 mm Hg systolic and 90 mm Hg diastolic and home BP ≥135 mm Hg systolic and/or 85 mm Hg diastolic. RESULTS: Among 933 participants, the prevalence of sustained hypertension, MH, and white-coat hypertension was 28.3%, 7.9%, and 11.9%, respectively. Among subjects whose clinic BP were in the normotensive range (n = 558), the prevalence of MH was 13%; 12% among untreated and 27% among treated individuals. The mutually adjusted odds ratios of having MH among all participants with normotensive clinic BP were 1.33 (95% confidence interval, 1.10-1.60) for a 10-year higher age, 1.59 (1.09-2.40) for a 10 mm Hg increment in systolic clinic BP, and 1.16 (1.08-1.28) for a 10 mg/dl higher random blood glucose. The corresponding estimates in the untreated population were 1.24 (1.03-1.51), 1.56 (1.04-2.44), and 1.16 (1.08-1.29), respectively. CONCLUSIONS: MH is common in Nigeria and increasing age, clinic systolic BP, and random blood glucose are the risk factors.

Urinary sodium excretion and its association with blood pressure in Nigeria: A nationwide population survey.

Assessment of level of salt intake in a population is the first step toward planning strategies aimed at salt reduction. As a surrogate of salt intake, we measured a single 24-hour urine sodium (uNa) of free-living 2503 adults in a nationally representative sample of Nigerians drawn from 12 rural and urban communities; and evaluated the community-level association of uNa with blood pressure (BP). Overall, the median (interquartile range (IQR)) of uNa was 99 (105) mmol, ranging from 23.8 (32.4) in rural north-central to 172.8 (131.0) mmol in urban northwestern region. Daily uNa was significantly higher (p < .001) in men compared to women (107.1 vs 93.9 mmol); and urban compared to rural dwellers (114.9 vs 86.0mmol). About one-half of participants excreted uNa in excess of recommended daily maximum value (86mmol). In a model adjusted for age, sex, body mass index (BMI), level of education, place of residence, and use of antihypertensive medication; being a man (odds ratio, OR 1.69, 95% confidence Interval CI, 1.21-2.37, p = .002) and being < 60 years of age (OR 1.74, 95% CI 1.23-2.45, p = .002), were associated with excreting higher than recommended uNa. In a fully adjusted model of the community-level analysis, urinary sodium, potassium, and sodium-to-potassium ratio each showed no significant independent association with both systolic and diastolic BPs. Among adult Nigerians, the median daily uNa excretion was 99 mmol and it had no significant association with blood pressure indices.

A Custom Genotyping Array Reveals Population-Level Heterogeneity for the Genetic Risks of Prostate Cancer and Other Cancers in Africa.

Although prostate cancer is the leading cause of cancer mortality for African men, the vast majority of known disease associations have been detected in European study cohorts. Furthermore, most genome-wide association studies have used genotyping arrays that are hindered by SNP ascertainment bias. To overcome these disparities in genomic medicine, the Men of African Descent and Carcinoma of the Prostate (MADCaP) Network has developed a genotyping array that is optimized for African populations. The MADCaP Array contains more than 1.5 million markers and an imputation backbone that successfully tags over 94% of common genetic variants in African populations. This array also has a high density of markers in genomic regions associated with cancer susceptibility, including 8q24. We assessed the effectiveness of the MADCaP Array by genotyping 399 prostate cancer cases and 403 controls from seven urban study sites in sub-Saharan Africa. Samples from Ghana and Nigeria clustered together, whereas samples from Senegal and South Africa yielded distinct ancestry clusters. Using the MADCaP array, we identified cancer-associated loci that have large allele frequency differences across African populations. Polygenic risk scores for prostate cancer were higher in Nigeria than in Senegal. In summary, individual and population-level differences in prostate cancer risk were revealed using a novel genotyping array. SIGNIFICANCE: This study presents an Africa-specific genotyping array, which enables investigators to identify novel disease associations and to fine-map genetic loci that are associated with prostate and other cancers.

Herbal Drug use in Sickle Cell Disease Management; Trends and Perspectives in Sub-Saharan Africa - A Systematic Review.

INTRODUCTION: Nigeria has the largest burden of Sickle Cell Disease (SCD) with estimated 100,000 new born affected annually. SCD is a Hemoglobin (Hb) disorder with the major form resulting from the substitution of a polar glutamate (Glu) by non-polar Valine (Val) in an invariant region of Hbß chain-subunit. Species of Hb found in the sickle cell trait are HbA and HbS in a 60:40 proportion, in SCD only HbS, in the HbC disease only HbC, and in the SC disease it's HbS and HbC in a 50:50 equal proportion. OBJECTIVE: This paper reviews herbal medicines usage in sub-Saharan Africa (sSA) to ameliorate the crisis associated with SCD. The model Hb tetramer suggests a higher membrane affinity of HbS and HbC, promoting dehydration of RBCs, with concomitant in vivo crystallization. Some drawbacks using these herbal drugs include; poor bioavailability and the lack of proper pharmacovigilance monitoring procedures arising from weak governance structure combined with under reporting of herbal usage to physicians were discussed. Probable epigenetic loci that could be targeted using phytomedicines for effective SCD management were also discussed. METHODS: Using search engines, several databases including Google scholar, PubMed, Academic Resource Index were utilized as a source for relevant publications/ literature. The protein coordinates for the Hb tetramer were obtained from the Protein Data Bank (PDB). CONCLUSION: Manipulation of epigenetics to achieve better SCD management involves careful thinking. Herein, we discuss some epigenetic interactions that could be putatively tweaked with a view of enhancing soluble bioactive small molecular components with the potential to reactivate γ -globin genes, thereby boosting immune response in patient with SCD.

Office and Home Blood Pressures as Determinants of Electrocardiographic Left Ventricular Hypertrophy Among Black Nigerians Compared With White Flemish.

BACKGROUND: The association of electrocardiographic left ventricular hypertrophy (ECG-LVH) with blood pressure (BP) in Blacks living in sub-Saharan Africa remains poorly documented. METHODS: In 225 Black Nigerians and 729 White Flemish, we analyzed QRS voltages and voltage-duration products and 12 criteria diagnostic of ECG-LVH in relation to office BP (mean of 5 consecutive readings) and home BP (duplicate morning and evening readings averaged over 1 week). RESULTS: In multivariable analyses, QRS voltage and voltage-duration indexes were generally higher in Blacks than Whites. By using any of 12 criteria, ECG-LVH was more prevalent among Black than White men (54.4% vs. 36.0%) with no ethnic difference among women (17.1%). Precordial voltages and voltage-duration products increased with office and home systolic BP (SBP), and increases were up to 3-fold steeper in Blacks. In Blacks vs. Whites, increases in the Sokolow-Lyon voltage associated with a 10-mm Hg higher SBP were 0.18 mV (95% confidence interval [CI], 0.09-0.26) vs. 0.06 mV (0.02-0.09) and 0.17 mV (0.07-0.28) vs. 0.11 mV (CI, 0.07-0.15) for office and home BP, respectively, with a significant ethnic gradient (P < 0.05). The risk of ECG-LVH increased more with office and home BP in Blacks than Whites. CONCLUSIONS: Associations of ECG voltages and voltage-duration products and risk of ECG-LVH with BP are steeper in Black Nigerians compared with a White reference population. In resource-poor settings of sub-Saharan Africa, the ECG in combination with office and home BP is an essential instrument in risk stratification across the entire BP range.

Preliminary Evaluation of a Point-of-Care Testing Device (SickleSCAN™) in Screening for Sickle Cell Disease.

Sickle cell disease affects about 150,000 births annually in Nigeria. Early diagnosis is hampered by factors such as centralized and urban localization of laboratories, high cost of diagnostic equipment and inadequate skilled manpower to operate them. The need for a low-cost, portable, easy-to-use diagnostic test for sickle cell disease is critical, especially in resource-poor countries. In this study, we evaluated the performance characteristics of a novel point-of-care testing device (SickleSCAN™), and its acceptability and feasibility, as a possible screening tool for sickle cell disease. In the first phase, we assessed the performance characteristics of SickleSCAN™ by evaluating 57 subjects comprising both children and adults attending a primary health center, for Hb SS (ßS/ßS; HBB: c.20A>T), Hb SC (ßS/ßC; HBB: c.19G>A) and Hb AS (ßA/ßS) using SickleSCAN™, cellulose acetate electrophoresis (CAE) and high performance liquid chromatography (HPLC). Performance characteristics such as diagnostic sensitivity and specificity were compared to HPLC as a standard method. We subsequently undertook a second phase wherein the acceptability and feasibility of the device for sickle cell disease screening, was evaluated using semi-structured and structured questionnaires among 197 healthcare personnel and 221 subjects, respectively. Sickle cell disease was carried by 3.4% of the subjects. The diagnostic sensitivity, specificity and test efficiency of SickleSCAN™ for sickle cell disease (Hb SS and Hb SC), were 100.0, 98.2 and 98.2%, respectively. Findings from this study showed SickleSCAN™ to be a viable screening tool that can easily be applied in community-based screening for early diagnosis of sickle cell disease with little expertise and low cost.

The post-Ebola virus disease scourge in Nigeria: Individual levels of preparedness among physicians in the Federal Capital Territory Abuja.

BACKGROUND: Ebola virus disease (EVD) is a viral hemorrhagic illness with great propensity for spread across international borders. The latest outbreak in the West African region, which involved Nigeria, was the worst among previously documented 25 outbreaks since discovery in 1976. The Nigerian response toward attaining Ebola free status was phenomenal and a case study for most nations. However, the persistence of EVD in West Africa is still a risk to recurrence, hence, the need to assess the level of consciousness of Nigerian physicians towards this. METHODOLOGY: A cross-sectional study utilizing the instrument of a pretested semi-structured questionnaire was conducted among physicians practicing within the federal capital city of Nigeria. General knowledge, treatment, prevention, and reporting of EVD were assessed and appropriate statistical analyses done using SPSS 20. RESULTS: Of the 101 respondents, 45% and 87% showed excellent level (>80% score) of "general knowledge" and "reporting" on EVD, respectively. However, only 51% respondents had good (60-80%) knowledge on EVD treatment. Three percent correctly identified the "EVD helpline" phone-numbers for reporting suspected cases. Furthermore, 43.6% admitted the availability of personal protective equipment (PPE) in their hospitals while 35.6% had witnessed a demonstration of the use. The distribution of the PPEs appeared skewed - 74.4% (teaching-hospitals), 16% (private-hospitals), and the primary health care centers (9.6%). CONCLUSION: A majority of the physicians showed good level of preparedness as it relates to general knowledge on EVD, knowledge on good clinical practice, use of protocols and standard precautions and PPE. The identification of deficits in knowledge on treatment of EVD and flow path for the notification of suspected cases requires urgent redress given the risk of re-occurrence in the country.

Prevalence and Determinants of Masked Hypertension Among Black Nigerians Compared With a Reference Population.

Hitherto, diagnosis of hypertension in sub-Saharan Africa was largely based on conventional office blood pressure (BP). Data on the prevalence of masked hypertension (MH) in this region is scarce. Among individuals with normal office BP (<140/90 mm Hg), we compared the prevalence and determinants of MH diagnosed with self-monitored home blood pressure (≥135/85 mm Hg) among 293 Nigerians with a reference population consisting of 3615 subjects enrolled in the International Database on Home Blood Pressure in Relation to Cardiovascular Outcomes. In the reference population, the prevalence of MH was 14.6% overall and 11.1% and 39.6% in untreated and treated participants, respectively. Among Nigerians, the prevalence standardized to the sex and age distribution of the reference population was similar with rates of 14.4%, 8.6%, and 34.6%, respectively. The mutually adjusted odds ratios of having MH in Nigerians were 2.34 (95% confidence interval, 1.39-3.94) for a 10-year higher age, 1.92 (1.11-3.31) and 1.70 (1.14-2.53) for 10- or 5-mm Hg increments in systolic or diastolic office BP, and 3.05 (1.08-8.55) for being on antihypertensive therapy. The corresponding estimates in the reference population were similar with odds ratios of 1.80 (1.62-2.01), 1.64 (1.45-1.87), 1.13 (1.05-1.22), and 2.84 (2.21-3.64), respectively. In conclusion, MH is as common in Nigerians as in other populations with older age and higher levels of office BP being major risk factors. A significant proportion of true hypertensive subjects therefore remains undetected based on office BP, which is particularly relevant in sub-Saharan Africa, where hypertension is now a major cause of death.

Evaluation of mobile smartphones app as a screening tool for environmental noise monitoring.

Noise is a global occupational and environmental health hazard with considerable social and physiological impact and, therefore, there is a need for regular measurements to boost monitoring and regulations of environmental noise levels in our communities. This necessitates a readily available, inexpensive, and easy to use noise measuring device. We aimed to test the sensitivity and validity of mobile "smart" phones for this purpose. This was a comparative analysis of a cross sectional study done between January 2014 and February 2015. Noise levels were measured simultaneously at different locations within Abuja Nigeria at day and night hours in real time environments. A sound level meter (SLM) (Extech407730 Digital Soundmeter, serial no.: 2310135, calibration no: 91037) and three smartphones (Samsung Galaxy note3, Nokia S, and Techno Phantom Z running on Android "Apps" Androidboy1) were used. Statistical calculations were done with Pearson correlation, T-test and Consistency within American National Standards Institute acceptable standard errors. Noise level readings for both daytime and night with the SLM and the mobile phones showed equivalent values. All noise level meters measured were <100dB. The daytime readings were nearly identical in six locations and the maximum difference in values between the SLM and Smartphone instruments was 3db, noted in two locations. Readings in dBA showed strong correlation (r = 0.9) within acceptable error limits for Type 2 SLM devices and no significant difference in the values (p = 0.12 & 0.58) for both day and night. Sensitivity of the instrument yielded 92.9%. The androidboy1 "app" performance in this study showed a good correlation and comparative high sensitivity to the Standard SLM (type 2 SLM device). However there is the need for further studies.

The sensitivity and specificity of Lassa virus IgM by ELISA as screening tool at early phase of Lassa fever infection.

BACKGROUND: Early diagnosis, prompt treatment, and disease containment are vital measures in the management of Lassa fever (LF), a lethal and contagious arenaviral hemorrhagic disease prevalent in West Africa. Lassa Virus (LAV)-specific Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) test, the gold standard for diagnosis, is unavailable in most centers. Serologic detection of LAV IgM is a more accessible tool and this work was to investigate its adequacy as an early marker for LF. PATIENTS AND METHODS: A prospective case-control study conducted July 2007-March 2011 in a tertiary referral health center in Nigeria. Blood samples for test and control were evaluated for Lassa specific antigens and IgM using RT-PCR (primers S36+ and LVS 339) and indirect ELISA (Lassa Nucleo-protein (NP)-Antigen) respectively. RT-PCR outcome was used as standard to test for the sensitivity and specificity of IgM. RESULTS: Of the 37 confirmed cases of LF infection by RT-PCR, 21 (57%) were IgM positive. Amongst the 35 confirmed negative cases (control group), eight were IgM positive. The diagnostic sensitivity and specificity of the IgM assay were 57% and 77% respectively. The negative and positive predictive values of the IgM serological assay were 63% and 72%, respectively, while the efficiency of the test was 67%. CONCLUSION: The specificity and sensitivity of IgM as a screening tool for early detection of LF appear weak and, hence, the need for a reliable LF "rapid screening kit" since RT-PCR is unavailable in most centers. In the interim, "high clinical index of suspicion," irrespective of IgM status, requires urgent referral to confirmatory centers.