Antioxidant supplementation for sickle cell disease.

BACKGROUND: Sickle cell disease (SCD) refers to a group of genetic disorders characterized by the presence of an abnormal haemoglobin molecule called haemoglobin S (HbS). When subjected to oxidative stress from low oxygen concentrations, HbS molecules form rigid polymers, giving the red cell the typical sickle shape. Antioxidants have been shown to reduce oxidative stress and improve outcomes in other diseases associated with oxidative stress. Therefore, it is important to review and synthesize the available evidence on the effect of antioxidants on the clinical outcomes of people with SCD. OBJECTIVES: To assess the effectiveness and safety of antioxidant supplementation for improving health outcomes in people with SCD. SEARCH METHODS: We used standard, extensive Cochrane search methods. The latest search date was 15 August 2023. SELECTION CRITERIA: We included randomized and quasi-randomized controlled trials comparing antioxidant supplementation to placebo, other antioxidants, or different doses of antioxidants, in people with SCD. DATA COLLECTION AND ANALYSIS: Two authors independently extracted data, assessed the risk of bias and certainty of the evidence, and reported according to Cochrane methodological procedures. MAIN RESULTS: The review included 1609 participants in 26 studies, with 17 comparisons. We rated 13 studies as having a high risk of bias overall, and 13 studies as having an unclear risk of bias overall due to study limitations. We used GRADE to rate the certainty of evidence. Only eight studies reported on our important outcomes at six months. Vitamin C (1400 mg) plus vitamin E (800 mg) versus placebo Based on evidence from one study in 83 participants, vitamin C (1400 mg) plus vitamin E (800 mg) may not be better than placebo at reducing the frequency of crisis (risk ratio (RR) 1.18, 95% confidence interval (CI) 0.64 to 2.18), the severity of pain (RR 1.33, 95% CI 0.40 to 4.37), or adverse effects (AE), of which the most common were headache, nausea, fatigue, diarrhoea, and epigastric pain (RR 0.56, 95% CI 0.31 to 1.00). Vitamin C plus vitamin E may increase the risk of SCD-related complications (acute chest syndrome: RR 2.66, 95% CI 0.77 to 9.13; 1 study, 83 participants), and increase haemoglobin level (median (interquartile range) 90 (81 to 96) g/L versus 93.5 (84 to 105) g/L) (1 study, 83 participants) compared to placebo. However, the evidence for all the above effects is very uncertain. The study did not report on quality of life (QoL) of participants and their caregivers, nor on frequency of hospitalization. Zinc versus placebo Zinc may not be better than placebo at reducing the frequency of crisis at six months (rate ratio 0.62, 95% CI 0.17 to 2.29; 1 study, 36 participants; low-certainty evidence). We are uncertain whether zinc is better than placebo at improving sickle cell-related complications (complete healing of leg ulcers at six months: RR 2.00, 95% CI 0.60 to 6.72; 1 study, 34 participants; very low-certainty evidence). Zinc may be better than placebo at increasing haemoglobin level (g/dL) (MD 1.26, 95% CI 0.44 to 1.26; 1 study, 36 participants; low-certainty evidence). The study did not report on severity of pain, QoL, AE, and frequency of hospitalization. N-acetylcysteine versus placebo N-acetylcysteine (NAC) 1200 mg may not be better than placebo at reducing the frequency of crisis in SCD, reported as pain days (rate ratio 0.99 days, 95% CI 0.53 to 1.84; 1 study, 96 participants; low-certainty evidence). Low-certainty evidence from one study (96 participants) suggests NAC (1200 mg) may not be better than placebo at reducing the severity of pain (MD 0.17, 95% CI -0.53 to 0.87). Compared to placebo, NAC (1200 mg) may not be better at improving physical QoL (MD -1.80, 95% CI -5.01 to 1.41) and mental QoL (MD 2.00, 95% CI -1.45 to 5.45; very low-certainty evidence), reducing the risk of adverse effects (gastrointestinal complaints, pruritus, or rash) (RR 0.92, 95% CI 0.75 to 1.14; low-certainty evidence), reducing the frequency of hospitalizations (rate ratio 0.98, 95% CI 0.41 to 2.38; low-certainty evidence), and sickle cell-related complications (RR 5.00, 95% CI 0.25 to 101.48; very low-certainty evidence), or increasing haemoglobin level (MD -0.18 g/dL, 95% CI -0.40 to 0.04; low-certainty evidence). L-arginine versus placebo L-arginine may not be better than placebo at reducing the frequency of crisis (monthly pain) (RR 0.71, 95% CI 0.26 to 1.95; 1 study, 50 participants; low-certainty evidence). However, L-arginine may be better than placebo at reducing the severity of pain (MD -1.41, 95% CI -1.65 to -1.18; 2 studies, 125 participants; low-certainty evidence). One participant allocated to L-arginine developed hives during infusion of L-arginine, another experienced acute clinical deterioration, and a participant in the placebo group had clinically relevant increases in liver function enzymes. The evidence is very uncertain whether L-arginine is better at reducing the mean number of days in hospital compared to placebo (MD -0.85 days, 95% CI -1.87 to 0.17; 2 studies, 125 participants; very low-certainty evidence). Also, L-arginine may not be better than placebo at increasing haemoglobin level (MD 0.4 g/dL, 95% CI -0.50 to 1.3; 2 studies, 106 participants; low-certainty evidence). No study in this comparison reported on QoL and sickle cell-related complications. Omega-3 versus placebo Very low-certainty evidence shows no evidence of a difference in the risk of adverse effects of omega-3 compared to placebo (RR 1.05, 95% CI 0.74 to 1.48; 1 study, 67 participants). Very low-certainty evidence suggests that omega-3 may not be better than placebo at increasing haemoglobin level (MD 0.36 g/L, 95% CI -0.21 to 0.93; 1 study, 67 participants). The study did not report on frequency of crisis, severity of pain, QoL, frequency of hospitalization, and sickle cell-related complications. AUTHORS' CONCLUSIONS: There was inconsistent evidence on all outcomes to draw conclusions on the beneficial and harmful effects of antioxidants. However, L-arginine may be better than placebo at reducing the severity of pain at six months, and zinc may be better than placebo at increasing haemoglobin level. We are uncertain whether other antioxidants are beneficial for SCD. Larger studies conducted on each comparison would reduce the current uncertainties.

Comparative analysis of fibroblast growth Factor-23 as a correlate of cardiovascular disease among individuals with chronic kidney disease, hypertensives, and healthy controls.

Background: Chronic kidney disease (CKD) is a global growing public health epidemic with attending morbidity and huge financial cost. Cardiovascular disease (CVD), a major complication of CKD, contributes to its excessive mortality rate. The aetio-pathogenesis of the excess burden of CVD in CKD is a feature yet to be unravelled. Fibroblast growth factor-23 (FGF-23) has been implicated as a risk factor for CVD among patients with CKD. However, most of these studies were predominantly among the Caucasian population. Aim: This study aims to determine the correlation between FGF-23 and CVD among Nigerians with CKD. Patients and Methods: A cross-sectional comparative study composed of three groups: participants with CKD, hypertensives without CKD, and healthy individuals, represented as group 1, 2, and 3, respectively. Information obtained included demographic data and occurrence of risk factors for CVD. Cardiovascular risks were assessed by echocardiography and all the participants had kidney function tests done with plasma FGF-23. Results: The study sample size consisted of 135 participants. The mean (SD) age for participants with CKD and controls were 50.2 (12.7), 54.3 (15.5), and 40.2 (14.1) years, respectively. The median [interquartile range (IQR)] of plasma FGF-23 for participants with CKD 210 (139-304) RU/ml, and controls 124 (86-170) RU/ml, and 71 (38 - 89) RU/ml P < 0.001. Most participants with CKD had left ventricular hypertrophy (LVH) (80.0%), compared to the controls; 28.9% and 6.7% P < 0.001. Similarly, majority of participants with CKD had elevated plasma FGF-23 with LVH (85.7%) compared to controls 55.6% and 11.5%, whereas for aortic valve calcification with elevated plasma FGF-23 among CKD and controls were 53.6% (P = 0.29), 37.0% (P = 0.03), and 19.2% (P = 0.06), respectively. Conclusion: Individuals with CKD had frequencies of elevated plasma FGF-23, LVH, and cardiac valve calcification, which are surrogates of cardiovascular events.

Impact of Impaired Kidney Function on Outcomes of Nigerians with COVID-9 Infection: Report of Two Cases from the University College Hospital, Ibadan.

COVID-19 infection predominantly affects the respiratory system; however, other systems and organs are also affected. The kidneys are among the organs commonly affected by SARS-CoV-2 and this has been reported to be a predictor of increased severity, need for intensive care (ICU), admission, and death. We presented two cases of COVID-19 that were associated with co-morbidities that include diabetes mellitus, systemic hypertension and impaired kidney function. The relationship of the multiple co-morbidities particularly the impaired kidney function with the outcomes of COVID-19 infection and the challenges of offering dialysis for patients with COVID-19 infection with kidney failure were discussed. The two cases presented also highlighted the state of preparedness for the management of COVID-19 and its various complications and co-morbidities, particularly kidney failure in a tertiary hospital in Nigeria at onset of the COVID-19 outbreak.

L'infection au COVID-19 affecte principalement les voies respiratoires système; cependant, d'autres systèmes et organes sont également affectés. Les reins font partie des organes les plus fréquemment touchés par SRAS-CoV-2 et cela a été rapporté comme étant un prédicteur de gravité accrue, besoin de soins intensifs (USI),l'admission, et la mort. Nous avons présenté deux cas de COVID-19 associés avec des comorbidités qui incluent le diabète sucré, systémique hypertension et le rénale affaibli. La relation des comorbidités multiples en particulier le rénale affaibli fonction des résultats de l'infection au COVID-19 et de la défis de l'offre de dialyse aux patients atteints de COVID-19 une infection avec insuffisance rénale a été discutée. Les deux cas présentés ont également mis en évidence l'état de préparation à la gestion du COVID-19 et de ses divers complications et comorbidités, en particulier insuffisance rénale dans un hôpital tertiaire au Nigéria au début du COVID-19 épidémie. Mots clés: lésion rénale aiguë, maladie rénale chronique, comorbidité, COVID-19.

Exposure to Agrochemicals and Markers of Kidney Damage among Farmers in Rural Communities in Southwestern Nigeria.

BACKGROUND: Chronic kidney disease of unknown origin (CKDu) is assuming an epidemic proportion, especially in farming communities worldwide. We explored the relationship between CKD markers and agrochemical exposure among rural farmers in South Western Nigeria. METHODS: We studied selected farming communities in Southwestern Nigeria where the use of agrochemicals was widespread. A pre-tested questionnaire was administered to participants. Anthropometric data, information on use of agro-chemicals; urine and blood samples were obtained. Informed consent was obtained from participants. The study was approved by the Institutional Ethics committee and complied with 1975 Helsinki declaration, as revised in 2000. RESULTS: A total of 438 farmers made up of 202 males (46.1%) and 236 females (53.9%) were studied. The mean microalbuminuria was 30.2 ±11.7 mg/dl. Majority of the farmers had CKD stage 2(42.0%) and CKD stage 3 (37.7%). The type of farming engaged in had a positive, but not significant, correlation with eGFR (r=0.012, p=0.832). There was positive correlation between type of farming and GFR category (r=0.24, p=0.000). Frequency of use of hexachlorocyclohexane had a positive and significant correlation with eGFR (r=0.111, p=0.045). Annual crop farming had a correlation with UACR (r=0.149, p=0.024). CONCLUSION: Annual crop farming had a positive correlation with UACR, eGFR and GFR category. The prolonged use of agrochemicals on an annual basis can cause kidney damage.

Barriers to the use of hydroxyurea in the management of sickle cell disease in Nigeria.

Hydroxyurea (HU) is a well-known Hb F-inducing agent with proven clinical and laboratory efficacy for patients with sickle cell disease. However, concerns about its long-term safety and toxicity have limited its prescription by physicians and acceptability by patients. Thus, this study aims to evaluate clinician's barriers to the use of HU in the management of patients with sickle cell disease in Nigeria. An online survey targeted physicians in pediatrics, hematology, medicine, family medicine and general medical practice managing sickle cell disease in Nigeria. The survey was in four sections: demographic, knowledge and experience with HU, and barriers to the use of HU. Ninety-one (73.0%) of 123 contacts completed the survey. Seventy-three percent and 74.0% of the respondents noted that HU reduced transfusion rates and improved overall quality of life (QOL) of patients, respectively. While the majority of the practitioners (55.6%) see between 10-50 patients per month, most (66.7%) write <5 prescriptions for HU per month. Lack of a national guideline for use of HU, especially in children (52.0%), concern for infertility (52.0%), and safety profile of HU in pregnancy and lactation (48.2%), top the factors considered by the respondents as major barriers to the use of HU. Hydroxyurea is grossly under prescribed in Nigeria, despite that the vast majority of physicians who attend patients with sickle cell disease know about its clinical efficacy. Evidence-based clinical practice guidelines could be explored as a way to standardize practices and improve confidence of practitioners to improve physicians' prescription of HU in the management of sickle cell disease.

Fertility of N'dama and Bunaji cattle to artificial insemination following oestrus synchronization with PRID and PGF2alpha in the hot humid zone of Nigeria.

A study was undertaken to determine the effectiveness of a progesterone-releasing intravaginal device (PRID) and prostaglandin F2 alpha (PGF2alpha) in synchronizing oestrus in N'dama and Bunaji cows and heifers and the fertility following artificial insemination at the synchronized oestrus. A total of 116 cows and heifers (58 N'dama and 58 Bunaji) were used in two separate trials. In the first trial, oestrus was synchronized using a PRID, which was inserted for 12 days; in the second trial, oestrus was synchronized by giving two injections of PGF2alpha 13 days apart. Only animals that did not respond to the first injection were given the second injection. At the end of each treatment period, the animals were observed for oestrus for 7 days and inseminated approximately 12 h following detection of oestrus. Standing to be mounted was the single criterion used to judge an animal to have been in oestrus. PGF2alpha and PRID were both effective in synchronizing oestrus in N'dama and Bunaji cows and heifers. The respective oestrus response rates, pregnancy rate and conception rates for PRID and PGF2alpha were 85.7%, 53.6% and 62.5% for PRID, and 91.7%, 68.3% and 74.6% for PGF2alpha. N'dama cattle showed significantly (p<0.05) better oestrus response rate, pregnancy rate and conception rate than Bunaji cattle following both PRID and PGF2alpha treatments. The pregnancy rate and conception rate following PGF2alpha treatment were better (p < 0.05) than for PRID, although the oestrus response rate did not differ. It is concluded that both PRID and PGF2alpha are effective in synchronizing oestrus in N'dama and Bunaji cattle in the hot humid zone of Nigeria and the fertility to artificial insemination at the synchronized oestrus was normal and acceptable. Thus, PRID and PGF2alpha can effectively be used in intensive breeding programmes for the rapid multiplication and distribution of both cattle breeds, especially the N'dama, which is a unique and beneficial animal genetic resource for the tsetse infested hot humid zone of Nigeria.