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.

Assessment of the utility of a screening tool for COVID-19 diagnosis in an accident and emergency department in Lagos, Nigeria: A pilot study.

The use of reverse transcription-polymerase chain reaction (RT-PCR) is the gold standard laboratory test for diagnosing SARS-CoV-2 infection. However, it has the disadvantage of a long turnaround time and cost. The Nigeria Centre for Disease Control (NCDC) formulated a case definition for COVID-19. We sought to determine the utility of a 14-item, point-weighted clinical screening questionnaire adapted from the NCDC case definition in identifying patients more likely to have the disease. This was to aid prompt clinical decision-making. Methods: We retrospectively reviewed the data of 113 non-surgical patients presenting to the Accident and Emergency Department (A and E) of Lagos University Teaching Hospital, Lagos, Nigeria. Patients were stratified based on screening scores into low (0-2), moderate (3-5) and high (6) pre-test categories. Patients with low and high scores ≥6 were admitted to the A and E and the COVID-19 holding ward, respectively, while the moderate group had chest computed tomography scans to aid further decision-making, pending the outcome of their RT-PCR results. The validity of the triage score as compared to the RT-PCR test result was calculated and the kappa score of agreement was utilised to evaluate the concordance between two triage scores. The optimum cut-off score was also obtained based on the maximal Younden's index. Results: The frequencies of low, moderate and high pre-test scores were 34 (30%), 43 (38.1%) and 36 (31.9%), respectively. Overall, 38.1% (43/113) were RT-PCR positive. RT-PCR was positive in 26.5% (9/34) with low screening scores, 55.8% (24/43) with moderate scores and 27.8% (10/36) with high scores. The sensitivity and specificity of a high score of 6 were 25% and 92.86%, while the lower score of 3 had sensitivity and specificity of 62.5% and 58.6%, respectively. Conclusion: The screening tool showed a high specificity in its initial design, which suggests that anyone with a low score using this tool has a high probability of testing negative. We recommend a cut-off score of 4 (score A) or 6 (score B) of the current screening tool be used to increase the chances of identifying persons with COVID-19 for RT-PCR testing.

Use of exchange blood transfusion in the management of severe COVID-19 infection in pregnancy: experience from Lagos, Nigeria.

Coronavirus disease 2019 (COVID-19) presents with symptoms that may be mild or severe. The individual with the severe form of the disease usually presents with a constellation of respiratory symptoms typical of acute respiratory distress syndrome. In this report, we present our experience of the successful management of an oxygen-dependent pregnant woman with severe COVID-19 infection who had 2 sessions of partial exchange blood transfusion. We discussed the principles that informed this intervention and the need to adopt this novel approach in the care of severe COVID-19 infection.

A Comparative Study of Serum Ferritin Levels Among Unfit and Fit Blood Donors.

BACKGROUND: Cheap methodologies are being utilized by low-resource countries to determine blood donors' fitness. Important hematological biomarkers might have to be evaluated to enhance the use of these methods. AIMS: The study evaluated the pattern of serum ferritin in 18-24 fit and unfit prospective blood donors (PDBs) and the prevalence of iron store deficiency. SETTINGS AND DESIGN: This study was a cross-sectional, comparative study which was conducted at the blood donor clinic of the Lagos University Teaching Hospital. MATERIALS AND METHODS: Blood samples were collected by venipuncture into sodium-ethylenediaminetetraacetic acid and plain bottles. The latter was centrifuged and used for ferritin determination via human ferritin enzyme-linked immunosorbent assay test kit, while the former was used for red cell indices analysis using an autoanalyzer. STATISTICAL ANALYSIS: Data were analyzed using SPSS version 20, values were presented as mean ± standard deviation, and P ≤ 0.05 was considered statistically significant. RESULTS: A total of 263 PDB were recruited into the study consisting of 210 (79%) males and 53 (21%) females, with a mean age of 32.88 ± 8.22. Only 110 (41.8%) of the participants were considered fit, while 153 (58.2%) were unfit using copper sulfate specific gravity. There was no statistically significant difference (P = 0.301) in the mean level of serum ferritin in unfit blood donors (74.5 ± 90.8 µg/L) compared to that of the fit blood donors (61.5 ± 54.5 µg/L). The prevalence of iron store depletion among blood donors in Lagos state was 11.8% (31 of 263) with a higher proportion (7.6%) occurring among unfit donors. However, low levels of serum ferritin (<15 µg/L) were significantly associated with the occurrence of anemia (hemoglobin < 12.5 g/gl) among unit donors (19%; P = 0.05). CONCLUSION: Although serum ferritin depletion appears to be higher in the unfit blood donors, the use of serum ferritin as an index for the screening and determination of PDBs' fitness requires further evaluation.

Use of exchange blood transfusion in the management of severe COVID-19 infection in pregnancy: experience from Lagos, Nigeria

Coronavirus disease 2019 (COVID-19) presents with symptoms that may be mild or severe. The individual with the severe form of the disease usually presents with a constellation of respiratory symptoms typical of acute respiratory distress syndrome. In this report, we present our experience of the successful management of an oxygen-dependent pregnant woman with severe COVID-19 infection who had 2 sessions of partial exchange blood transfusion. We discussed the principles that informed this intervention and the need to adopt this novel approach in the care of severe COVID-19 infection.