RESUMO
PURPOSE: The traditional standard of care for Graves' ophthalmopathy (GO) is glucocorticoid therapy, which is associated with many long-term side effects. The aim of this systematic review and meta-analysis was to compare the traditional therapy to novel monoclonal antibodies (e.g. rituximab [RTX], teprotumumab, and tocilizumab [TCZ]). METHODS: We searched the Medline, Embase, and Cochrane Central Register of Controlled Trials databases. We included randomized controlled trials (RCTs) that compared different monoclonal antibodies (e.g. RTX, teprotumumab, and TCZ) with glucocorticoids or placebo in patients with GO. We evaluated the clinical activity score (CAS), proptosis, subjective diplopia using the Gorman score, quality of life (QoT), adverse events, change in lid fissure, NOSPECS score, and TSH receptor antibody (TRAb) levels. The odds ratio (OR) was used to represent dichotomous outcomes. The continuous outcomes were represented as standardized mean difference (SMD). Data were pooled using the inverse variance weighting method. Risk of bias was assessed using the revised Cochrane risk-of-bias tool for randomized trials. RESULTS: Six (n = 571) RCTs were deemed eligible. The different monoclonal antibodies were significantly more efficacious than glucocorticoid/placebo in terms of reduction in CAS (SMD = -1.44, 95% confidence interval (CI): -1.91--0.97, P < 0.00001, I2 = 74%), change in proptosis (SMD = -4.96, 95% CI: -8.02--1.89, P = 0.002, I2 = 99%), QoL (SMD = 2.64, 95% CI: 0.50-4.79, P = 0.02, I2 = 97%), and Gorman score for diplopia (OR = 3.42, 95% CI: 1.62-7.22, P = 0.001, I2 = 8%). However, monoclonal antibodies have shown higher rates of adverse events (OR = 2.91, 95% CI: 1.12-7.56, P = 0.03, I2 = 62%). No significant difference was found with respect to lid fissure, NOSPECS, and TRAb levels. CONCLUSION: This meta-analysis demonstrated that monoclonal antibodies were associated with more favorable clinical outcomes than standard steroid therapy or placebo, especially with regard to CAS, change in proptosis, diplopia, and QoL, with teprotumumab being superior. In addition, only minor safety concerns were identified with monoclonal antibodies though less worrisome than using traditional steroids.
RESUMO
BACKGROUND: Neonatal thrombocytopenia (NTCP) is a common hematological disorder whose platelet count falls below the normal limit of 150 x 109/L. NTCP can cause late complications if left untreated. The current study aimed to evaluate the accuracy of the umbilical cord complete blood count (UC CBC) in detecting early-onset neonatal thrombocytopenia (EO-NTCP). Further, the prevalence of NTCP was also investigated. Methods: A cross-sectional study with a matched control was conducted on all newborns delivered at a tertiary care center in Jeddah, Saudi Arabia, between May 2016 and 2019. After exclusions, 40 neonates with EO-NTCP (cases) and 80 without EO-NTCP (controls) were included. The case-to-control ratio was 1:2. The results of UC CBC were compared with those of follow-up CBC, performed within 72 hours. A p-value of <0.05 was considered statistically significant. All data were analyzed using IBM SPSS version 28 for Windows (IBM Corp., Armonk, NY). RESULTS: The prevalence of NTCP was approximately 1.02% (111/10,936). Lack of antenatal care was found in 12 (30%) neonates with EO-NTCP vs. 10 (12.5%) neonates without EO-NTCP (p = 0.02). Neonates with EO-NTCP were more likely to have experienced intrauterine growth restriction (5 (37.5%) vs. 5 (6.3%), p < 0.001) and oligohydramnios (5 (12.5%) vs. 0 (0%), p = 0.003). Neonates who developed EO-NTCP were more likely to be admitted to the NICU (34 (85%) vs. 35 (43.8%), p < 0.001) and receive antibiotics (22 (55%) vs. 25 (31.3%), p = 0.012). Also, neonates with EO-NTCP were more frequently diagnosed with neonatal sepsis (7 (17.5%) vs. 3 (3.8%), p = 0.015) and more likely to receive platelet transfusions (15 (37.5% vs. 1 (1.3%), p < 0.001). They also had a higher median length of hospital stay (13 (interquartile range (IQR) 3-28) vs. 4 (IQR 2-9) days, p = 0.006). The mortality rates of neonates with EO-NTCP and those without were 6 (15%) vs. 2 (2.5%) neonates (p = 0.016). The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of UC CBC were 62.50%, 97.50%, 20.40%, and 99.61%, respectively. CONCLUSION: The prevalence of EO-NTCP in King Abdulaziz Medical City is comparable to international and national figures, and it is associated with preceding maternal comorbidities, serious neonatal morbidity, and even mortality. Therefore, proper antenatal care is vital in preventing maternal and neonatal morbidities, including the risks of NTCP and its related complications. With high NPV, using UC CBC as a universal screening method could assist in safely discharging newborns. However, because of its low sensitivity, a comprehensive clinical examination with confirmatory laboratory tests are still the cornerstone in diagnosing EO-NTCP. Future trials should aim to study the cost-effectiveness of universal UC CBC and the long-term outcomes of infants diagnosed with EO-NTCP.
