Ocrelizumab Concentration Is a Good Predictor of SARS-CoV-2 Vaccination Response in Patients with Multiple Sclerosis

Ocrelizumab, an anti-CD20 monoclonal antibody, counteracts induction of humoral immune responses after severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) vaccinations in patients with multiple sclerosis (MS). We aimed to assess if serum ocrelizumab concentration measured at the time of vaccination could predict the humoral response after SARS-CoV-2 vaccination. In 52 patients with MS, we found ocrelizumab concentration at the time of vaccination to be a good predictor for SARS-CoV-2 IgG anti-RBD titers after vaccination (comparable to B-cell count). As the course of ocrelizumab concentration may be predicted using pharmacokinetic models, this may be a superior biomarker to guide optimal timing for vaccinations in B-cell depleted patients with MS. ANN NEUROL 2023;93:103–108     

Parent and teacher perceptions of child behaviour following cardiac surgery

To determine if parents whose children had undergone successful cardiac surgery perceived their children any differently from parents of children who had not undergone surgery, we used the Achenbach Child Behaviour Checklist (CBCL) to compare parent and teacher perceptions in these two groups. Subjects included 168 children who had undergone cardiac surgery 4 to 8 years previously and 51 controls. On the behaviour scale of the CBCL, the teachers' mean t scores showed no significant difference bctween the cardiac and control groups, in contrast to the parents' scores where parents perceived a higher degree of behavioural problems in children who had undergone cardiac surgery. On the Social competence scale of the CBCL, the parents scored their children who had undergone cardiac surgery as less Socially competent than did the parents of the controls. Teachers' scores showed no difference between groups.     

Secretory leukocyte protease inhibitor (SLPI) in mucosal fluids inhibits HIV-1

Despite the presence of HIV-1 in the oral cavity, transmission of the virus through saliva has not been proven. Consistent with these observations, we recently identified an endogenous 12 kD protein, secretory leukocyte protease inhibitor (SLPI), in saliva which blocks HIV-1 infection in vitro. Whereas other salivary proteins tested were inactive, purified native or recombinant SLPI inhibited HIV-1 infection of human monocytes at 100 ng ml^?1. Levels of SLPI quantitated by ELISA in saliva from control and HIV-1 infected individuals exceeded this level, consistent with in vivo antiviral activity. As in saliva, levels of SLPI mRNA determined by Northern hybridization, and protein as assessed by immunohistochemistry in the salivary glands of control and infected populations were comparable. In contrast to adults, oral transmission occurs in infants, possibly due to their lack of fully developed salivary glands. To determine whether the inadequate antiviral protection might be compensated for by maternal sources, we evaluated breast milk samples obtained 6 months postpartum. Levels of SLPI were significantly lower than in saliva and not sufficient to provide antiviral protection in contrast to colostrum samples in which SLPI levels were equivalent to those in saliva and able to inhibit HIV-1 infection when tested in vitro. These data suggest that breast milk may provide transient antiviral activity in the newborn, but that this maternal source of SLPI is of insufficient duration to maintain protection against mucosal transmission of the virus over time. The high functional levels of SLPI in saliva and the low levels in mature breast milk correlate with negligible rates of HIV-1 transmission by saliva and higher rates by breast feeding.     

Single intravenous administration of TB‐402 for the prophylaxis of venous thromboembolism after total knee replacement: a dose‐escalating,randomized, controlled trial

Summary. Background: TB‐402 is a novel anticoagulant monoclonal antibody with a prolonged antithrombotic effect resulting from its partial factor (F)VIII inhibition and long half‐life. We evaluated the efficacy and safety of a single administration of TB‐402 for the prevention of venous thromboembolism (VTE) after total knee replacement (TKR). Patients and methods: This was a phase II, dose‐escalating, randomized, enoxaparin‐controlled, open‐label study. Patients were post‐operatively assigned to a single dose of TB‐402 (0.3, 0.6 or 1.2 mg kg^?1) or enoxaparin 40 mg for at least 10 days (n = 75 per group; 3:1 TB‐402 to enoxaparin). The primary efficacy outcome was total VTE defined as asymptomatic deep vein thrombosis (DVT) detected by bilateral venography and symptomatic VTE by day 7 to 11. The principal safety outcome was the incidence of major bleeding and clinically relevant non‐major bleeding. Results: Total VTE was lower in all TB‐402 groups compared with enoxaparin: 16.7%(95% CI 9.8–26.9), 23.9%(95% CI 15.3–35.3), 24.1%(95% CI 16.0–34.5) and 39.0%(95% CI 28.8–50.1) for TB‐402 0.3, 0.6, 1.2 mg kg^?1 and enoxaparin, respectively (P = 0.003 for TB‐402 0.3 mg kg^?1 vs. enoxaparin). The incidence of total VTE in the pooled TB‐402 groups was 21.6% (95%CI 16.6–27.5), an absolute risk reduction vs. enoxaparin of 17.4% (95% CI 5.2–29.6). Major or clinically relevant non‐major bleeding was observed in 3/75(4.0%), 4/74(5.4%), 7/87(8.0%) and 3/79(3.8%) patients for TB‐402 0.3, 0.6, 1.2 mg kg^?1 and enoxaparin, respectively. Conclusions: TB‐402, as a single post‐operative administration, was associated with a lower rate of VTE in all doses tested, compared with enoxaparin. The incidence of major and clinically relevant non‐major bleeding was similar to enoxaparin 40 mg for TB‐402 0.3 and 0.6 mg kg^?1.     

处方回顾性评估:衡量结核病防治服务质量的一个基本方法

遏制结核病策略1和结核病关怀国际标准2的第一个组成部分即为:使用推荐的抗结核药品剂型和剂量,组成标准治疗方案,治愈结核病患者,使其恢复健康和劳动能力,并减少结核分枝杆菌的传播,从而预防耐药结核病的发生和传播。在这一期的国际结核病与肺部疾病杂志上,江     

How participatory is parental consent in low literacy rural settings in low income countries? Lessons learned from a community based study of infants in South India

Background  

A requisite for ethical human subjects research is that participation should be informed and voluntary. Participation during the informed consent process by way of asking questions is an indicator of the extent to which consent is informed.