The efficacy and safety of maternal tenofovir disoproxil fumarate (TDF) in reducing mother-to-infant hepatitis B virus (HBV) transmissions is not clearly understood. We conducted a prospective, multicenter trial and enrolled 118 hepatitis B surface antigen (HBsAg)-and hepatitis B e antigen-positive pregnant women with HBV DNA 7.5 log 10 IU/mL. The mothers received no medication (control group, n 5 56, HBV DNA 8.22 6 0.39 log 10 IU/mL) or TDF 300 mg daily (TDF group, n 5 62, HBV DNA 8.18 6 0.47 log 10 IU/mL) from 30-32 weeks of gestation until 1 month postpartum. Primary outcome was infant HBsAg at 6 months old. At delivery, the TDF group had lower maternal HBV DNA levels (4.29 6 0.93 versus 8.10 6 0.56 log 10 IU/mL, P < 0.0001). Of the 121/123 newborns, the TDF group had lower rates of HBV DNA positivity at birth (6.15% versus 31.48%, P 5 0.0003) and HBsAg positivity at 6 months old (1.54% versus 10.71%, P 5 0.0481). Multivariate analysis revealed that the TDF group had lower risk (odds ratio 5 0.10, P 5 0.0434) and amniocentesis was associated with higher risk (odds ratio 6.82, P 5 0.0220) of infant HBsAg positivity. The TDF group had less incidence of maternal alanine aminotransferase (ALT) levels above two times the upper limit of normal for 3 months (3.23% versus 14.29%, P 5 0.0455), a lesser extent of postpartum elevations of ALT (P 5 0.007), and a lower rate of ALT over five times the upper limit of normal (1.64% versus 14.29%, P 5 0.0135) at 2 months postpartum. Maternal creatinine and creatinine kinase levels, rates of congenital anomaly, premature birth, and growth parameters in infants were comparable in both groups. At 12 months, one TDF-group child newly developed HBsAg positivity, presumably due to postnatal infection and inefficient humoral responses to vaccines. Conclusions: Treatment with TDF for highly viremic mothers decreased infant HBV DNA at birth and infant HBsAg positivity at 6 months and ameliorated maternal ALT elevations. (HEPATOLOGY 2015;62:375-386) D espite the 75%-90% reduction of chronic hepatitis B viral (HBV) infection following universal infant immunization, active/passive immunoprophylaxis has not eradicated mother-toinfant HBV transmission. [1][2][3][4] Approximately 10% of chronic HBV infections cannot be prevented.5-7 The major risks of chronic HBV infection in the immunization era are maternal hepatitis B surface antigen (HBsAg)/hepatitis B e antigen (HBeAg) positivity and high maternal viral load.5-9 Moreover, after immunoprophylaxis, children with HBV infection have a higher risk of developing hepatocellular carcinoma. 10,11 To achieve the goal of global eradication of HBV infection, better strategies aimed at interrupting Abbreviations: ALT, alanine aminotransferase; anti-HBs, antibody to hepatitis B surface antigen; D0, day 0, initiation of TDF treatment (baseline); D1M, 1 month after TDF treatment; HBeAg, hepatitis B e antigen; HBsAg, hepatitis B surface antigen; HBV, hepatitis B virus; P0, at partum; PXM, X months postpartum; SNR, signal-to-noise ratio; TDF, tenofov...

Healthcare professionals should consider the small but significant increased risk of ventricular arrhythmia and cardiovascular death when prescribing azithromycin and moxifloxacin. Additional research is needed to determine whether the increased risk of mortality is caused by the drugs or related to the severity of infection or the pathogens themselves.

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IntroductionAcute kidney injury (AKI) affects more than 50% of critically ill patients. The formation of calcitriol, the active vitamin D metabolite, from the main inactive circulating form, 25-hydroxyvitamin D (25(OH)D), occurs primarily in the proximal renal tubules. This results in a theoretical basis for reduction in levels of calcitriol over the course of an AKI. Vitamin D deficiency is highly prevalent in critically ill adults, and has been associated with increased rates of sepsis, longer hospital stays and increased mortality. The primary objective of this study is to perform serial measurements of 25(OH)D and calcitriol (1,25(OH)2D), as well as parathyroid hormone (PTH) and fibroblast growth factor 23 (FGF23) levels, in critically ill adult patients with and without AKI, and to determine whether patients with AKI have significantly lower vitamin D metabolite concentrations. The secondary objectives are to describe dynamic changes in vitamin D metabolites, PTH and FGF23 during critical illness; to compare vitamin D metabolite concentrations in patients with AKI with and without renal replacement therapy; and to investigate whether there is an association between vitamin D status and outcomes.Methods and analysis230 general adult intensive care patients will be recruited. The AKI arm will include 115 critically ill patients with AKI Kidney Disease Improving Global Outcome stage II or stage III. The comparison group will include 115 patients who require cardiovascular or respiratory support, but who do not have AKI. Serial measurements of vitamin D metabolites and associated hormones will be taken on prespecified days. Patients will be recruited from two large teaching Trusts in England. Data will be analysed using standard statistical methods.Ethics and disseminationEthical approval was obtained. Upon completion, the study team will submit the study report for publication in a peer-reviewed scientific journal and for conference presentation.Trial registration numberNCT02869919; Pre-results.