Trends in antiretroviral use in pregnancy in the UK and Ireland, 2008-2018.

INTRODUCTION: HIV treatment recommendations have evolved over time, reflecting both growing availability of new antiretrovirals and accumulating evidence on their safe and effective use. We analysed patterns of antiretroviral use among diagnosed pregnant women living with HIV delivering in the UK and Ireland between 2008 and 2018 using national surveillance data. METHODS: All singleton pregnancies with known outcomes and known timing of antiretroviral initiation reported to the National Surveillance of HIV in Pregnancy and Childhood were included. Every individual instance of specific antiretroviral use was the unit of analysis in generating a snapshot of antiretroviral use overall and over calendar time. The final analysis was restricted to the 14 most frequently prescribed antiretrovirals. RESULTS: There were 12 099 singleton pregnancies reported during 2008-2018 and a total of 38 214 individual uses of the 14 most commonly prescribed antiretrovirals, the majority of which were started before conception (70.9%). In 2008, 37.7% (482/1279) of pregnancies were conceived under treatment, reaching 80.9% (509/629) by 2018. Patterns of antiretroviral use have changed over time, particularly for third agents. Between 2008 and 2018 the most frequently used protease inhibitor shifted from lopinavir to darunavir, whereas use of integrase inhibitors increased steadily over time. CONCLUSIONS: These national surveillance data enable investigation of the 'real-world' use of antiretrovirals in pregnancy on a population level. Findings demonstrate mixed responsiveness of antiretroviral prescription to changes in pregnancy guideline recommendations and may also reflect changes in commissioning and in the characteristics of pregnant women living with HIV.

Brief Report: Surveillance of Congenital Anomalies After Exposure to Raltegravir or Elvitegravir During Pregnancy in the United Kingdom and Ireland, 2008-2018.

BACKGROUND: The indisputable benefits of antiretroviral therapy (ART) in the reduction of mother-to-child-transmission of HIV have to be carefully balanced with the risks of embryo-fetal toxicities due to fetal exposure to maternal ART. The recent report of a potential safety signal with dolutegravir use in pregnancy and potential increased rate of neural tube defects has raised the question of a potential class effect for integrase strand inhibitors. To contribute real-world evidence, we evaluated data on pregnant women receiving raltegravir (RAL) or elvitegravir (EVG) in the United Kingdom and Ireland. METHODS: The National Study of HIV in Pregnancy and Childhood is a comprehensive population-based surveillance study collecting data on all HIV-positive pregnant women and their children. We collected data on all pregnancies exposed to an ART regimen containing RAL or EVG resulting in live birth, stillbirth, and induced abortion with an expected date of delivery between September 2008 and April 2018. Pregnancies were stratified into 3 groups of earliest exposure. RESULTS: A total of 908 pregnancies were exposed to a RAL- or EVG-based regimen (875 to RAL and 33 to EVG). There were 886 live-born infants exposed to RAL, 8 pregnancies ended in stillbirth, and 9 in induced abortions. Among the 886 live-born infants, there were 23 (2.59%, 95% confidence interval: 1.65 to 3.86) reported congenital anomalies, 2 nervous system defects but no reported neural tube defects. Of the 33 pregnancies exposed to EVG, 31 resulted in live-born infants with no congenital anomaly and the remaining 2 pregnancies ended in induced abortion. CONCLUSIONS: The prevalence of congenital anomalies is consistent with national population estimates for 2008-2016 in the United Kingdom. More data are needed on safety of RAL and EVG in pregnancy.

HIV treatment in pregnancy.

Almost 25 years since antiretroviral therapy (ART) was first shown to prevent mother-to-child transmission of HIV, 76% of pregnant women living with HIV (over 1 million women) receive ART annually. This number is the result of successes in universal ART scale-up in low-income and middle-income countries. Despite unprecedented ART-related benefits to maternal and child health, challenges remain related to ART adherence, retention in care, and unequal access to ART. Implementation research is ongoing to understand and to address obstacles that lead to loss to follow-up. The biological mechanisms that underlie observed associations between antenatal ART and adverse outcomes in pregnancy and birth are not completely understood, with further research needed as well as strengthening of the systems to assess safety of antiretroviral drugs for the mother and HIV-exposed child. In the treat-all era, as duration of treatment and options for ART expand, pregnant women will remain a priority population for treatment optimisation to promote their health and that of their ART-exposed children.

Accuracy of serum procalcitonin for the diagnosis of sepsis in neonates and children with systemic inflammatory syndrome: a meta-analysis.

BACKGROUND: A number of biomarkers have been studied for the diagnosis of sepsis in paediatrics, but no gold standard has been identified. Procalcitonin (PCT) was demonstrated to be an accurate biomarker for the diagnosis of sepsis in adults and showed to be promising in paediatrics. Our study reviewed the diagnostic accuracy of PCT as an early biomarker of sepsis in neonates and children with suspected sepsis. METHODS: A comprehensive literature search was carried out in Medline/Pubmed, Embase, ISI Web of Science, CINAHL and Cochrane Library, for studies assessing PCT accuracy in the diagnosis of sepsis in children and neonates with suspected sepsis. Studies in which the presence of infection had been confirmed microbiologically or classified as "probable" by chart review were included. Studies comparing patients to healthy subjects were excluded. We analysed data on neonates and children separately. Our primary outcome was the diagnostic accuracy of PCT at the cut-off of 2-2.5 ng/ml, while as secondary outcomes we analysed PCT cut-offs <2 ng/ml and >2.5 ng/ml. Pooled sensitivities and specificities were calculated by a bivariate meta-analysis and heterogeneity was graphically evaluated. RESULTS: We included 17 studies, with a total of 1408 patients (1086 neonates and 322 children). Studies on neonates with early onset sepsis (EOS) and late onset sepsis (LOS) were grouped together. In the neonatal group, we calculated a sensitivity of 0.85, confidence interval (CI) (0.76; 0.90) and specificity of 0.54, CI (0.38; 0.70) at the PCT cut-off of 2.0-2.5 ng/ml. In the paediatric group it was not possible to undertake a pooled analysis at the PCT cut-off of 2.0-2.5 ng/ml, due to the paucity of the studies. CONCLUSIONS: PCT shows a moderate accuracy for the diagnosis of sepsis in neonates with suspected sepsis at the cut-off of 2.0-2.5 ng/ml. More studies with high methodological quality are warranted, particularly in neonates, studies considering EOS and LOS separately are needed to improve specificity. TRIAL REGISTRATION: PROSPERO Identifier: CRD42016033809 . Registered 30 Jan 2016.

Does extensive upper abdomen surgery during primary cytoreduction impact on long-term quality of life?

OBJECTIVES: The objective of this study was to evaluate the feasibility in terms of safety and quality of life in a sample of Italian patients affected by advanced ovarian cancer and submitted to either extensive upper abdomen or standard surgery, through validated questionnaires. METHODS: From January 2006 to November 2011, a prospective, observational study was conducted to compare quality of life in patients affected by advanced ovarian cancer and submitted to primary cytoreduction in the Division of Gynecology of the University Campus Bio-Medico of Rome. After surgery patients were stratified into 2 groups (group A: standard surgery or group B: extensive upper abdomen surgery). All patients were submitted to standard chemotherapy. At completion of treatment, during the first follow-up visit, all eligible patients were asked to fill in quality of life questionnaire-C30 (QLQ-C30) (version 3.0) and European Organisation for Research and Treatment of cancer quality of life questionnaire-OV28 (QLQ-OV28) questionnaires. RESULTS: Eighty-nine patients were enrolled into our study. Nine were excluded, so finally 80 patients were considered in this study. Group A included 40 patients and underwent standard surgery (pelvic surgery); group B, included 40 patients and underwent extensive upper abdomen surgery. There were no statistical differences in terms of major surgical complication rates (15% vs. 10%). We registered same times of beginning of chemotherapy (median, 19 vs 21 days) and no severe related toxicities. Quality-of-life scores of both questionnaires were comparable between groups, with the exception of Global Health Status in QLC-30. CONCLUSIONS: Upper abdomen surgery is a feasible and safe therapeutic option. Patients present same times of beginning of chemotherapy without an increase in chemorelated toxicities and experience the same general quality of life.