Principles of Anti-infective Dosing in Pregnancy

AbstractPurposeAnti-infectives are among the most commonly prescribed medications in pregnancy. However, detailed information on the pharmacokinetics and pharmacodynamics of these medications in pregnancy is limited, leading to uncertainty among clinicians regarding the tolerability and efficacy of treatments. The purposes of this review were to highlight key physiologic changes during pregnancy that influence drug behavior, and to discuss areas of active research related to anti-infective drugs in pregnancy.MethodsA review of literature in PubMed was performed for topics related to physiologic changes of pregnancy, postcesarean surgical site infections, vaccines in pregnancy, and intrauterine infections. The literature was reviewed and pertinent sources were utilized for this article.FindingsPhysiologic changes during pregnancy may impact drug disposition and efficacy. Cefazolin regimens are the current prophylactic treatment of choice for postcesarean surgical site infections. Vaccines are provided in pregnancy for both maternal and neonatal benefit. Broad-spectrum antibiotics continue to be used as first-line therapy for intrauterine infections.ImplicationsContinued efforts to broaden the knowledge base on anti-infective drug behavior in pregnancy will result in increased therapeutic options for this population

Contextualising Apartheid at the End of Empire: Repression, ‘Development’ and the Bantustans

This article examines the global dynamics of late colonialism and how these informed South African apartheid. More specifically, it locates the programmes of mass relocation and bantustan ‘self-government’ that characterised apartheid after 1959 in relation to three key dimensions. Firstly, the article explores the global circulation of idioms of ‘development’ and trusteeship in the first half of the twentieth century and its significance in shaping segregationist policy; secondly, it situates bantustan ‘selfgovernment’ in relation to the history of decolonisation and the partitions and federations that emerged as late colonial solutions; and, thirdly, it locates the tightening of rural village planning in the bantustans after 1960 in relation to the elaboration of anti-colonial liberation struggles, repressive southern African settler politics and the Cold War. It argues that, far from developing policies that were at odds with the global ‘wind of change’, South African apartheid during the 1960s and 1970s reflected much that was characteristic about late colonial strategy

Dense genotyping of immune-related disease regions identifies 14 new susceptibility loci for juvenile idiopathic arthritis

Analysis of the ImmunoChip single nucleotide polymorphism (SNP) array in 2816 individuals, comprising the most common subtypes (oligoarticular and RF negative polyarticular) of juvenile idiopathic arthritis (JIA) and 13056 controls strengthens the evidence for association to three known JIA-risk loci (HLA, PTPN22 and PTPN2) and has identified fourteen risk loci reaching genome-wide significance (p < 5 × 10(-8)) for the first time. Eleven additional novel regions showed suggestive evidence for association with JIA (p < 1 × 10(-6)). Dense-mapping of loci along with bioinformatic analysis has refined the association to one gene for eight regions, highlighting crucial pathways, including the IL-2 pathway, in JIA disease pathogenesis. The entire ImmunoChip loci, HLA region and the top 27 loci (p < 1 × 10(-6)) explain an estimated 18%, 13% and 6% risk of JIA, respectively. Analysis of the ImmunoChip dataset, the largest cohort of JIA cases investigated to date, provides new insight in understanding the genetic basis for this childhood autoimmune disease

Dense genotyping of immune-related disease regions identifies 14 new susceptibility loci for juvenile idiopathic arthritis

Analysis of the ImmunoChip single nucleotide polymorphism (SNP) array in 2816 individuals, comprising the most common subtypes (oligoarticular and RF negative polyarticular) of juvenile idiopathic arthritis (JIA) and 13056 controls strengthens the evidence for association to three known JIA-risk loci (HLA, PTPN22 and PTPN2) and has identified fourteen risk loci reaching genome-wide significance (p < 5 × 10(-8)) for the first time. Eleven additional novel regions showed suggestive evidence for association with JIA (p < 1 × 10(-6)). Dense-mapping of loci along with bioinformatic analysis has refined the association to one gene for eight regions, highlighting crucial pathways, including the IL-2 pathway, in JIA disease pathogenesis. The entire ImmunoChip loci, HLA region and the top 27 loci (p < 1 × 10(-6)) explain an estimated 18%, 13% and 6% risk of JIA, respectively. Analysis of the ImmunoChip dataset, the largest cohort of JIA cases investigated to date, provides new insight in understanding the genetic basis for this childhood autoimmune disease

Gender differences in mortality and quality of life after septic shock: A post-hoc analysis of the ARISE study

PURPOSE: To assess the impact of gender and pre-menopausal state on short- and long-term outcomes in patients with septic shock. MATERIAL AND METHODS: Cohort study of the Australasian Resuscitation in Sepsis Evaluation (ARISE) trial, an international randomized controlled trial comparing early goal-directed therapy (EGDT) to usual care in patients with early septic shock, conducted between October 2008 and April 2014. The primary exposure in this analysis was legal gender and the secondary exposure was pre-menopausal state defined by chronological age (≤ 50 years). RESULTS: 641 (40.3%) of all 1591 ARISE trial participants in the intention-to-treat population were females and overall, 337 (21.2%) (146 females) patients were 50  years of age or younger. After risk-adjustment, we could not identify any survival benefit for female patients at day 90 in the younger (≤50 years) (adjusted Odds Ratio (aOR): 0.91 (0.46-1.89), p = .85) nor in the older (>50 years) age-group (aOR: 1.10 (0.81-1.49), p = .56). Similarly, there was no gender-difference in ICU, hospital, 1-year mortality nor quality of life measures. CONCLUSIONS: This post-hoc analysis of a large multi-center trial in early septic shock has shown no short- or long-term survival effect for women overall as well as in the pre-menopausal age-group