Eligibility of patients with Staphylococcus aureus bacteraemia for early oral switch

To identify people with low-risk Staphylococcus aureus bacteraemia (SAB), the SABATO investigators screened 5063 people, finding 213 (4·2%) meeting their eligibility criteria1. This low proportion of eligible patients led the authors to question if low-risk SAB is clinically relevant. We aimed to determine the clinical relevance of the SABATO definition of low-risk SAB, and if the trial population was representative of potentially eligible real-world patients. Data was collected retrospectively for 464 consecutive adults with SAB at our institution (Supplementary Figure), approved by the South East Scotland Research Ethics Committee (23/SS/0025). We then applied the SABATO inclusion and exclusion criteria to identify potentially eligible real-world patients.Of the 464 patients in our cohort, 71 (15·3%) would have been potentially eligible for inclusion in the trial. Acquisition of SAB in these patients was mainly nosocomial (35/71, 49·3%). Key cohort characteristics reported by the trial were very similar when comparing trial participants with potentially eligible real-world patients, although the median Charlson Comorbidity Index was lower in the trial cohort (Table). An intravenous catheter was the most common source of SAB in both cohorts, but there was a higher proportion of SAB from an unknown source in the real-world group (p=0·0015). An unknown source is a risk factor for complications2,3 and further evaluation combined with intensive follow-up of early oral switch should be considered in this group.Implanted prosthetic material is a component of the IDSA definition of complicated SAB4 but with certain caveats was not an absolute exclusion criterion in the SABATO trial. Nine potentially eligible real-world patients had prosthetic material in situ (n=4 cardiac devices and n=5 orthopaedic implants). This data was not reported for trial participants but could further increase confidence in applicability of the findings. No laboratory or physiology data from the time of the index blood culture was reported but might have been helpful to quantify disease severity and guide patient selection (Supplementary Table). We suggest this supports standardised collection and reporting of cohort characteristics in SAB trials to improve comparability between studies, which is often complicated by variability in the cohort characteristics reported5.We conclude that the sub-group of low-risk SAB studied in the SABATO trial is clinically relevant and find the similarities between randomised and real-world eligible patients re-assuring. Implementation of SABATO findings should be done cautiously and studied prospectively, especially when applied to patients with SAB of unknown source who were infrequently included in the trial.<br/

Effectiveness and Safety of Adalimumab Biosimilar SB5 in IBD:Outcomes in Originator to SB5 Switch, Double Biosimilar Switch and Bio-Naieve SB5 Observational Cohorts

BACKGROUND AND AIMS: Multiple adalimumab [ADA] biosimilars are now approved for use in inflammatory bowel disease [IBD]; however, effectiveness and safety data remain scarce. We aimed to investigate long-term outcomes of the ADA biosimilar SB5 in IBD patients following a switch from the ADA originator [SB5-switch cohort] or after start of SB5 [SB5-start cohort]. METHODS: We performed an observational cohort study in a tertiary IBD referral centre. All IBD patients treated with Humira underwent an elective switch to SB5. We identified all these patients in a biological prescription database that prospectively registered all ADA start and stop dates including brand names. Data on IBD phenotype, C-reactive protein [CRP], drug persistence, ADA drug and antibody levels, and faecal calprotectin were collected. RESULTS: In total, 481 patients were treated with SB5, 256 in the SB5-switch cohort (median follow-up: 13.7 months [IQR 8.6–15.2]) and 225 in the SB5-start cohort [median follow-up: 8.3 months [4.2–12.8]). Of the SB5-switch cohort, 70.8% remained on SB5 beyond 1 year; 90/256 discontinued SB5, mainly due to adverse events [46/90] or secondary loss of response [37/90]. In the SB5-start cohort, 81/225 discontinued SB5, resulting in SB5-drug persistence of 60.3% beyond 1 year. No differences in clinical remission [p = 0.53], CRP [p = 0.80], faecal calprotectin [p = 0.40] and ADA trough levels [p = 0.55] were found between baseline, week 26 and week 52 following switch. Injection site pain was the most frequently reported adverse event. CONCLUSION: Switching from ADA originator to SB5 appeared effective and safe in this study with over 12 months of follow-up

Heterogeneity in Staphylococcus aureus Bacteraemia Clinical Trials Complicates Interpretation of Findings

We systematically evaluated randomized-controlled trials (RCTs) for Staphylococcus aureus bacteremia (SAB). There was intertrial heterogeneity in cohort characteristics, including bacteremia source, complicated SAB, and comorbidities. Reporting of cohort characteristics was itself variable, including bacteremia source and illness severity. Selection bias was introduced by exclusion criteria relating to comorbidities, illness severity, infection types, and source control. Mortality was lower in RCT control arms compared with observational cohorts. Differences in outcome definitions impedes meta-analysis. These issues complicate the interpretation and application of SAB RCT results. The value of these trials should be maximized by a standardized approach to recruitment, definitions, and reporting

Genetic predisposition to hypertension is associated with preeclampsia in European and Central Asian women

Preeclampsia is a serious complication of pregnancy, affecting both maternal and fetal health. In genome-wide association meta-analysis of European and Central Asian mothers, we identify sequence variants that associate with preeclampsia in the maternal genome at ZNF831/20q13 and FTO/16q12. These are previously established variants for blood pressure (BP) and the FTO variant has also been associated with body mass index (BMI). Further analysis of BP variants establishes that variants at MECOM/3q26, FGF5/4q21 and SH2B3/12q24 also associate with preeclampsia through the maternal genome. We further show that a polygenic risk score for hypertension associates with preeclampsia. However, comparison with gestational hypertension indicates that additional factors modify the risk of preeclampsia. Studies to identify maternal variants associated with preeclampsia have been limited by sample size. Here, the authors meta-analyze eight GWAS of 9,515 preeclamptic women, identifying five variants associated with preeclampsia and showing that genetic predisposition to hypertension is a major risk factor for preeclampsia.Peer reviewe

Genetic predisposition to hypertension is associated with preeclampsia in European and Central Asian women

Abstract Preeclampsia is a serious complication of pregnancy, affecting both maternal and fetal health. In genome-wide association meta-analysis of European and Central Asian mothers, we identify sequence variants that associate with preeclampsia in the maternal genome at ZNF831/20q13 and FTO/16q12. These are previously established variants for blood pressure (BP) and the FTO variant has also been associated with body mass index (BMI). Further analysis of BP variants establishes that variants at MECOM/3q26, FGF5/4q21 and SH2B3/12q24 also associate with preeclampsia through the maternal genome. We further show that a polygenic risk score for hypertension associates with preeclampsia. However, comparison with gestational hypertension indicates that additional factors modify the risk of preeclampsia. Studies to identify maternal variants associated with preeclampsia have been limited by sample size. Here, the authors meta-analyze eight GWAS of 9,515 preeclamptic women, identifying five variants associated with preeclampsia and showing that genetic predisposition to hypertension is a major risk factor for preeclampsia