Fractional flow reserve (FFR_CT) using computed tomography coronary angiography (CTCA) determines both the presence of coronary artery disease and vessel-specific ischaemia. We tested whether an evaluation strategy based on FFR_CT would improve economic and clinical outcomes compared with standard care. Overall, 1400 patients with stable chest pain in 11 centres were randomized to initial testing with CTCA with selective FFR_CT (experimental group) or standard clinical care pathways (standard group). The primary endpoint was total cardiac costs at 9 months. Secondary endpoints were angina status, quality of life, major adverse cardiac and cerebrovascular events, and use of invasive coronary angiography. Randomized groups were similar at baseline. Most patients had an initial CTCA: 439 (63%) in the standard group vs. 674 (96%) in the experimental group, 254 of whom (38%) underwent FFR_CT. Mean total cardiac costs were higher by £114 (+8%) in the experimental group, with a 95% confidence interval from −£112 (−8%) to +£337 (+23%), though the difference was not significant (P = 0.10). Major adverse cardiac and cerebrovascular events did not differ significantly (10.2% in the experimental group vs. 10.6% in the standard group) and angina and quality of life improved to a similar degree over follow-up in both randomized groups. Invasive angiography was reduced significantly in the experimental group (19% vs. 25%, P = 0.01). A strategy of CTCA with selective FFR_CT in patients with stable angina did not differ significantly from standard clinical care pathways in cost or clinical outcomes, but did reduce the use of invasive coronary angiography. Summarising trial design and main results.

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported. The REMoDL-B phase III adaptive trial compared rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) versus R-CHOP + bortezomib (RB-CHOP) in patients with diffuse large B-cell lymphoma (DLBCL), stratified by molecular subtype. Primary analysis at a median follow-up of 30 months found no effect of bortezomib on progression-free survival (PFS) or overall survival (OS). Retrospective analysis using a gene expression–based classifier identified a molecular high-grade (MHG) group with worse outcomes. We present an updated analysis for patients successfully classified by the gene expression profile (GEP). Eligible patients were age older than 18 years with untreated DLBCL, fit enough for full-dose chemotherapy, and with adequate biopsies for GEP. Of 1,077 patients registered, 801 were identified with Activated B-Cell (ABC), Germinal Center B-cell, or MHG lymphoma. At a median follow-up of 64 months, there was no overall benefit of bortezomib on PFS or OS (5-year PFS hazard ratio [HR], 0.81; P = .085; OS HR, 0.86; P = .32). However, improved PFS and OS were seen in ABC lymphomas after RB-CHOP: 5-year OS 67% with R-CHOP versus 80% with RB-CHOP (HR, 0.58; 95% CI, 0.35 to 0.95; P = .032). Five-year PFS was higher in MHG lymphomas: 29% versus 55% (HR, 0.46; 95% CI, 0.26 to 0.84). Patients with ABC and MHG DLBCL may benefit from the addition of bortezomib to R-CHOP in initial therapy.

Background: Geographical inequalities in overweight and obesity prevalence among children are well established in cross-sectional research. We aimed to examine how environmental area characteristics at birth are related to these outcomes in childhood. Methods: Anonymised antenatal and birth data recorded by University Hospital Southampton linked to school-measured weight and height data for children within Southampton, UK, were utilised (14,084 children at ages 4–5 and 5637 at ages 10–11). Children’s home address at birth was analysed at the Lower and Middle layer Super Output Area (LSOA/MSOA) levels (areas with average populations of 1500 and 7000, respectively). Area-level indices (walkability, relative density of unhealthy food outlets, spaces for social interaction), natural greenspace coverage, supermarket density and measures of air pollution (PM_2.5, PM₁₀ and NO_x) were constructed using ArcGIS Network Analyst. Overweight/obesity was defined as a body mass index (BMI; kg/m²) greater than the 85th centile for sex and age. Population-average generalised estimating equations estimated the risk of being overweight/obese for children at both time points. Confounders included maternal BMI and smoking in early pregnancy, education, ethnicity and parity. We also examined associations for a subgroup of children who moved residence between birth and outcome measurement. Results: There were mixed results between area characteristics at birth and overweight/obesity at later ages. MSOA relative density of unhealthy food outlets and PM₁₀ were positively associated with overweight/obesity, but not among children who moved. LSOA greenspace coverage was negatively associated with the risk of being overweight/obese at ages 10–11 in all children (relative risk ratio 0.997, 95% confidence interval 0.995–0.999, p = 0.02) and among children who moved. Conclusions: Local access to natural greenspaces at the time of birth was inversely associated with becoming overweight or obese by age 10–11, regardless of migration. Increased access/protection of greenspace may have a role in the early prevention of childhood obesity.

Objective: Maternal overweight and obesity during pregnancy increases the risk of large-for-gestational age (LGA) birth and childhood obesity. We aimed to investigate the association between maternal weight change between subsequent pregnancies and risk of having a LGA birth. Design: Population-based cohort. Setting: Routinely collected antenatal healthcare data between January 2003 and September 2017 at University Hospital Southampton, England. Participants: Health records of women with their first two consecutive singleton live-birth pregnancies were analysed (n=15 940). Primary outcome measure: Risk of LGA, recurrent LGA and new LGA births in the second pregnancy. Results: Of the 15 940 women, 16.0% lost and 47.7% gained weight (≥1 kg/m ² ) between pregnancies. A lower proportion of babies born to women who lost ≥1 kg/m ² (12.4%) and remained weight stable between −1 and 1 kg/m ² (11.9%) between pregnancies were LGA compared with 13.5% and 15.9% in women who gained 1–3 and ≥3 kg/m ² , respectively. The highest proportion was in obese women who gained ≥3 kg/m ² (21.2%). Overweight women had a reduced risk of recurrent LGA in the second pregnancy if they lost ≥1 kg/m ² (adjusted relative risk (aRR) 0.69, 95% CI 0.48 to 0.97) whereas overweight women who gained ≥3 kg/m ² were at increased risk of new LGA after having a non-LGA birth in their first pregnancy (aRR 1.35, 95% CI 1.05 to 1.75). Normal-weight women who gained weight were also at increased risk of new LGA in the second pregnancy (aRR 1.26, 95% CI 1.06 to 1.50 with gain of 1–3 kg/m ² and aRR 1.34, 95% CI 1.09 to 1.65 with gain of ≥3 kg/m ² ). Conclusions: Losing weight after an LGA birth was associated with a reduced LGA risk in the next pregnancy in overweight women, while interpregnancy weight gain was associated with an increased new LGA risk. Preventing weight gain between pregnancies is an important measure to achieve better maternal and offspring outcomes.

Although survival rates for pediatric acute lymphoblastic leukemia are now excellent, this is at the expense of prolonged chemotherapy regimens. We report the long‐term immune effects in children treated according to the UK Medical Research Council UKALL 2003 protocol. Peripheral blood lymphocyte subsets and immunoglobulin levels were studied in 116 participants, at six time points, during and for 18‐month following treatment, with 30‐39 patients analyzed at each time point.Total lymphocytes were reduced during maintenance chemotherapy and remained low 18 months following treatment completion. CD4 T cells remained significantly reduced 18 months after treatment, but CD8 cells and natural killer cells recovered to normal values. The fall in naïve B‐cell numbers during maintenance was most marked, but numbers recovered rapidly after cessation of treatment. Memory B cells, particularly nonclass‐switched memory B cells, remained below normal levels 18 months following treatment. All immunoglobulin subclasses were reduced during treatment compared to normal values, with IgM levels most affected.This study demonstrates that immune reconstitution differs between lymphocyte compartments. Although total B‐cell numbers recover rapidly, disruption of memory/naïve balance persists and T‐cell compartment persist at 18 months. This highlights the impact of modern chemotherapy regimens on immunity, and thus, infectious susceptibility and response to immunization.