To map the current status of head-to-head comparative randomized evidence and to assess whether funding may impact on trial design and results. From a 50% random sample of the randomized controlled trials (RCTs) published in journals indexed in PubMed during 2011, we selected the trials with ≥ 100 participants, evaluating the efficacy and safety of drugs, biologics, and medical devices through a head-to-head comparison. We analyzed 319 trials. Overall, 238,386 of the 289,718 randomized subjects (82.3%) were included in the 182 trials funded by companies. Of the 182 industry-sponsored trials, only 23 had two industry sponsors and only three involved truly antagonistic comparisons. Industry-sponsored trials were larger, more commonly registered, used more frequently noninferiority/equivalence designs, had higher citation impact, and were more likely to have "favorable" results (superiority or noninferiority/equivalence for the experimental treatment) than nonindustry-sponsored trials. Industry funding [odds ratio (OR) 2.8; 95% confidence interval (CI): 1.6, 4.7] and noninferiority/equivalence designs (OR 3.2; 95% CI: 1.5, 6.6), but not sample size, were strongly associated with "favorable" findings. Fifty-five of the 57 (96.5%) industry-funded noninferiority/equivalence trials got desirable "favorable" results. The literature of head-to-head RCTs is dominated by the industry. Industry-sponsored comparative assessments systematically yield favorable results for the sponsors, even more so when noninferiority designs are involved.

Background: Prenatal diagnosis of coarctation of the aorta (CoA) is still challenging and affected by high rates of false-positive diagnoses. The aim of this study was to ascertain the strength of association and to quantify the diagnostic accuracy of different ultrasound signs in predicting CoA prenatally. Methods: Medline, Embase, CINAHL, and Cochrane databases were searched. Random-effects and hierarchical summary receiver operating characteristic model meta-analyses were used to analyze the data. Results: Seven hundred ninety-four articles were identified, and 12 (922 fetuses at risk for CoA) articles were included. Mean mitral valve diameter z score was lower ( P <0.001) and the mean tricuspid valve diameter z score was higher in fetuses with CoA than in those without CoA ( P =0.01). Mean aortic valve diameter z score was lower in fetuses with CoA than in healthy fetuses ( P ≤0.001), but the ascending aorta diameter, expressed as z score or millimeters, was similar between groups ( P =0.07 and 0.47, respectively). Mean aortic isthmus diameter z scores measured either in sagittal ( P =0.02) or in 3-vessel trachea view ( P <0.001) were lower in fetuses with CoA. Conversely, the mean pulmonary artery diameter z score, the right/left ventricular and pulmonary artery/ascending aorta diameter ratios were higher ( P <0.001, P =0.02, and P =0.02, respectively) in fetuses with CoA in comparison with controls, although aortic isthmus/arterial duct diameter ratio was lower in fetuses with CoA than in those without CoA ( P <0.001). The presence of coarctation shelf and aortic arch hypoplasia were more common in fetuses with CoA than in controls (odds ratio, 26.0; 95% confidence interval, 4.42–153; P <0.001 and odds ratio, 38.2; 95% confidence interval, 3.01–486; P =0.005), whereas persistent left superior vena cava ( P =0.85), ventricular septal defect ( P =0.12), and bicuspid aortic valve ( P =0.14) did not carry an increased risk for this anomaly. Multiparametric diagnostic models integrating different ultrasound signs for the detection of CoA were associated with an increased detection rate. Conclusions: The detection rate of CoA may improve when a multiple-criteria prediction model is adopted. Further large multicenter studies sharing the same imaging protocols are needed to develop objective models for risk assessment in these fetuses.

Objectives: To develop a prenatal ultrasound staging system for placenta accreta spectrum (PAS) disorders in women with placenta previa and to evaluate its association with surgical outcome, placental invasion and the clinical staging system for PAS disorders proposed by the International Federation of Gynecology and Obstetrics (FIGO).Methods: This was a secondary retrospective analysis of prospectively collected data from women with placenta previa. We classified women according to the following staging system for PAS disorders, based upon the presence of ultrasound signs of PAS in women with placenta previa: PAS0, placenta previa with no ultrasound signs of invasion or with placental lacunae but no evidence of abnormal uterus–bladder interface; PAS1, presence of at least two of placental lacunae, loss of the clear zone or bladder wall interruption; PAS2, PAS1 plus uterovescical hypervascularity; PAS3, PAS1 or PAS2 plus evidence of increased vascularity in the inferior part of the lower uterine segment potentially extending into the parametrial region. We explored whether this ultrasound staging system correlates with surgical outcome (estimated blood loss (EBL, mL), units of packed red blood cells (PRBC), fresh frozen plasma (FFP) and platelets (PLT) transfused, operation time (min), surgical complications defined as the occurrence of any damage to the bladder, ureters or bowel, length of hospital stay (days) and admission to intensive care unit (ICU)) and depth of placental invasion. The correlation between the present ultrasound staging system and the clinical grading system proposed by FIGO was assessed. Prenatal and surgical management were not based on the proposed prenatal ultrasound staging system. Linear and multiple regression models were used.Results: Two‐hundred and fifty‐nine women were included in the analysis. Mean EBL was 516 ± 151 mL in women with PAS0, 609 ± 146 mL in those with PAS1, 950 ± 190 mL in those with PAS2 and 1323 ± 533 mL in those with PAS3, and increased significantly with increasing severity of PAS ultrasound stage. Mean units of PRBC transfused were 0.05 ± 0.21 in PAS0, 0.10 ± 0.45 in PAS1, 1.19 ± 1.11 in PAS2 and 4.48 ± 2.06 in PAS3, and increased significantly with PAS stage. Similarly, there was a progressive increase in the mean units of FFP transfused from PAS1 to PAS3 (0.0 ± 0.0 in PAS1, 0.25 ± 1.0 in PAS2 and 3.63 ± 2.67 in PAS3). Women presenting with PAS3 on ultrasound had significantly more units of PLT transfused (2.37 ± 2.40) compared with those with PAS0 (0.03 ± 0.18), PAS1 (0.0 ± 0.0) or PAS2 (0.0 ± 0.0). Mean operation time was longer in women with PAS3 (184 ± 32 min) compared with those with PAS1 (153 ± 38 min) or PAS2 (161 ± 28 min). Similarly, women with PAS3 had longer hospital stay (7.4 ± 2.1 days) compared with those with PAS0 (3.4 ± 0.6 days), PAS1 (6.4 ± 1.3 days) or PAS2 (5.9 ± 0.8 days). On linear regression analysis, after adjusting for all potential confounders, higher PAS stage was associated independently with a significant increase in EBL (314 (95% CI, 230–399) mL per one‐stage increase; P < 0.001), units of PRBC transfused (1.74 (95% CI, 1.33–2.15) per one‐stage increase; P < 0.001), units of FFP transfused (1.19 (95% CI, 0.61–1.77) per one‐stage increase; P < 0.001), units of PLT transfused (1.03 (95% CI, 0.59–1.47) per one‐stage increase; P < 0.001), operation time (38.8 (95% CI, 31.6–46.1) min per one‐stage increase; P < 0.001) and length of hospital stay (0.83 (95% CI, 0.46–1.27) days per one‐stage increase; P < 0.001). On logistic regression analysis, increased severity of PAS was associated independently with surgical complications (odds ratio, 3.14 (95% CI, 1.36–7.25); P = 0.007), while only PAS3 was associated with admission to the ICU (P < 0.001). All women with PAS0 on ultrasound were classified as having Grade‐1 PAS disorder according to the FIGO grading system. Conversely, of the women presenting with PAS1 on ultrasound, 64.1% (95% CI, 48.4–77.3%) were classified as having Grade‐3, while 35.9% (95% CI, 22.7–51.6%) were classified as having Grade‐4 PAS disorder, according to the FIGO grading system. All women with PAS2 were categorized as having Grade‐5 and all those with PAS3 as having Grade‐6 PAS disorder according to the FIGO system.Conclusion: Ultrasound staging of PAS disorders is feasible and correlates with surgical outcome, depth of invasion and the FIGO clinical grading system. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.