Prediction of fetal and neonatal outcomes after preterm manifestations of placental insufficiency: systematic review of prediction models.

OBJECTIVES: To identify all prediction models for fetal and neonatal outcomes in pregnancies with preterm manifestations of placental insufficiency (gestational hypertension, pre-eclampsia, HELLP syndrome or fetal growth restriction with its onset before 37 weeks' gestation) and to assess the quality of the models and their performance on external validation. METHODS: A systematic literature search was performed in PubMed, Web of Science and EMBASE. Studies describing prediction models for fetal/neonatal mortality or significant neonatal morbidity in patients with preterm placental insufficiency disorders were included. Data extraction was performed using the CHARMS checklist. Risk of bias was assessed using PROBAST. Literature selection and data extraction were performed by two researchers independently. RESULTS: Our literature search yielded 22 491 unique publications. Fourteen were included after full-text screening of 218 articles that remained after initial exclusions. The studies derived a total of 41 prediction models, including four models in the setting of pre-eclampsia or HELLP, two models in the setting of fetal growth restriction and/or pre-eclampsia and 35 models in the setting of fetal growth restriction. None of the models was validated externally, and internal validation was performed in only two studies. The final models contained mainly ultrasound (Doppler) markers as predictors of fetal/neonatal mortality and neonatal morbidity. Discriminative properties were reported for 27/41 models (c-statistic between 0.6 and 0.9). Only two studies presented a calibration plot. The risk of bias was assessed as unclear in one model and high for all other models, mainly owing to the use of inappropriate statistical methods. CONCLUSIONS: We identified 41 prediction models for fetal and neonatal outcomes in pregnancies with preterm manifestations of placental insufficiency. All models were considered to be of low methodological quality, apart from one that had unclear methodological quality. Higher-quality models and external validation studies are needed to inform clinical decision-making based on prediction models. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Randomised trial of no hydration vs. sodium bicarbonate hydration in patients with chronic kidney disease undergoing acute computed tomography-pulmonary angiography.

BACKGROUND: Hydration to prevent contrast-induced acute kidney injury (CI-AKI) induces a diagnostic delay when performing computed tomography-pulmonary angiography (CTPA) in patients suspected of having acute pulmonary embolism. AIM: To analyze whether withholding hydration is non-inferior to sodium bicarbonate hydration before CTPA in patients with chronic kidney disease (CKD). METHODS: We performed an open-label multicenter randomized trial between 2009 and 2013. One hundred thirty-nine CKD patients were randomized, of whom 138 were included in the intention-to-treat population: 67 were randomized to withholding hydration and 71 were randomized to 1-h 250 mL 1.4% sodium bicarbonate hydration before CTPA. Primary outcome was the increase in serum creatinine 48-96 h after CTPA. Secondary outcomes were the incidence of CI-AKI (creatinine increase > 25%/> 0.5 mg dL(-1) ), recovery of renal function, and the need for dialysis within 2 months after CTPA. Withholding hydration was considered non-inferior if the mean relative creatinine increase was ≤ 15% compared with sodium bicarbonate. RESULTS: Mean relative creatinine increase was -0.14% (interquartile range -15.1% to 12.0%) for withholding hydration and -0.32% (interquartile range -9.7% to 10.1%) for sodium bicarbonate (mean difference 0.19%, 95% confidence interval -5.88% to 6.25%, P-value non-inferiority < 0.001). CI-AKI occurred in 11 patients (8.1%): 6 (9.2%) were randomized to withholding hydration and 5 (7.1%) to sodium bicarbonate (relative risk 1.29, 95% confidence interval 0.41-4.03). Renal function recovered in 80.0% of CI-AKI patients within each group (relative risk 1.00, 95% confidence interval 0.54-1.86). None of the CI-AKI patients developed a need for dialysis. CONCLUSION: Our results suggest that preventive hydration could be safely withheld in CKD patients undergoing CTPA for suspected acute pulmonary embolism. This will facilitate management of these patients and prevents delay in diagnosis as well as unnecessary start of anticoagulant treatment while receiving volume expansion.

Meta-analysis of the efficacy and safety of new oral anticoagulants in patients with cancer-associated acute venous thromboembolism.

INTRODUCTION: Treatment of acute venous thromboembolism (VTE) in cancer patients is challenging, owing to a high risk of recurrent VTE and bleeding complications. The anticoagulants of choice are low molecular weight heparins (LMWHs), because of a proven higher efficacy than vitamin K antagonists (VKAs) and a similar bleeding profile. The recently introduced new oral anticoagulants (NOACs) have the potential to be alternative options for these patients, as these drugs share practical advantages with LMWH, are administered orally, and had similar efficacy to VKAs but a lower bleeding risk in phase 3 studies in the general VTE population. METHODS: A systematic literature search was performed to identify phase 3 trials investigating NOACs for the treatment of VTE. The efficacy outcome was recurrent VTE, and the safety outcome was major and clinically relevant non-major bleeding. Pooled incidence rates and risk ratios (RRs) were calculated for cancer patients and non-cancer patients separately. RESULTS AND DISCUSSION: Five studies were included, with 19 060 patients, of whom 973 (5.1%) had active cancer. The pooled incidence rates of recurrent VTE were 4.1% (95% confidence interval [CI] 2.6-6.0) in cancer patients treated with NOACs, and 6.1% (95% CI 4.1-8.5) in patients treated with VKAs (RR 0.66, 95% CI 0.38-1.2). The pooled incidence rates of major or non-major clinically relevant bleeding were 15% (95% CI 12-18) in cancer patients treated with NOACs, and 16% (95% CI 9.9-22) in patients treated with VKAs (RR 0.94, 95% CI 0.70-1.3). These results form a solid basis for the initiation of a head-to-head comparison of NOACs with LMWH in cancer patients.

Effectiveness and safety of novel oral anticoagulants as compared with vitamin K antagonists in the treatment of acute symptomatic venous thromboembolism: a systematic review and meta-analysis.

INTRODUCTION: New direct oral anticoagulants (NOACs) constitute a novel treatment option for acute venous thromboembolism (VTE), with practical advantages. Individual studies have demonstrated comparable efficacy to that of vitamin K antagonists (VKAs) and have suggested a more favorable safety profile . We performed a meta-analysis to determine the efficacy and safety of NOACs as compared with those of VKAs in patients with acute VTE. METHODS: We searched MEDLINE, EMBASE, the Cochrane Database of Systematic Reviews and the Clinical Trials Registry up to October 2013. Eligible studies included phase 3 trials comparing NOACs with VKAs in patients with acute VTE. Relative risks (RRs), absolute risk differences and numbers needed to treat (NNTs) to prevent one event were calculated for recurrent VTE, fatal pulmonary embolism (PE), overall mortality, major bleeding, and other bleeding complications, with random-effects models. RESULTS: Five studies were included, investigating four NOACs (rivaroxaban, dabigatran, apixaban, and edoxaban) in 24 455 patients with acute VTE. RRs for recurrent VTE, fatal PE and overall mortality for NOACs vs. VKAs were 0.88 (95% confidence interval [CI] 0.74-1.05), 1.02 (95% CI 0.39-5.96), and 0.97 (95% CI 0.83-1.14), respectively. The RR for major bleeding was 0.60 (95% CI 0.41-0.88). The NNT with NOACs instead of VKA to prevent one major bleed was 149. The RR and NNT for fatal bleeding were 0.36 (95% CI 0.15-0.87) and 1111. A fixed-effect network analysis did not demonstrate significant differences between individual NOACs and rivaroxaban. CONCLUSIONS: NOACs have comparable efficacy to that of VKAs, and are associated with a significantly lower risk of bleeding complications, although the NNT to prevent one major bleed was relatively high.

Impact of chronic kidney disease on the risk of clinical outcomes in patients with cancer-associated venous thromboembolism during anticoagulant treatment.

BACKGROUND: Information on recurrent venous thromboembolic events (VTEs) and major bleeding risks during anticoagulant treatment in patients with cancer-associated VTEs and chronic kidney disease (CKD) is scarce, although it is of relevance in establishing better tailored management strategies in these patients. OBJECTIVES: We compared risks of recurrent VTEs and major bleeds in cancer-associated VTE patients with and without CKD. METHODS: A total of 1684 patients diagnosed with a cancer-associated VTE between 2001 and 2011 were followed for 180 days after VTE diagnosis. Patients were treated mainly with low-molecular-weight heparin (LMWH) or vitamin-K antagonists (VKA). Primary outcomes were recurrent VTE and major bleeding. Secondary outcome was fatal bleeding. RESULTS: Recurrent VTEs occurred in 15.9/100 patient years (py) in patients without CKD (eGFR > 60 mL min(-1) ), 19.5/100 py in those with CKD stage 3A (eGFR 45-60 mL min(-1) ), 14.9/100 py in those with CKD 3B (eGFR 30-45 mL min(-1) ), and 6.8/100 py in patients with CKD 4-5 (eGFR < 30 mL min(-1) ). Major bleeding occurred in 11.4/100 py in patients without CKD, 18.5/100 py in those with CKD stage 3A, 16.0/100 py in those with CKD 3B, and 40.8/100 py in patients with CKD 4-5. Fatal bleeding occurred in 1.1/100 py, 3.4/100 py, 6.3/100 py and 15.7/100 py, respectively. These increased bleeding risks in CKD patients were mainly observed in those on LMWH treatment, not VKA. CONCLUSIONS: The risk of major bleeding was increased in CKD patients with VTE and cancer, and was most prominent in those treated with LMWH and an eGFR < 30 mL min(-1) . These results indicate that LMWH should be used with caution in this specific population.

A comparison of the acid-inhibitory effects of esomeprazole and pantoprazole in relation to pharmacokinetics and CYP2C19 polymorphism.

BACKGROUND: Esomeprazole and pantoprazole are metabolized in the liver and the polymorphic CYP2C19 enzyme is involved in that process. This genetic polymorphism determines fast (70% of Caucasians), intermediate (25-30% of Caucasians) and slow (2-5% of Caucasians) metabolism of PPIs. AIM: To compare the acid-inhibitory effects of esomeprazole 40 mg and pantoprazole 40 mg at 4, 24 and 120 h after oral administration in relation to CYP2C19 genotype and pharmacokinetics. METHODS: CYP2C19*2, *3, *4, *5 and *17 genotypes were determined in healthy Helicobacter pylori-negative Caucasian subjects. 7 wt/wt, 7 wt/*2, 2 wt/*17, 2 *2/*17 and 1 *2/*2 were included in a randomized investigator-blinded cross-over study with esomeprazole 40 mg and pantoprazole 40 mg. Intragastric 24-h pH-monitoring was performed on days 0, 1 and 5 of oral dosing. RESULTS: A total of 19 subjects (mean age 24 years, 7 male) completed the study. At day 1 and 5, acid-inhibition with esomeprazole was significantly greater and faster than with pantoprazole. Differences in acid-inhibition and pharmacokinetics between wt/wt and wt/*2 genotype were significant for pantoprazole at day 1 and 5. CONCLUSIONS: Esomeprazole provides acid-inhibition faster than and superior to pantoprazole after single and repeated administration. The acid-inhibitory effect and the kinetics of pantoprazole are influenced by CYP2C19 genotype.

Concentration and size distribution of particles in abstracted groundwater.

Particle number concentrations have been counted and particle size distributions calculated in groundwater derived by abstraction wells. Both concentration and size distribution are governed by the discharge rate: the higher this rate the higher the concentration and the higher the proportion of larger particles. However, the particle concentration in groundwater derived from abstraction wells, with high groundwater flow velocities, is much lower than in groundwater from monitor wells, with minimal flow velocities. This inconsistency points to exhaustion of the particle supply in the aquifer around wells due to groundwater abstraction for many years. The particle size distribution can be described with the help of a power law or Pareto distribution. Comparing the measured particle size distribution with the Pareto distribution shows that particles with a diameter >7 microm are under-represented. As the particle size distribution is dependent on the flow velocity, so is the value of the "Pareto" slope beta.

Glass and antimony electrodes for long-term pH monitoring: a dynamic in vitro comparison.

OBJECTIVE: To compare the performance of combined glass microelectrodes with monocrystalline and polycrystalline antimony electrodes with external reference in a 24-h dynamic in vitro study. DESIGN AND METHODS: In an artificial stomach, the pH of the contents titrated from pH1-7 and back by NaOH and HCI was simultaneously measured at 37 degrees C with antimony and glass probes connected to three recording devices. The recorded data were compared with data monitored continuously by a laboratory pH measurement system. The sensitivity and drift of glass microelectrodes were also analysed in intensive-care unit patients during intragastric pH monitoring for up to 96 h. RESULTS: The sensitivities of antimony polycrystalline, monocrystalline and of glass electrodes were 54.6, 55.3, and 61.8 mV/pH, respectively. The hysteresis was 6.4, 7.2 and 2.75 mV for antimony polycrystalline, monocrystalline and for glass electrodes, respectively. The drift in 24 h was -0.1 pH for glass over the pH range 1-7, and +0.3 pH over pH 1-2.5, and +0.15 pH over pH 2.5-7 for both of the antimony electrodes. The response times of both antimony and glass electrodes were similar over the pH range 2.5-7. The difference in the percentages of time below pH 1.5 was significant: 28.2% for glass, 17.3% for antimony polycrystalline and 18.1% for monocrystalline electrodes, respectively (P < 0.05). However, the difference in the percentages of time below pH 4 was not significant. After 96 h intragastric pH monitoring in six intensive-care unit patients, the mean drift of glass electrodes was 0.15 pH (range, pH 0.1-0.2) and the mean change in sensitivity 1.2%. CONCLUSIONS: (1) Antimony electrodes may be acceptable for intra-oesophageal pH monitoring but are not suitable for intragastric use. (2) The use of glass microelectrodes is recommended for intragastric pH monitoring, particularly when extended monitoring over periods longer than 24 h is required.

Multipurpose anthropometric facial anglemeter.

We have developed a multipurpose anglemeter for measuring the face that enables us to determine accurately the size of six profile angles by both direct and indirect anthropometry in markedly reduced time.