Category: Statistics

Minerva Pediatr (Torino). 2022 Apr 4. doi: 10.23736/S2724-5276.22.06683-6. Online ahead of print.

ABSTRACT

BACKGROUND: One of the possible adverse outcomes of magnesium sulfate (MgSO4) administration for preterm fetal neuroprotection is hypermagnesemia in the newborn. The objectives of this study were to evaluate the association between antenatal MgSO4 administration for neuroprotection and neonatal serum magnesium levels in the first days of life.

METHODS: A single-center retrospective case-control study was conducted on preterm neonates born in our institution between January 2017 and December 2019. Prenatal, perinatal, and postnatal parameters were recorded, and demographic information was collected. Comparative analysis between the group of neonates exposed to antenatal MgSO4 and the control group was performed.

RESULTS: A total of 98 patients were enrolled in the study, 49 of them were exposed to antenatal MgSO4 for neuroprotection. The serum magnesium levels in the 5 first days of life were higher in the case group, and higher than the normal range of serum magnesium levels (>2.4 mg/dL), with a statistical significance. The number of days needed to normalize serum magnesium levels was higher in the case group compared to the control group (median of 7 days [1-8] versus 2 days [1-5]).

CONCLUSIONS: Our findings show that antenatal administration of MgSO4 is associated with high serum magnesium levels in neonates. This group of patients needs close electrolyte monitoring during the first days of life. Parenteral nutrition supplemented with magnesium should only be considered after evaluation of serum magnesium levels.

PMID:35373935 | DOI:10.23736/S2724-5276.22.06683-6

J Biomed Mater Res B Appl Biomater. 2022 Apr 4. doi: 10.1002/jbm.b.35066. Online ahead of print.

ABSTRACT

The study aims to compare the way modern resin-based composites (RBCs) respond to mechanical stress related to the tooth structure they are designed to replace. Eight representative light-cured RBCs, including ormocers, giomers, RBCs with nano and agglomerated nanoparticles, prepolymerized, or compact fillers, were selected. Flexural strength, FS and modulus/E, were measured in a three-point bending test. A fractographic analysis determined the origin of fracture. The quasi-static (indentation hardness/H_IT , indentation modulus/E_IT ) and viscoelastic (storage modulus/E’, loss modulus/E″, loss factor/tan δ) behavior was assessed by a depth-sensing indentation test equipped with a dynamic-mechanical analysis module. One and multiple-way analysis of variance (ANOVA), Tukey honestly significant difference (HSD) post-hoc tests (α = 0.05), and Weibull statistics were applied. Parameter material exhibited the highest effect on E (p < .001, η_P² = .857), followed by FS (η_P² = .729), and the strain (η_P² = .553). Highest material reliability was identified in the RBCs with nano and agglomerated nanoparticles. The most frequent type of failure originated from volume (81.3%), followed by edge (10.6%), and corner (8.1%) flaws. Enamel evidenced three times higher H_IT , E_IT , and E’ values as RBCs and dentin, and the smallest deviation from ideal elasticity. Ormocers exhibited the highest damping capacity, followed by the RBCs with prepolymerized fillers. Damping capacity and static mechanical properties are mutually exclusive. Analyzed RBCs and the tooth structure are better adapted to the relevant frequency for chewing than for higher frequencies. RBCs are comparable to dentin in terms of their mechanical performance, but apart from the damping behavior, they are far inferior to enamel. Damping ability of analyzed material could be exploited for correlation with the clinical behavior.

PMID:35373907 | DOI:10.1002/jbm.b.35066

N Engl J Med. 2022 Apr 4. doi: 10.1056/NEJMoa2109191. Online ahead of print.

ABSTRACT

BACKGROUND: Childhood cardiovascular risk factors predict subclinical adult cardiovascular disease, but links to clinical events are unclear.

METHODS: In a prospective cohort study involving participants in the International Childhood Cardiovascular Cohorts (i3C) Consortium, we evaluated whether childhood risk factors (at the ages of 3 to 19 years) were associated with cardiovascular events in adulthood after a mean follow-up of 35 years. Body-mass index, systolic blood pressure, total cholesterol level, triglyceride level, and youth smoking were analyzed with the use of i3C-derived age- and sex-specific z scores and with a combined-risk z score that was calculated as the unweighted mean of the five risk z scores. An algebraically comparable adult combined-risk z score (before any cardiovascular event) was analyzed jointly with the childhood risk factors. Study outcomes were fatal cardiovascular events and fatal or nonfatal cardiovascular events, and analyses were performed after multiple imputation with the use of proportional-hazards regression.

RESULTS: In the analysis of 319 fatal cardiovascular events that occurred among 38,589 participants (49.7% male and 15.0% Black; mean [±SD] age at childhood visits, 11.8±3.1 years), the hazard ratios for a fatal cardiovascular event in adulthood ranged from 1.30 (95% confidence interval [CI], 1.14 to 1.47) per unit increase in the z score for total cholesterol level to 1.61 (95% CI, 1.21 to 2.13) for youth smoking (yes vs. no). The hazard ratio for a fatal cardiovascular event with respect to the combined-risk z score was 2.71 (95% CI, 2.23 to 3.29) per unit increase. The hazard ratios and their 95% confidence intervals in the analyses of fatal cardiovascular events were similar to those in the analyses of 779 fatal or nonfatal cardiovascular events that occurred among 20,656 participants who could be evaluated for this outcome. In the analysis of 115 fatal cardiovascular events that occurred in a subgroup of 13,401 participants (31.0±5.6 years of age at the adult measurement) who had data on adult risk factors, the adjusted hazard ratio with respect to the childhood combined-risk z score was 3.54 (95% CI, 2.57 to 4.87) per unit increase, and the mutually adjusted hazard ratio with respect to the change in the combined-risk z score from childhood to adulthood was 2.88 (95% CI, 2.06 to 4.05) per unit increase. The results were similar in the analysis of 524 fatal or nonfatal cardiovascular events.

CONCLUSIONS: In this prospective cohort study, childhood risk factors and the change in the combined-risk z score between childhood and adulthood were associated with cardiovascular events in midlife. (Funded by the National Institutes of Health.).

PMID:35373933 | DOI:10.1056/NEJMoa2109191

Diabetes Obes Metab. 2022 Apr 4. doi: 10.1111/dom.14709. Online ahead of print.

ABSTRACT

AIM: To assess whether low-carbohydrate (LC) diets are associated with differences in weight loss and well-being in people with obesity, and to assess their cardiovascular and renal safety.

METHODS: Meta-analysis of Randomized Controlled Trials longer than 3 months, retrieved through an extensive search on MedLine and Embase online databases, comparing weight loss with LC diets and control diets in people with BMI >30 kg/m² .

RESULTS: We retrieved 25 trials. LC diets were associated with significant reduction of body weight at 3-4 (MD -2.59 [-3.93, -1.25] kg), and at 6-8 months (MD -2.64 [-4.32, -0.95]), no diffeence at 10-14 and 18-30 months, vs controls. Compared with controls, LC diets were associated with significantly greater BMI reduction at 3-4 months (-1.66 [-2.70, -0.61] kg/m²⁾ , but not at other timepoints. Since only four trials reported data on renal function and psychological parameters, renal safety and impact on well-being could not be assessed. Differences in fasting plasma glucose at any time point were not statistically significant. No significant difference in total or LDL Cholesterol or blood pressure were found in the long-term, whereas a long-term reduction of triglycerides (23.26 [-45.53, -0.98] mg/dl, at 18-30 months), and increase of HDL cholesterol, MD 4.94 [0.30, 9.57] mg/dl at 18-30 months), was observed.

CONCLUSION: LC diets are associated with greater short-term weight loss than non-carbohydrate-restricted diets and a longer-term favorable effect on cardiovascular risk factors. Further evidence on long-term efficacy and renal safety is needed before LC diets can be recommended as the preferred diets in obese persons. This article is protected by copyright. All rights reserved.

PMID:35373905 | DOI:10.1111/dom.14709

Pediatr Blood Cancer. 2022 Apr 4:e29697. doi: 10.1002/pbc.29697. Online ahead of print.

ABSTRACT

PURPOSE: To determine if proton therapy reduces doses to cranial organs at risk (OARs) as compared to photon therapy in children with non-germinomatous germ cell tumors (NGGCT) receiving whole ventricular radiotherapy (WVRT).

METHODS AND MATERIALS: Dosimetric data for patients with NGGCT prospectively enrolled in stratum 1 of the Children’s Oncology Group study ACNS1123 who received 30.6 Gy WVRT were compared. Target segmentation was standardized using a contouring atlas. Doses to cranial OARs were compared between proton and photon treatments. Clinically relevant dose-volume parameters that were analyzed included mean dose and dose to 40% of the OAR volume (D40).

RESULTS: Mean and D40 doses to the supratentorial brain, cerebellum, and bilateral temporal, parietal, and frontal lobes were statistically significantly lower amongst proton-treated patients, as compared to photon-treated patients. In a subgroup analysis of patients uniformly treated with a 3-mm planning target volume, patients who received proton therapy continued to have statistically significantly lower doses to brain OARs.

CONCLUSIONS: Children treated with proton therapy for WVRT had lower doses to normal brain structures, when compared to those treated with photon therapy. Proton therapy should be considered for patients receiving WVRT for NGGCT.

PMID:35373903 | DOI:10.1002/pbc.29697

Diabetes Obes Metab. 2022 Apr 4. doi: 10.1111/dom.14706. Online ahead of print.

ABSTRACT

BACKGROUND: In Europe regulatory approval of the Medtronic Minimed^TM 670G is limited to those above 7 years. Thus, additional information on the incremental differences between using a sensor-augmented pump (SAP) without automated insulin delivery (AID), using it with predictive low-glucose suspension (PLGM) or as hybrid closed loop (HCL) in preschool and school children is needed.

METHODS: We conducted a monocentric, randomized, controlled, two-phase cross-over study in 38 children 2-6 and 7-14 years of age. Primary endpoint was percentage of time in range (TIR) of 70-180 mg/dl. Other CGM metrics, HbA1c, patient related outcomes (DISABKIDS questionnaire, Fear of Hypoglycemia Survey) and safety events were also assessed. Results from 2 weeks SAP, 8 weeks PLGM and 8 weeks HCL were compared using a paired t-test or Wilcoxon signed-rank test.

RESULTS: Overall we found a high rate of TIR target (>70%) achievement with HCL in preschool (88%) and school children (50%), with average times in Auto Mode of 93% and 87% respectively. Preschool children achieved a mean TIR of 73±6% (+8% vs. SAP, +6% vs. PLGM) and school children 69±8% ( +15% vs. SAP and +14% vs. PLGM). Overall HbA1c improved from 7.4±0.9% to 6.9±0.5%. (p=0.0002). Diabetes burden and worries and fear of hypoglycemia remained on low levels without significant changes vs. PLGM. No events of severe hypoglycemia or diabetic ketoacidosis occurred.

CONCLUSIONS: Preschool children profit from AID at least as much as those age 7 and above. To ensure safe use and prescribing modalities, regulatory approval is required also for young children. This article is protected by copyright. All rights reserved.

PMID:35373894 | DOI:10.1111/dom.14706

Pediatr Blood Cancer. 2022 Apr 4:e29575. doi: 10.1002/pbc.29575. Online ahead of print.

ABSTRACT

BACKGROUND: Pediatric low-grade gliomas (PLGG) are the most common brain tumors diagnosed during childhood and represent a heterogeneous group associating variable molecular abnormalities. To go further and develop specific statistical patterns between tumor molecular background, imaging features, and patient outcome, a retrospective study was performed in a group of non-neurofibromatosis type 1 (non-NF1) grade 1 PLGGs.

PATIENTS AND METHODS: Seventy-eight children, followed from 2004 to 2017, were retrospectively reported. In this population, we analyzed radiological and molecular parameters. Their therapeutic management comprised surgery or surgery plus chemotherapies.

RESULTS: Considering all 78 patients, 59 had only a surgical removal and 19 patients were treated with postoperative chemotherapy. Twelve progressions were reported in the partially resected and chemotherapeutic groups, whereas four deaths occurred only in the highly treated patients. As expected, in the global cohort, PLGG with BRAF p.V600E and/or CDKN2A loss exhibited poor outcomes and we evidenced significant associations between those molecular characteristics and their imaging presentation. In the chemo-treated patients, when associating initial and 6-month magnetic resonance imaging (MRI) parameters to the molecular features, the good risk situations were significantly linked to the presence of a large tumor cyst at diagnosis and the appearance during treatment of a higher cystic proportion that we called cystic conversion.

CONCLUSION: So, additionally to the presence of BRAF p.V600E or CDKN2A deletion in grade 1 PLGGs, the absence on diagnostic MRI of cystic parts and/or cystic conversion at 6-month chemotherapy were significantly linked to a worst prognosis and response to treatment. These imaging features should be considered as prognostic markers in future PLGG studies.

PMID:35373885 | DOI:10.1002/pbc.29575

BJOG. 2022 Apr 4. doi: 10.1111/1471-0528.17174. Online ahead of print.

ABSTRACT

OBJECTIVE: To establish pregnancy-specific reference ranges for fasting and postprandial total serum bile acids (TSBA) concentrations.

DESIGN: Cross-sectional study.

SETTING: Tertiary care university hospital.

POPULATION: Healthy pregnant women at term admitted to the Obstetrics Department over one year. Exclusion criteria were an established diagnosis of intrahepatic cholestasis of pregnancy (ICP) or any co-existing condition of increased risk for ICP.

METHODS AND MAIN OUTCOME MEASURES: Both fasting (8-14 hours of fasting) and postprandial (2 hours after meal) TSBA concentrations were measured in 612 women (528 fasting and 377 postprandial samples) by automated enzymatic-spectrophotometric assay.

RESULTS: Reference intervals of 4.4-14.1 μmol/L for fasting TSBA, and 4.7-20.2 μmol/L for postprandial TSBA were established. The postprandial values were significantly higher than the fasting measurements, with a median increase of 1.0 μmol/L (p< 0.0001). A correlation between fasting TSBA concentrations and postprandial concentrations was found, as well as with fetal gender, parity, and assisted reproductive technologies. A seasonal pattern was noticed for both fasting and postprandial TSBA, with the highest values in the winter season (p < 0.01 and 0.02, respectively).

CONCLUSIONS: Normal pregnancy is associated with mild hypercholanaemia, therefore a higher threshold should be considered for the diagnosis of ICP. We suggest using the upper reference limit observed in our healthy pregnant population (14 μmol/L for fasting and 20 μmol/L for postprandial TSBA). As the fasting measurement is more specific for the diagnosis, and the postprandial is essential for severity assessment, it is recommended to measure both values, rather than use random samplings.

PMID:35373886 | DOI:10.1111/1471-0528.17174

Head Neck. 2022 Apr 4. doi: 10.1002/hed.27033. Online ahead of print.

ABSTRACT

BACKGROUND: To assess the prognostic value of the systemic inflammation response index (SIRI) combined with plasma load of Epstein-Barr virus (EBV) DNA in children and adolescents with locoregionally advanced nasopharyngeal carcinoma (CALANPC).

METHODS: A total of 205 consecutive patients with CALANPC were enrolled. We used recursive partitioning analysis (RPA) to classify patients into various risk groups, with a primary endpoint of overall survival (OS).

RESULTS: Elevated SIRI (≥1.53) and EBV DNA (≥4000 copy/ml) were significantly associated with inferior OS in CALANPC. RPA categorized patients into low- and high-risk groups based on prognostic factors. Survival curves showed excellent discrimination in OS (95.3% vs 77.6%; p < 0.001) between the low- and high-risk groups. A significant improvement was confirmed using the prognostic methods for conventional TNM staging systems (p < 0.05).

CONCLUSIONS: The combination of SIRI with EBV DNA provided a more detailed understanding of patient risks, and enhanced risk discrimination in CALANPC.

PMID:35373866 | DOI:10.1002/hed.27033

Lasers Surg Med. 2022 Apr 4. doi: 10.1002/lsm.23542. Online ahead of print.

ABSTRACT

PURPOSE: High-powered lasers are commonly used for tissue resection in surgeries, including liver resection, medically known as hepatectomy; however, such lasers inevitably induce thermal damage that causes postoperative complications. This study aims to explore the effects of water cooling and different laser output modes on laser-induced thermal damage during hepatectomy.

METHODS: To avoid the influence of superposition, a 980-nm diode laser was used for a single-point hepatectomy. Eighteen Sprague-Dawley rats were used to explore the effects of water cooling and different laser output modes. A constant energy 10-J laser was used to cut the liver tissue with a power of 10 W and time of 1 second. The rats were randomly divided into six groups. The first three groups were assigned as test subjects for different laser output modes. Group 1 was operated with a continuous laser output for a duration of 1 second. Groups 2 and 3 were operated with a pulsed laser output for a duration of 1 second and a pulse width of 0.5 and 0.25 seconds, respectively. Groups 4, 5, and 6 were assigned for the water cooling test. Water cooling was performed based on the parameters of the first three groups. Medical saline (0.9% NaCl) was used for water cooling. The main observation indicators were resection efficiency and thermal damage, including the area of the thermal damage zone. Resection efficiency is calculated by dividing the resection area by the total thermal damage area.

RESULTS: In the three water cooling groups, the area of the resection, carbonized, sub-boiling coagulated, and total thermal damage zones were 0.0677, 0.00, 1.7293, and 2.2982 mm² in Group 4; 0.0465, 0.00, 1.3205, and 1.8414 mm² in Group 5; and 0.0565, 0.00, 1.4301, and 1.9650 mm² in Group 6, respectively. Compared with the first three groups, the water cooling groups exhibited significantly reduced thermal damage areas of in the carbonized, sub-boiling coagulated, and total thermal damage zones (p < 0.001 for all). In addition, there was no statistical difference in the resection area, vacuolated area, and resection efficiency. Furthermore, there was no statistical difference in the area of each thermal damage zone between the continuous and pulsed output groups. The resection efficiencies were 4.82%, 3.34%, 3.73%, 3.93%, 3.36%, and 3.01% in Groups 1 to 6, respectively. Moreover, there was no statistical difference (p > 0.05) in the resection efficiencies.

CONCLUSION: Water cooling can reduce the total laser-induced thermal damage area and prevent tissue carbonization. Therefore, this cooling method can be used as a simple and safe strategy for controlling thermal damage during hepatectomy.

PMID:35373842 | DOI:10.1002/lsm.23542