Corresponding Confidence Intervals Research Articles

Protective efficacy and safety of radiation-attenuated and chemo-attenuated Plasmodium Falciparum sporozoite vaccines against controlled and natural malaria infection: a systematic review and meta-analysis of randomized controlled trials.

Despite the significant burden of Plasmodium falciparum (Pf) malaria and the licensure of two vaccines for use in infants and young children that are partially effective in preventing clinical malaria caused by Pf, a highly effective vaccine against Pf infection is still lacking. Live attenuated vaccines using Pf sporozoites as the immunogen (PfSPZ Vaccines) hold promise for addressing this gap. Here we review the safety and efficacy of two of the most promising PfSPZ approaches: PfSPZ Vaccine (radiation attenuated PfSPZ) and PfSPZ-CVac (chemo-attenuated PfSPZ). We conducted a systematic review and meta-analysis by searching PubMed, EMBASE, SCOPUS, CENTRAL, and WOS until 22nd December 2021. We included randomized controlled trials (RCTs) of these two vaccine approaches that measured protection against parasitaemia following controlled human malaria infection (CHMI) in malaria-naive and malaria-exposed adults or following exposure to naturally transmitted Pf malaria in African adults and children (primary outcome) and that also measured the incidence of solicited and unsolicited adverse events as indicators of safety and tolerability after vaccination (secondary outcome). We included randomized controlled trials (RCTs) that measured the detected parasitaemia after vaccination (primary outcome) and the incidence of various solicited and unsolicited adverse events (secondary outcome). The quality of the included RCTs using the Cochrane ROB 1 tool and the quality of evidence using the GRADE system were evaluated. We pooled dichotomous data using the risk ratio (RR) for development of parasitemia in vaccinees relative to controls as a measure of vaccine efficacy (VE), including the corresponding confidence interval (CI). This study was registered with PROSPERO (CRD42022308057). We included 19 RCTs. Pooled RR favoured PfSPZ Vaccine (RR: 0.65 with 95% CI [0.53, 0.79], P = 0.0001) and PfSPZ-table (RR: 0.42 with 95% CI [0.27, 0.67], P = 0.0002) for preventing parasitaemia, relative to normal saline placebo. Pooled RR showed no difference between PfSPZ Vaccine and the control in the occurrence of any solicited adverse event (RR: 1.00 with 95% CI [0.82, 1.23], P = 0.98), any local solicited adverse events (RR: 0.73 with 95% CI [0.49, 1.08], P = 0.11), any systemic solicited adverse events (RR: 0.94 with 95% CI [0.75, 1.17], P = 0.58), and any unsolicited adverse event (RR: 0.93 with 95% CI [0.78, 1.10], P = 0.37). PfSPZ and PfSPZ-CVacs showed comparable efficacy. Therefore, they can introduce a promising strategy for malaria prophylaxis, but more large-scale field trials are required to sustain efficacy and yield clinically applicable findings.

An evaluation of confidence intervals for a cumulative proportion to enable decisions at interim reviews of single-arm trials

BackgroundClinical trials often include interim analyses of the proportion of participants experiencing an event by a fixed time-point. A pre-specified proportion excluded from a corresponding confidence interval (CI) may lead an independent monitoring committee to recommend stopping the trial. Frequently this cumulative proportion is estimated by the Kaplan-Meier estimator with a Wald approximate CI, which may have coverage issues with small samples. MethodsWe reviewed four alternative CI methods for cumulative proportions (Beta Product Confidence Procedure (BPCP), BPCP Mid P, Rothman-Wilson, Thomas-Grunkemeier) and two CI methods for simple proportions (Clopper-Pearson, Wilson). We conducted a simulation study comparing CI methods across true event proportions for 12 scenarios differentiated by sample sizes and censoring patterns. We re-analyzed interim data from A5340, a HIV cure trial considering the proportion of participants experiencing virologic failure. ResultsOur simulation study highlights the lower and upper tail error probabilities for each CI method. Across scenarios, we found differences in the performance of lower versus upper bounds. No single method is always preferred. The upper bound of a Wald approximate CI performed reasonably with some error inflation, whereas the lower bound of the BPCP Mid P method performed well. For a trial design similar to A5340, we recommend BPCP Mid P. ConclusionsThe design of future single-arm interim analyses of event proportions should consider the most appropriate CI method based on the relevant bound, anticipated sample size and event proportion. Our paper summarizes available methods, demonstrates performance in a simulation study, and includes code for implementation.

Overweight/obesity and dental caries in Brazilian children and adolescents: a systematic review and meta-analysis.

This review aimed to assess the association between overweight/obesity and dental caries in Brazilian children/adolescents. Searches were performed in the Web of Science, Scopus, Cochrane, PubMed, Embase and SciELO, Lilacs and Open Grey literature databases up to June 2022. The Joanna Briggs Institute checklist for analytical cross-sectional studies, the checklist for cohort studies, and the checklist for case-control studies were used. A total of 41 publications were included, and 15 meta-analyses were performed. The authors analyzed the differences in weighted mean difference (MD) and odds ratios (OR), and their corresponding confidence intervals (CI) (95%) for dental caries among eutrophic and obese and/or overweight children/adolescents. Meta-analyses showed that there was no association between overweight and/or obesity and dental caries in Brazilian children/adolescents for most anthropometric reference curves using BMI (Body Mass Index). A greater experience of dental caries was associated with well-nourished adolescents in permanent dentition, compared with obese individuals in the same dentition, as classified by the CDC 2000 curve (OR = 2.53, 95% CI;1.49-4.29; p = 0.0006; I2 = 0%) in dichotomous outcome studies, and (MD = 0.61, 95%CI: 0.08-1.15; p = 0.02; I2 = 0%) in continuous studies. The strength of the evidence of the results was classified as very low, low or moderate. It was concluded that there is no association between overweight and/or obesity and dental caries in Brazilian children/adolescents for most anthropometric reference curves using BMI. A greater experience of dental caries was associated with well-nourished adolescents in permanent dentition, compared with obese individuals in the same dentition, as classified by the CDC 2000 curve.

Effects of Complete Oral Motor Intervention and Nonnutritive Sucking Alone on the Feeding Performance of Premature Infants: A Systematic Review and Meta-Analysis.

We explore the effect of complete oral motor intervention (OMI) and nonnutritive sucking (NNS) alone on oral feeding in preterm infants through a meta-analysis. We searched the Embased, Medline, Cochrane Library, and Web of Science databases for randomized controlled trials up to 8 August 2023, based on established selection criteria. Quality evaluations of the studies were carried out by applying both the Cochrane risk of bias assessment tool and the Jadad scale. The outcome measures of three clinical indicators included transition time to oral feeding, weight gain, and hospitalization duration. We conducted a meta-analysis using a random-effects model to determine the pooled effect sizes, expressed as standardized mean differences (SMDs) and their corresponding confidence intervals (CIs). Additionally, we undertook a subgroup analysis and meta-regression to investigate any potential moderating factors. Eight randomized controlled trials with 419 participants were selected. Meta-analysis revealed that receiving a complete OMI had significantly reduced transition time compared with those receiving NNS alone in preterm newborns (SMD, -1.186; 95% CI, -2.160 to -0.212, p = 0.017). However, complete OMI had no significant effect on shortened hospitalization duration (SMD, -0.394; 95% CI, -0.979 to 0.192, p = 0.188) and increased weight gain (SMD, 0.346; 95% CI, -0.147 to 0.838, p = 0.169) compared with NNS alone. In brief, a complete OMI should not be replaced by NNS alone. However, we were unable to draw decisive conclusions because of the limitations of our meta-analysis. Future well-designed randomized controlled trials are necessary to confirm our conclusion.

Frequentist model averaging for analysis of dose-response in epidemiologic studies with complex exposure uncertainty.

In epidemiologic studies, association estimates of an exposure with disease outcomes are often biased when the uncertainties of exposure are ignored. Consequently, corresponding confidence intervals (CIs) will not have correct coverage. This issue is particularly problematic when exposures must be reconstructed from physical measurements, for example, for environmental or occupational radiation doses that were received by a study population for which radiation doses cannot be measured directly. To incorporate complex uncertainties in reconstructed exposures, the two-dimensional Monte Carlo (2DMC) dose estimation method has been proposed and used in various dose reconstruction efforts. The 2DMC method generates multiple exposure realizations from dosimetry models that incorporate various sources of errors to reflect the uncertainty of the dose distribution as well as the uncertainties in individual doses in the exposed population. Traditional measurement-error model approaches, typically based on using mean doses in the dose-exposure analysis, do not fully account exposure uncertainties. A recently developed statistical approach that overcomes many of these limitations by analyzing multiple exposure realizations in relation to disease risk is Bayesian model averaging (BMA). The analytic advantage of the BMA is its ability to better accommodate complex exposure uncertainty in the risk estimation, but a practical. Drawback is its significant computational complexity. In this present paper, we propose a novel frequentist model averaging (FMA) approach which has all the analytical advantages of the BMA method but is much simpler to implement and computationally faster. We show in simulations that, like BMA, FMA yields 95% confidence intervals for association parameters that close to 95% coverage rate. In simulations, the FMA has shorter length of CIs than those of another frequentist approach, the corrected information matrix (CIM) method. We illustrate the similarities in performance of BMA and FMA from a study of exposures from radioactive fallout in Kazakhstan.

Effect size and inferential statistical techniques coupled with machine learning for assessing the association between prolactin concentration and metabolic homeostasis

Background and objectiveRecent guidelines classify low prolactin levels as low as <7 ng/mL and high levels as >25 ng/mL, while the “Homeostatically Functionally Increased Transient Prolactinemia” (HomeoFIT-PRL) range (25–100 ng/mL) suggests that a temporary increase in prolactin could be metabolically beneficial if no related health issues are present. The aim of this study was to investigate the association between mean prolactin concentrations and disturbances in glycidic and lipidic metabolism and to identify the gray zone associated with prolactin inflection points that correlate with these metabolic changes. MethodsThis cross-sectional study involved 65,795 adults who underwent HOMA-IR, glucose, insulin, total cholesterol, HDL-c, LDL-c, and triglyceride tests. Data was categorized into 106 partitions based on prolactin results. Employing an approach referred to in this study as “Hierarchical Multicriteria Analysis of Differences Between Groups - Statistical and Effect Size Approach” (HiMADiG-SESA) comparing the mean concentrations of metabolic tests across prolactin ranges. A machine learning model was utilized to determine inflection points and their corresponding confidence intervals (CIs). These CIs helped establish gray zones in mean prolactin results related to metabolic changes. ResultsStatistically and clinically, metabolic test means differed for prolactin <7 ng/mL, except insulin. In the HomeoFIT-PRL range, means were lower except for HDL-c. The gray zones of the mean prolactin results associated with changes in glycidic and lipidic metabolism were 9.58–12.87 ng/mL and 13.81–18.73 ng/mL, respectively. ConclusionA strong correlation was identified between mean prolactin concentrations and the results of metabolism tests below the gray zones associated with inflection points, indicating the potential role of prolactin in the appearance of metabolic disorders. Mean prolactin results can provide deeper insight into metabolic balance.

Intended delivery mode and neonatal outcomes in pregnancies with fetal growth restriction

Objective: To compare neonatal outcomes in pregnancies with fetal growth restriction (FGR) by intended delivery mode. Methods: This is a retrospective cohort study of singleton pregnancies with FGR that were delivered ≥34.0 weeks gestation. Neonatal outcomes were compared according to the intended delivery mode, which the attending obstetrician determined. Of note, none of the subjects had a contraindication to labor. Crude and adjusted odds ratios (ORs) and corresponding confidence intervals (CIs) were calculated via logistic regression models to assess the potential association between intended delivery mode and neonatal morbidity defined as a composite outcome (i.e. umbilical artery pH ≤7.1, 5-min Apgar score ≤7, admission to the neonatal intensive care unit, hypoglycemia, intrapartum fetal distress requiring expedited delivery, and perinatal death). A sensitivity analysis excluded intrapartum fetal distress requiring emergency cesarean delivery from the composite outcome since only patients with spontaneous labor or labor induction could meet this criterion. Potential confounders in the adjusted effects models included maternal age, body mass index, hypertensive disorders, diabetes, FGR type (i.e. early or late), and oligohydramnios. Results: Seventy-two (34%) patients had an elective cesarean delivery, 73 (34%) had spontaneous labor and were expected to deliver vaginally, and 67 (32%) underwent labor induction. The composite outcome was observed in 65.3%, 89%, and 88.1% of the groups mentioned above, respectively (p < 0.001). Among patients with spontaneous labor and those scheduled for labor induction, 63% and 47.8% required an emergency cesarean delivery for intrapartum fetal distress. Compared to elective cesarean delivery, spontaneous labor (OR 4.32 [95% CI 1.79, 10.42], p = 0.001; aOR 4.85 [95% CI 1.85, 12.66], p = 0.001), and labor induction (OR 3.92 [95% CI 1.62, 9.49] p = 0.002; aOR 5.29 [95% CI 2.01, 13.87], p = 0.001) had higher odds of adverse neonatal outcomes. Conclusion: In this cohort of FGR, delivering at ≥34 weeks of gestation, pregnancies with spontaneous labor, and those that underwent labor induction had higher odds of neonatal morbidity than elective cesarean delivery.

Is Thyroid Dysfunction Associated with Unruptured Intracranial Aneurysms? A Population-Based, Nested Case-Control Study from Korea.

Background: Few risk factors for the development of intracranial aneurysms (IAs) are known. We investigated the potential role of thyroid diseases in IA development using nationwide real-world data. Methods: A nested case-control study within the National Health Insurance Service-National Sample Cohort data from 2002 to 2019 was performed. A total of 5335 patients with unruptured IA were matched by age and sex with 80,025 controls at a ratio of 1:15. We estimated the odds ratios (ORs) and corresponding confidence intervals [CIs] between thyroid diseases and unruptured IA using a multivariable conditional logistic regression model. Results: Tobacco smoking, use of antihypertensive medication, and hypothyroidism were significantly associated with an elevated risk for unruptured IA in univariate analysis. In multivariable analysis, a history of hypothyroidism was associated with unruptured IA (adjusted OR: 1.46 [CI: 1.26-1.69]). Among patients with hypothyroidism, long-term use of thyroid hormone for >5 years was associated with a reduced risk for unruptured IA (adjusted OR: 0.69 [CI: 0.48-0.99]). A history of hyperthyroidism was associated with a reduced risk for unruptured IAs (adjusted OR: 0.71 [CI: 0.54-0.93]). In secondary analyses of the data according to sex, the respective observed associations between hypothyroidism and hyperthyroidism and the risk of IAs were found to be statistically significant in females but not in males. Conclusions: Hypothyroidism is associated with an increased risk of unruptured IAs, whereas hyperthyroidism is associated with a reduced risk. Overall, the findings suggest that thyroid hormones may play a protective role in the development of unruptured IAs. Further studies are needed to clarify potential direct causality and the biologic mechanisms relating thyroid dysfunction and unruptured IA.

Abstract 13435: The Efficacy and Safety of Botulinum Toxin Type A to Prevent Postoperative Atrial Fibrillation in Patients Undergoing Cardiac Surgery: A Meta-Analysis of Randomized Controlled Trials

Background: Postoperative atrial fibrillation (POAF) is prevalent in about 30 to 60 percent of patients undergoing cardiac surgery leading to worse outcomes. However, effective POAF therapies are lacking. Botulinum toxin type A (BTX) epicardial injection can prevent POAF by impairing cholinergic signaling. Methods: We conducted a systematic review and meta-analysis synthesizing randomized controlled trials (RCTs), which were retrieved by systematically searching: PubMed, EMBASE, Web of Science, SCOPUS, and Cochrane through November 23 rd , 2022. RevMan version 5.4 software was used to pool dichotomous outcomes using risk ratio (RR) and continuous outcomes using mean difference (MD) presented with the corresponding confidence interval (CI). Results: Three RCTs with a total of 509 patients (308 in the BTX group and 205 in the placebo group) were included in our analysis. Two RCTs included patients undergoing open-chest cardiac surgery, including coronary artery bypass graft (CABG) and/ or valve surgery, while one RCT included patients undergoing CABG only. There was no difference between BTX and placebo regarding POAF incidence (RR: 0.81 with 95% CI [0.65, 1.00], P= 0.05), postoperative hospital length of stay in days (MD: -0.03 with 95% CI [-0.54, 0.49], P= 0.91), all-cause mortality, (RR: 1.64 with 95% CI [0.22, 12.17], P= 0.63), any adverse event (RR: 1.03 with 95% CI [0.94, 1.12], P= 0.51), and any serious adverse event (RR: 0.89 with 95% CI [0.68, 1.15], P= 0.36). Conclusion: There was no difference between epicardial fat injection of BTX versus placebo for preventing POAF; however, BTX showed a similar safety profile compared to placebo and our analysis can be underpowered to detect a significant effect. Hence, further large-scale RCTs are warranted to investigate BTX for POAF, especially in high-risk cohorts.

Effects of curcumin/turmeric supplementation on the liver enzymes, lipid profiles, glycemic index, and anthropometric indices in non-alcoholic fatty liver patients: An umbrella meta-analysis.

Non-alcoholic fatty liver disease (NAFLD) is one of the leading causes of chronic liver disease worldwide. The evidence for curcumin's effects on patients with NAFLD is accumulating; however, meta-analyses have reported mixed results. The current umbrella meta-analysis aimed to assess the present evidence and provide an accurate estimate of the overall effects of curcumin/turmeric on NAFLD patients. The Web of Science, Scopus, PubMed, ScienceDirect, and Google Scholar databases were searched till March 2023 using MeSH terms and related keywords based on the PICO criteria. Meta-analysis studies evaluating the effects of curcumin/turmeric supplementation on NAFLD patients that reported the effect sizes (ES) and corresponding confidence intervals (CI) were eligible for inclusion in this study. All articles were screened by considering the eligibility criteria by two independent reviewers and required data were extracted from the included meta-analyses. The meta-analysis was performed utilizing a random-effects model by STATA software. Findings of 11 meta-analyses of 99 randomized controlled trials comprising 5546 participants revealed that curcumin/turmeric supplementation reduced AST (ES = -1.072, 95% CI (-1.656, -0.488), p = 0.000), ALT (ES = -0.625, 95% CI (-1.170, -0.134), p = 0.014), and TG (ES = -0.469, 95% CI (-1.057, 0.119), p = 0.128) levels, and HOMA-IR (ES = -0.291, 95% CI (-0.368, -0.214), p = 0.000), BMI (ES = -0.205, 95% CI (-0.304, -0.107), p = 0.000), and WC (ES = -1.290, 95% CI (-2.038, -0.541), p = 0.001) in comparison to the control group. However, the effects of curcumin on GGT, ALP, TC, LDL-C, HDL-C, FBS, and HbA1C levels and body weight were not significant. The findings suggest the beneficial effects of curcumin/turmeric supplementation in patients with NAFLD, such as improving liver function, decreasing serum TG levels, ameliorating insulin resistance, and reducing general and central obesity. Nevertheless, high-quality research is further required to prove these achievements.

Utilization of high-cost prostate cancer therapies by oncologists in the merit-based incentive payment system (MIPS).

73 Background: TheMerit-Based Incentive Payment System (MIPS) is currently the only federally mandated value-based payment model for oncologists. MIPS uses cost and quality metrics to assign oncologists an overall MIPS score, where higher scores correspond to greater payments for practices. The extent to which MIPS delineates between oncologists administering high-cost anti-cancer therapeutics with unproven benefit is unknown. In this study, we investigated administration of low-value prostate cancer therapies by differently scored oncologists. Methods: We identified MIPS scores for oncologists using publicly available data for the year 2019. We cross referenced these scores with the 20% restricted sample of Medicare fee-for-service claims for 2019 using provider National Provider Identifications (NPIs). We then identified patients who were treated by these oncologists for prostate cancer using ICD-10 diagnosis codes for prostate cancer. Use of Sipuleucel-T (Provenge) and Radium Ra 223 dichloride (Xofigo), two low-value treatments with unproven benefit in prostate cancer, was identified using HCPCS codes in the claims file. The top 25 and bottom 25 percentile of oncologists based on their MIPS scores were identified using summary statistics. Odds ratios (OR) and corresponding confidence intervals (CI) were generated for Sipuleucel-T and Radium Ra 223 dichloride use by top 25 and bottom 25 percentile MIPS scores. Results: We identified 533,966 claims for prostate cancer treated by oncologists with a MIPS score in 2019. Of these claims, there were 100 instances of Sipuleucel-T use and 308 instances of Radium Ra 223 dichloride use (500 instances of Sipuleucel-T and 1540 instances of Radium Ra 223 dichloride if scaled to national use). Oncologists in the lowest 25% of MIPS scores less likely administered Sipuleucel-T (OR 0.25, 95% CI 0.12, 0.54) while those in the highest 25% did not show a significant trend (OR 1.36, 95% CI 0.90, 2.07). Oncologists in the lowest 25% of MIPS scores more likely administered Radium Ra 223 dichloride (OR 1.53, 95% CI 1.21, 1.95) while those in the highest 25% less likely administered the drug (OR 0.66, 95% CI 0.49, 0.88). Conclusions: Low MIPS scoring oncologists were less likely to utilize Sipuleucel-T and more likely to use Radium Ra 223 dichloride to treat prostate cancer. Our findings suggest that the MIPS program may be ineffective at measuring and incentivizing high value care among oncologists. Specialty-specific recalibration of cost and quality measures is needed to ensure that policy efforts to promote value-based care do not compromise healthcare quality and outcomes. [Table: see text]

Different computed tomography parameters for defining myosteatosis in patients with advanced non-small cell lung cancer

Myosteatosis, excess muscle fat infiltration, is a novel prognostic factor in cancer patients. To define myosteatosis, skeletal muscle radiodensity (SMD) is most commonly used, while intramuscular adipose tissue (IMAT) is newly introduced. We aimed to compare SMD-defined and IMAT-defined myosteatosis for predicting overall survival (OS) in patients with advanced non-small cell lung cancer (NSCLC) and to explore whether patients with both low SMD and high IMAT had a shorter OS than patients with low SMD or high IMAT alone. We consecutively and prospectively recruited adult patients with stage IIIB or IV NSCLC at a teaching hospital. The mean SMD of all skeletal muscle areas and the area of IMAT on the unenhanced chest computed tomography (CT) images at the 12th thoracic vertebral level were segmented using Mimics version 21.0. Myosteatosis was defined by either low SMD (SMD-defined myosteatosis) or high IMAT (IMAT-defined myosteatosis). The optimal cutoffs for low SMD and high IMAT were also determined using the maximally selected rank statistics method. We calculated hazard ratios (HRs) and the corresponding confidence intervals (CIs) to evaluate the associations of OS with low SMD, high IMAT, and a combination of them. We included 565 patients (345 men and 220 women; mean age 58.5±9.0 years). Lower IMAT exhibited a tendency toward a favorable prognosis in men (p=0.0015) and women (p<0.0001); whereas higher SMD tended to have a favorable prognosis in men (p=0.0006) and women (p<0.0001). At baseline, 423 (74.9%) participants had high IMAT, 432 (76.5%) participants had low SMD and 370 (65.5%) participants had both high IMAT and low SMD. Compared to those without either high IMAT or low SMD, the participants with either high IMAT or low SMD had a shorter OS, while the participants with both High IMAT and Low SMD had the shortest OS (log-rank p<0.0001). After adjustment for the same confounders, high IMAT (HR, 1.44; 95% CI, 1.10-1.87) and low SMD (HR, 1.92; 95% CI, 1.36-2.43) were separately associated with poor prognosis. Moreover, the combination of high IMAT and low SMD indicated a higher risk of poor prognosis (HR, 2.43; 95% CI, 1.62-3.66). Both SMD-defined and IMAT-defined myosteatosis are highly prevalent in patients with advanced NSCLC and may serve as independent prognostic factors for OS. The diagnosis of myosteatosis might consider a combination of low SMD and high IMAT because this would help identify patients at a higher risk of mortality.

Positional error compensation for aviation drilling robot based on Bayesian linear regression

The quality of aircraft components is directly affected by the positional accuracy of aviation drilling robot, which may further affect the assembly accuracy, flight performance and service life of aircraft. In this work, positional error compensation based on Bayesian linear regression (BLR) is proposed to improve the positional accuracy of aviation drilling robot. Firstly, the stochastic model of robot positional error is constructed by utilizing kinematic error model involving with random uncertainties. It proves that the positional error of robot joint space follows the Gaussian process (GP) and can be modeled through a linear regression model. Secondly, BLR is utilized to construct the positional error model of aviation drilling robot, which can provide the predicted positional error and the corresponding confidence interval (CI) of target position. These predicted values and CIs are used to realize error compensation. Experimental results show that, after error compensation, the average/maximum absolute positional error of the self-developed aviation drilling robot is decreased from 1.393mm/1.795 mm–0.081mm/0.167 mm. This indicates that the BLR-based positional error compensation is conductive to ameliorating the positional accuracy of aviation drilling robot. This study lays the foundation for the positional error compensation of industrial robots in aircraft assembly.

Abdominal circumference growth velocity as a predictor of adverse perinatal outcomes in small-for-gestational-age fetuses

Objective To assess the predictive value of abdominal circumference growth velocity (ACGV) between the second and third trimesters to predict adverse perinatal outcomes in a cohort of small-for-gestational-age fetuses without evidence of placental insufficiency (i.e. fetal growth restriction). Material and methods This is a single-center retrospective cohort study of all singleton pregnancies with small-for-gestational-age fetuses diagnosed and delivered at a quaternary institution. Crude and adjusted odds ratios (ORs) and corresponding confidence intervals (CIs) were calculated via logistic regression models to assess the potential association between abnormal ACGV (i.e. ≤10th centile) and adverse perinatal outcomes defined as a composite outcome (i.e. umbilical artery pH <7.1, 5-min Apgar score <7, admission to the neonatal intensive care unit, hypoglycemia, intrapartum fetal distress requiring expedited delivery, and perinatal death). Furthermore, the area under the receiver-operating characteristic curve (AUC) of three logistic regression models based on estimated fetal weight and ACGV for predicting the composite outcome is also reported. Results A total of 154 pregnancies were included for analysis. The median birthweight for the cohort was 2,437 g (interquartile range [IQR] 2280, 2635). Overall, the primary composite outcome was relatively common (29.2%). In addition, there was a significant association between abnormal ACGV and adverse perinatal outcomes (OR 3.37, 95% CI 1.60, 7.13; adjusted OR 4.30, 95% CI 1.77, 10.49). Likewise, the AUC for the ACGV was marginally higher (0.64) than the estimated fetal weight (0.54) and ACGV + estimated fetal weight (0.54). Still, no significant difference was detected between the curves (p = 0.297). Conclusions Our results suggest that an ACGV below the 10th centile is a risk factor for adverse perinatal outcomes among small-for-gestational-age fetuses.

The role of probiotic supplementation in inflammatory biomarkers in adults: an umbrella meta-analysis of randomized controlled trials.

Despite the increasing evidence for probiotics' anti-inflammatory effects, the results of meta-analyses remain inconsistent. The present umbrella meta-analysis aimed to investigate the effects of probiotic supplementation on inflammatory biomarkers. We performed a wide-ranging systematic search in several databases, including PubMed, Web of Science, Scopus, EMBASE, and Google Scholar up to April 2023. The overall effect sizes were calculated using effect size (ES) values and their corresponding confidence intervals (CI). Out of a total of 580 related articles, 39 studies were qualified for inclusion in the analysis. The results of the analysis revealed a significant reduction of C-reactive protein (CRP) (ES = -1.02; 95% CI: -1.23, -0.80, p < 0.001; I2: 94.1%, p < 0.001), TNF-α (ES = -0.35; 95% CI: -0.50, -0.20, p < 0.001; I2: 75.6%, p < 0.001), and interleukin-6 (IL-6) levels (ES = -0.36; 95% CI: -0.59, -0.13, p = 0.002; I2: 85.6%, p < 0.001), following probiotic supplementation. Probiotic supplementation significantly reduced serum concentrations of TNF-a, CRP, and IL-6. Thus, probiotic supplementation can be considered adjuvant therapy to alleviate inflammation in various inflammatory conditions.

Endoscopic Versus Conservative Therapy for Bleeding Peptic Ulcer with Adherent Clot: A Comprehensive Systematic Review and Meta-Analysis.

Peptic ulcers with adherent clots are associated with a high-risk of rebleeding and mortality. However, the optimal management of bleeding ulcers with adherent clots remains unclear. We conducted this systematic review and meta-analysis to compare endoscopic therapy and conservative therapy to manage bleeding ulcers with adherent clots. We systematically searched PubMed, Embase, and Web of Science databases through October 2022 to include all studies comparing the endoscopic and conservative therapeutic approaches for bleeding ulcers with adherent clots. Our primary outcome was rebleeding (overall and 30-day). The secondary outcomes were mortality (overall and 30-day), need for surgery, and length of hospital stay (LOS). The random-effects model was used to calculate the pooled odds ratios (OR) and mean differences (MD) with the corresponding confidence intervals (CI) for proportional and continuous variables, respectively. Eleven studies (9 RCTs) with 833 patients (431 received endoscopic therapy vs. 402 received conservative therapy) were included. Overall, endoscopic therapy was associated with lower overall rebleeding (OR 0.41, 95% CI 0.22-0.79, P = 0.007), 30-day rebleeding (OR 0.43, 95% CI 0.21-0.89, P = 0.002), overall mortality (OR 0.47, 95% CI 0.23-0.95, P = 0.04), 30-day mortality (OR 0.43, 95% CI 0.21-0.89, P = 0.002), need for surgery (OR 0.44, 95% CI 0.21-0.95, P = 0.04), and LOS (MD - 3.17 days, 95% CI - 4.14, - 2.19, P < 0.00001). However, subgroup analysis of randomized controlled trials (RCTs) showed no significant difference in overall mortality (OR 0.78, 95% CI 0.24-2.52, P = 0.68) between the two strategies, with numerically lower but statistically non-significant rates of overall rebleeding (7.2% vs. 18.5%, respectively; OR 0.42, 95% CI 0.17-1.05, P = 0.06), statistically lower rate of need for surgery (OR 0.28, 95% CI 0.08-0.96, P = 0.04) with endoscopic therapy compared to conservative therapy. Our meta-analysis demonstrates that endoscopic therapy was overall associated with lower rates of rebleeding (overall and 30-day), mortality (overall and 30-day), need for surgery, and LOS, compared to conservative therapy for the management of bleeding ulcers with adherent clots. However, subgroup analysis of RCTs showed that endoscopic therapy was associated with numerically lower but statistically non-significant rates of overall rebleeding and a statistically lower rate of need for surgery compared to conservative therapy with similar overall mortality rates. Combined treatment with thermal therapy and injection therapy was the most effective treatment modality in reducing rebleeding risk. Further large-scale RCTs are needed to validate our findings.

Associations between diet quality and migraine headaches: a cross-sectional study

ABSTRACT Aims We evaluated associations between diet quality and migraine outcomes. Methods The current work represented a cross-sectional study on 262 patients with migraine (20–50 y). Diet quality was assessed using the standard healthy eating index 2015 (HEI-2015) and alternative healthy eating index 2010 (AHEI-2010). A validated 168-item food frequency questionnaire was used to assess dietary intake. Migraine outcomes included clinical factors (severity, duration, frequency, and disability related to migraine) and serum nitric oxide (NO). Associations between diet quality indices and migraine outcomes were evaluated using linear regressions, and β and 95% corresponding confidence interval (CI) were reported. Results HEI-2015 was inversely associated with migraine frequency (β = −4.75, 95% CI: −6.73, −2.76) in patients with the highest HEI scores (third tertile) vs. those with the lowest scores (first tertile) after adjusting for relevant confounders. AHEI-2010 was inversely associated with migraine frequency (β = −3.67, 95% CI: −5.65, −1.69) and migraine-related disability (β = −2.74, 95% CI: −4.79, −0.68) in adjusted models. Also, AHEI-2010 was inversely associated with migraine severity in patients in the second vs. first tertile (β = −0.56; 95% CI: −1.08, −0.05). We detected no associations between diet quality and NO levels (All P > 0.14). Conclusions Improved diet quality may be associated with favorable migraine outcomes (lower headache frequency, severity, and migraine-related disability). Future studies are required to confirm and delineate the causal mechanisms of our observations.

Poly(adenosine diphosphate-ribose) polymerase inhibitor combinations in first-line metastatic castrate-resistant prostate cancer setting: a systematic review and meta-analysis.

To compare radiographic progression-free survival (rPFS), overall survival (OS), and treatment-emergent adverse events (TEAEs) among patients with metastatic castrate-resistant prostate cancer (mCRPC) receiving a combination of first-line poly(adenosine diphosphate-ribose) polymerase inhibitors (PARPi) plus androgen receptor axis-targeted agents (ARAT) vs placebo/ARAT. We conducted a systematic review/meta-analysis of all published Phase III randomised controlled trials using EMBASE, MEDLINE, and Cochrane (inception until 6 June 2023). Published full-text manuscripts and conference abstracts were inclusion eligible. Study selection/data extraction were independently performed by two authors. The Cochrane Risk-of-Bias 2 Tool was used, and certainty of evidence assessed using the Grading of Recommendations, Assessment, Development, and Evaluations framework. Pooled hazard ratios (HRs) and relative risks, with corresponding confidence intervals (CIs), were generated using random-effects models. Three trials were identified: PROpel, MAGNITUDE, and TALAPRO-2. Compared to placebo/ARAT, the PARPi/ARAT combination was associated with a 35% rPFS improvement in the overall cohort (HR 0.65, 95% CI 0.56-0.76), with 68%, 45%, and 26% improvements in the BReast CAncer gene 1/gene 2 (BRCA1/2)-mutated (BRCA1/2m; P < 0.001), homologous recombination repair-mutated (HRRm; P < 0.001), and non-HRRm cohorts (P = 0.003), respectively. OS data maturity ranged from 31% to 48%, with overall cohort OS data unavailable from MAGNITUDE. The PROpel/TALAPRO-2 pooled analysis demonstrated a 16% OS improvement in the overall cohort (HR 0.84, 95 CI 0.72-0.98; P = 0.02). OS in the HRRm (HR 0.76, 95% CI 0.61-0.95) and the BRCA1/2m cohorts (HR 0.53, 95% CI 0.18-1.56) were improved, with a higher effect magnitude compared to the overall cohort. This combination was associated with a 45% relative risk increase in Grade ≥3 TEAEs, including 6.22-fold for Grade ≥3 anaemia (31.9% vs 4.9%). The addition of PARPi to ARAT in the first-line mCRPC setting is associated with rPFS benefits across subgroups, with the greatest magnitude of benefit in BRCA1/2m patients. OS benefits remain inconsistent irrespective of HRRm status, with significant increases in Grade ≥3 TEAEs, particularly anaemia. Currently, we suggest this combined approach be selectively offered to HRRm patients, preferentially BRCA1/2m.

Defibrillation strategies for refractory ventricular fibrillation out-of-hospital cardiac arrest: A systematic review and network meta-analysis.

Double sequential external defibrillation (DSED) and vector-change defibrillation (VCD) have been suggested to enhance clinical outcomes for patients with ventricular fibrillation (VF) refractory of standard defibrillation (SD). Therefore, this network meta-analysis aims to evaluate the comparative efficacy of DSED, VCD, and SD for refractory VF. A systematic review and network meta-analysis synthesizing randomized controlled trials (RCTs) and comparative observational studies retrieved from PubMed, EMBASE, WOS, SCOPUS, and Cochrane through November 15th, 2022. R software netmeta and netrank package (R version 4.2.0) and meta-insight software were used to pool dichotomous outcomes using odds ratio (OR) presented with the corresponding confidence interval (CI). Our protocol was prospectively published in PROSPERO with ID: CRD42022378533. We included seven studies with a total of 1632 participants. DSED was similar to SD in survival to hospital discharge (OR: 1.14 with 95% CI [0.55, 2.83]), favorable neurological outcome (modified Rankin scale ≤2 or cerebral performance category ≤2) (OR: 1.35 with 95% CI [0.46, 3.99]), and return of spontaneous circulation (ROSC) (OR: 0.81 with 95% CI [0.43; 1.5]). In addition, VCD was similar to SD in survival to hospital discharge (OR: 1.12 with 95% CI [0.27, 4.57]), favorable neurological outcome (OR: 1.01 with 95% CI [0.18, 5.75]), and ROSC (OR: 0.88 with 95% CI [0.24; 3.15]). Double sequential external defibrillation and VCD were not associated with enhanced outcomes in patients with refractory VF out-of-hospital cardiac arrest, compared to SD. However, the current evidence is still inconclusive, warranting further large-scale RCTs.

The Geras virtual frailty rehabilitation program to build resilience in older adults with frailty during COVID-19: a randomized feasibility trial

BackgroundThe Coronavirus (COVID-19) pandemic has exacerbated the risk for poor physical and mental health outcomes among vulnerable older adults. Multicomponent interventions could potentially prevent or reduce the risk of becoming frail; however, there is limited evidence about utilizing alternative modes of delivery where access to in-person care may be challenging. This randomized feasibility trial aimed to understand how a multicomponent rehabilitation program can be delivered remotely to vulnerable older adults with frailty during the pandemic.MethodsParticipants were randomized to either a multimodal or socialization arm. Over a 12-week intervention period, the multimodal group received virtual care at home, which included twice-weekly exercise in small group physiotherapy-led live-streamed sessions, nutrition counselling and protein supplementation, medication consultation via a videoconference app, and once-weekly phone calls from student volunteers, while the socialization group received only once-weekly phone calls from the volunteers. The RE-AIM (Reach, Effectiveness, Adoption, Implementation and Maintenance) framework was used to evaluate the feasibility of the program. The main clinical outcomes were change in the 5-times sit-to-stand test (5 × STS) and Depression, Anxiety and Stress Scale (DASS-21) scores. The feasibility outcomes were analyzed using descriptive statistics and expressed as frequencies and mean percent with corresponding confidence intervals (CI). Analysis of covariance (ANCOVA) was used for the effectiveness component.ResultsThe program enrolled 33% (n = 72) of referrals to the study (n = 220), of whom 70 were randomized. Adoption rates from different referral sources were community self-referrals (60%), community organizations (33%), and healthcare providers (25%). At the provider level, implementation rates varied from 75 to 100% for different aspects of program delivery. Participant’s adherence levels included virtual exercise sessions 81% (95% CI: 75–88%), home-based exercise 50% (95% CI: 38–62%), protein supplements consumption 68% (95% CI: 55–80%), and medication optimization 38% (95% CI: 21–59%). Most participants (85%) were satisfied with the program. There were no significant changes in clinical outcomes between the two arms.ConclusionThe GERAS virtual frailty rehabilitation study for community-dwelling older adults living with frailty was feasible in terms of reach of participants, adoption across referral settings, adherence to implementation, and participant’s intention to maintain the program. This program could be feasibly delivered to improve access to socially isolated older adults where barriers to in-person participation exist. However, trials with larger samples and longer follow-up are required to demonstrate effectiveness and sustained behavior change.Trial registrationClinicalTrials.gov NCT04500366. Registered August 5, 2020, https://clinicaltrials.gov/ct2/show/NCT04500366