Tag: statistics

BJU Int. 2023 Jan 29. doi: 10.1111/bju.15981. Online ahead of print.

ABSTRACT

OBJECTIVES: To synthesize available data regarding the disease-free survival (DFS) benefit of adjuvant immune checkpoint inhibitors (ICIs) for patients with RCC and evaluate the overall safety profile of ICIs in this setting.

MATERIALS AND METHODS: We utilized PubMed, Embase, and relevant conference proceedings to identify phase III randomized controlled trials comparing adjuvant ICI versus placebo/observation for RCC. The primary outcome of interest was DFS. Variables for subgroup analyses were program death-ligand 1 (PD-L1) expression, sarcomatoid features, nephrectomy type, and disease-risk category. Secondary outcomes included grade ≥ 3 adverse events (AEs), immune-related AEs, and treatment discontinuation due to AEs. All outcomes were analyzed using random-effects models owing to inter-study heterogeneity.

RESULTS: Among the four included studies, one demonstrated a significant DFS benefit. There was considerable clinical and statistical heterogeneity (I² =64%) due to differences in inclusion criteria and interventions. While pooled results across the four studies did not demonstrate a significant benefit in DFS overall (HR 0.85, 95% CI 0.69-1.04), there was significant benefit among patients with positive PD-L1 expression (HR 0.72, 95% CI 0.55-0.94) and sarcomatoid features (HR 0.59, 95% CI 0.38-0.91).

CONCLUSION: The evidence base to date regarding ICI as adjuvant therapy in RCC is mixed – conclusions are limited by considerable heterogeneity between studies. However, pooled analyses suggest that patients with positive PD-L1 expression or sarcomatoid features are most likely to benefit from adjuvant immunotherapy.

PMID:36709462 | DOI:10.1111/bju.15981

J Biomol Struct Dyn. 2023 Jan 29:1-19. doi: 10.1080/07391102.2023.2171131. Online ahead of print.

ABSTRACT

Dengue hemorrhagic fever (DHF) is severe dengue with a hallmark of vascular leakage. β-tryptase has been found to promote vascular leakage in DHF patients, which could be a potential target for DHF treatment. This study aims to develop a theoretical background for designing and selecting human β-tryptase inhibitors through computational studies. Thirty-four α-keto-[1,2,3]-oxadiazoles scaffold-based compounds were used to generate 2D-QSAR models and for molecular docking studies with β-tryptase (PDB Code 4A6L). In addition, molecular dynamics (MD) simulation and molecular mechanics generalised born surface area (MM-GBSA) analysis on the binding of the reported most active compound, compound 11e, towards β-tryptase were performed. Finally, a structure-based pharmacophore model was generated. The selected 2D-QSAR models have statistically proven good models by internal and external validation as well as the y-randomization test. The docking results of compound 11e showed lower CDOCKER energy than the 4A6L co-crystallised ligand and a similar binding pattern as the 4A6L co-crystallised ligand. From molecular dynamics simulation, 4A6L in compound 11e bound state has RMSD below 2 Å throughout the 500 ns simulation, indicating the docked complex is stable. Besides, MM-GBSA analysis suggested the 4A6L-compound 11e docked complex (-66.04 Kcal/mol) is structurally as stable as the 4A6L-native ligand co-crystallized structure (-66.84 Kcal/mol). The best pharmacophore model identified features included hydrogen bond acceptor, ionic interaction, hydrophobic interaction, and aromatic ring, which contribute to the inhibitory potency of a compound. This study supplied insight and knowledge for developing novel chemical compounds with improved inhibition of β-tryptase.Communicated by Ramaswamy H. Sarma.

PMID:36709457 | DOI:10.1080/07391102.2023.2171131

Epidemiology. 2023 Jan 30. doi: 10.1097/EDE.0000000000001596. Online ahead of print.

ABSTRACT

BACKGROUND: Instrumental variables (IVs) can be used to provide evidence as to whether a treatment X has a causal effect on an outcome Y. Even if the instrument Z satisfies the three core IV assumptions of relevance, independence, and the exclusion restriction, further assumptions are required to identify the average causal effect (ACE) of X on Y. Sufficient assumptions for this include: homogeneity in the causal effect of X on Y; homogeneity in the association of Z with X; and no effect modification.

METHODS: We describe the no simultaneous heterogeneity assumption, which requires the heterogeneity in the X-Y causal effect to be mean independent of (i.e., uncorrelated with) both Z and heterogeneity in the Z-X association. This happens, for example, if there are no common modifiers of the X-Y effect and the Z-X association, and the X-Y effect is additive linear. We illustrate the assumption of no simultaneous heterogeneity using simulations and by re-examining selected published studies.

RESULTS: Under no simultaneous heterogeneity, the Wald estimand equals the ACE even if both homogeneity assumptions and no effect modification (which we demonstrate to be special cases of – and therefore stronger than – no simultaneous heterogeneity) are violated.

CONCLUSIONS: The assumption of no simultaneous heterogeneity is sufficient for identifying the ACE using IVs. Since this assumption is weaker than existing assumptions for ACE identification, doing so may be more plausible than previously anticipated.

PMID:36709456 | DOI:10.1097/EDE.0000000000001596

Braz J Psychiatry. 2022 Sep 30;44(6):644-649. doi: 10.47626/1516-4446-2022-2601.

ABSTRACT

OBJECTIVE: Multimorbidity, or the occurrence of two or more chronic conditions, is a global challenge, with implications for mortality, morbidity, disability, and life quality. Psychiatric disorders are common among the chronic diseases that affect patients with multimorbidity. It is still not well understood whether psychiatric symptoms, especially depressive symptoms, moderate the effect of multimorbidity on cognition.

METHODS: We used a large (n=2,681) dataset to assess whether depressive symptomatology moderates the effect of multimorbidity on cognition using structural equation modelling.

RESULTS: It was found that the more depressive symptoms and chronic conditions, the worse the cognitive performance, and the higher the educational level, the better the cognitive performance. We found a significant but weak (0.009; p = 0.04) moderating effect.

CONCLUSION: We have provided the first estimate of the moderating effect of depression on the relation between multimorbidity and cognition, which was small. Although this moderation has been implied by many previous studies, it was never previously estimated.

PMID:36709433 | DOI:10.47626/1516-4446-2022-2601

Andrology. 2023 Jan 28. doi: 10.1111/andr.13396. Online ahead of print.

ABSTRACT

BACKGROUND: Since the 1970s, several studies found that sperm concentration (SC) and total sperm count (TSC) constantly worsened over time, mainly in high-income countries.

OBJECTIVES: To evaluate whether the decreasing trend in sperm count is continuing in Western European countries and USA, we performed a systematic review and meta-regression analysis.

MATERIALS AND METHODS: Embase and Pubmed/Medline were searched for papers published in English in the 2000-2020 period limiting the search to data collected in the USA and in Western European countries.

RESULTS: We identified 62 articles and pooled information on 24,196 men (range 10-2,523), collected from 1993 to 2018. Considering all the studies, random-effects meta-regression analyses showed no significant trend for SC (slope per year -0.07 mil/mL, p-value = 0.86). Negative trends of SC were detected in Scandinavian countries (slope per year -1.11 mil/mL, 95%CI: -2.40 to +0.19; p-value = 0.09), but the findings were statistically not significant. No significant trends of SC were detected in Central Europe (slope per year +0.23, 95%CI -2.51 to +2.96; p-value = 0.87), the USA (slope per year +1.08, 95%CI -0.42 to +2.57; p-value = 0.16) and Southern Europe (slope per year +0.19, 95%CI -0.99 to +1.37; p-value = 0.75). We have analysed separately findings from studies including sperm donors, fertile men, young unselected men (unselected men, study mean age<25 years) and unselected men (unselected men, study mean age≥25 years). No significant trends of SC were observed among sperm donors (slope per year -2.80, 95%CI -6.76 to +1.17; p-value 0.16), unselected men (slope per year -0.23, 95%CI -1.58 to +1.12; p-value 0.73), young unselected men (slope per year -0.49, 95%CI -1.76 to +0.79; p-value 0.45), fertile men (slope per year +0.29, 95%CI -1.09 to +1.67; p-value 0.68).

DISCUSSION AND CONCLUSION: The results of this analysis show no significant trends in SC in USA and selected Western European countries. This article is protected by copyright. All rights reserved.

PMID:36709405 | DOI:10.1111/andr.13396

J Perinatol. 2023 Jan 28. doi: 10.1038/s41372-023-01622-7. Online ahead of print.

ABSTRACT

OBJECTIVE: To determine the anesthetic approach with the least adverse events and better cardiorespiratory stability profile, used in infants undergoing laser photocoagulation for retinopathy of prematurity.

STUDY DESIGN: A systematic review was conducted. PubMed, Scopus, and Cochrane Library were searched until 27^th October 2021. Reference lists of relevant studies, and abstract books of international annual meetings of pediatric Οphthalmology for the years 2020 and 2021 were also looked at, as well as Clinical trials registry ( https://clinicaltrials.gov/ ).

RESULT: Overall 18 primary studies (3 randomized controlled trials, 3 cohorts, 12 case series) were included, investigating different anesthetic modalities. Cardiopulmonary instability was more common, and hypothermia was less common in the sedation groups of pentazocine/midazolam and fentanyl/midazolam, compared to the general anesthesia group of air/oxygen/sevoflurane (AOS). Cardiorespiratory instability was also more common in sedation with propofol/ketamine compared to general anesthesia with AOS, while postoperative mechanical ventilation was more frequently needed in the latter. Αpnea, need for supplemental oxygen and cardiorespiratory instability was more frequent in infants receiving fentanyl as opposed to ketamine. Fentanyl compared to morphine presented no differences in safety parameters. Finally, topical anesthesia showed the greatest instability with a higher mean postoperative cardiorespiratory index, compared to both sedation and general anesthesia. Episodes of life-threatening events were reported after topical anesthesia, while hypothermia and oliguria presented less often after topical, compared to general anesthesia and sedation.

CONCLUSION: Significant heterogeneity among studies precludes direct comparisons and generalizability of the results. No specific anesthetic modality for treatment of ROP with laser photocoagulation was shown to be superior in terms of safety. Well-designed studies are required to establish the optimal anesthetic approach, considering that laser photocoagulation still remains one of the main therapeutic modalities for ROP.

PMID:36709402 | DOI:10.1038/s41372-023-01622-7

Commun Biol. 2023 Jan 28;6(1):116. doi: 10.1038/s42003-023-04497-8.

NO ABSTRACT

PMID:36709395 | DOI:10.1038/s42003-023-04497-8

Sci Rep. 2023 Jan 28;13(1):1561. doi: 10.1038/s41598-023-28442-1.

ABSTRACT

The current multiphase, invitro study developed and validated a 3-dimensional convolutional neural network (3D-CNN) to generate partial dental crowns (PDC) for use in restorative dentistry. The effectiveness of desktop laser and intraoral scanners in generating data for the purpose of 3D-CNN was first evaluated (phase 1). There were no significant differences in surface area [t-stat(df) = – 0.01 (10), mean difference = – 0.058, P > 0.99] and volume [t-stat(df) = 0.357(10)]. However, the intraoral scans were chosen for phase 2 as they produced a greater level of volumetric details (343.83 ± 43.52 mm³) compared to desktop laser scanning (322.70 ± 40.15 mm³). In phase 2, 120 tooth preparations were digitally synthesized from intraoral scans, and two clinicians designed the respective PDCs using computer-aided design (CAD) workflows on a personal computer setup. Statistical comparison by 3-factor ANOVA demonstrated significant differences in surface area (P < 0.001), volume (P < 0.001), and spatial overlap (P < 0.001), and therefore only the most accurate PDCs (n = 30) were picked to train the neural network (Phase 3). The current 3D-CNN produced a validation accuracy of 60%, validation loss of 0.68-0.87, sensitivity of 1.00, precision of 0.50-0.83, and serves as a proof-of-concept that 3D-CNN can predict and generate PDC prostheses in CAD for restorative dentistry.

PMID:36709380 | DOI:10.1038/s41598-023-28442-1

Sci Rep. 2023 Jan 28;13(1):1619. doi: 10.1038/s41598-023-28683-0.

ABSTRACT

Carbon monoxide (CO) poisoning is a public health concern in developing countries especially in China with a high disease burden. We aimed to focus on non-occupational CO poisoning caused by household coal heating secular trends based on registry data in Jinan, China, and we aim to provide further evidence and suggestions for public health policy. We analyzed the occurrence and development trend and assess the spatial-temporal epidemiological characteristics of non-occupational CO poisoning caused by household coal heating in Jinan between 2007 and 2021. Among total of 6588 CO poisoning, 5616 cases (85.25%) and 180 deaths caused by household coal heating was identified during study period. The cumulative incidence rate was 5.78 per 100,000 person-years and the mortality rate was 0.19 per 100,000 person-years. The incidence in urban areas (6.55 per 100,000 person-years) was higher than rural areas (5.04 per 100,000 person-years), and there was a statistical difference between urban and rural (P < 0.001) (P < 0.001). The poisoning time point mainly occurs in the sleep stage. In Jinan, socioeconomic status, accessibility to health services and rural status are determinants for CO poisoning incidence and mortality. Implementation of urban and rural central heating renovation is an effective way to further reduce the disease burden of CO poisoning in the future.

PMID:36709374 | DOI:10.1038/s41598-023-28683-0

Sci Rep. 2023 Jan 28;13(1):1567. doi: 10.1038/s41598-023-27934-4.

ABSTRACT

In the face of the global pandemic caused by the disease COVID-19, researchers have increasingly turned to simple measures to detect and monitor the presence of the disease in individuals at home. We sought to determine if measures of neuromotor coordination, derived from acoustic time series, as well as phoneme-based and standard acoustic features extracted from recordings of simple speech tasks could aid in detecting the presence of COVID-19. We further hypothesized that these features would aid in characterizing the effect of COVID-19 on speech production systems. A protocol, consisting of a variety of speech tasks, was administered to 12 individuals with COVID-19 and 15 individuals with other viral infections at University Hospital Galway. From these recordings, we extracted a set of acoustic time series representative of speech production subsystems, as well as their univariate statistics. The time series were further utilized to derive correlation-based features, a proxy for speech production motor coordination. We additionally extracted phoneme-based features. These features were used to create machine learning models to distinguish between the COVID-19 positive and other viral infection groups, with respiratory- and laryngeal-based features resulting in the highest performance. Coordination-based features derived from harmonic-to-noise ratio time series from read speech discriminated between the two groups with an area under the ROC curve (AUC) of 0.94. A longitudinal case study of two subjects, one from each group, revealed differences in laryngeal based acoustic features, consistent with observed physiological differences between the two groups. The results from this analysis highlight the promise of using nonintrusive sensing through simple speech recordings for early warning and tracking of COVID-19.

PMID:36709368 | DOI:10.1038/s41598-023-27934-4