Category: Statistics

Zhongguo Zhong Yao Za Zhi. 2022 Sep;47(18):4829-4834. doi: 10.19540/j.cnki.cjcmm.20220601.501.

ABSTRACT

Human use experience(HUE) is important for the research and development of Chinese medicine. For the sake of more reliable data, the Professional Committee for Clinical Evaluation of Chinese Medicine of Chinese Pharmaceutical Association drafted the Expert Consensus on Human Use Experience Research of Traditional Chinese Medicine. It highlights that the research on HUE should have clear purposes, describe the theoretical basis of traditional Chinese medicine(TCM) for the clinical indications and prescriptions and the clinical value of prescriptions, especially the advantages or characteristics in clinical orientation and target population, evaluate the dosages and number of medicinals of prescriptions, verify the accordance with the preparation process of new Chinese medicine, analyze feasibility of the process for large-scale production and the rationality of the dosage form, and assess the medicinal material resources. Moreover, such research should have reasonable protocol and the collection of clinical data on HUE must comply with medical ethics and avoid conflicts of interest. The collection method should be selected depending on the characteristics of clinical data. Quality control measures should be formulated to ensure the authenticity, accuracy, completeness, reliability, and traceability of clinical data. The definitions on the clinical data should be uniform and clear, and methods should be adopted to avoid bias. The data can be statistically analyzed after the processing. Through the study of HUE, the clinical orientation, target population, commonly used dosage, course of treatment, preliminary efficacy and safety of Chinese medicine prescriptions will be clarified. On this basis, the data on the HUE should be discussed and conclusions will be drawn. Finally, a standardized report will be formed.

PMID:36164892 | DOI:10.19540/j.cnki.cjcmm.20220601.501

Zhongguo Zhong Yao Za Zhi. 2022 Sep;47(17):4691-4697. doi: 10.19540/j.cnki.cjcmm.20220421.401.

ABSTRACT

To investigate the effect of Rehmanniae Radix on depression-like behavior and monoamine neurotransmitters of chronic unpredictable mild stress(CUMS) model rats. CUMS combined with isolated feeding was used to induce the depression model of rats. The depression-like behavior of rats was evaluated by sucrose preference test, open field test, and forced swim test. Hematoxylin-Eosin(HE) staining was used to investigate the pathological changes of neurons in the CA1 and CA3 area of hippocampus. Ultra performance liquid chromatography-tandem mass spectrometry(UPLC-MS) was used to detect the contents of 5-hydroxytryptamine(5-HT), 5-hydroxyindoleacetic acid(5-HIAA), dopamine(DA), 3,4-dihydroxyphenylacetic acid(DOPAC), homovanillic acid(HVA), norepinephrine(NE), and 3-methoxy-4-hydroxyphenyl glycol(MHPG) in rats. Western blot was used to detect the protein expressions of tryptophan hydroxylase 2(TPH2), serotonin transporter(SERT), and monoamine oxidase A(MAO-A) in the hippocampus of rats. Compared with the normal group, depressive-like behavior of rats was obvious in the model group. The arrangements of neurons in the CA1 and CA3 area of hippocampus were loose and disorderly. The levels of 5-HT, 5-HIAA, and 5-HT/5-HIAA in the hippocampal area were decreased(P<0.01). The protein expression of TPH2 was decreased(P<0.01), but those of SERT and MAO-A were increased(P<0.01). In the Rehmanniae Radix groups with 1.8 g·kg~(-1) and 7.2 g·kg~(-1), the depression-like behavior of CUMS rats and pathological changes of neurons in CA1, CA3 area of hippocampus were improved. The protein expression of TPH2(P<0.05, P<0.01) was increased, and those of SERT and MAO-A were down-regulated(P<0.05, P<0.01). The levels of 5-HT, 5-HIAA, and 5-HT/5-HIAA in hippocampus were increased(P<0.05, P<0.01). The changes in DA, DOPAC, HVA, DA/(DOPAC +HVA), NE, DHPG, and NE/DHPG were not statistically significant. The results suggested that Rehmanniae Radix improved depression-like behavior of CUMS rats, and the mechanism might be related to the regulation of synthesis, transportation, and metabolism of 5-HT neurotransmitter in the hippocampus.

PMID:36164876 | DOI:10.19540/j.cnki.cjcmm.20220421.401

Rev Esp Quimioter. 2022 Sep 23:martinez23sep2022. doi: 10.37201/req/040.2022. Online ahead of print.

ABSTRACT

OBJECTIVE: Recent research suggests that the use of antibiotics could reduce the efficacy of checkpoint inhibitors, in addition to other well-known factors. It could be due to gut microbiota modification, which impact over the immune system response. However, the information available so far is contradictory. The objective of this research was to clarify whether antibiotic use influences efficacy of checkpoint inhibitors treatments in non-small cell lung cancer patients in clinical practice.

METHODS: Therefore, a retrospective observational study was designed. Use of antibiotics among patients treated with atezolizumab, pembrolizumab or nivolumab was assessed within 2 months of checkpoint inhibitors treatments initiation.

RESULTS: A total of 140 patients were included, mostly men, with good performance status (ECOG 0-1), all of them previously treated with chemotherapy. An antibiotic prescription was identified in 31% of these patients, mainly fluoroquinolones or beta-lactams. The most frequent indication was respiratory infection. Both progression-free survival and overall survival were lower for patients treated with anti-infective drugs, although this difference was not statistically significant.

CONCLUSIONS: More studies are needed to draw conclusions about the impact of antibiotics on the efficacy of immunotherapy.

PMID:36164854 | DOI:10.37201/req/040.2022

Am J Bot. 2022 Sep 27. doi: 10.1002/ajb2.16074. Online ahead of print.

ABSTRACT

PREMISE: Understanding evolutionary history and classifying discrete units of organisms remains an overwhelming task, and lags in this discipline concomitantly impede an accurate documentation of biodiversity and conservation management. Rapid advances and improved accessibility of sensitive high throughput sequencing tools are fortunately quickening the resolution of morphological complexes that generally are underestimating species diversity. This seems to be the case of the persisting taxonomic quandary of the Hairpin Banksias (B. spinulosa sens. lat.), a group of eastern Australian flowering shrubs demonstrating a continuum of morphological diversity from which the critically endangered B. vincentia has been described.

METHODS: To assist conservation while testing the current taxonomy of this group, high-throughput sequencing was used to infer a population-scale evolutionary scenario for a sample-set comprehensive in its representation of morphological diversity and a two-and-a-half thousand kilometer distribution.

KEY RESULTS: Banksia spinulosa sens. lat. represents two clades, each with an internal genetic structure shaped through historical separation by biogeographic barriers. This structure conflicts with the existing taxonomy for the group. Corroboration between phylogeny and population statistics aligns with the hypothesis that B. collina, B. neoanglica, and B. vincentia should not be classified as species.

CONCLUSIONS: The pattern here supports how morphological diversity can be indicative of a locally expressed suite of traits rather than relationship. Over-splitting in the Hairpin Banksias is atypical since genomic analyses often reveal that species diversity is underestimated. However, we show that erring on overestimation can yield negative consequences, such as the disproportionate prioritisation of a geographically anomalous population. This article is protected by copyright. All rights reserved.

PMID:36164832 | DOI:10.1002/ajb2.16074

Int J Epidemiol. 2022 Sep 26:dyac178. doi: 10.1093/ije/dyac178. Online ahead of print.

ABSTRACT

BACKGROUND: There has been a large influx of COVID-19 seroprevalence studies, but comparability between the seroprevalence estimates has been an issue because of heterogeneities in testing platforms and study methodology. One potential source of heterogeneity is the response or participation rate.

METHODS: We conducted a review of participation rates (PR) in SARS-CoV-2 seroprevalence studies collected by SeroTracker and examined their effect on the validity of study conclusions. PR was calculated as the count of participants for whom the investigators had collected a valid sample, divided by the number of people invited to participate in the study. A multivariable beta generalized linear model with logit link was fitted to determine if the PR of international household and community-based seroprevalence studies was associated with the factors of interest, from 1 December 2019 to 10 March 2021.

RESULTS: We identified 90 papers based on screening and were able to calculate the PR for 35 out of 90 papers (39%), with a median PR of 70% and an interquartile range of 40.92; 61% of the studies did not report PR.

CONCLUSIONS: Many SARS-CoV-2 seroprevalence studies do not report PR. It is unclear what the median PR rate would be had a larger portion not had limitations in reporting. Low participation rates indicate limited representativeness of results. Non-probabilistic sampling frames were associated with higher participation rates but may be less representative. Standardized definitions of participation rate and data reporting necessary for the PR calculations are essential for understanding the representativeness of seroprevalence estimates in the population of interest.

PMID:36164817 | DOI:10.1093/ije/dyac178

Langenbecks Arch Surg. 2022 Sep 27. doi: 10.1007/s00423-022-02694-3. Online ahead of print.

ABSTRACT

OBJECTIVES: Totally laparoscopic total gastrectomy has been developed with difficulty in intracorporeal esophagojejunostomy. Although mechanical stapling has been widely used for intracorporeal esophagojejunostomy, manual suture holds great promise with the emergence of high-resolution 3D vision and robotic surgery. After exploration of how to improve the safety and efficiency of intracorporeal suture for esophagojejunostomy, we recommended the technique of single-layer running “trapezoid-shaped” suture. The cost-effectiveness was analyzed by comparing with conventional mechanical stapling.

METHODS: The study retrospectively reviewed the patients undergoing laparoscopic gastrectomy for gastric cancer from January 2010 to December 2021. The patients were divided into two cohorts based on the methods of intracorporeal esophagojejunostomy: manual suture versus stapling suture. Propensity score matching was performed to match patients from the two cohorts at a ratio of 1:1. Then group comparison was made to determine whether manual suture was non-inferior to stapling suture in terms of operation time, anastomotic complications, postoperative hospital stay, and surgical cost.

RESULTS: The study included 582 patients with laparoscopic total gastrectomy. The manual and stapling suture for esophagojejunostomy were performed in 50 and 532 patients, respectively. In manual suture cohort, the median time for the whole operation and digestive tract reconstruction were 300 min and 110 min. There was no anastomotic bleeding and stenosis but two cases of anastomotic leak which occurred at 3 days after surgery. The median length of postoperative hospital stay was 11 days. After propensity score matching, group comparison yielded two variables with statistical significance: time for digestive tract reconstruction and surgery cost. The manual suture cohort spent less money but more time for esophagojejunostomy. Intriguingly, the learning curve of manual suture revealed that the time for digestive tract reconstruction was declined with accumulated number of operations.

CONCLUSIONS: Laparoscopic single-layer running “trapezoid-shaped” suture appears safe and cost-effective for intracorporeal esophagojejunostomy after total gastrectomy. Although the concern remains about prolonged operation time for beginners of performing the suture method, adequate practice is expected to shorten the operation time based on our learning curve analysis.

PMID:36163379 | DOI:10.1007/s00423-022-02694-3

Sci Rep. 2022 Sep 26;12(1):15993. doi: 10.1038/s41598-022-20280-x.

ABSTRACT

The most common site of metastasis of prostate cancer (PCa) is bone. Skeletal-related events can increase the risk of death in patients with PCa by 28%. Due to the low detection rate of lesions in patients with low prostate-specific antigen (PSA) levels, the value of ^99mTc methylene diphosphonate (^99mTc-MDP) bone scintigraphy is limited. Prostate-specific membrane antigen (PSMA) is a small molecular probe that can efficiently and specifically detect PCa lesions. This prospective study aimed to evaluate the difference between ^99mTc-PSMA single-photon emission computed tomography (SPECT)/CT and ^99mTc-MDP SPECT/CT in the detection of bone metastasis in PCa. A total of 74 men with pathologically confirmed PCa from October 2019 to November 2021 were prospectively enrolled in this study. The median age was 70 (range, 55-87) years. All patients underwent both ^99mTc-PSMA SPECT/CT and ^99mTc-MDP SPECT/CT at an average interval of 12.1 (range, 1-14) days. The detected imaging-positive bone lesions were scored as “typical metastasis” or “equivocal metastasis” by a standard reporting schema. Subsequent therapy modality details were observed through follow-up. Twenty-five of the 74 patients were diagnosed with bone metastases. ^99mTc-PSMA SPECT/CT and ^99mTc-MDP SPECT/CT detected 20 and 18 bone metastases, with sensitivities of 80.0% (20/25) and 72.0% (18/25), specificities of 100.0% (49/49) and 81.3% (40/49), and AUCs of 88.0% and 84.9%, respectively. There was a significant difference in the AUC between the two imaging methods (P < 0.001). In an analysis of the number of bone metastasis lesions, the proportion of “typical metastasis” versus “equivocal metastasis” detected by the two imaging methods was 26.3:1 (PSMA) and 2.9:1 (MDP), and the difference was statistically significant (P = 0.005). There was a significant difference in the detection of bone metastatic lesions by ^99mTc-PSMA and ^99mTc-MDP when the maximum diameter of the lesions was ≤ 0.6 cm (P < 0.05). The optimal cut-off value for PSA was 2.635 ng/mL (PSMA) and 15.275 ng/mL (MDP). ^99mTc-PSMA SPECT/CT led to a change in management to a more individualized therapy modality for 11 of 74 men (14.9%). ^99mTc-PSMA SPECT/CT was superior to ^99mTc-MDP SPECT/CT in the detection of bone metastases in PCa, especially for small lesions and in patients with low PSA levels, and demonstrated an additional benefit of providing information on extraskeletal metastases. With regard to therapy, ^99mTc-PSMA scans might have utility in improving the subsequent therapy modality.

PMID:36163353 | DOI:10.1038/s41598-022-20280-x

Nat Commun. 2022 Sep 26;13(1):5645. doi: 10.1038/s41467-022-33269-x.

ABSTRACT

Disability progression in multiple sclerosis remains resistant to treatment. The absence of a suitable biomarker to allow for phase 2 clinical trials presents a high barrier for drug development. We propose to enable short proof-of-concept trials by increasing statistical power using a deep-learning predictive enrichment strategy. Specifically, a multi-headed multilayer perceptron is used to estimate the conditional average treatment effect (CATE) using baseline clinical and imaging features, and patients predicted to be most responsive are preferentially randomized into a trial. Leveraging data from six randomized clinical trials (n = 3,830), we first pre-trained the model on the subset of relapsing-remitting MS patients (n = 2,520), then fine-tuned it on a subset of primary progressive MS (PPMS) patients (n = 695). In a separate held-out test set of PPMS patients randomized to anti-CD20 antibodies or placebo (n = 297), the average treatment effect was larger for the 50% (HR, 0.492; 95% CI, 0.266-0.912; p = 0.0218) and 30% (HR, 0.361; 95% CI, 0.165-0.79; p = 0.008) predicted to be most responsive, compared to 0.743 (95% CI, 0.482-1.15; p = 0.179) for the entire group. The same model could also identify responders to laquinimod in another held-out test set of PPMS patients (n = 318). Finally, we show that using this model for predictive enrichment results in important increases in power.

PMID:36163349 | DOI:10.1038/s41467-022-33269-x

J Neurointerv Surg. 2022 Sep 26:neurintsurg-2022-019266. doi: 10.1136/jnis-2022-019266. Online ahead of print.

ABSTRACT

BACKGROUND: Successful recanalization after endovascular thrombectomy serves as the primary endpoint in clinical trials and is a crucial predictor of long-term outcomes. Radiographic outcomes for various interventions have been shown to vary based on the type of interpreter, including the site interventionalist compared with an independent reader.

OBJECTIVE: To compare angiographic outcomes in stroke thrombectomy procedures based on the type of reader.

METHODS: A systematic literature search was conducted in Medline, EMBASE, Scopus, and Web-of-Science through February 2022. We included primary studies that reported core laboratory-read and operator angiographic outcomes after mechanical thrombectomy for ischemic stroke. Furthermore, study-defined successful recanalization data were collected.

RESULTS: Eight studies were included with 4797 patients, 51.2% of whom were male. Four thousand, four hundred and thirty-one patients had core readings, and 4211 had operator readings. Study-defined successful recanalization was significantly higher for operator (84%, 3543/4211) examinations than for core laboratory-read (78.4%, 3476/4431) examinations (p<0.001; OR=1.462, 95% CI 1.175 to 1.819). The modified Thrombolysis in Cerebral Infarction (mTICI) scale score of ≥2 b was higher for operator (85%, 3341/3929) examinations than for core laboratory-read (78.6%, 3107/3952) examinations (p<0.001; OR=1.349, 95% CI 1.071 to 1.701). mTICI 3 was significantly higher for operator (54.6%, 1000/1832) examinations than for core laboratory-read (39.9%, 731/1832) examinations (p<0.001; OR=1.823, 95% CI 1.598 to 2.081).

CONCLUSION: Operator angiographic reads are statistically significantly higher than core laboratory-read readings following stroke thrombectomy, especially for complete recanalization. These differences should be considered when interpreting reports of angiographic outcomes after thrombectomy.

PMID:36163347 | DOI:10.1136/jnis-2022-019266

Heart Lung Circ. 2022 Sep 23:S1443-9506(22)01089-7. doi: 10.1016/j.hlc.2022.08.016. Online ahead of print.

ABSTRACT

OBJECTIVE: Data regarding optimal electrode positioning for direct current cardioversion (DCCV) of atrial fibrillation (AF) has been inconsistent. This meta-analysis was conducted to systematically compare the efficacy of anteroposterior (AP) versus anterolateral (AL) electrode placement for DCCV of AF.

METHODS: Electronic databases were searched for randomised controlled trials (RCTs) comparing AP versus AL electrode positioning in patients undergoing DCCV for AF. Primary endpoints were first-shock success and overall DCCV success. Subgroup analysis was performed by defibrillator waveform (monophasic versus biphasic). Meta-regression analyses were performed to assess for significant moderators.

RESULTS: Twelve (12) RCTs, including a total of 2,046 patients, met inclusion criteria. Neither first-shock success (relative risk [RR] 0.92; 95% CI 0.79-1.07; p=0.28) nor overall DCCV success (RR 1.01; 95% CI 0.96-1.05; p=0.78) were significantly different with AP versus AL electrode positioning. The mean number of shocks (mean difference [MD] 0.3, 95% CI -0.4 to 0.9), energy level of first successful shock (MD 3 joules; 95% CI -20 to 27) and cumulative energy delivered (MD 39 joules; 95% CI -168 to 246) were similar in AP versus AL arms. In subgroup analysis of six RCTs using biphasic defibrillators, improvement in first-shock success (RR 0.85; 95% CI 0.69-1.03; p=0.10) and overall DCCV success (RR 0.97; 95% CI 0.93-1.01; p=0.09) with AL electrode positioning did not reach statistical significance. Meta-regression analyses identified older age, higher body mass index, and longer AF duration as significant moderators favouring AL electrode positioning.

CONCLUSIONS: Pooled analysis of randomised data overall does not show a significant difference in efficacy between AP versus AL electrode positioning. Meta-regression and subgroup analyses suggest that, in contemporary practice with use of biphasic defibrillators, there may be a subset of AF patients in whom AL electrode positioning improves efficacy of DCCV.

PMID:36163316 | DOI:10.1016/j.hlc.2022.08.016