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Nevin Manimala Statistics

Paediatric surgical trials, their fragility index, and why to avoid using it to evaluate results

Pediatr Surg Int. 2022 May 7. doi: 10.1007/s00383-022-05133-y. Online ahead of print.

ABSTRACT

BACKGROUND: The fragility index has been gaining ground in the evaluation of comparative clinical studies. Many scientists evaluated trials in their fields and deemed them to be fragile, although there is no consensus on the definition of fragility. We aimed to calculate the fragility index and its permutations for paediatric surgical trials.

METHODS: We searched pubmed for prospectively conducted paediatric surgical trials with intervention and control group without limitations and calculated their (reverse) fragility indices and respective quotients along with posthoc-power. Relationships between variables were evaluated using Spearman’s ρ. We also calculated S values by negative log transformation base-2 of P values.

RESULTS: Of 516 retrieved records, we included 87. The median fragility index was 1.5 (interquartile range: 0-4) and the median reverse fragility index was 3 (interquartile range: 2-4), although they were statistically not different (Mood’s test: χ2 = 0.557, df = 1, P = 0.4556). P values and fragility indices were strongly inversely correlated (ρ = – 0.71, 95% confidence interval: – 0.53 to – 0.85, P < 0.0001), while reverse fragility indices were moderately correlated to P values (ρ = 0.5, 95% confidence interval: 0.37-0.62, P < 0.0001). A fragility index of 1 resulted from P values between 0.039 and 0.003, which resulted in S values between 4 and 8.

CONCLUSIONS: Fragility indices, reverse fragility indices, and their respective fragility quotients of paediatric surgical trials are low. The fragility index can be viewed as no more than a transformed P value with even more substantial limitations. Its inherent penalisation of small studies irrespective of their clinical relevance is particularly harmful for paediatric surgery. Consequently, the fragility index should be avoided.

PMID:35524787 | DOI:10.1007/s00383-022-05133-y

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Nevin Manimala Statistics

Suggested reviewers: friends or foes?

J Comp Physiol A Neuroethol Sens Neural Behav Physiol. 2022 May 7. doi: 10.1007/s00359-022-01553-2. Online ahead of print.

ABSTRACT

Peer review, a core element of the editorial processing of manuscripts submitted for publication in scientific journals, is widely criticized as being flawed. One major criticism is that many journals allow or request authors to suggest reviewers, and that these ‘preferred reviewers’ assess papers more favorably than do reviewers not suggested by the authors. To test this hypothesis, a retrospective analysis was conducted of 162 manuscripts submitted to the Journal of Comparative Physiology A between 2015 and 2021. Out of these manuscripts, 83 were finally rejected and 79 were finally accepted for publication. In neither group could a statistically significant difference be detected in the rating of manuscripts between reviewers suggested by the authors and reviewers not suggested by the authors. Similarly, pairwise comparison of the same manuscripts assessed by one reviewer suggested by the authors and one reviewer not suggested by the authors did not reveal any significant difference in the median recommendation scores between these two reviewer types. Thus, author-suggested reviewers are not necessarily, as commonly assumed, less neutral than reviewers not suggested by the authors, especially if their qualification and impartiality is vetted by the editor before they are selected for peer review.

PMID:35524786 | DOI:10.1007/s00359-022-01553-2

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Nevin Manimala Statistics

Detection and treatment of lung adenocarcinoma at pre-/minimally invasive stage: is it lead-time bias?

J Cancer Res Clin Oncol. 2022 May 7. doi: 10.1007/s00432-022-04031-z. Online ahead of print.

ABSTRACT

OBJECTIVES: This study investigates whether lead-time bias contributes to the excellent survival of AIS and MIA.

METHODS: We enrolled patients with resected adenocarcinoma from 2008 to 2012. Age, sex, smoke history, surgical approach, radiological features, invasive stage and postoperative follow-up data were documented. 1:1 PSM was performed to balance the influence of sex and smoking status on survival. After matching, the average age of the two groups was compared to calculate the lead time of diagnosis. The gain in life years for adenocarcinoma diagnosed at pre-/minimally invasive stage was estimated by subtracting the “lead time” and “median survival year of IAC” from “the life expectancy of AIS/MIA patients” referring to the Centre for Health and Information.

RESULTS: There were 124 AIS/MIA patients and 1148 IAC patients. The frequency of female and never-smoking patients in AIS/MIA group was much higher than that in IAC group. PSM analysis identified 124 patient pairs. No cancer-related death and recurrence were observed among AIS/MIA patients 5 years after surgery. For IAC patients, the 5-year disease-specific survival rate was 73.5% and the median survival is 13.5 years. The average age of AIS/MIA group and IAC group are 53.6 years and 58.2 years, respectively. The lead time between diagnosis of AIS/MIA and IAC is 4.6 years. Referring to the Centre for Health and Information, the life expectancy of patients with AIS/MIA diagnosed at 53.6 years old is 28.9 years. With adjustment for the lead time, the gain in life years for adenocarcinoma diagnosed at pre-/minimally invasive stage is 10.8 years.

CONCLUSIONS: With adjustment for the lead time between diagnosis of AIS/MIA and IAC, resecting lung adenocarcinoma at pre-/minimally invasive stage can improve life expectancy. The excellent survival of AIS/MIA is not lead-time bias.

PMID:35524781 | DOI:10.1007/s00432-022-04031-z

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Nevin Manimala Statistics

Oral Glucose Tolerance Test Measures of First-Phase Insulin Response and their Predictive Ability for Type 1 Diabetes

J Clin Endocrinol Metab. 2022 May 7:dgac285. doi: 10.1210/clinem/dgac285. Online ahead of print.

ABSTRACT

CONTEXT: Decreased first-phase insulin response (FPIR) during intravenous glucose tolerance testing (IVGTT) is an early indicator of β-cell dysfunction and predictor of type 1 diabetes (T1D).

OBJECTIVE: Assess whether oral glucose tolerance test (OGTT) measures could serve as FPIR alternatives in their ability to predict T1D in autoantibody positive (Aab+) subjects.

DESIGN: OGTT and IVGTT were performed within 30 days of each other. Eleven OGTT variables were evaluated for: 1) correlation with FPIR, and 2) T1D prediction.

SETTING: Type 1 Diabetes TrialNet “Oral Insulin for Prevention of Diabetes in Relatives at Risk for T1D” (TN-07) and Diabetes Prevention Trial-Type 1 Diabetes (DPT-1) studies clinical sites.

PATIENTS: TN-07 (n=292; age 9.4±6.1 years) and DPT-1 (n=194; age 15.1±10.0 years) Aab+ relatives of T1D individuals.

MAIN OUTCOME MEASURES: 1) Correlation coefficients of OGTT-measures with FPIR, and 2) T1D prediction at 2-years using area under receiver operating characteristic (ROCAUC) curves.

RESULTS: Index60 showed the strongest correlation in DPT-1 (r=-0.562) but was weaker in TN-07 (r=-0.378). C-peptide index consistently showed good correlation with FPIR across studies (TN-07, r=0.583; DPT-1, r=0.544; p<0.0001). Index60 and C-peptide index had the highest ROCAUCs for T1D prediction (0.778 vs. 0.717 in TN-07; 0.763 vs. 0.721 in DPT-1, respectively; p=NS), followed by FPIR (0.707 in TN-07; 0.628 in DPT-1).

CONCLUSIONS: C-peptide index was the strongest measure to correlate with FPIR in both studies. Index60 and C-peptide index had the highest predictive accuracy for T1D and were comparable. OGTTs could be considered instead of IVGTTs for subject stratification in T1D prevention trials.

PMID:35524749 | DOI:10.1210/clinem/dgac285

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Nevin Manimala Statistics

Comprehensive geriatric assessment in older people: an umbrella review of health outcomes

Age Ageing. 2022 May 1;51(5):afac104. doi: 10.1093/ageing/afac104.

ABSTRACT

BACKGROUND: Comprehensive geriatric assessment (CGA) has been in use for the last three decades. However, some doubts remain regarding its clinical use. Therefore, we aimed to capture the breadth of outcomes reported and assess the strength of evidence of the use of comprehensive geriatric assessment (CGA) for health outcomes in older persons.

METHODS: Umbrella review of systematic reviews of the use of CGA in older adults searching in Pubmed, Embase, Scopus, Cochrane library and CINHAL until 05 November 2021. All possible health outcomes were eligible. Two independent reviewers extracted key data. The grading of evidence was carried out using the GRADE for intervention studies, whilst data regarding systematic reviews were reported as narrative findings.

RESULTS: Among 1,683 papers, 31 systematic reviews (19 with meta-analysis) were considered, including 279,744 subjects. Overall, 13/53 outcomes were statistically significant (P < 0.05). There was high certainty of evidence that CGA reduces nursing home admission (risk ratio [RR] = 0.86; 95% confidence interval [CI]: 0.75-0.89), risk of falls (RR = 0.51; 95%CI: 0.29-0.89), and pressure sores (RR = 0.46; 95%CI: 0.24-0.89) in hospital medical setting; decreases the risk of delirium (OR = 0.71; 95%CI: 0.54-0.92) in hip fracture; decreases the risk of physical frailty in community-dwelling older adults (RR = 0.77; 95%CI: 0.64-0.93). Systematic reviews without meta-analysis indicate that CGA improves clinical outcomes in oncology, haematology, and in emergency department.

CONCLUSIONS: CGA seems to be beneficial in the hospital medical setting for multiple health outcomes, with a high certainty of evidence. The evidence of benefits is less strong for the use of CGA in other settings.

PMID:35524746 | DOI:10.1093/ageing/afac104

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Nevin Manimala Statistics

Comparison of Dimensional Changes Between CAD-CAM Milled Complete Denture Bases and 3D Printed Complete Denture Bases: An In Vitro Study

J Prosthodont. 2022 May 7. doi: 10.1111/jopr.13538. Online ahead of print.

ABSTRACT

PURPOSE: This study compared the dimensional changes between the computer-aided design and computer-aided manufacturing (CAD-CAM) milled complete denture bases (CDBs) and three-dimensional (3D) printed CDBs.

MATERIALS AND METHODS: One maxillary completely edentulous stone model was fabricated with three reference points at the incisive papilla, right molar, and left molar areas marked as X, Y, and Z, respectively. It was scanned to produce a standard tessellation language (STL) file, which was imported to a metal milling machine software to produce the metal model. This metal model was used to fabricate 30 CDBs for analysis in this study. The CDBs were divided into three groups (n = 10 each) according to the fabrication method used as follows: Group 1, CAD-CAM milled CDBs; Group 2, 3D printed CDBs; and Group 3, conventional compression molded CDBs. The CDBs of all groups were scanned after fabrication, and the dimensional changes in each were evaluated by two methods. The first was the two-dimensional evaluation method that involved linear measurement of the distances between the reference points (X-Y, X-Z, and Y-Z) of the scanned reference cast and dentures. The second method was the 3D evaluation method that involved the superimposition of the STL files of the dentures on the STL file of the reference cast. Data were calculated and were statistically analyzed using one-way analysis of variance and Tukey’s pairwise post hoc tests.

RESULTS: There was a significant difference in the dimensional accuracy between the CAD-CAM milled, 3D printed, and conventional compression molded CDBs (P<0.05).

CONCLUSION: The dimensional accuracy of the CAD-CAM milling system in complete denture fabrication is superior to that of the compression molding and 3D printing systems. This article is protected by copyright. All rights reserved.

PMID:35524633 | DOI:10.1111/jopr.13538

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Nevin Manimala Statistics

Radiographic Assessment of Aseptic Loosening of Tumor-Type Knee Prosthesis in Distal Femur

Orthop Surg. 2022 May 7. doi: 10.1111/os.13297. Online ahead of print.

ABSTRACT

OBJECTIVE: To measure the full-length anteroposterior and lateral radiographs of lower limbs after the resection of a tumor in the distal femur and tumor-type knee prosthesis replacement and to analyze the factors leading to aseptic loosening of the prosthesis.

METHODS: A total of 26 cases of tumor-type knee prosthesis replacement or revision due to the distal femoral tumor at our hospital from January 2007 to December 2019 were retrospectively analyzed. The patients were divided into the loosening and unloosening groups depending on whether aseptic loosening occurred after surgery. Full-length anteroposterior and lateral radiographs of lower limbs were used to measure bone resection length, length of prosthesis, distance of proximal apex of the medullary stem of the femoral prosthesis from the maximum arc of the anterior femoral arch, diameter of the medullary stem, etc. Data were analyzed, and the risk factors for aseptic loosening of the prosthesis were explored.

RESULTS: The ratio of the prosthetic length to the femoral length (63.72 ± 5.21) and the ratio of the femoral medullary stem diameter to the femoral diameter (26.03 ± 8.45) were smaller in the loosening group than in the unloosening group. The difference was statistically significant (p < 0.05). The distance between the apex of the medullary stem and the maximum arc of the anterior femoral arch was significantly shorter in the loosening group (3.47 ± 2.96) than in the unloosening group, and the difference was statistically significant (p < 0.05). The measurement of the lower limb alignment showed significant differences between the loosening and unloosening groups in terms of HKAA, mLDFA, and distance between the lower limb alignment and the center of the knee joint (p < 0.05). The logistic regression analysis showed that less than 30% ratio between the medullary stem diameter and the femoral diameter, less than 3 cm distance between the apex of the medullary stem and the maximum curvature of the anterior arch of the femur, distance between the lower limb alignment and the center of the knee joint, and presence of varus knee and valgus knee after the surgery were the risk factors for aseptic loosening of the prosthesis.

CONCLUSIONS: The diameter of the femoral medullary stem of the prosthesis, the apex position of the prosthetic stem, and the lower limb alignment are the risk factors for aseptic loosening of the prosthesis.

PMID:35524629 | DOI:10.1111/os.13297

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Nevin Manimala Statistics

Emerging experience with selected new categories in the ICD-11: complex PTSD, prolonged grief disorder, gaming disorder, and compulsive sexual behaviour disorder

World Psychiatry. 2022 Jun;21(2):189-213. doi: 10.1002/wps.20960.

ABSTRACT

Among the important changes in the ICD-11 is the addition of 21 new mental disorders. New categories are typically proposed to: a) improve the usefulness of morbidity statistics; b) facilitate recognition of a clinically important but poorly classified mental disorder in order to provide appropriate management; and c) stimulate research into more effective treatments. Given the major implications for the field and for World Health Organization (WHO) member states, it is important to examine the impact of these new categories during the early phase of the ICD-11 implementation. This paper focuses on four disorders: complex post-traumatic stress disorder, prolonged grief disorder, gaming disorder, and compulsive sexual behaviour disorder. These categories were selected because they have been the focus of considerable activity and/or controversy and because their inclusion in the ICD-11 represents a different decision than was made for the DSM-5. The lead authors invited experts on each of these disorders to provide insight into why it was considered important to add it to the ICD-11, implications for care of not having that diagnostic category, important controversies about adding the disorder, and a review of the evidence generated and other developments related to the category since the WHO signaled its intention to include it in the ICD-11. Each of the four diagnostic categories appears to describe a population with clinically important and distinctive features that had previously gone unrecognized as well as specific treatment needs that would otherwise likely go unmet. The introduction of these categories in the ICD-11 has been followed by a substantial expansion of research in each area, which has generally supported their validity and utility, and by a significant increase in the availability of appropriate services.

PMID:35524599 | DOI:10.1002/wps.20960

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Nevin Manimala Statistics

Regression-based heterogeneity analysis to identify overlapping subgroup structure in high-dimensional data

Biom J. 2022 May 7. doi: 10.1002/bimj.202100119. Online ahead of print.

ABSTRACT

Heterogeneity is a hallmark of complex diseases. Regression-based heterogeneity analysis, which is directly concerned with outcome-feature relationships, has led to a deeper understanding of disease biology. Such an analysis identifies the underlying subgroup structure and estimates the subgroup-specific regression coefficients. However, most of the existing regression-based heterogeneity analyses can only address disjoint subgroups; that is, each sample is assigned to only one subgroup. In reality, some samples have multiple labels, for example, many genes have several biological functions, and some cells of pure cell types transition into other types over time, which suggest that their outcome-feature relationships (regression coefficients) can be a mixture of relationships in more than one subgroups, and as a result, the disjoint subgrouping results can be unsatisfactory. To this end, we develop a novel approach to regression-based heterogeneity analysis, which takes into account possible overlaps between subgroups and high data dimensions. A subgroup membership vector is introduced for each sample, which is combined with a loss function. Considering the lack of information arising from small sample sizes, an l2$l_2$ norm penalty is developed for each membership vector to encourage similarity in its elements. A sparse penalization is also applied for regularized estimation and feature selection. Extensive simulations demonstrate its superiority over direct competitors. The analysis of Cancer Cell Line Encyclopedia data and lung cancer data from The Cancer Genome Atlas show that the proposed approach can identify an overlapping subgroup structure with favorable performance in prediction and stability.

PMID:35524586 | DOI:10.1002/bimj.202100119

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Nevin Manimala Statistics

Phenotypic architecture of sociality and its associated genetic polymorphisms in zebrafish

Genes Brain Behav. 2022 May 7:e12809. doi: 10.1111/gbb.12809. Online ahead of print.

ABSTRACT

Sociality relies on motivational and cognitive components that may have evolved independently, or may have been linked by phenotypic correlations driven by a shared selective pressure for increased social competence. Furthermore, these components may be domain-specific or of general-domain across social and non-social contexts. Here, we used zebrafish to test if the motivational and cognitive components of social behavior are phenotypically linked and if they are domain specific or of general domain. The behavioral phenotyping of zebrafish in social and equivalent non-social tests shows that the motivational (preference) and cognitive (memory) components of sociality: (1) are independent from each other, hence not supporting the occurrence of a sociality syndrome; and (2) are phenotypically linked to non-social traits, forming two general behavioral modules, suggesting that sociality traits have been co-opted from general-domain motivational and cognitive traits. Moreover, the study of the association between single nucleotide polymorphisms (SNPs) and each behavioral module further supports this view, since several SNPs from a list of candidate “social” genes, are statistically associated with the motivational, but not with the cognitive, behavioral module. Together, these results support the occurrence of general-domain motivational and cognitive behavioral modules in zebrafish, which have been co-opted for the social domain.

PMID:35524578 | DOI:10.1111/gbb.12809