Nevin Manimala Statistics

Association of metabolic score for insulin resistance and its 6-year change with incident type 2 diabetes mellitus

J Diabetes. 2021 Feb 28. doi: 10.1111/1753-0407.13161. Online ahead of print.


BACKGROUND: The evidence for the association between metabolic score for insulin resistance (METS-IR) and type 2 diabetes mellitus (T2DM) is limited. We aimed to explore the association of METS-IR and its 6-year change with risk of incident T2DM in a rural Chinese population.

METHODS: We analyzed data for 12 107 participants (mean age 50.48 years). A Cox proportional-hazard model was used to estimate the association of METS-IR with incident T2DM by using hazard ratios (HRs) and 95% confidence intervals (CIs); a logistic regression model was used to assess the association of 6-year METS-IR change with incident T2DM by using odds ratios (ORs) and 95% CIs. We used subgroup analyses of the association of METS-IR and its 6-year change with incident T2DM by sex, age, and baseline fasting plasma glucose (FPG) level as well as restricted cubic splines to describe the dose-response association.

RESULTS: The association of METS-IR and 6-year METS-IR change with incident T2DM was significant (per SD unit increase: HR = 1.80, 95% CI: 1.60-2.02 for METS-IR, OR = 1.42, 95% CI: 1.28-1.57 and OR = 1.59, 95% CI: 1.44-1.76 for relative and absolute METS-IR change). The significant association remained on subgroup analyses by sex, age, and baseline FPG level. Dose-response analysis demonstrated that the probability of incident T2DM was significantly increased with increasing METS-IR and 6-year METS-IR change.

CONCLUSIONS: Increased METS-IR and 6-year METS-IR change were positively associated with risk of incident T2DM in a rural Chinese population. METS-IR may be a vital indicator for identifying T2DM.

PMID:33644990 | DOI:10.1111/1753-0407.13161

Nevin Manimala Statistics

Molecular and biological features of Culex quinquefasciatus homozygous larvae for two cqm1 alleles that confer resistance to Lysinibacillus sphaericus larvicides

Pest Manag Sci. 2021 Feb 28. doi: 10.1002/ps.6349. Online ahead of print.


BACKGROUND: Culex quinquefasciatus resistance to the binary toxin from Lysinibacillus sphaericus larvicides can occur because of mutations in the cqm1 gene that prevents the expression of the toxin receptor, Cqm1 α-glucosidase. In a resistant laboratory-selected colony maintained for more than 250 generations, cqm1REC and cqm1REC-2 resistance alleles were identified. The major allele initially found, cqm1REC, became minor and was replaced by cqm1REC-2. This study aimed to investigate the features associated with homozygous larvae for each allele to understand the reasons for the allele replacement and to generate knowledge on resistance to microbial larvicides.

RESULTS: Homozygous larvae for each allele were compared. Both larvae displayed the same level of resistance to the binary toxin (3500-fold); therefore, a change in phenotype was not the reason for the replacement observed. The lack of Cqm1 expression did not reduce the total specific α-glucosidase activity for homozygous cqm1REC and cqm1REC-2 larvae, which were statistically similar to the susceptible strain, using artificial or natural substrates. The expression of eight cqm1 paralog α-glucosidases was demonstrated in resistant and susceptible larvae. Bioassays in which cqm1REC or cqm1REC-2 homozygous larvae were reared under stressful conditions showed that most adults produced were cqm1REC-2 homozygous (69%). Comparatively, in the offspring of a heterozygous sub-colony reared under optimal conditions for twenty generations, the cqm1REC allele assumed a higher frequency (0.72).

CONCLUSION: Homozygous larvae for each allele exhibited a similar resistant phenotype. However, they presented specific advantages that might favor their selection and can be used in designing resistance management practices. This article is protected by copyright. All rights reserved.

PMID:33644981 | DOI:10.1002/ps.6349

Nevin Manimala Statistics

Clinical implications of sperm DNA damage in IVF and ICSI: updated systematic review and meta-analysis

Biol Rev Camb Philos Soc. 2021 Mar 1. doi: 10.1111/brv.12700. Online ahead of print.


The clinical effect of sperm DNA damage in assisted reproduction has been a controversial topic during recent decades, leading to a variety of clinical practice recommendations. While the latest European Society of Human Reproduction and Embryology (ESHRE) position report concluded that DNA damage negatively affects assisted reproduction outcomes, the Practice Committee of the American Society for Reproductive Medicine (ASRM) does not recommend the routine testing of DNA damage for in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI). Herein, our aim was to perform a systematic review and meta-analysis of studies investigating whether sperm DNA damage affects clinical outcomes in IVF and ICSI, in order to contribute objectively to a consistent clinical recommendation. A comprehensive systematic search was conducted according to PRISMA guidelines from the earliest available online indexing year until March 2020, using the MEDLINE-PubMed and EMBASE databases. We included studies analysing IVF and/or ICSI treatments performed in infertile couples in which sperm DNA damage was well defined and assessed. Studies also had to include information about pregnancy, implantation or live birth rates as primary outcomes. The NHLBI-NIH quality assessment tool was used to assess the quality of each study. Meta-analyses were conducted using the Mantel-Haenszel method with random-effects models to evaluate the Risk Ratio (RR) between high-DNA-damage and control groups, taking into account the 95% confidence intervals. Heterogeneity among studies was evaluated using the I2 statistic. We also conducted sensitivity analyses and post-hoc subgroup analyses according to different DNA fragmentation assessment techniques. We identified 78 articles that met our inclusion and quality criteria and were included in the qualitative analysis, representing a total of 25639 IVF/ICSI cycles. Of these, 32 articles had sufficient data to be included in the meta-analysis, comprising 12380 IVF/ICSI cycles. Meta-analysis revealed that, considering IVF and ICSI results together, implantation rate (RR = 0.74; 95% CI = 0.61-0.91; I2 = 69) and pregnancy rate (RR = 0.83; 0.73-0.94; I2 = 58) are negatively influenced by sperm DNA damage, although after adjustment for publication bias the relationship for pregnancy rate was no longer significant. The results showed a non-significant but detrimental tendency (RR = 0.78; 0.58-1.06; I2 = 72) on live birth rate. Meta-analysis also showed that IVF outcomes are negatively influenced by sperm DNA damage, with a statistically significant impact on implantation (RR = 0.68; 0.52-0.89; I2 = 50) and pregnancy rates (RR = 0.72; 0.55-0.95; I2 = 72), although the latter was no longer significant after correction for publication bias. While it did not quite meet our threshold for significance, a negative trend was also observed for live birth rate (RR = 0.48; 0.22-1.02; I2 = 79). In the case of ICSI, non-significant trends were observed for implantation (RR = 0.79; 0.60-1.04; I2 = 72) or pregnancy rates (RR = 0.89; 0.78-1.02; I2 = 44), and live birth rate (RR = 0.92; 0.67-1.27; I2 = 70). The current review provides the largest evidence to date supporting a negative association between sperm DNA damage and conventional IVF treatments, significantly reducing implantation and pregnancy rates. The routine use of sperm DNA testing is therefore justified, since it may help improve the outcomes of IVF treatments and/or allow a given couple to be advised on the most suitable treatment. Further well-designed controlled studies on a larger number of patients are required to allow us to reach more precise conclusions, especially in the case of ICSI treatments.

PMID:33644978 | DOI:10.1111/brv.12700

Nevin Manimala Statistics

MRI Findings of Arachnoiditis, Revisited. Is Classification Possible?

J Magn Reson Imaging. 2021 Feb 28. doi: 10.1002/jmri.27583. Online ahead of print.


BACKGROUND: Prior imaging studies characterizing lumbar arachnoiditis have been based on small sample numbers and have reported inconsistent results.

PURPOSE: To review the different imaging patterns of lumbosacral arachnoiditis, their significance, and clinical implications.

STUDY TYPE: Retrospective.

POPULATION: A total of 96 patients (43 women; average age 61.3 years) with imaging findings of arachnoiditis (postsurgical: N = 49; degenerative: N = 29; vertebral fracture: N = 6; epidural and subdural hemorrhage: N = 3, infectious: N= 1; other: N = 8) from January 2009 to April 2018.

FIELD STRENGTH/SEQUENCE: Sagittal and axial T2-weighted Turbo Spin Echo at 1.5 T and 3 T.

ASSESSMENT: Chart review was performed to assess the cause of arachnoiditis, and imaging was reviewed by two musculoskeletal and three neurology radiologists, blinded to the clinical data and to each other’s imaging interpretation. Previous classification included a three-group system based on the appearance of the nerve roots on T2-weighted images. A fourth group was added in our review as “nonspecified” and was proposed for indeterminate imaging findings that did not fall into the classical groups. The presence/absence of synechiae/fibrous bands that distort the nerve roots and of spinal canal stenosis was also assessed.

STATISTICAL TESTS: The kappa score was used to assess agreement between readers for both classification type and presence/absence of synechiae.

RESULTS: Postsurgical (51%) and degenerative changes (30%) were the most common etiologies. About 7%-55% of arachnoiditis were classified as group 4. There was very poor classification agreement between readers (kappa score 0.051). There was also poor interreader agreement for determining the presence of synechiae (kappa 0.18) with, however, strong interreader agreement for the presence of synechia obtained between the most experienced readers (kappa 0.89).

DATA CONCLUSION: This study demonstrated the lack of consensus and clarity in the classification system of lumbar arachnoiditis. The presence of synechia has high interreader agreement only among most experienced readers and promises to be a useful tool in assessing arachnoiditis.


PMID:33644967 | DOI:10.1002/jmri.27583

Nevin Manimala Statistics

How to use statistics to claim antagonism and synergism from binary mixture experiments

Pest Manag Sci. 2021 Feb 28. doi: 10.1002/ps.6348. Online ahead of print.


We review statistical approaches applicable for the analysis of data from binary mixture experiments, which are commonly used in pesticide science for evaluating antagonistic or synergistic effects. Specifically, two different situations are reviewed, one where every pesticide is only available at a single dose level and a mixture simply combines these doses, and one where the pesticides and their mixture are used at increasing doses. The former corresponds to using factorial designs whereas the latter corresponds to fixed-ratio designs. We consider dose addition and independent action as references for lack of antagonistic and synergistic effects. Data from factorial designs should be analyzed using two-way analysis of variance models whereas data from fixed-ratio designs should be analyzed using nonlinear dose-response analysis. In most cases, independent action seems the more natural choice for factorial designs. In contrast, dose addition is more appropriate for fixed-ratio designs although dose addition is not equally compatible with all types of dose-response data. Fixed-ratio designs should be preferred as they allow validation of the assumed dose-response relationship and, consequently, provide much stronger claims about antagonistic and synergistic effects than factorial designs. Finally, it should be noted that, in any case, simple ways of summarizing pesticide mixture effects may come at the price of more or less restrictive modelling assumptions. This article is protected by copyright. All rights reserved.

PMID:33644956 | DOI:10.1002/ps.6348

Nevin Manimala Statistics

Proton pump inhibitor use and the efficacy of chemotherapy in metastatic colorectal cancer: a post hoc analysis of a randomized phase 3 trial (AXEPT)

Oncologist. 2021 Feb 28. doi: 10.1002/onco.13735. Online ahead of print.


BACKGROUND: Concomitant use of proton pump inhibitors (PPIs) with capecitabine was suggested to be associated with poor outcomes in gastrointestinal cancers. We analyzed the differential impact of PPI use on capecitabine and fluorouracil using the dataset from the AXEPT trial, a phase III randomized trial that demonstrated the non-inferiority of modified XELIRI (mXELIRI; capecitabine plus irinotecan) with FOLFIRI (leucovorin, fluorouracil, and irinotecan), both either with or without bevacizumab in patients with metastatic colorectal cancer.

PATIENTS AND METHODS: Out of the per-protocol set (n=620), patients with information on concomitant medications (n=482) were included in this post-hoc analysis. PPI use was defined as concomitant exposure of capecitabine and the use of any PPI for 20% or more of the study period. The treatment-by-PPI-use interaction was examined after adjusting for stratification factors.

RESULTS: Of the 482 patients, 49 (10.1%) used PPI. Among the PPI users, the mXELIRI group tended to have poorer overall survival compared with the FOLFIRI group. In contrast, among the non-users, the overall survival of the mXELIRI group was significantly better than that of the FOLFIRI group. Similarly, a trend of worse progression-free survival with mXELIRI compared with FOLFIRI was observed in PPI users but not in non-users. Treatment-by-PPI-use interaction was significant for overall survival and progression-free survival.

CONCLUSION: The significant interaction between PPI use and the type of fluoropyrimidine in terms of overall and progression-free survival suggests that fluorouracil could be a more favourable option than capecitabine for patients with metastatic colorectal cancer using PPIs.

IMPLICATIONS FOR PRACTICE: This study showed a significant interaction between the use of proton pump inhibitors (PPIs) and the type of fluoropyrimidines. This interaction mainly comes from the positive impact of PPIs in the survival outcomes in the fluorouracil arm rather than a negative impact of PPIs in the capecitabine arm. The possible drug-drug interaction shown in this study suggests that fluorouracil, rather than capecitabine, could be a more appropriate choice of fluoropyrimidine for patients who are taking PPIs in the treatment of metastatic colorectal cancer.

PMID:33644953 | DOI:10.1002/onco.13735

Nevin Manimala Statistics

Correction of Artifacts Induced by B0 Inhomogeneities in Breast MRI Using Reduced-Field-of-View Echo-Planar Imaging and Enhanced Reversed Polarity Gradient Method

J Magn Reson Imaging. 2021 Mar 1. doi: 10.1002/jmri.27566. Online ahead of print.


BACKGROUND: Diffusion-weighted (DW) echo-planar imaging (EPI) is prone to geometric distortions due to B0 inhomogeneities. Both prospective and retrospective approaches have been developed to decrease and correct such distortions.

PURPOSE: The purpose of this work was to evaluate the performance of reduced-field-of-view (FOV) acquisition and retrospective distortion correction methods in decreasing distortion artifacts for breast imaging. Coverage of the axilla in reduced-FOV DW magnetic resonance imaging (MRI) and residual distortion were also assessed.

STUDY TYPE: Retrospective.

POPULATION/PHANTOM: Breast phantom and 169 women (52.4 ± 13.4 years old) undergoing clinical breast MRI.

FIELD STRENGTH/SEQUENCE: A 3.0 T/ full- and reduced-FOV DW gradient-echo EPI sequence.

ASSESSMENT: Performance of reversed polarity gradient (RPG) and FSL topup in correcting breast full- and reduced-FOV EPI data was evaluated using the mutual information (MI) metric between EPI and anatomical images. Two independent breast radiologists determined if coverage on both EPI data sets was adequate to evaluate axillary nodes and identified residual nipple distortion artifacts.

STATISTICAL TESTS: Two-way repeated-measures analyses of variance and post hoc tests were used to identify differences between EPI modality and distortion correction method. Generalized linear mixed effects models were used to evaluate differences in axillary coverage and residual nipple distortion.

RESULTS: In a breast phantom, residual distortions were 0.16 ± 0.07 cm and 0.22 ± 0.13 cm in reduced- and full-FOV EPI with both methods, respectively. In patients, MI significantly increased after distortion correction of full-FOV (11 ± 5% and 18 ± 9%, RPG and topup) and reduced-FOV (8 ± 4% both) EPI data. Axillary nodes were observed in 99% and 69% of the cases in full- and reduced-FOV EPI images. Residual distortion was observed in 93% and 0% of the cases in full- and reduced-FOV images.

DATA CONCLUSION: Minimal distortion was achieved with RPG applied to reduced-FOV EPI data. RPG improved distortions for full-FOV images but with more modest improvements and limited correction near the nipple.


PMID:33644939 | DOI:10.1002/jmri.27566

Nevin Manimala Statistics

The CXCR5 T follicular helper cell compartment in children with antibody deficiencies-in search of a prognostic marker of childhood hypogammaglobulinemia

Allergol Immunopathol (Madr). 2021 Mar 1;49(2):113-121. doi: 10.15586/aei.v49i2.34. eCollection 2021.


BACKGROUND: Novel immunodiagnostic markers are required in order to discriminate between mild hypogammaglobulinemia and severe humoral primary immune deficiencies in children. The efficacy of an antibody response to infections and vaccines is underpinned by T follicular helper (Tfh) cells, activating an immunoglobulin class switch recombination, somatic hypermutations, and affinity maturation.

OBJECTIVE: To determine the formation of the Tfh cells in antibody deficient children and to define their importance as prognostic markers helpful in defining the severity of hypogammaglobulinemia.

METHODS: We retrospectively reviewed medical records of 200 children aged from 2 months to 10 years, in whom hypogammaglobulinemia was assessed, from January to December 2019. In all the children studied, a flow cytometric analysis of the Tfh cell compartment was performed.

RESULTS: In young infants aged from 2 to 9 months, the mean relative frequency of the Tfh population was lower than in the control population. Concomitantly, the relative values of Tfh cells, corresponding with the 95th percentile, were below the reference values in all age groups.

CONCLUSIONS: A deficiency of Tfh cells in young infants mirrors the immaturity of the humoral immune response, whereas in older children Tfh cells are proposed as a prognostic marker facilitating to distinguish between mild hypogammaglobulinemia and the developing common variable immunodeficiency.

PMID:33641302 | DOI:10.15586/aei.v49i2.34

Nevin Manimala Statistics

Evaluation of some predictive parameters for baked-milk tolerance in children with cow’s milk allergy

Allergol Immunopathol (Madr). 2021 Mar 1;49(2):53-59. doi: 10.15586/aei.v49i2.64. eCollection 2021.


BACKGROUND: Inclusion of baked-milk products to the diet appears to markedly accelerate tolerance to unheated milk compared to a strict avoidance diet.

OBJECTIVE: : The present study aims to investigate the predictors of baked-milk tolerance in children with Immunoglobulin E (IgE)-mediated cow’s milk (CM) allergy.

METHODS: The study included 80 patients diagnosed with IgE-mediated CM allergy upon oral food challenge (OFC) testing at our clinic. Patients who developed and did not develop reactions during OFC with baked milk were compared considering clinical and laboratory parameters.

RESULTS: Eighty patients with CM allergy comprised 48 male and 32 female infants with an average age of 7.25 ± 2.45 (3-13) months. We found that 62.5% of them showed tolerance to baked milk in the OFC test performed with cakes containing 2.6-g milk protein. When the patients who tolerated and could not tolerate baked-milk products were compared for test results, we detected a statistically significant intergroup difference regarding diameter of wheal in skin prick test (SPT) performed with muffin slurry, levels of specific Immunoglobulin E (sIgE) in CM, sheep’s milk (SM), goat’s milk (GM), casein, and the amount of unheated milk consumed until a reaction developed in the OFC test performed with unheated milk (P < 0.05).

CONCLUSION: We defined novel decision points based on CM, SM, GM, casein sIgE levels, wheal diameter in SPT with muffin slurry, and the amount of milk ingested during OFC performed with unheated milk that may be useful in predicting outcomes of baked-milk ingestion.

PMID:33641294 | DOI:10.15586/aei.v49i2.64

Nevin Manimala Statistics

Antibodies to Der p 1 and Der p 2 in allergic patients

Allergol Immunopathol (Madr). 2021 Mar 1;49(2):46-52. doi: 10.15586/aei.v49i2.59. eCollection 2021.


INTRODUCTION AND OBJECTIVES: Atopic individuals are characterized by increased IgE production and Th2 response if exposed to certain antigens. It is known that the mother transfers anti-mite antibodies to the fetus and newborn, IgG thru the placenta, and IgA thru breastfeeding, but it is not clear whether there is a protective mechanism mediated by them concerning the development of future allergies. This study aimed to compare the levels of IgA, IgG, and IgE antibodies specific to Der p 1 and Der p 2 between atopic and healthy individuals.

METHODS: Serum samples of 98 patients and 44 healthy controls were subjected to quantification for specific IgE, IgG, and IgA antibodies against Der p 1 and Der p 2 by ImmunoCap® and ELISA, and subjected to statistical analysis as indicated.

RESULTS: Atopic patients had higher serum levels of IgE, IgG, and IgA specific to Der p 1 and Der p 2. The correlation was more robust between IgE and IgG antibodies.

CONCLUSIONS: Allergic patients produce higher levels of antibodies against Der p 1 and Der p 2 compared with healthy individuals. The mechanisms involved still require detailed studies.

PMID:33641293 | DOI:10.15586/aei.v49i2.59