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Nevin Manimala Statistics

Yes, no, maybe: Replication and the importance of methodology

Eur J Pain. 2021 Jul 3. doi: 10.1002/ejp.1835. Online ahead of print.

ABSTRACT

This journal recently published a paper by Rong et al., entitled “Persistent moderate to severe pain and long-term cognitive decline.” (Rong et al., 2021). The authors demonstrate that, to a small but statistically significant degree, older adults with persistent moderate-to-severe pain (an approximation for chronic pain) experience a faster rate of late-life cognitive decline than older adults without pain. Given these findings, should clinicians be alert for accelerated cognitive decline in older adults with chronic pain? Rong and colleagues argue yes. But, interestingly, using the same data source, an earlier study by Veronese and colleagues concluded that there was no evidence for an effect (Veronese et al., 2018). What are we to make of this?

PMID:34216525 | DOI:10.1002/ejp.1835

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Nevin Manimala Statistics

Extended versus segmental colectomy for mid-transverse colon cancers: an unsolved question

Colorectal Dis. 2021 Jul 3. doi: 10.1111/codi.15801. Online ahead of print.

ABSTRACT

We read with interest the paper by Park et al [1]. The authors analyzed a population of 107 patients with mid-transverse colon cancer (MTCC), who underwent either extended hemicolectomy (EC=70) or segmental colectomy (SC=37) [1]. No statistically significant difference was found in perioperative and long-term outcomes, following propensity score matching [1]. In particular, the authors underlined the lack of significant differences in 3-year disease-free survival (DFS; 86.5% vs. 90.9%, p = 0.675) and 5-year overall survival (OS; 87.4% vs. 93.0%, p = 0.349) [1].

PMID:34216529 | DOI:10.1111/codi.15801

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Nevin Manimala Statistics

Predictors of Phylogeographic Structure among co-distributed taxa across the complex Australian Monsoonal Tropics

Mol Ecol. 2021 Jul 3. doi: 10.1111/mec.16057. Online ahead of print.

ABSTRACT

Differences in the geographic scale and depth of phylogeographic structure across co-distributed taxa can reveal how microevolutionary processes such as population isolation and persistence drive diversification. In turn, environmental heterogeneity, species’ traits and historical biogeographic barriers may influence the potential for isolation and persistence. Using extensive SNP data and a combination of population genetic summary statistics and landscape genomic analyses, we explore predictors of the scale and depth of phylogeographic structure in co-distributed lizard taxa from the topographically and climatically complex monsoonal tropics (AMT) of Australia. We first resolve intraspecific lineages and then test whether genetic divergence across space within lineages is related to isolation by distance, resistance and/or environment, and whether these factors differ across genera or between rock-related versus habitat generalist taxa. We then test whether microevolutionary processes within lineages explain differences in the geographic scale and depth of intraspecific phylogeographic lineages. Results indicate that landscape predictors of phylogeographic structure differ between taxa. Within lineages, there was prevalent isolation by distance, but the strength of isolation by distance is independent on the taxonomic family, habitat specialization and climate. Isolation by environment is the strongest predictor of landscape-scale genetic divergence for all taxa, with both temperature and precipitation acting as limiting factors. The strength of isolation by distance does not predict the geographic scale of phylogeographic structure. However, more localized lineages had higher mean individual heterozygosity and less negative Tajima’s D. This result implies that finer-scale phylogeographic structuring within species is associated with larger and more stable populations and, hence, persistence.

PMID:34216506 | DOI:10.1111/mec.16057

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Nevin Manimala Statistics

Association between serum secretory phospholipase A2 and risk of ischemic stroke

Eur J Neurol. 2021 Jul 3. doi: 10.1111/ene.15004. Online ahead of print.

ABSTRACT

BACKGROUND AND PURPOSE: Previous literature has demonstrated an association between high serum levels of type-II secretory phospholipase A2 (sPLA2) concentration and an increased risk of coronary artery disease. However, such association has not been established in terms of ischemic stroke risk. We aimed to evaluate the association between both sPLA2 concentration and activity as continuous variables with risk of future ischemic stroke.

METHODS: We conducted a nested case-control study using data from the European Prospective Investigation into Cancer – Norfolk study. Cases (n=145) in the current study were participants who developed ischemic stroke during follow-up, with controls (n=290) matched in a 2:1 ratio based on age and sex. Statistical analyses were performed using SPSS (version 25.0, Chicago, Ill) software. Logistic regression was used to determine odds ratios (OR) and corresponding 95% confidence intervals (95% CIs) for ischemic stroke.

RESULTS: After adjusting for a wide array of cardiovascular confounders, sPLA2 activity was found to be associated with an increased risk of ischemic stroke using both multiple imputations with chained equations and complete case analysis: OR 1.20 (95% CI: 1.01-1.43) and OR 1.23 (95% CI: 1.01 -1.49), respectively. However, sPLA2 concentration was not found to be associated with increased risk of ischemic stroke.

CONCLUSIONS: The activity of sPLA2, but not sPLA2 concentration, is associated with an increased risk of future ischemic stroke. This finding may be significant in risk group stratification, allowing targeted prophylactic treatment, or the development of novel therapeutic agents.

PMID:34216520 | DOI:10.1111/ene.15004

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Nevin Manimala Statistics

Epidemiologic, immunologic, and virus characteristics in patients with paired SARS-CoV-2 serology and reverse transcription polymerase chain reaction testing

J Infect Dis. 2021 Jul 3:jiab349. doi: 10.1093/infdis/jiab349. Online ahead of print.

ABSTRACT

BACKGROUND: The natural history and clinical progression of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections can be better understood using combined serological and reverse transcription polymerase chain reaction (RT-PCR) testing.

METHODS: Nasopharyngeal swabs and serum were collected at a single time-point from patients at an urban, public hospital August – November 2020 and tested for SARS-CoV-2 using RT-PCR, viral culture, and anti-Spike pan-Ig antibody testing. Participant demographics and symptoms were collected through interview. Chi-squared and Fisher’s exact tests were used to identify associations between RT-PCR and serology results with presence of viable virus and frequency of symptoms.

RESULTS: Among 592 participants, 129 (21.8%) had evidence of SARS-CoV-2 infection by RT-PCR or serology. Presence of SARS-CoV-2 antibodies was strongly associated with lack of viable virus (p-value=0.016). COVID-19 symptom frequency was similar for patients testing RT-PCR positive/seronegative and patients testing RT-PCR positive/seropositive. Patients testing RT-PCR positive/seronegative reported headaches, fatigue, diarrhea and vomiting at rates not statistically significantly different from those testing RT-PCR negative/seropositive.

CONCLUSIONS: While patients testing SARS-CoV-2 seropositive were unlikely to test positive for viable virus and were therefore low-risk for forward transmission, COVID-19 symptoms were common. Paired SARS-CoV-2 RT-PCR and antibody testing provides more nuanced understanding of patients’ COVID-19 status.

PMID:34216468 | DOI:10.1093/infdis/jiab349

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Nevin Manimala Statistics

Follow-up genotoxicity assessment of Ames-positive/equivocal chemicals using the improved thymidine kinase gene mutation assay in DNA repair-deficient human TK6 cells

Mutagenesis. 2021 Jul 3:geab025. doi: 10.1093/mutage/geab025. Online ahead of print.

ABSTRACT

Genotoxicity testing plays an important role in the safety assessment of pharmaceuticals, pesticides, and chemical substances. Among the guidelines for various genotoxicity tests, the in vitro genotoxicity test battery comprises the bacterial Ames test and mammalian cell assays. Several chemicals exhibit conflicting results for the bacterial Ames test and mammalian cell genotoxicity studies, which may stem from the differences in DNA repair capacity or metabolism, between different cell types or species. For better understanding the mechanistic implications regarding conflict outcomes between different assay systems, it is necessary to develop in vitro genotoxicity testing approaches with higher specificity towards DNA-damaging reagents. We have recently established an improved thymidine kinase (TK) gene mutation assay (TK assay) that is deficient in DNA excision repair system using human lymphoblastoid TK6 cells lacking XRCC1 and XPA (XRCC1 -/-/XPA -/-), the core factors of base excision repair and nucleotide excision repair, respectively. This DNA repair-deficient TK6 cell line is expected to specifically evaluate the genotoxic potential of chemical substances based on the DNA damage. We focused on four reagents, N-(1-naphthyl)ethylenediamine dihydrochloride (NEDA), p-phenylenediamine (PPD), auramine, and malachite green (MG) as the Ames test-positive chemicals. In our assay, assessment using XRCC1 -/-/XPA -/- cells revealed no statistically significant increase in the mutant frequencies after treatment with NEDA, PPD, and MG, suggesting the chemicals to be non-genotoxic in humans. The observations were consistent with that of the follow-up in vivo studies. In contrast, the mutant frequency was markedly increased in XRCC1 -/-/XPA -/- cells after treatment with auramine. The results suggest that auramine is the genotoxic reagent that preferentially induces DNA damages resolved by BER and/or NER in mammals. Taken together, BER/NER deficient cell-based genotoxicity testing will contribute to elucidate the mechanism of genotoxicity and therefore play a pivotal role in the accurate safety assessment of chemical substances.

PMID:34216473 | DOI:10.1093/mutage/geab025

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Nevin Manimala Statistics

Comparison of the 2011 and 2019 Kampo Medicine Curricula Across All Japanese Medical Schools

Tokai J Exp Clin Med. 2021 Jul 20;46(2):75-82.

ABSTRACT

OBJECTIVE: To examine how Kampo education in Japanese medical schools changed between 2011 and 2019.

METHODS: We administered nationwide postal questionnaire surveys about current characteristics of Kampo medicine education in all 82 Japanese medical schools, directed to the persons responsible for Kampo education at each university. One survey was conducted in 2011 and one in 2019. Analysis used Welch’s t-test and a chi-squared test.

RESULTS: The average class meeting time was shorter in 2019 than in 2011. The proportion of class meetings that were about Kampo saw a statistically significant increase in the third year and a significant decrease in the fourth and sixth years of medical school. Curriculum standardisation, preparation of simple textbooks, and fostering Kampo medicine instructors were the primary problems in both years. The proportion of mainstream medical education contents focusing on traditional Japanese Kampo medicine did not change over time, nor did the percentage of those considering using standardised textbooks. Other changes were statistically nonsignificant.

CONCLUSION: In Japanese medical schools, the number of class meetings teaching Kampo medicine has increased; however, this number is not statistically significant. Persistent problems in Kampo education, including curriculum standardisation, need to be addressed.

PMID:34216479

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Nevin Manimala Statistics

Relapse of Plasmodium vivax and Plasmodium ovale malaria with and without primaquine treatment in a non-endemic area

Clin Infect Dis. 2021 Jul 3:ciab610. doi: 10.1093/cid/ciab610. Online ahead of print.

ABSTRACT

BACKGROUND: The effect of primaquine in preventing P. vivax relapses from dormant stages is well established. For P. ovale, the relapse characteristics and the use primaquine is not as well studied. We set to evaluate the relapsing properties of these two species, in relation to primaquine use among imported malaria cases in a non-endemic setting.

METHODS: We performed a nationwide retrospective study of malaria diagnosed in Sweden 1995-2019, by reviewing medical records of 3254 cases. All episodes of P. vivax (n=972) and P. ovale (n=251) were selected for analysis.

RESULTS: First time relapses were reported in 80/857 (9.3%) P. vivax and 9/220 (4.1%) P. ovale episodes, respectively (p<0.01). Without primaquine, the risk for relapse was higher in P. vivax, 20/60 (33.3%), compared to 3/30 (10.0%) in P. ovale (HR 3.5, 95% CI 1.0-12.0). In P. vivax, patients prescribed primaquine had a reduced risk of relapse compared to episodes without relapse preventing treatment, 7.1% vs 33.3%, (HR 0.2, 95%CI 0.1-0.3). In P. ovale, the effect of primaquine on the risk of relapse did not reach statistical significance, with relapses seen in 2.8% of the episodes compared to 10.0% in patients not receiving relapse preventing treatment (HR 0.3, 95% CI 0.1-1.1).

CONCLUSION: The risk of relapse was considerably lower in P. ovale than in P. vivax infections indicating different relapsing features between the two species. Primaquine was effective in preventing P. vivax relapse. In P. ovale, relapse episodes were few and the supportive evidence for primaquine remains limited.

PMID:34216464 | DOI:10.1093/cid/ciab610

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Nevin Manimala Statistics

Evaluation of Liposomal Bupivacaine at Split Thickness Skin Graft Donor Sites Through a Randomized, Controlled Trial

J Burn Care Res. 2021 Jul 3:irab129. doi: 10.1093/jbcr/irab129. Online ahead of print.

ABSTRACT

Split thickness skin grafts (STSG) are commonly required in reconstructive surgery but may cause significant pain. The goal of this investigator-initiated trial is to evaluate the effect of liposomal bupivacaine on donor site pain and opioid consumption. A parallel, randomized, controlled trial of adult acute burn patients with <20% total body surface area burns (TBSA) was conducted to evaluate the efficacy of liposomal bupivacaine at STSG donor sites. The control group received standard subcutaneous infiltration of dilute lidocaine solution at the STSG donor site, and the experimental group received dilute liposomal bupivacaine infiltration in a similar fashion. Donor site pain scores and opioid consumption in morphine equivalents (MEE) were evaluated. A total of 25 patients were enrolled in each group. There were no statistical differences in demographic variables, and TBSA was 4.0% in both groups (p=.94). There were no statistical differences in pain scores at any time point postoperatively (mean control range 3.1/10-4.9/10, experimental range 3.3/10-4.3/10, p=.12-.96). There were no statistical differences in opioid consumption at 24, 48, or 72 hours postoperatively between the groups (mean control MEE range 49.3-71.1, experimental MEE range 63.6-75.8, p=.34-.85). The average length of stay was 7.7 days in both groups (p=.88). No adverse events occurred in either group. There is no statistical benefit to the use of liposomal bupivacaine for infiltration at STSG donor sites compared to standard of care with respect to pain control, opioid use, or length of stay when evaluated in a randomized, controlled fashion.

PMID:34216466 | DOI:10.1093/jbcr/irab129

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Nevin Manimala Statistics

Phase behaviour and crystal structures of 2′,3′-difluorinated p-terphenyl derivatives

Acta Crystallogr C Struct Chem. 2021 Jul 1;77(Pt 7):435-440. doi: 10.1107/S2053229621006367. Epub 2021 Jun 28.

ABSTRACT

The crystal structures of difluorine derivatives of p-terphenyls (nTm) have been determined by single-crystal X-ray diffraction. For the unsymmetrical substituted compounds 2′,3′-difluoro-4-methyl-p-terphenyl (1T0, C19H14F2) and 4-ethyl-2′,3′-difluoro-4”-methyl-p-terphenyl (1T2, C21H18F2), the crystal structure is disordered, with molecules statistically entering the crystal in up and down orientations, with full superposition of all the atoms, except for those of the terminal groups (H/methyl for 1T0 and methyl/ethyl for 1T2). For triclinic 2′,3′-difluoro-4,4”-dimethyl-p-terphenyl (1T1, C20H16F2), with the space group P-1, the two crystallographically independent molecules have the same conformation, which is different from monoclinic 1T0 (space group C2) and 1T2 (space group C2/c). A common feature of the conformation of the three compounds is the noncoplanar twisted arrangement of the three rings of the p-terphenyl moiety. Two-dimensional (2D) Hirshfeld fingerprint plots are consistent with H…H and C…H contacts in the crystal packing. For the three compounds, the phase behaviour has been investigated by POM (Petra/Osiris/Molinspiration) and differential scanning calorimetry (DSC) analysis. 1T2 is mesogenic, with enantiotropic nematic behaviour.

PMID:34216450 | DOI:10.1107/S2053229621006367