Nevin Manimala

Diabet Med. 2021 Jul 21:e14653. doi: 10.1111/dme.14653. Online ahead of print.

ABSTRACT

AIMS: Currently, there is a growing body of research demonstrating that spin – the misinterpretation and distortion of a study’s findings – is common in different fields of medicine. To our knowledge, no study has investigated its presence in systematic reviews focused on diabetic therapies.

METHODS: We performed a cross-sectional study by searching MEDLINE and Embase for systematic reviews focused on pharmacologic treatments for type 2 diabetes mellitus. Our search retrieved 26,490 records, from which 199 studies were extracted in a masked, duplicate fashion. Each study was evaluated for the nine most severe types of spin and other study design parameters. Spin was presented as frequencies and odds ratios to identify associations between study characteristics.

RESULTS: Spin was identified in the abstracts of 15 systematic reviews (15/199, 7.5%). Spin type 5 was the most common type identified (7/199, 3.5%). Spin types 1, 2, 4, and 8 were not identified. In the last 5 years (2016-2021), 7 systematic reviews contained spin within their abstract. There was no association between spins presence and any extracted study characteristic .

CONCLUSIONS: Our findings show that spin infrequently occurs in abstracts of systematic reviews focused on pharmacologic therapies for type 2 diabetes mellitus. However, any amount of spin can lead to the distortion of a reader’s interpretation of the study’s findings. Thus, we provide recommendations with rationale to prevent spin in future systematic reviews.

PMID:34289158 | DOI:10.1111/dme.14653

Clin Exp Pharmacol Physiol. 2021 Jul 21. doi: 10.1111/1440-1681.13552. Online ahead of print.

ABSTRACT

Although oral isotretinoin has been widely used as a basic treatment of acne in adolescents, several studies have noted some alterations in thyroid functions during oral isotretinoin therapy. Therefore, the present study aims at evaluating the possible changes in thyroid-stimulating hormone (TSH), free thyroxin (fT4) and free triiodothyronine (fT3) levels during isotretinoin treatment and analyzing the possible factors which may contribute to such changes. In the present study, forty-seven patients received (0.5 mg/kg oral isotretinoin) for treatment of severe acne. TSH, fT4 and fT3 were measured at baseline, after 3 and 6 months. ANOVA tests were used for statistical analyses. The levels of fT4 and fT3 decreased significantly during isotretinoin treatment (from 0.85 ± 0.04 and 3.1 ± 0.26 at baseline to 0.81± 0.023 and 2.76 ±0.2 after 6 months respectively). The decrease was accompanied by significant elevation of TSH (0.66 ± 0.05 at baseline to 0.695 ± 0.05 after 6 months). The duration of therapy (but not the dose) has significantly affected all the hormonal changes. Previous incomplete or intermittent isotretinoin treatment had significantly influenced the changes in fT4 only, while gender affected the changes of TSH. Isotretinoin treatment can decrease fT4, fT3 and increase TSH. The pattern of these changes was affected by gender and previous isotretinoin therapy. Different doses of isotretinoin did not affect the hormonal changes, but the duration has been the major influencing factor.

PMID:34289152 | DOI:10.1111/1440-1681.13552

J Med Virol. 2021 Jul 21. doi: 10.1002/jmv.27218. Online ahead of print.

ABSTRACT

AIM: Both SARS-COV-2 and influenza viruses cause similar clinical presentations. It is essential to assess severely ill patients presenting with a viral syndrome for diagnostic and prognostic purposes. We aimed to compare clinical and biochemical features between pneumonia patients with COVID-19 and H1N1 METHOD: Sixty patients diagnosed with COVID-19 pneumonia and 61 patients diagnosed with influenza pneumonia hospitalized between October 2020- January 2021 and October 2017- December 2019 respectively. All the clinical data and laboratory results, Chest Computed Tomography(CT) scans, intensive care unit (ICU) admission, invasive mechanical ventilation (IMV), and outcomes were retrospectively evaluated.

RESULTS: The median age was 65 (range 32-96) years for patients with a COVID-19 diagnosis and 58 (range 18-83) years for patients with influenza (p= 0,002). Comorbidity index was significantly higher in COVID-19 patients. (p=0,010). DM and HT were statistically significantly more common in COVID-19 patients. (p:0,019, p: 0,008 respectively). Distribution of severe disease and mortality was not significantly different among COVID-19 patients than influenza patients.(p:0,096, p= 0,049).). In comparison to inflammation markers; CRP levels were significantly higher in influenza patients than COVID-19 patients. (p= 0,033). The presence of sputum was predictive for influenza (OR 0,342[95% CI, 2.1,130-0,899]). CRP and platelet were also predictive for COVID-19 (OR 4.764 [95% CI, 1,003-1,012] and OR 0,991 [95% CI 0,984-0,998] respectively.

CONCLUSION: We conclude that sputum symptom by itself much more detected in influenza patients. Besides that lower CRP and higher PLT count would be discriminative for COVID-19. This article is protected by copyright. All rights reserved.

PMID:34289142 | DOI:10.1002/jmv.27218

J Med Virol. 2021 Jul 21. doi: 10.1002/jmv.27217. Online ahead of print.

ABSTRACT

BACKGROUND: The DNA repair genes have a crucial function in the base excision repair (BER) mechanism among different cancerous disorders, particularly hepatocellular carcinoma. The foremost objective of this study is to explore the association of genetic variants of the APEX1 p.Asp148Glu and the XRCC1 p.Gln399Arg with the susceptibility of hepatocellular carcinoma and to identify the computational bioinformatics frameworks of these missense variants.

MATERIALS AND METHODS: A total of 250 participants were enrolled in this work, including 150 HCC patients and 100 cancer-free controls. The genomic DNA was characterized and genotyped by applying the PCR-CTPP method.

RESULTS: The frequency of the APEX (rs1130409*Glu) allele was statistically significant with increased risk of HCC (OR = 1.66, 95% CI = 1.12-2.45), while the XRCC1 (rs25487*Gln) allele conferred a protection against the progression of HCC (OR = 0.64, 95% CI = 0.42-0.96). Furthermore, HCC patients carrying the APEX1 p.Asp148Glu and the XRCC1 p.Gln399Arg variants indicated no significant difference with the clinical, and laboratory parameters (P-value > 0.05).

CONCLUSION: Our findings confirmed that the APEX1 p.Asp148Glu variant was associated with increased risk of HCC, while the XRCC1 p.Gln399Arg variant revealed protection against the development of HCC. This article is protected by copyright. All rights reserved.

PMID:34289138 | DOI:10.1002/jmv.27217

Cancer. 2021 Jul 21. doi: 10.1002/cncr.33810. Online ahead of print.

ABSTRACT

BACKGROUND: It is critical patients understand the terms used to describe oncology treatments; however, even basic chemotherapy terminology can be misunderstood. Rural communities tend to have especially low levels of health literacy compared with nonrural communities. To address low health literacy in rural communities, this study tested rural participants’ understanding of previously developed educational chemotherapy videos that were designed for an underserved urban population. Participants were also asked for feedback to determine if the videos could be improved.

METHODS: Fifty English-speaking patients who reside in counties classified as rural according to the Rural-Urban Continuum Code designations (RUCC 4-9) participated in the study. Participants were asked to define 6 chemotherapy terms before and after viewing a short, animated video explaining the term in English. Rates of correct and incorrect definitions provided by participants were also compared with previously published results from an urban cohort.

RESULTS: All participants had statistically significantly higher rates of correct definitions for all 6 terms following the video intervention. Palliative chemotherapy understanding improved the most (10% correct prevideo and 76% postvideo intervention). For each video, the majority of participants (77%-92%) suggested no changes to the videos.

CONCLUSION: Given the prevalence of low health literacy in rural communities, it is important to have effective educational interventions to improve the understanding of basic oncology-treatment terminology. This study found that short, educational videos, originally designed for an underserved urban population, can significantly improve understanding of commonly misunderstood chemotherapy terminology in a rural setting as well.

LAY SUMMARY: Chemotherapy terminology can be confusing to patients. Understanding can be especially difficult in areas with low health literacy, such as underserved urban and rural communities. To address this concern, previously developed short, animated videos describing basic chemotherapy terminology were found to improve patient understanding in an underserved urban setting. In this study, the videos were tested in a rural population and their effectiveness was established. Participants in the rural setting were significantly more likely to correctly define all 6 tested terms after watching the videos. Educational tools for high-need populations are essential to ensure patients can understand the treatment they receive.

PMID:34289098 | DOI:10.1002/cncr.33810

Cancer. 2021 Jul 21. doi: 10.1002/cncr.33582. Online ahead of print.

ABSTRACT

BACKGROUND: US population-based cancer registries can be used for surveillance of human papillomavirus (HPV) types found in HPV-associated cancers. Using this framework, HPV prevalence among high-grade cervical precancers and invasive cervical cancers were compared before and after HPV vaccine availability.

METHODS: Archived tissue from 2 studies of cervical precancers and invasive cervical cancers diagnosed from 1993-2005 (prevaccine) were identified from 7 central cancer registries in Florida; Hawaii; Iowa; Kentucky; Louisiana; Los Angeles County, California; and Michigan; from 2014 through 2015 (postvaccine) cases were identified from 3 registries in Iowa, Kentucky, and Louisiana. HPV testing was performed using L1 consensus polymerase chain reaction analysis. HPV-type-specific prevalence was examined grouped by hierarchical attribution to vaccine types: HPV 16, 18, HPV 31, 33, 45, 52, 58, other oncogenic HPV types, and other types/HPV negative. Generalized logit models were used to compare HPV prevalence in the prevaccine study to the postvaccine study by patient age, adjusting for sampling factors.

RESULTS: A total of 676 precancers (328 prevaccine and 348 postvaccine) and 1140 invasive cervical cancers (777 prevaccine and 363 postvaccine) were typed. No differences were observed in HPV-type prevalence by patient age between the 2 studies among precancers or invasive cancers.

CONCLUSIONS: The lack of reduction in vaccine-type prevalence between the 2 studies is likely explained by the low number of cases and low HPV vaccination coverage among women in the postvaccine study. Monitoring HPV-type prevalence through population-based strategies will continue to be important in evaluating the impact of the HPV vaccine.

PMID:34289090 | DOI:10.1002/cncr.33582

Syst Biol. 2021 Jul 21:syab060. doi: 10.1093/sysbio/syab060. Online ahead of print.

ABSTRACT

Whole genome comparisons based on Average Nucleotide Identities (ANI) and the Genome-to-genome distance calculator have risen to prominence in rapidly classifying prokaryotic taxa using whole genome sequences. Some implementations have even been proposed as a new standard in species classification and have become a common technique for papers describing newly sequenced genomes. However, attempts to apply whole genome divergence data to delineation of higher taxonomic units and to phylogenetic inference have had difficulty matching those produced by more complex phylogenetic methods. We present a novel method for generating statistically supported phylogenies of archaeal and bacterial groups using a combined ANI and alignment fraction-based metric. For the test cases to which we applied the developed approach we obtained results comparable with other methodologies up to at least the family-level. The developed method uses non-parametric bootstrapping to gauge support for inferred groups. This method offers the opportunity to make use of whole-genome comparison data, that are already being generated, to quickly produce phylogenies including support for inferred groups. Additionally, the developed ANI methodology can assist classification of higher taxonomic groups.

PMID:34289044 | DOI:10.1093/sysbio/syab060

Genome Biol Evol. 2021 Jul 20:evab167. doi: 10.1093/gbe/evab167. Online ahead of print.

ABSTRACT

Tests based on the dN/dS statistic are used to identify positive selection of non-synonymous polymorphisms. Using these tests on alignments of all orthologues from related species can provide insights into which gene categories have been most frequently positively selected. However, longer alignments have more power to detect positive selection, creating a detection bias that could create misleading results from functional enrichment tests. Most studies of positive selection in plant pathogens focus on genes with specific virulence functions, with little emphasis on broader molecular processes. Furthermore, no studies in plant pathogens have accounted for detection bias due to alignment length when performing functional enrichment tests. To address these research gaps, we analyse 12 genomes of the phytopathogenic fungal genus Botrytis, including two sequenced in this study. To establish a temporal context, we estimated fossil-calibrated divergence times for the genus. We find that Botrytis likely originated 16-18 million years ago in the Miocene and underwent continuous radiation ending in the Pliocene. An untargeted scan of Botrytis single copy orthologues for positive selection with three different statistical tests uncovered evidence for positive selection among proteases, signalling proteins, CAZymes and secreted proteins. There was also a strong over-representation of transcription factors among positively selected genes. This over-representation was still apparent after two complementary controls for detection bias due to sequence length. Positively selected sites were depleted within DNA binding domains, suggesting changes in transcriptional responses to internal and external cues or protein-protein interactions have undergone positive selection more frequently than changes in promoter fidelity.

PMID:34289036 | DOI:10.1093/gbe/evab167

Cereb Cortex. 2021 Jul 21:bhab131. doi: 10.1093/cercor/bhab131. Online ahead of print.

ABSTRACT

We aimed to identify symptom-related neuroimaging biomarkers for patients with dysgenesis of the corpus callosum (dCC) by summarizing neurological symptoms reported in clinical evaluations and correlating them with retrospectively collected structural/diffusion brain magnetic resonance imaging (MRI) measures from 39 patients/controls (mean age 8.08 ± 3.98). Most symptoms/disorders studied were associated with CC abnormalities. Total brain (TB) volume was related to language, cognition, muscle tone, and metabolic/endocrine abnormalities. Although white matter (WM) volume was not related to symptoms studied, gray matter (GM) volume was related to cognitive, behavioral, and metabolic/endocrine disorders. Right hemisphere (RH) cortical thickness (CT) was linked to language abnormalities, while left hemisphere (LH) CT was linked to epilepsy. While RH gyrification index (GI) was not related to any symptoms studied, LH GI was uniquely related to cognitive disorders. Between patients and controls, GM volume and LH/RH CT were significantly greater in dCC patients, while WM volume and LH/RH GI were significantly greater in controls. TB volume and diffusion indices for tissue microstructures did not show differences between the groups. In summary, our brain MRI-based measures successfully revealed differential links to many symptoms. Specifically, LH GI abnormality can be a predictor for dCC patients, which is uniquely associated with the patients’ symptom. In addition, patients with CC abnormalities had normal TB volume and overall tissue microstructures, with potentially deteriorated mechanisms to expand/fold the brain, indicated by GI.

PMID:34289021 | DOI:10.1093/cercor/bhab131

Brain. 2021 Jul 20:awab274. doi: 10.1093/brain/awab274. Online ahead of print.

ABSTRACT

Wilson’s disease is an autosomal-recessive disorder of copper metabolism with neurological and hepatic presentations. Chelation therapy is used to ‘de-copper’ patients but neurological outcomes remain unpredictable. A range of neuroimaging abnormalities have been described and may provide insights into disease mechanisms, in addition to prognostic and monitoring biomarkers. Previous quantitative MRI analyses have focussed on specific sequences or regions of interest, often stratifying chronically-treated patients according to persisting symptoms as opposed to initial presentation. In this cross-sectional study, we performed a combination of unbiased, whole-brain analyses on T1-weighted, fluid-attenuated inversion recovery, diffusion-weighted and susceptibility-weighted imaging data from 40 prospectively-recruited patients with Wilson’s disease (age range 16-68). We compared patients with neurological (n = 23) and hepatic (n = 17) presentations to determine the neuroradiological sequelae of the initial brain injury. We also subcategorized patients according to recent neurological status, classifying those with neurological presentations or deterioration in the preceding six months as having ‘active’ disease. This allowed us to compare patients with active (n = 5) and stable (n = 35) disease and identify imaging correlates for persistent neurological deficits and copper indices in chronically-treated, stable patients. Using a combination of voxel-based morphometry and region-of-interest volumetric analyses, we demonstrate that grey matter volumes are lower in the basal ganglia, thalamus, brainstem, cerebellum, anterior insula and orbitofrontal cortex when comparing patients with neurological and hepatic presentations. In chronically-treated, stable patients, the severity of neurological deficits correlated with grey matter volumes in similar, predominantly subcortical regions. In contrast, the severity of neurological deficits did not correlate with the volume of white matter hyperintensities, calculated using an automated lesion segmentation algorithm. Using tract-based spatial statistics, increasing neurological severity in chronically-treated patients was associated with decreasing axial diffusivity in white matter tracts whereas increasing serum non-caeruloplasmin-bound (‘free’) copper and active disease were associated with distinct patterns of increasing mean, axial and radial diffusivity. Whole-brain quantitative susceptibility mapping identified increased iron deposition in the putamen, cingulate and medial frontal cortices of patients with neurological presentations relative to those with hepatic presentations and neurological severity was associated with iron deposition in widespread cortical regions in chronically-treated patients. Our data indicate that composite measures of subcortical atrophy provide useful prognostic biomarkers, whereas abnormal mean, axial and radial diffusivity are promising monitoring biomarkers. Finally, deposition of brain iron in response to copper accumulation may directly contribute to neurodegeneration in Wilson’s disease.

PMID:34289020 | DOI:10.1093/brain/awab274