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Nevin Manimala Statistics

Ozone exposure and blood transcriptome: A randomized, controlled, crossover trial among healthy adults

Environ Int. 2022 Apr 12;163:107242. doi: 10.1016/j.envint.2022.107242. Online ahead of print.

ABSTRACT

RATIONALE: Transcriptome-wide analysis is powerful in studying systemic RNA changes following environmental exposures. However, impacts of ozone inhalation on circulating transcriptome have not yet been examined.

OBJECTIVES: To explore the impact of acute ozone exposure on circulating transcriptome using RNA sequencing (RNA-seq).

METHODS: We recruited 32 healthy young adults in a randomized, crossover, controlled exposure trial. Each participant completed two 2-h exposure sessions of ozone (200 ppb) and clean air, respectively. Blood samples were collected at the end of each session and were used for RNA-seq. The differentially expressed genes associated with ozone exposure were assessed using Bayesian adjusted statistics from linear models in the limma R package.

RESULTS: A total of 29 participants finished this trial and donated their blood samples for transcriptome analysis. The average concentration of ozone was 7.8 ± 2.6 ppb under clean air and 201.1 ± 1.7 ppb under ozone exposure session. A total of 1899 genes were significantly changed (1067 up-regulated and 832 down-regulated) by ozone exposure at a false discovery rate < 0.05, in which 403 genes had a fold change of > 1.2 or < 0.8. The top 10 terms of biological processes showed that most of the differentially expressed genes were related to various functions, such as neutrophil degranulation, immune response, and neutrophil activation. Pathway enrichment analysis showed dozens of pathways were dysregulated after ozone exposure, including mitochondrial dysfunction, and glucocorticoid receptor signaling.

CONCLUSION: For the first time this trial characterized the genome-wide changes of mRNA in response to ozone exposure. We identified a range of differentially expressed genes that were involved in dozens of biological processes and pathways, providing novel biological insights into the systemic health effects of ozone.

PMID:35430440 | DOI:10.1016/j.envint.2022.107242

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Nevin Manimala Statistics

Rhinosinusitis Quality-of-Life Assessment: A Persian Adaptation and Validation

Arch Iran Med. 2022 Mar 1;25(3):178-181. doi: 10.34172/aim.2022.30.

ABSTRACT

BACKGROUND: Rhinosinusitis involves inflammation within the paranasal sinuses and the nasal mucosa. It is a very common chronic health condition. This paper performs a validation process on the Persian translation of the rhinosinusitis quality-of-life questionnaire (RhinoQOL), for use in clinical assessment of chronic rhinosinusitis (CRS) patients. The Lund-Mackay score is also used widely in assessing CRS, and this study aims to describe its relationship to RhinoQOL.

METHODS: The Persian RhinoQOL adaptation was carried out on 110 CRS patients. A follow-up questionnaire was completed two weeks later. Psychometric properties were determined by statistical analysis (reliability, reproducibility, validity, responsiveness). A total of 45 patients were included for radiologic score calculation. The Spearman’s test was used for assessing the correlation between the RhinoQOL scores and Lund-Mackay score.

RESULTS: Internal reliability was excellent for the impact scale (Cronbach’s alpha=0.92). Cronbach’s alpha was 0.63 and 0.55 for frequency and irritation scales, which reflects lower internal consistency values. Temporal stability or Test-retest reliability was excellent across all three scales. ICC was 0.96, 0.97, and 0.99 for RhinoQOL frequency, irritation, and impact scales. No significant correlation was observed between the Lund-Mackay score and RhinoQOL scores in terms of frequency, irritation and impact scales.

CONCLUSION: The Persian version of RhinoQOL appears to be as reliable, valid, and sensitive to change as the English version.

PMID:35429960 | DOI:10.34172/aim.2022.30

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Nevin Manimala Statistics

Rates and Reasons of Laboratory Sample Rejection due to Pre-analytical Errors in Clinical Settings

Arch Iran Med. 2022 Mar 1;25(3):166-170. doi: 10.34172/aim.2022.28.

ABSTRACT

BACKGROUND: Laboratory analysis errors in procedure or interpretation may be seen during the process of completing physician test orders. They may also result in rejection of the requests due to some applicability reasons. Hence, this study was carried out to determine the rate and reasons for such rejections in clinical settings.

METHODS: This cross-sectional comparative study was performed on 104008 laboratory tests in a one-year period in terms of the percentage and type of errors that occurred in Shahid Bahonar Hospital in Kerman, Iran, in 2018. The types of studied errors included hemolysis, sample clotting, insufficient sample size, and mistakes in labels or absence of labels on the sample.

RESULTS: In this study, 104008 laboratory tests were performed, with 2299 (2.21%) sample rejections, 456 (32.31%) complete blood count (CBC) sample clotting; 417 (29.38 %) hemolysis; and 150 (17.47 %) inadequate sample volume as the majority of errors. There was no statistically significant relationship between pre-analysis errors and clinical aspects (P=0.124).

CONCLUSION: According to the results, it may be concluded that considering the high prevalence of laboratory errors in comparison with the majority of other studies, continuous training courses and determination of the causes of these errors are crucial to attaining better function and basic knowledge.

PMID:35429958 | DOI:10.34172/aim.2022.28

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Nevin Manimala Statistics

Urinary phthalate metabolite mixtures in pregnancy and fetal growth: Findings from the infant development and the environment study

Environ Int. 2022 Apr 9;163:107235. doi: 10.1016/j.envint.2022.107235. Online ahead of print.

ABSTRACT

BACKGROUND: Prenatal phthalate exposure has been linked to reductions in fetal growth in animal and laboratory studies, but epidemiologic evidence is equivocal.

OBJECTIVE: Examine the association between prenatal phthalate metabolite mixtures and fetal growth and evaluate whether that association is modified by fetal sex or omega-3 intake during pregnancy.

METHODS: Analyses included 604 singleton pregnancies from TIDES, a prospective pregnancy cohort with spot urine samples and questionnaires collected in each trimester. Pregnancy-averaged phthalate exposure estimates were calculated as the geometric means of specific-gravity corrected phthalate metabolites. Fetal growth outcomes included birthweight and length, and ultrasound-derived size and velocity of estimated fetal weight, femur length, abdominal and head circumferences in the second and third trimesters. We used a novel application of quantile g-computation to estimate the joint association between pregnancy-averaged phthalate exposure and fetal growth, and to examine effect modification of that association by infant sex or omega-3 intake during pregnancy.

RESULTS: There were few statistically significant differences in birth size and fetal growth by exposure. A one-quartile increase in the phthalate mixture was modestly associated with reduced birthweight(β [95% confidence interval)]: -54.6 [-128.9, 19.7] grams; p = 0.15) and length (-0.2 [-0.6, 0.2] centimeters; p = 0.40). A one-quartile increase in the phthalate mixture was associated with reduced birth length in males (-0.5 [-1.0, 0.0] centimeters) but not for females (0.1 [-0.2, 0.3] centimeters); interaction p = 0.05. The phthalate metabolite mixture was inversely associated with ultrasound-derived fetal growth among those with adequate omega-3 intake. For example, a one-quartile increase in the phthalate mixture was associated with reduced abdominal circumference in the third trimesters in those with adequate omega-3 intake (-3.3 [-6.8, 0.1] millimeters) but not those with inadequate omega-3 intake (1.8 [-0.8, 4.5] millimeters); interaction p = 0.01.

CONCLUSION: Prenatal phthalate exposure was not significantly associated with fetal growth outcomes, with some exceptions for certain subgroups.

PMID:35429919 | DOI:10.1016/j.envint.2022.107235

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Nevin Manimala Statistics

Trends in the Incidence Rates of Breast and Gynecological Cancers in Asia from 1998-2012: An Ecological Study

Arch Iran Med. 2022 Feb 1;25(2):112-117. doi: 10.34172/aim.2022.18.

ABSTRACT

BACKGROUND: There is limited evidence on the epidemiology and time trend analysis of incidence rates of gynecological cancer in Asia as a whole. We conducted this study to demonstrate breast and gynecological cancers incidence and trends in selected Asian populations.

METHODS: We conducted this ecological study using cancer and population data from cancer incidence in five continents (CI5). We extracted the data of breast, uterine, cervix and ovary cancers in selected Asian populations from 1998 to 2012 from CI5plus. We used Joinpoint regression model (version 4.8.0.1) to evaluate the annual percentage change (APC), which characterizes trends in cancer rates over time, and the average annual percent changes (AAPCs), which describes the average APCs over a period of multiple years. Results were considered statistically significant at P < 0.05.

RESULTS: Between breast and gynecological cancers, breast cancer has the highest incidence rates among women in Asia. The time trend of the incidence rates showed a constant growth in breast, ovary and corpus uteri cancers. This rising trend was obviously sharper for uterine cancer (AAPC 95% CI = 3.4 [3.0, 3.7]) followed by breast [AAPC 95% CI = 2.1 (2.0, 2.2)] and ovarian cancers (AAPC 95% CI = 0.5 [-0.4, 1.3]). The age-adjusted incidence rate (ASR) of cervical cancer displayed a declining trend from 1998 to 2012 (AAPC 95% CI = -1.4 [-2.4, -0.5]).

CONCLUSION: Incidence rates of breast and gynecological cancers have a rising trend in Asian countries. However, breast and gynecological cancers have different patterns of time trend.

PMID:35429948 | DOI:10.34172/aim.2022.18

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Do urinary metals associate with the homeostasis of inflammatory mediators? Results from the perspective of inflammatory signaling in middle-aged and older adults

Environ Int. 2022 Apr 9;163:107237. doi: 10.1016/j.envint.2022.107237. Online ahead of print.

ABSTRACT

OBJECTIVE: We aimed to investigate whether urinary metal mixtures are associated with the homeostasis of inflammatory mediators in middle-aged and older adults.

METHODS: A four-visit repeated-measures study was conducted with 98 middle-aged and older adults from five communities in Beijing, China. Only one person was lost to follow-up at the third visit. Ultimately, 391 observations were included in the analysis. The urinary concentrations of 10 metals were measured at each visit using inductively coupled plasma mass spectrometry (ICP-MS) with a limit of detection (LOD) ranging from 0.002 to 0.173 µg/L, and the detection rates were all above 84%. Similarly, 14 serum inflammatory mediators were measured using a Beckman Coulter analyzer and the Bio-Plex MAGPIX system. A linear mixed model (LMM), LMM with least absolute shrinkage and selection operator regularization (LMMLASSO), and Bayesian kernel machine regression (BKMR) were adopted to explore the effects of urinary metal mixtures on inflammatory mediators.

RESULTS: In LMM, a two-fold increase in urinary cesium (Cs) and chromium (Cr) was statistically associated with -35.22% (95% confidence interval [CI]: -53.17, -10.40) changes in interleukin 6 (IL-6) and -11.13% (95 %CI: -20.67, -0.44) in IL-8. Urinary copper (Cu) and selenium (Se) was statistically associated with IL-6 (88.10%, 95%CI: 34.92, 162.24) and tumor necrosis factor-alpha (TNF-α) (22.32%, 95%CI: 3.28, 44.12), respectively. Similar results were observed for the LMMLASSO and BKMR. Furthermore, Cr, Cs, Cu, and Se were significantly associated with other inflammatory regulatory network mediators. For example, urinary Cs was statistically associated with endothelin-1, and Cr was statistically associated with endothelin-1 and intercellular adhesion molecule 1 (ICAM-1). Finally, the interaction effects of Cu with various metals on inflammatory mediators were observed.

CONCLUSION: Our findings suggest that Cr, Cs, Cu, and Se may disrupt the homeostasis of inflammatory mediators, providing insight into the potential pathophysiological mechanisms of metal mixtures and chronic diseases.

PMID:35429917 | DOI:10.1016/j.envint.2022.107237

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Nevin Manimala Statistics

Overall survival with palbociclib plus endocrine therapy versus capecitabine in postmenopausal patients with hormone receptor-positive, HER2-negative metastatic breast cancer in the PEARL study

Eur J Cancer. 2022 Apr 13;168:12-24. doi: 10.1016/j.ejca.2022.03.006. Online ahead of print.

ABSTRACT

BACKGROUND: An earlier analysis of the PEARL phase III study showed that palbociclib plus endocrine therapy (ET) does not improve progression-free survival (PFS) over capecitabine in aromatase inhibitor-resistant, hormone receptor-positive/human epidermal growth factor receptor 2-negative metastatic breast cancer (MBC) patients. Here, we report the final overall survival (OS) analysis.

METHODS: Postmenopausal patients (N = 601) were randomized 1:1 to capecitabine or palbociclib plus ET (exemestane, Cohort 1; fulvestrant, Cohort 2). OS was analysed in Cohort 2, the wild-type ESR1 population and the overall population. Additionally, we analysed subsequent systemic therapies and explored PFS2 (time from randomization to the end of the first subsequent therapy/death).

RESULTS: OS was 31.1 months for palbociclib plus fulvestrant and 32.8 months for capecitabine (adjusted hazard ratio [aHR] 1.10, 95% confidence interval [CI] 0.81-1.50, P = 0.550). In the wild-type ESR1 population, OS was 37.2 months for palbociclib plus ET and 34.8 months for capecitabine (aHR 1.06, 95% CI 0.81-1.37, P = 0.683). In OS analyses, no subgroup showed superiority for palbociclib plus ET over capecitabine. OS in the overall population was 32.6 months for palbociclib plus ET and 30.9 months for capecitabine (P = 0.995). Subsequent systemic therapy was given to 79.8% and 82.9% of patients with palbociclib plus ET and capecitabine, respectively. Median PFS2 was similar between study arms (Cohort 2, P = 0.941; wild-type ESR1 population, P = 0.827). No new safety findings were observed.

CONCLUSIONS: Palbociclib plus ET did not show a statistically superior OS compared to capecitabine in MBC patients progressing on aromatase inhibitors.

TRIAL REGISTRATION: NCT02028507 (ClinTrials.gov), 2013-003170-27 (EudraCT).

PMID:35429901 | DOI:10.1016/j.ejca.2022.03.006

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Nevin Manimala Statistics

Micronutrients in tinnitus: A National Health and Nutrition Examination Survey analysis

Am J Otolaryngol. 2022 Apr 7;43(3):103460. doi: 10.1016/j.amjoto.2022.103460. Online ahead of print.

ABSTRACT

PURPOSE: Micronutrients and their supplementation have been investigated in the development, severity, and treatment of tinnitus. This study aimed to evaluate associations between tinnitus parameters and levels of zinc, manganese, and vitamin B12.

MATERIALS AND METHODS: This retrospective study analyzed National Health and Nutrition Examination Survey 2011-2012 and 2015-2016 participants aged 20-69 who answered whether they had symptoms of tinnitus in the past year. Persons with tinnitus symptoms further reported how regularly they had symptoms and how disruptive symptoms were. Multivariable regressions accounting for age, gender, and race/ethnicity were used to evaluate the influence of low serum/blood levels of zinc, manganese, and vitamin B12 on tinnitus presence, regularity, and disruptiveness.

RESULTS: This study included 9439 participants, with 16.2% of the sample reporting tinnitus symptoms. In multivariable regression models, low blood manganese was associated with tinnitus regularity (proportional OR: 1.47 [95% CI: 1.06, 2.05], p = 0.0213) and tinnitus disruptiveness (proportional OR: 1.78 [95% CI: 1.08, 2.96], p = 0.0250), but not tinnitus presence (p = 0.4813). Low serum zinc and low serum vitamin B12 did not have statistically significant associations with analyzed tinnitus parameters.

CONCLUSIONS: A nationally representative analysis found that low blood manganese was significantly associated with tinnitus regularity and disruptiveness, but found that serum zinc and vitamin B12 had no association with tinnitus parameters. These findings suggest that low micronutrient levels are unlikely to be contributors to tinnitus; however, the results suggest further research on manganese supplementation in patients with tinnitus may be merited.

PMID:35429847 | DOI:10.1016/j.amjoto.2022.103460

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Nevin Manimala Statistics

White matter microstructural damage in chronic ischemic stroke affecting the left inferior frontal gyrus: Association with cognitive functions

Clin Neurol Neurosurg. 2022 Apr 2;217:107238. doi: 10.1016/j.clineuro.2022.107238. Online ahead of print.

ABSTRACT

Brain ischemia affects the integrity of local white matter and regions that are distant to the primary lesion location. In this study, we analyzed the patterns of white matter microstructural damage and the cognitive performance of 22 patients with left hemisphere stroke. Patients were divided in two groups: one with target lesion affecting the left inferior frontal gyrus (left inferior frontal gyrus, LIFG, n = 11) and the other without ischemic lesion in this region (non-left inferior frontal gyrus, NLIFG, n = 11). Each group was compared with 11 matched healthy controls. Tract-Based Spatial Statistics was used to assess differences in diffusion tensor indices between the groups and for the association of white matter structure with cognitive performance. When compared to Controls, the LIFG showed extensive intra- and interhemispheric disconnection, with surrogate markers for tissue loss with demyelination in the corpus callosum, and microstructural changes that are independent of gross tissue loss in the contralateral hemisphere. The NLIFG group presented discrete alterations in white matter from the ipsilateral hemisphere, with surrogate markers for tissue loss with axonal injury. When LIFG is compared to NLIFG, white matter abnormalities with no gross tissue loss were observed in the corpus callosum and in the contralateral hemisphere. In addition LIFG had worse performance on cognitive functions. In conclusion, our results identify different diffusion profiles for LIFG and NLIFG groups, suggesting more extensive and pronounced white matter damage in the commissural and interhemispheric connections in the LIFG group, in addition to more pronounced cognitive impairment.

PMID:35429854 | DOI:10.1016/j.clineuro.2022.107238

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Ibuprofen prescription following adult tonsillectomy reduces postoperative opioid use

Am J Otolaryngol. 2022 Apr 5;43(3):103436. doi: 10.1016/j.amjoto.2022.103436. Online ahead of print.

ABSTRACT

BACKGROUND: Based on a 2018 American Academy of Otolaryngology – Head and Neck Surgery survey, an average of 37 tablets of opioid medication, or about a week’s worth of medication, were prescribed after adult tonsillectomy. Nearly 15% of patients will still be taking opioids one year after an initial weeklong prescription, according to data from the Centers for Disease Control and Prevention. Non-steroidal anti-inflammatory medications have traditionally been avoided in adult tonsillectomy patients due to concern for increased bleeding risk from platelet dysfunction, despite little evidence supporting this claim. This study sought to demonstrate that ibuprofen prescriptions after tonsillectomy could be a safe and effective way to reduce postoperative opioid use.

METHODS: This study was a retrospective chart review of patients undergoing tonsillectomy with one surgeon over three years. Half of the patients received a prescription for postoperative opioid medications and were counseled against taking ibuprofen. The other half of patients were prescribed ibuprofen following surgery and only provided with opioid analgesia as a rescue medication. The New Mexico Prescription Monitoring System was used to verify opioid prescriptions. Descriptive statistics and logistic regression were used to analyze the data.

RESULTS: Ninety-nine patients were included in analysis, with 53 in the first group that did not receive ibuprofen and 46 in the second group that did receive ibuprofen. There was no difference in the bleeding rate between the two groups. Significantly fewer patients in the ibuprofen group filled postoperative opioid prescriptions when compared to the group that did not receive ibuprofen (40% vs. 96.2%, p < 0.0001, OR = 0.02).

CONCLUSION: Ibuprofen is a safe and effective analgesic following adult tonsillectomy and significantly reduces the proportion of patients who must fill a postoperative opioid prescription.

PMID:35429845 | DOI:10.1016/j.amjoto.2022.103436