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Nevin Manimala Statistics

Serum Specific Antibodies Do Not Seem to Have an Additional Role in the Diagnosis of Hypersensitivity Pneumonitis

Med Lav. 2023 Oct 24;114(5):e2023042.

ABSTRACT

BACKGROUND: We aimed to investigate the contribution of serum IgG testing to the history of exposure in the diagnosis of fibrotic hypersensitivity pneumonitis.

METHODS: A single-center, retrospective, cross-sectional study including 63 patients pathologically diagnosed with fibrotic hypersensitivity pneumonitis in line with the guidelines of the American Thoracic Society. Descriptive statistics were presented and Kappa statistic was performed to evaluate the compatibility between panel and the history of exposure.

RESULTS: The median age was 63 (22-81) years and 34 (54%) were male. Forty-six patients (73%) had a positive history of exposure. Thirty-nine patients (61.9%) had a positive HP/Avian panel. The most common exposure agent was mold (34.9%), followed by parakeet (31.7%). The antibody detected the most was penicillium chrysogenum lgG (36.5%), followed by aspergillus fumigatus (31.8%). There was no compatibility between HP/Avian panel and history of exposure (kappa coefficient= 0.18, p= 0.14). When the exposure was only assessed based on the history, 4 (6.35%) patients were diagnosed as fibrotic hypersensitivity pneumonitis with low confidence, 6 (9.52%) with moderate confidence, 11 (17.46%) with high confidence and 42 (66.67%) with definite confidence; whereas 4 (6.35%) patients were diagnosed as fibrotic hypersensitivity pneumonitis with low confidence, 6 (9.52%) with moderate confidence, 9 (14.29%) patients with high confidence and 44 (69.84%) patients with definite confidence if exposure was evaluated with history and/or panel.

CONCLUSIONS: Serum specific precipitating antibody panel does not seem to provide additional value to the history of exposure in the diagnosis of fibrotic hypersensitivity pneumonitis.

PMID:37878260

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Nevin Manimala Statistics

Association of body mass index with risk of cardiometabolic disease, multimorbidity and mortality: a multi-state analysis based on the Kailuan cohort

Endocrine. 2023 Oct 25. doi: 10.1007/s12020-023-03570-w. Online ahead of print.

ABSTRACT

PURPOSE: To evaluate the association of body mass index (BMI) with risk of first cardiometabolic disease (FCMD), cardiometabolic multimorbidity (CMM) and death.

METHODS: 87,512 participants free of CMD were included from the Kailuan cohort, which was established during 2006-2007 and followed up until 2020. BMI was classified as underweight ( < 18.5 kg/m2), healthy weight (18.5-23.9 kg/m2), overweight (24.0-27.9 kg/m2), mildly obese (28.0-31.9 kg/m2), and severely obese ( ≥ 32.0 kg/m2). FCMD was defined as the first onset of diabetes, heart disease, or stroke, and CMM as the coexistence of at least two CMD. The hazard ratio (HR) and 95% confidence interval (95%CI) were estimated with multi-state models.

RESULTS: 20,577 participants developed FCMD, 2232 developed CMM afterwards, and 10,191 died. Individuals with higher BMI was more likely to develop FCMD and CMM. Compared with healthy weight, the HR (95%CI) of severe obesity for transition from health to FCMD and from FCMD to CMM was 3.12 (2.91, 3.34) and 1.92 (1.60, 2.31), respectively. On the other hand, underweight was consistently associated with higher mortality risk regardless of initial status, whereas severe obesity was only related to increased risk for transition from health to death (HR: 1.36; 95%CI: 1.17, 1.56) but not for transition from FCMD (HR: 0.70; 95%CI: 0.57, 0.87) or CMM (HR: 0.80; 95%CI: 0.54, 1.19) to death.

CONCLUSION: Our findings highlighted the importance of maintaining healthy weight for primary and secondary prevention of CMD and reflected the demand for more accurate measurement and comprehensive management of obesity for CMD patients.

PMID:37878230 | DOI:10.1007/s12020-023-03570-w

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Nevin Manimala Statistics

Distribution and in-vitro bioaccessibility of potentially toxic metals in surface soils from a mining and a non-mining community in Ghana: implications for human health

Environ Geochem Health. 2023 Oct 25. doi: 10.1007/s10653-023-01776-5. Online ahead of print.

ABSTRACT

The concentration and bioaccessibility of potentially toxic metals, including As, Cd, Cr, Cu, Mn, Ni, Pb and Zn, were determined in surface soil samples from a mining community (Kenyasi) and a non-mining community (Sunyani) in Ghana, to investigate the contribution of mining activities to the environmental burden of potentially toxic metals. The study found significant differences in metal concentrations (p < 0.05) in As, Cd, Cu, Mn, Ni, and Zn, but no significant difference (p > 0.05) in Pb and Cr between the two communities. The study found a moderate correlation between pH and metal concentrations in the mining community and a moderate positive correlation with As, Cd, Cr, Cu, Ni, and Zn in the non-mining community. The distribution pattern revealed elevated levels of toxic metals in the southeastern corridor of the mining community, which is close to a gold mine. Most heavy metals were concentrated in the commercial community’s southern zone, with more residents and private elementary schools. Metal bioaccessibility was variable, and except for Cu and Zn, the mean bioaccessibility was less than 50% for a given metal. Contamination factor, geoaccumulation index, and soil enrichment factor suggested very high contamination of Cd, and a considerable to moderate contamination of As, Ni, Zn, and Cu at both the mining and non-mining communities. The above observations and the pollution and risk indices employed in this study confirmed that the mining community was more polluted (PLI = 2.145) than the non-mining community (PLI = 1.372). The total metal hazard (HI) exceeded thresholds by three and four times at non-mining and mining sites. Regular monitoring is necessary, especially in the mining community, to prevent soil metal accumulation.

PMID:37878226 | DOI:10.1007/s10653-023-01776-5

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Assessment of retinal and choroidal vessel density and nerve fibre layer thickness changes after orbitotomy in patients with severe non-active thyroid orbitopathy: a prospective study

Int Ophthalmol. 2023 Oct 25. doi: 10.1007/s10792-023-02790-3. Online ahead of print.

ABSTRACT

PURPOSE: To evaluate the optical coherence tomography angiogram changes in non-active severe thyroid-related ophthalmopathy patients after cosmetic bone decompression.

METHODS: Eighteen patients (25 eyes) with severe not active not compressive (NANC) TED who were candidates for decompression surgery for cosmetic reasons were included in this study, and a 3 × 3 mm macular scan was used to measure vessel density and RNFL thickness. Whole macular vessel density in its superficial, deep and choriocapillaris layers was evaluated. The following data were extracted for each of layers: superior and inferior hemispheres, fovea, parafoveal vessel density, its superior and inferior hemispheres, and temporal, superior, nasal and inferior quadrant.

RESULTS: The mean RPC increased postoperatively, which was statistically significant in small vessels of peripapillary area (p-value = 0.045). The mean RNFL thickness decreased after surgery and it was statistically significant in the peripapillary (p-value = 0.032) and Inferior-Hemifield area (p-value = 0.036). The choriocapillaris changes were significant in Superior-Hemifield (p-value = 0.031) and Fovea (p-value = 0.03).

CONCLUSION: Thyroid-associated orbitopathy patients have a tendency to decrease vascular density and correlated with disease activity more than stage of orbitopathy. There was not a strong and even discrepant result in linkage of RNFL thickness and other optic nerve function tests and TED patient status and it is needed to do studies with more epidemiologic power and same methodology of study to be more comparable.

PMID:37878198 | DOI:10.1007/s10792-023-02790-3

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Ceftazidime-avibactam versus polymyxins in treating patients with carbapenem-resistant Enterobacteriaceae infections: a systematic review and meta-analysis

Infection. 2023 Oct 25. doi: 10.1007/s15010-023-02108-6. Online ahead of print.

ABSTRACT

OBJECTIVE: Carbapenem-resistant Enterobacteriaceae (CRE) pose a significant threat to human health and have emerged as a major public health concern. We aimed to compare the efficacy and the safety of ceftazidime-avibactam (CAZ-AVI) and polymyxin in the treatment of CRE infections.

METHODS: A systematic review and meta-analysis was performed by searching the databases of EMBASE, PubMed, and the Cochrane Library. Published studies on the use of CAZ-AVI and polymyxin in the treatment of CRE infections were collected from the inception of the database until March 2023. Two investigators independently screened the literature according to the inclusion and exclusion criteria, evaluated the methodological quality of the included studies and extracted the data. The meta-analysis was performed using RevMan 5.4 software.

RESULTS: Ten articles with 833 patients were included (CAZ-AVI 325 patients vs Polymyxin 508 patients). Compared with the patients who received polymyxin-based therapy, the patients who received CAZ-AVI therapy had significantly lower 30-days mortality (RR = 0.49; 95% CI 0.01-2.34; I2 = 22%; P < 0.00001), higher clinical cure rate (RR = 2.70; 95% CI 1.67-4.38; I2 = 40%; P < 0.00001), and higher microbial clearance rate (RR = 2.70; 95% CI 2.09-3.49; I2 = 0%; P < 0.00001). However, there was no statistically difference in the incidence of acute kidney injury between patients who received CAZ-AVI and polymyxin therapy (RR = 1.38; 95% CI 0.69-2.77; I2 = 22%; P = 0.36). In addition, among patients with CRE bloodstream infection, those who received CAZ-AVI therapy had significantly lower mortality than those who received polymyxin therapy (RR = 0.44; 95% CI 0.27-0.69, I2 = 26%, P < 0.00004).

CONCLUSIONS: Compared to polymyxin, CAZ-AVI demonstrated superior clinical efficacy in the treatment of CRE infections, suggesting that CAZ-AVI may be a superior option for CRE infections.

PMID:37878197 | DOI:10.1007/s15010-023-02108-6

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Association between persistent organic pollutants in human milk and the infant growth and development throughout the first year postpartum in a cohort from Rio de Janeiro, Brazil

Environ Sci Pollut Res Int. 2023 Oct 25. doi: 10.1007/s11356-023-30316-y. Online ahead of print.

ABSTRACT

Persistent organic pollutants (POPs) are compounds that are recalcitrant and ubiquitous that bioaccumulate in human milk (HM) and can impact infant growth and development. We explore the association between POP concentration in HM at 2-50 days postpartum and infant growth and development trajectory throughout the first year of life. A cohort of 68 healthy adult Brazilian women and their infants were followed from 28 to 35 gestational weeks to 12 months postpartum. HM samples were collected between 2 and 50 days postpartum, and POP concentrations were analyzed using gas chromatography with mass spectrometry. Concentrations of POPs >limit of quantification (LOQ) were defined as presence, and concentrations ≤LOQ as an absence. Growth z-scores were analyzed according to WHO growth charts and infant development scores according to Age & Stages Questionnaires at 1 (n = 66), 6 (n = 50), and 12 months (n = 45). Linear mixed effects (LME) models were used to investigate the association of POPs in HM with infant growth and development. Benjamini-Hochberg (BH) correction for multiple testing was performed to reduce the false discovery ratio. P < 0.1 was considered for models with the interaction between POPs and time/sex. After BH correction, adjusted LME models with time interaction showed (1) a positive association between the presence of β hexachlorocyclohexane and an increase in head circumference-for-age z-score (β = 0.003, P = 0.095); (2) negative associations between total POPs (β = -0.000002, P = 0.10), total organochlorine pesticides (β = -0.000002, P = 0.10), and dichlorodiphenyldichloroethylene concentrations in HM (β = -0.000002, P = 0.10) and fine motor scores. No statistical difference between the sexes was observed. Postnatal exposure to organochlorine pesticides in HM shows a positive association with the trajectory of head circumference-for-age z-score and a negative association with the trajectories of fine motor skills scores. Future studies on POP variation in HM at different postpartum times and their effect on infant growth and development should be encouraged.

PMID:37878172 | DOI:10.1007/s11356-023-30316-y

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The use of weighted multiple linear regression to estimate QTL × QTL × QTL interaction effects of winter wheat (Triticum aestivum L.) doubled-haploid lines

J Appl Genet. 2023 Oct 25. doi: 10.1007/s13353-023-00795-3. Online ahead of print.

ABSTRACT

Knowledge of the magnitude of gene effects and their interactions, their nature, and contribution to determining quantitative traits is very important in conducting an effective breeding program. In traditional breeding, information on the parameter related to additive gene effect and additive-additive interaction (epistasis) and higher-order additive interactions would be useful. Although commonly overlooked in studies, higher-order interactions have a significant impact on phenotypic traits. Failure to account for the effect of triplet interactions in quantitative genetics can significantly underestimate additive QTL effects. Understanding the genetic architecture of quantitative traits is a major challenge in the post-genomic era, especially for quantitative trait locus (QTL) effects, QTL-QTL interactions, and QTL-QTL-QTL interactions. This paper proposes using weighted multiple linear regression to estimate the effects of triple interaction (additive-additive-additive) quantitative trait loci (QTL-QTL-QTL). The material for the study consisted of 126 doubled haploid lines of winter wheat (Mandub × Begra cross). The lines were analyzed for 18 traits, including percentage of necrosis leaf area, percentage of leaf area covered by pycnidia, heading data, and height. The number of genes (the number of effective factors) was lower than the number of QTLs for nine traits, higher for four traits and equal for five traits. The number of triples for unweighted regression ranged from 0 to 9, while for weighted regression, it ranged from 0 to 13. The total aaagu effect ranged from – 14.74 to 15.61, while aaagw ranged from – 23.39 to 21.65. The number of detected threes using weighted regression was higher for two traits and lower for four traits. Forty-nine statistically significant threes of the additive-by-additive-by-additive interaction effects were observed. The QTL most frequently occurring in threes was 4407404 (9 times). The use of weighted regression improved (in absolute value) the assessment of QTL-QTL-QTL interaction effects compared to the assessment based on unweighted regression. The coefficients of determination for the weighted regression model were higher, ranging from 0.8 to 15.5%, than for the unweighted regression. Based on the results, it can be concluded that the QTL-QTL-QTL triple interaction had a significant effect on the expression of quantitative traits. The use of weighted multiple linear regression proved to be a useful statistical tool for estimating additive-additive-additive (aaa) interaction effects. The weighted regression also provided results closer to phenotypic evaluations than estimator values obtained using unweighted regression, which is closer to the true values.

PMID:37878169 | DOI:10.1007/s13353-023-00795-3

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Blood lipid profile, HbA1c, fasting glucose, and diabetes: a cohort study and a two-sample Mendelian randomization analysis

J Endocrinol Invest. 2023 Oct 25. doi: 10.1007/s40618-023-02209-x. Online ahead of print.

ABSTRACT

PURPOSE: The prevalence of diabetes is increasing worldwide. The associations between the lipid profile and glycated hemoglobin (HbA1c), fasting glucose, and diabetes remain unclear, so we aimed to perform a cohort study and a two-sample Mendelian randomization (MR) study to investigate the causality between blood lipid profile and HbA1c, fasting glucose, and diabetes.

METHODS: A total of 25,171 participants from the Taiwan Biobank were enrolled. We applied a cohort study and an MR study to assess the association between blood lipid profile and HbA1c, fasting glucose, and diabetes. The summary statistics were obtained from the Asian Genetic Epidemiology Network (AGEN), and the estimates between the instrumental variables (IVs) and outcomes were calculated using the inverse-variance weighted (IVW) method. A series of sensitivity analyses were performed.

RESULTS: In the cohort study, high-density lipoprotein cholesterol (HDL-C) was negatively associated with HbA1c, fasting glucose, and diabetes, while the causal associations between HDL-C and HbA1c (βIVW = – 0.098, p = 0.003) and diabetes (βIVW = – 0.594, p < 0.001) were also observed. Furthermore, there was no pleiotropy effect in this study using the MR-Egger intercept test and MR-PRESSO global test.

CONCLUSIONS: Our results support the hypothesis that a genetically determined increase in HDL-C is causally related to a reduction in HbA1c and a lower risk of diabetes.

PMID:37878156 | DOI:10.1007/s40618-023-02209-x

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Current use of drains and management of seroma following mastectomy and axillary surgery: results of a United Kingdom national practice survey

Breast Cancer Res Treat. 2023 Oct 25. doi: 10.1007/s10549-023-07042-7. Online ahead of print.

ABSTRACT

PURPOSE: Up to 40% of the 56,000 women diagnosed with breast cancer each year in the UK undergo mastectomy. Seroma formation following surgery is common, may delay wound healing, and be uncomfortable or delay the start of adjuvant treatment. Multiple strategies to reduce seroma formation include surgical drains, flap fixation and external compression exist but evidence to support best practice is lacking. We aimed to survey UK breast surgeons to determine current practice to inform the feasibility of undertaking a future trial.

METHODS: An online survey was developed and circulated to UK breast surgeons via professional and trainee associations and social media to explore current attitudes to drain use and management of post-operative seroma. Simple descriptive statistics were used to summarise the results.

RESULTS: The majority of surgeons (82/97, 85%) reported using drains either routinely (38, 39%) or in certain circumstances (44, 45%). Other methods for reducing seroma such as flap fixation were less commonly used. Wide variation was reported in the assessment and management of post-operative seromas. Over half (47/91, 52%) of respondents felt there was some uncertainty about drain use after mastectomy and axillary surgery and two-thirds (59/91, 65%) felt that a trial evaluating the use of drains vs no drains after simple breast cancer surgery was needed.

CONCLUSIONS: There is a need for a large-scale UK-based RCT to determine if, when and in whom drains are necessary following mastectomy and axillary surgery. This work will inform the design and conduct of a future trial.

PMID:37878150 | DOI:10.1007/s10549-023-07042-7

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Screening Plasma Proteins for the Putative Drug Targets for Carpal Tunnel Syndrome

Cell Mol Neurobiol. 2023 Oct 25. doi: 10.1007/s10571-023-01428-3. Online ahead of print.

ABSTRACT

Carpal tunnel syndrome (CTS) is one of the most common work-related musculoskeletal disorders. The present study sought to identify putative causal proteins for CTS. We conducted a two-sample Mendelian randomization (MR) analysis to evaluate the causal association between 2859 plasma proteins (N = 35,559) and CTS (N = 1,239,680) based on the published GWAS summary statistics. Then we replicated the significant associations using an independent plasma proteome GWAS (N = 10,708). Sensitivity analyses were conducted to validate the robustness of MR results. Multivariate MR and mediation analyses were conducted to evaluate the mediation effects of body mass index (BMI), type 2 diabetes (T2D), and arm tissue composition on the association between putative causal proteins and CTS. Colocalization analysis was used to examine whether the identified proteins and CTS shared causal variant(s). Finally, we evaluated druggability of the identified proteins. Ten plasma proteins were identified as putative causal markers for CTS, including sCD14, PVR, LTOR3, CTSS, SIGIRR, IFNL3, ASPN, TM11D, ASIP, and ITIH1. Sensitivity analyses and reverse MR analysis validated the robustness of their causal effects. Arm tissue composition, BMI, and T2D may play a fully/partial mediating role in the causal relationships of ASIP, TM11D, IFNL3, PVR, and LTOR3 with CTS. The association of ASPN and sCD14 with CTS were supported by colocalization analysis. Druggability assessment demonstrated that sCD14, CTSS, TM11D, and IFNL3 were potential drug therapeutic targets. The present study identified several potential plasma proteins that were causally associated with CTS risk, providing new insights into the pathogenesis of protein-mediated CTS and offering potential targets for new therapies.

PMID:37878141 | DOI:10.1007/s10571-023-01428-3