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Nevin Manimala Statistics

Associations between short-term exposure to ambient air pollution and lung function in adults

J Expo Sci Environ Epidemiol. 2023 May 13. doi: 10.1038/s41370-023-00550-0. Online ahead of print.

ABSTRACT

BACKGROUND: Evidence of the acute effects of high-level air pollution on small airway function and systemic inflammation in adults is scarce.

OBJECTIVE: To examined the associations of short-term (i.e., daily) exposure to multiple air pollutants with lung function and inflammatory markers.

METHODS: We assessed short-term (daily) effects of air pollutants, including particulate matter with aerodynamic diameter less than 2.5 μm (PM2.5) and 10 μm (PM10), nitrogen dioxide (NO2), sulfur dioxide (SO2) and carbon monoxide (CO), on lung function and peripheral immune cell counts over various lag times using generalized linear regression models.

RESULTS: A total of 4764 adults were included from the general community-dwelling population in Shanghai, China. Exposure to air pollutants and lung function were negatively correlated. Decline in FEF between 25% and 75% of vital capacity (FEF25-75%) were found associated with PM2.5, SO2, and CO, and decline in forced expiratory volume in 3 s (FEV3) to forced vital capacity (FVC) ratio were associated with all examined pollutants, indicating obstruction in small airways. Obstructed airflow in large and middle airways as indicated by decline in FEV1/FVC were also associated with all pollutants. In subgroup analysis, significant negative associations between the five pollutants and SAD parameters were found only in males but not in females. The difference in the associations of SO2 with FEF75% between males and females achieved statistical significance. Additionally, all examined pollutants were significantly associated with lower peripheral neutrophil count.

IMPACT STATEMENT: Acute exposure to air pollutants were associated with airflow-limitation. Both small airways and proximal airways were affected. Acute exposure to air pollutants were accompanied with a lower neutrophil count.

PMID:37179406 | DOI:10.1038/s41370-023-00550-0

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Cognitive decline and risk of dementia in older adults after diagnosis of chronic obstructive pulmonary disease

NPJ Prim Care Respir Med. 2023 May 13;33(1):20. doi: 10.1038/s41533-023-00342-x.

ABSTRACT

Cognitive screening has been proposed for older adults diagnosed with chronic obstructive pulmonary disease (COPD). Therefore, we examined the change over time in cognitive function and the risk of incident dementia in older adults after COPD diagnosis. A sample of 3,982 participants from the population-based cohort study Good Aging in Skåne was followed for 19 years, and 317 incident COPD cases were identified. The cognitive domains of episodic memory, executive function, and language were assessed using neuropsychological tests. Mixed models for repeated measures and a Cox model were implemented. Participants performed, on average, worse over time on all neuropsychological tests after COPD diagnosis in comparison to those without COPD, although statistical significance differences were only observed for episodic memory and language. The groups had a comparable risk of developing dementia. In conclusion, our results indicate that cognitive screening in the early stages of COPD may be of limited clinical relevance.

PMID:37179395 | DOI:10.1038/s41533-023-00342-x

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Univariate versus multivariate spectrophotometric data analysis of triamterene and xipamide; a quantitative and qualitative greenly profiled comparative study

BMC Chem. 2023 May 13;17(1):47. doi: 10.1186/s13065-023-00956-9.

ABSTRACT

Triamterene (TRI) and xipamide (XIP) mixture is used as a binary medication of antihypertension which is considered as a major cause of premature death worldwide. The purpose of this research is the quantitative and qualitative analysis of this binary mixture by green univariate and multivariate spectrophotometric methods. Univariate methods were zero order absorption spectra method (D0) and Fourier self-deconvolution (FSD), as TRI was directly determined by D0 at 367.0 nm in the range (2.00-10.00 µg/mL), where XIP show no interference. While XIP was determined by FSD at 261.0 nm in the range (2.00-8.00 µg/mL), where TRI show zero crossing. Multivariate methods were Partial Least Squares, Principal Component Regression, Artificial Neural Networks, and Multivariate Curve Resolution-Alternating Least Squares. A training set of 25 mixtures with different quantities of the tested components was used to construct and evaluate them, 3 latent variables were displayed using an experimental design. A set of 18 synthetic mixtures with concentrations ranging from (3.00-7.00 µg/mL) for TRI and (2.00-6.00 µg/mL) for XIP, were used to construct the calibration models. A collection of seven synthetic mixtures with various quantities was applied to build the validation models. All the proposed approaches quantitative analyses were evaluated using recoveries as a percentage, root mean square error of prediction, and standard error of prediction. Strong multivariate statistical tools were presented by these models, and they were used to analyze the combined dosage form available on the Egyptian market. The proposed techniques were evaluated in accordance with ICH recommendations, where they are capable of overcoming challenges including spectral overlaps and collinearity. When the suggested approaches and the published one were statistically compared, there was no discernible difference between them. The green analytical method index and eco-scale tools were applied for assessment of the established models greenness. The suggested techniques can be used in product testing laboratories for standard pharmaceutical analysis of the substances being studied.

PMID:37179391 | DOI:10.1186/s13065-023-00956-9

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Implementation of a primary care asthma management quality improvement programme across 68 general practice sites

NPJ Prim Care Respir Med. 2023 May 13;33(1):21. doi: 10.1038/s41533-023-00341-y.

ABSTRACT

Despite national and international guidelines, asthma is frequently misdiagnosed, control is poor and unnecessary deaths are far too common. Large scale asthma management programme such as that undertaken in Finland, can improve asthma outcomes. A primary care asthma management quality improvement programme was developed with the support of the British Lung Foundation (now Asthma + Lung UK) and Optimum Patient Care (OPC) Limited. It was delivered and cascaded to all relevant staff at participating practices in three Clinical Commissioning Groups. The programme focussed on improving diagnostic accuracy, management of risk and control, patient self-management and overall asthma control. Patient data were extracted by OPC for the 12 months before (baseline) and after (outcome) the intervention. In the three CCGs, 68 GP practices participated in the programme. Uptake from practices was higher in the CCG that included asthma in its incentivised quality improvement programme. Asthma outcome data were successfully extracted from 64 practices caring for 673,593 patients. Primary outcome (Royal College of Physicians Three Questions [RCP3Q]) data were available in both the baseline and outcome periods for 10,328 patients in whom good asthma control (RCP3Q = 0) increased from 36.0% to 39.2% (p < 0.001) after the intervention. The odds ratio of reporting good asthma control following the intervention was 1.15 (95% CI 1.09-1.22), p < 0.0001. This asthma management programme produced modest but highly statistically significant improvements in asthma outcomes. Key lessons learnt from this small-scale implementation will enable the methodology to be improved to maximise benefit in a larger scale role out.

PMID:37179388 | DOI:10.1038/s41533-023-00341-y

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Image analysis-based tumor infiltrating lymphocytes measurement predicts breast cancer pathologic complete response in SWOG S0800 neoadjuvant chemotherapy trial

NPJ Breast Cancer. 2023 May 13;9(1):38. doi: 10.1038/s41523-023-00535-0.

ABSTRACT

We assessed the predictive value of an image analysis-based tumor-infiltrating lymphocytes (TILs) score for pathologic complete response (pCR) and event-free survival in breast cancer (BC). About 113 pretreatment samples were analyzed from patients with stage IIB-IIIC HER-2-negative BC randomized to neoadjuvant chemotherapy ± bevacizumab. TILs quantification was performed on full sections using QuPath open-source software with a convolutional neural network cell classifier (CNN11). We used easTILs% as a digital metric of TILs score defined as [sum of lymphocytes area (mm2)/stromal area(mm2)] × 100. Pathologist-read stromal TILs score (sTILs%) was determined following published guidelines. Mean pretreatment easTILs% was significantly higher in cases with pCR compared to residual disease (median 36.1 vs.14.8%, p < 0.001). We observed a strong positive correlation (r = 0.606, p < 0.0001) between easTILs% and sTILs%. The area under the prediction curve (AUC) was higher for easTILs% than sTILs%, 0.709 and 0.627, respectively. Image analysis-based TILs quantification is predictive of pCR in BC and had better response discrimination than pathologist-read sTILs%.

PMID:37179362 | DOI:10.1038/s41523-023-00535-0

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Women’s subjective perceptions and background factors associated with poor maternal childbirth experience among induced and spontaneous onset of labour: a two-year tertiary hospital cohort study

BMC Pregnancy Childbirth. 2023 May 13;23(1):349. doi: 10.1186/s12884-023-05665-8.

ABSTRACT

BACKGROUND: Women undergoing induction of labour (IOL) more often have poor childbirth experience compared to women with spontaneous onset of labour (SOL). For understanding and optimizing childbirth experience in IOL, we investigated the subjective maternal reasons and perceptions leading to poor childbirth experience in IOL compared to SOL, as well as the background factors and delivery outcomes associated with the poor experience.

METHODS: Two-year retrospective cohort study included 836/19442 deliveries (4.3%) with poor childbirth experience in induced or spontaneous onset at term in Helsinki University Hospital. Poor childbirth experience occurred in 389/5290 (7.4%) cases of IOL and in 447/14152 (3.2%) of SOL. Childbirth experience was measured after delivery using Visual Analog Scale (VAS) score, with poor experience defined as VAS < 5. The primary outcome of the study were the maternal reasons for poor childbirth experience. The parameters were collected in the hospital database and statistical analyses were performed by using Mann-Whitney U-test and t-test.

RESULTS: The subjective maternal reasons for poor childbirth experience were pain (n = 529, 63.3%), long labour (n = 209, 25.0%), lack of support by care givers (n = 108, 12.9%), and unplanned caesarean section (CS) (n = 104, 12.4%). The methods of labour analgesia were similar among the women who expressed pain as the main reason compared with those who didn’t. When comparing the reasons according to the onset of labour, IOL group more often reported unplanned CS (17.2% vs. 8.3%; p < 0.001) and lack of support by the care givers (15.4% vs. 10.7%; p = 0.04), while SOL group more often named pain (68.7% vs. 57.1%; p = 0.001) and rapid labour (6.9% vs. 2.8%; p = 0.007). In multivariable logistic regression model, IOL was associated with lower risk for pain compared to SOL (adjusted OR 0.6, 95%CI 0.5-0.8; p < 0.01). Primiparas more often reported long labour (29.3% vs. 14.3%; p < 0.001) and concern over own or baby’s wellbeing (5.7% vs. 2.1%; p = 0.03) compared to multiparas. Women who feared childbirth more often reported lack of support compared to women with no fear (22.6% vs. 10.7%; p < 0.001).

CONCLUSION: The main reasons for poor childbirth experience were pain, long labour, unplanned CS and the lack of support by care givers. The childbirth experience is complex and could be optimized by information, support and presence of care givers especially in induced labour.

PMID:37179323 | DOI:10.1186/s12884-023-05665-8

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The effect of bromelain in periodontal surgery: a double-blind randomized placebo-controlled trial

BMC Oral Health. 2023 May 13;23(1):286. doi: 10.1186/s12903-023-02971-7.

ABSTRACT

BACKGROUND: Periodontitis is a persistent inflammatory condition. Eliminating the infection and reducing its risk factors are the first steps in treating periodontitis. When the anti-infective therapy is complete, there may still be deep periodontal pockets and prolonged inflammation. Surgical pocket reduction or elimination is indicated under these circumstances. We aimed to evaluate the effect of bromelain on bleeding on probing (BOP), gingival index (GI), and plaque index (PI) after pocket elimination surgery.

METHODS: This double-blind randomized placebo-controlled trial included 28 candidates for pocket elimination surgery referred to the private office of a periodontist in Bandar Abbas, Iran, from April 18 to August 18, 2021. Patients’ general characteristics, such as age and sex, were recorded. Additionally, periodontal indices including BOP, PI, GI, and pocket probing depth (PPD) were evaluated in all subjects. All patients underwent pocket elimination surgery. Afterwards, they were randomized into two groups. The first group received 500 mg Anaheal (bromelain) capsules twice a day before meal for one week. The second group received placebo, prepared in similar shape and color by the same pharmaceutical company. BOP, PI, GI, and PPD were assessed four weeks after completion of the treatment course (five weeks after surgery).

RESULTS: Four weeks after intervention, BOP was significantly lower with Anaheal compared to placebo (0% vs. 35.7%, P = 0.014). However, there was no significant difference in GI between groups (P = 0.120). Mean PI was lower (17.71 ± 2.12 vs. 18.28 ± 2.49) and mean PPD higher (3.10 ± 0.71 vs. 2.64 ± 0.45) in the Anaheal group, but the differences did not reach statistically significant levels (P = 0.520 and P = 0.051, respectively).

CONCLUSIONS: One-week treatment with Anaheal at a dose of 1 g/d after pocket elimination surgery resulted in significantly lower BOP compared to placebo.

TRIAL REGISTRATION: Iranian Registry of Clinical Trials (IRCT), IRCT20201106049289N1. Registered 06/04/2021. Registered prospectively, https://www.irct.ir/trial/52181 .

PMID:37179311 | DOI:10.1186/s12903-023-02971-7

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Cirrhosis in intrahepatic cholangiocarcinoma: prognostic importance and impact on survival

BMC Gastroenterol. 2023 May 13;23(1):151. doi: 10.1186/s12876-023-02710-w.

ABSTRACT

CONTEXT: Cholangiocarcinoma (CCA), a malignancy of the biliary tract epithelium is of increasing importance due to its rising incidence worldwide. There is a lack of data on cirrhosis in intrahepatic CCA (iCCA) and how it affects overall survival and prognosis.

OBJECTIVES: The primary objective of this study was to examine if there were differences in survival outcomes between iCCA patients with concomitant cirrhosis and those without cirrhosis.

METHODS: The National Cancer Database (NCDB) was used to identify and study patients with iCCA from 2004 to 2017. The presence of cirrhosis was defined using CS Site-Specific Factor 2 where 000 indicated no cirrhosis and 001 indicated the presence of cirrhosis. Descriptive statistics were utilized for patient demographics, disease staging, tumor, and treatment characteristics. Kaplan-Meier (KM) method with log-rank test and a multivariate logistic regression model was used to assess if the presence of cirrhosis in iCCA was associated with survival status and long-term survival (60 or more months after diagnosis).

RESULTS: There were 33,160 patients with CCA in NCDB (2004-2017), of which 3644 patients were diagnosed with iCCA. One thousand fifty-two patients (28.9%) had cirrhosis as defined by Ishak Fibrosis score 5-6 on biopsy and 2592 patients (71.1%) did not meet the definition for cirrhosis. Although in univariate analyses using KM/log-rank tests showed a survival advantage for non-cirrhotic patients, there was no statistically significant association found between cirrhosis and survival status (OR = 0.82, p = 0.405) or long-term survival (OR = 0.98, p = 0.933) when multivariate analysis was used. iCCA patients with cirrhosis and Stage 1 tumor had the highest median OS (132 months) vs 73.7 months in the non-cirrhotic arm, while patients with stage IV disease who had cirrhosis had half the survival time of those without. Our data thus indicates that the presence of cirrhosis is not an independent prognostic factor for survival.

PMID:37179301 | DOI:10.1186/s12876-023-02710-w

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Value of information analysis for pandemic response: intensive care unit preparedness at the onset of COVID-19

BMC Health Serv Res. 2023 May 13;23(1):485. doi: 10.1186/s12913-023-09479-4.

ABSTRACT

BACKGROUND: During the early stages of the COVID-19 pandemic, there was considerable uncertainty surrounding epidemiological and clinical aspects of SARS-CoV-2. Governments around the world, starting from varying levels of pandemic preparedness, needed to make decisions about how to respond to SARS-CoV-2 with only limited information about transmission rates, disease severity and the likely effectiveness of public health interventions. In the face of such uncertainties, formal approaches to quantifying the value of information can help decision makers to prioritise research efforts.

METHODS: In this study we use Value of Information (VoI) analysis to quantify the likely benefit associated with reducing three key uncertainties present in the early stages of the COVID-19 pandemic: the basic reproduction number ([Formula: see text]), case severity (CS), and the relative infectiousness of children compared to adults (CI). The specific decision problem we consider is the optimal level of investment in intensive care unit (ICU) beds. Our analysis incorporates mathematical models of disease transmission and clinical pathways in order to estimate ICU demand and disease outcomes across a range of scenarios.

RESULTS: We found that VoI analysis enabled us to estimate the relative benefit of resolving different uncertainties about epidemiological and clinical aspects of SARS-CoV-2. Given the initial beliefs of an expert, obtaining more information about case severity had the highest parameter value of information, followed by the basic reproduction number [Formula: see text]. Resolving uncertainty about the relative infectiousness of children did not affect the decision about the number of ICU beds to be purchased for any COVID-19 outbreak scenarios defined by these three parameters.

CONCLUSION: For the scenarios where the value of information was high enough to justify monitoring, if CS and [Formula: see text] are known, management actions will not change when we learn about child infectiousness. VoI is an important tool for understanding the importance of each disease factor during outbreak preparedness and can help to prioritise the allocation of resources for relevant information.

PMID:37179300 | DOI:10.1186/s12913-023-09479-4

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Proteomics and cytokine analyses distinguish myalgic encephalomyelitis/chronic fatigue syndrome cases from controls

J Transl Med. 2023 May 13;21(1):322. doi: 10.1186/s12967-023-04179-3.

ABSTRACT

BACKGROUND: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex, heterogenous disease characterized by unexplained persistent fatigue and other features including cognitive impairment, myalgias, post-exertional malaise, and immune system dysfunction. Cytokines are present in plasma and encapsulated in extracellular vesicles (EVs), but there have been only a few reports of EV characteristics and cargo in ME/CFS. Several small studies have previously described plasma proteins or protein pathways that are associated with ME/CFS.

METHODS: We prepared extracellular vesicles (EVs) from frozen plasma samples from a cohort of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) cases and controls with prior published plasma cytokine and plasma proteomics data. The cytokine content of the plasma-derived extracellular vesicles was determined by a multiplex assay and differences between patients and controls were assessed. We then performed multi-omic statistical analyses that considered not only this new data, but extensive clinical data describing the health of the subjects.

RESULTS: ME/CFS cases exhibited greater size and concentration of EVs in plasma. Assays of cytokine content in EVs revealed IL2 was significantly higher in cases. We observed numerous correlations among EV cytokines, among plasma cytokines, and among plasma proteins from mass spectrometry proteomics. Significant correlations between clinical data and protein levels suggest roles of particular proteins and pathways in the disease. For example, higher levels of the pro-inflammatory cytokines Granulocyte-Monocyte Colony-Stimulating Factor (CSF2) and Tumor Necrosis Factor (TNFα) were correlated with greater physical and fatigue symptoms in ME/CFS cases. Higher serine protease SERPINA5, which is involved in hemostasis, was correlated with higher SF-36 general health scores in ME/CFS. Machine learning classifiers were able to identify a list of 20 proteins that could discriminate between cases and controls, with XGBoost providing the best classification with 86.1% accuracy and a cross-validated AUROC value of 0.947. Random Forest distinguished cases from controls with 79.1% accuracy and an AUROC value of 0.891 using only 7 proteins.

CONCLUSIONS: These findings add to the substantial number of objective differences in biomolecules that have been identified in individuals with ME/CFS. The observed correlations of proteins important in immune responses and hemostasis with clinical data further implicates a disturbance of these functions in ME/CFS.

PMID:37179299 | DOI:10.1186/s12967-023-04179-3