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- ItemOpen AccessData-driven identification of plasma metabolite clusters and metabolites of interest for potential detection of early-stage non-small cell lung cancer cases versus cancer-free controls(2022-10-12) Kim, Julian O.; Balshaw, Robert; Trevena, Connel; Banerji, Shantanu; Murphy, Leigh; Dawe, David; Tan, Lawrence; Srinathan, Sadeesh; Buduhan, Gordon; Kidane, Biniam; Qing, Gefei; Domaratzki, Michael; Aliani, MichelAbstract Background Metabolomics is a potential means for biofluid-based lung cancer detection. We conducted a non-targeted, data-driven assessment of plasma from early-stage non-small cell lung cancer (ES-NSCLC) cases versus cancer-free controls (CFC) to explore and identify the classes of metabolites for further targeted metabolomics biomarker development. Methods Plasma from 250 ES-NSCLC cases and 250 CFCs underwent ultra-high-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UHPLC-QTOF-MS) in positive and negative electrospray ionization (ESI) modes. Molecular feature extraction, formula generation, and find-by-ion tools annotated metabolic entities. Analysis was restricted to endogenous metabolites present in ≥ 80% of samples. Unsupervised hierarchical cluster analysis identified clusters of metabolites. The metabolites with the strongest correlation with the principal component of each cluster were included in logistic regression modeling to assess discriminatory performance with and without adjustment for clinical covariates. Results A total of 1900 UHPLC-QTOF-MS assessments identified 1667 and 2032 endogenous metabolites in the ESI-positive and ESI-negative modes, respectively. After data filtration, 676 metabolites remained, and 12 clusters of metabolites were identified from each ESI mode. Multivariable logistic regression using the representative metabolite from each cluster revealed effective classification of cases from controls with overall diagnostic accuracy of 91% (ESI positive) and 94% (ESI negative). Metabolites of interest identified for further targeted analysis include the following: 1b, 3a, 12a-trihydroxy-5b-cholanoic acid, pyridoxamine 5′-phosphate, sphinganine 1-phosphate, gamma-CEHC, 20-carboxy-leukotriene B4, isodesmosine, and 18-hydroxycortisol. Conclusions Plasma-based metabolomic detection of early-stage NSCLC appears feasible. Further metabolomics studies targeting phospholipid, steroid, and fatty acid metabolism are warranted to further develop noninvasive metabolomics-based detection of early-stage NSCLC.
- ItemOpen AccessScreening for prostate cancer: protocol for updating multiple systematic reviews to inform a Canadian Task Force on Preventive Health Care guideline update(2022-10-26) Bennett, Alexandria; Beck, Andrew; Shaver, Nicole; Grad, Roland; LeBlanc, Allana; Limburg, Heather; Gray, Casey; Abou-Setta, Ahmed; Klarenbach, Scott; Persaud, Navindra; Thériault, Guylène; Thombs, Brett D.; Todd, Keith J.; Bell, Neil; Dahm, Philipp; Loblaw, Andrew; Del Giudice, Lisa; Yao, Xiaomei; Skidmore, Becky; Rolland-Harris, Elizabeth; Brouwers, Melissa; Little, Julian; Moher, DavidAbstract Purpose To inform updated recommendations by the Canadian Task Force on Preventive Health Care on screening for prostate cancer in adults aged 18 years and older in primary care. This protocol outlines the planned scope and methods for a series of systematic reviews. Methods Updates of two systematic reviews and a de novo review will be conducted to synthesize the evidence on the benefits and harms of screening for prostate cancer with a prostate-specific antigen (PSA) and/or digital rectal examination (DRE) (with or without additional information) and patient values and preferences. Outcomes for the benefits of screening include reduced prostate cancer mortality, all-cause mortality, and incidence of metastatic prostate cancer. Outcomes for the harms of screening include false-positive screening tests, overdiagnosis, complications due to biopsy, and complications of treatment including incontinence (urinary or bowel), and erectile dysfunction. The quality of life or functioning (overall and disease-specific) and psychological effects outcomes are considered as a possible benefit or harm. Outcomes for the values and preferences review include quantitative or qualitative information regarding the choice to screen or intention to undergo screening. For the reviews on benefits or harms, we will search for randomized controlled trials, quasi-randomized, and controlled studies in MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials. For the review on values and preferences, we will search for experimental or observational studies in MEDLINE, Embase, and PsycInfo. For all reviews, we will also search websites of relevant organizations, gray literature, and reference lists of included studies. Title and abstract screening, full-text review, data extraction, and risk of bias assessments will be completed independently by pairs of reviewers with any disagreements resolved by consensus or by consulting with a third reviewer. The GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach will be used to assess the certainty of the evidence for each outcome. Discussion The series of systematic reviews will be used by the Canadian Task Force on Preventive Health Care to update their 2014 guideline on screening for prostate cancer in adults aged 18 years and older. Systematic review registration This review has been registered with PROSPERO (CRD42022314407) and is available on the Open Science Framework (osf.io/dm32k).
- ItemOpen AccessChanges in concentrations of cervicovaginal immune mediators across the menstrual cycle: a systematic review and meta-analysis of individual patient data(2022-10-05) Hughes, Sean M.; Levy, Claire N.; Katz, Ronit; Lokken, Erica M.; Anahtar, Melis N.; Hall, Melissa B.; Bradley, Frideborg; Castle, Philip E.; Cortez, Valerie; Doncel, Gustavo F.; Fichorova, Raina; Fidel, Paul L.; Fowke, Keith R.; Francis, Suzanna C.; Ghosh, Mimi; Hwang, Loris Y.; Jais, Mariel; Jespers, Vicky; Joag, Vineet; Kaul, Rupert; Kyongo, Jordan; Lahey, Timothy; Li, Huiying; Makinde, Julia; McKinnon, Lyle R.; Moscicki, Anna-Barbara; Novak, Richard M.; Patel, Mickey V.; Sriprasert, Intira; Thurman, Andrea R.; Yegorov, Sergey; Mugo, Nelly R.; Roxby, Alison C.; Micks, Elizabeth; Hladik, FlorianAbstract Background Hormonal changes during the menstrual cycle play a key role in shaping immunity in the cervicovaginal tract. Cervicovaginal fluid contains cytokines, chemokines, immunoglobulins, and other immune mediators. Many studies have shown that the concentrations of these immune mediators change throughout the menstrual cycle, but the studies have often shown inconsistent results. Our understanding of immunological correlates of the menstrual cycle remains limited and could be improved by meta-analysis of the available evidence. Methods We performed a systematic review and meta-analysis of cervicovaginal immune mediator concentrations throughout the menstrual cycle using individual participant data. Study eligibility included strict definitions of the cycle phase (by progesterone or days since the last menstrual period) and no use of hormonal contraception or intrauterine devices. We performed random-effects meta-analyses using inverse-variance pooling to estimate concentration differences between the follicular and luteal phases. In addition, we performed a new laboratory study, measuring select immune mediators in cervicovaginal lavage samples. Results We screened 1570 abstracts and identified 71 eligible studies. We analyzed data from 31 studies, encompassing 39,589 concentration measurements of 77 immune mediators made on 2112 samples from 871 participants. Meta-analyses were performed on 53 immune mediators. Antibodies, CC-type chemokines, MMPs, IL-6, IL-16, IL-1RA, G-CSF, GNLY, and ICAM1 were lower in the luteal phase than the follicular phase. Only IL-1α, HBD-2, and HBD-3 were elevated in the luteal phase. There was minimal change between the phases for CXCL8, 9, and 10, interferons, TNF, SLPI, elafin, lysozyme, lactoferrin, and interleukins 1β, 2, 10, 12, 13, and 17A. The GRADE strength of evidence was moderate to high for all immune mediators listed here. Conclusions Despite the variability of cervicovaginal immune mediator measurements, our meta-analyses show clear and consistent changes during the menstrual cycle. Many immune mediators were lower in the luteal phase, including chemokines, antibodies, matrix metalloproteinases, and several interleukins. Only interleukin-1α and beta-defensins were higher in the luteal phase. These cyclical differences may have consequences for immunity, susceptibility to infection, and fertility. Our study emphasizes the need to control for the effect of the menstrual cycle on immune mediators in future studies.
- ItemOpen AccessEvaluation of factors that influenced the length of hospital stay using data mining techniques(2022-10-29) Eskandari, Mehrnoosh; Alizadeh Bahmani, Amir H.; Mardani-Fard, Heydar A.; Karimzadeh, Iman; Omidifar, Navid; Peymani, PayamAbstract Background length of stay (LOS) is the time between hospital admission and discharge. LOS has an impact on hospital management and hospital care functions. Methods A descriptive, retrospective study was designed on about 27,500 inpatients between March 2019 and 2020. Required data were collected from six wards (CCU, ICU, NICU, General, Maternity, and Women) in a teaching hospital. Clinical data such as demographic characteristics (age, sex), type of ward, and duration of hospital stay were analyzed by the R-studio program. Violin plots, bar charts, mosaic plots, and tree-based models were used to demonstrate the results. Results The mean age of the population was 40.8 ± 19.2 years. The LOS of the study population was 2.43 ± 4.13 days. About 60% of patients were discharged after staying one day in the hospital. After staying one day in the hospital, 67% of women were discharged. However, 23% of men were discharged within this time frame. The majority of LOS in the CCU, ICU, and NICU ranged from 5 to 9 days.; In contrast, LOS was one day in General, Maternity, and Woman wards. Due to the tree plot, there was a different LOS pattern between Maternity-Women and the CCU-General-ICU-NICU wards group. Conclusion We observed that patients with more severe diseases hospitalized in critical care wards had a longer LOS than those not admitted to critical care wards. The older patient had longer hospital LOS than the younger. By excluding Maternity and Woman wards, LOS in the hospital was comparable between males and females and demonstrated a similar pattern.
- ItemOpen AccessBirth registration coverage according to the sex of the head of household: an analysis of national surveys from 93 low- and middle-income countries(2022-10-19) Wendt, Andrea; Hellwig, Franciele; Saad, Ghada E.; Faye, Cheikh; Boerma, Ties; Barros, Aluisio J. D.; Victora, Cesar G.Abstract Background Within-country inequalities in birth registration coverage (BRC) have been documented according to wealth, place of residence and other household characteristics. We investigated whether sex of the head of household was associated with BRC. Methods Using data from nationally-representative surveys (Demographic and Health Survey or Multiple Indicator Cluster Survey) from 93 low and middle-income countries (LMICs) carried out in 2010 or later, we developed a typology including three main types of households: male-headed (MHH) and female-led with or without an adult male resident. Using Poisson regression, we compared BRC for children aged less than 12 months living the three types of households within each country, and then pooled results for all countries. Analyses were also adjusted for household wealth quintiles, maternal education and urban-rural residence. Results BRC ranged from 2.2% Ethiopia to 100% in Thailand (median 79%) while the proportion of MHH ranged from 52.1% in Ukraine to 98.3% in Afghanistan (median 72.9%). In most countries the proportion of poor families was highest in FHH (no male) and lowest in FHH (any male), with MHH occupying an intermediate position. Of the 93 countries, in the adjusted analyses, FHH (no male) had significantly higher BRC than MHH in 13 countries, while in eight countries the opposite trend was observed. The pooled analyses showed t BRC ratios of 1.01 (95% CI: 1.00; 1.01) for FHH (any male) relative to MHH, and also 1.01 (95% CI: 1.00; 1.01) for FHH (no male) relative to MHH. These analyses also showed a high degree of heterogeneity among countries. Conclusion Sex of the head of household was not consistently associated with BRC in the pooled analyses but noteworthy differences in different directions were found in specific countries. Formal and informal benefits to FHH (no male), as well as women’s ability to allocate household resources to their children in FHH, may explain why this vulnerable group has managed to offset a potential disadvantage to their children.