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Changes in concentrations of cervicovaginal immune mediators across the menstrual cycle: a systematic review and meta-analysis of individual patient data

BMC Med. 2022 Oct 5;20(1):353. doi: 10.1186/s12916-022-02532-9.

ABSTRACT

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.

PMID:36195867 | DOI:10.1186/s12916-022-02532-9

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Management of oesophageal foreign bodies in children: a 10-year retrospective analysis from a tertiary care center

BMC Emerg Med. 2022 Oct 4;22(1):166. doi: 10.1186/s12873-022-00723-4.

ABSTRACT

OBJECTIVE: Oesophageal foreign bodies (EFBs) are a common emergency issue in paediatrics, and few studies have revealed its clinical features and treatment methods. We conducted this retrospective study to provide our 10-year clinical evidence for the diagnosis and treatment of EFB and reduce the incidence of complications.

METHODS: We retrospectively reviewed all paediatric cases diagnosed with EFB from January 2012 to December 2021 at Shenzhen Children’s Hospital. The age and sex of the patients, types of foreign bodies (FBs), preoperative examination, location and duration of FB impaction, clinical symptoms, surgical methods, therapeutic effects and complications were analysed.

RESULTS: Among the 1355 cases, 759 were boys and 596 were girls, with a median age of 2.9 years (4 months to 16 years). The shortest FB lodged time was 1 hour, while the longest time was 3 months. The types of foreign bodies included coins and blunt objects (812,59.9%), bones and sharp objects (278,20.5%), button batteries (86,6.3%), food impactions (84,6.2%), toys (51,3.8%) and plastic objects (44,3.2%). A total of 720 of 812 cases impacted by coins and blunt subjects were successfully treated with a Foley catheter without any complications. A total of 558 patients underwent rigid oesophageal endoscopy under general anaesthesia, and foreign bodies were successfully removed in 525 cases. No FB was found in 33 cases, and FBs pushed into the lower digestive tract during operation in 5 cases. Oesophageal injury was found in 130 cases (23.3%). Our study showed that the age of the patient, time of foreign body incarceration, type of foreign body, location of the lodged foreign body, and fever or cough were risk factors leading to oesophageal foreign body complications, and the differences were statistically significant (P < 0.05).

CONCLUSION: Children with EFB have a risk of complications, especially if the FB is a button battery. The appropriate surgical method should be selected through the analysis of the clinical characteristics of the foreign body in the oesophagus and the risk factors for complications to reduce the incidence of complications. Health education and effective care are the keys to the prevention of EFB.

PMID:36195854 | DOI:10.1186/s12873-022-00723-4

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Violence against women from partners and other household members during COVID-19 in Burkina Faso and Kenya

BMC Public Health. 2022 Oct 5;22(1):1857. doi: 10.1186/s12889-022-14197-3.

ABSTRACT

BACKGROUND: Global evidence indicates increases in gender-based violence (GBV) during the COVID-19 pandemic following mitigation measures, such as stay at home orders. Indirect effects of the pandemic, including income loss, strained social support, and closed or inaccessible violence response services, may further exacerbate GBV and undermine help-seeking. In Kenya and Burkina Faso, as in many settings, GBV was prevalent prior to the COVID-19 pandemic. Studies specific to COVID-impact on GBV in Kenya indicate mixed results and there remains a lack of evidence from Burkina Faso. Our study takes a comprehensive lens by addressing both intimate partner violence (IPV) and non-partner household abuse through the COVID-19 pandemic in two priority settings.

METHODS: Annual, national cross-sections of women ages 15-49 completed survey data collection in November-December 2020 and December 2020-March 2021; the GBV module was limited to one woman per household [Kenya n = 6715; Burkina n = 4065]. Descriptive statistics, Venn diagrams, and logistic and multinomial regression characterized prevalence of IPV and other household abuse, frequency relative to the COVID-19 pandemic, help-seeking behaviors, and predictors of IPV and household abuse across the socioecological framework.

RESULTS: In both settings, past-year IPV prevalence exceeded non-partner household abuse (Kenya: 23.5%IPV, 11.0%household; Burkina Faso: 25.7%IPV, 16.2%household). Over half of those affected in each setting did not seek help; those that did turned first to family. Among those with past-year experiences, increased frequency since COVID-19 was noted for IPV (16.0%Burkina Faso; 33.6%Kenya) and household violence (14.3%Burkina Faso; 26.2%Kenya). Both context-specific (i.e., financial autonomy in Burkina Faso) and universal (i.e., COVID-related income loss) risk factors emerged.

CONCLUSION: Past-year IPV and household violence against women in Kenya and Burkina Faso were prevalent, and in some cases, intensified during the COVID-19 pandemic. Across settings, help-seeking from formal services was notably low, likely reflecting shame, blame, and stigmatization identified as barriers in pre-COVID literature. Both primary prevention and survivor-centered support services, including those related to economic empowerment, should be integrated within COVID-recovery efforts, and extended into the post-pandemic period to fully meet women’s safety needs.

PMID:36195851 | DOI:10.1186/s12889-022-14197-3

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Evaluation of children with severe neurological impairment admitted to hospital with pain and irritability

BMC Pediatr. 2022 Oct 4;22(1):571. doi: 10.1186/s12887-022-03632-4.

ABSTRACT

BACKGROUND: Pain is the most common symptom reported by caregivers of children with severe neurological impairment (SNI), a descriptive term for children with disorders affecting the neurological system across multiple domains. In SNI, cognition, communication, and motor skills are impaired and other organ systems are impacted. Pain is difficult to identify and treat in children with SNI because of communication impairment. When a clear cause of pain is not determined, the term “Pain and Irritability of Unknown Origin (PIUO)” is used to describe pain-like behaviours. This study explores the clinical care received by children with SNI admitted to hospital after presenting to the emergency department of a tertiary pediatric hospital with pain or irritability. Findings are compared to the approach suggested in the PIUO pathway, an integrated clinical pathway for identifying and treating underlying causes of pain and irritability in children with complex conditions and limited communication.

METHODS: Retrospective chart review of children (age 0 to 18 years inclusive) with diagnoses compatible with SNI presenting with pain, irritability, and/or unexplained crying that required hospitalization between January 1st, 2019 and December 31st, 2019. Descriptive statistics were used to analyze the clinical care received by children in whom a source of pain was identified or not. In children for whom no cause of pain was identified, investigations completed were compared to the PIUO pathway.

RESULTS: Eight hospital admissions of six unique children were included for data analysis. A cause for pain and irritability was identified and resolved in three patients. In children with PIUO, there were gaps in history taking, physical examination, and investigations that might have allowed a cause of pain and irritability to be found. Pain was assessed using the r-FLACC pain scale and varying medications for pain/irritability were given during each hospital admission.

CONCLUSION: Children with SNI admitted to a tertiary pediatric hospital did not undergo a standardized approach to identifying a cause of pain and irritability. Future efforts should explore the effectiveness of the PIUO pathway, a standardized approach to reducing and resolving pain in children with SNI.

PMID:36195849 | DOI:10.1186/s12887-022-03632-4

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Correlation scan: identifying genomic regions that affect genetic correlations applied to fertility traits

BMC Genomics. 2022 Oct 5;23(1):684. doi: 10.1186/s12864-022-08898-7.

ABSTRACT

Although the genetic correlations between complex traits have been estimated for more than a century, only recently we have started to map and understand the precise localization of the genomic region(s) that underpin these correlations. Reproductive traits are often genetically correlated. Yet, we don’t fully understand the complexities, synergism, or trade-offs between male and female fertility. In this study, we used reproductive traits in two cattle populations (Brahman; BB, Tropical Composite; TC) to develop a novel framework termed correlation scan (CS). This framework was used to identify local regions associated with the genetic correlations between male and female fertility traits. Animals were genotyped with bovine high-density single nucleotide polymorphisms (SNPs) chip assay. The data used consisted of ~1000 individual records measured through frequent ovarian scanning for age at first corpus luteum (AGECL) and a laboratory assay for serum levels of insulin growth hormone (IGF1 measured in bulls, IGF1b, or cows, IGF1c). The methodology developed herein used correlations of 500-SNP effects in a 100-SNPs sliding window in each chromosome to identify local genomic regions that either drive or antagonize the genetic correlations between traits. We used Fisher’s Z-statistics through a permutation method to confirm which regions of the genome harboured significant correlations. About 30% of the total genomic regions were identified as driving and antagonizing genetic correlations between male and female fertility traits in the two populations. These regions confirmed the polygenic nature of the traits being studied and pointed to genes of interest. For BB, the most important chromosome in terms of local regions is often located on bovine chromosome (BTA) 14. However, the important regions are spread across few different BTA’s in TC. Quantitative trait loci (QTLs) and functional enrichment analysis revealed many significant windows co-localized with known QTLs related to milk production and fertility traits, especially puberty. In general, the enriched reproductive QTLs driving the genetic correlations between male and female fertility are the same for both cattle populations, while the antagonizing regions were population specific. Moreover, most of the antagonizing regions were mapped to chromosome X. These results suggest regions of chromosome X for further investigation into the trade-offs between male and female fertility. We compared the CS with two other recently proposed methods that map local genomic correlations. Some genomic regions were significant across methods. Yet, many significant regions identified with the CS were overlooked by other methods.

PMID:36195838 | DOI:10.1186/s12864-022-08898-7

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EVI1 expression in early-stage breast cancer patients treated with neoadjuvant chemotherapy

BMC Cancer. 2022 Oct 5;22(1):1040. doi: 10.1186/s12885-022-10109-1.

ABSTRACT

BACKGROUND: Overexpression of the EVI1 (ecotropic viral integration site 1) oncogene has recently been implicated as a prognostic factor in breast cancer (BC), particularly in triple-negative BC (TNBC). In this study we aimed to investigate frequency and clinical relevance of EVI1 expression in newly diagnosed BC treated with neoadjuvant chemotherapy.

METHODS: EVI1 expression was determined by immunohistochemistry using H-score as a cumulative measurement of protein expression in pretherapeutic biopsies of BC patients treated with anthracycline/taxane based neoadjuvant chemotherapy within the GeparTrio trial. EVI1 was analyzed as a continuous variable and dichotomized into low or high based on median expression. Endpoints were pathological complete response (pCR), disease-free survival (DFS) and overall survival (OS).

RESULTS: Of the 993 tumors analyzed, 882 had available subtype information: 50.8% were HR + /HER2-, 15% HR + /HER2 + , 9.8% HR-/HER2 + , and 24.5% TNBC. Median EVI1 H-score was 112.16 (range 0.5-291.4). High EVI1 expression was significantly associated with smaller tumor size (p = 0.002) but not with BC subtype. Elevated EVI1 levels were not significantly associated with therapy response and survival in the entire cohort or within BC subtypes. However, TNBC patients with high EVI1 showed a trend towards increased pCR rates compared to low group (37.7% vs 27.5%, p = 0.114; odds ratio 1.60 (95%CI 0.90-2.85, p = 0.110) and numerically better DFS (HR = 0.77 [95%CI 0.48-1.23], log-rank p = 0.271) and OS (HR = 0.76 [95% 0.44-1.31], log-rank p = 0.314) without reaching statistical significance.

CONCLUSION: EVI1 was not associated with response to neoadjuvant therapy or patient survival in the overall cohort. Further analyses are needed to verify our findings especially in the pathological work-up of early-stage HER2-negative BC patients.

TRIAL REGISTRATION: NCT00544765.

PMID:36195836 | DOI:10.1186/s12885-022-10109-1

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A Machine Learning Approach for the Prediction of Severe Acute Kidney Injury Following Traumatic Brain Injury

Neurocrit Care. 2022 Oct 4. doi: 10.1007/s12028-022-01606-z. Online ahead of print.

ABSTRACT

BACKGROUND: Acute kidney injury (AKI), a prevalent non-neurological complication following traumatic brain injury (TBI), is a major clinical issue with an unfavorable prognosis. This study aimed to develop and validate machine learning models to predict severe AKI (stage 3 or greater) incidence in patients with TBI.

METHODS: A retrospective cohort study was conducted by using two public databases: the Medical Information Mart for Intensive Care IV (MIMIC)-IV and the eICU Collaborative Research Database (eICU-CRD). Recursive feature elimination was used to select candidate predictors obtained within 24 h of intensive care unit admission. The area under the curve and decision curve analysis curves were used to determine the discriminatory ability. On the other hand, the calibration curve was employed to evaluate the calibrated performance of the newly developed machine learning models.

RESULTS: In the MIMIC-IV database, there were 808 patients diagnosed with moderate and severe TBI (msTBI) (msTBI is defined as Glasgow Coma Score < 12). Of these, 60 (7.43%) patients experienced severe AKI. External validation in the eICU-CRD indicated that the random forest (RF) model had the highest area under the curve of 0.819 (95% confidence interval 0.783-0.851). Furthermore, in the calibration curve, the RF model was well calibrated (P = 0.795).

CONCLUSIONS: In this study, the RF model demonstrated better discrimination in predicting severe AKI than other models. An online calculator could facilitate its application, potentially improving the early detection of severe AKI and subsequently improving the clinical outcomes among patients with msTBI.

PMID:36195818 | DOI:10.1007/s12028-022-01606-z

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Patient and provider experience with virtual care in a large, ambulatory care hospital in Ontario, Canada during the COVID-19 pandemic: An observational study

J Med Internet Res. 2022 Aug 22. doi: 10.2196/38604. Online ahead of print.

ABSTRACT

BACKGROUND: Virtual care use increased during the COVID-19 pandemic. The impact on patient and provider experience of that shift is unclear.

OBJECTIVE: We evaluated patient and provider experience with virtual visits across an academic, ambulatory hospital in Toronto, Canada and assessed predictors of positive experience with virtual care.

METHODS: Survey data was analyzed from consenting patients who attended at least one virtual visit (video or telephone) and from consenting providers who delivered at least one virtual visit. Distributions for demographic variables and responses to survey questions are reported, with statistical significance assessed using chi-square tests and t-tests. Ordinal logistic regression was used to identify any patient predictors of responses.

RESULTS: During the study period, 253 patients (mean age(SD) 45.1 years (15.6)) completed 517 video visit surveys and 147 patients (41.6 (16.4)), completed 209 telephone visit surveys. A total of 75 and 94 providers completed the survey in June 2020 and June 2021, respectively. On a scale of 1-10 regarding likelihood to recommend virtual care to others, fewer providers rated a score of 8 or above compared to patients (providers: 66.0% for video and 52.2% for telephone versus patients: 80.3% for video and 71.8% for telephone). Patients of non-White ethnicity had lower odds of rating a high score of 9 or 10 compared to white patients (OR(95% CI) 0.52(0.28-0.99)).

CONCLUSIONS: Patient experiences with virtual care were generally positive, but provider experiences were less so. Findings suggest potential differences in patient experience by ethnicity, warranting further investigation into equity concerns with virtual care.

PMID:36194862 | DOI:10.2196/38604

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Validation of a 3-Dimensional-Printed Infant Tibia for Intraosseous Needle Insertion Training

Simul Healthc. 2022 Sep 23. doi: 10.1097/SIH.0000000000000689. Online ahead of print.

ABSTRACT

INTRODUCTION: Current bone models used for pediatric intraosseous (IO) placement training are expensive or lack anatomic and/or functional fidelity. This technical report describes the development and validation of a 3-dimensional printed (3DP) tibia from a pediatric lower extremity computed tomography scan for IO procedural training.

METHODS: Multiple 3DP tibia models were printed using a dual-extrusion fused-filament fabrication printer. Models underwent iterative optimization until 2 final models, one of polypropylene (3DP clear) and the other of polylactic acid/polypropylene (3DP white), were selected. Using an exploratory sequential mixed-methods design, a novel IO bone model assessment tool was generated. Physicians then used the assessment tool to evaluate and compare common IO bone models to the novel 3DP models during IO needle insertion.

RESULTS: Thirty physicians evaluated the provided pediatric IO bone models. Compared with a chicken bone as a reference, the 3DP white bone had statistically significantly higher mean scores of anatomy, heft, sense of being anchored in the bone, quality of bone resistance, and “give” when interfaced with an IO needle. Twenty-two of the 30 participants ranked the 3DP white bone as either 1st or 2nd in terms of ranked preference of pediatric IO bone model. A 3DP white bone costs $1.10 to make.

CONCLUSIONS: The 3DP IO tibia models created from real-life computed tomography images have high degrees of anatomic and functional realism. These IO training models are easily replicable, highly appraised, and can be printed at a fraction of the cost of commercially available plastic models.

PMID:36194860 | DOI:10.1097/SIH.0000000000000689

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Direct Comparison of Diagnostic Accuracy of Fast Kilovoltage Switching Dual-Energy Computed Tomography and Magnetic Resonance Imaging for Detection of Enhancement in Renal Masses

J Comput Assist Tomogr. 2022 Sep 6. doi: 10.1097/RCT.0000000000001361. Online ahead of print.

ABSTRACT

PURPOSE: The aim of the study was to compare diagnostic accuracy of dual-energy computed tomography (DECT) and magnetic resonance imaging (MRI) to detect enhancement in renal masses.

METHODS: Adults renal masses of 10 mm or greater with both fast kilovoltage potential switching DECT and contrast-enhanced MRI performed within 12 months were retrospectively included. Two blinded radiologists independently evaluated for enhancement subjectively (5-point Likert scales) and quantitatively (signal intensity ratio ≥15% for MRI, iodine concentration ≥1.2 or ≥2.0 mg/mL for DECT). Per-lesion diagnostic accuracy, with histologic reference standard for solid masses, was expressed as the area under the receiver operator curve (AUC) for each index test. Differences were evaluated for statistical significance using the DeLong test.

RESULTS: We included 24 patients with 41 masses: 17 solid renal masses and 24 Bosniak 1 or 2 cysts. There was no significant difference in diagnostic accuracy comparing subjective enhancement by MRI and using iodine overlay DECT for reader 1 (AUC 0.99 vs 0.99, P = 0.38) or reader 2 (AUC 1.00 vs 0.94, P = 0.12) Interobserver agreement was κ = 0.61 for DECT and κ = 0.71 for MRI. There was no significant difference either in accuracy between quantitative assessment using signal intensity ratio or iodine concentration for reader 1 (AUC 0.94 vs 0.94, P = 0.88) or reader 2 (AUC 0.97 vs 0.92, P = 0.16). False-negative results in both subjective and quantitative assessment were nearly exclusively seen in papillary renal cell carcinoma, occurring with both DECT and MRI.

CONCLUSIONS: We detected no significant differences in accuracy for detecting enhancement in renal masses comparing MRI and DECT. Our results require further investigation in larger sample sizes, but suggest that DECT may be comparable to MRI for detection of enhancement in renal masses.

PMID:36194830 | DOI:10.1097/RCT.0000000000001361