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Nevin Manimala Statistics

Interobserver variability in the histopathological evaluation of melanoma: analysis of 60 case reports

Actas Dermosifiliogr. 2024 Jul 5:S0001-7310(24)00530-1. doi: 10.1016/j.ad.2024.05.023. Online ahead of print.

ABSTRACT

INTRODUCTION: Since the field of dermatopathology is not an exact science, it is prone to personal subjectivity, which sometimes causes disagreements on the diagnosis and assessment of some histological features. In the case of melanoma, some variables such as regression are associated with low interobserver agreement. On the contrary, other variables such as the measurement of Breslow thickness show high reproducibility.

OBJECTIVE: The main objective of our study was to investigate multiple features of 60 consecutive cases of melanoma to establish interobserver reproducibility.

METHODS AND MAIN RESULTS: We conducted an observational and descriptive study at Hospital de Manises, Valencia, Spain, IVO Foundation, Valencia, Spain, and Hospital 12 de Octubre, Madrid, Spain. The mean level of agreement of all study variables was moderate (Cohen’s kappa coefficient statistic = 0.5). The highest agreement corresponded to polypoid morphology, pigmentation, ulceration, and solar elastosis. On the other hand, the lowest level agreement was reached for the presence of cellular pleomorphism and tumor necrosis.

CONCLUSIONS: Our mean level of agreement was moderate, which reflects that some of the measured characteristics such as cellular pleomorphism or the presence of necrosis cannot be used for future studies or must be redefined and their reproducibility, reestablished. When conducting a research study, it is necessary to analyze the study variables to demonstrate their validity to measure or classify a certain feature. It is also advisable to warrant that that the variables are reproducible to be able to use them for other studies or in the routine clinical practice.

PMID:38972585 | DOI:10.1016/j.ad.2024.05.023

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Nevin Manimala Statistics

Multiple pandemic waves vs multi-period/multi-phasic epidemics: Global shape of the COVID-19 pandemic

J Theor Biol. 2024 Jul 5:111881. doi: 10.1016/j.jtbi.2024.111881. Online ahead of print.

ABSTRACT

The overall course of the COVID-19 pandemic in Western countries has been characterised by complex sequences of phases. In the period before the arrival of vaccines, these phases were mainly due to the alternation between the strenghtening/lifting of social distancing measures, with the aim to balance the protection of health and that of the society as a whole. After the arrival of vaccines, this multi-phasic character was further emphasised by the complicated deployment of vaccination campaigns and the onset of virus’ variants. To cope with this multi-phasic character, we propose a theoretical approach to the modeling of overall pandemic courses, that we term multi-period/multi-phasic, based on a specific definition of phase. This allows a unified and parsimonious representation of complex epidemic courses even when vaccination and virus’ variants are considered, through sequences of weak ergodic renewal equations that become fully ergodic when appropriate conditions are met. Specific hypotheses on epidemiological and intervention parameters allow reduction to simple models. The framework suggest a simple, theory driven, approach to data explanation that allows an accurate reproduction of the overall course of the COVID-19 epidemic in Italy since its beginning (February 2020) up to omicron onset, confirming the validity of the concept.

PMID:38972568 | DOI:10.1016/j.jtbi.2024.111881

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Nevin Manimala Statistics

Modelling future bone mineral density: Simplicity or complexity?

Bone. 2024 Jul 5:117178. doi: 10.1016/j.bone.2024.117178. Online ahead of print.

ABSTRACT

BACKGROUND: Osteoporotic fractures are a major global public health issue, leading to patient suffering and death, and considerable healthcare costs. Bone mineral density (BMD) measurement is important to identify those with osteoporosis and assess their risk of fracture. Both the absolute BMD and the change in BMD over time contribute to fracture risk. Predicting future fracture in individual patients is challenging and impacts clinical decisions such as when to intervene or repeat BMD measurement. Although the importance of BMD change is recognised, an effective way to incorporate this marginal effect into clinical algorithms is lacking.

METHODS: We compared two methods using longitudinal DXA data generated from subjects with two or more hip DXA scans on the same machine between 2000 and 2018. A simpler statistical method (ZBM) was used to predict an individual’s future BMD based on the mean BMD and the standard deviation of the reference group and their BMD measured in the latest scan. A more complex deep learning (DL)-based method was developed to cope with multidimensional longitudinal data, variables extracted from patients’ historical DXA scan(s), as well as features drawn from the ZBM method. Sensitivity analyses of several subgroups was conducted to evaluate the performance of the derived models.

RESULTS: 2948 white adults aged 40-90 years met our study inclusion: 2652 (90 %) females and 296 (10 %) males. Our DL-based models performed significantly better than the ZBM models in women, particularly our Hybrid-DL model. In contrast, the ZBM-based models performed as well or better than DL-based models in men.

CONCLUSIONS: Deep learning-based and statistical models have potential to forecast future BMD using longitudinal clinical data. These methods have the potential to augment clinical decisions regarding when to repeat BMD testing in the assessment of osteoporosis.

PMID:38972532 | DOI:10.1016/j.bone.2024.117178

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Reproductive health assessment and reports of fertility counseling in pediatric and adolescent patients with sickle cell disease after hematopoietic cell transplantation

Transplant Cell Ther. 2024 Jul 4:S2666-6367(24)00492-5. doi: 10.1016/j.jtct.2024.06.029. Online ahead of print.

ABSTRACT

BACKGROUND: Conditioning regimens for hematopoietic cell transplant (HCT) in patients with sickle cell disease (SCD) place patients at risk for reproductive health issues.

OBJECTIVE: The purpose of this study was to assess reproductive health and reports of fertility counseling in patients with SCD who received a transplant.

STUDY DESIGN: This was a secondary analysis of gonadal hormone production, future infertility risk assessment and parent-proxy/patient reports of fertility counseling in SCD transplant recipients who are currently pubertal and were enrolled in the Atlanta sites of the Sickle Cell Transplant Evaluation of Long-term and Late Effects Registry (STELLAR) between May 2017 and October 2023. Clinical information was abstracted from medical records and reproductive health survey data from the STELLAR database. Descriptive statistics were reported as median (IQR) or percentages.

RESULTS: There were 20 females and 12 males in the study population. Females were median (IQR) 19.6 (9.4) years old and males 20.8 (11.4) years old at the time of the study. Transplants most commonly occurred in the decade 2010 – 2019 at 10.7 (4.8) years old for females and 11.1 (4.1) years old for males. Most participants received bone marrow stem cells (95.0% females, 100.0% males) from matched sibling donors (90.0% females, 100.0% males). Participants received one of seven HCT conditioning regimens with cyclophosphamide equivalent doses ranging from 3,388mg/m2 to 9,706mg/m2. The majority of females (90.0%) had diminished ovarian reserve with low anti-Mullerian hormone levels, and 61.1% had premature ovarian insufficiency with two follicle-stimulating hormone levels (FSH) ≥ 40 mIU/mL post-HCT. All males had normal testosterone levels, but 63.6% had elevated FSH levels suggestive of impaired spermatogenesis post-HCT. Parent-proxies (for patients < 18 years old) and patients ≥ 18 years old completed surveys 9.0 years (5.2) and 7.9 years (9.3) since HCT in females and males respectively. Twenty five percent of parent-proxies and 45% of patients reported that they had not been informed by a healthcare provider of the risk of infertility post-transplant.

CONCLUSION: There are high rates of gonadal dysfunction post-HCT, but many parent-proxies and patients do not recall being told of the risk for future infertility. More effective methods of education are warranted to ensure SCD patients and their families clearly understand the risk for reproductive health issues post-HCT.

PMID:38972510 | DOI:10.1016/j.jtct.2024.06.029

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Nevin Manimala Statistics

Sociodemographic Factors Associated with Emergent Eye-Related Emergency Department Visits: A Multicenter Analysis

Am J Ophthalmol. 2024 Jul 5:S0002-9394(24)00294-0. doi: 10.1016/j.ajo.2024.06.031. Online ahead of print.

ABSTRACT

OBJECTIVE: To compare sociodemographic factors in patients presenting to the emergency department (ED) with emergent and non-emergent eye-related concerns.

DESIGN: Cross-sectional multicenter study.

SUBJECTS: 60,677 patients with eye-related concerns who visited EDs at Bascom Palmer Eye Institute, Wills Eye Hospital, Massachusetts Eye and Ear, and Johns Hopkins Hospital/Wilmer Eye Institute from January 1st, 2019 until December 31st, 2019.

METHODS: Descriptive statistics were performed using STATA 17.

MAIN OUTCOME MEASURES: 1) Sociodemographic factors associated with emergent diagnoses, 2) Visit patterns across ED settings (i.e. standard ED vs eye ED), and 3) the most common emergent and non-emergent diagnoses.

RESULTS: A total of 60,677 eye-related ED encounters were included in the study, including 22,434 at Bascom Palmer Eye Institute, 16,124 at Wills Eye Hospital, 15,487 at Massachusetts Eye and Ear, and 6,632 at Johns Hopkins Hospital/Wilmer Eye Institute. Most patients had non-emergent diagnoses (56.7%). Males (OR 1.85, 95% CI 1.79-1.92) were more likely to have an emergent diagnosis than females. Patients with private/employer-based insurance (OR 0.88, 95% CI 0.81-0.96), Medicare (OR 0.80, 95% CI 0.72-0.87), and Medicaid (OR 0.81, 95% CI 0.74-0.89) were all less likely to have an emergent diagnosis than uninsured patients. Those with veteran/military insurance (OR 1.08, 95% CI 0.87-1.34) were equally likely to have an emergent diagnosis compared to uninsured patients. Non-White Hispanic patients (OR 1.26, 95% CI 1.12-1.42) were more likely to present with an emergent condition than White patients. Patient seen in the standard ED setting were more likely to have emergent diagnoses than those who visited standalone eye EDs (P < 0.001). The most common emergent diagnoses were corneal abrasion (12.97%), extraocular foreign body (7.61%), and corneal ulcer (7.06%). The most common non-emergent diagnoses were dry eye (7.90%), posterior vitreous detachment (7.76%), and chalazion (6.57%).

CONCLUSIONS: ED setting was associated with the acuity of patient diagnoses. Lack of insurance coverage and non-White Hispanic race/ethnicity were associated with emergent eye-related ED visits. Improving access to ophthalmic care in these populations may reduce the incidence of preventable eye emergencies related to untreated chronic conditions. This combined with measures to redirect non-emergent issues to outpatient clinics may alleviate ED overload.

PMID:38972497 | DOI:10.1016/j.ajo.2024.06.031

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Assessment of diagnostic delay, morbidity, and mortality outcomes in 302 calciphylaxis patients over a 17-year period: A retrospective cohort study

J Am Acad Dermatol. 2024 Jul 5:S0190-9622(24)00997-6. doi: 10.1016/j.jaad.2024.06.058. Online ahead of print.

ABSTRACT

BACKGROUND: Calciphylaxis patients historically have experienced diagnostic challenges and high morbidity, however limited data is available examining these characteristics over time.

OBJECTIVE: The primary goals were to a) investigate factors associated with diagnostic delay of calciphylaxis and b) assess morbidity outcomes. The secondary goal was to provide updated mortality rates.

METHODS: A retrospective review of 302 adult patients diagnosed with calciphylaxis between January 1, 2006 and December 31, 2022 was conducted. Univariate and multivariate statistical analyses were performed.

RESULTS: Non-nephrogenic calciphylaxis (p=0.0004) and involvement of the fingers (p=0.0001) were significantly associated with an increased diagnostic delay, whereas involvement of the arms (p=0.01) and genitalia (p=0.022) resulted in fewer days to diagnosis. Almost all patients with genitalia, finger, or toe involvement had nephrogenic disease. The number of complications per patient decreased with time, especially for wound infections (p=0.028), increase in lesion number (p=0.012), and recurrent hospitalizations (p=0.020). Updated 1-year mortality rates were 36.70% and 30.77% for nephrogenic and non-nephrogenic calciphylaxis, respectively.

LIMITATIONS: Limitations include the retrospective nature and data from a single institution.

CONCLUSION: Diagnostic delay, particularly in non-nephrogenic calciphylaxis, and complications per patient decreased with time, highlighting the importance of continued awareness to expedite diagnosis. Mortality rates have continued to improve in recent years.

PMID:38972479 | DOI:10.1016/j.jaad.2024.06.058

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Nevin Manimala Statistics

Quiescent frame, contrast-enhanced coronary magnetic resonance angiography reconstructed using limited number of physiologic frames from 5D free-running acquisitions

Magn Reson Imaging. 2024 Jul 4:S0730-725X(24)00184-X. doi: 10.1016/j.mri.2024.07.008. Online ahead of print.

ABSTRACT

BACKGROUND: 5D, free-running imaging resolves sets of 3D whole-heart images in both cardiac and respiratory dimensions. In an application such as coronary imaging when a single, static image is of interest, computationally expensive offline iterative reconstruction is still needed to compute the multiple 3D datasets.

PURPOSE: Evaluate how the number of physiologic bins included in the reconstruction affects the computational cost and resulting image quality of a single, static volume reconstruction.

STUDY TYPE: Retrospective.

SUBJECTS: 15 pediatric patients following Ferumoxytol infusion (4 mg/kg).

FIELD STRENGTH/SEQUENCE: 1.5 T/Ungated 5D free-running GRE sequence.

ASSESSMENT: The raw data of each subject were binned and reconstructed into a 5D (x-y-z-cardiac-respiratory) images. 1, 3, 5, 7, and 9 bins adjacent to both sides of the retrospectively determined cardiac resting phase and 1, 3 bins adjacent to the end-expiration phase are used for limited frame reconstructions. The static volume within each limited reconstruction was compared with the corresponding full 5D reconstruction using the structural similarity index measure (SSIM). A non-linear regression model was used to fit SSIM with the percentage of data used compared to full reconstruction (% data). A linear regression model was used to fit computation time with % raw data used. Coronary artery sharpness is measured on each limited reconstructed images to determine the minimal number of cardiac and respiratory bins needed to preserve image quality.

STATISTICAL TESTS: The coefficient of determination (R2) is computed for each regression model.

RESULTS: The % of data used in the reconstruction was linearly related to the computational time (R2 = 0.99). The SSIM of the static image from the limited reconstructions is non-linearly related with the % of data used (R2 = 0.85). Over the 15 patients, the model showed SSIM of 0.9 with 22% of data, and SSIM of 0.95 with 45% of data. The coronary artery sharpness of images reconstructed using no less than 5 cardiac and all respiratory phases is not significantly different from the full reconstructed images using all cardiac and respiratory bins.

DATA CONCLUSION: Reconstruction using only a limited number of acquired physiological states can linearly reduce the computational cost while preserving similarity to the full reconstruction image. It is suggested to use no less than 5 cardiac and all respiratory phases in the limited reconstruction to best preserve the original quality seen on the full reconstructed images.

PMID:38972471 | DOI:10.1016/j.mri.2024.07.008

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A Closer Look into Gastrointestinal Bleeding in Heart Failure Patients

Curr Probl Cardiol. 2024 Jul 5:102739. doi: 10.1016/j.cpcardiol.2024.102739. Online ahead of print.

ABSTRACT

BACKGROUND: The frequency and risk factors for gastrointestinal bleed (GIB) in patients with heart failure with reduced ejection fraction (HFrEF) have not been extensively researched.

OBJECTIVE: We aim to assess the frequency of GIB in this subset of patients and identify potential risk factors for bleeding. This study will evaluate the frequency of commonly used antiplatelet and anticoagulation agents in the HFrEF population, as well as look at some of the endoscopic features of the GIB.

METHODS: A retrospective cohort analysis of 670 patients admitted between November 2021 to August 2023 to a single urban, tertiary teaching institution with acute HFrEF ICD-10 codes. Upper or lower GIB (hematemesis, coffee ground emesis, melena or hematochezia during admission) was identified on a manual chart review. Patients with GIB were defined as our cases. No GIB was defined as our controls. Sub analysis included comparing the use of anticoagulant and antiplatelet between the cohort. Independent t test assessed statistical differences in the case and control groups RESULTS: Out of the 670 patients, 134 (20%) were identified with GIB. The cases were older than the controls (median age 77 vs. 70 years) (p = 0.001), had a lower hemoglobin (9 g/dL vs. 12 g/dL) (p =<0.05), and had higher BNP levels (7,938 pg/ml vs. 6472 pg/ml) (IQR: 3,239, 23,701) (p =<0.01). Among the anticoagulant users, 64% of cases were on an anticoagulant compared to 42% of the controls (p<0.05). Among the antiplatelet users, 68% of the controls were on one or more antiplatelet agents, compared to 52% in the controls (p = 0.01). When combining AC and AP treatment, there was no statistical difference between cases and controls. Ninety-three (69%) patients from cases had cross-sectional imaging with only 23 (25%) showing abnormal findings which included diverticulosis, colitis, and GI masses. When comparing upper endoscopy findings, the presence of esophageal diseases (esophagitis and esophageal varices) and gastric/duodenal diseases (gastritis, gastric ulcer, duodenal ulcer and AVM) were significantly higher in cases compared to controls (p < 0.05). In addition to the colonoscopy findings, polyps and diverticulosis were more prevalent in the cases compared to the controls (p = 0.01).

CONCLUSION: Heart failure patients are at risk of developing GIB. Age and high BNP on admission are risk factors for GIB, the higher the BNP levels the higher risk of GIB. Anticoagulant and antiplatelet use are associated with a higher risk of bleeding. However, the addition of dual antiplatelet therapy or concurrent antiplatelet and anticoagulation does not increase the risk of GIB. Some of the most common upper endoscopy findings include esophagitis/gastritis and esophageal/gastric ulcer. In terms of colonoscopy, findings include colonic mass, diverticulosis and hemorrhoids.

PMID:38972470 | DOI:10.1016/j.cpcardiol.2024.102739

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Temporal relationship between sarcoidosis and malignancies in a nationwide cohort of 1942 patients

Postgrad Med J. 2024 Jul 8:qgae045. doi: 10.1093/postmj/qgae045. Online ahead of print.

ABSTRACT

PURPOSE: To investigate the phenotype of sarcoidosis according to the time when a malignancy is diagnosed (preexisting to the diagnosis of sarcoidosis, concomitant, or sequential) and to identify prognostic factors associated with malignancies in a large cohort of patients with sarcoidosis.

METHODS: We searched for malignancies in the SARCOGEAS cohort, a multicenter nationwide database of consecutive patients diagnosed with sarcoidosis according to the ATS/ESC/WASOG criteria. Solid malignancies were classified using the International Statistical Classification of Diseases and Related Health Problems 10th Revision (ICD-10) nomenclature, and hematological malignancies using the 2016 WHO classification. We excluded patients with a biopsy-proven diagnosis of sarcoidosis based exclusively on demonstrating granulomas in tissues also involved by malignant cells.

RESULTS: Out of 1942 patients with sarcoidosis, 233 (12%) developed 250 malignancies, including solid (n = 173), hematological (n = 57), and both types of malignancies (n = 3). Concerning the time interval between the diagnoses of both conditions, 83 (36%) patients were diagnosed with malignancy at least 1 year before sarcoidosis diagnosis, 22 (9%) had s synchronous diagnosis of both diseases, and 118 (51%) developed malignancies at least 1 year after the diagnosis of sarcoidosis (the remaining cases developed malignancies in different time intervals). The multivariate-adjusted model showed that individuals with sarcoidosis who developed a malignancy had an hazard ratio (HR) of 2.27 [95% confidence interval (CI), 1.62-3.17] for having an asymptomatic clinical phenotype at diagnosis of sarcoidosis and that spleen (presence vs. absence: HR = 2.06; 95% CI, 1.21-3.51) and bone marrow (presence vs. absence: HR = 3.04; 95% CI, 1.77-5.24) involvements were independent predictors for the development of all-type malignancies. No predictive factors were identified when the analysis was restricted to the development of solid malignancies. The analysis limited to the development of hematological malignancies confirmed the presence of involvement in the spleen (HR = 3.73; 95% CI, 1.38-10.06) and bone marrow (presence vs. absence: HR = 8.00; 95% CI, 3.15-20.35) at the time of sarcoidosis diagnosis as predictive factors.

CONCLUSION: It is essential to consider the synchronous or metachronous timing of the diagnosis of malignancies in people with sarcoidosis. We found that half of the malignancies were diagnosed after a diagnosis of sarcoidosis, with spleen and bone marrow involvement associated with a four to eight times higher risk of developing hematological malignancies. Key messages What is already known on this topic Malignancies are one of the comorbidities more frequently encountered in people with sarcoidosis What this study adds Malignancies occur in 12% of patients with sarcoidosis Malignancy may precede, coincide with, or follow the diagnosis of sarcoidosis One-third were identified before sarcoidosis, and half were diagnosed after Spleen and bone marrow involvement are risk factors for developing hematological malignancies How this study might affect research, practice or policy Patients with sarcoidosis should be regularly monitored for neoplasms, informed of the increased risk, and educated on early detection. Those with spleen or bone marrow involvement must be closely followed.

PMID:38972066 | DOI:10.1093/postmj/qgae045

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Evaluation and optimisation of phenolic compounds extracted by supercritical carbon dioxide from the seeds of Plantago ovata and their comparison with conventional extraction

Nat Prod Res. 2024 Jul 7:1-9. doi: 10.1080/14786419.2024.2375319. Online ahead of print.

ABSTRACT

This study’s main objectives are to evaluate and confirm the effects of the extraction process, operating conditions, solvent type and solvent polarity on the yield and quality of the extracts. Supercritical carbon dioxide (scCO2) and Soxhlet were specially used in this study to extract bioactive chemicals from the seeds of a natural plant known as Plantago ovata. No studies have been published so far regarding the extraction from the seeds of this plant using scCO2.The effects of three operating parameters (pressure, temperature and particle size) on the extraction yield, total phenolic content, total flavonoid content (TFC), total tannin content (TTC) and antioxidant activity were assessed in this study using the Box-Behnken statistical experimental design (BBD). The chemical components in the extracts were separated and identified using gas chromatography mass spectrometry. According to the antioxidant activity results, scCO2 failed to produce bioactive compounds with interesting properties when operated within operating range conditions.

PMID:38972058 | DOI:10.1080/14786419.2024.2375319