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Nevin Manimala Statistics

TARA: Training and Representation Alteration for AI Fairness and Domain Generalization

Neural Comput. 2022 Jan 11:1-38. doi: 10.1162/neco_a_01468. Online ahead of print.

ABSTRACT

We propose a novel method for enforcing AI fairness with respect to protected or sensitive factors. This method uses a dual strategy performing training and representation alteration (TARA) for the mitigation of prominent causes of AI bias. It includes the use of representation learning alteration via adversarial independence to suppress the bias-inducing dependence of the data representation from protected factors and training set alteration via intelligent augmentation to address bias-causing data imbalance by using generative models that allow the fine control of sensitive factors related to underrepresented populations via domain adaptation and latent space manipulation. When testing our methods on image analytics, experiments demonstrate that TARA significantly or fully debiases baseline models while outperforming competing debiasing methods that have the same amount of information-for example, with (% overall accuracy, % accuracy gap) = (78.8, 0.5) versus the baseline method’s score of (71.8, 10.5) for Eye-PACS, and (73.7, 11.8) versus (69.1, 21.7) for CelebA. Furthermore, recognizing certain limitations in current metrics used for assessing debiasing performance, we propose novel conjunctive debiasing metrics. Our experiments also demonstrate the ability of these novel metrics in assessing the Pareto efficiency of the proposed methods.

PMID:35016212 | DOI:10.1162/neco_a_01468

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Nevin Manimala Statistics

Full-field Electroretinography Changes Associated with Age-related Macular Degeneration: A Systematic Review with Meta-Analyses

Ophthalmologica. 2022 Jan 11. doi: 10.1159/000521834. Online ahead of print.

ABSTRACT

BACKGROUND: To systematically review the literature and to perform meta-analyses on full-field electroretinography (ffERG) between healthy controls and age-related macular degeneration (AMD) to map the extent of retinal dysfunction.

SUMMARY: We systematically searched 11 databases on 3 March 2021. Eligible studies had to measure retinal function using ffERG in eyes with AMD and in healthy controls. We extracted data on a-wave and b-wave function in dark- and light-adapted ffERG, and calculated summary estimates on differences between eyes with AMD and controls using weighted mean differences (WMD). Subgroup analyses were made for early and late AMD. Six studies (n=481 eyes) were eligible for review (301 with any AMD, 180 controls). For dark-adapted data, any AMD was associated with reduced a-wave amplitude (WMD: -17.16 µV; 95% CI: -31.79 to -2.52 µV; P=0.02) and b-wave amplitude (WMD: -28.70 µV; 95% CI: -51.40 to -6.01 µV; P=0.01). For light-adapted data, any AMD was associated with longer a-wave implicit time (WMD: 0.92 ms; 95% CI: 0.12 to 1.72 ms; P=0.02), reduced b-wave amplitude (WMD: -13.26 µV; 95% CI: -18.64 to -7.88 µV; P<0.0001), and longer b-wave implicit time (WMD: 0.69 ms; 95% CI: 0.30 to 1.08 ms; P=0.0006). Subgroup analyses found that these changes were only statistically significant in eyes with late AMD, not early AMD. Key messages: Reduced retinal function on ffERG is present in eyes with AMD, in particular those with late AMD. These findings suggest that AMD is a pan-retinal disease with AMD-associated photoreceptor dysfunction beyond the macula.

PMID:35016191 | DOI:10.1159/000521834

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Causes of Death in End-Stage Kidney Disease: Comparison between the United States Renal Data System and a Large Integrated Health Care System

Am J Nephrol. 2022 Jan 11:1-9. doi: 10.1159/000520466. Online ahead of print.

ABSTRACT

INTRODUCTION: Using a large diverse population of incident end-stage kidney disease (ESKD) patients from an integrated health system, we sought to evaluate the concordance of causes of death (CODs) between the underlying COD from the United States Renal Data System (USRDS) registry and CODs obtained from Kaiser Permanente Southern California (KPSC).

METHODS: A retrospective cohort study was performed among incident ESKD patients who had mortality records and CODs reported in both KPSC and USRDS databases between January 1, 2007, and December 31, 2016. Underlying CODs reported by the KPSC were compared to the CODs reported by USRDS. Overall and subcategory-specific COD agreements were assessed using Cohen’s weighted kappa statistic (95% CI). Proportions of positive and negative agreement were also determined.

RESULTS: Among 4,188 ESKD patient deaths, 4,118 patients had CODs recorded in both KPSC and USRDS. The most common KPSC CODs were circulatory system diseases (35.7%), endocrine/nutritional/metabolic diseases (24.2%), genitourinary diseases (12.9%), and neoplasms (9.6%). Most common USRDS CODs were cardiac disease (46.9%), withdrawal from dialysis (12.6%), and infection (10.1%). Of 2,593 records with causes listed NOT as “Other,” 453 (17.4%) had no agreement in CODs between the USRDS and the underlying, secondary, tertiary, or quaternary causes recorded by KPSC. In comparing CODs recorded within KPSC to the USRDS, Cohen’s weighted kappa (95% CI) was 0.20 (0.18-0.22) with overall agreement of 36.4%.

CONCLUSION: Among an incident ESKD population with mortality records, we found that there was only fair or slight agreement between CODs reported between the USRDS registry and KPSC, a large integrated health care system.

PMID:35016183 | DOI:10.1159/000520466

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Effect of Expanded Hemodialysis with Theranova® in Patients with COVID-19

Blood Purif. 2022 Jan 11:1-9. doi: 10.1159/000520891. Online ahead of print.

ABSTRACT

INTRODUCTION: Cytokine storm control is the main target for improving severe COVID-19 by using immunosuppressive treatment. Effective renal replacement therapy (RRT) could give us an advantage removing cytokines in patients with RRT requirements superimposed on COVID-19.

METHODS: This is a prospective observational study in COVID-19 patients who required hemodialysis (HD). Patients were assigned to online hemodiafiltration (OL-HDF) and expanded HD (HDx) according to Brescia group recommendations. We measured several cytokines, β2 microglobulin and albumin levels pre/post-dialysis and on 1st-2nd week. We compared levels among both techniques and control group (HD without COVID-19).

RESULTS: We included 26 patients: 18 with COVID-19 on RRT (5 of them had acute kidney injury [AKI]) and 8 controls. We confirm higher cytokine levels in COVID-19 patients than controls and even higher in patients with AKI than in those with chronic kidney disease. Most cytokines raised during HD session, except IL-10 and TNFα. IL-10 was eliminated by any dialysis technique, while clearance of TNFα was higher in the HDx group. HDx achieved a deeper normalization of cytokines and β2 microglobulin reduction. Mortality was higher in the OL-HDF group than the HDx group.

DISCUSSION: Not all cytokines behave equally along HD session. The following characteristics should be taken into account, such as intrinsic kinetic profile during a HD session. HDx seems to get better performance, probably due to the combination of different factors; however, we did not reach statistical significance due to the small sample size, dropout, and reduction of AKI incidence during the 2nd pandemic wave.

CONCLUSION: HDx appears to provide better clearance for TNFα and β2 microglobulin during HD session and associates lower mortality. We propose the HDx technique for COVID-19 patients with RRT requirements since it seems to be safe and more effective than OL-HDF. Further studies are still needed, but we hope that our preliminary data may help us in future pandemic waves of SARS-CoV-2 or other viruses still to come.

PMID:35016172 | DOI:10.1159/000520891

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Salivary Cortisol Awakening Response as a Predictor for Depression Severity in Adult Patients with a Major Depressive Episode Performing a Daily Exercise Program

Neuropsychobiology. 2022 Jan 11:1-10. doi: 10.1159/000521234. Online ahead of print.

ABSTRACT

INTRODUCTION: The hypothalamic-pituitary-adrenal axis function in depression has been the subject of considerable interest, and its function has been tested with a variety of methods. We investigated associations between saliva cortisol at awakening and the 24-h urine cortisol output, both measured at study baseline, with endpoint depression scores.

METHODS: Patients were admitted to a psychiatric inpatient ward with a major depressive episode and were started on fixed duloxetine treatment. They delivered saliva samples at awakening and 15, 30, and 60 min post-awakening and sampled urine for 24 h. Subsequently, they started a daily exercise program maintained for a 9-week period. Clinician-rated depression severity was blindly assessed with the Hamilton Depression Rating 6-item subscale (HAM-D6). The cortisol awakening response was quantified by the area under the curve with respect to the ground (AUCG) and with respect to the rise (AUCI) using saliva cortisol levels in the 1-h period after awakening. Analysis of expected associations between depression severity, AUCG, AUCI, exercise, and 24-h cortisol output was performed in a general linear model.

RESULTS: In all, 35 participants delivered saliva or 24-h urine samples. The mean age was 49.0 years (SD = 11.0) with 48.6% females with a mean baseline HAM-D6 score of 12.2 (SD = 2.3). In a statistical model investigating the association between HAM-D6 at week 9 as a dependent variable and AUCI, concurrent HAM-D6, gender, smoking, and exercise volume as covariates, we found a significant effect of AUCI, concurrent HAM-D6, and exercise. The following statistics were found: AUCI (regression coefficient 0.008; F value = 9.1; p = 0.007), concurrent HAM-D6 (regression coefficient 0.70; F value = 8.0; p = 0.01), and exercise (regression coefficient -0.005; F value = 5.7; p = 0.03). The model had an R2 of 0.43. The association between HAM-D6 endpoint scores and the AUCI showed that higher AUCI values predicted higher HAM-D6 endpoint values. The association between HAM-D6 endpoint scores and the exercise level showed that a high exercise level was associated with lower HAM-D6 endpoint values.

CONCLUSION: The results thus showed that high AUCI values predicted less improvement of depression and high exercise levels predicted more improvement of depression. These findings need to be confirmed in larger samples to test if more covariates can improve prediction of depression severity.

PMID:35016170 | DOI:10.1159/000521234

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Nevin Manimala Statistics

Symptoms of depression, anxiety and stress from COVID-19 in a family medicine unit

Rev Med Inst Mex Seguro Soc. 2021 Aug 2;59(4):274-280.

ABSTRACT

BACKGROUND: The COVID-19 pandemic has come to change our way of life, completely modifying even the form of coexistence, which can lead anyone to suffer from anxiety, stress or depression, either out of fear of getting infected, losing a loved one or simply because of the limitation to go outside.

OBJECTIVE: To determine the presence of symptoms of depression, anxiety and stress in the face of the COVID-19 pandemic in the beneficiaries of a family medicine unit of first level of care and to establish their relationship with age.

MATERIAL AND METHODS: Observational, relational, crosssectional study, in 185 beneficiaries of a family medicine unit from June 15th to August 15th, 2020. Sociodemographic data were requested, and the DASS-21 scale was applied to search for symptoms of depression, anxiety and stress. Univariate analysis was performed with measures of central tendency and dispersion. For the bivariate analysis, Pearson’s correlation coefficient was used to identify the relationship between age and stress.

RESULTS: Symptoms of depression were found in 11.9%, anxiety in 22.7% and stress in 14.5% of the participants. A weak negative relationship (r = -0.199, p = 0.007) was found between age and stress.

CONCLUSION: There are symptoms of depression, anxiety and stress, with a weak, statistically significant negative relationship between age and stress.

PMID:35014771

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Nevin Manimala Statistics

Safety and efficacy of anti-EGFR monoclonal antibody (SCT200) as second-line therapy in advanced esophageal squamous cell carcinoma

Cancer Biol Med. 2022 Jan 12:j.issn.2095-3941.2021.0388. doi: 10.20892/j.issn.2095-3941.2021.0388. Online ahead of print.

ABSTRACT

OBJECTIVE: The mainstay treatment of esophageal squamous cell carcinoma (ESCC) involves chemotherapy and immunotherapy. However, alternative therapies are required for patients who are refractory or intolerant to existing therapies.

METHODS: In this single-arm, multicenter, open-label phase Ib study, 30 patients received an intravenous infusion of SCT200, an antiepidermal growth factor receptor (EGFR) monoclonal antibody, 6.0 mg/kg once a week for 6 weeks, followed by 8.0 mg/kg once every 2 weeks until disease progression or intolerable toxicity. The primary endpoint was the objective response rate (ORR). The secondary endpoints were progression-free survival (PFS), overall survival (OS), and safety.

RESULTS: Thirty patients were enrolled between July 2018 and May 2019. The ORR was 16.7% (95% CI: 5.6%-34.7%). The median PFS and OS were 3.1 months (95% CI: 1.5-4.3) and 6.8 months (95% CI: 4.7-10.1), respectively. A numerical difference without any statistical significance in ORR was observed in patients with different EGFR expressions (≥ 50%: 25.0% vs. < 50%: 0%, P = 0.140) or TP53 mutation abundance (< 10%: 23.8% vs. ≥ 10%: 0%, P = 0.286). Improved median PFS (3.4 vs. 1.4 months, P = 0.006) and OS (8.0 vs. 4.2 months, P = 0.027) were associated with TP53 mutation abundance of < 10%. The most common treatment-related adverse events of grade 3 or 4 (occurring in ≥ 2 patients) were hypomagnesemia [7 (23.3%)] and rash [2 (6.7%)]. No treatment-related death occurred.

CONCLUSIONS: SCT200 monotherapy as the second- or further-line treatment for advanced ESCC showed favorable efficacy, with an acceptable safety profile. TP53 mutation abundance might serve as a potential predictive biomarker.

PMID:35014769 | DOI:10.20892/j.issn.2095-3941.2021.0388

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Nevin Manimala Statistics

Maternal pre-pregnancy body mass index, gestational weight gain, and pubertal timing in daughters: A systematic review and meta-analysis of cohort studies

Obes Rev. 2022 Jan 11:e13418. doi: 10.1111/obr.13418. Online ahead of print.

ABSTRACT

The timing of daughter’s puberty onset is constantly earlier. It is still unclear about the maternal pre-pregnancy body mass index (BMI) and gestational weight gain (GWG) as important prenatal factors that may affect offspring’s onset of puberty. Thus, we evaluated the association among maternal pre-pregnancy BMI, GWG, and daughters’ early pubertal development based on the existing literature. Literature review was conducted in different databases, including Web of Science, Pubmed, Wiley, ScienceDirect, Web of Science, and Chinese National Knowledge Infrastructure databases up to June 2021. We selected random effects model or fixed effects model for meta-analysis according to the I2 statistics value to obtain the summary measurement. A total of 12 cohort studies were included. Compared to maternal pre-pregnancy normal weight, maternal pre-pregnancy overall overweight/obesity (RR = 1.24; 95% CI 1.17 to 1.32), obesity (RR = 1.35; 95% CI 1.23 to 1.48), and overweight (RR = 1.17; 95% CI 1.09 to 1.26) were significantly associated with the increased risk of earlier timing of pubertal onset in daughters. Daughters born of mothers with pre-pregnancy overall overweight/obesity, obesity, and overweight had earlier pubertal onset compared to those born of mothers with normal weight ([mean difference = -3.03, 95% CI: -3.97 to -2.10], [mean difference = -3.50, 95% CI: -5.38 to -1.62], and [mean difference = -2.89, 95% CI: -4.07 to -1.71], respectively). The effects were also significant in the assessed three milestones (menarche, breast development, and pubic hair development). Maternal excessive GWG increased the risk of early pubertal timing in daughters (RR = 1.19; 95% CI 1.09 to 1.30).

PMID:35014751 | DOI:10.1111/obr.13418

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Fetal and maternal outcomes after maternal biologic use during conception and pregnancy: a systematic review and meta-analysis

BJOG. 2022 Jan 11. doi: 10.1111/1471-0528.17093. Online ahead of print.

ABSTRACT

BACKGROUND: Biologic medications, specifically the TNF-α inhibitors, have become increasingly prevalent in the treatment of chronic inflammatory disease (CID) in pregnancy.

OBJECTIVE: To determine pregnancy outcomes in women with CID exposed to biologics during pregnancy.

SEARCH STRATEGY: PubMed and EMBASE databases were searched through January 1998-July 2021.

SELECTION CRITERIA: Peer reviewed, English language cohort, case-control, cross-sectional studies, and case series which contained original data.

DATA COLLECTION AND ANALYSIS: Two authors independently conducted data extraction. A meta-analysis of proportions using a random-effects model was used to pool outcomes. Linear regression analysis was used to compare the mean of proportions of outcomes across exposure groups using the ‘treated’ group as the reference category. All studies were evaluated using an appropriate quality assessment tool described by McDonald et al. The GRADE approach was used to assess the overall certainty of evidence.

MAIN RESULTS: 35 studies, 11172 pregnancies, were eligible for inclusion. Analysis showed pooled proportions for congenital malformations: treated 0.04(95% CI 0.03-0.04; I2 77) vs disease matched 0.04(0.03-0.05. I2 86) p=0.238. Preterm delivery treated 0.04(0.10-0.14. I2 88) vs disease matched 0.10(0.09-0.12. I2 87) p=0.250. Severe neonatal infection: treated 0.05(0.03-0.07. I2 88) vs disease matched 0.05(0.02-0.07. I2 94) p=0.970. Low birth weight: treated 0.10(0.07-0.12. I2 93) vs disease matched 0.08(0.07-0.09. I2 0) p=0.241. The pooled Miscarriage: treated 0.13(0.10-0.15. I2 77) vs disease matched 0.08(0.04-0.11. I2 5) p=0.078. Pre-eclampsia; treated 0.01(0.01-0.02. I2 0) vs disease matched 0.01(0.00-0.01. I2 0). p=0.193. No statistical differences in proportions were observed. GRADE certainty of findings were low to very low.

CONCLUSION: We demonstrated comparable pregnancy outcomes in pregnancies exposed to biologics, disease matched controls and CID free pregnancies using the GRADE approach.

PMID:35014759 | DOI:10.1111/1471-0528.17093

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Metformin use is associated with a decrease in risk of hospitalization and mortality in COVID-19 diabetic patients: a population-based study in Lombardy

Diabetes Obes Metab. 2022 Jan 10. doi: 10.1111/dom.14648. Online ahead of print.

ABSTRACT

AIMS: We compared the association of metformin use and COVID-19 outcomes in a cohort of 31 966 patients with diabetes in Lombardy.

METHODS: We used a COVID-19 linkable administrative regional database to select diabetic patients over 40 years old. They had at least two prescriptions of antidiabetic drugs in 2019 and a positive test for SARS-CoV-2 between February 15, 2020 and March 15, 2021. The association of metformin use and clinical outcomes was assessed by multivariable logistic regression analyses and after propensity score matching. Clinical outcomes were all-cause mortality, in-hospital mortality, hospitalization for COVID-19 and admission to an intensive care unit (ICU).

RESULTS: In multivariable models metformin use was associated with a significantly lower risk of total mortality (OR 0.70; 95% CI 0.66-0.75), in-hospital mortality (OR 0.68; 95% CI 0.63-0.73), hospitalization for COVID-19 (OR 0.86; 95% CI 0.81-0.91) and ICU admission (OR 0.81; 95% CI 0.69-0.94) compared with metformin non-users. Results were similar in propensity score analysis; metformin was associated with significantly lower risk of total mortality (OR 0.79; 95% CI, 0.73-0.86), in-hospital mortality (OR 0.74; 95% CI, 0.67-0.81) and ICU admission (OR 0.77; 95% CI, 0.63-0.95).

CONCLUSIONS: In this large cohort, metformin use was associated with a protective effect in COVID-19 clinical outcomes, suggesting that it might be a potentially useful drug to prevent severe COVID-19 disease, although randomized clinical trials (RCT) are needed to confirm this. While awaiting the results of RCT, we suggest continuing prescribing metformin to diabetic patients with COVID-19. This article is protected by copyright. All rights reserved.

PMID:35014746 | DOI:10.1111/dom.14648