Nevin Manimala

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

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

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

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

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

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

Vet Dermatol. 2022 Jan 11. doi: 10.1111/vde.13053. Online ahead of print.

ABSTRACT

BACKGROUND: Oclacitinib administered at the licensed dose twice daily for two weeks and then once daily as required is recommended for the treatment of atopic dogs. In some cases, the once-daily regimen is insufficient to control the clinical signs.

OBJECTIVES: To provide preliminary safety and efficacy data on the prolonged twice-daily administration of oclacitinib in atopic dogs.

ANIMALS: Fifty-three client-owned atopic dogs.

METHODS AND MATERIALS: The medical records of dogs with atopic dermatitis treated with oclacitinib twice daily for more than two weeks were reviewed retrospectively. Animal details, treatment dose and duration, concurrent diseases, adjunctive medications and possible adverse events were recorded. Treatment efficacy was assessed retrospectively and, when available, the selected blood parameters before and during the treatment were compared. Statistical analyses of the collected data were performed.

RESULTS: The median treatment duration was 113 days. Excellent-to-good efficacy was observed in 38 dogs (72%), including 24 of 33 dogs that failed to respond to the once-daily regimen. Eight dogs showed a poor response despite the addition of systemic glucocorticoids. Pyoderma, gastrointestinal signs and otitis externa were the most frequent adverse events recorded whilst on treatment. Blood tests performed in 35 dogs showed slightly decreased leucocyte, neutrophil, eosinophil and monocyte counts that remained within the reference ranges in most cases. Three dogs developed hypercholesterolemia.

CONCLUSIONS AND CLINICAL RELEVANCE: Prolonged twice-daily administration of oclacitinib generally was well-tolerated and was effective in most of the treated dogs. Regular clinical evaluation and blood tests are advisable for this treatment regimen.

PMID:35014745 | DOI:10.1111/vde.13053

Vet Dermatol. 2022 Jan 11. doi: 10.1111/vde.13055. Online ahead of print.

ABSTRACT

BACKGROUND: Previous studies have shown that patch testing with food extracts can assist formulation of elimination diets (ED) in human patients with suspected adverse food reactions (AFR). Little is known about the use of these tests in dogs.

OBJECTIVES: To evaluate the effectiveness of a combination of prick and patch testing in current protocols, and food challenge (FC) tests in dogs with AFR.

METHODS AND MATERIALS: Prick and patch tests were performed on 21 dogs with chronic, nonseasonal pruritus. Dogs then were fed an ED formulated on the basis of the results. All dogs with improved clinical signs then were challenged with a food to which there had been a positive reaction in the tests. Six dogs subsequently were challenged with a food to which they had been negative on testing. Pruritus Visual Analog Scale (pVAS) and Canine Atopic Dermatitis Extent and Severity Index, 4th iteration (CADESI-04) were evaluated on Day (D)0, D30 and D60 of the ED. Sensitivity (SE), specificity (SP), positive (PPV) and negative (NPV) predictive values, and the Kappa (κ)value were calculated.

RESULTS: Of the 21 dogs, there was a significant mean improvement in pVAS and CADESI-04 scores in 16 (76%) dogs after D30 (P < 0.01) and D60 (P < 0.01) of the ED. There were no statistical differences between D30 and D60. The combination of tests had SE, SP, PPV, NPV and κ values of 80%, 66.7%, 66.7%, 80% and -0.17, respectively.

CONCLUSIONS AND CLINICAL RELEVANCE: The combination of prick and patch testing reached high values of SE and NPV. A diagnosis of AFR was made in 76% of the dogs, and test results were useful for the selection of an ED.

PMID:35014738 | DOI:10.1111/vde.13055

Indoor Air. 2022 Jan 11. doi: 10.1111/ina.12980. Online ahead of print.

ABSTRACT

This study examines whether exposure to secondhand smoke (SHS) increases the risk of acute respiratory infections (ARI) among children aged 0-59 months. Study utilized nationally representative data from National Family Health Survey (2015-2016), which adopted two-stage stratified random sampling. Four mutually exclusive groups based on the type of cooking fuel usage and SHS exposure were created. Descriptive statistics and multivariate logistics regression analysis were applied. At the national level, 10.5% prevalence of ARI was reported during 2015-2016. About 47.9% (95%CI 47.7-48.2) of households was exposed to SHS and used solid biomass fuel for cooking. Nearly, 20.7% of households with clean fuel usage was exposed to SHS. Regression analysis suggests that the likelihood of ARI among children who were living in households with solid biomass fuel usage and exposed to SHS was 11% (95%CI 1.06-1.17) greater than children living in households with clean fuel usage with no SHS exposure. Moreover, our results further revealed that the odds of ARI among children living in households with clean fuel but exposed to SHS were 19% (95%CI 1.13-1.25) higher than the children living in the household with no SHS exposure and clean fuel use. Children living in households exposed to SHS are at higher risk of ARI.

PMID:35014716 | DOI:10.1111/ina.12980

Stat Med. 2022 Jan 11. doi: 10.1002/sim.9264. Online ahead of print.

ABSTRACT

Semiparametric accelerated failure time (AFT) models are a useful alternative to Cox proportional hazards models, especially when the assumption of constant hazard ratios is untenable. However, rank-based criteria for fitting AFT models are often nondifferentiable, which poses a computational challenge in high-dimensional settings. In this article, we propose a new alternating direction method of multipliers algorithm for fitting semiparametric AFT models by minimizing a penalized rank-based loss function. Our algorithm scales well in both the number of subjects and number of predictors, and can easily accommodate a wide range of popular penalties. To improve the selection of tuning parameters, we propose a new criterion which avoids some common problems in cross-validation with censored responses. Through extensive simulation studies, we show that our algorithm and software is much faster than existing methods (which can only be applied to special cases), and we show that estimators which minimize a penalized rank-based criterion often outperform alternative estimators which minimize penalized weighted least squares criteria. Application to nine cancer datasets further demonstrates that rank-based estimators of semiparametric AFT models are competitive with estimators assuming proportional hazards in high-dimensional settings, whereas weighted least squares estimators are often not. A software package implementing the algorithm, along with a set of auxiliary functions, is available for download at github.com/ajmolstad/penAFT.

PMID:35014701 | DOI:10.1002/sim.9264