Nevin Manimala

Hepatology. 2021 Mar 17. doi: 10.1002/hep.31809. Online ahead of print.

ABSTRACT

Nonalcoholic fatty liver disease (NAFLD) is the most prevalent cause of liver disease in children. Mercury (Hg), a ubiquitous toxic metal, has been proposed as an environmental factor contributing to toxicant-associated fatty liver disease. We investigated the effect of prenatal exposure to Hg on childhood liver injury by combining epidemiological results from a multicenter mother-child cohort with complementary in vitro experiments on monocyte cells that are known to play a key role in liver immune homeostasis and NAFLD. We used data from 872 mothers and their children (median age, 8.1 years; interquartile range [IQR], 6.5-8.7) from the European Human Early-Life Exposome (HELIX) cohort. We measured Hg concentration in maternal blood during pregnancy (median, 2.0 μg/L; IQR, 1.1-3.6). We also assessed serum levels of alanine aminotransferase (ALT), a common screening tool for pediatric NAFLD, and plasma concentrations of inflammation-related cytokines in children. We found that prenatal Hg exposure was associated with a phenotype in children that was characterized by elevated ALT (≥22.1 U/L for females and ≥25.8 U/L for males) and increased concentrations of circulating interleukin (IL)-1β, IL-6, IL-8, and tumor necrosis factor α (TNF-α). Consistently, inflammatory monocytes exposed in vitro to a physiologically relevant dose of Hg demonstrated significant up-regulation of genes encoding these four cytokines and increased concentrations of IL-8 and TNF-α in the supernatants. CONCLUSION: These findings suggest that developmental exposure to Hg can contribute to inflammation and increased NAFLD risk in early life.

PMID:33730435 | DOI:10.1002/hep.31809

Int J Paediatr Dent. 2021 Mar 17. doi: 10.1111/ipd.12781. Online ahead of print.

ABSTRACT

BACKGROUND: The number of child abuse cases is increasing worldwide therefore it is important to educate individuals having contact with children about it. This includes dentists who play a pivotal role in detecting and reporting these cases.

AIM: To identify and compare the final year dental student’s knowledge, attitudes and practice in relation to child abuse.

DESIGN: A 38-item and four part online questionnaire was distributed to students of 11 dental schools in 10 countries. SPSS and GraphPad Prism were used for data analysis. The levels of statistical significance were determined using a chi-square test. P ≤ 0.05 was considered to be statistically significant.

RESULTS: A total of 660 students completed the survey. Fifty-six percent of the students received formal training on child abuse, and 86% wanted additional training. The knowledge of child abuse was significantly higher in Australia, USA and Jordan compared to other countries. The internet (60.3%) was widely used as an information source for child abuse.

CONCLUSIONS: The study showed that dental students lack knowledge and experience in recognising and reporting child abuse. Most respondents indicated a desire for additional training, therefore dental schools should review what they are currently teaching and make changes as appropriate.

PMID:33730406 | DOI:10.1111/ipd.12781

J Appl Behav Anal. 2021 Mar 17. doi: 10.1002/jaba.823. Online ahead of print.

ABSTRACT

Although in-vivo behavioral skills training (BST) is often effective, it may be too resource-intensive for organizations that rely on volunteers. Alternatives to in-vivo BST include video models or interactive computer training (ICT), but the utility of these procedures for training volunteers remains largely unknown. We used a randomized control trial to teach multiple skills to new volunteers at a therapeutic riding center. A total of 60 volunteers were assigned to one of three groups using block randomization. Depending on group assignment, volunteers received instructions and modeling through in-vivo interactions, a video model, or ICT. All volunteers completed in-vivo role plays with feedback. Skills were measured by unblinded observers during role plays. There were no statistically significant differences in accuracy of role-play performance between volunteers in the in-vivo BST and ICT groups, but both outperformed the video-model group. The ICT and video model required statistically significantly less time from a live instructor than did in-vivo training. Thus, although in-vivo BST remains best practice, ICT may be a viable alternative when training resources are limited.

PMID:33730397 | DOI:10.1002/jaba.823

J Oral Pathol Med. 2021 Mar 17. doi: 10.1111/jop.13170. Online ahead of print.

ABSTRACT

BACKGROUND: Oral lichen planus (OLP) is a common chronic inflammatory condition with an undefined malignant transformation potential. There have been many attempts at providing a specific definition of OLP without conclusive outcomes. A new set of diagnostic criteria was proposed in 2016 by the American Academy of Oral and Maxillofacial Pathology (AAOMP) in an endeavour to resolve this issue, and this has not yet been evaluated. This study aimed to assess the utility of AAOMP proposed criteria for the diagnosis of OLP.

METHODS: Five pathologists blindly assessed a cohort of 215 digital whole slide images (WSI) obtained from haematoxylin and eosin stained microscopic slides. Forty-six WSI were included twice to assess the intra-observer agreement. Included cases were diagnosed clinically as either OLP or oral lichenoid reaction. Each pathologist was asked to utilize the AAOMP histopathological criteria while assessing slides. The variations in diagnoses were assessed by unweighted kappa statistics.

RESULTS: The level of intra-observer agreement was very good (0.801 to 0.899). The level of inter-observer agreement among the observers varied from good (0.658) to very good (0.842) when the responses were categorized as evident/compatible OLP versus no OLP, and was good (0.62 to 0.725) when the responses were categorized as evident OLP, versus compatible OLP, versus no OLP. The clinico-pathological correlation was 87.6%.

CONCLUSION: A reliable level of agreement can be achieved by pathologists for the diagnosis of OLP using the AAOMP criteria for differentiation between lichenoid and other conditions. There are still limitations in discriminating OLP from oral lichenoid lesions microscopically.

PMID:33730381 | DOI:10.1111/jop.13170

Ther Innov Regul Sci. 2021 Mar 17. doi: 10.1007/s43441-021-00268-x. Online ahead of print.

ABSTRACT

The FDA IND safety reporting Final Rule (21CFR 312.32) applies to all human drugs and biological products being studied under an Investigational New Drug (IND). A sponsor must file an IND safety report for any serious unexpected suspected adverse reaction (SUSAR) of a medicinal product being investigated. Some events may be obviously drug-related (e.g., agranulocytosis, anaphylactic reaction, drug-induced hepatic injury, Stevens-Johnson Syndrome). For serious adverse events that are not interpretable as individual occurrences, additional processes and procedures need to be employed for identifying and assessing risks in the accumulating safety data. The approaches shared in this manuscript apply principally to safety reporting of events that are anticipated to occur in the patient population-regardless of study participation. For these events, the study sponsor should periodically review the data in the aggregate and make a judgment as to whether there is a reasonable possibility of an event having been caused by the study drug rather than the underlying condition of the patient or a concomitant therapy. Factors cited for consideration are the size and consistency of the difference in event frequency between the test and control groups, supportive preclinical findings, evidence of a dose response relationship, plausible mechanism of action, known class effect and occurrence of other related adverse events. Examples are provided that demonstrate the flexibility sponsors have in meeting the spirit of the Final Rule; some combination and variation of methods from the examples could be employed. The important thing, as expressed by Jacqueline Corrigan-Curay (Director of the Office of Medical Policy, Center for Drug Evaluation and Research, FDA), is to have a thoughtful process; a system in place to look for clinically important imbalances, applying the best clinical and quantitative judgment, while maintaining trial integrity (Ball et al. in Interdisciplinary aggregate assessments for IND safety reporting: a dialogue among colleagues from industry, Academia and the FDA. ASA biopharmaceutical section regulatory-industry statistics workshop, 2018).

PMID:33730364 | DOI:10.1007/s43441-021-00268-x

Adv Ther. 2021 Mar 17. doi: 10.1007/s12325-021-01674-1. Online ahead of print.

ABSTRACT

INTRODUCTION: The present study aimed to investigate the effect of anti-cytomegalovirus (anti-CMV) therapy at different stages on retinal detachment in patients with acquired immunodeficiency syndrome (AIDS) and cytomegalovirus retinitis (CMVR).

METHODS: Ninety-seven patients with AIDS and CMVR diagnosed and treated at the Ophthalmology and Infection Center of Beijing You’an Hospital, affiliated with Capital Medical University, from November 2017 to January 2020 were retrospectively analyzed. Of the 138 eyes included, 30 eyes with concomitant retinal detachment were enrolled as the study subjects. The eyes with retinal detachment were divided into a pre-induction group, an intra-induction group, and a post-induction group of anti-CMV therapy. The occurrence and characteristics of retinal detachment at different stages of anti-CMV therapy were observed.

RESULTS: Retinal detachment occurred in 30 of the 138 eyes of 97 patients, with an incidence of retinal detachment of 21.74%. Retinal detachment occurred in eight eyes in the pre-induction group, with an incidence of 26.67%, and in four eyes in the intra-induction group, with an incidence of 13.33%. The difference in incidence between the two groups was statistically significant (P = 0.000). Retinal detachment occurred in 18 eyes in the post-induction group, with an incidence of 60%. The difference in incidence between the intra-induction group and the post-induction group was statistically significant (P = 0.001).

CONCLUSION: The incidence of retinal detachment at the intra-induction stages of anti-CMV therapy was lower than that at the pre-induction stage, and retinal detachment during the anti-CMV therapy predominantly occurred after the end of the induction stage.

PMID:33730351 | DOI:10.1007/s12325-021-01674-1

J Endocrinol Invest. 2021 Mar 17. doi: 10.1007/s40618-021-01537-0. Online ahead of print.

ABSTRACT

INTRODUCTION: Thyrotropin stimulating hormone (TSH) suppression in patients with differentiated thyroid cancer (DTC) aims to decrease the growth and proliferation of thyroid cancer cells. However, the effect of TSH-suppressive therapy on bone microarchitecture remains undefined.

METHODS: Cross-sectional study including 43 women with DTC undergoing TSH-suppressive therapy (sTSH) compared to 20 women also on levothyroxine (LT4) therapy but with TSH in the low-normal range (nTSH) since the thyroid surgery. Bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry (DXA), and trabecular bone score (TBS) was evaluated using the TBS iNsigth software. Fracture risk assessed by FRAX, with and without TBS, was calculated. The relationship between suppressive therapy-related parameters and bone parameters was investigated.

RESULTS: The TBS mean values were not significantly different in the sTSH and nTSH groups (1.273 ± 0.12 vs 1.307 ± 0.14, p = 0.7197). In both groups, postmenopausal women had degraded microarchitecture (TBS 1.216 ± 0.11 vs 1.213 ± 0.09, p = 0.9333), while premenopausal women had normal microarchitecture (1.328 ± 0.11 vs 1.401 ± 0.12, p = 0.195). The percentage of all postmenopausal women with degraded TBS was 54.7%, while the percentage of osteoporosis diagnoses was 16.1%. The TBS-adjusted FRAX-probability of fracture was similar in sTSH and nTSH groups. Body mass index (BMI) and menopausal status were the only variables associated with TBS and BMD.

CONCLUSION: Trabecular microarchitecture assessed by TBS was similar between women on long-term suppressive therapy in DTC and those on LT4 replacement therapy aiming at a TSH level within the low-normal reference range. Low TBS values were observed in postmenopausal women of both groups, suggesting that not only suppressed TSH levels but also a low-normal TSH is associated with deteriorated bone microarchitecture in postmenopausal women following total thyroidectomy.

PMID:33730348 | DOI:10.1007/s40618-021-01537-0

Int J Behav Med. 2021 Mar 17. doi: 10.1007/s12529-021-09973-1. Online ahead of print.

ABSTRACT

BACKGROUND: Test anxiety may be better thought of as a biopsychosocial process affecting academic performance during the days leading up to an exam, rather than a static appraisal of attitudes related to test taking. This was a passive observational study following students 2 days before a midterm exam and was designed to test the Sleep Anxiety Performance Process (SAPP) model in the context of a psychology statistics exam.

METHODS: Undergraduates (N = 167) enrolled in a statistics class, January-November 2015. Participants completed an electronic battery of measures and Sleep Mood Study Diaries (SMS) during the mornings, 2 days before a statistics exam. Instructors confirmed exam scores.

RESULTS: A path model showed a reciprocal bi-directional relationship between Sleep Quality and restfulness (Q&R) and test anxiety 2 days before a scheduled exam, with test anxiety measured in the morning, before the exam predicting exam performance. Prior exam performance, being a non-native English speaker (ESL), and class performance motivation also predicted exam performance.

CONCLUSIONS: These data support the SAPP model’s premise that that sleep and anxiety feed one another, as a reciprocal process, that collectively impairs academic performance, with direct effects on academic performance, but with implications for overall student health.

PMID:33730347 | DOI:10.1007/s12529-021-09973-1

Pain Ther. 2021 Mar 17. doi: 10.1007/s40122-021-00248-x. Online ahead of print.

ABSTRACT

INTRODUCTION: A previous Delphi survey from the Rational Use of Analgesics (RUA) project involving Italian palliative care specialists revealed some discrepancies between current guidelines and clinical practice with a lack of consensus on items regarding the use of strong opioids in treating cancer pain. Those results represented the basis for a new Delphi study addressing a better approach to pain treatment in patients with cancer.

METHODS: The study consisted of a two-round multidisciplinary Delphi study. Specialists rated their agreement with a set of 17 statements using a 5-point Likert scale (0 = totally disagree and 4 = totally agree). Consensus on a statement was achieved if the median consensus score (MCS) (expressed as value at which at least 50% of participants agreed) was at least 4 and the interquartile range (IQR) was 3-4.

RESULTS: This survey included input from 186 palliative care specialists representing all Italian territory. Consensus was reached on seven statements. More than 70% of participants agreed with the use of low dose of strong opioids in moderate pain treatment and valued transdermal route as an effective option when the oral route is not available. There was strong consensus on the importance of knowing opioid pharmacokinetics for therapy personalization and on identifying immediate-release opioids as key for tailoring therapy to patients’ needs. Limited agreement was reached on items regarding breakthrough pain and the management of opioid-induced bowel dysfunction.

CONCLUSION: These findings may assist clinicians in applying clinical evidence to routine care settings and call for a reappraisal of current pain treatment recommendations with the final aim of optimizing the clinical use of strong opioids in patients with cancer.

PMID:33730338 | DOI:10.1007/s40122-021-00248-x

Diabetes Ther. 2021 Mar 17. doi: 10.1007/s13300-021-01049-3. Online ahead of print.

ABSTRACT

INTRODUCTION: We aimed to examine the impact of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic on diabetic ketoacidosis (DKA) rates in children with type 1 diabetes (T1D).

METHODS: A retrospective cross-sectional study of 11 Israeli pediatric emergency departments (ED) was conducted. Children with T1D who attended the ED between March 1, 2020 and May 31, 2020 were compared with those who attended the ED between March 1, 2019 and May 31, 2019.

RESULTS: Overall, 150 and 154 children with T1D attended the EDs during the 3-month study periods in 2020 and 2019, respectively. Among patients with established T1D, DKA rates significantly increased in 2020 compared to 2019 [38/64 (59.3%) vs 31/74 (41.9%); p < 0.043]. There was a non-statistically significant trend toward a higher rate of DKA in patients with newly diagnosed T1D [46/86 (53.4%) vs 31/80 (38.7%); p = 0.063]. No differences were observed in the rates of severe DKA in 2020 compared to 2019 among patients with established T1D [10/64 (15.6%) vs 6/74 (8.1%); p = 0.184], and newly diagnosed T1D [16/86 (18.6%) vs 14/80 (17.5%); p = 0.858]. No differences were observed in the rates of intensive care unit admissions in 2020 compared to 2019 among patients with established T1D [14/64 (21.8%) vs 14/74 (18.9%); p = 0.672], and newly diagnosed T1D [26/86 (30.2%) vs 21/80 (26.2%); p = 0.977].

CONCLUSIONS: Increased rates of DKA in children with established T1D were observed during the first 3 months of the outbreak in Israel. The findings suggest that the severity of DKA at ED presentation in children with T1D was not influenced by the pandemic.

PMID:33730335 | DOI:10.1007/s13300-021-01049-3