Category: Nevin Manimala

J Clin Pharm Ther. 2021 Nov 2. doi: 10.1111/jcpt.13556. Online ahead of print.

ABSTRACT

WHAT IS KNOWN AND OBJECTIVES: There is clear evidence for an association between irritable bowel syndrome (IBS) and visceral hypersensitivity. This clinical study aimed to assess the adjunct role of ethosuximide, an antiepileptic drug with T-type calcium channel blocking activity, in the relieving of IBS-related abdominal pain.

METHODS: This is a prospective, 3-month, randomized and controlled study of parallel groups. Fifty outpatients who met the inclusion criteria participated in the trial. Patients were allocated randomly: 25 received mebeverine 135 mg three times daily (t.i.d), whereas the other 25 received mebeverine 135 mg t.i.d and ethosuximide 500 mg t.i.d. At baseline and 12 weeks after starting the drug, patients were evaluated by a gastroenterologist. Serum tumour necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), interleukin-8 (IL-8), faecal myeloperoxidase and faecal neutrophile gelatinase-associated lipocalin (NGAL) levels were tested before and after treatment. The Numeric Pain Rating Scale (NRS) was assessed before and after three months of therapy.

RESULTS AND DISCUSSION: After 12 weeks, the ethosuximide group showed a statistically and significantly greater reduction in the serum levels of TNF-α, IL-6, IL-8, faecal myeloperoxidase and faecal NGAL in comparison with the control group after the treatment. Moreover, the ethosuximide group showed a statistically significant decrease in NRS compared with the mebeverine group.

WHAT IS NEW AND CONCLUSION: Ethosuximide could be a promising adjunct to antispasmodics in the treatment of IBS patients. Trial registration identifier: NCT04217733.

PMID:34726293 | DOI:10.1111/jcpt.13556

Stat Med. 2021 Nov 2. doi: 10.1002/sim.9241. Online ahead of print.

ABSTRACT

Alzheimer’s disease (AD) is an incurable and progressive disease that starts from mild cognitive impairment and deteriorates over time. Examining the effects of patients’ longitudinal cognitive decline on time to conversion to AD and obtaining a reliable diagnostic model are therefore critical to the evaluation of AD prognosis and early treatment. Previous studies either assess patients’ cognitive impairment through a single cognitive test or assume it changes linearly across time, thereby leading to an incomplete measure of cognitive decline or overlooking the subtle trajectory pattern of patients’ cognitive impairment. This study develops a new joint model to address these shortcomings. First, a dynamic factor analysis model is adopted to characterize cognitive impairment through multiple cognitive measures in a comprehensive manner. Second, a spline-based random coefficient model is proposed to reveal possibly nonlinear trajectories of patients’ cognitive decline. Finally, a proportional hazard model is considered to examine the effects of time-invariant markers and time-variant cognitive impairment on AD hazards. A Bayesian approach coupled with spline approximation techniques and MCMC methods is developed to conduct statistical inference. The application of the proposed method to the Alzheimer’s Disease Neuroimaging Initiative study provides new insights into the prevention of AD and shows a high prediction capacity of the proposed method.

PMID:34726280 | DOI:10.1002/sim.9241

Mol Med Rep. 2021 Dec;24(6):876. doi: 10.3892/mmr.2021.12516. Epub 2021 Nov 2.

ABSTRACT

Ascending aortic diameter is not an accurate parameter for surgical indication in patients with bicuspid aortic valve (BAV). Thus, the present study aimed to identify specific microRNAs (miRNAs/miRs) and their expression levels in aortic wall aneurysm associated with BAV according to severity of medial degeneration and to elucidate the association between the tissue expression levels of the miRNAs with their expression in plasma. Aortic wall and blood specimens were obtained from 38 patients: 12 controls and 26 patients with BAV with ascending aortic aneurysm. Of the patients with BAV, 19 had cusp fusions of right and left, 5 of right and non‑coronary, and 2 of left and non‑coronary. Two groups of patients were identified according to the grade of medial degeneration (MD): Low‑grade D group (LGMD) and high‑grade MD group (HGMD). Expression level of miR‑122, miR‑130, miR‑718 and miR‑486 were validated by reverse transcription‑quantitative PCR in plasma and tissue samples. MD grade was found to be independent from the BAV phenotype. The HGD group showed increased expression levels of MMP‑9 and MMP‑2, and an increase in the number of apoptotic cells. Tissue expression levels of miR‑718 and miR‑122 were lower in the LGMD and HGD groups compared with expression in the control group; the HGD group showed increased levels of miR‑486. Plasma expression levels of miR‑122 were decreased in the LGMD and HGD groups, and miR‑718 was only reduced in the HGD group. On the contrary, expression of miR‑486 was increased in the LGMD and HGD groups. The data suggested that miR‑486 may be considered as a non‑invasive biomarker of aortic wall degeneration. Dysregulation of this putative biomarker may be associated with high risk of dissection and rupture in patients with BAV.

PMID:34726256 | DOI:10.3892/mmr.2021.12516

Laryngoscope. 2021 Nov 2. doi: 10.1002/lary.29918. Online ahead of print.

ABSTRACT

BACKGROUND: Diversity within the medical profession with respect to sex and racial minorities has been shown to have a positive effect on health and healthcare. Characterization of a field is key to evaluating trends and the advancement of diversity in an otolaryngology subspecialty.

STUDY DESIGN: Observational study.

METHODS: A comprehensive list of all the academic laryngologists was compiled from the Accreditation Council for Graduate Medical Education accredited otolaryngology residency programs in 2020. The last 20 past presidents of the American Laryngological Association (ALA) and American Broncho-Esophogological Association (ABEA) were analyzed. Academic rank and years in practice were determined from departmental websites, with online search tools used as secondary resources. The h-index was utilized as a measure of research productivity. Regression analysis was performed to analyze these variables.

RESULTS: There are 184 academic laryngologists in the 124 programs. The majority of the population is Caucasian 76.6% (141/184), followed by Asian 16.3% (30/184), African American 4.34% (8/184), and then Hispanic 1% (2/184). There are 47 full professors with 83% Caucasian, 14.1% Asian, and 2.1% African American and 91.5% male and only 8.5% female. Past ALA presidents were 90% male and for the ABEA 75% male. H-index revealed a statistically significant difference between Caucasian and African American colleagues [P value (<.0005)].

CONCLUSIONS: Minorities are disproportionately underrepresented in laryngology. Women are less likely to be in leadership roles in laryngology and become full professors. Laryngology lags behind other surgical specialties in the representation of minorities and women. Continued efforts should be made to increase diversity in the field of laryngology, especially in regard to underrepresented minorities.

LEVEL OF EVIDENCE: N/A Laryngoscope, 2021.

PMID:34726277 | DOI:10.1002/lary.29918

Rhinology. 2021 Nov 2. doi: 10.4193/Rhin21.286. Online ahead of print.

ABSTRACT

BACKGROUND: Epistaxis is the main complaint in patients with Hereditary haemorrhagic telangiectasia (HHT). Even though the role of epistaxis in affecting the quality of life (QoL) is well-known, little is known about epidemiological and clinical factors contributing to epistaxis severity and QoL.

METHODOLOGY: This is a cross-sectional study, including adult patients with HHT with epistaxis. All patients underwent an otolaryngological evaluation with nasal endoscopy. Epistaxis severity was graded using the FID score, and QoL was evaluated with the Short-Form Health Survey (SF-36). Descriptive statistics were produced for demographic characteristics; the Shapiro-Wilk test was used to test the normal distribution of quantitative variables. Correlation between the quantitative variables was evaluated with Pearson’s correlation coefficient. Both univariate and multivariate linear regression models were fitted to find associations between demographic or clinical factors and the FID score or SF-36.

RESULTS: A total of 234 patients with HHT were included in the study. The univariate analysis highlighted the association between high blood pressure, septal perforation, nocturnal epistaxis, surgery, blood transfusion, hormonal therapy and both FID score and QoL. Sex, allergic rhinitis and nasal polyposis were neither related to epistaxis severity nor perceived health.

CONCLUSIONS: Epistaxis severity and QoL in patients with HHT are influenced by several clinical factors both dependent and independent from HHT. Some of the results are consistent with those already published, but for the first time, we extended the analysis to different clinical parameters, such as endoscopic findings, never assessed before.

PMID:34726201 | DOI:10.4193/Rhin21.286

J Clin Endocrinol Metab. 2021 Nov 2:dgab798. doi: 10.1210/clinem/dgab798. Online ahead of print.

ABSTRACT

CONTEXT: The apparent increased incidence of congenital hypothyroidism (CH) is partly due to increased detection of transient disease.

OBJECTIVE: To identify predictors of transient CH (T-CH) and establish a predictive tool for its earlier differentiation from permanent CH (P-CH).

DESIGN: Retrospective cohort study of patients diagnosed with CH from 2006-2015 through Newborn Screening Ontario (NSO).

RESULTS: Of 469 cases, 360 (76.8%) were diagnosed with P-CH vs. 109 (23.2%) with T-CH. Doses of levothyroxine predicting T-CH were <3.9 mcg/kg at 6 months, <3.0 mcg/kg at 1 and 2 years, and <2.5 mcg/kg at 3 years. Descriptive statistics and multivariable logistic modeling demonstrated several diverging key measures between patients with T-CH versus P-CH, with optimal stratification at 1-year of age. Thyroid imaging was the strongest predictor (p<0.001). Excluding imaging, significant predictors in the first year of life included thyroxine dose/kg (p<0.001-0.002), rise in TSH above the reference interval during treatment (p=0.002), screening TSH (p=0.03), and a history of maternal thyroid disease (p=0.02). Based on the 1-year model without imaging, a risk score was developed to identify children with T-CH who may benefit from an earlier trial off therapy, to reduce excess medicalization and healthcare costs.

CONCLUSION: A levothyroxine dose of <3 mcg/kg at 1 and 2 years of age and <2.5 mcg/kg at 3 years of age can be predictive of T-CH. A novel risk score was developed that can be clinically applied to predict the likelihood of a successful trial off therapy for a given patient at 1 year of age.

PMID:34726229 | DOI:10.1210/clinem/dgab798

Menopause. 2021 Nov 1. doi: 10.1097/GME.0000000000001873. Online ahead of print.

ABSTRACT

OBJECTIVES: Bilateral oophorectomy permanently reduces endogenous estrogen exposure and may increase cardiovascular mortality in women. This study aimed to investigate the association between bilateral oophorectomy and cardiovascular mortality and whether this association was conditional on hysterectomy or on the use of hormone therapy at the time of study entry.

METHODS: A prospective cohort study of 25,338 female nurses aged ≥ 45 years within the Danish Nurse Cohort. Nurses were enrolled in 1993 or 1999 and followed until death, emigration, or end of follow-up on December 31, 2018, whichever came first. Exposure was bilateral oophorectomy. Outcome was cardiovascular mortality. Associations were estimated using Poisson regression models with log person-years as the offset.

RESULTS: A total of 2,040 (8.1%) participants underwent bilateral oophorectomy. During a mean follow-up of 21.2 (SD: 5.6) years, 772 (3.0%) nurses died from cardiovascular disease. In adjusted analyses, a 31% higher rate of cardiovascular mortality was observed after bilateral oophorectomy (aMRR 1.31; 95% CI, 0.88-1.96) compared with women who retained their ovaries. No evidence of effect modification by use of hormone therapy at baseline or by hysterectomy on the association between bilateral oophorectomy and cardiovascular mortality was observed.

CONCLUSION: Bilateral oophorectomy may be associated with cardiovascular mortality in women, but the estimate was not statistically significant. Additionally, we were unable to make firm conclusions regarding the possible modifying role of hormone therapy and hysterectomy on this potential association. Additional studies are needed to replicate this work.

PMID:34726195 | DOI:10.1097/GME.0000000000001873

Elife. 2021 Nov 2;10:e70817. doi: 10.7554/eLife.70817.

ABSTRACT

As part of an initiative to improve rigor and reproducibility in biomedical research, the U.S. National Institutes of Health now requires the consideration of sex as a biological variable in preclinical studies. This new policy has been interpreted by some as a call to compare males and females with each other. Researchers testing for sex differences may not be trained to do so, however, increasing risk for misinterpretation of results. Using a list of recently published articles curated by Woitowich et al. (eLife, 2020; 9:e56344), we examined reports of sex differences and non-differences across nine biological disciplines. Sex differences were claimed in the majority of the 147 articles we analyzed; however, statistical evidence supporting those differences was often missing. For example, when a sex-specific effect of a manipulation was claimed, authors usually had not tested statistically whether females and males responded differently. Thus, sex-specific effects may be over-reported. In contrast, we also encountered practices that could mask sex differences, such as pooling the sexes without first testing for a difference. Our findings support the need for continuing efforts to train researchers how to test for and report sex differences in order to promote rigor and reproducibility in biomedical research.

PMID:34726154 | DOI:10.7554/eLife.70817

Elife. 2021 Nov 2;10:e74135. doi: 10.7554/eLife.74135.

ABSTRACT

A survey reveals that many researchers do not use appropriate statistical analyses to evaluate sex differences in biomedical research.

PMID:34726155 | DOI:10.7554/eLife.74135

Transcult Psychiatry. 2021 Nov 2:13634615211043767. doi: 10.1177/13634615211043767. Online ahead of print.

ABSTRACT

Gender-based violence (GBV) among female refugees/asylum seekers is a major underreported/understudied psychosocial issue. The aims of this study were: to describe the proportion of GBV-related experiences among female refugees/asylum seekers referred to a Cultural Consultation Service (CCS) in Montreal; to describe their sociodemographic and clinical characteristics; and to compare these characteristics among women who make GBV their principal refugee claim (Group A), those who did not but had suffered GBV (Group B1), and those who had never reported GBV (Group B2). Data on sociodemographic and clinical variables and GBV were gathered by chart review. Data were analyzed using chi-square for categorical and ANOVA for continuous comparisons. A total of 91 female refugees/asylum seekers were evaluated from 2000 to 2013; 80% (73/91) having reported GBV, with 38.5% (35/91) using GBV as the principal reason for seeking asylum in Canada (Group A), mainly due to intimate partner violence (IPV). Fully 66.6% (38/56) of women who sought asylum for reasons other than GBV reported having experienced GBV (Group B1). When compared to the other groups, Group A women exhibited a number of statistically significant differences: they tended to migrate alone (p < .001), be divorced/single (p = .02), have more suicidal thoughts/behaviors (p < .001), and report a history of IPV (p < .001). Women from Group B1 were more likely to be diagnosed with Affective Disorders (p = .045), and to have suffered sexual violence (p < .001). Results suggest that GBV is frequently experienced by refugee/asylum seeker women in this small, tertiary care clinical sample. When assessing refugee women such as these, differences in the kind of violence suffered, migration process, family/social support, and clinical related features should be taken into account and explored by clinicians in a culturally appropriate and safe manner.

PMID:34726100 | DOI:10.1177/13634615211043767