Nevin Manimala

BMJ Open. 2021 Mar 23;11(3):e044996. doi: 10.1136/bmjopen-2020-044996.

ABSTRACT

INTRODUCTION: Motor neuron disease (MND) is a rapidly progressive and fatal neurodegenerative disorder with limited treatment options. The Motor Neuron Disease Systematic Multi-Arm Randomised Adaptive Trial (MND-SMART) is a multisite UK trial seeking to address the paucity in effective disease-modifying drugs for people with MND (pwMND). Historically, neurological trials have been plagued by suboptimal recruitment and high rates of attrition. Failure to recruit and/or retain participants can cause insufficiently representative samples, terminated trials or invalid conclusions. This study investigates patient-specific factors affecting recruitment and retention of pwMND to MND-SMART. Improved understanding of these factors may improve trial protocol design, optimise recruitment and retention.

METHODS AND ANALYSIS: PwMND on the Scottish MND Register, Clinical Audit Research and Evaluation of MND (CARE-MND), will be invited to participate in a prospective observational cohort study that investigates factors affecting trial participation and attrition. We hypothesise that patient-specific factors will significantly affect trial recruitment and retention. Participants will complete the Hospital Anxiety and Depression Scale, 9-Item Patient Health Questionnaire and State-Trait Anxiety Inventory-Form Y to evaluate neuropsychiatric symptoms, the ALS-Specific Quality of Life Questionnaire-Brief Form and Centre for Disease Control and Prevention-Health-Related Quality of Life for quality of life and a novel study-specific questionnaire on Attitudes towards Clinical Trial Participation (ACT-Q). Clinical data on phenotype, cognition (Edinburgh Cognitive and Behavioural ALS Screen) and physical functioning (Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised) will also be collated. Caregivers will complete the Brief Dimensional Apathy Scale. After 12 months, a data request to MND-SMART will evaluate recruitment and retention. Descriptive statistics will summarise and compare assessments and participants reaching impairment thresholds. Variable groupings: attitudes, quality of life, cognition, behaviour, physical functioning, neuropsychiatric and phenotype. Univariate and multivariable logistic regression will explore association with participation/withdrawal in MND-SMART; presented as ORs and 95% CIs.

ETHICS AND DISSEMINATION: Ethical approval was provided by the West of Scotland Research Ethics Committee 3 (20/WS/0067) on 12 May 2020. The results of this study will be published in a peer-reviewed journal, presented at academic conferences and disseminated to participants and the public.

PMID:33757953 | DOI:10.1136/bmjopen-2020-044996

BMJ Open. 2021 Mar 23;11(3):e044933. doi: 10.1136/bmjopen-2020-044933.

ABSTRACT

PURPOSE: A multicentre prospective cohort study, known as the Chinese Pregnant Women Cohort Study (CPWCS), was established in 2017 to collect exposure data during pregnancy (except environmental exposure) and analyse the relationship between lifestyle during pregnancy and obstetric outcomes. Data about mothers and their children’s life and health as well as children’s laboratory testing will be collected during the offspring follow-up of CPWCS, which will enable us to further investigate the longitudinal relationship between exposure in different periods (during pregnancy and childhood) and children’s development.

PARTICIPANTS: 9193 pregnant women in 24 hospitals in China who were in their first trimester (5-13 weeks gestational age) from 25 July 2017 to 26 November 2018 were included in CPWCS by convenience sampling. Five hospitals in China which participated in CPWCS with good cooperation will be selected as the sample source for the Chinese Pregnant Women Cohort Study (Offspring Follow-up) (CPWCS-OF).

FINDINGS TO DATE: Some factors affecting pregnancy outcomes and health problems during pregnancy have been discovered through data analysis. The details are discussed in the ‘Findings to date’ section.

FUTURE PLANS: Infants and children and their mothers who meet the criteria will be enrolled in the study and will be followed up every 2 years. The longitudinal relationship between exposure (questionnaire data, physical examination and biospecimens, medical records, and objective environmental data collected through geographical information system and remote sensing technology) in different periods (during pregnancy and childhood) and children’s health (such as sleeping problem, oral health, bowel health and allergy-related health problems) will be analysed.

TRAIL REGISTRATION NUMBER: CPWCS was registered with ClinicalTrials.gov on 18 January 2018: NCT03403543. CPWCS-OF was registered with ClinicalTrials.gov on 24 June 2020: NCT04444791.

PMID:33757952 | DOI:10.1136/bmjopen-2020-044933

BMJ Open. 2021 Mar 23;11(3):e043985. doi: 10.1136/bmjopen-2020-043985.

ABSTRACT

INTRODUCTION: There is a substantial literature finding that moderate alcohol consumption is protective against certain health conditions. However, more recent research has highlighted the possibility that these findings are methodological artefacts, caused by confounding and other biases. While modern analytical and study design approaches can mitigate confounding and thus enhance causal inference in observational studies, they are not routinely applied in research assessing the relationship between alcohol use and long-term health outcomes. The purpose of this systematic review is to identify observational studies that employ these analytical/design-based approaches in assessing whether relationships between alcohol consumption and health outcomes are non-linear. This review seeks to evaluate, on a per-outcome basis, what these studies find the strength and form of the relationship between alcohol consumption and health to be.

METHODS AND ANALYSIS: Electronic databases (MEDLINE, PsycINFO, Embase and SCOPUS) were searched in May 2020. Study selection will comply with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Articles will be screened against eligibility criteria intended to capture studies using observational data to assess the relationship between varying levels of alcohol exposure and any long-term health outcome (actual or surrogate), and that have employed at least one of the prespecified approaches to enhancing causal inference. Risk of bias of included articles will be assessed using study design-specific tools. A narrative synthesis of the results is planned.

ETHICS AND DISSEMINATION: Formal ethics approval is not required given there will be no primary data collection. The results of the study will be disseminated through published manuscripts, conferences and seminar presentations.

PROSPERO REGISTRATION NUMBER: CRD42020185861.

PMID:33757947 | DOI:10.1136/bmjopen-2020-043985

BMJ Open. 2021 Mar 23;11(3):e037935. doi: 10.1136/bmjopen-2020-037935.

ABSTRACT

OBJECTIVE: Scientific authorship is a vital marker of achievement in academic careers and gender equity is a key performance metric in research. However, there is little understanding of gender equity in publications in biomedical research centres funded by the National Institute for Health Research (NIHR). This study assesses the gender parity in scientific authorship of biomedical research.

DESIGN: Descriptive, cross-sectional, retrospective bibliometric study.

SETTING: NIHR Oxford Biomedical Research Centre (BRC).

DATA: Data comprised 2409 publications that were either accepted or published between April 2012 and March 2017. The publications were classified as basic science studies, clinical studies (both trial and non-trial studies) and other studies (comments, editorials, systematic reviews, reviews, opinions, book chapters, meeting reports, guidelines and protocols).

MAIN OUTCOME MEASURES: Gender of authors, defined as a binary variable comprising either male or female categories, in six authorship categories: first author, joint first authors, first corresponding author, joint corresponding authors, last author and joint last authors.

RESULTS: Publications comprised 39% clinical research (n=939), 27% basic research (n=643) and 34% other types of research (n=827). The proportion of female authors as first author (41%), first corresponding authors (34%) and last author (23%) was statistically significantly lower than male authors in these authorship categories (p<0.001). Of total joint first authors (n=458), joint corresponding authors (n=169) and joint last authors (n=229), female only authors comprised statistically significant (p<0.001) smaller proportions, that is, 15% (n=69), 29% (n=49) and 10% (n=23) respectively, compared with male only authors in these joint authorship categories. There was a statistically significant association between gender of the last author with gender of the first author (p<0.001), first corresponding author (p<0.001) and joint last author (p<0.001). The mean journal impact factor (JIF) was statistically significantly higher when the first corresponding author was male compared with female (Mean JIF: 10.00 vs 8.77, p=0.020); however, the JIF was not statistically different when there were male and female authors as first authors and last authors.

CONCLUSIONS: Although the proportion of female authors is significantly lower than the proportion of male authors in all six categories of authorship analysed, the proportions of male and female last authors are comparable to their respective proportions as principal investigators in the BRC. These findings suggest positive trends and the NIHR Oxford BRC doing very well in gender parity in the senior (last) authorship category. Male corresponding authors are more likely to publish articles in prestigious journals with high impact factor while both male and female authors at first and last authorship positions publish articles in equally prestigious journals.

PMID:33757940 | DOI:10.1136/bmjopen-2020-037935

Am J Obstet Gynecol MFM. 2021 Mar 21:100349. doi: 10.1016/j.ajogmf.2021.100349. Online ahead of print.

ABSTRACT

BACKGROUND: The social and physical environments in which people live affect the emergence, prevalence and severity of both infectious and non-infectious diseases. There is limited data on how such social determinants of health (SDH), including neighborhood socioeconomic conditions, affect the risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and severity of coronavirus disease 2019 (COVID-19) during pregnancy.

OBJECTIVES: Our objective was to determine how SDH are associated with SARS-CoV-2 infection and the severity of COVID-19 illness in hospitalized pregnant patients in New York during the global COVID-19 pandemic.

STUDY DESIGN: This cross-sectional study evaluated all pregnant patients who delivered and had polymerase chain reaction (PCR) testing for SARS-CoV-2 between March 15, 2020 and June 15, 2020 at seven hospitals within Northwell Health, the largest academic health system in New York. During the study period, universal SARS-CoV-2 testing protocols were implemented at all sites. PCR testing was performed using nasopharyngeal swabs. Patients were excluded if the following variables were not available: PCR results, race, ethnicity, and/or ZIP code of residence. Clinical data were obtained from the enterprise electronic health record system. For each patient, ZIP code was used as a proxy for neighborhood. Socioeconomic characteristics were determined by linking to ZIP code data from the United States Census Bureau’s American Community Survey (ACS) and the Internal Revenue Service’s Statistics of Income (SOI) Division. Specific variables of interest included mean persons per household, median household income, percent unemployment, and percent with less than high school education. Medical records were manually reviewed for all subjects with positive PCR test results in order to correctly identify symptomatic patients and then classify those subjects using the National Institutes of Health (NIH) severity of illness categories. Classification was based on the highest severity of illness throughout gestation and not necessarily at the time of presentation for delivery.

RESULTS: A total of 4,873 patients were included in the study. The PCR test positivity rate was 11% (n=544). Among this group, 359 patients (66%) were asymptomatic or presymptomatic, 115 (21%) had mild or moderate COVID-19, and 70 (13%) had severe or critical COVID-19. On multiple logistic regression modeling, pregnant patients who tested positive for SARS-CoV-2 were more likely to be younger, of higher parity, belong to minoritized racial and ethnic groups, have public health insurance, have limited English proficiency, and/or reside in low-income neighborhoods with less educational attainment. On ordinal logit regression modeling, obesity, income, and education were significantly associated with COVID-19 severity.

CONCLUSION: Social and physical determinants of health play a significant role in determining the risk of infection. Severity of COVID-19 illness was not associated with race or ethnicity but was associated with maternal obesity and neighborhood level characteristics such as educational attainment and household income.

PMID:33757936 | DOI:10.1016/j.ajogmf.2021.100349

Am J Obstet Gynecol MFM. 2021 Mar 20:100353. doi: 10.1016/j.ajogmf.2021.100353. Online ahead of print.

ABSTRACT

BACKGROUND: Non-Hispanic Black (NHB) maternal race is a known risk factor for preterm birth (PTB). However, the contribution of paternal race is not as well established.

OBJECTIVES: We sought to evaluate the risk of PTB among NHB, NH White (NHW), and mixed NHB/NHW dyads.

STUDY DESIGN: This is a population-based cohort study of all live births in the United States from 2015-2017, using live birth records from the National Vital Statistics System. Singleton, non-anomalous infants whose live birth record included maternal and paternal self-reported race as either NHW or NHB were included. The primary outcome was PTB <37 weeks’ gestation; secondary outcomes included PTB <34 and <28 weeks’ gestation, and delivery gestational age (as a continuous variable). Data were analyzed using chi-square, t-test, ANOVA, and logistic regression. A Kaplan-Meier survival curve was also generated.

RESULTS: There were 11,809,599 live births during the study period; 4,008,622 births met inclusion criteria. Of included births, 291,647 (7.3%) occurred <37 weeks’ gestation. Using the maternal race/paternal race convention, PTB <37 weeks’ gestation was most common among NHB/NHB dyads (n=70,987; 10.8%), followed by NHB/NHW (n=3,137, 9.5%), NHW/NHB (n=9,136, 8.3%), and NHW/NHW (n=209,387, 6.5%), p<0.001 for trend. Births <34 weeks’ (N=74,474) and <28 weeks’ gestation (N= 18,474) were also more common among NHB/NHB dyads. Specifically, 24,351 (3.7%) NHB/NHB, 1,017 (3.1%) NHB/NHW, 2,408 (2.2%) NHW/NHB, and 46,698 NHW/NHW dyads delivered <34 weeks, and 7,988 NHB/NHB (1.2%), 313 (1.0%) NHB/NHW, 584 (0.5%) NHW/NHB, and 9,589 (0.3%) NHW/NHW dyads delivered <28 weeks. NHW/NHW dyads delivered at a mean 38.8 ± standard deviation of 1.7 weeks’ gestation, while NHW/NHB, NHB/NHW, and NHB/NHB dyads delivered at 38.6 ± 2.0, 38.5 ± 2.3, and 38.3 ± 2.4 weeks’, respectively, p<0.001. Adjusted odds ratios (aORs) for the association between maternal/paternal race and PTB were highest for NHB/NHB dyads at each gestational age cutoff: aOR=1.60, 95% CI: 1.11,1.19 (<37 weeks’), aOR=2.47, 95% CI: 2.41,2.53 (<34 weeks’), and aOR=4.22, 95% CI: 4.04,4.41 (<28 weeks’) compared to the NHW referent group. Models adjusted for insurance status, chronic hypertension, tobacco use during pregnancy, history of prior PTB, and male fetus. In the Kaplan-Meier survival analysis, NHB/NHB dyads delivered earliest across the range of delivery gestational ages as compared to all other combinations of dyads.

CONCLUSIONS: NHB paternal race is a risk factor for preterm birth and should be considered when evaluating maternal a priori risk for prematurity. Future research should investigate the mechanisms behind this finding, including determining the contribution of factors such as racism, maternal and paternal genetics and epigenetics to an individual’s risk of PTB.

PMID:33757934 | DOI:10.1016/j.ajogmf.2021.100353

Gynecol Obstet Fertil Senol. 2021 Mar 20:S2468-7189(21)00070-2. doi: 10.1016/j.gofs.2021.03.020. Online ahead of print.

ABSTRACT

One of the major symptoms of climacteric syndrome is hot flushes (HF). They are most often experienced as very disabling. Estrogen therapy is the most effective treatment. However, it may be contraindicated in some women. The aim of this article is to provide a review of the scientific literature on pharmacological and non-pharmacological alternatives in this context. Only randomized trials and meta-analyses of randomized trials were considered. This review shows that some treatments usually used in non-gynecological or endocrinological disease have significant effect in reducing the frequency and/or severity of HF. Hence, some selective serotonin reuptake inhibitors (paroxetine, citalopram and escitalopram), serotonin and norepinephrine reuptake inhibitors (venlafaxine, desvenlafaxine) gabapentin, pregabalin and clonidine have a statistically effect as compared with placebo in reducing, the frequency and/or severity of HF. Some phytoestrogens, such as genistein, may also reduce the frequency of HF. Regarding non-pharmacological interventions, hypnosis, acupuncture or yoga have been analyzed with significant beneficial results, even if their evaluation is difficult by the absence of a good placebo group in most trials. By contrast, other approaches, both pharmacological or non-pharmacological, appear to be ineffective in the management of HT. These include homeopathy, vitamin E, alanine, omega 3, numerous phytoestrogens (red clover, black cohosh…), primrose oil, physical activity. In women suffering from breast cancer, several additional problems are added. On the one hand because all phytoestrogens are contraindicated and on the other hand, in patients using tamoxifen, because the molecules, that interact with CYP2D6, are to be formally avoided because of potential interaction with this anti-estrogen treatment. In conclusion, several pharmacological and non-pharmacological alternatives have significant efficacy in the management of severe HF.

PMID:33757925 | DOI:10.1016/j.gofs.2021.03.020

Photodiagnosis Photodyn Ther. 2021 Mar 20:102261. doi: 10.1016/j.pdpdt.2021.102261. Online ahead of print.

ABSTRACT

AIM: The study aimed to evaluate the microtensile bond strength (μTBS) of giomer, an ion-releasing restorative material, to caries-affected dentin (CAD) when different cavity disinfectant protocols were applied before the restoration.

MATERIAL AND METHODS: Thirty extracted non-carious human third molars were embedded in acrylic resin. The occlusal portions of the samples were excised using an IsoMet saw. After creating artificial caries, samples were divided into six groups (n = 12): sound dentin with no disinfection (Group SD), CAD with no disinfection (Group CAD), CAD disinfected with 2% chlorhexidine gluconate (Group CHX), CAD disinfected with 6% NaOCl (Group NaOCl), CAD disinfected with photodynamic therapy with methylene blue photosensitizer (Group PDT), and CAD disinfected with Er,Cr:YSGG (Group ECYL). Following disinfection protocols, the universal adhesive was applied, and all samples were restored using giomer. Subsequently, μTBS analyses were performed, and data were analyzed statistically.

RESULTS: The highest μTBS values were obtained from the SD and CAD groups, which exhibited no statistical differences (p > 0.05). The PDT and ECYL groups had higher μTBS values compared with the CHX and NaOCl groups (p < 0.05), and all disinfection protocols decreased the bond strength to CAD (p < 0.05).

CONCLUSION: The microtensile bond strength of disinfected CAD was greater with Er,Cr:YSGG laser and photodynamic therapy treatment than with chemical disinfectants. Giomer may enhance the bond strength to CAD, which has a weaker bonding potential than sound dentin due to structural differences. However, disinfection protocols adversely affect adhesion between the restorative material and CAD.

PMID:33757911 | DOI:10.1016/j.pdpdt.2021.102261

Neuroimage. 2021 Mar 20:117988. doi: 10.1016/j.neuroimage.2021.117988. Online ahead of print.

ABSTRACT

While mirror neurons have been found in several monkey brain regions, their existence in the human brain is still largely inferred from indirect non-invasive measurements like functional MRI. It has been proposed that, beyond showing overlapping brain responses during action observation and execution tasks, candidate mirror neuron regions should demonstrate cross-modal action specificity, in line with a defining physiological characteristic of these neurons in the monkey brain. Although cross-modal fMRI adaptation has been put forward as a suited method to test this key feature of cross-modal action specificity in the human brain, so far, the overall usefulness of this technique to demonstrate mirror neuron activity remains unclear. To date, it has never been tested to what extent monkey brain regions known to house mirror neurons, would yield uni- and/or cross-modal fMRI adaptation effects. We therefore performed an fMRI adaptation experiment while male rhesus macaques either performed or observed two different goal-directed hand actions. Executing grasp/lift or touch/press actions in the dark, as well as observing videos of these monkey hand actions, yielded robust responses throughout the brain, including overlapping fMRI responses in parietal and premotor mirror neuron regions. Uni-modal adaptation effects were mostly restricted to the visual modality and the early visual cortices. Both frequentist and Bayesian statistical analyses however suggested no evidence for cross-modal fMRI adaptation effects in monkey parietal and premotor mirror neuron regions. Overall, these findings suggest monkey mirror neuron activity does not readily translate into cross-modal repetition suppression effects that can be detected by fMRI.

PMID:33757907 | DOI:10.1016/j.neuroimage.2021.117988

World Neurosurg. 2021 Mar 20:S1878-8750(21)00443-5. doi: 10.1016/j.wneu.2021.03.073. Online ahead of print.

ABSTRACT

BACKGROUND: and purpose: AHA/ASA guidelines recommend endovascular stroke therapy (EST) with tissue plasminogen activator (rt-PA) for eligible patients in acute ischemic stroke (AIS). Using the National Inpatient Sample database, we evaluated trends in treatment with rt-PA and EST for AIS and their outcomes.

METHODS: This is a cross-sectional observational study of AIS admitted in US hospitals 2012-2016. Patients were grouped into those who received rt-PA alone, EST alone, and rtPA+EST. Survey statistical procedures were performed. Multivariable regression analysis with pairwise comparisons of each treatment group with no treatment group was performed for discharge outcomes.

RESULTS: The study included 2,290,520 AIS patients with mean age 70.46 years. Treatment rates increased from 2012 to 2016 for rt-PA by 7% per year (5.86% to 7.67%, odds ratio [OR]=1.07, 95% confidence interval [CI] 1.05-1.08); and EST by 38% per year (0.55% to 1.75%, OR=1.38, 95% CI 1.31-1.45); but not rt-PA+EST (0.54% to 0.57%, OR=1.04, 95% CI 0.99-1.08). Mean length of stay reduced from 2012 to 2016 for rt-PA (6.07 to 4.91days, p<0.0001), and rt-PA+EST (9.19 to 7.10days, p=0.0067) but not for EST (9.61 to 8.51days, p=0.5074). The odds of patients discharged home increased by 8%, 9% and 15% among patients who received rt-PA alone, EST alone and rt-PA+EST respectively, compared to no treatment group.

CONCLUSION: The utilization of rt-PA alone and EST alone increased but that of rt-PA+EST remained unchanged from 2012 to 2016 in NIS.

PMID:33757890 | DOI:10.1016/j.wneu.2021.03.073