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Nevin Manimala Statistics

De novo FZR1 loss-of-function variants cause developmental and epileptic encephalopathies

Brain. 2021 Nov 11:awab409. doi: 10.1093/brain/awab409. Online ahead of print.

ABSTRACT

FZR1, which encodes the Cdh1 subunit of the Anaphase Promoting Complex, plays an important role in neurodevelopment by regulating the cell cycle and by its multiple post-mitotic functions in neurons. In this study, evaluation of 250 unrelated patients with developmental and epileptic encephalopathies and a connection on GeneMatcher led to the identification of three de novo missense variants in FZR1. Whole-exome sequencing in 39 patient-parent trios and subsequent targeted sequencing in an additional cohort of 211 patients was performed to identify novel genes involved in developmental and epileptic encephalopathy. Functional studies in Drosophila were performed using three different mutant alleles of the Drosophila homolog of FZR1 fzr. All three individuals carrying de novo variants in FZR1 had childhood onset generalized epilepsy, intellectual disability, mild ataxia and normal head circumference. Two individuals were diagnosed with the developmental and epileptic encephalopathy subtype Myoclonic Atonic Epilepsy. We provide genetic-association testing using two independent statistical tests to support FZR1 association with developmental epileptic encephalopathies. Further, we provide functional evidence that the missense variants are loss-of-function alleles using Drosophila neurodevelopment assays. Using three fly mutant alleles of the Drosophila homolog fzr and overexpression studies, we show that patient variants can affect proper neurodevelopment. With the recent report of a patient with neonatal-onset with microcephaly who also carries a de novo FZR1 missense variant, our study consolidates the relationship between FZR1 and developmental epileptic encephalopathy, and expands the associated phenotype. We conclude that heterozygous loss-of-function of FZR1 leads to developmental epileptic encephalopathies associated with a spectrum of neonatal to childhood onset seizure types, developmental delay and mild ataxia. Microcephaly can be present but is not an essential feature of FZR1-encephalopathy. In summary, our approach of targeted sequencing using novel gene candidates and functional testing in Drosophila will help solve undiagnosed myoclonic atonic epilepsy or developmental epileptic encephalopathy cases.

PMID:34788397 | DOI:10.1093/brain/awab409

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The impact of left ventricular size on outcomes after centrifugal-flow left ventricular assist device implantation

Eur J Cardiothorac Surg. 2021 Nov 11:ezab480. doi: 10.1093/ejcts/ezab480. Online ahead of print.

ABSTRACT

OBJECTIVES: The influence of preoperative left ventricular size in outcomes following centrifugal-flow left ventricular assist device (LVAD) implantation has not been well characterized.

METHODS: A cohort of 313 patients who received a centrifugal-flow LVAD at a single institution was analysed. Using a maximally selected log-rank statistic, we investigated whether a left ventricular end-diastolic dimension (LVEDD) cut-off point was associated with worse outcomes. The cohort was then divided in 2 groups based on the LVEDD cut-off point.

RESULTS: An LVEDD cut-off point of 59 mm was found to predict worse survival. Smaller LVEDD patients (≤59 mm, N = 52) were older and more likely to have a history of coronary artery disease compared those with a larger LVEDD (>59 mm, N = 261). Smaller LVEDD patients had lower survival compared to larger LVEDD patients (71% vs 85% at 1 year and 58% vs 80% at 2 years, P = 0.003). The need for temporary right ventricular mechanical support was significantly higher in the smaller LVEDD cohort (11.5% vs 1.9%, P = 0.002). Pump flows at time of discharge were lower in the smaller LVEDD group (3.8 vs 4.2 l/min, P = 0.005), who also had a higher incidence of late right ventricular failure (23% vs 12%, P = 0.02), higher rates of gastrointestinal bleeding (0.416 vs 0.256 events per patient-year, P = 0.025) and higher readmissions secondary to low flow alarms (0.429 vs 0.240 events per patient-year, P = 0.007). Multivariable analysis demonstrated that smaller LVEDD, older age, high BUN and high bilirubin levels were independent predictors of worse survival.

CONCLUSIONS: In patients receiving a centrifugal-flow LVAD, smaller preoperative LVEDD (≤59 mm) was associated with lower survival and higher incidence of adverse outcomes.

PMID:34788417 | DOI:10.1093/ejcts/ezab480

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Bone Marrow Collection

Am J Clin Pathol. 2021 Nov 11:aqab165. doi: 10.1093/ajcp/aqab165. Online ahead of print.

ABSTRACT

OBJECTIVES: Bone marrow collections are often difficult, and creating quality smears and touch preparations at the bedside can prove challenging. The objective of this study is to compare the quality of bone marrow specimens between unassisted and assisted bone marrow collections by a bone marrow technologist.

METHODS: Data for this study were collected from 422 hematopathology reports over 14 months. We recorded the bone marrow quality of the different parts (aspirate smears, touch imprints, core biopsy, and clot/particle sections) as adequate, suboptimal, or inadequate. Student t test statistical analysis was performed between the corresponding parts in the two groups.

RESULTS: Our results demonstrate that the quality of assisted bone marrow specimens is significantly better compared with unassisted specimens, particularly for the aspirate smears (P < .0001) and touch imprints (P < .0001). Notably, the quality of aspirate smears was improved, which is important for cytologic evaluation.

CONCLUSIONS: We conclude that assistance by a bone marrow technologist resulted in a significant improvement in the quality of bone marrow collection.

PMID:34788366 | DOI:10.1093/ajcp/aqab165

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Interaction effect of coping self-efficacy and received support in daily life of hematopoietic cell transplant patient-caregiver dyads

PLoS One. 2021 Nov 17;16(11):e0260128. doi: 10.1371/journal.pone.0260128. eCollection 2021.

ABSTRACT

OBJECTIVES: According to the social cognitive theory, social support and self-efficacy may interact with each other i.e. compete or account jointly for better adaptation. This study examined the nature of the interaction between coping self-efficacy and received social support in daily lives of patient-caregiver dyads after cancer treatment. We tested whether the effect of daily fluctuations in coping self-efficacy and received support on daily affect was synergistic (positive jointed effect), compensatory (positive competing effect), or interference (negative competing effect).

DESIGN: A dyadic daily-diary study conducted for 28 days after hospital discharge following hematopoietic cell transplantation.

METHODS: Coping self-efficacy, received support, and positive and negative affect were measured in 200 patient-caregiver dyads. The analysis was based on the actor-partner interdependence moderation model using multilevel structural equation modeling.

RESULTS: Statistically significant effect of interaction between daily coping self-efficacy and received support on negative affect was found, although only in the caregivers. In that group, higher daily received support compensated for lower daily coping self-efficacy but had a negative effect when coping self-efficacy was significantly higher than typical. Also, direct beneficial effects of higher daily coping self-efficacy and received support on caregiver positive affect were found. In the patients, higher daily coping self-efficacy was directly associated with better daily affect.

CONCLUSIONS: Diverse effects of daily coping self-efficacy and received social support were found-the interference effect in the caregivers and the main effect of coping self-efficacy in the patients. Higher daily coping self-efficacy and optimal received social support may provide resilience against affect disturbance after cancer treatment.

PMID:34788348 | DOI:10.1371/journal.pone.0260128

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Evaluation of the United States COVID-19 vaccine allocation strategy

PLoS One. 2021 Nov 17;16(11):e0259700. doi: 10.1371/journal.pone.0259700. eCollection 2021.

ABSTRACT

BACKGROUND: Anticipating an initial shortage of vaccines for COVID-19, the Centers for Disease Control (CDC) in the United States developed priority vaccine allocations for specific demographic groups in the population. This study evaluates the performance of the CDC vaccine allocation strategy with respect to multiple potentially competing vaccination goals (minimizing mortality, cases, infections, and years of life lost (YLL)), under the same framework as the CDC allocation: four priority vaccination groups and population demographics stratified by age, comorbidities, occupation and living condition (congested or non-congested).

METHODS AND FINDINGS: We developed a compartmental disease model that incorporates key elements of the current pandemic including age-varying susceptibility to infection, age-varying clinical fraction, an active case-count dependent social distancing level, and time-varying infectivity (accounting for the emergence of more infectious virus strains). The CDC allocation strategy is compared to all other possibly optimal allocations that stagger vaccine roll-out in up to four phases (17.5 million strategies). The CDC allocation strategy performed well in all vaccination goals but never optimally. Under the developed model, the CDC allocation deviated from the optimal allocations by small amounts, with 0.19% more deaths, 4.0% more cases, 4.07% more infections, and 0.97% higher YLL, than the respective optimal strategies. The CDC decision to not prioritize the vaccination of individuals under the age of 16 was optimal, as was the prioritization of health-care workers and other essential workers over non-essential workers. Finally, a higher prioritization of individuals with comorbidities in all age groups improved outcomes compared to the CDC allocation.

CONCLUSION: The developed approach can be used to inform the design of future vaccine allocation strategies in the United States, or adapted for use by other countries seeking to optimize the effectiveness of their vaccine allocation strategies.

PMID:34788345 | DOI:10.1371/journal.pone.0259700

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School reopening and risks accelerating the COVID-19 pandemic: A systematic review and meta-analysis protocol

PLoS One. 2021 Nov 17;16(11):e0260189. doi: 10.1371/journal.pone.0260189. eCollection 2021.

ABSTRACT

BACKGROUND: One of the most recent concerns of this pandemic regards the role of schools reopening in disease transmission, as well as the impact of keeping schools closed. While school reopening seems critical for the education and mental health of children, adolescents, and adults, so far the literature has not systematically reached a consensus whether to recommend the return to schools in a way that would be safe for students and staff.

OBJECTIVE: To synthesize and critically evaluate the scientific evidence on the potential risk of accelerating the Coronavirus Disease 2019 (COVID-19) pandemic among children, adolescents, young adults, and adults with school reopening.

METHODS: This systematic review and meta-analysis protocol was elaborated following the PRISMA-P. We will include all observational study designs, which report on the potential risk of accelerating the COVID-2019 pandemic with school reopening. Electronic databases included were MEDLINE/PubMed, Cochrane Library, EMBASE, Web of Science, SCOPUS and CNKI. Additional sources will be also retrieved, including Clinical trials.gov-NIH, The British Library, Pro Quest Dissertations Database, Public Health Gray Literature Sources and Health Evidence, Google Scholar, and pre-prints [medRXiv]. No restriction to language or date will be used as search strategy. In an independently manner, two investigators will select studies, perform data extraction, as well as perform a critical appraisal of the risk of bias and overall quality of the selected observational studies, based on their designs. The heterogeneity among the studies will be assessed using the I2 statistic test. According to the results of this test, we will verify whether a meta-analysis is feasible. If feasibility is confirmed, a random-effect model analysis will be carried out. For data analysis, the calculation of the pooled effect estimates will consider a 95% CI and alpha will be set in 0.05 using the R statistical software, v.4.0.4. In addition, we will rate the certainty of evidence based on Cochrane methods and in accordance with the Grading of Recommendations Assessment, Development and Evaluation (GRADE).

EXPECTED RESULTS: This systematic review and meta-analysis will provide better insights into safety in the return to school in the context of the COVID-2019 pandemic, at a time when vaccination advances unevenly in several countries around the world. Hence, consistent data and robust evidence will be provided to help decision-makers and stakeholders in the current pandemic scenario.

PROSPERO REGISTRATION NUMBER: CRD42021265283; https://clinicaltrials.gov.

PMID:34788344 | DOI:10.1371/journal.pone.0260189

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Fellowship program directors and trainees across the United States find parental leave policies to be inconsistent, inaccessible, and inadequate

PLoS One. 2021 Nov 17;16(11):e0260057. doi: 10.1371/journal.pone.0260057. eCollection 2021.

ABSTRACT

INTRODUCTION: Determine the consistency, accessibility, and adequacy of parental leave policies for adult and pediatric medicine fellowship programs.

METHODS: We administered a 40-question survey to fellowship program directors (PDs) and trainees in adult and pediatric cardiology, hematology/oncology, gastroenterology, and pulmonology/critical care fellowship programs in the United States. We used Chi-square tests to compare proportions for categorical variables and t-tests to compare means for continuous variables.

RESULTS: A total of 190 PDs from 500 programs (38.0%) and 236 trainees from 142 programs (28.4%) responded. Most respondents did not believe that parental leave policies were accessible publicly (322/426; 75.6%), on password-protected intranet (343/426; 80.5%), or upon request (240/426; 56.3%). The PDs and trainees broadly felt that parental leave for fellows should be 5-10 weeks (156/426; 36.6%) or 11-15 weeks (165/426; 38.7%). A majority of PDs felt that there was no increased burden upon other fellows (122/190; 64.2%) or change in overall well-being (110/190; 57.9%). When asked about the biggest barrier to parental leave support, most PDs noted time constrains of fellowship (101/190; 53.1%) and the limited number of fellows (43/190; 22.6%). Trainees similarly selected the time constraints of training (88/236; 37.3%), but nearly one-fifth chose the culture in medicine (44/236; 18.6%). There were no statistically significant differences in answers based on the respondents’ sex, specialty, or subspecialty.

DISCUSSION: Parental leave policies are broadly in place, but did not feel these were readily accessible, standardized, or of optimum length. PDs and trainees noted several barriers that undermine support for better parental leave policies, including time constraints of fellowship, the limited number of fellows for coverage, and workplace culture. Standardization of parental leave policies is advisable to allow trainees to pursue fellowship training and care for their newborns without undermining their educational experiences.

PMID:34788326 | DOI:10.1371/journal.pone.0260057

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Relationships between core self-evaluation, leader empowering behavior, and job security among Jordan University Hospital nurses

PLoS One. 2021 Nov 17;16(11):e0260064. doi: 10.1371/journal.pone.0260064. eCollection 2021.

ABSTRACT

Nurses are facing real stressors due to patients’ needs and leaders’ demands. The aim of this study is to explore the perceived level of core self-evaluation (CSE), leader empowering behavior (LEB), and job security among Jordan University Hospital nurses in Amman, the capital of Jordan. Furthermore, it investigates the relationship between the selected variables. Differences of gender, educational level, experience, and site of work are also examined with job security. Moreover, it evaluates the contribution of CSE, LEB, gender, educational level, experience, and site of work in predicting job security among Jordan University Hospital nurses. A descriptive cross-sectional design was adopted for this study. A convenience sample of 214 nurses from Jordan University Hospital was completed the CSE scale, LEB scale, and job security scale. Descriptive statistics, Pearson correlation coefficient, t-test, one-way analysis of variance, and stepwise regression were used to analyze the results. The results indicate that job security is found to be at high level, whereas LEB and CSE are found to be at moderate levels among nurses. Significant positive relationships are found between CSE, LEB, and job security. Male nurses and medical/surgical floors reported higher levels of job security than female nurses and intensive care units. Finally, the results show that LEB and gender are significant predictors of job security among nurses. We suggest that managers of nurses should apply leadership behaviors in order to increase their job security and career empowerment.

PMID:34788327 | DOI:10.1371/journal.pone.0260064

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The effects of quality of evidence communication on perception of public health information about COVID-19: Two randomised controlled trials

PLoS One. 2021 Nov 17;16(11):e0259048. doi: 10.1371/journal.pone.0259048. eCollection 2021.

ABSTRACT

BACKGROUND: The quality of evidence about the effectiveness of non-pharmaceutical health interventions is often low, but little is known about the effects of communicating indications of evidence quality to the public.

METHODS: In two blinded, randomised, controlled, online experiments, US participants (total n = 2140) were shown one of several versions of an infographic illustrating the effectiveness of eye protection in reducing COVID-19 transmission. Their trust in the information, understanding, feelings of effectiveness of eye protection, and the likelihood of them adopting it were measured.

FINDINGS: Compared to those given no quality cues, participants who were told the quality of the evidence on eye protection was ‘low’, rated the evidence less trustworthy (p = .001, d = 0.25), and rated it as subjectively less effective (p = .018, d = 0.19). The same effects emerged compared to those who were told the quality of the evidence was ‘high’, and in one of the two studies, those shown ‘low’ quality of evidence said they were less likely to use eye protection (p = .005, d = 0.18). Participants who were told the quality of the evidence was ‘high’ showed no statistically significant differences on these measures compared to those given no information about evidence quality.

CONCLUSIONS: Without quality of evidence cues, participants responded to the evidence about the public health intervention as if it was high quality and this affected their subjective perceptions of its efficacy and trust in the provided information. This raises the ethical dilemma of weighing the importance of transparently stating when the evidence base is actually low quality against evidence that providing such information can decrease trust, perception of intervention efficacy, and likelihood of adopting it.

PMID:34788299 | DOI:10.1371/journal.pone.0259048

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Magnitude of client satisfaction and its associated factors with outpatient pharmacy service at Dubti General Hospital, Afar, North East Ethiopia: A cross sectional study

PLoS One. 2021 Nov 17;16(11):e0260104. doi: 10.1371/journal.pone.0260104. eCollection 2021.

ABSTRACT

INTRODUCTION: In Ethiopia the pharmacy service has had several gaps among these were low patient satisfaction, and poor availability of essential pharmaceuticals. In addition, previous studies showed variation in magnitude of client satisfaction, and there is no previous study in the study area. Therefore, the aim of the study was to determine client satisfaction with outpatient pharmacy service and associated factors among adult clients at Dubti General Hospital in Afar, Ethiopia.

METHODS: A hospital based cross sectional study design was employed from February 1 to March 30, 2020 at Dubti General Hospital. Participants were selected by systematic random sampling method. Bivariate and multivariate binary logistic regression was computed to assess statistical association between the outcome variable, and independent variables. AOR with 95% CI were used to show statistical Significance at P <0.05.

RESULTS: The overall satisfaction towards outpatient pharmacy service was 165(40.5%). Regarding associated factors, service payment insured through their workplace was positively associated with satisfaction (AOR = 3.178, 95% CI: 1.294-7.80) where as availability of some medications (AOR = 0.393, 95% CI: 0.208-0.741), unfair medication cost (AOR = 0.613, 95% CI: 0.607-0.910), and lack of organized pharmacy work flow (AOR = 0.105, 95% CI: 0.049-0.221) were negatively associated with clients’ satisfaction.

CONCLUSION: The clients’ satisfaction in this study is low that warrants immediate corrective measures. Corrective measures should be taken based on identified gaps such as improving drug availability, pharmacy work flow, and cost of medications.

PMID:34788317 | DOI:10.1371/journal.pone.0260104