articles+ search results

COVID-19 vaccines, TRANSPLANTATION of organs, tissues, etc., SARS-CoV-2 Omicron variant, IMMUNOGLOBULINS, and DURABILITY

Solid organ transplant recipients (SOTRs) have reduced immunogenicity to SARS-CoV-2 vaccines and are at increased risk of severe COVID-19 when compared to the general population.[1] Previously, a fourth dose (D4) of SARS-CoV-2 vaccine has shown improved antibody responses in SOTRs, but given the decreasing titers seen by 6 months post-dose 2 and 3, immune responses achieved after D4 could decrease in a similar fashion.[[2]] This study assesses the durability and kinetics of vaccine-induced antibody responses in SOTRs post-D4 and evaluates these responses in the context of the Omicron variant, which requires higher levels of antibody to neutralize. In this study of antibody responses after a fourth dose of SARS-CoV-2 vaccine in SOTRs with 6 months of follow up, 61% demonstrated antibody titers associated in prior studies with potential SARS-CoV-2 Omicron variant neutralization at 3 months. 3 c 5/18 SOTRs with low titers and 8/39 SOTRs with high titers were unable to provide titers at 3-months post-D4. [Extracted from the article]

Background Methods and materials Results Conclusions Plain Language Summary Hippocampal avoidance (HA) has been shown to preserve cognitive function in adult patients with cancer treated with whole‐brain radiation therapy for brain metastases. However, the feasibility of HA in pediatric patients with brain tumors has not been explored because of concerns of increased risk of relapse in the peri‐hippocampal region. Our aim was to determine patterns of recurrence and incidence of peri‐hippocampal relapse in pediatric patients with medulloblastoma (MB).We identified pediatric patients with MB treated with protons between 2002 and 2016 and who had recurrent disease. To estimate the risk of peri‐hippocampal recurrence, three hippocampal zones (HZs) were delineated corresponding to ≤5 mm (HZ‐1), 6 to 10 mm (HZ‐2), and >10 mm (HZ‐3) distance of the recurrence from the contoured hippocampi. To determine the feasibility of HA, three standard‐risk patients with MB were planned using either volumetric‐modulated arc therapy (VMAT) or intensity‐modulated proton therapy (IMPT) plans.Thirty‐eight patients developed a recurrence at a median of 1.6 years. Of the 25 patients who had magnetic resonance imaging of the recurrence, no patients failed within the hippocampus and only two patients failed within HZ‐1. The crude incidence of peri‐hippocampal failure was 8%. Both HA‐VMAT and HA‐IMPT plans were associated with significantly reduced mean dose to the hippocampi (p < .05). HA‐VMAT and HA‐IMPT plans were associated with decreased percentage of the third and lateral ventricles receiving the prescription craniospinal dose of 23.4 Gy.Peri‐hippocampal failures are uncommon in pediatric patients with MB. Hippocampal avoidance should be evaluated in a prospective cohort of pediatric patients with MB.In this study, the patterns of disease recurrence in patients with a pediatric brain tumor known as medulloblastoma treated with proton radiotherapy were examined. The majority of failures occur outside of an important structure related to memory formation called the hippocampus. Hippocampal sparing radiation plans using proton radiotherapy were generated and showed that dose to the hippocampus was able to be significantly reduced. The study provides the rationale to explore hippocampal sparing in pediatric medulloblastoma in a prospective clinical trial. [ABSTRACT FROM AUTHOR]

Background: Mild Cognitive Impairment with Suspected non‐Alzheimer's Pathophysiology (SNAP‐MCI) represents a group of patients with Alzheimer's disease (AD) like neurodegeneration without beta‐amyloid pathology. While this group likely has a heterogeneous etiology, tau pathology, as in Primary Age‐Related Tauopathy (PART), has been hypothesized to play a major role. We investigate tau positron emission tomography (PET) uptake in the medial temporal lobe (MTL) in SNAP‐MCI and the association of MTL Tau‐PET uptake with structural measures and delayed recall in beta‐amyloid negative (A‐) MCI patients. Method: 237 MCI patients and 301 A‐ controls with available beta‐amyloid and tau PET and magnetic resonance images (within 200 days) were included. Baseline hippocampal volume and entorhinal cortex (ERC) and Brodmann areas (BA)35 thickness were obtained using an in‐house developed pipeline and annualized atrophy rates were estimated in an unbiased fashion using follow‐up MRIs within 4.5 years. Βeta‐amyloid status (A+/‐) was determined by a standard cut‐off (Florbetapir: 1.11; Florbetaben: 1.08) and neurodegeneration status (N+/‐) by hippocampal volumes, corrected for intracranial volume, using the 90th percentile of A+ AD patients as the cut‐off. Tau‐PET standardized uptake value ratio (SUVR) in the ERC/BA35 was calculated. A composite z‐score of delayed recall at baseline and change over 2 years was obtained. Result: SNAP‐MCI had significantly higher ERC/BA35 Tau‐PET SUVR than A‐ controls (Table 1, corrected for age) and qualitatively higher than A‐N‐ MCI (p=0.10). ERC/BA35 Tau‐PET SUVR in A‐N‐ MCI was not significantly different from A‐ controls. In A‐ MCI patients, ERC/BA35 Tau‐PET SUVR was significantly associated with BA35 thickness and hippocampal, ERC and BA35 atrophy rates, corrected for beta‐amyloid PET SUVR (Table 2; Figure 1). MTL structural measures, but not ERC/BA35 Tau‐PET SUVR, were associated with cross‐sectional and longitudinal delayed recall measures (Table 3; Figure 2). Conclusion: SNAP‐MCI had elevated ERC/BA35 Tau‐PET SUVR and ERC/BA35 Tau‐PET SUVR was associated with MTL structural measures in A‐ MCI patients. This indicates that tau pathology might be an important driver of neurodegeneration in the absence of beta‐amyloid pathology, supporting the notion that PART contributes to SNAP‐MCI. Additionally, MTL structure was associated with memory performance, consistent with SNAP not being a benign condition. [ABSTRACT FROM AUTHOR]

Background: While previous studies have demonstrated the effect of Alzheimer's disease (AD) CSF testing in changing diagnosis, we lack an understanding of how this testing affects clinical management. Therefore, we assessed changes in clinical management associated with AD CSF biomarker testing when ordered as part of routine clinical management. Method: The 'Investigating the Impact of Alzheimer's Disease Diagnostics in British Columbia' (IMPACT‐AD BC) study (NCT05002699) is a longitudinal study examining the impact of AD CSF testing on clinical management, personal utility and health care economics in British Columbia, Canada. After AD CSF testing was ordered as part of routine care (where the clinical scenario met the appropriate use criteria), the patient and their physician were eligible to participate in the study. The primary outcome was the change in management (pre‐ v. post‐biomarker results) in a composite measure including 1) AD drug therapy, 2) other relevant drug therapy, 3) other diagnostic procedures, and 4) referral or counselling. Result: Participants (n = 129) had a median age of 63 (IQR:58‐68); 49% were female. Cognitive impairment at baseline consisted of 7% with subjective cognitive impairment, 53% with mild cognitive impairment, and 40% with dementia. CSF biomarker profiles were consistent with an amyloid‐beta pathology (i.e., A+) in 72% of cases. Changes in clinical management because of testing occurred in 83% of cases including: referrals and counseling (57%), imaging (47%) and other diagnostic procedures (e.g., neuropsychological testing) (42%), and use of AD drug therapies (40%). For those with a non‐AD pre‐biomarkers diagnosis, 42% were changed to AD post‐biomarkers; for those with an AD pre‐biomarkers diagnosis, 18% were changed to non‐AD post‐biomarkers. Conclusion: This study has revealed substantial changes in clinical management as a direct result of AD CSF biomarker testing in routine care. An understanding of the implications of biomarker testing will in turn help us: improve appropriate utilization, understand the broader impacts on persons living with dementia and on the health care system, and prepare for expanded use of this testing with the availability of disease‐modifying therapeutics. [ABSTRACT FROM AUTHOR]

COVID-19 vaccines, ANTIBODY formation, HEART transplant recipients, LUNG transplantation, HIV seroconversion, and BOOSTER vaccines

Antibody response to a third dose of SARS-CoV-2 vaccine in heart and lung transplant recipients Morbidity and mortality from SARS-CoV-2 infection in heart (HT) and lung transplant (LT) recipients are high, especially for LT recipients, despite vaccination.[1] Despite severe COVID-19 outcomes, HT/LT recipients represent <10% of solid organ transplant recipients (SOTRs) included in cohort studies evaluating two and three dose regimens.[2] There is now strong evidence to support that SOTRs in a greater immunosuppressed state (common among HT/LT recipients) are at increased risk for persistent seronegative state post-D3.[[3]] Therefore, we evaluated antispike antibody responses before and after a third vaccine dose (D3) in HT/LT recipients to quantify post-D3 antibody responses. Effect of Mycophenolate mofetil dosing on antibody response to SARS-CoV-2 vaccination in heart and lung transplant recipients. [Extracted from the article]

TELECOMMUNICATION, CANCER, PRIMARY care, ELECTRONIC health records, and MEDICAL personnel

Previous research has identified communication and care coordination problems for patients with cancer. Healthcare providers (HCPs) have reported communication issues due to the incompatibility of electronic medical records (EMR) software and not being consistently copied on patient reports. We evaluated an asynchronous web-based communication system ("eOncoNote") for primary care providers and cancer specialists to improve cancer care coordination. The objectives were to examine patients' perceptions of the role of eOncoNote in their healthcare, and HCPs' experiences of implementing eOncoNote. Qualitative interviews were conducted with patients with breast and prostate cancer, primary care providers, and cancer specialists. Eighteen patients and fourteen HCPs participated. Six themes were identified from the patient interviews focusing on HCP and patient roles related to care coordination and patient awareness of communication among their HCPs. Four themes were identified from HCP interviews related to the context of care coordination and experience with eOncoNote. Both patients and HCPs described the important role patients and caregivers play in care coordination. The results show that patients were often unaware of the communication between their HCPs and assumed they were communicating. HCPs encountered challenges incorporating eOncoNote into their workflow. [ABSTRACT FROM AUTHOR]

NURSING licensure, OCCUPATIONAL roles, PROFESSIONAL ethics, TEAMS in the workplace, STATISTICS, EVALUATION of human services programs, NURSING, PROFESSIONS, RESEARCH methodology, HUMAN services programs, PRE-tests & post-tests, LEARNING strategies, INTERPROFESSIONAL relations, COMMUNICATION, QUESTIONNAIRES, DESCRIPTIVE statistics, INTERDISCIPLINARY education, NURSING students, STUDENT attitudes, STATISTICAL sampling, DATA analysis software, THEMATIC analysis, and TRAINING of athletic trainers

Background: The purpose of this article is to describe the development, implementation, and evaluation of a Simulation Interprofessional Education (Sim‐IPE) activity for healthcare students from different disciplines (athletic training [AT] and nursing). The objective for the Sim‐IPE activity was to engage AT and prelicensure nursing students in a realistic healthcare scenario to enhance knowledge about one another's profession, develop interprofessional skills, collaborate with one another, and communicate effectively as a team as they performed care. Methods: This mixed methods study employed a one‐time posttest design for a convenience sample of AT and prelicensure nursing students following a simulation intervention. Students completed the Student Perceptions of Interprofessional Clinical Education‐Revised (SPICE‐R) survey and answered open‐ended response questions. Results: Thirteen students (N = 13) from Cohort 1 and 12 students (N = 12) from Cohort 2 completed the SPICE‐R survey. Most students strongly agreed/agreed for each of the SPICE‐R survey questions. Qualitative findings indicated the students positively perceived the Sim‐IPE activity as it helped them discover the value of interprofessional patient care. Discussion: The quantitative findings indicated that the students found the Sim‐IPE an effective learning methodology to achieve the objectives while the qualitative findings gave further insight into the students' perceptions of interprofessional teamwork and the value of the prebrief session conducted before the simulation. The findings will inform future Sim‐IPE activities involving additional groups of healthcare students. [ABSTRACT FROM AUTHOR]

GENETIC variation, SLEEP, MISSENSE mutation, GENETIC testing, CLOCK genes, SLEEP disorders, and EXOMES

Rare variants in ten genes have been reported to cause Mendelian sleep conditions characterised by extreme sleep duration or timing. These include familial natural short sleep (ADRB1, DEC2/BHLHE41, GRM1 and NPSR1), advanced sleep phase (PER2, PER3, CRY2, CSNK1D and TIMELESS) and delayed sleep phase (CRY1). The association of variants in these genes with extreme sleep conditions were usually based on clinically ascertained families, and their effects when identified in the population are unknown. We aimed to determine the effects of these variants on sleep traits in large population-based cohorts. We performed genetic association analysis of variants previously reported to be causal for Mendelian sleep and circadian conditions. Analyses were performed using 191,929 individuals with data on sleep and whole-exome or genome-sequence data from 4 population-based studies: UK Biobank, FINRISK, Health-2000-2001, and the Multi-Ethnic Study of Atherosclerosis (MESA). We identified sleep disorders from self-report, hospital and primary care data. We estimated sleep duration and timing measures from self-report and accelerometery data. We identified carriers for 10 out of 12 previously reported pathogenic variants for 8 of the 10 genes. They ranged in frequency from 1 individual with the variant in CSNK1D to 1,574 individuals with a reported variant in the PER3 gene in the UK Biobank. No carriers for variants reported in NPSR1 or PER2 were identified. We found no association between variants analyzed and extreme sleep or circadian phenotypes. Using sleep timing as a proxy measure for sleep phase, only PER3 and CRY1 variants demonstrated association with earlier and later sleep timing, respectively; however, the magnitude of effect was smaller than previously reported (sleep midpoint ~7 mins earlier and ~5 mins later, respectively). We also performed burden tests of protein truncating (PTVs) or rare missense variants for the 10 genes. Only PTVs in PER2 and PER3 were associated with a relevant trait (for example, 64 individuals with a PTV in PER2 had an odds ratio of 4.4 for being "definitely a morning person", P = 4x10-8; and had a 57-minute earlier midpoint sleep, P = 5x10-7). Our results indicate that previously reported variants for Mendelian sleep and circadian conditions are often not highly penetrant when ascertained incidentally from the general population. Author summary: Clinically ascertained family-based studies have previously identified rare genetic variation associated with causing life-long sleep conditions, specifically shorter sleep, and earlier or later sleep timing. However, the effects of previously reported genetic variants on sleep duration and timing when identified incidentally through population-based studies are not known. Here, we take advantage of up to 191,929 individuals from four population-based studies, including the UK Biobank, to estimate the effects of these variants on sleep duration and timing using self-reported and accelerometer-based sleep estimates coupled with sequencing data. Our analysis revealed no association between variants previously reported and extreme sleep conditions. Two variants located in two genes (PER3 and CRY1) showed evidence of association with sleep timing, but their estimated effects (~5 to 7 minutes) on sleep timing are much smaller relative to those previously reported. Our results indicate that previously reported variants are not causal for extreme sleep conditions in the general population. Finally, although we were unable to analyse a previously reported variant in the PER2 gene associated with sleep timing, additional analysis in the UK Biobank revealed carries of protein-truncating variants in this gene have an approximately 1-hour earlier sleep midpoint compared to non-carriers. These population-based estimates are important because of the recent dramatic increase in direct-to-consumer and health service genome-wide genetic testing. [ABSTRACT FROM AUTHOR]

ALCOHOL drinking, ENERGY consumption, WARNING labels, INCOME, WEIGHT gain, and CONSUMPTION (Economics)

Background: Alcohol is a discretionary, energy dense, dietary component. Compared to non-drinkers, people who consume alcohol report higher total energy intake and may be at increased risk of weight gain, overweight, and obesity, which are key preventable risk factors for illness. However, accurate consumer knowledge of the energy content in alcohol is low. To inform future behaviour change interventions among drinkers, this study investigated individual characteristics associated with changing alcohol consumption due to energy-related concerns.Methods: An online survey was undertaken with 801 Australian adult drinkers (18-59 years, 50.2% female), i.e. who consumed alcohol at least monthly. In addition to demographic and health-related characteristics, participants reported past-year alcohol consumption, past-year reductions in alcohol consumption, frequency of harm minimisation strategy use (when consuming alcohol), and frequency of changing alcohol consumption behaviours because of energy-related concerns.Results: When prompted, 62.5% of participants reported changing alcohol consumption for energy-related reasons at least 'sometimes'. Women, those aged 30-44 years, metropolitan residents, those with household income $80,001-120,000, and risky/more frequent drinkers had increased odds of changing consumption because of energy-related concerns, and unemployed respondents had reduced odds.Conclusions: Results indicate that some sociodemographic groups are changing alcohol consumption for energy-related reasons, but others are not, representing an underutilised opportunity for health promotion communication. Further research should investigate whether messaging to increase awareness of alcohol energy content, including through systems-based policy actions such as nutritional/energy product labelling, would motivate reduced consumption across a broader range of drinkers. [ABSTRACT FROM AUTHOR]

TRANSPLANTATION of organs, tissues, etc., COVID-19 vaccines, MESSENGER RNA, VACCINATION, and ANTIBODY formation

Heterologous vaccination ("mixing platforms") for the third (D3) dose of SARS‐CoV‐2 vaccine is a potential strategy to improve antibody responses in solid organ transplant recipients (SOTRs), but data are mixed regarding potential differential immunogenicity. We assessed for differences in immunogenicity and tolerability of homologous (BNT162b2 or mRNA‐1273; D3‐mRNA) versus heterologous (Ad.26.COV2.S; D3‐JJ) D3 among 377 SARS‐CoV‐2‐infection naïve SOTRs who remained seronegative after two mRNA vaccines. We measured anti‐spike titers and used weighted Poisson regression to evaluate seroconversion and development of high‐titers, comparing D3‐JJ to D3‐mRNA, at 1‐, 3‐, and 6 month post‐D3. 1‐month post‐D3, seroconversion (63% vs. 52%, p =.3) and development of high‐titers (29% vs. 25%, p =.7) were comparable between D3‐JJ and D3‐mRNA recipients. 3 month post‐D3, D3‐JJ recipients were 1.4‐fold more likely to seroconvert (80% vs. 57%, weighted incidence‐rate‐ratio: wIRR = 1.101.401.77, p =.006) but not more likely to develop high‐titers (27% vs. 22%, wIRR = 0.440.921.93, p =.8). 6 month post‐D3, D3‐JJ recipients were 1.41‐fold more likely to seroconvert (88% vs. 59%, wIRR = 1.04 1.411.93, p =.029) and 2.63‐fold more likely to develop high‐titers (59% vs. 21%, wIRR = 1.382.635.00, p =.003). There was no differential signal in alloimmune events or reactogenicity between platforms. SOTRs without antibody response after two mRNA vaccines may derive benefit from heterologous Ad.26.COV2.S D3. Solid organ transplant recipients with negative anti‐spike antibody after a two‐dose mRNA SARS‐CoV‐2 vaccine series are more likely to seroconvert after receiving a third dose of the heterologous vaccine Ad.26.COV2.S, compared to a homologous mRNA vaccine. [ABSTRACT FROM AUTHOR]

COVID-19 vaccines, TRANSPLANTATION of organs, tissues, etc., IMMUNE response, MESSENGER RNA, and SARS-CoV-2 Delta variant

Heterologous vaccination has been explored in small populations of solid organ transplant recipients (SOTRs),1-4 yet 38% of participants had persistently suboptimal response indicating potential role for further vaccine doses.1 The US CDC currently recommends immunocompromised adults who received an Ad26.COV2.S prime to receive one additional dose of SARS-CoV-2 mRNA vaccine, either BNT162b2 or mRNA-1273, followed by two mRNA vaccine boosters, although the efficacy of this strategy in immunocompromised persons is not known. A third dose of SARS-CoV-2 vaccine increases neutralizing antibodies against variants of concern in solid organ transplant recipients. Immunogenicity of Ad26.COV2.S prime and two subsequent doses of mRNA SARS-CoV-2 vaccines in solid organ transplant recipients: A case series. [Extracted from the article]

SEDENTARY lifestyles, GLOBAL Positioning System, HOME environment, SCHOOL environment, BUILT environment, SOCIAL support, CROSS-sectional method, SELF-evaluation, POPULATION geography, PHYSICAL activity, SOCIAL context, ACCELEROMETRY, SELF-efficacy, QUESTIONNAIRES, DESCRIPTIVE statistics, STATISTICAL models, and ADOLESCENCE

Background: A better understanding of the extent to which psychosocial and environmental correlates of physical activity are specific to locations would inform intervention optimization. Purpose: To investigate cross-sectional associations of location-general and location-specific variables with physical activity and sedentary time in three common locations adolescents spend time. Methods: Adolescents (N = 472,Mage = 14.1,SD = 1.5) wore an accelerometer and global positioning systems (GPS) tracker and self-reported on psychosocial (e.g., self-efficacy) and environmental (e.g., equipment) factors relevant to physical activity and sedentary time. We categorized each survey item based on whether it was specific to a location to generate psychosocial and environmental indices that were location-general or specific to either school, non-school, or home location. Physical activity (MVPA) and sedentary time were based on time/location match to home, school, or all "other" locations. Mixed-effects models investigated the relation of each index with location-specific activity. Results: The location-general and non-school physical activity psychosocial indices were related to greater MVPA at school and "other" locations. The school physical activity environment index was related to greater MVPA and less sedentary time at school. The home activity environment index was related to greater MVPA at home. The non-school sedentary psychosocial index was related to less sedentary time at home. Interactions among indices revealed adolescents with low support on one index benefited (i.e., exhibited more optimal behavior) from high support on another index (e.g., higher scores on the location-general PA psychosocial index moderated lower scores on the home PA environment index). Concurrent high support on two indices did not provide additional benefit. Conclusions: No psychosocial or environment indices, including location-general indices, were related to activity in all locations. Most of the location-specific indices were associated with activity in the matching location(s). These findings provide preliminary evidence that psychosocial and environmental correlates of activity are location specific. Future studies should further develop location-specific measures and evaluate these constructs and whether interventions may be optimized by targeting location-specific psychosocial and environmental variables across multiple locations. [ABSTRACT FROM AUTHOR]

MATURITY onset diabetes of the young, GRANULE cells, INSULIN, STEM cells, and INTRACELLULAR calcium

Mutations in HNF1A cause Maturity Onset Diabetes of the Young (HNF1A-MODY). To understand mechanisms of β-cell dysfunction, we generated stem cell-derived pancreatic endocrine cells with hypomorphic mutations in HNF1A. HNF1A-deficient β-cells display impaired basal and glucose stimulated-insulin secretion, reduced intracellular calcium levels in association with a reduction in CACNA1A expression, and accumulation of abnormal insulin granules in association with SYT13 down-regulation. Knockout of CACNA1A and SYT13 reproduce the relevant phenotypes. In HNF1A deficient β-cells, glibenclamide, a sulfonylurea drug used in the treatment of HNF1A-MODY patients, increases intracellular calcium, and restores insulin secretion. While insulin secretion defects are constitutive in β-cells null for HNF1A, β-cells heterozygous for hypomorphic HNF1A (R200Q) mutations lose the ability to secrete insulin gradually; this phenotype is prevented by correction of the mutation. Our studies illuminate the molecular basis for the efficacy of treatment of HNF1A-MODY with sulfonylureas, and suggest promise for the use of cell therapies. hPSCs model of Maturity Onset Diabetes of the Young caused by mutations in the transcription factor HNF1A (HNF1A-MODY), regulates the expression of genes required for the formation of dense-core insulin granules and calcium-dependent insulin secretion, demonstrating a basis to treat HNF1A-MODY patients with sulfonylureas. [ABSTRACT FROM AUTHOR]

COVID-19 vaccines, TRANSPLANTATION of organs, tissues, etc., VACCINES, and IMMUNE response

Fewer than 45% of solid organ transplant recipients (SOTRs) mount a detectable antispike antibody level after two doses of mRNA SARS-CoV-2 vaccination (D2).1 Various vaccination strategies, including mixing platforms, have been proposed, but there is no consensus on the optimal vaccination sequence to improve immunogenicity.2,3 Although using similar technology, the mRNA-1273 vaccine has been associated with higher peak antibody responses than the use of BNT162b2 in immunosuppressed populations, potentially related to a higher vaccine antigen dose.3,4 We therefore studied whether the use of mRNA-1273 versus BNT162b2 as a third primary vaccine dose (D3) might generate a more robust antibody response in SOTR who remained seronegative after two doses of BNT162b2. Improved humoral immunogenicity with mRNA-1273 versus BNT162b2 as third vaccine dose among solid organ transplant recipients seronegative after two BNT162b2 doses METHODS From our national observational study, approved by the Johns Hopkins Institutional Review Board (IRB00248540),4 we included adult SOTRs who tested seronegative after two doses of BNT162b2 and received either a D3-BNT162b2 or D3-mRNA-1273. [Extracted from the article]

MOTHERS, PARENT attitudes, SOCIAL norms, AGE distribution, CROSS-sectional method, INTERNET, FATHERS, SEX distribution, PARENTING, ALCOHOL drinking, DESCRIPTIVE statistics, PARENT-child relationships, and PARENTS

Aims This study aimed to examine perceived social norms, the effect of parental drinking on these norms, alcohol use in front of children, and how norms and consumption vary based on child age and gender of the parent. Methods A cross-sectional online panel survey was undertaken with n  = 1000 Australian adults (including 670 parents) aged 18–59 years. The survey assessed: alcohol consumption in front of children; normative attitudes towards drinking in the presence of children; and perceived social norms. Results Overall, 33.9% of parents reported drinking a glass of alcohol each day or a couple of times a week, 18.2% reported getting slightly drunk and 7.8% indicated getting visibly drunk each day or a couple of times a week with their children present. In total, 37.5% reported drinking in front of their children at least weekly. Fathers were more likely to drink in front of children than mothers. Most parents deemed drinking small amounts of alcohol in front of children as acceptable but did not accept drunkenness. Respondents were less concerned about a father drinking one or two drinks in front of their children than a mother. Social expectations were not related to child age, but norms related to others' perceived behaviour were. Conclusions Many parents, particularly fathers consume alcohol in front of their children. There is a need to target health promotion strategies to adults and parents consuming in excess of health guidelines, and to the many parents who are consuming alcohol at higher levels in front of their children. [ABSTRACT FROM AUTHOR]

BLACK feminism, HISTORY of feminism, FEMINISM, BLACK feminists, WORLD history, CONVERSATION, and RACISM

This roundtable stems from a Zoom event, "New Directions in Feminism and Global Race Studies (a Book Conversation)" with authors Tiffany N. Florvil, Kaiama L. Glover, Annette K. Joseph-Gabriel, Katherine M. Marino, Robin Mitchell, and Jacqueline-Bethel Tchouta Mougoué, hosted by Samantha Pinto. These scholars discussed their recently published books, which expand how we think about transnational feminism and global Black feminisms in the Americas, the Caribbean, Africa, and Europe. The lightly edited transcript of the conversation explores how putting Black women at the center of histories of global feminisms and race studies transforms these fields and the questions that are usually asked. The authors also discussed navigating research challenges and confronting racism in the sources and in the archives. The conversation underscores the importance of intellectual community, as well as the relevance and urgency of Black feminist scholarship today. [ABSTRACT FROM AUTHOR]

The left atrium is an early sensor of left ventricular (LV) dysfunction. Still, the prognostic value of left atrial (LA) function (strain) on cardiac magnetic resonance (CMR) in dilated cardiomyopathy (DCM) remains unknown. The goal of this study was to evaluate the prognostic value of CMR-derived LA strain in DCM. Patients with DCM from the Maastricht Cardiomyopathy Registry with available CMR imaging were included. The primary endpoint was the combination of sudden or cardiac death, heart failure (HF) hospitalization, or life-threatening arrhythmias. Given the nonlinearity of continuous variables, cubic spline analysis was performed to dichotomize. A total of 488 patients with DCM were included (median age: 54 [IQR: 46-62] years; 61% male). Seventy patients (14%) reached the primary endpoint (median follow-up: 6 [IQR: 4-9] years). Age, New York Heart Association (NYHA) functional class >II, presence of late gadolinium enhancement (LGE), LV ejection fraction (LVEF), LA volume index (LAVI), LV global longitudinal strain (GLS), and LA reservoir and conduit strain were univariably associated with the outcome (all P < 0.02). LA conduit strain was a stronger predictor of outcome compared with reservoir strain. LA conduit strain, NYHA functional class >II, and LGE remained associated in the multivariable model (LA conduit strain HR: 3.65 [95% CI: 2.01-6.64; P < 0.001]; NYHA functional class >II HR: 1.81 [95% CI: 1.05-3.12; P = 0.033]; and LGE HR: 2.33 [95% CI: 1.42-3.85; P < 0.001]), whereas age, N-terminal pro–B-type natriuretic peptide, LVEF, left atrial ejection fraction, LAVI, and LV GLS were not. Adding LA conduit strain to other independent predictors (NYHA functional class and LGE) significantly improved the calibration, accuracy, and reclassification of the prediction model (P < 0.05). LA conduit strain on CMR is a strong independent prognostic predictor in DCM, superior to LV GLS, LVEF, and LAVI and incremental to LGE. Including LA conduit strain in DCM patient management should be considered to improve risk stratification. [Display omitted] [ABSTRACT FROM AUTHOR]

COVID-19, SARS-CoV-2, and REMDESIVIR

Profoundly B-cell-depleted patients can have prolonged severe acute respiratory syndrome coronavirus 2 infections with evidence of active viral replication, due to inability to mount an adequate humoral response to clear the virus. We present 3 B-cell-depleted patients with prolonged coronavirus disease 2019 infection who were successfully treated with a combination of casirivimab/imdevimab and remdesivir. [ABSTRACT FROM AUTHOR]

TEACHERS, TEACHING of controversial topics, STUDENTS, DISCUSSION in education, and SOCIAL conditions of students

Controversial topics may be uncomfortable for teachers to include in their in-class discussions. However, there are considerable cognitive and social-emotional benefits to engagement in controversial conversations, or classroom discussion about controversial topics. It is critical that teachers support students in respectful discussion to help them develop skills such as problem solving, critical thinking, and the ability to consider issues from multiple perspectives. These skills can enable students to meet larger educational goals such as engaged citizenship. The goal of this article is to highlight the benefits of controversial conversations in the classroom and describe teaching approaches that facilitate effective controversial conversations. First, we identify important factors for teachers' consideration in supporting effective and beneficial controversial conversations. Second, we provide examples of topics of conversations that may be appropriate for students of varying ages. Third, we review how the structure of conversation, scaffolding, classroom context, relationships, and students' individual differences can shape controversial conversations. [ABSTRACT FROM AUTHOR]

SOFT robotics, LYMPHEDEMA, SLEEVES, AIR pressure, MICROFLUIDICS, VALVES, MICROFLUIDIC devices, and DRAINAGE

A proof of concept of a novel air microfluidics-enabled soft robotic sleeve to enable lymphedema treatment is presented. Compression sleeves represent the current, suboptimal standard of care, and stationary pumps assist with lymph drainage; however, effective systems that are truly wearable while performing daily activities are very scarce. This problematic trade-off between performance and wearability requires a new solution, which is addressed by an innovative microfluidic device. Its novelty lies in the use of light, small, and inexpensive air microfluidic chips (35 × 20 × 5 mm3 in size) that bring three major advantages compared to their traditional counterparts. First, each chip is designed with 16 fluidic channels with a cross-sectional area varying from 0.04 to 1 mm2, providing sequential inflation and uniform deflation capability to eight air bladders, thereby producing intentional gradient compression to the arm to facilitate lymph fluid circulation. The design is derived from the fundamentals of microfluidics, in particular, hydraulic resistance and paths of least resistance. Second, the air microfluidic chip enables miniaturization of at least eight bulky energy-consuming valves to two miniature solenoid valves for control increasing wearability. Third, the air microfluidic chip has no moving parts, which reduces the noise and energy needed. The cost, simplicity, and scale-up potential of developing methods for making the system are also detailed. The sequential inflation, uniform deflation, and pressure gradient are demonstrated, and the resulted compression and internal air bladder pressure were evaluated. This air microfluidics-enabled sleeve presents tremendous potential toward future improvements in self-care lymphedema management. [ABSTRACT FROM AUTHOR]

COMMUNICABLE diseases, INFECTIOUS arthritis, HOSPITAL patients, CELLULITIS, DRUG abuse, DRUGS, and FISHER exact test

Injection drug use poses a public health challenge. Clinical experience indicates that people who inject drugs (PWID) are hospitalized frequently for infectious diseases, but little is known about outcomes when admitted. Charts were identified from local hospitals between 2013–2018 using consultation lists and hospital record searches. Included individuals injected drugs in the past six months and presented with infection. Charts were accessed using the hospital information system, undergoing primary and secondary reviews using Research Electronic Data Capture (REDCap). The Wilcoxon rank-sum test was used for comparisons between outcome categories. Categorical data were summarized as count and frequency, and compared using Fisher's exact test. Of 240 individuals, 33% were admitted to the intensive care unit, 36% underwent surgery, 12% left against medical advice (AMA), and 9% died. Infectious diagnoses included bacteremia (31%), abscess (29%), endocarditis (29%), cellulitis (20%), sepsis (10%), osteomyelitis (9%), septic arthritis (8%), pneumonia (7%), discitis (2%), meningitis/encephalitis (2%), or other (7%). Sixty-six percent had stable housing and 60% had a family physician. Fifty-four percent of patient-initiated discharges were seen in the emergency department within 30 days and 29% were readmitted. PWID are at risk for infections. Understanding their healthcare trajectory is essential to improve their care. [ABSTRACT FROM AUTHOR]

COVID-19, SEDENTARY behavior, PHYSICAL activity, HOSPITAL care, and PATIENTS' attitudes

Many patients with COVID-19 experience severe and even fatal disease. Survivors may have long-term health consequences, but data on physical activity and sedentary behaviour are scarce. Therefore, we objectively assessed physical activity (PA) patterns among post-hospitalised patients with COVID-19 and explored associations with patient characteristics, disease severity and cardiac dysfunction. We objectively assessed PA, sedentary behaviour and sleep duration for 24 h/day during 8 days at 3-6 months after COVID-19 hospitalisation. PA and sedentary time were compared across pre-defined subgroups based on patient and disease characteristics, cardiac biomarker release during hospitalisation, abnormal transthoracic echocardiogram at 3-6 months post-hospitalisation and persistence of symptoms post-discharge. PA and sedentary behaviour were assessed in 37 patients (60 ± 10 years old; 78% male). Patients spent 4.2 [3.2; 5.3] h/day light-intensity PA and 1.0 [0.8; 1.4] h/day moderate-to-vigorous intensity PA. Time spent sitting was 9.8 [8.7; 11.2] h/day, which was accumulated in 6 [5; 7] prolonged sitting bouts (≥30 min) and 41 [32; 48] short sitting bouts (<30 min). No differences in PA and sedentary behaviour were found across subgroups, but sleep duration was higher in patients with versus without persistent symptoms (9.1 vs. 8.3 h/day, p = 0.02). Taken together, high levels of sedentary time are common at 3–6 months after COVID-19 hospitalisation, whilst PA and sedentary behaviour are not impacted by patient or disease characteristics. [ABSTRACT FROM AUTHOR]

DISABILITY awareness, PEOPLE with disabilities, CRITICAL thinking, RESEARCH personnel, and STRATEGIC planning

Objective: The main objectives were to 1) search and map current disability awareness and training activities in Quebec, Canada, 2) collectively reflect on these practices, and 3) develop a five-year strategic plan.Methods: We used an integrated knowledge translation approach whereby researchers and community partners were involved in all stages. This project consisted of two sequential phases: 1) an environmental scan (web review and interview) of current practices, and 2) a reflection process with an external expert-facilitator in social transformation. Outcome results and process data are reported.Results: We identified 129 activities (71 training, 58 awareness) from 39 organizations (from 123 organizations initially invited). A wide range of characteristics were collected for each activity which allowed for the identification of gaps. The working group met seven times in one year to discuss results from phase 1 and co-create a five-year strategic plan. Main priorities are 1) the development of a methodology for measuring collective impact and 2) content synchronization of activities.Conclusion: Involvement of partners and researchers enabled a concerted and efficient approach to the development of a five-year strategic plan.Practice Implications: A transition committee led by partners will ensure implementation and sustainability of the plan across the province. [ABSTRACT FROM AUTHOR]

ANTIBODY formation, VACCINE effectiveness, HEART transplant recipients, SARS-CoV-2, and MESSENGER RNA

While several studies have observed that solid organ transplant recipients experience diminished antibody responses to SARS-CoV-2 mRNA vaccination, data specific to heart and lung transplant (HT/LT) recipients remains sparse. US adult HT and LT recipients completed their vaccine series between January 7 and April 10, 2021. Reactogencity and SARS-CoV-2 anti-spike antibody were assessed after a priming dose (D1) and booster dose (D2). Modified Poisson regression with robust variance estimator was used to evaluate associations between participant characteristics and antibody development. Of 134 heart recipients, there were 38% non-responders (D1-/D2-), 48% booster responders (D1-/D2+), and 14% priming dose responders (D1+/D2+). Of 103 lung recipients, 64% were non-responders, 27% were booster responders, and 9% were priming dose responders. Lung recipients were less likely to develop antibodies (p <.001). Priming dose antibody response was associated with younger recipient age (p =.04), transplant-to-vaccination time ≥6 years (p <.01), and lack of anti-metabolite maintenance immunosuppression (p <.001). Pain at injection site was the most commonly reported reaction (85% after D1, 76% after D2). Serious reactions were rare, the most common being fatigue (2% after D1 and 3% after D2). No serious adverse events were reported. HT and LT recipients experienced diminished antibody response following vaccination; reactogenicity was comparable to that of the general population. LT recipients may exhibit a more impaired antibody response than HT recipients. While current recommendations are to vaccinate eligible candidates and recipients, further studies characterizing the cell-mediated immune response and clinical efficacy of these vaccines in this population are needed. [ABSTRACT FROM AUTHOR]

PROFESSIONAL education, IDENTITY (Psychology), PROFESSIONAL identity, INTERPERSONAL conflict, CONFLICT management, and CURRICULUM

This article describes the development and assessment of teaching strategies to enhance student professional identity development by shifting the pedagogical focus from content knowledge to the practice of interpersonal and conflict resolution skills, and reflection to create awareness, observe growth, and find meaning. [ABSTRACT FROM AUTHOR]

GENDER mainstreaming and REHABILITATION

COVID-19 pandemic, MEDICAL personnel, PEOPLE with epilepsy, SOCIAL distancing, and CAREGIVER attitudes

• The COVID-19 and Epilepsy (COV-E) global surveys were launched in Brazil during the first wave of the pandemic. • People with epilepsy reported worsening seizure control, psychosocial stress, and impaired mental health. • There were difficulties in obtaining drug supplies because of canceled appointments. • Discussion of risk, including SUDEP, was infrequent even before the pandemic. • The surveys remain open to enable new participants to enter data providing insights as the pandemic evolves. The COVID-19 pandemic has had an unprecedented impact on people and healthcare services. The disruption to chronic illnesses, such as epilepsy, may relate to several factors ranging from direct infection to secondary effects from healthcare reorganization and social distancing measures. As part of the COVID-19 and Epilepsy (COV-E) global study, we ascertained the effects of COVID-19 on people with epilepsy in Brazil, based on their perspectives and those of their caregivers. We also evaluated the impact of COVID-19 on the care delivered to people with epilepsy by healthcare workers. We designed separate online surveys for people with epilepsy and their caregivers. A further survey for healthcare workers contained additional assessments of changes to working patterns, productivity, and concerns for those with epilepsy under their care. The Brazilian arm of COV-E initially collected data from May to November 2020 during the country's first wave. We also examined national data to identify the Brazilian states with the highest COVID-19 incidence and related mortality. Lastly, we applied this geographic grouping to our data to explore whether local disease burden played a direct role in difficulties faced by people with epilepsy. Two hundred and forty-one people returned the survey, 20% were individuals with epilepsy (n = 48); 22% were caregivers (n = 53), and 58% were healthcare workers (n = 140). Just under half (43%) of people with epilepsy reported health changes during the pandemic, including worsening seizure control, with specific issues related to stress and impaired mental health. Of respondents prescribed antiseizure medication, 11% reported difficulty taking medication on time due to problems acquiring prescriptions and delayed or canceled medical appointments. Only a small proportion of respondents reported discussing significant epilepsy-related risks in the previous 12 months. Analysis of national COVID-19 data showed a higher disease burden in the states of Sao Paulo and Rio de Janeiro compared to Brazil as a whole. There were, however, no geographic differences observed in survey responses despite variability in the incidence of COVID-19. Our findings suggest that Brazilians with epilepsy have been adversely affected by COVID-19 by factors beyond infection or mortality. Mental health issues and the importance of optimal communication are critical during these difficult times. Healthcare services need to find nuanced approaches and learn from shared international experiences to provide optimal care for people with epilepsy as the direct burden of COVID-19 improves in some countries. In contrast, others face resurgent waves of the pandemic. [ABSTRACT FROM AUTHOR]

GENETIC variation, REWARD (Psychology), and BRAIN imaging

PATIENT advocacy, EMPATHY, INTERVIEWING, INTERNSHIP programs, UNDERGRADUATES, UNIVERSITIES & colleges, NURSING students, STUDENT attitudes, THEMATIC analysis, and BULLYING

The two aims of this study were, first, to explore nursing students' experiences and perspectives of reporting poor care and second, examine the process by which they raised concerns. The nursing literature is replete with studies which explore nursing students' experiences of clinical placement. However only a small number explore students experiences of challenging poor care and how this is enacted in the practice setting. Fourteen nursing students from undergraduate pre-registration nursing programs across three universities, two in the United Kingdom (UK) and one in Australia. This paper reports findings from narrative interviews about students' clinical experiences of reporting poor care. Data were audio recorded, transcribed verbatim and analyzed using a constant comparison approach. Emerging themes were identified, discussed and verified by the researchers. Four montages from the narratives highlight the overarching themes: bullying, patient advocacy, lack of empathy and poor care. They demonstrate how, driven by an ethical imperative, students speak up when they witness poor care despite the difficulties of doing so: in some cases, the students in this study were prepared to continue speaking out even when initial concerns were dismissed. Both practice and university teams have a responsibility to support students' development as ethical and courageous practitioners, able to recognize when care falls below an acceptable standard. • This paper highlights the vital role that students play in highlighting poor nursing care practices. • Nursing students are capable of reporting poor nursing care even when it might come at a cost to themselves. • Clinicians and academics must support students to challenge poor nursing care practices. [ABSTRACT FROM AUTHOR]

COVID-19, TRANSPLANTATION of organs, tissues, etc., COVID-19 pandemic, SARS-CoV-2, and MEDICAL research

Immunosuppression and comorbidities might place solid organ transplant (SOT) recipients at higher risk from COVID‐19, as suggested by recent case series. We compared 45 SOT vs. 2427 non‐SOT patients who were admitted with COVID‐19 to our health‐care system (March 1, 2020 ‐ August 21, 2020), evaluating hospital length‐of‐stay and inpatient mortality using competing‐risks regression. We compared trajectories of WHO COVID‐19 severity scale using mixed‐effects ordinal logistic regression, adjusting for severity score at admission. SOT and non‐SOT patients had comparable age, sex, and race, but SOT recipients were more likely to have diabetes (60% vs. 34%, p <.001), hypertension (69% vs. 44%, p =.001), HIV (7% vs. 1.4%, p =.024), and peripheral vascular disorders (19% vs. 8%, p =.018). There were no statistically significant differences between SOT and non‐SOT in maximum illness severity score (p =.13), length‐of‐stay (sHR: 0.91.11.4, p =.5), or mortality (sHR: 0.10.41.6, p =.19), although the severity score on admission was slightly lower for SOT (median [IQR] 3 [3, 4]) than for non‐SOT (median [IQR] 4 [3–4]) (p =.042) Despite a higher risk profile, SOT recipients had a faster decline in disease severity over time (OR = 0.760.810.86, p <.001) compared with non‐SOT patients. These findings have implications for transplant decision‐making during the COVID‐19 pandemic, and insights about the impact of SARS‐CoV‐2 on immunosuppressed patients. [ABSTRACT FROM AUTHOR]

COVID-19, MEDICAL research, COVID-19 treatment, VIRUS diseases, and COMMUNICABLE diseases

Keywords: clinical research/practice; infection and infectious agents; infection and infectious agents - viral; infectious disease EN clinical research/practice infection and infectious agents infection and infectious agents - viral infectious disease 2306 2306 1 06/07/21 20210601 NES 210601 I To the Editor: i We thank Drs. The 45 SOT recipients included 28 kidney, six liver, two liver/kidney, five lung, three heart, and one composite tissue allograft recipient. Outcomes of COVID-19 in hospitalized solid organ transplant recipients compared to a matched cohort of non-transplant patients at a national healthcare system in the United States. [Extracted from the article]

DROWSINESS, ALZHEIMER'S disease, GENOME-wide association studies, SLEEP, RESEARCH, SEQUENCE analysis, RESEARCH methodology, MEDICAL cooperation, EVALUATION research, COMPARATIVE studies, and RESEARCH funding

Background: It is established that Alzheimer's disease (AD) patients experience sleep disruption. However, it remains unknown whether disruption in the quantity, quality or timing of sleep is a risk factor for the onset of AD.Methods: We used the largest published genome-wide association studies of self-reported and accelerometer-measured sleep traits (chronotype, duration, fragmentation, insomnia, daytime napping and daytime sleepiness), and AD. Mendelian randomization (MR) was used to estimate the causal effect of self-reported and accelerometer-measured sleep parameters on AD risk.Results: Overall, there was little evidence to support a causal effect of sleep traits on AD risk. There was some suggestive evidence that self-reported daytime napping was associated with lower AD risk [odds ratio (OR): 0.70, 95% confidence interval (CI): 0.50-0.99). Some other sleep traits (accelerometer-measured 'eveningness' and sleep duration, and self-reported daytime sleepiness) had ORs of a similar magnitude to daytime napping, but were less precisely estimated.Conclusions: Overall, we found very limited evidence to support a causal effect of sleep traits on AD risk. Our findings provide tentative evidence that daytime napping may reduce AD risk. Given that this is the first MR study of multiple self-report and objective sleep traits on AD risk, findings should be replicated using independent samples when such data become available. [ABSTRACT FROM AUTHOR]

ANTIBODY formation, VIRAL vaccines, COVID-19 pandemic, IMMUNE response, TRANSPLANTATION of organs, tissues, etc., MESSENGER RNA, and VACCINATION

This follow-up study measures the antibody response following the second dose of SARS-CoV-2 mRNA vaccine in recipients of solid organ transplants. [ABSTRACT FROM AUTHOR]

ANTIBODY formation, VACCINES, MESSENGER RNA, COVID-19, IMMUNOCOMPROMISED patients, and TRANSPLANTATION of organs, tissues, etc.

This study quantifies antispike protein antibody responses to first-dose messenger RNA (mRNA) COVID-19 vaccines in solid organ transplant recipients to better understand the immunogenicity of the vaccines in immunocompromised individuals. [ABSTRACT FROM AUTHOR]

COVID-19 pandemic, LIVER transplantation, COVID-19, MEDICAL care, and PANDEMICS

COVID‐19 has profoundly affected the American health care system; its effect on the liver transplant (LT) waitlist based on COVID‐19 incidence has not been characterized. Using SRTR data, we compared observed LT waitlist registrations, waitlist mortality, deceased donor LTs (DDLT), and living donor LTs (LDLT) 3/15/2020‐8/31/2020 to expected values based on historical trends 1/2016‐1/2020, stratified by statewide COVID‐19 incidence. Overall, from 3/15 to 4/30, new listings were 11% fewer than expected (IRR = 0.84 0.890.93), LDLTs were 49% fewer (IRR = 0.37 0.510.72), and DDLTs were 9% fewer (IRR = 0.85 0.910.97). In May, new listings were 21% fewer (IRR = 0.74 0.790.84), LDLTs were 42% fewer (IRR = 0.39 0.580.85) and DDLTs were 13% more (IRR = 1.07 1.151.23). Centers in states with the highest incidence 3/15‐4/30 had 59% more waitlist deaths (IRR = 1.09 1.592.32) and 34% fewer DDLTs (IRR = 0.50 0.660.86). By August, waitlist outcomes were occurring at expected rates, except for DDLT (13% more across all incidences). While the early COVID‐affected states endured major transplant practice changes, later in the pandemic the newly COVID‐affected areas were not impacted to the same extent. These results speak to the adaptability of the transplant community in addressing the pandemic and applying new knowledge to patient care. This registry‐based study of liver transplantation in the United States describes the substantial impact of the COVID‐19 pandemic on waitlist events over time and highlights the resiliency of the transplant community. [ABSTRACT FROM AUTHOR]

BIOSIMILARS, DRUG efficacy, PRODUCT safety, PRODUCT reviews, and INFORMATION sharing

The World Health Organization (WHO) issued guidelines for the regulatory evaluation of biosimilars in 2009 and has provided considerable effort toward helping member states implement the evaluation principles in the guidelines into their regulatory practices. Despite this effort, a recent WHO survey (conducted in 2019–2020) has revealed four main remaining challenges: unavailable/insufficient reference products in the country; lack of resources; problems with the quality of some biosimilars (and even more with noninnovator products); and difficulties with the practice of interchangeability and naming of biosimilars. The following have been identified as opportunities/solutions for regulatory authorities to deal with the existing challenges: (1) exchange of information on products with other regulatory authorities and accepting foreign licensed and sourced reference products, hence avoiding conducting unnecessary (duplicate) bridging studies; (2) use of a "reliance" concept and/or joint review for the assessment and approval of biosimilars; (3) review and reassessment of the products already approved before the establishment of a regulatory framework for biosimilar approval; and (4) setting appropriate regulatory oversight for good pharmacovigilance, which is essential for the identification of problems with products and establishing the safety and efficacy of interchangeability of biosimilars. [ABSTRACT FROM AUTHOR]

SOFT contact lenses, CONTACT lenses, ALLERGIC conjunctivitis, BLEPHARITIS, EYE diseases, MEIBOMIAN glands, DIAGNOSIS, DISEASE complications, OPTOMETRY, DRY eye syndromes, CORNEA diseases, CONJUNCTIVA, and TEARS (Body fluid)

Contact lens-related complications are common, affecting around one third of wearers, although most are mild and easily managed. Contact lenses have well-defined anatomical and physiological effects on the ocular surface and can result in other consequences due to the presence of a biologically active material. A contact lens interacts with the tear film, ocular surface, skin, endogenous and environmental microorganisms, components of care solutions and other antigens which may result in disease specific to contact lens wear, such as metabolic or hypersensitivity disorders. Contact lens wear may also modify the epidemiology or pathophysiology of recognised conditions, such as papillary conjunctivitis or microbial keratitis. Wearers may also present with intercurrent disease, meaning concomitant or pre-existing conditions unrelated to contact lens wear, such as allergic eye disease or blepharitis, which may complicate the diagnosis and management of contact lens-related disease. Complications can be grouped into corneal infection (microbial keratitis), corneal inflammation (sterile keratitis), metabolic conditions (epithelial: microcysts, vacuoles, bullae, tight lens syndrome, epithelial oedema; stromal: superficial and deep neovascularisation, stromal oedema [striae/folds], endothelial: blebs, polymegethism/ pleomorphism), mechanical (corneal abrasion, corneal erosion, lens binding, warpage/refractive error changes; superior epithelial arcuate lesion, mucin balls, conjunctival epithelial flaps, ptosis, discomfort), toxic and allergic disorders (papillary conjunctivitis, solution-induced corneal staining, incomplete neutralisation of peroxide, Limbal Stem Cell Deficiency), tear resurfacing disorders/dry eye (contact lens-induced dry eye, Meibomian gland dysfunction, lid wiper epitheliopathy, lid parallel conjunctival folds, inferior closure stain, 3 and 9 o'clock stain, dellen, dimple veil) or contact lens discomfort. This report summarises the best available evidence for the classification, epidemiology, pathophysiology, management and prevention of contact lens-related complications in addition to presenting strategies for optimising contact lens wear. [ABSTRACT FROM AUTHOR]

COVID-19 pandemic, PEOPLE with epilepsy, AT-risk people, EPILEPSY, MEDICAL care, and COVID-19

• The COVID-19 and Epilepsy (COV-E) global surveys were launched in May 2020. • UK respondents (n = 463) report changes in seizure frequency, mental health, and sleep. • Discussion of risk, including of SUDEP, was infrequent even before the pandemic. • COVID-19 is having far-reaching consequences on people with epilepsy. • Our study exemplifies the importance of delivering optimal care to mitigate risk. The COVID-19 pandemic has caused global anguish unparalleled in recent times. As cases rise, increased pressure on health services, combined with severe disruption to people's everyday lives, can adversely affect individuals living with chronic illnesses, including people with epilepsy. Stressors related to disruption to healthcare, finances, mental well-being, relationships, schooling, physical activity, and increased isolation could increase seizures and impair epilepsy self-management. We aim to understand the impact that COVID-19 has had on the health and well-being of people with epilepsy focusing on exposure to increased risk of seizures, associated comorbidity, and mortality. We designed two online surveys with one addressing people with epilepsy directly and the second for caregivers to report on behalf of a person with epilepsy. The survey is ongoing and has yielded 463 UK-based responses by the end of September 2020. Forty percent of respondents reported health changes during the pandemic (n = 185). Respondents cited a change in seizures (19%, n = 88), mental health difficulties (34%, n = 161), and sleep disruption (26%, n = 121) as the main reasons. Thirteen percent found it difficult to take medication on time. A third had difficulty accessing medical services (n = 154), with 8% having had an appointment canceled (n = 39). Only a small proportion reported having had discussions about epilepsy-related risks, such as safety precautions (16%, n = 74); mental health (29%, n = 134); sleep (30%, n = 140); and Sudden Unexpected Death in Epilepsy (SUDEP; 15%, n = 69) in the previous 12 months. These findings suggest that people with epilepsy are currently experiencing health changes, coupled with inadequate access to services. Also, there seems to be a history of poor risk communication in the months preceding the pandemic. As the UK witnesses a second COVID-19 wave, those involved in healthcare delivery must ensure optimal care is provided for people with chronic conditions, such as epilepsy, to ensure that avoidable morbidity and mortality is prevented during the pandemic, and beyond. [ABSTRACT FROM AUTHOR]

KIDNEY transplantation, URINARY tract infections, NOSOLOGY, and DIAGNOSIS

Infections remain a major threat to successful kidney transplantation (KT). To characterize the landscape and impact of post‐KT infections in the modern era, we used United States Renal Data System (USRDS) data linked to the Scientific Registry of Transplant Recipients (SRTR) to study 141 661 Medicare‐primary kidney transplant recipients from January 1, 1999 to December 31, 2014. Infection diagnoses were ascertained by International Classification of Diseases, Ninth Revision (ICD‐9) codes. The cumulative incidence of a post‐KT infection was 36.9% at 3 months, 53.7% at 1 year, and 78.0% at 5 years. The most common infections were urinary tract infection (UTI; 46.8%) and pneumonia (28.2%). Five‐year mortality for kidney transplant recipients who developed an infection was 24.9% vs 7.9% for those who did not, and 5‐year death‐censored graft failure (DCGF) was 20.6% vs 10.1% (P <.001). This translated to a 2.22‐fold higher mortality risk (adjusted hazard ratio [aHR]: 2.152.222.29, P <.001) and 1.92‐fold higher DCGF risk (aHR: 1.841.911.98, P <.001) for kidney transplant recipients who developed an infection, although the magnitude of this higher risk varied across infection types (for example, 3.11‐fold higher mortality risk for sepsis vs 1.62‐fold for a UTI). Post‐KT infections are common and substantially impact mortality and DCGF, even in the modern era. Kidney transplant recipients at high risk for infections might benefit from enhanced surveillance or follow‐up to mitigate these risks. This national study of kidney transplant recipients shows that infections are common, are associated with approximately twofold increased risk of both mortality and death‐censored graft failure, and thus are still an important driver of posttransplant outcomes. [ABSTRACT FROM AUTHOR]

COVID-19, SOCIAL responsibility, LIBRARY school students, and STAY-at-home orders

Population of the study The online intervention classes focused mainly on Library and Information Science Students from across universities in Africa. Among the 100 level students, few of the excerpts of the responses are presented below: I did not have any experience in Library and Information Science as some of my classmates do. Among the 300 Level Students, participants discussed more about the insight they have on careers they could pursue in the field of Library and Information Science. All the students are studying Library and Information Science in their respective universities. [Extracted from the article]

KIDNEY transplantation, ORGAN donors, PEDIATRICS, KIDNEY failure, TRANSPLANTATION of organs, tissues, etc., STATISTICAL significance, DESCRIPTIVE statistics, and COVID-19 pandemic

Background: In March 2020, COVID-19 infections began to rise exponentially in the USA, placing substantial burden on the healthcare system. As a result, there was a rapid change in transplant practices and policies, with cessation of most procedures. Our goal was to understand changes to pediatric kidney transplantation (KT) at the national level during the COVID-19 epidemic. Methods: Using SRTR data, we examined changes in pediatric waitlist registration, waitlist removal or inactivation, and deceased donor and living donor (DDKT/LDKT) events during the start of the disease transmission in the USA compared with the same time the previous year. Results: We saw an initial decrease in DDKT and LDKT by 47% and 82% compared with expected events and then a continual increase, with numbers reaching expected prepandemic levels by May 2020. In the early phase of the pandemic, waitlist inactivation and removals due to death or deteriorating condition rose above expected values by 152% and 189%, respectively. There was a statistically significant decrease in new waitlist additions (IRR 0.49 0.65 0.85) and LDKT (IRR 0.17 0.38 0.84) in states with high vs. low COVID activity. Transplant recipients during the pandemic were more likely to have received a DDKT, but had similar calculated panel–reactive antibody (cPRA) values, waitlist time, and cause of kidney failure as before the pandemic. Conclusions: The COVID-19 pandemic initially reduced access to kidney transplantation among pediatric patients in the USA but has not had a sustained effect. [ABSTRACT FROM AUTHOR]

Background: Vascular dementia (VaD) is often difficult to distinguish from Alzheimer's disease (AD).[O'Brien_2015] Areas of cognitive/clinical decline due to cerebrovascular diseases depend on the frequency and location of the lesions, and may overlap with those found in AD.[Suri_2014] Moreover, AD and cerebrovascular diseases frequently occur simultaneously, leading to heterogeneous 'mixed dementia (MixD)'.[Wang_2012][Langa_2004] It is unclear whether the presence of both neurodegenerative and cerebrovascular pathologies further aggravates dementia‐related imaging abnormalities. We investigated whether the lobar distribution of white matter hyperintensities (WMHs) on MRI differed among AD, VaD and MixD. Method: N=17 participants (cross‐sectional; subtypes:7 MixD/5 Subcortical VaD/5 AD; Sex: 11M/6F; Age: 75±8yrs) were scanned on a 3T Philips Achieva. T1‐weighted MP‐RAGE images were processed with Freesurfer 6.0. Areas of WMHs were segmented on Fluid Attenuated Inversion Recovery (3D‐FLAIR) images using a combination of intensity thresholding and manual correction. Left and right frontal, temporal, occipital and parietal lobes plus basal ganglia volumes were constructed using the Freesurfer segmentation outputs. Individual WMH masks were transformed to their respective T1‐weighted spaces, and the ratios of WMH volumes to different lobar volumes were calculated. Result: Average WMH volumes were (mean±SD) AD: 5191±4693mm3, MixD: 34680±17059mm3 (sig. greater than AD), SVaD: 20896±14920mm3 (n.s. from MixD or AD). We used a linear model to predict the ratios of WMH to lobar volumes from the diagnosis subtypes, adjusting for age and sex. A significant diagnosis‐subtype effect was found in both the left and right frontal lobes. (p=0.012 and 0.045, respectively). In the left frontal lobe, the proportion of WMHs was significantly greater in the MixD subgroup compared to the AD (p=0.0045) or the VaD (p=0.026) subtypes. In the right frontal lobe, the proportion was greater in the MixD subtype compared to the AD (p=0.018) but not compared to VaD (p=0.074) subtype. AD vs. VaD were not significantly different in either sides (p=0.5). Conclusion: The MixD subtype of our pilot study cohort was characterized by a significantly greater presence of WMHs in the frontal lobar areas. Future studies are warranted to investigate the characteristics of underlying tissue abnormalities that could be specific to the diagnosis subtypes. [ABSTRACT FROM AUTHOR]

Background: Alzheimer's disease (AD) with cerebrovascular disease is known as 'mixed' dementia (MixD).[Wang_2012][Langa_2004] MixD can have heterogeneous clinical/imaging presentations. This makes it difficult to distinguish MixD from AD or vascular dementia (VaD) using structural markers such as atrophy or white matter hyperintensity (WMH) volumes. [Suri_2014] We explored whether WM tissue properties on MRI, represented by R2* and diffusion‐tensor (DTI) images, could distinguish MixD from AD or VaD. Method: N=17 participants (cross‐sectional; 7 MixD/5 Subcortical VaD/5 AD; Sex: 11M/6F; Age: 75±8yrs) were scanned on a 3T Philips Achieva. WMHs were segmented on 3D‐Fluid Attenuated Inversion Recovery images. T1‐weighted MP‐RAGE images were segmented into the grey/white‐matters using SPM12. These outputs were combined to construct WMH and normal‐appearing WM (NAWM) masks. DTI images were processed using FSL. R2* images were computed using in‐house software. For each participant, the average R2*, fractional anisotropy (FA) and mean diffusivity (MDf) values were calculated within the WMH and NAWM masks. Result: Average WMH volumes were (mean±SD) AD: 5191±4693mm3, MD: 34680±17059mm3 (p<.05 compared to AD), SVaD: 20896±14920mm3 (p>.05 compared to MixD or AD). A linear model was used to predict the measured R2*, FA or MDf values from the diagnosis subtypes, adjusting for age and sex. R2* results: Pairwise t‐tests revealed significantly lower R2* values within the WMHs compared to NAWM (all subtypes p<0.0005). MixD had significantly lower WMH R2* values compared to AD (p=0.01) or VaD (p=0.02) subgroups. DTI results: Pairwise t‐tests revealed significantly higher MDf values within the WMHs compared to NAWM (all subtypes p<0.009). FA values were significantly lower within the WMHs compared to NAWM for the MixD (p=0.0002) and VaD (p=0.03) but not the AD (p=0.09) subtype. Conclusion: Our MixD cohort was characterized by potentially disrupted fiber integrity (represented by decreased FA) and increased water content (represented by lower R2*) within the WMH areas. These abnormalities likely represent etiologies caused by both neurodegenerative and cerebrovascular factors. Future studies that incorporate measures of neurodegeneration or neuroinflammation, such as biofluid markers, may help to further characterize WM tissue abnormalities in MixD compared to those found in 'pure' AD or VaD. [ABSTRACT FROM AUTHOR]

Background: Increased burden of white‐matter hyperintensities (WMHs) on MRI is common among different types of dementia. WMHs can be caused by various underlying etiologies and are non‐specific markers of tissue abnormality. Therefore, global measures such as WMH burdens may not distinguish between degrees of cognitive impairment. We explored the associations between lobar‐specific WMH volumes and cognitive dysfunction across different dementia subtypes. Method: N=57 participants (7 Alzheimer's disease [AD]/5 subcortical vascular dementia [SVaD]/7 mixed dementia [MixD]/38 vascular cognitive impairment [VCI]; Sex:34M/23F; Age:73±8yrs; pooled from three independent studies) were scanned on 3T MRI. WMHs were segmented on 3D‐FLAIR (MixD/AD/SVaD) or dual‐echo PD/T2‐weighted (VCI) images. T1‐weighted images were processed with Freesurfer 6.0. Left and right frontal, temporal, occipital and parietal lobes plus basal ganglia volumes were constructed using the Freesurfer segmentation outputs. We calculated the proportion of WMH burden within each lobe, i.e. the ratio of lobar WMH volume over the lobar volume. The Montreal Cognitive Assessment (MoCA) was used as a measure of cognitive function. We used a general linear model to determine the association between the WMH/lobar volume ratios and the MoCA scores. Covariates included age, sex, and presence of AD‐related (yes for MixD/AD, no for rest) and vascular‐related conditions (yes for SVaD/VCI/MixD, no for AD). Additionally, we assessed the relationship between the MoCA scores and the ratio of total WMH burden over the whole‐brain parenchymal volume. Result: The model yielded a significant association between the MoCA scores and WMH/lobar ratios within the left (p=0.031) and the right (p=0.035) frontal lobes, with higher ratios predicting lower MoCA scores. The effect was not significant within the temporal, occipital, parietal lobes and the basal ganglia. The effect was insignificant at the whole‐brain level (p=0.08). Conclusion: We found a significant association between the frontal lobe WMH burden and the MoCA scores, especially sensitive to frontal executive functions. This suggests that region‐specific assessments of WMHs may provide improved imaging‐cognitive correlations over the global WMH burden. Future studies with more consistent imaging protocols and broader cognitive/clinical assessments are warranted to further characterize the relationship between WMHs and cognitive impairment. [ABSTRACT FROM AUTHOR]

COVID-19, TRANSPLANTATION of organs, tissues, etc., SARS-CoV-2, CRITICALLY ill, and KIDNEYS

In our first survey of transplant centers in March 2020, >75% of kidney and liver programs were either suspended or operating under restrictions. To safely resume transplantation, we must understand the evolving impact of COVID‐19 on transplant recipients and center‐level practices. We therefore conducted a six‐week follow‐up survey May 7‐15, 2020, and linked responses to the COVID‐19 incidence map, with a response rate of 84%. Suspension of live donor transplantation decreased from 72% in March to 30% in May for kidneys and from 68% to 52% for livers. Restrictions/suspension of deceased donor transplantation decreased from 84% to 58% for kidneys and from 73% to 42% for livers. Resuming transplantation at normal capacity was envisioned by 83% of programs by August 2020. Exclusively using local recovery teams for deceased donor procurement was reported by 28%. Respondents reported caring for a total of 1166 COVID‐19–positive transplant recipients; 25% were critically ill. Telemedicine challenges were reported by 81%. There was a lack of consensus regarding management of potential living donors or candidates with SARS‐CoV‐2. Our findings demonstrate persistent heterogeneity in center‐level response to COVID‐19 even as transplant activity resumes, making ongoing national data collection and real‐time analysis critical to inform best practices. [ABSTRACT FROM AUTHOR]