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Background: Nervous system post-acute sequelae of COVID-19 (NS-PASC) include cognitive and mental health symptoms. To further define these, we applied a Research Domain Criteria (RDoC) approach to examine motor, positive valence (PV) and negative valence (NV) systems, and social processing data in The COVID Mind Study of NS-PASC. Method(s): NS-PASC participants (>3 months after COVID-19) referred from a NeuroCOVID Clinic and non-COVID controls from New Haven, CT and Baltimore, MD completed an RDoC test battery for cognition (language, declarative and working memory, cognitive control, perception), motor, PV, NV, and social processes. To date, 3T MRI with diffusion tensor imaging was performed in 11 NS-PASC to assess white matter integrity (global white matter fractional anisotropy [FA]) as a contributor to alterations identified on the RDoC tests. Analysis of Covariance examined group differences after adjusting for sex, race, ethnicity, age, and years of education. Result(s): 25 NS-PASC participants (age 43.4+/-11.3 yrs, 76% female, 402 days after COVID-19 symptom onset) and 29 controls (age 46.2.6+/-13.1 yrs, 66% female) completed the battery. Controls were more racially diverse and less educated than NS-PASC (43% vs. 12% Black, p=0.005;14.5 vs. 16.1 yrs of education, p< 0.05). Means and statistics for RDoC between NS-PASC and controls are shown in Table. NS-PASC performed worse in language, verbal working and declarative memory, and perception and reported greater cognitive control difficulties (e.g., behavioral inhibition, set shifting) without issues on performance-based metrics (Stroop, Trail Making Test-Part B), and had slower motor function. NS-PASC reported more NV issues including greater symptoms of depression, rumination in response to depressive mood, apathy, childhood trauma, anxiety, and perceived stress. There were no differences in PV and social processing. In a subset of NS-PASC participants who underwent MRI, there was a dynamic range of FA values with a mean of 0.509 (IQR 0.481 - 0.536). Conclusion(s): Our findings extend previous PASC studies characterizing cognitive and mental health alterations, indicating that additional RDoC assessments warrant focus, including alterations in motor and the negative valence system. In future analyses, we will examine white matter integrity as a pathophysiologic contributor to these RDoC systems.
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Background: Decreased hospital admissions for acute exacerbations of COPD (AECOPD) have been reported during the COVID-19 pandemic, but not in relation to admissions for pneumonia, influenza and COVID-19 admissions. Aim(s): To study hospital admission rate for AECOPD, pneumonia, influenza and COVID-19, respectively, in COPD patients during the pandemic compared with a prepandemic period. Method(s): Anonymized data on hospital admissions of patients with COPD and a primary diagnosis code for AECOPD, pneumonia, influenza or COVID-19, were obtained from the hospital patient admission register. The pandemic period (February 2020 - May 2021) was compared to a period prior to the pandemic (June 2017 - January 2020). Monthly admission rates were compared using ANCOVA statistics, controlling for admission month. Result(s): Monthly mean admission rates for AECOPD were 51 (95%CI 45-57) vs. 79 (95%CI 74-83;p<0.001), pneumonia 12 (95%CI 9-15) vs. 27 (95%CI 25-29;p<0.001) and influenza 0 (95%CI -2-1) vs. 3 (95%CI 2-4;p<0.001). Reduced AECOPD rates coincided with rising COVID-19 admissions (Figure 1). Total mean admission rates, including COVID-19, remained reduced, 82 (95%CI 75-90) vs. 109 (95%CI 104-114;p<0.001), across the pandemic period. Conclusion(s): The overall burden of hospital admissions among COPD patients for AECOPD, pneumonia, influenza and COVID-19 was significantly reduced during the pandemic, despite the rise in COVID-19 admissions. (Figure Presented).
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Introduction: Immunohematology laboratory in Legnano's hospital runs on DxH900 analyzer (Beckman Coulter Inc.) Monocyte Distribution Width (MDW), a CE IVD marked and FDA cleared early sepsis indicator for Emergency Department (ED) and COVID-19 adult patients;it is available since 2018, and quite well represented in literature with 31 PubMed citations. Legnano adopted cut-off: 20 (K2 EDTA). Method(s): From January 2020 to July 2021 we collected MDW data requested from ED patients in Legnano's hospital, adopting sepsis-3 criteria. Based on clinical patient folders, three group were analyzed: controls, sepsis, and septic shock. Data collections include age, sex, White Blood Cells, MDW, C-reactive protein, procalcitonin, lactate, saturation, antibiotic treatment, hemocultures, COVID-19 and department. Moreover, Covariance Analysis blending ANOVA and regression, was conducted modeling MDW in relationship with age and sex. Result(s): 129 controls (C): 51 females, 76 males, two unknown;91 sepsis (S): 32 females, 58 males, one unknown;23 septic shock (K): 10 females, 12 males, one unknown. All groups rejected Normal Distribution with D'Agostino-Pearson test. MDW C: minimum 14.480, maximum 27.860, median 17.030 (IC 95% 16.805-17.418), standard deviation 2.260. MDW S: minimum 20.240, maximum 51.390, median 25.72 (IC 95% 24.297-27.238), standard deviation 6.08. MDW K: minimum 22.07, maximum 63.98, median 29.27 (IC 95% 24.168-32.911), standard deviation 9.424. In C eight patients had MDW from 21.1 to 22.5 and five from 24.4 to 27.8;five had COVID-19, four pneumonia and two respiratory failure. In S 75 Hemocultures were available, 37 positive and 38 negative;in K 11 positive and nine negative;in control group one positive and four negative. In S e K group, all patients except one with negative hemocultures had antibiotic treatment. MDW median value in sepsis group with negative Hemocultures was 23.94 (IC 95% 22.675-26.6);in the same group with positive Hemocultures MDW median value was 27.55 (IC 95% 25.695-28.598). ANCOVA in all groups did not outline any significant difference between both age and sex, in line with MDW Instruction for use. Conclusion(s): In this study MDW demonstrated correlation with the severity of disease.
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Randomized controlled trials with a pretest-posttest design frequently yield ordered categorical outcome data. Focusing on the estimation of the win probability that a treated participant would have a better score than (or win over) a control participant, we developed methods for analysis and sample size planning for such trials. We exploited the analysis of covariance framework with the dependent variable being individual participants' win fractions at posttest and the covariate being the win fractions at pretest. The win fractions were obtained using the mid-ranks of the ordinal data. Simulation evaluation based on a recent randomized trial on COVID-19 suggests that the methods perform very well. A sample SAS code for data analysis is presented.
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COVID-19 , Humans , Randomized Controlled Trials as Topic , Computer Simulation , Sample Size , ProbabilityABSTRACT
INTRODUCTION: Admissions to Pediatric Intensive Care Units (PICUs) for respiratory illnesses, particularly RSV and Influenza (INF), have decreased during the COVID-19 pandemic. The differences in trends for RSV and INF admissions to PICUs across different regions in the U.S. are unknown. Changes in these trends before (2014-19), during (2019-20), and towards the end of the pandemic (2021- 22), and utilization patterns across regions have not been evaluated. This analysis aimed at addressing these questions. METHOD(S): 874,066 USA PICU cases from the Virtual Pediatric Systems database (myvps.org), from Q1-2014 to Q2-2022, were used to study RSV and INF in patients < 18 years. The geographic regions according to U.S. Census definition included Mid-West (MW), Northeast (NE), South (S), and West (W). RSV and INF were defined by ICD-9 and ICD-10 codes. After removing low-risk patients (PRISM III POD < 0.004) the cohort size was 492,642. Segmented regression analysis (Muggeo 2016) was used to fit the trends in yearly rates for RSV and INF. Least-squares linear fits were applied to data segments before and after breakpoints (change in slope) to determine the correlation coefficients of each segment. Fisher's Z-transform was used to investigate significant differences between segments before and after their respective breakpoints. Utilization amongst regions was done by ANCOVA analysis, and Bonferroni corrected p-values for the most prevalent procedures in the cohorts. RESULT(S): All regions showed an increase in RSV and INF between 2014-19, but decreasing during 2020-21. In 2021- 22 all regions showed an increase trend in INF, but RSV increased only in MW and S compared to NE and W. Further analysis using RSV segmented regression revealed: MW, NE, and W breakpoints (positive to negative) in: 2018, 2019, and 2019, respectively. For INF, breakpoints for MW, NE, S, and W were detected in: 2019, 2020, 2019, and 2019, respectively. CPAP use in W was greater than S (p< 0.02). All other procedure comparisons had p-values>0.05. CONCLUSION(S): RSV and INF increased in all regions during pre-COVID. RSV and INF decreased in all regions during COVID. INF increased in all the regions towards the end of pandemic. RSV increased in MW and S near the end of the pandemic. Differences in use of CPAP for RSV were found between W and S.
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Background: The COVID-19 pandemic has led to the suspension of community-based dementia services worldwide, where evidence-based interventions for dementia, like Cognitive Stimulation Therapy (CST), were delivered. Treatment access is paramount during the pandemic and beyond for people with dementia to maintain functioning and well-being. This study aimed to evaluate the feasibility and acceptability of a virtual, 14-session program of Individual Cognitive Stimulation Therapy (V-iCST) in the UK. Method(s): A single-blind feasibility randomized controlled trial (RCT) was conducted in the UK. Thirty-four people with mild to moderate dementia were recruited from dementia organizations and networks. Seventeen were randomly assigned to receive V-iCST (14, 45-min sessions) and 17 to treatment as usual (TAU) over seven weeks. Feasibility and acceptability data, for example, recruitment, attrition, attendance, adverse effects, and fidelity, were collected. Outcome measures on cognitive function, quality of life (QoL), mood, and communication were collected pre and post-test. Analysis of covariance was used to compare changes in V-iCST and TAU. Result(s): We have successfully completed recruitment. Results on feasibility, acceptability, and preliminary efficacy will be available at the conference. Conclusion(s): We hypothesize that V-iCST is feasible and acceptable and will have positive effects on cognitive, QoL, mood, and communication. Findings will be available at the conference. Copyright © 2022 the Alzheimer's Association.
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Background: Immunosuppressive therapies may impact immune response to COVID-19 vaccines in persons with multiple sclerosis (pwMS). Accordingly, effects of vaccination in pwMS treated with disease-modifying therapies (DMTs) need further elucidation. Aim(s): To investigate COVID-19 BNT162b2 vaccine effect concerning antibody seroconversion, T cells-associated cytokines production and immunophenotype assessment in pwMS under three different DMTs: cladribine, fingolimod, ocrelizumab. Method(s): Enzyme immunoassay test was used for anti-spike IgG detection in 98 DMTs-treated pwMS completing first vaccination cycle. In a subset of patients (n=47), serum T cells-associated cytokines (GrB, IFN-gamma and TNF-alpha) were quantified using an automatic ELISA (ELLA) and blood immunophenotype was assessed by flow cytometry. ANCOVA followed by post hoc tukey's test was used to compare anti-spike IgG response in the different DMTs, Student's paired t-test was used to evaluate differences between pre- and post-vaccination in pairwise samples and Pearson's correlation was applied to evaluate association between spike-specific IgG antibody titer and lymphocytes count. Result(s): More pwMS treated with ocrelizumab (63%) lacked anti-spike IgG compared to patients treated with cladribine (14%) and fingolimod (20%) (p<0.001). When present, the anti-spike IgG titer in the ocrelizumab group was lower than in cladribine- (p<0.001) and in fingolimod-treated pwMS (p=0.003). No significant differences in lymphocytes count and T-cell associated cytokines were observed in cladribine- and in fingolimod-treated pwMS, while in pwMS on ocrelizumab a significant increase in GrB serum levels (p=0.021) and a trend of increased CD4+ T cells count were observed after vaccination. Specifically considering non-seroconverted ocrelizumab-treated pwMS, a significant increase of GrB serum levels (p=0.008) and of CD4+ T lymphocytes count (p=0.040) was foundafter vaccination and a negative correlation was observed between anti-spike IgG production and CD4+T cells count (rho=-0.452, p=0.014). Conclusion(s): Our data confirmed differences in spike-specific antibodies among different DMTs and provided evidence of T-cell immunity preservation and activations after BNT162b2 vaccination in ocrelizumab-treated pwMS, specifically in pwMS patients lacking anti-spike IgG, suggesting a protective T-cell response that might explain why the ongoing treatment with ocrelizumab is not associated with a higher risk of COVID-19 infection.
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Aims: Following COVID-19 a substantial number of patients report persistent fatigue and insomnia. As these symptoms have overlapping features, insomnia can be easily underdiagnosed in post COVID-19 related fatigue (PCRF). The main object of this study was to determine the prevalence of insomnia in patients with PCRF and investigate their sleep characteristics. Data of PCRF patients were compared with those of patients with chronic fatigue syndrome (CFS/ME), a condition also characterized by persistent fatigue. Method(s): In this cross-sectional study insomnia severity, assessed with the Insomnia Severity Index (ISI), and prevalence of clinical insomnia (ISI score >=10), were determined in patients with PCRF (n = 114) and compared with CFS/ME patients (n = 59) using ANCOVA and logistic regression, respectively. Linear regression analyses were used to evaluate if fatigue severity, concentration problems, pain, depressive symptoms and having PCRF or CFS/ME were associated with insomnia severity. Sleep characteristics assessed with sleep diary and accelerometer were determined in patients with PCRF and compared with CFS/ME patients using ANCOVA. Result(s): In PCRF patients the mean (SD) insomnia severity was 11.46 (5.7) and prevalence of clinical insomnia was 64%. Both did not differ significantly from CFS/ME. Insomnia severity was significantly associated with depressive symptoms (beta = 0.49, p = 0.006) and higher age (beta = -0.08, p = 0.04). In PCRF the mean subjective sleep duration in h was 7.39 (1.00), sleep onset latency 0.97 (0.62) and wake after sleep onset 1.24 (0.72). The PCRF group reported a significantly shorter sleep duration than the CFS/ME group (p = 0.002), with a moderate effect size (d = 0.59). Conclusion(s): Insomnia severity and prevalence of clinical insomnia is high in PCRF. Insomnia should be assessed and if present treated with insomnia focused therapy in patients reporting post COVID-19 related chronic fatigue.
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Objective: The study aims to evaluate the impact of distance education on Pharmacy, Pharm.D and postgraduate students' satisfaction and its associated factors during COVID-19 pandemic. Method(s): A cross-sectional web-based survey was distributed online for Pharmacy, Pharm.D and postgraduate Diploma and Master Students across Jordanian universities. Expiratory factor analysis (EFA) and Cronbach's alpha were conducted to examine the validity and the internal consistency of the survey, respectively. Analysis of Covariance (ANCOVA), Chi square test and t-test were conducted to evaluate the variables associated with students' satisfaction with distance learning. Result(s): A total of 860 students completed the survey. The EFA generated a three-factor model including positive impact, negative impact and general impact. The mean scores of the factors were 2.84 (SD=1.03), 2.78 (SD=0.92) and 2.34 (SD=1.22) respectively. Several factors were associated with students' level of satisfaction with distant learning including gender, nationality, university type and field of study. Conclusion(s): Distance education had negative impact on Pharmacy and Pharm.D. students' satisfaction, which opens the doors for the necessity to improve the distance education for university students. Variables including gender, nationality, university type and field of study were associated with students' level of satisfaction. Copyright © 2022 DSR Publishers/The University of Jordan. All Rights Reserved.
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Purpose : During the COVID-19 pandemic, mask-associated dry eye (MADE) has increased worldwide possibly because the breath leaks from the top of the masks changes the ocular surface conditions. We tested the hypothesis that surgical taping of the top edge of the mask to the skin reduces the risk of ocular surface damage. Methods : We enrolled 60 volunteers (30 females, 30 males;mean age, 27.1±5.2 years) who wear face masks over 5 hours a day. We measured the fluorescein tear break-up time (FBUT), ocular surface temperature, and conjunctival blood flow before wearing masks, after wearing masks taped on the top edge, and after wearing masks without tape. We used the Ocular Surface Disease Index (OSDI) to record participants' symptoms of MADE and measured their corneal tactile and pain sensitivity using a Cochet-Bonnet esthesiometer. Results : The FBUT with masks without tape (4.4±2.4 seconds) was significantly shorter than that without masks (6.4±3.1 seconds) and with taped masks (5.8±3.2 seconds) (P<0.01 and P=0.05, respectively, Tukey HSD test). There was no significant difference in the FBUT between use of no masks and taped masks (P>0.05). The differences in the corneal and conjunctival temperatures after wearing masks without tape (0.19±0.28 and 0.13±0.28°C, respectively) were significantly higher than after wearing taped masks (0.05±0.27 and 0.06±0.24°C, respectively, P<0.01, paired t-test). The conjunctival blood flow with masks without tape was significantly higher than that of taped masks (P<0.01). Of the 60 subjects, 13 (21.7%) subjects reported MADE symptoms. In the MADE group, the OSDI (P=0.001, analysis of covariance) was significantly higher and the FBUT of masks without tape (P=0.006) was significantly shorter than in the non-MADE group. Pain sensitivity in the MADE group was significantly higher than in the non-MADE group (P<0.01), indicating that subjects in the MADE group were significantly hypersensitive to corneal pain. Conclusions : Wearing masks decreased FBUT and increased ocular surface temperature and blood flow. Taping the top edge of the mask prevented those changes. Fitting masks tightly to the nose or applying tape over the mask may reduce the MADE risk, which can be associated with ocular surface hypersensitivity.
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Background: A hyperinfammatory response compatible with features of macrophage activation syndrome (MAS) contributes to this worse outcome in patients with Coronavirus Disease 2019 (COVID-19). Glucocorticoids have become the standard of care for those requiring oxygen support or mechanical ventilation. More targeted anti-infammatory treatments with tocilizumab and anakinra have also been shown to be effective. Objectives: More studies are being awaited to clarify the features of patients who would beneft more, and we investigated the characteristics of the surviving and dead patients who received anakinra. Methods: The records of hospitalized adult patients between March 2020 and May 2021 in a tertiary referral center were evaluated. Diagnosis of COVID-19-re-lated MAS was based on the expert opinion and preliminary criteria developed by our group that patients with a score of ≥45 were accepted COVID-19-related MAS.1 Patients who received anakinra constituted the study group. Anakinra dose was determined according to the clinical and infammatory parameters;and doses varied between daily 100-300 mg SC to 400-800 mg IV. Laboratory data of surviving and died patients were comparatively analyzed by using the ANCOVA method on the relevant days (baseline, anakinra-onset day, frst response to anakinra treatment, and discharge or death). The temporal variation (drug onset day-frst response day, drug onset day-discharge, or death day) was evaluated using the ANOVA method. A 50% reduction of CRP compared to the anakinra start day was accepted as the frst response to the treatment. Results: Out of 1080 hospitalized patients, 218 (151 male, 67 female, mean age 60.0±14.1) who received anakinra were identifed. Among them, 125 (57.3%) patients were followed in the ward, 21 (9.6%) did not need oxygen treatment during the hospitalization;69 (31.6%) patients were followed at ICU, 40 of them were intubated, 30 (13.7%) died in ICU. Anakinra had been started in a mean of 4.8 days of hospitalization. Twenty had tocilizumab initially and then received anak-inra because of ongoing infammatory parameters. The majority (83.5%) received steroid treatment (79.5% methylprednisolone, 5% of dexamethasone), and 6 received one IV pulse 250 mg of methylprednisolone;36 (16.5%) were followed before September 2020 and received anakinra without steroids because of the standard of care at that period. Only CRP was different between the alive and dead patients for the baseline parameters (p=0.05). On the frst day of drug treatment, CRP and procalcitonin values were signifcantly higher in dead patients (Table 1). A 50% decrease in CRP level was achieved in 3.1 days in survivors and 4.7 days in dead patients. D-dimer (p=0.018), CRP (p=0.006), LDH (p=0.003), procalcitonin (p=0.005), creatinine kinase (p=0.001), and fbrinogen levels (p=0.05) were significantly different between the surviving and dead patients when the measurements between the frst drug administration day and response day were compared. Neu-trophil, lymphocyte count, ferritin, D-dimer, CRP, LDH, AST, procalcitonin, creati-nine kinase, and fbrinogen levels were signifcantly different between the patients when the parameters between the frst drug administration day and discharge/death day were compared. Dead patients had higher CRP values and they did not show a continuing CRP decrease with the steroids and anakinra (Figure 1). Conclusion: Retrospective analysis of 218 patients suggests that starting anakinra earlier in hospitalized patients may provide better results, and a decrease in CRP, ferritin, D-dimer values, as well as an increase in lymphocyte count, are associated with favorable outcomes. Increasing values of D-dimer and troponin during treatment are associated with worse outcomes, possibly indicating cardiovascular and thrombotic pathologies not responding to anakinra. Changes in the CRP values are found to help monitor the response to anakinra. Other infammatory pathways could be targeted in those who are not responding to appropriate doses of anakinra within 5 days.
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Background: A highly controversial question is whether or not corticosteroids should be prescribed for patients with early diffuse cutaneous systemic sclerosis (dcSSc). Although the painful and disabling features of early dcSSc (including tight itchy skin, contractures, fatigue) have an infammatory basis and are likely to respond to corticosteroids, corticosteroids are a risk factor for potentially life-threatening scleroderma renal crisis. Objectives: Our aim was to examine safety and efficacy of moderate dose prednisolone in patients with early dcSSc. Specific objectives were to evaluate whether moderate dose prednisolone reduced pain and disability, and improved skin score, and whether prednisolone was safe with particular reference to renal function Methods: PRedSS set out as a Phase II, multicentre, double-blind randomised controlled trial, converted to open-label because of the Covid-19 pandemic. Patients were randomised to receive either moderate dose prednisolone (approximately 0.3 mg/kg) or matching placebo (or no treatment during open-label) for 6 months. The co-primary endpoints were the Health Assessment Questionnaire Disability Index (HAQ-DI) and modifed Rodnan skin core (mRSS) at 3 months. Over 20 secondary endpoints included patient reported outcome measures refecting pain, itch, anxiety and depression, fatigue and helplessness. 72 participants randomised 1:1 were planned and anticipated to yield 60 evaluable, giving over 80% power for each co-primary outcome in ANCOVA analyses [assumptions;HAQ-DI (a = 0.025, ô =-0.6, o = 0.9, p = 0.6), mRSS (a = 0.025, ô =-5.5, a = 8.2, p = 0.6)]. Mixed Models for Repeated Measures (week 6, month 3, month 6) were ftted with covariates trial arm, baseline score, anti-Scl-70 and their interactions with time point. An unstructured covariance matrix was assumed with the primary focus being the trial arm effect at 3 months. Results: The study terminated early due to the Covid-19 pandemic and consequently did not meet the recruitment target of 72 patients. Thirty-five patients (Table 1) were randomised (17 to prednisolone and 18 to placebo/control, 25 during the double-blind phase), of whom 34 completed the 3 month assessment. The adjusted mean difference between treatment groups at 3 months in HAQ-DI score was-0.10 (97.5% CI-0.29 to 0.10), p=0.25, and in mRSS-3.90 (97.5% CI-8.83 to 1.03), p=0.070, both favouring prednisolone but not signifcantly. Patients in the prednisolone group experienced less pain, helplessness and anxiety than control patients at 3 months: mean difference in pain scores-0.49, 95%CI (-0.93 to-0.06), p=0.027, in Hospital Anxiety and Depression (HADS) anxiety scores-2.05, 95%CI (-3.73 to-0.37), p=0.018, and in helplessness scores-1.54, 95%CI (-3.01 to-0.07), p=0.040. There were no renal crises. Conclusion: PRedSS exemplifed the challenges of running a clinical trial of an investigational medicinal product potentially associated with increased infection risk during the Covid-19 pandemic. Because PRedSS was terminated prior to target recruitment, it was underpowered, and any conclusions have to be extremely cautious. Although PRedSS suggested some beneft from moderate dose predni-solone, the small sample indicates the need for a further randomised trial.
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Background: The novel coronavirus (COVID-19) can cross the blood-brain barrier resulting in neuroinflammation that can cause significant damage to the peripheral and central nervous systems. Inflammation has been linked to psychotic symptoms, which have been observed following influenzas and SARS-CoV-1. Maternal influenza while in utero is also linked to later development of psychotic disorders. Some who do not develop psychosis display subclinical symptoms called schizotypy, which includes odd behavior, perceptual aberrations, and thought, speech and social impairments. The present study compared schizotypal symptoms in persons who contracted COVID-19 and recovered, to those who developed long COVID. Method: Individuals who contracted COVID-19 were recruited via social media and completed self-report measures of premorbid health, COVID-19 positivity, symptoms, and recovery, along with the schizotypal personality questionnaire (SPQ) online using Qualtrics. Results: One-third of the sample (N=88) recovered within one month of acute illness, and two-thirds (N = 153) remained symptomatic > 3 months later. A 2 (recovered, long COVID) x 2 (male, female) ANCOVA controlling for age indicated that there were no differences between those that recovered within one month and those with long COVID on SPQ scores (F(1, 154) = 3.00, p = .085). There were also no differences between the groups regarding SPQ subscales. There was an interaction effect between sex and total people that contracted COVID-19 on total SPQ scores (F(1, 154) = 12.69, p = .001). Compared to normative data, those who contracted COVID-19 scored higher in social anxiety (t(161) = 6.39, p = .001), constricted affect (t(159) = 2.54, p = .012), no close friends (t(161) = 5.03, p = .001), and ideas of reference (t(161) = - 5.26, p = .001). Discussion: Results suggest that increased social anxiety, constricted affect, lack of close friends, and ideas of reference are present in those with COVID-19, which may reflect pandemic effects on disease pathophysiology.
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Background: The coronavirus disease 2019 (COVID-19) crisis has greatly impressed medical education by shifting traditional edu-cational methods to e-learning. Objectives: This study evaluated the undergraduate medical students’ attitudes toward e-learning during the COVID-19 pandemic Methods: This cross-sectional study included undergraduate medical students of Mashhad University of Medical Sciences, Mash-had, Iran, in the academic year 2020-21 by census sampling method, whose attitude toward e-learning was evaluated based on the Ghanizadeh et al. scale. Categorical variables were demonstrated with frequency and percentage, and quantitative variables were described using the mean and standard deviation. An independent-sample t test was run to study the hypothesis. Analysis of covariance (ANCOVA) was performed to compare pre-clinical and clinical groups’ attitudes toward e-learning after gender control. Statistical analyses were performed by SPSS 23. Results: The study enrolled 528 undergraduate medical students. The findings indicated that 85.4% of the students agreed with the necessity of more effective e-learning in medical education, and 95.5% believed that e-learning should play a complementary role in medical education. It was found that clinical students had a marginally statistically significantly better attitude toward e-learning than pre-clinical students (t =-2.04, df = 526, P = 0.041). Nevertheless, no significant difference was observed between the two groups after gender control (t = 2.87, P = 0.091). It was shown that males had more positive attitudes toward e-learning than females (t = 2.28, df = 526, P = 0.023). Conclusions: The results revealed acceptable attitudes toward e-learning. Although many students declared e-learning’s usefulness and confirmed its complementary role in medical education, some announced that it could not replace in-person training.
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Analysis of means (ANOM) is a graphical alternative for the analysis of variance (ANOVA) that was primarily developed for multiple mean comparisons. The ANOM is a simple graphical display that provides a visualization of statistically significant results and it allows validating their practical significance without deep statistics knowledge. The classical ANOM has been developed to analyze fixed mean effects, and its recent developments allow testing random and mixed effects. On the other hand, analysis of covariance (ANCOVA) is an extension of ANOVA that applies to test means in the presence of uncontrollable concomitant/nuisance variables. To effectively communicate the statistical findings from ANCOVA to a general audience on some public interest issue areas such as COVID-19, visualization of statistically significant results is a practical approach. This paper provides a graphical alternative for multiple group comparisons in ANCOVA as an extension of the ANOM. The proposed graphical alternative is validated and compared with the ANCOVA using a Monte Carlo simulation study. The simulation results indicated that the proposed method stands strong for practical ANCOVA problems. In addition, a COVID-19 application and two additional applications related to toxicology and business are used to exhibit the value of the proposed graphical procedure in practice.
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Background and Aims: A large subset of PWD assume that physical activity alone can bring glycemic control irrespective of the stage of diabetes. During Covid, there was an increased emphasis on physical activity in PWD. People with uncontrolled diabetes were avoiding physical visits to hospitals due to the fear of contracting the disease. In this scenario, we analysed the effects of physical activity on glycemic control as measured by CGM in terms of TIR. Methods: We analysed the EMR of T2D patients who performed CGM atleast once from March 2021 - June 2021 after the lockdown period and extracted data on exercise (type, frequency and duration of exercise), BMI and TIR. Out of 603 T2D, 332 (those who performed at least one kind of physical activity) were categorised into the study group (SG) and 271 (those without any physical activity) into the control group (CG). Results: TIR was compared between SG and CG using analysis of covariance model with TIR as the dependent variable, treatment as a fixed effect and BMI as a cofactor. There was no significant difference (p = 0.7305) in TIR between the groups. When taken together, 16.3% achieved a TIR >70% and 6.5% achieved a TIR >90% irrespective of physical activity. Percentage of patients in various TIR categories is shown(Fig.1) Conclusions: Physical activity alone as an independent parameter may not have a significant role in improving TIR. The findings emphasize the fact that physical acvity should be combined with medical nutrition therapy and therapeutic interventions for better optimal outcomes in the management of diabetes. (Figure Presented).
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The optimal timing of commencing adjuvant endocrine therapy (ET) relative to adjuvant radiotherapy (RT) (i.e. concurrent with or sequential to radiotherapy) remains unknown. A systematic review performed by our team was unable to answer this question due to a lack of high quality, randomized data on concurrent versus sequential ET and RT. Surveys of physicians confirmed this uncertainty and highlighted theoretical concerns for increased side effects with concurrent treatment. Respondents showed keen interest in obtaining real world, randomized data to guide clinical practice. REaCT-RETT is a pragmatic, randomized, non-inferiority trial comparing concurrent and sequential ET and RT in early breast cancer (EBC). The primary endpoint will assess the change in ET side effects at baseline and 3 months post radiation, using the Functional Assessment of Cancer Therapy-Endocrine Subscale (FACT-ES), with primary analysis based on an analysis of covariance (ANCOVA). With a sample size of 176 patients (88 per arm), an ANCOVA would have 80% power (α=0.05) to detect effect sizes as small as 0.25 regardless of the correlation with covariates. It is hypothesized that concurrent therapy will be non-inferior to sequential therapy in terms of ET side effects. Secondary endpoints will examine RT toxicity, ET compliance, quality of S life, and cost-effectiveness. Patients with HR positive EBC planned to receive both adjuvant ET and RT were eligible. Patients who previously received ET for invasive breast cancer, or RT in the same breast, were excluded. The trial is conducted by The Ottawa Hospital's (TOH) innovative Rethinking Clinical Trials (REaCT) program (https://react.ohri.ca/) which strives to improve access to patient-centered, pragmatic clinical trials by removing barriers for patients and researchers. Integral features of the program include broad eligibility criteria, a verbal consent model, and pragmatic data collection and assessment procedures. REaCT is the largest pragmatic cancer clinical trials program in Canada, with over 3, 200 patients randomized in 18 clinical trials at 15 sites across Canada. REaCT-RETT accrued patients from September 2019 to January 2021. Data collection is ongoing, with final patient follow up expected April 2022. The timing of accrual provided a unique opportunity to adapt in response to restrictions due to the COVID-19 pandemic, which began to impact trial sites in March 2020. The target sample size was met with 262 patients randomized (1:1) across 3 sites in Ontario, 98% from TOH. A mean of 19 patients/month were accrued prior to the pandemic, compared to a mean of 13 patients/month after March 2020. Twenty-two patients were removed due to withdrawal of consent, ineligibility, or physician choice, and the pandemic was not a significant contributing factor. Since March 2020 there have been 772 patient follow ups, of which 47% (364/772) have been virtual. Only 10% (102/1028) of trial mandated appointments have been missed to date. Compliance with baseline and 3-month FACT-ES questionnaires for the primary endpoint in evaluable patients was 90% (215/240) and 83% (198/240), respectively. The pandemic posed several challenges to the REaCT-RETT study including a decline in patient accrual, poor accrual at peripheral sites due to delayed opening, and a rapid switch to virtual patient care. However, the nimble REaCT methodology enabled virtual patient consent and data collection during the pandemic, allowing the trial to continue successfully, with final data expected for presentation summer 2022. Finally, despite the challenges of COVID-19 we have seen that patients and physicians remain interested in research, and we are applying valuable lessons learned to forthcoming REaCT trials to strengthen their performance during and beyond the ongoing pandemic.
ABSTRACT
Background: Our main goal was to evaluate the efficacy of transcranial direct current stimulation (tDCS) for improving attention in adult patients with attention-deficit/hyperactivity disorder (ADHD) without concurrent treatment with stimulants. Methods: In this parallel, double-blind study, patients with ADHD were randomly assigned to receive active (A-tDCS) or sham tDCS (S-tDCS) using a home-based device. Treatment consisted of one daily stimulation session (30-min, 2-mA, prefrontal cortex) for 4 weeks. The primary outcome measure was a clinician-applied Adult ADHD Report Scale (AARS), inattention section (range 0-36, higher values indicating increased inattention). Analysis of the primary outcome was performed using an ANCOVA controlled for prespecified covariates (baseline AARS, sex, age, ADHD subtype). Results: From July 2019 to July 2021, a total of 147 subjects were assessed for eligibility, and 64 were randomized (mean age=38 years, 30 females). A total of 9 subjects dropped out of the study (4 due to the COVID-19 pandemic). The remaining 59 performed an average of 25 tDCS sessions. Baseline (mean±SD) AARS was 27±3.6 in S-tDCS and 27.6±4 in A-tDCS. In the intention-to-treat analysis (missing data imputed using last observation carried forward), there was a significant decrease of 3.9 (1.50 - 6.44 95% CI) points in the AARS after A-tDCS when compared to S-tDCS (p = 0.002, partial η2 = 0.15). Mild headache and moderate skin redness were more common in A-tDCS. Conclusions: A-tDCS was efficacious in improving symptoms of inattention when compared to S-tDCS and is a promising treatment for patients with ADHD who do not respond or do not tolerate stimulants. Supported By: DTL was supported by a CNPq postdoctoral fellowship (grant number 154116/2018-1), and supported by a NARSAD Young Investigator Grant from the Brain and Behavior Research Foundation (grant number 29486). Keywords: Adult ADHD, Transcranial Direct Current Stimulation (tDCS), Inattention, Clinical Trials
ABSTRACT
Purpose: A clear need exists to rigorously assess treatment strategies for chronic prearthritic hip disorders (PAHD). We assessed the preliminary effects of two physical therapist-led interventions that target two distinct mechanisms, abnormal movement patterns and sensory disturbances. Abnormal movement patterns, such as excessive hip adduction, may create altered mechanical stresses on hip joint structures, resulting in subsequent injury, pain and activity limitations. Movement pattern training (MoveTrain) may improve movement patterns and patient-reported outcomes, however further investigation is needed to be definitive. Sensory disturbances such as peripheral sensitization and central sensitization (aka nociplastic pain) may also contribute to pain persistence long after an initial injury. Joint mobilization (JtMob) is proposed to impart a neurophysiological response within the peripheral and central nervous system that results in pain reduction and improved mobility, yet the investigation of JtMob for the treatment of PAHD is limited. Methods: Patients, 18-40 years, with chronic PAHD were recruited. Baseline assessment included self-report questionnaire completion, clinical examination and quantitative sensory testing. The primary outcome was the Hip disability and Osteoarthritis Outcome Score (HOOS), a hip-specific, patient-reported outcome measure. Secondary outcomes included movement evoked pain assessed with a repetitive step down task and a repetitive deep squat task, and pain pressure threshold assessed at the anterior groin of the most bothersome hip (local pressure hypersensitivity) and the dominant thenar eminence (generalized pressure hypersensitivity). After baseline assessment, patients were randomized into 1 of 2 treatment groups, MoveTrain or JtMob. Randomization was stratified by sex and HOOS Symptoms quartile, as determined from data collected during previous study. Treatment was provided by 4 experienced physical therapists (2 in each treatment arm) who were trained in standardized procedures. Treatment for both groups included 10 supervised sessions over 12 weeks and incorporated assessment of patient goals, patient education and instruction in a home program. Patient education focused on patient-specific tasks, such as work or fitness activities, identified by each patient to be symptom-producing. The goal of MoveTrain was to reduce stresses on the hip joint by optimizing the biomechanics of daily and patient-specific tasks. The key element of MoveTrain was task-specific instruction to correct abnormal movement patterns demonstrated during daily tasks and patient-specific tasks. For example, hip adduction and femoral internal rotation were minimized during step-down tasks. The home program included repeated practice of the modified tasks. Difficulty of the tasks were progressed based on each patient’s performance. The goal of JtMob was to reduce pain and improve pain-free motion of the hip. The key element of JtMob was manual techniques provided by the physical therapist. Specific criteria were used to determine the joint mobilization techniques and parameters used for each patient. The patient’s symptom report to each technique was monitored and if indicated, the technique modified according to our outlined procedures. The home program included flexibility exercises. Immediately after treatment completion, patients returned for follow up assessment. Data collected at baseline and post-treatment were analyzed with analysis of covariance (ANCOVA) using a generalized linear model where change is the dependent variable and baseline is the covariate. The adjusted immediate treatment effect was calculated by subtracting the least squares mean change between baseline and post for MoveTrain minus JtMob from the ANCOVA, and assesses the between-group difference in change after adjusting for baseline. Results: Thirty-three patients with PAHD were randomized. Demographics are provided in Table 1. Four patients did not complete treatment or post-treatment testing (3 due to COVID pandemic, 1 lost t follow up);7 patients did not complete post-treatment laboratory testing (due to COVID), but did complete post-treatment questionnaires. Both groups demonstrated clinically important within-group improvements in the HOOS subscales and movement evoked pain ratings after treatment (Table 2). No changes were noted in pain pressure threshold for either group. After adjusting for baseline, there were no between-group differences in change in outcomes when comparing MoveTrain and JtMob. Conclusions: Our preliminary findings suggest that 12 weeks of physical therapist-led intervention, including either MoveTrain or JtMob, may result in improvements in patient-reported pain and activities limitations. Further investigation is needed to determine the sustained effects of each treatment and to determine if specific patient factors are associated with treatment prognosis. [Formula presented] [Formula presented]
ABSTRACT
Introduction: Acid sphingomyelinase deficiency (ASMD), also historically known as Niemann-Pick disease A (OMIM #257200) and B (OMIM#607616), is a rare and debilitating lysosomal storage disease caused by pathogenic variants in SMPD1 gene. Deficient activity of the lysosomal enzyme acid sphingomyelinase (ASM) leads to sphingomyelin accumulation in various organs. Visceral manifestations of ASMD include interstitial lung disease and pulmonary dysfunction, splenomegaly, hepatomegaly, dyslipidemia, thrombocytopenia, and anemia and are present across ASMD phenotypes (ASMD type A, B and A/B). In more severe cases of ASMD (ASMD type A), there are also central nervous system manifestations. No disease-specific treatment is currently approved for patients with ASMD. Olipudase alfa, an intravenous-recombinant-human ASM, is in late-stage development (Sanofi Genzyme) for the non-central-nervous-system manifestations of ASMD in children and adults. Two open-label trials, a phase 1b trial in 5 adults (NCT01722526) and a phase 1/2 trial in 20 children with chronic ASMD (ASCEND-Peds, NCT02292654) demonstrated improvement of pulmonary function, reduction of liver and spleen volume, reversal of dyslipidemia, decreased disease biomarkers, and in children, improved growth. A phase 2/3 placebo-controlled trial, the ASCEND study (NCT02004691) in 36 adults with ASMD who had splenomegaly and pulmonary dysfunction, has completed its primary analysis. Olipudase-alfa-treated patients compared to placebo-treated patients (1:1 randomization) had statistically significant increases in percent-predicted diffusing capacity of carbon monoxide (DLCO) and statistically significant decreases in spleen and liver volume after 1 year of placebo or olipudase alfa. Thirty-five of 36 patients continued in an open-label trial extension including 17 of the 18 patients who initially received placebo in the first year and all 18 patients who received olipudase alfa. Here we report Year 2 results of the ASCEND trial for the former placebo group after 1 year of olipudase alfa treatment and for the initial olipudase alfa group after 2 years of olipudase alfa treatment. Methods: All patients underwent gradual dose-escalation to 3.0 mg/kg every 2 weeks for approximately 14 weeks when starting olipudase alfa. Efficacy outcomes include percent-predicted DLCO, spleen volume, liver volume, lung high-resolution computerized tomography (HRCT) scores for ground glass appearance, histopathologic clearance of sphingomyelin in the liver, platelet count, plasma lyso-sphingomyelin, liver function, and lipid profile. Change from baseline results are presented as least-square mean (analysis of covariance [ANCOVA]) percent change ± standard error of the mean (SEM), except for ground glass appearance, which is the least-square mean ANCOVA absolute change from baseline, and percent liver tissue area occupied by sphingomyelin and plasma lyso-sphingomyelin, which are presented as mean changes ± standard deviation (SD). Absolute values at Baseline, Year 1, and Year 2 are presented as mean ± SD (Table). Results: Overall, 33 of 35 patients completed Year 2 of ASCEND;one former placebo patient withdrew due to COVID-19 travel restrictions, and one continuing olipudase alfa patient withdrew consent. COVID-19 travel restrictions also resulted in at least one missed assessment in six patients. In Year 2, improvements for patients in the former placebo group paralleled the olipudase alfa group in the primary analysis while clinical improvement continued for patients who received 2 years of olipudase alfa (Table). For patients in the former placebo group, percent-predicted DLCO increased by 28.0 ±6.2% (n=10);spleen volume decreased by 36.0 ±3.0% (n=11);liver volume decreased by 30.7 ±2.5% (n=11), and platelet count increased by 21.7 ±6.4% (n=15). In patients with 2 years of olipudase alfa treatment, percent-predicted DLCO increased by 22.2 ±3.4% (n=17) at Year 1 and 28.5±6.2% at Year 2 (n=10);spleen volume decreased by 39.5 ±2.4% (n=17) at Year 1 and 47.0 ±2.7% (n=14) at Year 2 liver volume decreased by 27.8 ±2.5% (n=17) at Year 1 and 33.4 ±2.2% (n=14) at Year 2, and platelet count increased by 16.6 ±4.0% at Year 1 (n=18) and 24.9 ±6.9% (n=13) at Year 2. HRCT ground glass appearance score decreased 0.30 ±0.5 (n=14) at Year 2 for patients in the former placebo group and decreased by 0.45 ±0.13 (n=18) at Year 1 and 0.48 ±0.07 (n=16) at Year 2 for patients continuing to receive olipudase alfa. Liver sphingomyelin clearance at Year 2 was 93.3 ±5.0% (n=10) for patients in the former placebo group and 92.7 ±5.8% at Year 1 (n=13) and 98.4 ±2.0% at Year 2 (n=10) for patients continuing to receive olipudase alfa. Plasma lyso-sphingomyelin decreased by 79.4 ±11.3% (n=14) for patients in the former placebo group and by 78.0 ±11.1% (n=18) at Year 1 and 64.4 ±28.5% (n=15) at Year 2 for patients continuing to receive olipudase alfa;several patients had transient increases due to missed infusions. Alanine aminotransferase decreased by 45.2 ±34.4% (n=15) for patients in the former placebo group, and by 36.5 ±8.4% (n=18) in Year 1 and 32.0 ±10.2% (n=12) in Year 2 for patients continuing to receive olipudase alfa. For patients in the former placebo group, high-density lipoprotein cholesterol (HDL-C) increased by 59.7 ±9.7% (n=14) and low-density lipoprotein cholesterol (LDL-C) decreased by 27.5 ±6.8% (n=13) in Year 2. For patients continuing to receive olipudase alfa, HDL-C increased by 40.0 ±6.8% (n=18) in Year 1 and 64.4 ±10.5% (n=12) in Year 2 and LDL-C decreased by 25.8 ±4.8% (n=18) in Year 1 and 23.0 ±7.1% (n=12) in Year 2. Overall, 99% of treatment-emergent adverse events were mild or moderate, with one treatment-related serious adverse event (extrasystoles in patient with previously documented cardiomyopathy). No patient discontinued due to an adverse event. Conclusion: During Year 2 of ASCEND, patients crossing over from placebo to olipudase alfa had the same magnitude and time course of clinical improvement seen in patients receiving olipudase alfa for 1 year, while continuing olipudase-alfa patients had sustained or further improvements. Olipudase alfa reduced sphingomyelin storage in the liver and lyso-sphingomyelin in plasma. Clinically, olipudase alfa improved pulmonary function, reduced splenomegaly and hepatomegaly, and improved liver function and dyslipidemia for up to 2 years. These results are consistent with the published 30- and 42-month data for adults reported in the long-term extension of the open-label Phase 1b study. Treatment with olipudase alfa reduces manifestations of chronic ASMD in adults and has sustained efficacy. [Formula presented]