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Improving the Understanding of Immunopathogenesis of Lymphopenia as a Correlate of SARS-CoV-2 Infection Risk and Disease Progression in African Patients: UGLY SARS-CoV-2 Study Protocol

JMIR Res Protoc. 2020 Nov 10. doi: 10.2196/21242. Online ahead of print.

ABSTRACT

BACKGROUND: COVID-19 pandemic caused by SARS-CoV-2 continued to impact health systems throughout the world with serious medical challenges being imposed on many African countries such as Nigeria. Although emerging studies have identified lymphopenia as a driver of cytokine storm, disease progression and poor outcomes in infected patients, its immunopathogenesis, environmental and genetic determinants remain unclear. Understanding the interplay of these determinants in the context of lymphopenia and COVID-19 complications in African patients may help in risk stratification and appropriate deployment of targeted treatment regimens with repurposed drugs to improve prognosis.

OBJECTIVE: This study is designed to investigate the role of vitamin D status, vasculopathy, apoptotic pathway and vitamin D receptor gene polymorphisms in the immunopathogenesis of lymphopenia among SARS-CoV-2 infected Africans.

METHODS: This cross-sectional study will enrol 200 study participants categorized as SARS-CoV-2 negative (n=69), COVID-19 mild (n=32), hospitalized (n=72) and recovered (n=37) from two purposively selected health facilities in Lagos State. Sociodemographic, travel history and co-morbidity information will be obtained from case file and study pre-tested interviewer-based structured questionnaire. Venous blood samples (5ml) collected between 8.00-10.00 h and aliquoted into EDTA and plain tubes will be used for complete blood count and CD4 T cells assays to determine lymphopenia (Lymphocyte count < 1000 cells/uL) and CD4 T lymphocyte levels as well as measuring the concentrations of vitamin D, caspase 3, sVCAM-1 and sFasL using an autoanalyzer, flow cytometry and ELISA techniques. Genomic DNA will be extracted from buffy coat and used as template for the amplification of apoptosis related genes (Bax, Bcl-2, BCl-2LI2) by PCR and genotyping of vitamin D receptor (VDR: Apa1, Foh1 and Bsm1) gene polymorphisms by PCR-RFLP and capillary sequencing. Total RNA will also be extracted, reverse transcribed and subsequently quantitated by RT-PCR to monitor the expression of apoptosis genes in the four categories of COVID-19 study participants enrolled. Data analyses, which include test of association between VDR gene polymorphisms and study outcomes (Lymphopenia and hypovitaminosis D prevalence, mild/moderate and severe infections) will be performed using the R Statistical Software. Hardy-Weinberg Equilibrium (HWE) and linkage disequilibrium analyses for alleles, genotype and haplotypes of the genotyped VDR gene will also be carried out.

RESULTS: A total of 45 participants comprising 37 SARS-CoV-2 negative and 8 COVID-19 recovered participants have been enrolled so far with their complete blood counts and CD4 T lymphocyte counts determined as well as having all their serum samples and genomic DNA and RNA sample extracted and stored at -200C until further analyses. Other expected outcomes include prevalence and distribution of lymphopenia and hypovitaminosis D among the control (SARS-CoV-2 negative), confirmed, hospitalized and recovered SARS-CoV-2 positive study participants, association lymphopenia with CD4 T lymphocyte level, serum vitamin D, sVCAM-1, sFasL and caspase 3 levels in hospitalized COVID-19 patients, expression levels of apoptosis related genes among hospitalized COVID-19 study participants, those with lymphopenia compared with those without lymphopenia and Frequency distribution of alleles, genotypes and haplotypes of VDR gene polymorphisms in COVID-19 afflicted Nigerians studied.

CONCLUSIONS: This study will aid in the genotypic and phenotypic stratification of COVID-19 afflicted Nigerian patients with and without lymphopenia to enable biomarker discovery and pave way for appropriate and timely deployment of patient-centered treatments to improve prognosis.

PMID:33621190 | DOI:10.2196/21242

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The Collaboration Structure in COVID-19 Critical Care: A Network Analysis

JMIR Hum Factors. 2021 Feb 22. doi: 10.2196/25724. Online ahead of print.

ABSTRACT

BACKGROUND: Few ICU staffing studies examine collaboration structures among healthcare workers. Knowledge about how healthcare workers (HWs) are connected to care for critically ill COVID-19 (C19) patients provides evidence for characterizing the relationship between team structures, care quality, and patient safety.

OBJECTIVE: To discover the distinctions of teamwork structures in C19 critical care by comparing HW collaboration associated with the management of critically ill patients with and without C19.

METHODS: In this retrospective study, we apply network analysis to the utilization of electronic health records (EHRs) of 76 critically ill patients (38 with and 38 without C19) admitted to a large academic medical center to learn HW collaboration. We use the EHRs for adult patients admitted to the C19 ICU at Vanderbilt University Medical Center (Nashville, Tennessee, USA) between March 17, 2020 and May 31, 2020. We matched each C19 patient on age, gender, and length of stay, with NC19 patients admitted to the Medical ICU (MICU) between December 1, 2019 and February 29, 2020. Then we use two sociometric measurements, including eigencentrality and betweenness, to quantify HWs’ status in the networks. Eigencentrality characterizes the degree to which an HW is likely to be a core person in the collaboration. Betweenness centrality refers to whether an HW lies on the path of others who are not directly connected, which is leveraged to characterize the broad skillsets of an HW. We further measure patient staffing intensity in terms of the number of HWs interacting with the EHR of a patient. We assess the extent to which the core and betweenness status of HWs, as well as patient staffing intensity, in C19 and Non-C19 (NC19) critical care are statistically different using Mann-Whitney U tests at the 95% confidence level.

RESULTS: HWs are likely to more frequently work with each other in C19 than NC19 critical care (median eigencentrality values of 0.096 vs. 0.057, respectively; p = 1.5×10e-9). Internal medicine physicians exhibit a higher core status in the C19 critical care than NC19 (p = 1.2 ×10e-3). Nurse practitioners exhibit a more betweenness status in the C19 than NC19 care (p = 3.10 ×10e-4). In comparison to the NC19 setting, the EHRs of C19 critically ill patients were utilized by a larger number of internal medicine nurse practitioners (p = 1.27 ×10e-5), cardiovascular nurses (p = 8.48 ×10e-6) and surgical ICU nurses (p = 1.62 ×10e-3), as well as a smaller number of resident physicians (p = 5.96 ×10e-4).

CONCLUSIONS: Network analysis methodologies and EHR utilization data provide a novel way to learn distinctions of collaboration structures in C19 critical care, which can be leveraged by healthcare organizations to understand the novel additions the C19 brings to the collaboration structure in urgent care.

PMID:33621187 | DOI:10.2196/25724

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Short-range forecasting of coronavirus disease 2019 (COVID-19) during early onset at county, health district, and state geographic levels: Comparative forecasting approach using seven forecasting methods

J Med Internet Res. 2021 Feb 22. doi: 10.2196/24925. Online ahead of print.

ABSTRACT

BACKGROUND: Forecasting methods rely on trends and averages of prior observations to forecast coronavirus disease 2019 (COVID-19) case counts. COVID-19 forecasts have received much media attention and numerous platforms have been created to inform the public. However, forecasting effectiveness varies by geographic scope and are affected by changing assumptions in behaviors and preventative measures in response to the pandemic. Due to time requirements for developing a COVID-19 vaccine, evidence is needed to inform short-term forecasting method selection at county, health district, and state levels.

OBJECTIVE: COVID-19 forecasts keep the public informed and contribute to public policy. As such, proper understanding of forecasting purposes and outcomes is needed to advance knowledge of health statistics for policy makers and the public. Using publicly available real-time data provided online, we evaluate the performance of seven forecasting methods utilized to forecast cumulative COVID-19 case counts. Forecasts are evaluated based on how well they forecast one-. three-, and seven-days forward when utilizing one-, three-, seven-, or all-prior days’ cumulative case counts during early onset. This study provides an objective evaluation of the forecasting methods to identify forecasting model assumptions that contribute to lower error in forecasting COVID-19 cumulative case growth. This information benefits professionals, decision makers, and the public relying on the data provided by short-term case count estimates at varied geographic levels.

METHODS: One-, three-, and seven-days forecasts are created at the county, health district, and state levels using: (1) a naïve approach; (2) Holt-Winters exponential smoothing (HW); (3) growth rate (Growth); (4) moving average (MA); (5) autoregressive (AR); (6) autoregressive moving average (ARMA); and (7) autoregressive integrated moving average (ARIMA). Forecasts rely on Virginia’s 3,463 historical county-level cumulative case counts from March 7 – April 22, 2020, as reported by The New York Times. Statistically significant results are identified using 95% confidence intervals of Median Absolute Error (MdAE) and Median Absolute Percentage Error (MdAPE) error metrics of the resulting 216,698 forecasts.

RESULTS: Next-day MA forecast with three-day lookback obtained the lowest MdAE (0.67, 0.49-0.84, P < .001) and statistically significantly differs from 39 (66.1%) to 53 (89.8%) of alternatives at each geographic level at a significance level of 0.01. For short-range forecasting, methods assuming stationary means of prior days’ counts outperform methods with assumptions of weak- or non-stationarity means. MdAPE results reveal statistically significant differences across geographic levels.

CONCLUSIONS: For short-range COVID-19 cumulative case count forecasting at the county, health district, and state levels during early onset: (1) MA is effective for forecasting one-, three-, and seven-days’ cumulative case counts; (2) exponential growth is not the best representation of case growth during early onset when the public is aware of the virus; and (3) geographic resolution is a factor in forecasting method selection. (This work received no external funding.).

PMID:33621186 | DOI:10.2196/24925

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Participation and engagement in family activities among girls and young women with Rett syndrome living at home with their parents – a cross-sectional study

Disabil Rehabil. 2021 Feb 23:1-11. doi: 10.1080/09638288.2021.1878394. Online ahead of print.

ABSTRACT

PURPOSE: To describe the extent of participation and engagement in family activities and explore variables potentially impacting on these factors in family activities among girls and young women with Rett syndrome (RTT) under the age of 21.

MATERIALS AND METHODS: The Child Participation in Family Activities (Child-PFA) questionnaire was sent to parents in the target group (n = 42). Additionally, age, number of siblings at home, ambulation level, clinical severity and level of hand function were recorded to explore possible impact. Data were analyzed using descriptive statistics, Fishers exact test and cross-tables.

RESULTS: 23 families participated. Highest degrees of participation and engagement were seen in social and stationary family activities. Indoor activities were frequent and showed high levels of participation and engagement, Outdoor activities were infrequent and showed low levels of participation despite a high degree of engagement. Routine activities were frequent but showed moderate to low participation and engagement. A negative association was found between participation in watching a movie and number of siblings living at home, and positive associations between engagement and age in three family activities.

CONCLUSION: Therapists working with this target group may benefit from focusing on engagement in routine activities and modification of family activities.IMPLICATIONS FOR REHABILITATIONTherapists may benefit from focusing on engagement in routine activities in the goal setting process and intervention as they occur on a daily basis, giving the opportunity for development of new skills.Therapists may benefit from focusing on assistive devices or other compensatory strategies for outdoor activities and activities that require a certain amount of hand function.Therapists may benefit from modifying the family’s activities so that they require more social and mental participation and focus on experiencing different types of sensory input e.g., sound, tactile, visual or vestibular input rather than taking part in the activity by using their hands.

PMID:33621156 | DOI:10.1080/09638288.2021.1878394

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Developmental Language Disorder and Uninhibited Primitive Reflexes in Young Children

J Speech Lang Hear Res. 2021 Feb 23:1-14. doi: 10.1044/2020_JSLHR-19-00423. Online ahead of print.

ABSTRACT

Purpose Developmental language disorder (DLD) is a developmental disorder where children fail to acquire language in the absence of a clear cause. Many studies have reported general motor deficits in children with DLD, but no studies have uncovered a cure. The purpose of our study is to better understand the underlying motor deficits in DLD, starting from uninhibited primary reflexes-which are the most basic stage of motor development. Knowledge of this motor-language relationship should lead to earlier and more targeted interventions in young children with DLD. Method Children with DLD (n = 75, age range: 4-10 years) and 99 age-matched typically developing (TD) children completed a nonword repetition test to assess DLD and six other tests to assess primitive reflexes. Results Children with DLD demonstrated higher levels of persistent primitive reflexes compared to TD children. As the scores for neuromotor immaturity increased, nonword repetition test scores decreased (r = -.44, p < .01). Results indicated that TD children exhibited lower neuromotor immaturity (M = 7.63, SD = 3.75) compared to children with DLD (M = 13.51, SD = 4.47). All primitive reflexes (the Moro reflex, the symmetrical tonic neck reflex in flexion and in extension, the asymmetrical tonic neck reflex, the tonic labyrinthine reflex, and the Galant reflex) turned out to be statistically significantly different for the TD and DLD groups (p < .001). We also observed some differences between sexes. Conclusions Children with impaired language development underwent slower neuromotor development. However, further research is needed to determine whether motor intervention programs that inhibit primitive reflexes are helpful for children with DLD.

PMID:33621124 | DOI:10.1044/2020_JSLHR-19-00423

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Speech-Language Pathologist Involvement in Multi-Tiered System of Supports Questionnaire: Advances in Interprofessional Practice

Lang Speech Hear Serv Sch. 2021 Feb 23:1-15. doi: 10.1044/2020_LSHSS-20-00084. Online ahead of print.

ABSTRACT

Purpose This article describes the development and initial validation of the Speech-Language Pathologist (SLP) Involvement in Multi-Tiered System of Supports (MTSS) Questionnaire. It was developed to measure the extent to which SLPs are involved in MTSS at their school site(s). Method A total of 567 SLPs practicing in the United States responded to up to 39 Likert-type items meant to reflect six domains: scope of practice, professional development, leadership, consulting/collaborating, assessment and analysis, and intervention. Measurement quality was evaluated in terms of score reliability and validity. An exploratory factor analysis was conducted to evaluate the internal structure of the questionnaire responses. A three-factor model with the following dimensions of Carrying out Roles and Responsibilities, Leading, and Planning and Providing Interventions was supported. Loadings for retained factors ranged from .35 to .87. Internal consistency estimates ranged from .87 to .92. Descriptive statistics summarized the overall involvement of SLPs in MTSS, and responses to questions to assess the feasibility and acceptability of this questionnaire were analyzed. Results Questionnaire responses indicated that SLPs infrequently engage in MTSS activities. The item with the highest mean was related to SLPs collaborating with teachers to help them address students’ speech and language disorders in their classrooms. Most of the SLPs who took the questionnaire found it easy to complete, but only some found the information to be useful. Conclusions The infrequent involvement of SLPs in MTSS indicates a need to disseminate information on the potentially valuable roles SLPs can play in MTSS implementation. This tool may be used by SLPs to better understand contributions they can make within an MTSS framework and self-reflect on their current levels of involvement. Supplemental Material https://doi.org/10.23641/asha.13874516.

PMID:33621114 | DOI:10.1044/2020_LSHSS-20-00084

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ROBUST: A Phase III Study of Lenalidomide Plus R-CHOP Versus Placebo Plus R-CHOP in Previously Untreated Patients With ABC-Type Diffuse Large B-Cell Lymphoma

J Clin Oncol. 2021 Feb 23:JCO2001366. doi: 10.1200/JCO.20.01366. Online ahead of print.

ABSTRACT

PURPOSE: Patients with the activated B-cell-like (ABC) subtype of diffuse large B-cell lymphoma (DLBCL) historically showed inferior survival with standard rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). Phase II studies demonstrated that adding the immunomodulatory agent lenalidomide to R-CHOP improved outcomes in ABC-type DLBCL. The goal of the global, phase III ROBUST study was to compare lenalidomide plus R-CHOP (R2-CHOP) with placebo/R-CHOP in previously untreated, ABC-type DLBCL.

METHODS: Histology and cell-of-origin type were prospectively analyzed by central pathology prior to random assignment and study treatment. Patients with ABC-DLBCL received lenalidomide oral 15 mg/d, days 1-14/21 plus standard R-CHOP21 versus placebo/R-CHOP21 for six cycles. The primary end point was progression-free survival (PFS) per independent central radiology review.

RESULTS: A total of 570 patients with ABC-DLBCL (n = 285 per arm) were stratified by International Prognostic Index score, age, and bulky disease, and randomly assigned to R2-CHOP or placebo/R-CHOP. Baseline demographics were similar between arms. Most patients completed six cycles of treatment: 74% R2-CHOP and 84% placebo/R-CHOP. The most common grade 3/4 adverse events for R2-CHOP versus placebo/R-CHOP were neutropenia (60% v 48%), anemia (22% v 14%), thrombocytopenia (17% v 11%), and leukopenia (14% v 15%). The primary end point of PFS was not met, with a hazard ratio of 0.85 (95% CI, 0.63 to 1.14) and P = .29; median PFS has not been reached for either arm. PFS trends favoring R2-CHOP over placebo/R-CHOP were seen in patients with higher-risk disease.

CONCLUSION: ROBUST is the first DLBCL phase III study to integrate biomarker-driven identification of eligible ABC patients. Although the ROBUST trial did not meet the primary end point of PFS in all patients, the safety profile of R2-CHOP was consistent with individual treatments with no new safety signals.

PMID:33621109 | DOI:10.1200/JCO.20.01366

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Monopolar versus bipolar transurethral resection of lateral wall-located bladder cancer under obturator nerve block: a single center prospective randomized study

Int Braz J Urol. 2021 May-Jun;47(3):584-593. doi: 10.1590/S1677-5538.IBJU.2020.0568.

ABSTRACT

INTRODUCTION: The aim of the present prospective-randomized study was to compare perioperative outcomes and complications of bipolar and monopolar TURBT for lateral wall-located non-muscle invasive bladder cancers (NMIBC) under obturator nerve block (ONB).

PATIENTS AND METHODS: 80 patients who underwent TURBT for lateral wall-located primary bladder tumors under ONB from March, 2016 to November, 2019 were included in the present study. The patients were randomized equally into two groups; monopolar TUR (M-TURBT) and bipolar TUR (B-TURBT). The primary and secondary outcomes were safety (obturator jerk and bladder perforation) and efficacy (complete tumor resection and sampling of the deep muscle tissue).

RESULTS: Obturator jerk was detected in 2 patients (5%) in M-TURBT while obturator jerk was not observed during B-TURBT (p=0.494). Bladder perforation was not observed in both groups. All of the patients underwent complete tumor resection. There was no significant difference in muscle tissue sampling (67.5% vs. 72.5%, p=0.626) and thermal tissue damage rates (12.5% vs. 25%, p=0.201). The majority of complications were low-grade and the differences in Clavien grade 1-3 complications between groups were not statistically significant.

CONCLUSION: In the treatment of lateral-wall located NMIBCs, either M-TURBT or B-TURBT can be safely and effectively performed by combining spinal anesthesia with ONB. Even so, it should be taken into consideration that low-grade postoperative hemorrhagic complications may occur in patients who undergo M-TURBT.

PMID:33621007 | DOI:10.1590/S1677-5538.IBJU.2020.0568

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Vasectomy re-reversal: effectiveness and parameters associated with its success

Int Braz J Urol. 2021 May-Jun;47(3):544-548. doi: 10.1590/S1677-5538.IBJU.2020.0310.

ABSTRACT

INTRODUCTION: When the vasectomy reversal (VR) fails, and the patient desires natural conception with his sperm, vasectomy re-reversal (VRR) is the only alternative.

PURPOSE: To determine the VRR effectiveness and whether specific parameters can be associated with its success.

MATERIALS AND METHODS: We retrospectively evaluated 18 consecutive vasectomized patients, who had failed their VR through bilateral vasovasostomy, and posteriorly were submitted to VRR. The parameters of the study were: age of the patients, elapsed time between vasectomy and VRR (V-VRRt), elapsed time between VR and VRR (VR-VRRt), presence of spermatozoa in the proximal vas deferens fluid (SptzVDF) in the VRR and results of semen analysis after VRR (SA-VRR).

RESULTS: The mean of the age of the patients was 44.11±6.55 years (32.0-57.0), the mean of V-VRRt was 11.76±6.46 years (1.5-25.0) and the mean of VR-VRRt was 2.13±2.27 years (0.5-10.0). SptzVDF in the VRR were found bilaterally in 8 patients, unilaterally in 4 and absent in 6. SA-VRR demonstrated normozoospermia in 9 patients, oligozoospermia in 3 and azoospermia in 6, with patency rate of 66.67%. SA-VRR showed statistically significant dependence only with SptzVDF in the VRR (p <0.01).

CONCLUSIONS: VRR was effective in restoring the obstruction in more than half of the patients. Furthermore, the presence of spermatozoa in the vas deferens fluid was the parameter associated with the VRR success.

PMID:33621001 | DOI:10.1590/S1677-5538.IBJU.2020.0310

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Quality of care in type 2 diabetes, progressand challenges from 2012 to 2018-19 forthe Mexican health system

Salud Publica Mex. 2020 Nov-Dec;62(6):618-626. doi: 10.21149/11876.

ABSTRACT

OBJECTIVE: To estimate changes in the quality of process of care and its association with glycaemic control in adults with type 2 diabetes.

MATERIALS AND METHODS: Changes in compliance of 14 process of care indicators for 9 038 adults with type 2 diabetes and glycaemic control in a subsample were estimated. Averages, weighted changes and associations without or controlling for other factors were estimated us-ing statistical weights for the combined data (Ensanut 2012 and Ensanut 2018-19).

RESULTS: From 2012 to 2018-19, glycaemic control doubled. Early detection of complications and increased insuline use improved, but identification and treatment of cardiovascular risk factors decreased. The overall quality of care was associated with optimal glycaemic control.

CONCLUSIONS: There are areas of opportunity for improvement of quality of care, that deserve comprehensive strategies and continuous monitoring.

PMID:33620960 | DOI:10.21149/11876