Category: Statistics

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

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

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

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

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

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

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

Spine (Phila Pa 1976). 2021 Mar 15;46(6):374-382. doi: 10.1097/BRS.0000000000003796.

ABSTRACT

STUDY DESIGN: Prospective comparative study.

OBJECTIVE: The aim of this study was to compare the spatiotemporal, kinematic, kinetic and electromyographic (EMG) gait variables in patients with adolescent idiopathic scoliosis (AIS) and congenital scoliosis and to compare these gait variables of scoliosis patients with healthy controls.

SUMMARY OF BACKGROUND DATA: Earlier studies have solely focussed on the possibility of altered gait patterns in AIS patients; not much light has been shed on the differences in gait patterns in congenital and adolescent scoliosis patients.

METHODS: Forty scoliosis patients (20 each with AIS and congenital scoliosis) and 20 healthy volunteers were prospectively recruited. After thorough clinical and radiological examination, all patients underwent gait analysis in accordance with standard protocols.The outcome measures included spatiotemporal, kinetic, kinematic and EMG activity. Composite indices for gait analysis-Gait Profile Score (GPS) and Gait Deviation Index (GDI)-were also calculated. Relevant statistical tests were applied to compare the different groups.

RESULTS: No significant difference was found between the AIS and congenital scoliosis groups with respect to baseline demographic and radiological parameters. The two subgroups of scoliosis patients (AIS and congenital) did not differ significantly with respect to any of the measured gait analysis parameters. However, when compared to the healthy age-matched control group, the scoliosis patients differed significantly with respect to gait speed, stride length, step length, GDI, GPS and peak EMG activation for erector spinae, biceps femoris, semimembranosus, rectus femoris, gastrocnemious, and tibialis anterior.

CONCLUSION: Our findings confirm the previous findings of literature regarding the alteration in gait patterns in scoliosis patients when compared to normal individuals. However, the lack of difference in gait analysis variables between AIS and congenital scoliosis patients suggests that this alteration in gait is secondary to the existence of the deformity and does not correlate with the onset or etiology of deformity.Level of Evidence: 2.

PMID:33620181 | DOI:10.1097/BRS.0000000000003796

Ann Noninvasive Electrocardiol. 2021 Feb 23:e12832. doi: 10.1111/anec.12832. Online ahead of print.

ABSTRACT

BACKGROUD: Present electrocardiogram (ECG) criteria for diagnosing left ventricular hypertrophy (LVH) usually have low sensitivity, while the newly proposed SD + SV4 criterion, namely the deepest S-wave amplitude in any lead (SD) plus SV4 amplitude, has been reported to have higher sensitivity and accuracy compared with other existing criteria. We aimed to further evaluate the diagnostic value of the SD + SV4 criterion in reference to the gold standard cardiac magnetic resonance imaging (CMR) in LVH diagnosis.

METHODS: This retrospective study enrolled 138 patients who received CMR examination-60 patients with reduced ejection fraction (EF) and 78 patients with preserved EF. The left ventricular mass index (LVMI) measured by CMR was used as the gold standard for diagnosing LVH.

RESULT: The diagnostic value of the SD + SV4 criterion was compared with other 4 commonly used criteria. By CMR, 29 out of 138 people (21%) were diagnosed with LVH in reference to CMR. The SD + SV4 criterion had markedly higher sensitivity in diagnosing LVH compared with other criteria, but no higher specificity. There was no significant difference in area under receiver operating characteristic (ROC) curve among these criteria. The SD + SV4 criterion was not markedly consistent with CMR in diagnosing LVH. Compared to the other criteria, the SD + SV4 criterion had the highest sensitivity in patients with reduced ejection fraction; however, the area under the curve (AUC) of the SD + SV4 criterion in patients with reduced EF was significantly lower than in patients with preserved EF.

CONCLUSION: The newly proposed SD + SV4 criterion did not have a better diagnostic value compared with other existing criteria, and the statistical power of the SD + SV4 criterion was influenced by EF.

PMID:33620147 | DOI:10.1111/anec.12832

Cancer Med. 2021 Feb 23. doi: 10.1002/cam4.3732. Online ahead of print.

ABSTRACT

PURPOSE: To date there has not been an extensive analysis of the outcomes of biomarker use in oncology.

METHODS: Data were pooled across four indications in oncology drawing upon trial outcomes from www.clinicaltrials.gov: breast cancer, non-small cell lung cancer (NSCLC), melanoma and colorectal cancer from 1998 to 2017. We compared the likelihood drugs would progress through the stages of clinical trial testing to approval based on biomarker status. This was done with multi-state Markov models, tools that describe the stochastic process in which subjects move among a finite number of states.

RESULTS: Over 10000 trials were screened, which yielded 745 drugs. The inclusion of biomarker status as a covariate significantly improved the fit of the Markov model in describing the drug trajectories through clinical trial testing stages. Hazard ratios based on the Markov models revealed the likelihood of drug approval with biomarkers having nearly a fivefold increase for all indications combined. A 12, 8 and 7-fold hazard ratio was observed for breast cancer, melanoma and NSCLC, respectively. Markov models with exploratory biomarkers outperformed Markov models with no biomarkers.

CONCLUSION: This is the first systematic statistical evidence that biomarkers clearly increase clinical trial success rates in three different indications in oncology. Also, exploratory biomarkers, long before they are properly validated, appear to improve success rates in oncology. This supports early and aggressive adoption of biomarkers in oncology clinical trials.

PMID:33620160 | DOI:10.1002/cam4.3732