Nevin Manimala

Econ Hum Biol. 2021 Feb 12;41:100988. doi: 10.1016/j.ehb.2021.100988. Online ahead of print.

ABSTRACT

In the U.S. in early 2020, heterogenous and incomplete county-scale data on COVID-19 hindered effective interventions in the pandemic. While numbers of deaths can be used to estimate actual number of infections after a time lag, counties with low death counts early on have considerable uncertainty about true numbers of cases in the future. Here we show that supplementing county-scale mortality statistics with socioeconomic data helps estimate true numbers of COVID-19 infections in low-data counties, and hence provide an early warning of future concern. We fit a LASSO negative binomial regression to select a parsimonious set of five predictive variables from thirty-one county-level covariates. Of these, population density, public transportation use, voting patterns and % African-American population are most predictive of higher COVID-19 death rates. To test the model, we show that counties identified as under-estimating COVID-19 on an early date (April 17) have relatively higher deaths later (July 1) in the pandemic.

PMID:33636583 | DOI:10.1016/j.ehb.2021.100988

Respir Med. 2021 Feb 12;179:106312. doi: 10.1016/j.rmed.2021.106312. Online ahead of print.

ABSTRACT

INTRODUCTION: Efforts to meet increased oxygen demands in COVID-19 patients are a priority in averting mechanical ventilation (MV), associated with high mortality approaching 76.4-97.2%. Novel methods of oxygen delivery could mitigate that risk. Oxygen hoods/helmets may improve: O₂-saturation (SaO2), reduce in-hospital mechanical ventilation and mortality rates, and reduce length of hospitalization in hypoxic Covid-19 patients failing on conventional high-flow oxygen delivery systems.

METHODS: DesignProspective Controlled Cohort Study. SettingSingle Center. ParticipantsAll patients admitted with a diagnosis of COVID-19 were reviewed and 136/347 patients met inclusion criteria. Study period3/6/2020 to 5/1/2020. 136 participants completed the study with known status for all outcome measures. Intervention or exposureOxygen hoods/helmets as compared to conventional high-flow oxygen delivery systems.

MAIN OUTCOME(S) AND MEASURE(S): 1) Pre and post change in oxygen saturation (SaO₂). 2) In-hospital Mechanical Ventilation (MV). 3) In-hospital Mortality. 4) Length of hospitalization.

RESULTS: 136 patients including 58-intervention and 78-control patients were studied. Age, gender, and other demographics/prognostic indicators were comparable between cohorts. Oxygen hoods averted imminent or immediate intubation/MV in all 58 COVID-19 patients failing on conventional high-flow oxygen delivery systems with a mean improvement in SaO₂ of 8.8%, p < 0.001. MV rates were observed to be higher in the control 37/78 (47.4%) as compared to the intervention cohort 23/58 (39.7%), a difference of 7.7%, a 27% risk reduction, not statistically significant, OR 95%CI 0.73 (0.37-1.5). Mortality rates were observed higher in the control 54/78 (69.2%) as compared to the intervention cohort 36/58 (62.1%), a difference of 7.1%, a 27% risk reduction, not statistically significant OR 95%CI 0.73 (0.36-1.5).

CONCLUSION: Oxygen hoods demonstrate improvement in SaO₂ for patients failing on conventional high-flow oxygen-delivery systems and prevented imminent mechanical ventilation. In-hospital mechanical ventilation and mortality rates were reduced with the use of oxygen hoods but not found to be statistically significant. The oxygen hood is a safe, effective oxygen-delivery system which may reduce intubation/MV and mortality rates. Their use should be considered in treating hypoxic COVID-19 patients. Further research is warranted.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04407260.

PMID:33636568 | DOI:10.1016/j.rmed.2021.106312

J Psychiatr Res. 2021 Feb 16;137:7-13. doi: 10.1016/j.jpsychires.2021.02.031. Online ahead of print.

ABSTRACT

Mental illnesses are chronic conditions in which an individual will often experience recurrent outcomes such as hospitalization, symptomatic relapse or self-harm behaviours. Most clinical research in psychiatry considers only the first event, and does not analyze subsequent recurrent events. Methods exist to analyze recurrent events; however, these methods are underused in the psychiatric research literature. This review identifies that recurrent events can be analyzed using a time homogenous or time-to-recurrent-event (TTRE) framework. The TTRE framework is underutilized in psychiatric research; however, this framework allows for longitudinal observations that are more congruent with the chronic nature of psychiatric illness than typical first event analyses. There are several readily available statistical models using the TTRE framework extending the standard Cox proportional hazards model. Our decision tool outlines four aspects of a research question to consider when selecting a TTRE model: (1) importance of event timing, (2) explanatory vs predictive, (3) common vs event-specific hazard, and (4) correlation of events within an individual. Analyzing recurrent events in psychiatric research provides an opportunity to address research questions aimed at understanding the longitudinal course of a chronic condition. These approaches may provide novel insights into risk factors or interventions for psychiatric illness, and ultimately improved outcomes for these chronic conditions.

PMID:33636563 | DOI:10.1016/j.jpsychires.2021.02.031

Vet Immunol Immunopathol. 2021 Feb 19;234:110216. doi: 10.1016/j.vetimm.2021.110216. Online ahead of print.

ABSTRACT

The pathogenesis of chronic inflammatory enteropathies (CIE) in dogs involves dysregulated innate immune responses. The receptor for advanced glycation end products (RAGE), a pattern recognition receptor, plays a role in chronic inflammation. Abrogation of proinflammatory RAGE signaling by ligand binding (e.g., S100/calgranulins) to soluble RAGE (sRAGE) might also be a novel therapeutic avenue. Serum sRAGE levels are decreased in canine CIE, but gastrointestinal tissue RAGE expression has not been investigated in dogs. Thus, the study aimed to evaluate the gastrointestinal mucosal RAGE expression in dogs with CIE. Further, the potential binding of RAGE to canine S100/calgranulin ligands was investigated. Epithelial RAGE expression was quantified in gastrointestinal (gastric, duodenal, ileal, and colonic) biopsies from 12 dogs with CIE and 9 healthy control dogs using confocal laser scanning microscopy. RAGE expression was compared between both groups of dogs and was tested for an association with patient characteristics, clinical variables, histologic lesion severity, and biomarkers of extra-gastrointestinal disease, systemic or gastrointestinal inflammation, function, or protein loss. Statistical significance was set at p < 0.05. RAGE:S100/calgranulin binding was assessed by immunoassay and electrophoretic techniques. RAGE expression was detected in all 59 biopsies from diseased and healthy control dogs evaluated. Epithelial RAGE expression in the duodenum and colon was significantly higher in dogs with CIE than in healthy controls (p < 0.04). Compared to healthy controls, RAGE expression in dogs with CIE also tended to be higher in the ileum but lower in the stomach. A slight (statistically not significant) shift towards more basal intestinal epithelial RAGE expression was detected in CIE dogs. Serum sRAGE was proportional to epithelial RAGE expression in the duodenum (p < 0.04), and RAGE expression in the colon inversely correlated with biomarkers of protein loss in serum (both p < 0.04). Several histologic morphologic and inflammatory lesion criteria and markers of inflammation (serum C-reactive protein and fecal calprotectin concentration) were related to epithelial RAGE expression in the duodenum, ileum, and/or colon. in vitro canine RAGE:S100A12 binding appeared more pronounced than RAGE:S100A8/A9 binding. This study showed a dysregulation of epithelial RAGE expression along the gastrointestinal tract in dogs with CIE. Compensatory regulations in the sRAGE/RAGE axis are an alternative explanation for these findings. The results suggest that RAGE signaling plays a role in dogs with CIE, but higher anti-inflammatory decoy receptor sRAGE levels paralleled RAGE overexpression. Canine S100/calgranulins were demonstrated to be ligands for RAGE.

PMID:33636544 | DOI:10.1016/j.vetimm.2021.110216

Neuroimage Clin. 2021 Feb 10;30:102582. doi: 10.1016/j.nicl.2021.102582. Online ahead of print.

ABSTRACT

Therapeutic hypothermia following neonatal encephalopathy due to birth asphyxia reduces death and cerebral palsy. However, school-age children without cerebral palsy treated with therapeutic hypothermia for neonatal encephalopathy still have reduced performance on cognitive and motor tests, attention difficulties, slower reaction times and reduced visuo-spatial processing abilities compared to typically developing controls. We acquired diffusion-weighted imaging data from school-age children without cerebral palsy treated with therapeutic hypothermia for neonatal encephalopathy at birth, and a matched control group. Voxelwise analysis (33 cases, 36 controls) confirmed reduced fractional anisotropy in widespread areas of white matter in cases, particularly in the fornix, corpus callosum, anterior and posterior limbs of the internal capsule bilaterally and cingulum bilaterally. In structural brain networks constructed using probabilistic tractography (22 cases, 32 controls), graph-theoretic measures of strength, local and global efficiency, clustering coefficient and characteristic path length were found to correlate with IQ in cases but not controls. Network-based statistic analysis implicated brain regions involved in visuo-spatial processing and attention, aligning with previous behavioural findings. These included the precuneus, thalamus, left superior parietal gyrus and left inferior temporal gyrus. Our findings demonstrate that, despite the manifest successes of therapeutic hypothermia, brain development is impaired in these children.

PMID:33636541 | DOI:10.1016/j.nicl.2021.102582

Neuroimage Clin. 2020 Dec 11;30:102523. doi: 10.1016/j.nicl.2020.102523. Online ahead of print.

ABSTRACT

Diffusion imaging is very useful for the diagnosis of sporadic Creutzfeldt-Jakob disease, but it has limitations in tracking disease progression as mean diffusivity changes non-linearly across the disease course. We previously showed that mean diffusivity changes across the disease course follow a quasi J-shaped curve, characterized by decreased values in earlier phases and increasing values later in the disease course. Understanding how MRI metrics change over-time, as well as their correlations with clinical deficits are crucial steps in developing radiological biomarkers for trials. Specifically, as mean diffusivity does not change linearly and atrophy mainly occurs in later stages, neither alone is likely to be a sufficient biomarker throughout the disease course. We therefore developed a model combining mean diffusivity and Volume loss (MRI Disease-Staging) to take into account mean diffusivity’s non-linearity. We then assessed the associations between clinical outcomes and mean diffusivity alone, Volume alone and finally MRI Disease-Staging. In 37 sporadic Creutzfeldt-Jakob disease subjects and 30 age- and sex-matched healthy controls, high angular resolution diffusion and high-resolution T1 imaging was performed cross-sectionally to compute z-scores for mean diffusivity (MD) and Volume. Average MD and Volume were extracted from 41 GM volume of interest (VOI) per hemisphere, within the images registered to the Montreal Neurological Institute (MNI) space. Each subject’s volume of interest was classified as either “involved” or “not involved” using a statistical threshold of ± 2 standard deviation (SD) for mean diffusivity changes and/or -2 SD for Volume. Volumes of interest were MRI Disease-Staged as: 0 = no abnormalities; 1 = decreased mean diffusivity only; 2 = decreased mean diffusivity and Volume; 3 = normal (“pseudo-normalized”) mean diffusivity, reduced Volume; 4 = increased mean diffusivity, reduced Volume. We correlated Volume, MD and MRI Disease-Staging with several clinical outcomes (scales, score and symptoms) using 4 major regions of interest (Total, Cortical, Subcortical and Cerebellar gray matter) or smaller regions pre-specified based on known neuroanatomical correlates. Volume and MD z-scores correlated inversely with each other in all four major ROIs (cortical, subcortical, cerebellar and total) highlighting that ROIs with lower Volumes had higher MD and vice-versa. Regarding correlations with symptoms and scores, higher MD correlated with worse Mini-Mental State Examination and Barthel scores in cortical and cerebellar gray matter, but subjects with cortical sensory deficits showed lower MD in the primary sensory cortex. Volume loss correlated with lower Mini-Mental State Examination, Barthel scores and pyramidal signs. Interestingly, for both Volume and MD, changes within the cerebellar ROI showed strong correlations with both MMSE and Barthel. Supporting using a combination of MD and Volume to track sCJD progression, MRI Disease-Staging showed correlations with more clinical outcomes than Volume or MD alone, specifically with Mini-Mental State Examination, Barthel score, pyramidal signs, higher cortical sensory deficits, as well as executive and visual-spatial deficits. Additionally, when subjects in the cohort were subdivided into tertiles based on their Barthel scores and their percentile of disease duration/course (“Time-Ratio”), subjects in the lowest (most impaired) Barthel tertile showed a much greater proportion of more advanced MRI Disease-Stages than the those in the highest tertile. Similarly, subjects in the last Time-Ratio tertile (last tertile of disease) showed a much greater proportion of more advanced MRI Disease-Stages than the earliest tertile. Therefore, in later disease stages, as measured by time or Barthel, there is overall more Volume loss and increasing MD. A combined multiparametric quantitative MRI Disease-Staging is a useful tool to track sporadic Creutzfeldt-Jakob- disease progression radiologically.

PMID:33636540 | DOI:10.1016/j.nicl.2020.102523

Epilepsy Behav. 2021 Feb 12;117:107855. doi: 10.1016/j.yebeh.2021.107855. Online ahead of print.

ABSTRACT

OBJECTIVES: We assessed the impact of COVID-19 on children with epilepsy and their families, focusing on epilepsy management, family routines, learning, and adherence to Centers for Disease Control and Prevention (CDC) pandemic guidelines (e.g., social distancing, mask wearing) within the first six months of the pandemic. Group differences in COVID-19 impact on families were also examined based on race and ethnicity, being medically and/or geographically underserved, and insurance status.

METHODS: Participants (n = 131) included children with epilepsy and their families from two clinical trials. The Impact of COVID-19 on Pediatric Epilepsy Management (ICPEM) measure was developed and administered to caregivers online from April 2020 to September 2020 across four large pediatric hospitals. Administration of the ICPEM occurred both during routine study assessments and an additional acute time point to obtain information early in the pandemic (e.g., April and May 2020). Descriptive statistics and t-tests were used for analyses.

RESULTS: Data indicate minor to moderate impact of COVID-19 on pediatric epilepsy management. Caregivers of children with epilepsy reported the most impact on education and social functioning. Adherence to CDC guidelines was reported to be high. Those having public insurance reported greater difficulties obtaining daily anti-seizure medications compared to those with private insurance.

CONCLUSIONS: This study presents important initial data regarding the impact of COVID-19 epilepsy management and daily functioning in children with epilepsy and their families. While the acute impact of COVID-19 restrictions appear to be mild to moderate, it is unclear what the long-term impact of the pandemic will be on families of children with epilepsy.

PMID:33636530 | DOI:10.1016/j.yebeh.2021.107855

Epilepsy Behav. 2021 Feb 23;117:107711. doi: 10.1016/j.yebeh.2020.107711. Online ahead of print.

ABSTRACT

OBJECTIVE: It remains unclear whether transcranial magnetic stimulation (TMS) can replace the Wada test to determine language hemisphere dominance (HD). Using the Wada test as the gold standard, this study aimed to investigate the accuracy of navigated TMS (nTMS) in determining language HD.

METHODS: This study enrolled nine right-handed patients with drug-resistant epilepsy. We hypothesized that application of nTMS to language-related areas of the language-dominant hemisphere would induce positive manifestation of language dysfunction (LD). To test our hypothesis, the patients were instructed to perform a visual object-naming task while nTMS was applied to the anterior (e.g., Broca’s area) and posterior (e.g., Wernicke’s area) regions, which are closely related to language processing. The Wada test result was used as the gold standard, and the diagnostic value of nTMS was assessed using the Kappa consistency test.

RESULTS: The nTMS-induced LD positive rate for the bilateral anterior language areas (85.7%) was higher than that for the posterior language areas (57.1%). There was high consistency between nTMS stimulation of the left anterior and posterior language areas and the Wada test results for determining language HD. In contrast, the consistency of stimulation of the right anterior and posterior transfer sites was moderate (Kappa value = 0.545, P = 0.171) and low, respectively. For the latter, no statistical calculation was performed because stimulation of the right posterior speech area was negative in all patients compared with the Wada test results.

CONCLUSIONS: Our findings revealed that using nTMS to stimulate language-related left anterior and posterior areas could predict language HD with high accuracy. When the stimulation performance of these areas is positive, nTMS and the Wada test are equally accurate. Observing only negative performance may indicate that language HD has been transferred to the right side.

PMID:33636527 | DOI:10.1016/j.yebeh.2020.107711

Adv Clin Exp Med. 2021 Feb 26. doi: 10.17219/acem/130357. Online ahead of print.

ABSTRACT

BACKGROUND: The laparoscopic totally extraperitoneal inguinal hernia repair (TEP), unlike the Lichtenstein tension-free mesh repair, allows for inspecting the femoral canal area for the presence of an occult femoral hernia.

OBJECTIVES: To determine the incidence of an unsuspected femoral hernia in patients undergoing TEP repair.

MATERIAL AND METHODS: Data was collected prospectively from 180 patients (23 women) who underwent hernia repair, including examination of the femoral canal, between November 2017 and March 2019, and the incidence of a femoral hernia was determined. Correlations between the incidence of a femoral hernia and sex, age and the type of inguinal hernia diagnosed in the patients (indirect, direct, both indirect and direct) were assessed.

RESULTS: Femoral hernias were found in 14 patients (7.77%). None of the hernias had previously been detected clinically. The incidence of a femoral hernia was higher in women (6/23, 26.07%) than in men (8/157, 5.09%). The incidence of a femoral hernia was higher in older patients: the average age of patients with a femoral hernia was 57.86 years (median: 60 years), whereas the average age of patients without a femoral hernia was 49.92 years (median: 49 years). However, the correlation was not statistically significant. No correlation was found between the incidence of a femoral hernia and the type of inguinal hernia diagnosed in the patients (direct, indirect, both indirect and direct).

CONCLUSIONS: The TEP repair allows for detecting and repairing an occult femoral hernia.

PMID:33636062 | DOI:10.17219/acem/130357

Int J Clin Pract. 2021 Feb 26:e14118. doi: 10.1111/ijcp.14118. Online ahead of print.

ABSTRACT

PURPOSE: To investigate the prediction values of the preoperative NLR, LMR, PLR, MPV, RDW for recurrence and progression of patients with non-muscle invasive bladder cancer (NMIBC).

METHODS: In this prospective study, 94 consecutive patients, newly diagnosed with NMIBC between July 2017 – August 2018 were included. The blood samples were collected from patients before transurethral resection of bladder tumor (TURB) and NLR, LMR, PLR, RDW, MPV values were calculated. The effect of these preoperative inflammatory parameters and other clinicopathological parameters on recurrence and progression rates were evaluated. Kaplan-Meier and multivariate Cox regression analyses were performed to identify significant prognostic variables.

RESULTS: The mean follow-up was 11 ± 6.4 months. Recurrence was observed in 35.1% and progression was detected in 7.4% of the patients. Neutrophil-lymphocyte ratio was statistically significantly associated with both recurrence (p = 0.01) and progression (p = 0.035) whereas lymphocyte-monocyte ratio was only associated with recurrence (p = 0.038). In the survival analyses, the relationship between recurrence and LMR was confirmed in both univariate (p = 0.021) and multivariate (p = 0.022) analyses. The relationship between NLR and recurrence was confirmed in univariate analysis (p = 0.019), however in multivariate analysis was found to be statistically insignificant (p = 0.051).

CONCLUSIONS: Lymphocyte-monocyte ratio might be an easy obtainable, non-invasive and cost-effective method for predicting recurrence of disease in patients with non-muscle invasive bladder cancer.

PMID:33636055 | DOI:10.1111/ijcp.14118