To describe the proportion of children screened by the Modified Checklist for Autism in Toddlers (M-CHAT), identify characteristics associated with screen completion, and examine associations between ...autism spectrum disorder (ASD) screening and later ASD diagnosis.
We examined data from children attending 18- and 24-month visits between 2013 and 2016 from 20 clinics within a health care system for evidence of screening with the M-CHAT and subsequent coding of ASD diagnosis at age >4.75 years. We interviewed providers for information about usual methods of M-CHAT scoring and ASD referral.
Of 36 233 toddlers, 73% were screened and 1.4% were later diagnosed with ASD. Hispanic children were less likely to be screened (adjusted prevalence ratio APR: 0.95, 95% confidence interval CI: 0.92-0.98), and family physicians were less likely to screen (APR: 0.12, 95% CI: 0.09-0.15). Compared with unscreened children, screen-positive children were more likely to be diagnosed with ASD (APR: 10.3, 95% CI: 7.6-14.1) and were diagnosed younger (38.5 vs 48.5 months,
< .001). The M-CHAT's sensitivity for ASD diagnosis was 33.1%, and the positive predictive value was 17.8%. Providers routinely omitted the M-CHAT follow-up interview and had uneven referral patterns.
A majority of children were screened for ASD, but disparities exist among those screened. Benefits for screen-positive children are improved detection and younger age of diagnosis. Performance of the M-CHAT can be improved in real-world health care settings by administering screens with fidelity and facilitating timely ASD evaluations for screen-positive children. Providers should continue to monitor for signs of ASD in screen-negative children.
The Coronavirus-19 disease (COVID-19) has claimed over 6.8 million lives since first being reported in late 2019. The virus that causes COVID-19 disease is highly contagious and spreads rapidly. To ...date, there are no approved prognostic tools that could predict why some patients develop severe or fatal disease outcomes. Early COVID-19 studies found an association between procalcitonin (PCT) and hospitalization or duration of mechanical ventilation and death but were limited by the cohort sizes. Therefore, this study was designed to confirm the associations of PCT with COVID-19 disease severity outcomes in a large cohort. For this retrospective data analysis study, 27,154 COVID-19-positive US veterans with post-infection PCT laboratory test data and their disease severity outcomes were accessed using the VA electronic healthcare data. Cox regression models were used to test the association between serum PCT levels and disease outcomes while controlling for demographics and relevant confounding variables. The models demonstrated increasing disease severity (ventilation and death) with increasing PCT levels. For PCT serum levels above 0.20 ng/ml, the unadjusted risk increased nearly 2.3-fold for mechanical ventilation (hazard ratio, HR, 2.26, 95%CI: 2.11-2.42) and in-hospital death (HR, 2.28, 95%CI: 2.16-2.41). Even when adjusted for demographics, diabetes, pneumonia, antibiotic use, white blood cell count, and serum C-reactive protein levels, the risks remained relatively high for mechanical ventilation (HR, 1.80, 95%CI: 1.67-1.94) and death (HR, 1.76, 95%CI: 1.66-1.87). These data suggest that higher PCT levels have independent associations with ventilation and in-hospital death in veterans with COVID-19 disease, validating previous findings. The data suggested that serum PCT level may be a promising prognostic tool for COVID-19 severity assessment and should be further evaluated in a prospective clinical trial.
Slow conduction areas and conduction block in the atria are considered pro-arrhythmic conditions. Studies examining the size and distribution of slow conduction regions in the context of persistent ...atrial fibrillation (AF) may help to develop improved therapeutic strategies for patients with AF. In this work, we studied the differences of size and number in slow conduction areas between control and persistent AF goats and the influence of propagation direction on the development of these pathological conduction areas. Epicardial atrial electrical activations from the left atrial roof were optically mapped with physiological pacing cycle lengths and for the shortest captured cycle lengths. The recordings were converted to local activation times and conduction velocity measures. Regions with slow conduction velocity (less than Formula: see text) were identified. The size of the connected regions and the number of non-connected regions were counted for propagation from different orthogonal directions. We found that regions of slow conduction significantly increases in our 15 persistent AF goat recordings in response to premature stimulation (24.4±4.3% increase to 36.6±4.4%, p < 0.001). This increase is driven by an increase of size from (3.70±0.89mm2 to 6.36±0.91mm2, p = 0.014) for already existing regions and not by generation of new slow conduction regions (11.6±1.8 vs. 13±1.9, p = 0.242). In 12 control goat recordings, no increase from baseline pacing to premature pacing was found. Similarly, size of the slow conduction areas and the count did not change significantly in control animals.
Accumulation of 7-ketocholesterol (7KC) occurs in age-related macular degeneration (AMD) and was found previously to promote fibrosis, an untreatable cause of vision loss, partly through induction of ...endothelial-mesenchymal transition. To address the hypothesis that 7KC causes mesenchymal transition of retinal pigment epithelial cells (RPE), we exposed human primary RPE (hRPE) to 7KC or a control. 7KC-treated hRPE did not manifest increased mesenchymal markers, but instead maintained RPE-specific proteins and exhibited signs of senescence with increased serine phosphorylation of histone H3, serine/threonine phosphorylation of mammalian target of rapamycin (p-mTOR), p16 and p21, β-galactosidase labeling, and reduced LaminB1, suggesting senescence. The cells also developed senescence-associated secretory phenotype (SASP) determined by increased IL-1β, IL-6, and VEGF through mTOR-mediated NF-κB signaling, and reduced barrier integrity that was restored by the mTOR inhibitor, rapamycin. 7KC-induced p21, VEGF, and IL-1β were inhibited by an inhibitor of protein kinase C. The kinase regulates IQGAP1 serine phosphorylation. Furthermore, after 7KC injection and laser-induced injury, mice with an IQGAP1 serine 1441-point mutation had significantly reduced fibrosis compared to littermate control mice. Our results provide evidence that age-related accumulation of 7KC in drusen mediates senescence and SASP in RPE, and IQGAP1 serine phosphorylation is important in causing fibrosis in AMD.
The prudent use of prescription opiate medications is a central aspect of postoperative pain management. The mortality associated with prescription opiate overdose is reaching epidemic proportions ...nationally, and is the leading cause of accidental death in greater than half the states in the United States. This study sought to determine the rates of preinjury opiate use in patients with orthopaedic trauma and the risk factors for prolonged use postinjury.
The Utah Controlled Substance Database was queried to determine the use of prescription opiates by all patients admitted to the orthopaedic trauma service for a two-year period with isolated musculoskeletal injuries. Usage three months prior to injury and six months postinjury was examined.
Six hundred and thirteen patients met inclusion criteria. Among patients with orthopaedic trauma, 15.5% had filled a prescription for opiates in the three months prior to injury, compared with 9.2% of the general population (p < 0.001). More than one prescription was filled by 12.2% of the patients with trauma preinjury compared with 6.4% of the general population (p < 0.001). Postoperatively, 68.4% of all patients filled opiate prescriptions for less than six weeks, 11.9% filled opiate prescriptions between six and twelve weeks, and 19.7% filled opiate prescriptions past twelve weeks. Patients with preinjury use of more than one opiate prescription in the three months preinjury were six times as likely to continue use past twelve weeks, and 3.5 times as likely to obtain opiates from a provider other than their surgeon (p < 0.001). Opiate use was briefest with upper-extremity injuries, followed by lower-extremity injuries and pelvic or acetabular injuries. Regression models demonstrate that risk factors for prolonged use of opiates include advancing age and extent of preinjury use.
Patients with orthopaedic trauma are significantly more likely than the general population to use prescription opiates prior to injury. Preinjury opiate use is predictive of prolonged use postinjury and predictive of patients who will seek opiates from other providers.
Use of empirical broad-spectrum antibiotics for pneumonia has increased owing to concern for resistant organisms, including methicillin-resistant Staphylococcus aureus (MRSA). The association of ...empirical anti-MRSA therapy with outcomes among patients with pneumonia is unknown, even for high-risk patients.
To compare 30-day mortality among patients hospitalized for pneumonia receiving empirical anti-MRSA therapy vs standard empirical antibiotic regimens.
Retrospective multicenter cohort study was conducted of all hospitalizations in which patients received either anti-MRSA or standard therapy for community-onset pneumonia in the Veterans Health Administration health care system from January 1, 2008, to December 31, 2013. Subgroups of patients analyzed were those with initial intensive care unit admission, MRSA risk factors, positive results of a MRSA surveillance test, and positive results of a MRSA admission culture. Primary analysis was an inverse probability of treatment-weighted propensity score analysis using generalized estimating equation regression; secondary analyses included an instrumental variable analysis. Statistical analysis was conducted from June 14 to November 20, 2019.
Empirical anti-MRSA therapy plus standard pneumonia therapy vs standard therapy alone within the first day of hospitalization.
Risk of 30-day all-cause mortality after adjustment for patient comorbidities, vital signs, and laboratory results. Secondary outcomes included the development of kidney injury and secondary infections with Clostridioides difficile, vancomycin-resistant Enterococcus species, or gram-negative bacilli.
Among 88 605 hospitalized patients (86 851 men; median age, 70 years interquartile range, 62-81 years), empirical anti-MRSA therapy was administered to 33 632 (38%); 8929 patients (10%) died within 30 days. Compared with standard therapy alone, in weighted propensity score analysis, empirical anti-MRSA therapy plus standard therapy was significantly associated with an increased adjusted risk of death (adjusted risk ratio aRR, 1.4 95% CI, 1.3-1.5), kidney injury (aRR, 1.4 95% CI, 1.3-1.5), and secondary C difficile infections (aRR, 1.6 95% CI, 1.3-1.9), vancomycin-resistant Enterococcus spp infections (aRR, 1.6 95% CI, 1.0-2.3), and secondary gram-negative rod infections (aRR, 1.5 95% CI, 1.2-1.8). Similar associations between anti-MRSA therapy use and 30-day mortality were found by instrumental variable analysis (aRR, 1.6 95% CI, 1.4-1.9) and among patients admitted to the intensive care unit (aRR, 1.3 95% CI, 1.2-1.5), those with a high risk for MRSA (aRR, 1.2 95% CI, 1.1-1.4), and those with MRSA detected on surveillance testing (aRR, 1.6 95% CI, 1.3-1.9). No significant favorable association was found between empirical anti-MRSA therapy and death among patients with MRSA detected on culture (aRR, 1.1 95% CI, 0.8-1.4).
This study suggests that empirical anti-MRSA therapy was not associated with reduced mortality for any group of patients hospitalized for pneumonia. These results contribute to a growing body of evidence that questions the value of empirical use of anti-MRSA therapy using existing risk approaches.
Abstract Background Hypomethylated cell-free DNA (cfDNA) from senescent placental trophoblasts may be involved in the activation of the inflammatory cascade to initiate labor. Objective To determine ...the changes in cfDNA concentrations, the methylation ratio, and inflammatory markers between women in labor at term versus women without labor. Study Design In this prospective cohort study, eligible participants carried a non- anomalous singleton fetus. Women with major medical comorbidity, preterm labor, progesterone use, aneuploidy, infectious disease, vaginal bleeding, abdominal trauma, or invasive procedures during the pregnancy were excluded. Maternal blood samples were collected at 28 weeks, 36 weeks, and at admission for delivery. Total cfDNA concentration, methylation ratio, and interleukin-6 (IL-6) were analyzed. The primary outcome was the difference in methylation ratio in women with labor versus without labor. Secondary outcomes included the longitudinal changes in these biomarkers corresponding to labor status. Results 55 women were included; 20 presented in labor on admission and 35 presented without labor. Women in labor had significantly higher methylation ratio (p= 0.001) and IL-6 (p<0.001) on admission for delivery than women without labor. After controlling for BMI and maternal age, methylation ratio (aRR 1.38, 95% CI 1.13-1.68) and IL-6 (aRR 1.12, 95%CI 1.07-1.17) remained higher in women presenting in labor. Total cfDNA was not significantly different in women with labor compared to women without. Longitudinally, total cfDNA (p<0.001 in labor, p=0.002 without labor) and IL-6 (p<0.001 in labor, p=0.01 without labor) increased significantly across gestation in both groups. The methylation ratio increased significantly in women with labor from 36 weeks to delivery (p=0.02). Conclusion Spontaneous labor at term is associated with a higher cfDNA methylation ratio and IL-6 compared to non-labored controls. As gestation advances, total cfDNA concentrations and IL-6 levels increase. A higher methylation ratio reflects a higher maternal contribution (versus placental) in women with labor, likely resulting from higher levels of neutrophils, lymphocytes, and uterine activation proteins at the time of labor. Although not significant, women in labor had a higher total cfDNA concentration and thus could theoretically have more hypomethylated DNA available for interaction with the inflammatory cascade. Larger studies are needed to investigate this theory.
Cigars are available in a range of pack quantities, which contrasts regulations requiring cigarettes to be sold in packs of 20 or greater. Smaller packages may be associated with increases in ...initiation while larger packs may lead consumers to smoke more. The purpose of this study was to inform pack quantity regulations by examining whether usual cigar pack quantity purchased was associated with use, initiation, and discontinuation among youth and adults for four cigar types: premium cigars, large cigars, cigarillos, and filtered cigars.
We analyzed waves 1-5 (2013-2019) of the adult and waves 2-5 (2014-2019) of the youth Population Assessment of Tobacco and Health (PATH) Study. Samples included those responding to the item on pack quantity and providing data at all waves (adults: premium cigars N = 536, large cigars N = 1,272, cigarillos N = 3,504, filtered cigars N = 1,281; youth: premium cigars N = 55, large cigars N = 217, cigarillos N = 1514, filtered cigars N = 266). Generalized estimating equation models examined the population-averaged effects of pack quantity on cigar use, initiation, and discontinuation.
Adult pack quantity was positively associated with the days used per month for premium cigars (b: 0.23, 95% CI: 0.11, 0.34), large cigars (b: 0.17, 95% CI: 0.08, 0.25), cigarillos (b: 0.12, 95% CI: 0.003, 0.24), and filtered cigars (b: 0.07, 95% CI: 0.04, 0.10), and positively associated with amount smoked per day for all cigar types. Youth pack quantity was positively associated with days used per month for premium cigars (b: 0.88, 95% CI: 0.33, 1.43), large cigars (b: 0.79, 95% CI: 0.43, 1.15), and cigarillos (b: 0.17, 95% CI: 0.01, 0.34). Adult initiation was associated with pack quantity for filtered cigars (b: -2.22, 95% CI: -4.29, -0.13), as those who initiated purchased smaller pack quantities compared to those who did not initiate that wave. Pack quantity was not associated with discontinuation for adults or youth.
Cigar use increased as usual pack quantity purchased increased across cigar types for youth and adults. Small increases in pack quantity (e.g., one additional cigar) are likely to result in consuming less than one additional day per month, though larger increases (e.g., 10 additional cigars per pack) may result in greater use.
Intraplaque hemorrhage (IPH) is associated with acute and future stroke. IPH is also associated with lumen markers of stroke risk including stenosis, plaque thickness, and ulceration. Whether IPH ...adds further predictive value to these other variables is unknown. The purpose of this study was to determine whether IPH improves carotid-source stroke prediction.
In this retrospective cross-sectional study, patients undergoing stroke workup were imaged with MRI and IPH detection. Seven hundred twenty-six carotid-brain image pairs were analyzed after excluding vessels with noncarotid plaque stroke sources (420) and occlusions (7) or near-occlusions (3). Carotid imaging characteristics were recorded, including percent diameter and mm stenosis, plaque thickness, ulceration, intraluminal thrombus, and IPH. Clinical confounders were recorded, and a multivariable logistic regression model was fitted. Backward elimination was used to determine essential carotid-source stroke predictors with a threshold 2-sided P<0.10. Receiver operating characteristic analysis was performed to determine discriminatory value.
Significant predictors of carotid-source stroke included intraluminal thrombus (odds ratio=103.6; P<0.001), IPH (odds ratio=25.2; P<0.001), current smoking (odds ratio=2.78; P=0.004), and thickness (odds ratio=1.24; P=0.020). The final model discriminatory value was excellent (area under the curve=0.862). This was significantly higher than the final model without IPH (area under the curve=0.814), or models using only stenosis as a continuous variable (area under the curve=0.770) or cutoffs of 50% and 70% (area under the curve=0.669), P<0.001.
After excluding patients with noncarotid plaque stroke sources, optimal discrimination of carotid-source stroke was obtained with intraluminal thrombus, IPH, plaque thickness, and smoking history but not ulceration and stenosis.
PDF
