Tag: pubmed

Psychiatr Genet. 2022 Mar 31:YPG.0000000000000316. doi: 10.1097/YPG.0000000000000316. Online ahead of print.

ABSTRACT

BACKGROUND: Autism spectrum disorder (ASD) is a clinically and genetically heterogeneous group of neurodevelopmental disorders. Despite the extensive efforts of scientists, the etiology of ASD is far from completely elucidated. In an effort to enlighten the genetic architecture of ASDs, a meta-analysis of all available genetic association studies (GAS) was conducted.

METHODS: We searched in the Human Genome Epidemiology Navigator (HuGE Navigator) and PubMed for available case-control GAS of ASDs. The threshold for meta-analysis was two studies per genetic variant. The association between genotype distribution and ASDs was examined using the generalized linear odds ratio (ORG). For variants with available allele frequencies, the examined model was the allele contrast.

RESULTS: Overall, 57 candidate genes and 128 polymorphisms were investigated in 159 articles. In total 28 genetic polymorphisms have been shown to be associated with ASDs, that are harbored in 19 genes. Statistically significant results were revealed for the variants of the following genes adenosine deaminase (ADA), bone marrow stromal cell antigen-1 (CD157/BST1), Dopamine receptor D1 (DRD1), engrailed homolog 2 (EN2), met proto-oncogene (MET), methylenetetrahydrofolate reductase (MTHFR), solute carrier family 6 member 4 (SLC6A4), Synaptosomal-associated protein, 25kDa (SNAP-25) and vitamin D receptor (VDR). In the allele contrast model of cases versus healthy controls, significant associations were observed for Adrenoceptor Alpha 1B (ADRA1B), acetyl serotonin O – methyltransferase (ASMT), complement component 4B (C4B), dopamine receptor D3 (DRD3), met proto-oncogene (MET), neuroligin 4, X-linked (NLGN4), neurexin 1 (NRXN1), oxytocin receptor (OXTR), Serine/Threonine-Protein Kinase PFTAIRE-1 (PFTK1), Reelin (RELN) and Ras-like without CAAX 2 (RIT2).

CONCLUSION: These significant findings provide further evidence for genetic factors’ implication in ASDs offering new perspectives in means of prevention and prognosis.

PMID:35353796 | DOI:10.1097/YPG.0000000000000316

PLoS Comput Biol. 2022 Mar 30;18(3):e1009965. doi: 10.1371/journal.pcbi.1009965. Online ahead of print.

ABSTRACT

Several important aspects related to SARS-CoV-2 transmission are not well known due to a lack of appropriate data. However, mathematical and computational tools can be used to extract part of this information from the available data, like some hidden age-related characteristics. In this paper, we present a method to investigate age-specific differences in transmission parameters related to susceptibility to and infectiousness upon contracting SARS-CoV-2 infection. More specifically, we use panel-based social contact data from diary-based surveys conducted in Belgium combined with the next generation principle to infer the relative incidence and we compare this to real-life incidence data. Comparing these two allows for the estimation of age-specific transmission parameters. Our analysis implies the susceptibility in children to be around half of the susceptibility in adults, and even lower for very young children (preschooler). However, the probability of adults and the elderly to contract the infection is decreasing throughout the vaccination campaign, thereby modifying the picture over time.

PMID:35353810 | DOI:10.1371/journal.pcbi.1009965

Pediatr Emerg Care. 2022 Mar 29. doi: 10.1097/PEC.0000000000002676. Online ahead of print.

ABSTRACT

BACKGROUND: Recent studies highlight the importance of physician readiness to practice beyond graduate training. The Accreditation Council for Graduate Medical Education mandates that pediatric emergency medicine (PEM) fellows be prepared for independent practice by allowing “progressive responsibility for patient care.” Prior unpublished surveys of program directors (PDs) indicate variability in approaches to provide opportunities for more independent practice during fellowship training.

OBJECTIVES: The aims of the study were to describe practices within PEM fellowship programs allowing fellows to work without direct supervision and to identify any barriers to independent practice in training.

DESIGN/METHODS: An anonymous electronic survey of PEM fellowship PDs was performed. Survey items were developed using an iterative modified Delphi process and pilot tested. Close-ended survey responses and demographic variables were summarized with descriptive statistics. Responses to open-ended survey items were reviewed and categorized by theme.

RESULTS: Seventy two of 84 PDs (88%) responded to the survey; however, not all surveys were completed. Of the 68 responses to whether fellows could work without direct supervision (as defined by the Accreditation Council for Graduate Medical Education) during some part of their training, 31 (45.6%) reported that fellows did have this opportunity. In most programs, clinical independence was conditional on specific measures including the number of clinical hours completed, milestone achievement, and approval by the clinical competency committee. Reported barriers to fellow practice without direct oversight included both regulatory and economic constraints.

CONCLUSIONS: Current training practices that provide PEM fellows with conditional clinical independence are variable. Future work should aim to determine best practices of entrustment, identify ideal transition points, and mitigate barriers to graduated responsibility.

PMID:35353795 | DOI:10.1097/PEC.0000000000002676

J Nerv Ment Dis. 2022 Mar 30. doi: 10.1097/NMD.0000000000001510. Online ahead of print.

ABSTRACT

This study aims to investigate the relationship between binge-watching addiction and family, emotional, conduct, cognitive and anger control problems, hyperactivity, Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV)-ADHD Index, DSM-IV-Inattention, and DSM-IV-Hyperactivity Impulsivity in a large sample of healthy Turkish adolescents. The association between binge-watching behavior addiction and mood disorders in healthy adolescents was examined in this cross-sectional study conducted in Turkey. Participants completed both measures, The Binge-Watching Addiction Questionnaire and The Conners-Wells’ Adolescent Self-Report Scale. An online survey of 189 adolescents was conducted. One hundred fourteen subjects (60.3%) were categorized into the binge-watcher group. Results showed important positive associations between binge-watching behavior and emotional, conduct, cognitive problems, and DSM-IV-Inattention. The conducted analysis showed an important association between high frequency of binge-watching and emotional problems (p < 0.001), conduct problems (p = 0.012), cognitive problems (p = 0.001), and inattention (p < 0.001). These findings contributed to our comprehension of adolescents’ psychological correlates of television viewing behavior. Further researches on the relationship between extreme binge-watching and psychiatric disorders of adolescents are recommended.

PMID:35353791 | DOI:10.1097/NMD.0000000000001510

Neurologist. 2022 Mar 30. doi: 10.1097/NRL.0000000000000434. Online ahead of print.

ABSTRACT

BACKGROUND AND PURPOSE: Stroke-associated pneumonia (SAP) has been found as a common complication in acute ischemic stroke (AIS) patients. Large artery atherosclerosis (LAA) infarct is a major subtype of AIS. This study aimed to build a clinical prediction model for SAP of LAA type AIS patients.

METHODS: This study included 295 patients with LAA type AIS. Univariate analyses and logistic regression analyses were conducted to determine the independent predictors for the modeling purpose. Nomogram used receiver operating characteristics to assess the accuracy of the model, and the calibration plots were employed to assess the fitting degree between the model and the practical scenario. One hundred and five patients were employed for the external validation to test the stability of the model.

RESULTS: From the univariate analysis, patients’ ages, neutrophil-to-lymphocyte ratios, National Institute of Health Stroke scale (NIHSS) scores, red blood cell, sex, history of coronary artery disease, stroke location and volume-viscosity swallow test showed statistical difference in the development group for the occurrence of SAP. By incorporating the factors above into a multivariate logistic regression analysis, patients’ ages, neutrophil-to-lymphocyte ratios, NIHSS, and volume-viscosity swallow test emerged as the independent risk factors of the development of SAP. The nomogram based on the mentioned 4 variables above achieved a receiver operating characteristic of 0.951 and a validation group of 0.946.

CONCLUSIONS: The proposed nomogram is capable of predicting predict the occurrence of SAP in LAA type AIS patients, and it may identify high-risk patients in time and present information for in-depth treatment.

PMID:35353784 | DOI:10.1097/NRL.0000000000000434

J Chin Med Assoc. 2022 Mar 31. doi: 10.1097/JCMA.0000000000000719. Online ahead of print.

ABSTRACT

BACKGROUND: Two antifibrotic medications, pirfenidone and nintedanib, have been approved as treatments for idiopathic pulmonary fibrosis (IPF), a life-threatening interstitial lung disease. However, there is insufficient current data regarding clinical predictors of survival for IPF patients in the era of antifibrotics.

METHODS: We retrospectively analyzed the medical records of IPF patients treated between April 2017 and May 2020. Univariate and multivariate Cox hazard proportional models were used to identify independent predictors of mortality among these patients with IPF.

RESULTS: A total of 40 IPF patients (average age: 75.58 ± 8.34 years) were included in the study, 27 (67.5%) of whom were treated with antifibrotic drugs. In the entire cohort, 14 (35%) patients died, and the overall survival of the study population was 48.52 ± 5 months (median: NA [29, NA] months). The univariate and multivariate Cox hazard proportional models indicated that chest tightness, finger clubbing, acute exacerbation after medication, decreased FVC%, and decreased FEV1% were clinical factors linked to all-cause mortality among all patients, although without statistical significance at the multivariate level. Meanwhile, only finger clubbing was a significant mortality predictor among patients who received antifibrotic medications. A mortality scoring system was built upon the aforementioned risk factors, with the exclusion of FVC%, whose individual mortality score was nearly zero.

CONCLUSION: Chest tightness, finger clubbing, acute exacerbation after medication, and decreased FVC% were clinical factors associated with mortality in IPF patients, although without statistical significance. A scoring system including these factors can be used to predict all-cause mortality in IPF patients. The mere intake of antifibrotic medications was not a significant mortality predictor in this study. This might be owed to the retrospective nature of the study, where many patients started the medications after the deterioration of their pulmonary function rather than from the start.

PMID:35353790 | DOI:10.1097/JCMA.0000000000000719

Neuropsychol Rehabil. 2022 Mar 30:1-24. doi: 10.1080/09602011.2022.2044863. Online ahead of print.

ABSTRACT

This study investigated whether experiential and video feedback on performance of prospective memory (PM) tasks embedded within a board game activity improved self-awareness of PM function in adults with moderate-severe traumatic brain injury. An observational pre-post study design with 26 participants from a larger trial of a 6-session PM rehabilitation programme. Sessions 3 and 4 included a board game activity with embedded time-, event-, and activity-based PM tasks. Verbal feedback was provided by therapists during the game and video feedback afterwards. Self-ratings of performance were used to divide the sample into under-estimators (n = 7), accurate estimators (n = 9) and over-estimators (n = 10) of actual PM performance. The discrepancy between self- and therapist ratings of PM performance was measured before and after the game, and following video feedback, and compared between timepoints using non-parametric statistics. Post-task self-evaluations were more accurate than pre-task self-evaluations for the under- and over-estimator groups. Under-estimators showed significant improvement in accuracy of ratings for activity-based PM. Over-estimators showed improvement for event-based PM. Further improvements after video feedback were not significant. The board game activity provided a vehicle for experiential feedback and a means of engaging both those with impaired self-awareness and heightened self-awareness of PM in cognitive rehabilitation.

PMID:35353028 | DOI:10.1080/09602011.2022.2044863

Am J Hosp Palliat Care. 2022 Mar 30:10499091221078978. doi: 10.1177/10499091221078978. Online ahead of print.

ABSTRACT

Background: Cardiac arrest is a critical condition with high clinical, economic, and emotional burden. The role of palliative medicine in the management of critical patients has grown and, in some areas, has shown reduced cost of stay. This study set out to examine the association of palliative care involvement in out of hospital post cardiac arrest patients and cost of stay. Methods: This is a single center retrospective analysis of all patients ≥18 years of age who were admitted at our institution from March 2018 to June 2019 with out of hospital cardiac arrest. Patients who immediately died in the emergency department were excluded. Patients were then classified according to whether palliative care was consulted. Total charges were obtained from the billing records and compared between those with palliative care compared to those without using Mann-Whitney U test. Results: A final sample of 98 patients that were included in the analysis. The mean age was 61.2 ± 17.3, 46% were female, and 61% were African American. Palliative care consultation was present in 27 (28%) of patients. There were no significant differences among age, gender, ethnicity, BMI, SOFA scores, and common comorbidities among those who did and did not have palliative care consultation. While there was a significantly longer ICU length of stay and mechanical ventilation days among patients with palliative care involvement P < .0001, the charges among patients with palliative care involvement were not statistically significantly different $59,245 ($3744-148,492) (median IQR) compared to those without palliative care $79,521 ($6540-157,952) P = .762. Conclusion: Length of stay increased with palliative care consultation which may relate more to the inherent clinical scenario. Cost of stay was not statistically significantly different.

PMID:35353018 | DOI:10.1177/10499091221078978

ACS Infect Dis. 2022 Mar 30. doi: 10.1021/acsinfecdis.1c00513. Online ahead of print.

ABSTRACT

Leishmaniasis is one of the neglected tropical diseases with a worldwide distribution, affecting humans and animals. In the absence of an effective vaccine, current treatment is through the use of chemotherapy; however, existing treatments have frequent appearance of drug resistance and therapeutic failure (TF). The identification of factors that contribute to TF in leishmaniasis will provide the basis for a future therapeutic strategy more efficient for the control of this disease. In this article, we have evaluated the transcriptomic changes in the host cells THP-1 after infection with clinical Leishmania infantum isolates from leishmaniasis patients with TF. Our results show that distinct L. infantum isolates differentially modulate host cell response, inducing phenotypic changes that probably may account for parasite survival and TF of patients. Analysis of differential expression genes (DEGs), with a statistical significance threshold of a fold change ≥ 2 and a false discovery rate value ≤ 0.05, revealed a different number of DEGs according to the Leishmanialine. Globally, there was a similar number of genes up- and downregulated in all the infected host THP-1 cells, with exception of Hi-L2221, which showed a higher number of downregulated DEGs. We observed a total of 58 DEGs commonly modulated in all infected host cells, including upregulated (log₂FC ≥ 1) and downregulated (log₂FC ≤ -1) genes. Based on the results obtained from the analysis of RNA-seq, volcano plot, and GO enrichment analysis, we identified the most significant transcripts of relevance for their possible contribution to the TF observed in patients with leishmaniasis.

PMID:35352952 | DOI:10.1021/acsinfecdis.1c00513

J Manag Care Spec Pharm. 2022 Mar 30:1-12. doi: 10.18553/jmcp.2022.21436. Online ahead of print.

ABSTRACT

BACKGROUND: People with type 2 diabetes (T2D) who change their basal insulin (BI) may have variable persistence with therapy. Compared with first-generation (long-acting) BI analogs (insulin glargine 100U/mL [Gla-100]; insulin detemir [IDet]), second-generation (longer-acting) BI analogs (insulin glargine 300U/mL [Gla-300]; insulin degludec) have similar glycated hemoglobin (HbA1c) attainment and lowered hypoglycemia risk, which could impact treatment persistence. OBJECTIVE: To compare persistence, adherence, health care resource utilization (HRU), and costs for individuals switching from neutral protamine Hagedorn insulin or a first-generation BI analog with either the second-generation BI, Gla-300, or an alternative first-generation BI analog (Gla-100 or IDet). METHODS: We used Optum Clinformatics claims data from adults (aged ≥ 18 years) with T2D who had received BI (neutral protamine Hagedorn, Gla-100, IDet) in the 6-month baseline period, and switched to either Gla-300 or an alternative first-generation BI (Gla-100 or IDet; treatment switch = index date) between April 1, 2015, and August 31, 2019. Participants were followed for 12 months, until plan disenrollment, or until death, whichever occurred first. Cohorts were propensity score matched (PSM) on baseline characteristics. The primary outcome was the proportion who were persistent with therapy at 12 months. Secondary outcomes were adherence (proportion of days covered); change in HbA1c; and all-cause, diabetes-related, and hypoglycemia-related HRU and costs. RESULTS: PSM generated 3,077 participants/group (mean age: 68 years, 52% female). Cohorts were well balanced except for hospitalization, which was adjusted in models as a covariate. During the 12-month follow-up period, participants who received Gla-300 vs first-generation BI had greater persistence with (45.5% vs 42.1%; adjusted P = 0.0001), and adherence to (42.8% vs 38.2%; adjusted P = 0.0006), BI therapy and a statistically larger reduction in HbA1c at 12 months (-0.65% vs -0.45%; adjusted P = 0.0040). The proportion of participants achieving HbA1c less than 8% (47.2% vs 40.9%; P < 0.0001), but not less than 7% (21.2% vs 20.8%), was significantly higher for Gla-300 vs first-generation BI. All-cause (45.3 vs 65.9 per 100 patient-years [P100PY]) and diabetes-related (21.5 vs 29.1 P100PY), but not hypoglycemia-related, hospitalizations (1.0 vs 1.5 P100PY) were significantly (P < 0.0001) lower for Gla-300 vs first-generation BI. Similarly, all-cause (111.9 vs 148.8 P100PY), diabetes-related (54.8 vs 74.2 P100PY), and hypoglycemia-related (2.9 vs 5.7 P100PY) emergency department (ED) visits were significantly lower for Gla-300 (all P < 0.0001). Costs for all-cause hospitalizations and hypoglycemia-related ED visits were significantly lower for Gla-300 vs first-generation BI. Although pharmacy costs were significantly higher for Gla-300 vs first-generation BI, all-cause total health care costs were not significantly different: $41,255 vs $45,316 per person per year, respectively. CONCLUSIONS: In this claims-based analysis of people with T2D receiving BI, switching to Gla-300 was associated with significantly better persistence, adherence, and HbA1c reduction compared with switching to an alternative first-generation BI analog. All-cause HRU was significantly lower; despite significantly higher pharmacy costs, total health care costs were similar. DISCLOSURES: This study was funded by Sanofi US. Medical writing support was provided by Helen Jones, PhD, CMPP, of Evidence Scientific Solutions and funded by Sanofi US. Dr Wright is on the speakers’ bureau and sits on the advisory boards for Abbot Diabetes, Bayer, Boehringer Ingelheim, Eli Lilly, and Sanofi; sits on the advisory board for Medtronic; and is a consultant for Abbot Diabetes, Bayer, Boehringer Ingelheim, and Eli Lilly. Dr Malone is on advisory boards for Novartis and Avalere and consults for Pear Therapeutics, Sarepta, and Strategic Therapeutics. Dr Trujillo sits on advisory boards for Novo Nordisk and Sanofi. Drs Gill, Zhou, and Preblick and Mr Li are employees and stockholders of Sanofi. Mr Huse is an employee of Evidera and a contractor for Sanofi. Dr Reid is a speaker and consultant for Novo Nordisk and Sanofi-Aventis and is a consultant for AstraZeneca and Intarcia.

PMID:35352995 | DOI:10.18553/jmcp.2022.21436