Nevin Manimala

Sci Rep. 2021 Nov 12;11(1):22203. doi: 10.1038/s41598-021-01290-7.

ABSTRACT

APACHE IVa provides typically useful and accurate predictions on in-hospital mortality and length of stay for patients in critical care. However, there are factors which may preclude APACHE IVa from reaching its ceiling of predictive accuracy. Our primary aim was to determine which variables available within the first 24 h of a patient’s ICU stay may be indicative of the APACHE IVa scoring system making occasional but potentially illuminating errors in predicting in-hospital mortality. We utilized the publicly available multi-institutional ICU database, eICU, available since 2018, to identify a large observational cohort for our investigation. APACHE IVa scores are provided by eICU for each patient’s ICU stay. We used Lasso logistic regression in an aim to build parsimonious final models, using cross-validation to select the penalization parameter, separately for each of our two responses, i.e., errors, of interest, which are APACHE falsely predicting in-hospital death (Type I error), and APACHE falsely predicting in-hospital survival (Type II error). We then assessed the performance of the models with a random holdout validation sample. While the extremeness of the APACHE prediction led to dependable predictions for preventing either type of error, distinct variables were identified as being strongly associated with the two different types of errors occurring. These included a primary set of predictors consisting of mean SpO2 and worst lactate for predicting Type I errors, and worst albumin and mean heart rate for Type II. In addition, a secondary set of predictors including changes recorded in care limitations for the patient’s treatment plan, worst pH, whether cardiac arrest occurred at admission, and whether vasopressor was provided for predicting Type I error; age, whether the patient was ventilated in day 1, mean respiratory rate, worst lactate, worst blood urea nitrogen test, and mean aperiodic vitals for Type II. The two models also differed in their performance metrics in their holdout validation samples, in large part due to the lower prevalence of Type II errors compared to Type I. The eICU database was a good resource for evaluating our objective, and important recommendations are provided, particularly identifying key variables that could lead to APACHE prediction errors when APACHE scores are sufficiently low to predict in-hospital survival.

PMID:34772961 | DOI:10.1038/s41598-021-01290-7

Sci Rep. 2021 Nov 12;11(1):22192. doi: 10.1038/s41598-021-01478-x.

ABSTRACT

Tropical organisms are more vulnerable to climate change and associated heat stress as they live close to their upper thermal limits (UTLs). UTLs do not only vary little across tropical species according to the basal versus plasticity ‘trade-off’ theory but may also be further constrained by low genetic variation. We tested this hypothesis, and its effects on ecosystem function using a diurnally active dung rolling beetle (telecoprid), Allogymnopleurus thalassinus (Klug, 1855) that inhabits arid environments. Specifically, (i) we tested basal heat tolerance (critical thermal maxima [CT_max] and heat knockdown time [HKDT]), and (ii) ecological functioning (dung removal) efficiency following dynamic chronic acclimation temperatures of variable high (VT-H) (28-45 °C) and variable low (VT-L) (28-16 °C). Results showed that A. thalassinus had extremely high basal heat tolerance (> 50 °C CT_max and high HKDT). Effects of acclimation were significant for heat tolerance, significantly increasing and reducing CT_max values for variable temperature high and variable temperature low respectively. Similarly, effects of acclimation on HKDT were significant, with variable temperature high significantly increasing HKDT, while variable temperature low reduced HKDT. Effects of acclimation on ecological traits showed that beetles acclimated to variable high temperatures were ecologically more efficient in their ecosystem function (dung removal) compared to those acclimated at variable low temperatures. Allogymnopleurus thalassinus nevertheless, had low acclimation response ratios, signifying limited scope for complete plasticity for UTLs tested here. This result supports the ‘trade-off’ theory, and that observed limited plasticity may unlikely buffer A. thalassinus against effects of climate change, and by extension, albeit with caveats to other tropical ecological service providing insect species. This work provides insights on the survival mechanisms of tropical species against heat and provides a framework for the conservation of these natural capital species that inhabit arid environments under rapidly changing environmental climate.

PMID:34772933 | DOI:10.1038/s41598-021-01478-x

Nat Commun. 2021 Nov 12;12(1):6570. doi: 10.1038/s41467-021-26357-x.

ABSTRACT

The Earth’s climate system is a classical example of a multiscale, multiphysics dynamical system with an extremely large number of active degrees of freedom, exhibiting variability on scales ranging from micrometers and seconds in cloud microphysics, to thousands of kilometers and centuries in ocean dynamics. Yet, despite this dynamical complexity, climate dynamics is known to exhibit coherent modes of variability. A primary example is the El Niño Southern Oscillation (ENSO), the dominant mode of interannual (3-5 yr) variability in the climate system. The objective and robust characterization of this and other important phenomena presents a long-standing challenge in Earth system science, the resolution of which would lead to improved scientific understanding and prediction of climate dynamics, as well as assessment of their impacts on human and natural systems. Here, we show that the spectral theory of dynamical systems, combined with techniques from data science, provides an effective means for extracting coherent modes of climate variability from high-dimensional model and observational data, requiring no frequency prefiltering, but recovering multiple timescales and their interactions. Lifecycle composites of ENSO are shown to improve upon results from conventional indices in terms of dynamical consistency and physical interpretability. In addition, the role of combination modes between ENSO and the annual cycle in ENSO diversity is elucidated.

PMID:34772916 | DOI:10.1038/s41467-021-26357-x

Med Sci Sports Exerc. 2021 Nov 10. doi: 10.1249/MSS.0000000000002824. Online ahead of print.

ABSTRACT

INTRODUCTION: Low-load resistance training with blood flow restriction (LL-BFR) has emerged as a viable alternative to conventional high-load (HL) resistance training regimens. Despite increasing evidence confirming comparable muscle adaptations between LL-BFR and HL resistance exercise, only very little is known about tendinous mechanical and morphological adaptations following LL-BFR. Therefore, the aim of the present study was to examine the effects of 14 weeks of LL-BFR and HL training on patellar tendon adaptations.

METHODS: N = 29 recreationally active male participants were randomly allocated into the following two groups: LL-BFR resistance training (20-35% one repetition maximum/1RM) or HL resistance training (70-85% 1RM). Both groups trained three times per week for 14 weeks. One week before and after the intervention, patellar tendon mechanical and morphological properties were assessed via ultrasound and magnetic resonance imaging (MRI). Additionally, changes in muscle cross-sectional area (CSA) were quantified by MRI and muscle strength via dynamic 1RM measurements.

RESULTS: The findings demonstrated that both LL-BFR and HL training resulted in comparable changes in patellar tendon stiffness (LL-BFR: + 25.2%, p = 0.003; HL: + 22.5%, p = 0.024) without significant differences between groups. Similar increases in tendon CSA were observed in HL and LL-BFR. Muscle mass and strength also significantly increased in both groups but were not statistically different between HL (+ 38%) and LL-BFR (+ 34%), except for knee extension 1RM where higher changes were seen in LL-BFR.

CONCLUSION: The present results support the notion that both HL and LL-BFR cause substantial changes in patellar tendon properties and the magnitude of changes are not significantly different between conditions. Further studies are needed which examine the physiological mechanisms underlying the altered tendon properties following LL-BFR training.

PMID:34772900 | DOI:10.1249/MSS.0000000000002824

Pediatr Emerg Care. 2021 Nov 10. doi: 10.1097/PEC.0000000000002569. Online ahead of print.

ABSTRACT

OBJECTIVES: Emergency department (ED) volumes have drawn attention to frequent users but less attention has been paid to children. This study examined sociodemographic and ED presentation characteristics of pediatric high-system ED users (HSUs) in 2 provinces in Canada.

METHODS: Cohorts of HSUs were created from the National Ambulatory Care Reporting System in 2015/2016 for children with the top 10% of ED presentations. Controls were random samples of non-HSU patients. Factors were explored in multivariable logistic regression models.

RESULTS: There were 151,497 HSUs (51.7% girls, average age, 6.4 years) and 591,545 controls (53.1% girls; average age, 7.4 years). High-system ED users were more likely to be younger (adjusted odds ratio [aOR], 0.89 per 5 years; 95% confidence interval [CI], 0.88-0.89), live in less populated areas (aOR, 1.85; 95% CI, 1.82-1.88), and from lowest income neighborhoods (aOR, 1.51; 95% CI, 1.48-1.54) than controls. High-system ED users had higher proportions of presentations for pediatric complex chronic (aOR, 1.25 per 0.25 increase; 95% CI, 1.21-1.29), respiratory (aOR, 1.14 per 0.25; 95% CI, 1.12-1.15), and mental health (aOR, 1.14 per 0.25; 95% CI, 1.13-1.16) conditions than controls.

CONCLUSIONS: Complex factors underlie pediatric health care utilization decisions. Findings identified conditions to target in interventions to improve health care access and utilization. Future work should engage children and families to design interventions.

PMID:34772876 | DOI:10.1097/PEC.0000000000002569

J Glaucoma. 2021 Nov 12. doi: 10.1097/IJG.0000000000001965. Online ahead of print.

ABSTRACT

PRECIS: Patient education and dosing self-efficacy are important factors related to ongoing adherence to glaucoma topical treatment, and patients view their disease management as a shared effort with their provider.

PURPOSE: Glaucoma affects nearly 3 million Americans and medication adherence has been reported to be as low as 20% in this patient population; however, key limitations to our understanding of this behavior in adults with glaucoma exist.

PATIENT AND METHODS: This research used an electronic survey including validated concepts related to topical medication use and an in-person interview to investigate the influencers of and solutions for challenges to medication adherence in adults with glaucoma. Patient eligibility was determined upon arrival to a regularly-scheduled visit to the Vanderbilt Eye Institute during which they were asked for consent to complete the survey. Responses were captured by tablet and assessed using descriptive and inferential statistics. The primary focus was instrument correlations with the Adherence to Refills and Medications Scale (ARMS) score, and were run between ARMS and the totaled score for each individual questionnaire as well as individual items. Recorded interviews were thematically assessed by multiple study team members.

RESULTS: Survey results of adults with glaucoma suggested that self-efficacy, forgetfulness, fear of side effects, and dosing ability were all related to self-reported medication adherence. Despite most having glaucoma for several years, discrepancies in disease knowledge were observed. Patient interviews uncovered three overall themes related to glaucoma treatment: (1) glaucoma management as a shared responsibility; (2) the importance of patient education; and (3) specific adherence facilitators and barriers.

CONCLUSION: Glaucoma medication adherence interventions may benefit from focusing on developing patient medication-taking self-efficacy, disease-related education, and engagement with their provider.

PMID:34772874 | DOI:10.1097/IJG.0000000000001965

J Chin Med Assoc. 2021 Nov 11. doi: 10.1097/JCMA.0000000000000659. Online ahead of print.

ABSTRACT

BACKGROUND: One new type of acupuncture and related techniques (ACNRT), is increasingly used by Rheumatoid arthritis (RA) patients to control their disease and improve their quality of life. However, the efficacy of using ACNRT in combination with western medicine (WM) for this purpose remains unknown.

METHODS: Randomized controlled trials of ACNRT and WM treatments for RA from January 1, 2000 to January 31, 2021 were searched for in the databases PubMed, Embase, Medline, and the Cochrane Central Register of Controlled Trials, as well as in three Chinese databases: China National Knowledge Infrastructure, Wanfang Data, and Airiti Library. The primary outcomes consisted of inflammatory markers including C reactive protein (CRP), erythrocyte sedimentation rate (ESR) and rheumatoid factor (RF). The secondary outcomes were clinical characteristics including pain visual analog scale (VAS) score; Disease Activity Score (DAS-28); swollen-joints count (SJC); tender-joints count (TJC); morning stiffness (MS); and the results of a health assessment questionnaire (HAQ). The three types of ACNRT used in the focal trials were acupuncture, moxibustion, and electro-acupuncture.Two qualified researchers extracted data from these trials’ results and independently assessed their risk of bias. Statistical analyses were performed using Comprehensive Meta-Analysis V3 software.

RESULTS: A total of 12 RCTs with 874 patients met the inclusion criteria. As compared with the patients who received WM treatment alone, those who were given integrated ACNRT/WM treatment showed greater reductions in CRP (weighted mean difference [WMD]:-6.299; 95% confidence interval [CI]:-9.082 to -3.517), ESR (WMD:-6.563; 95% CI:-8.604 to -4.522), VAS (WMD:-1.089; 95% CI:-1.575 to -0.602), DAS-28 (WMD:-0.633; 95% CI:-1.006 to -0.259), SJC (WMD:-1.921; 95% CI:-3.635 to -0.207), TJC (WMD:-1.491; 95% CI:-2.941 to -0.042).

CONCLUSION: This meta-analysis of RA provides reliable evidence in favor of ACNRT plus WM. However, longer-term, high-quality, repeatable, multi-center randomized controlled trials with larger sample sizes are needed.

PMID:34772862 | DOI:10.1097/JCMA.0000000000000659

JAAPA. 2021 Nov 10. doi: 10.1097/01.JAA.0000800260.99283.d3. Online ahead of print.

ABSTRACT

OBJECTIVE: To evaluate the effect of an arthritis center on patient care and operational throughput.

METHODS: A single-institution, retrospective review was conducted of patients with hip or knee osteoarthritis from January 2016 to October 2019. Our physician assistant (PA) led arthritis center opened in November 2017, and manages nonoperative treatment of osteoarthritis by formulating individualized treatment plans. Descriptive and inferential statistics comparing operational measures, treatment patterns, and patient satisfaction pre- and postcenter opening were performed.

RESULTS: Overall patient volume, new patient volume, and the proportion of new patients seen increased after the arthritis center opened. Encounters per patient and clinicians seen per patient decreased, while the rate of injections and surgery increased. Patient satisfaction improved after opening of the arthritis center.

CONCLUSIONS: The establishment of a dedicated PA-led arthritis center is associated with improved access to care, operational efficiency, and patient satisfaction in patients with hip and knee osteoarthritis.

PMID:34772855 | DOI:10.1097/01.JAA.0000800260.99283.d3

AIDS. 2021 Nov 11. doi: 10.1097/QAD.0000000000003131. Online ahead of print.

ABSTRACT

OBJECTIVE: To propose a unified continuum-of-care (CoC) analysis combining cross-sectional and longitudinal elements, incorporating time spent between stages.

DESIGN: The established 90-90-90 target follows a cross-sectional 4-stage CoC analysis, lacking information on timing of diagnosis, antiretroviral therapy (ART) initiation and viral suppression (VS) durability.

METHODS: Data were derived from the Athens Multicenter AIDS Cohort Study (AMACS). In the cross-sectional CoC, we added stratification of diagnosed people living with HIV (PLHIV) by estimated time from infection to diagnosis; of those who ever initiated ΑRT or achieved VS by corresponding current status (in 2018); and cumulative incidence function (CIF) of ART initiation and VS, treating loss-to-follow-up (LTFU) as competing event. VS was defined as viral load (VL)<500 copies/ml. VS durability was assessed by the CIF of VL rebound.

FINDINGS: 89.1% of PLHIV in 2018 were diagnosed (range of diagnoses: 1980-2018). Median time to diagnosis was 3.5 years (IQR:1.1-7.0). Among diagnosed 89.1% were ever treated, of whom 86.7% remained on ART. CIF of ART initiation and LTFU before ART initiation were 80.9% and 6.0% at 5 years since diagnosis, respectively. Among treated, 89.4% achieved VS, of whom 87.4% were currently virally suppressed. The CIF of VL rebound was 24.2% at 5 years since first VS but substantially reduced in more recent years.

INTERPRETATION: The proposed analysis highlights time gaps in CoC not evident by the standard cross-sectional approach. Our analysis highlights the need for early diagnosis and identifies late presenters as a key population for interventions that could decrease gaps in the CoC.

PMID:34772850 | DOI:10.1097/QAD.0000000000003131

Am J Surg Pathol. 2021 Nov 15. doi: 10.1097/PAS.0000000000001840. Online ahead of print.

ABSTRACT

The separation of benign from malignant mesothelial proliferations is often a difficult pathologic problem. UHRF1 (ubiquitin-like with plant homeodomain and ring finger domains-1) is a regulator of DNA methylation and an epigenetic driver of various human cancers. It has recently been reported that UHRF1 is overexpressed in mesotheliomas. We asked whether UHRF1 immunohistochemistry could be used to separate benign from malignant mesothelial proliferations. Initial studies showed that UHRF1 stained mesothelial cells but also endothelial and other non-neoplastic cells, so that accurate counting of positive mesothelial cells was difficult. Therefore, we ran dual UHRF1-AE1/AE3 stains on 2 tissue microarrays containing 40 reactive mesothelial proliferations and 61 mesotheliomas and only counted UHRF1 staining in keratin-positive cells. On average 10.3±8.6% (mean±SD; range: 0% to 36, median: 6.8%) of epithelioid mesothelioma cells stained compared with 5.3±4.8% (range: 0% to 15%, median: 4.1%) of reactive epithelial mesothelial cells. This difference was statistically significant but there was too much overlap to use diagnostically. In contrast, 37±26% (range: 2.5% to 95%, median: 31%) of cells in sarcomatoid mesotheliomas compared with 1.2±1.2% (range: 0% to 3.0%, median: 1.0%) of cells in reactive spindle cell mesothelial proliferations stained. To confirm this difference we stained whole sections of 21 sarcomatoid mesotheliomas and 19 cases of organizing pleuritis. Staining of mesothelial cells was seen in 2.1±2.4% (range: 0% to 6.8%, median: 1.0%) of organizing pleuritis cases and 44±22% (range: 14% to 90%, median: 41%) of sarcomatoid mesotheliomas. We conclude that dual UHRF1-AE1/AE3 immunohistochemistry is very useful for separating benign spindle cell mesothelial proliferations from sarcomatoid mesotheliomas.

PMID:34772842 | DOI:10.1097/PAS.0000000000001840