Nevin Manimala

J Assoc Physicians India. 2022 May;70(5):11-12.

ABSTRACT

BACKGROUND: Many studies found that only hypomagnesemia, but not hypermagnesemia is linked with increased mortality. However, reports of mortality due to magnesium dysregulation in the critical care setting are controversial.

OBJECTIVES: To study serum magnesium levels in critically ill patients on admission in intensive care unit (ICU) and its correlation with patient’s need and duration for ventilator support, duration of ICU stay, incidence of cardiac arrhythmias and mortality Methods: Two hundred forty six critically ill patients admitted in ICU with Acute Physiology and Chronic Health Evaluation (APACHE) II scores>10, were included for this prospective observational study. Serum total magnesium level was measured at the time of admission to ICU. Primary outcome measure was ICU mortality whereas, secondary outcome measures were patient’s need and duration for ventilator support, duration of ICU stay, and incidence of cardiac arrhythmias. Categorical and continuous variables were tested using Chi-square/Fisher’s exact test and analysis of variance respectively. Multivariate logistic regression analysis was carried out to determine association of serum magnesium levels with ICU mortality.

RESULTS: Incidence of ICU mortality was significantly higher in group of patients with hypomagnesemia compared to those with normal magnesium levels. Hypomagnesemia was associated with need and longer duration of ventilator support, longer duration of ICU stay, higher APACHE II score, QTc prolongation, higher incidence of cardiac arrhythmias compared to patients with normal magnesium levels. Hypomagnesemia was an independent and statistically significant determinant of ICU mortality.

CONCLUSIONS: Hypomagnesemia was associated with higher mortality rate, longer duration of ventilator support and ICU stay, and higher APACHE II score in critically ill patients.

PMID:35598126

Clin Transplant. 2022 May 21:e14716. doi: 10.1111/ctr.14716. Online ahead of print.

ABSTRACT

The Scientific Registry of Transplant Recipients (SRTR) held a consensus conference in 2012 that examined methods used by SRTR for constructing performance metrics and made recommendations on how to improve program-specific reports. That consensus conference provided 25 recommendations categorized as follows: statistical methods, risk adjustment, and outcomes and data. During the subsequent decade, SRTR has implemented most of these recommendations; these are described in this article along with plans for another consensus conference in 2022. With the present article, SRTR aims to create transparency in the field of transplant metrics and guide discussion in the planning of the next consensus conference in 2022. The new conference will revisit the previous topics and have a broader focus to improve the metrics and information that SRTR provides. Readers can provide feedback on topics to be discussed at the next consensus conference as early as possible, by emailing [email protected] with the subject line “Task 5 Public Comment.” This article is protected by copyright. All rights reserved.

PMID:35598080 | DOI:10.1111/ctr.14716

Med Phys. 2022 May 21. doi: 10.1002/mp.15765. Online ahead of print.

ABSTRACT

BACKGROUND: Fast and accurate multi-organs segmentation from CT scans is essential for radiation treatment planning. Self-attention based deep learning methodologies provide higher accuracies than standard methods but require memory and computationally intensive calculations, which restricts their use to relatively shallow networks.

PURPOSE: Our goal was to develop and test a new computationally fast and memory efficient bi-directional self-attention method called nested block self attention (NBSA), which is applicable to shallow and deep multi-organ segmentation networks.

METHODS: A new multi-organ segmentation method combining a deep multiple resolution residual network with computationally efficient self attention called nested block self attention (MRRN-NBSA) was developed and evaluated to segment 18 different organs from head and neck (HN) and abdomen organs. MRRN-NBSA combines features from multiple image resolutions and feature levels with self-attention to extract organ specific contextual features. Computationally efficiency is achieved by using memory blocks of fixed spatial extent for self-attention calculation combined with bi-directional attention flow. Separate models were trained for HN (n = 238) and abdomen (n = 30) and tested on set aside open-source grand challenge datasets for HN (n = 10) using public domain database of computational anatomy and blinded testing on 20 cases from Beyond the Cranial Vault dataset with overall accuracy provided by the grand challenge website for abdominal organs. Robustness to two-rater segmentations was also evaluated for HN cases using the open-source dataset. Statistical comparison of MRRN-NBSA against Unet, convolutional network based self attention using criss-cross attention (CCA), dual self-attention, and transformer-based (UNETR) methods was done by measuring the differences in the average Dice similarity coefficient (DSC) accuracy for all HN organs using the Kruskall-Wallis test, followed by individual method comparisons using paired, two-sided Wilcoxon-signed rank tests at 95% confidence level with Bonferroni correction used for multiple comparsions.

RESULTS: MRRN-NBSA produced an average high DSC of 0.88 for HN and 0.86 for the abdomen that exceeded current methods. MRRN-NBSA was more accurate than the computationally most efficient CCA (average DSC of 0.845 for HN, 0.727 for abdomen). Kruskal-Wallis test showed significant difference between evaluated methods (p=0.00025). Pair-wise comparisons showed significant differences between MRRN-NBSA than Unet (p=0.0003), CCA (p=0.030), dual (p=0.038), and UNETR methods (p=0.012) after Bonferroni correction. MRRN-NBSA produced less variable segmentations for submandibular glands (0.82 ± 0.06) compared to two raters (0.75 ± 0.31).

CONCLUSIONS: MRRN-NBSA produced more accurate multi-organ segmentations than current methods on two different public datasets. Testing on larger institutional cohorts is required to establish feasibility for clinical use. This article is protected by copyright. All rights reserved.

PMID:35598077 | DOI:10.1002/mp.15765

Ann Neurol. 2022 May 21. doi: 10.1002/ana.26417. Online ahead of print.

ABSTRACT

OBJECTIVE: Evidence on associations of lifestyle factors with Alzheimer’s pathology and cognition are ambiguous, potentially because they rarely addressed interrelationships of factors and sex effects. While considering these aspects, we examined the relationships of lifestyle factors with brain amyloid burden and cognition.

METHODS: We studied 178 cognitively normal individuals (women, 49%; 65.0 [7.6] years) and 54 individuals with mild cognitive impairment (women, 35%; 71.3 [8.3] years) enrolled in a prospective study of volunteers who completed ¹⁸ F-Flutemetamol amyloid positron emission tomography. Using structural equation modeling, we examined associations between latent constructs representing metabolic/vascular risk, physical activity, and cognitive activity with global amyloid burden and cognitive performance. Furthermore, we investigated the influence of sex in this model.

RESULTS: Overall, higher cognitive activity was associated with better cognitive performance and higher physical activity was associated with lower amyloid burden. The latter association was weakened to a non-significant level after excluding multivariate outliers. Examination of the moderating effect of sex in the model revealed an inverse association of metabolic/vascular risk with cognition in men whereas in women metabolic/vascular risk trended towards increased amyloid burden. Furthermore, a significant inverse association between physical activity and amyloid burden was found only in men. Inheritance of an APOE4 allele was associated with higher amyloid burden only in women.

INTERPRETATION: Sex modifies effects of certain lifestyle-related factors on amyloid burden and cognition. Notably, our results suggest that the negative impact of metabolic/vascular risk influences the risk of cognitive decline and Alzheimer’s disease through distinct paths in women and men. This article is protected by copyright. All rights reserved.

PMID:35598071 | DOI:10.1002/ana.26417

Biophys J. 2022 May 20:S0006-3495(22)00407-6. doi: 10.1016/j.bpj.2022.05.014. Online ahead of print.

ABSTRACT

Actin is one of the key structural components of the eukaryotic cytoskeleton that regulates cellular architecture and mechanical properties. Dynamic regulation of actin filament length and organization is essential for the control of many physiological processes including cell adhesion, motility and division. While previous studies have mostly focused on the mechanisms controlling the mean length of individual actin filaments, it remains poorly understood how distinct actin filament populations in cells maintain different lengths using the same set of molecular building blocks. Here we develop a theoretical model for the length regulation of multiple actin filaments by nucleation and growth rate modulation by actin binding proteins in a limiting pool of monomers. We first show that spontaneous nucleation of actin filaments naturally leads to heterogeneities in filament length distribution. We then investigate the effects of filament growth inhibition by capping proteins and growth promotion by formin proteins on filament length distribution. We find that filament length heterogeneity can be increased by growth inhibition, whereas growth promoters do not significantly affect length heterogeneity. Interestingly, a competition between filament growth inhibitors and growth promoters can give rise to bimodal filament length distribution as well as a highly heterogeneous length distribution with large statistical dispersion. We quantitatively predict how heterogeneity in actin filament length can be modulated by tuning F-actin nucleation and growth rates in order to create distinct filament subpopulations with different lengths. SIGNIFICANCE: Actin filaments organize into different functional network architectures within eukaryotic cells. To maintain distinct actin network architectures, it is essential to regulate the lengths of actin filaments. While the mechanisms controlling the lengths of individual actin filaments have been extensively studied, the regulation of length heterogeneity in actin filament populations is not well understood. Here we show that the modulation of actin filament growth and nucleation rates by actin binding proteins can regulate actin length distribution and create distinct sub-populations with different lengths. In particular, by tuning concentrations of formin, profilin and capping proteins, various aspects of actin filament length distribution can be controlled. Insights gained from our results may have significant implications for the regulation of actin filament length heterogeneity and architecture within a cell.

PMID:35598045 | DOI:10.1016/j.bpj.2022.05.014

BMC Psychol. 2022 May 21;10(1):128. doi: 10.1186/s40359-022-00842-4.

ABSTRACT

BACKGROUND: Empathy is one of the core medical professionalisms that distress, burnout, and lack of personal well-being is also recognized as an important influencer on lower empathy levels. Therefore, this study aimed to explore the mental health, burnout, and factors associated with the empathy levels among Thai, clinical-year medical students.

METHODS: This cross-sectional study surveyed all fourth-to sixth-year medical students at the Faculty of Medicine, Prince of Songkla University, in Thailand; at the end of the 2020 academic year. The questionnaires utilized were: (1) The personal and demographic information questionnaire, (2) The Toronto Empathy Questionnaire, (3) Thai Mental Health Indicator-15, and (4) The Maslach Burnout Inventory; Thai version. All data were analyzed using descriptive statistics, and factors associated with empathy levels were analyzed via the chi-square test and logistic regressions.

RESULTS: There were 466 participants, with a response rate of 91.5%. The majority were female (56.2%), and reported a below-average level of empathy (57.1%); with a median score (IQR) of 44 (40-48). The gender proportion of a below-average empathy level among male and female participants was 66.3% and 50.4%, respectively. Of the participants, 29.6% had poor mental health, 63.5% and 39.7% reported a high level of emotional exhaustion and depersonalization scores; even though most of them (96.6%) perceived having a high level of personal accomplishment. Multivariate analysis indicated that females, higher mental health, and a low level of depersonalization were statistically significant protective factors, which improved the empathy levels.

CONCLUSIONS: More than half of the clinical-year medical students reported below-average empathy levels. Female gender, better mental health, and a low level of depersonalization were related to the improvement of the empathy levels. Therefore, medical educators should emphasize the importance of focusing supporting students, of all genders and in regards to all stages of medical education, to increase their levels of empathy, to promote individual well-being, and to effectively prevent the phenomenon of student ‘burnout’.

PMID:35598029 | DOI:10.1186/s40359-022-00842-4

Alzheimers Res Ther. 2022 May 21;14(1):69. doi: 10.1186/s13195-022-01009-4.

ABSTRACT

BACKGROUND: Currently, Alzheimer’s disease (AD) cohort datasets are difficult to find and lack across-cohort interoperability, and the actual content of publicly available datasets often only becomes clear to third-party researchers once data access has been granted. These aspects severely hinder the advancement of AD research through emerging data-driven approaches such as machine learning and artificial intelligence and bias current data-driven findings towards the few commonly used, well-explored AD cohorts. To achieve robust and generalizable results, validation across multiple datasets is crucial.

METHODS: We accessed and systematically investigated the content of 20 major AD cohort datasets at the data level. Both, a medical professional and a data specialist, manually curated and semantically harmonized the acquired datasets. Finally, we developed a platform that displays vital information about the available datasets.

RESULTS: Here, we present ADataViewer, an interactive platform that facilitates the exploration of 20 cohort datasets with respect to longitudinal follow-up, demographics, ethnoracial diversity, measured modalities, and statistical properties of individual variables. It allows researchers to quickly identify AD cohorts that meet user-specified requirements for discovery and validation studies regarding available variables, sample sizes, and longitudinal follow-up. Additionally, we publish the underlying variable mapping catalog that harmonizes 1196 unique variables across the 20 cohorts and paves the way for interoperable AD datasets.

CONCLUSIONS: In conclusion, ADataViewer facilitates fast, robust data-driven research by transparently displaying cohort dataset content and supporting researchers in selecting datasets that are suited for their envisioned study. The platform is available at https://adata.scai.fraunhofer.de/ .

PMID:35598021 | DOI:10.1186/s13195-022-01009-4

BMC Res Notes. 2022 May 21;15(1):186. doi: 10.1186/s13104-022-06070-8.

ABSTRACT

OBJECTIVES: We assessed Case Fatality Rate (CFR) of COVID-19 as an indicator to situate the performance of Nigeria relative to other selected countries. We obtained case fatality rates of different countries from data sets available from open-sources. The CFRs were calculated as the rate of deaths compared with total cases. The values were compared with Nigeria’s COVID-19 CFR. Other relevant statistical comparisons were also conducted.

RESULTS: The worst performing countries with regards to CFR in descending order were Yemen (19.5%), Peru (9.0%) Mexico (7.6%), Sudan (7.4%) and Ecuador (6.3%) while the best performing nations were Bhutan (0.11%), Burundi (0.19%), Iceland (0.20%), Laos (0.21%) and Qatar (0.25%). The CFR of Nigeria was 1.39% which falls below the 50th percentile. Other comparison done showed significant difference in the CFR values between countries similar to Nigeria and countries that are dissimilar when HDI is used. (Mann-Whitney U test 126.0, p = 0.01). The trend of the CFR in Nigeria showed a steady decline and flattening of the CFR curve which does not seem to be affected by the spikes in the daily declared cases.

PMID:35597995 | DOI:10.1186/s13104-022-06070-8

Trials. 2022 May 21;23(1):424. doi: 10.1186/s13063-022-06385-8.

ABSTRACT

BACKGROUND: The COVID-19 pandemic has considerably disrupted nearly all aspects of daily life, including healthcare delivery and clinical research. Because pragmatic clinical trials are often embedded within healthcare delivery systems, they may be at high risk of disruption due to the dual impacts on the conduct of both care and research.

METHODS: We collected qualitative data using multiple methods to characterize the impact of COVID-19 on the research activities of 14 active pragmatic clinical trials in the National Institutes of Health (NIH) Health Care Systems Research Collaboratory. A COVID-19 impact questionnaire was administered electronically to principal investigators in June 2020. Text responses were analyzed thematically, and qualitative summaries were subsequently reviewed by five independent reviewers, who made iterative revisions. Additional COVID-19-related impacts were identified during virtual meetings with trial teams during April-July 2020 and combined with questionnaire responses for analysis.

RESULTS: Impacts of the pandemic were broadly classified into two main types: healthcare operations and social distancing. In some instances, trial delays created statistical challenges, particularly with trials using stepped-wedge designs, and necessitated changing data collection strategies or modifying interventions. The majority of projects used existing stakeholder-driven approaches to adapt interventions. Several benefits of these adaptions were identified, including expanded outreach capabilities and ability to study virtual intervention delivery. All trial teams were able to adapt to pandemic-related modifications.

CONCLUSION: In a group of 14 ongoing pragmatic clinical trials, there was significant impact of COVID-19 on trial activities. Engaging appropriate stakeholders was critical to designing and implementing trial modifications and making continued safe progress toward meeting research objectives.

PMID:35597988 | DOI:10.1186/s13063-022-06385-8

BMC Musculoskelet Disord. 2022 May 21;23(1):484. doi: 10.1186/s12891-022-05432-4.

ABSTRACT

BACKGROUND: There is no agreement about the best reconstructive option following resection of proximal humerus tumors. The purpose of this study was to compare the functional outcomes of endoprosthesis reconstruction versus nail cement spacer reconstruction after wide resection of proximal humeral tumors.

METHODS: This retrospective comparative study included 58 patients with proximal humerus tumors who had undergone tumor resection and reconstruction with modular endoprosthesis (humeral hemiarthroplasties) or cement spacer. Medical records were reviewed for the epidemiological, clinical, radiological, and operative data. Lung metastasis, local recurrence, and complication were also reviewed. The functional outcome was evaluated using the Musculoskeletal Tumor Society scoring (MSTS) system.

RESULTS: Nineteen patients with a mean age of 33.4 ± 17.5 years underwent reconstruction by modular endoprosthesis, and 39 patients with a mean age of 24.6 ± 14.3 years underwent reconstruction by cement spacer. The mean MSTS score was 24.8 ± 1.1 in the endoprosthesis group and 23.9 ± 1.4 in the spacer group, P = 0.018. Complications were reported in 5 (26.3%) patients in the endoprosthesis group and 11 (28.2%) patients in the spacer group, P = 0.879. There were no statistically significant differences in the functional outcomes in both patient groups with or without axillary or deltoid resection.

CONCLUSIONS: Both endoprostheses and cement spacers are durable reconstructions with almost equal functional outcomes with no added advantage of the expensive endoprosthesis.

PMID:35597987 | DOI:10.1186/s12891-022-05432-4