Nevin Manimala

J Magn Reson Imaging. 2022 Apr 14. doi: 10.1002/jmri.28196. Online ahead of print.

ABSTRACT

BACKGROUND: Hyperpolarized ¹³ C MRI quantitatively measures enzyme-catalyzed metabolism in cancer and metabolic diseases. Whole-abdomen imaging will permit dynamic metabolic imaging of several abdominal organs simultaneously in healthy and diseased subjects.

PURPOSE: Image hyperpolarized [1-¹³ C]pyruvate and products in the abdomens of healthy volunteers, overcoming challenges of motion, magnetic field variations, and spatial coverage. Compare hyperpolarized [1-¹³ C]pyruvate metabolism across abdominal organs of healthy volunteers.

STUDY TYPE: Prospective technical development.

SUBJECTS: A total of 13 healthy volunteers (8 male), 21-64 years (median 36).

FIELD STRENGTH/SEQUENCE: A 3 T. Proton: T₁ -weighted spoiled gradient echo, T₂ -weighted single-shot fast spin echo, multiecho fat/water imaging. Carbon-13: echo-planar spectroscopic imaging, metabolite-specific echo-planar imaging.

ASSESSMENT: Transmit magnetic field was measured. Variations in main magnetic field (ΔB₀ ) determined using multiecho proton acquisitions were compared to carbon-13 acquisitions. Changes in ΔB₀ were measured after localized shimming. Improvements in metabolite signal-to-noise ratio were calculated. Whole-organ regions of interests were drawn over the liver, spleen, pancreas, and kidneys by a single investigator. Metabolite signals, time-to-peak, decay times, and mean first-order rate constants for pyruvate-to-lactate (k_PL ) and alanine (k_PA ) conversion were measured in each organ.

STATISTICAL TESTS: Linear regression, one-sample Kolmogorov-Smirnov tests, paired t-tests, one-way ANOVA, Tukey’s multiple comparisons tests. P ≤ 0.05 considered statistically significant.

RESULTS: Proton ΔB₀ maps correlated with carbon-13 ΔB₀ maps (slope = 0.93, y-intercept = -2.88, R² = 0.73). Localized shimming resulted in mean frequency offset within ±25 Hz for all organs. Metabolite SNR significantly increased after denoising. Mean k_PL and k_PA were highest in liver, followed by pancreas, spleen, and kidneys (all comparisons with liver were significant).

DATA CONCLUSION: Whole-abdomen coverage with hyperpolarized carbon-13 MRI was feasible despite technical challenges. Multiecho gradient echo ¹ H acquisitions accurately predicted chemical shifts observed using carbon-13 spectroscopy. Carbon-13 acquisitions benefited from local shimming. Metabolite energetics in the abdomen compiled for healthy volunteers can be used to design larger clinical trials in patients with metabolic diseases.

EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 1.

PMID:35420227 | DOI:10.1002/jmri.28196

J Nurs Manag. 2022 Apr 14. doi: 10.1111/jonm.13634. Online ahead of print.

ABSTRACT

AIM: To identify the patient and hospital characteristics related to nursing needs and nursing hours in acute hospital settings.

BACKGROUND: To determine appropriate staffing levels, accumulating empirical data through direct observation and surveys reflecting the actual situation is necessary.

METHODS: In this cross-sectional study, we conducted direct observations of nurses in acute care hospitals from May 1 to August 31, 2020. Twenty-six hospitals in five cities participated, and 747 nursing personnel collected 1,681 patients’ data while performing nursing activities. The data of 1,605 individuals were analyzed using descriptive statistics, t-tests, analysis of variance, and linear regression.

RESULTS: Hospital size, admission day, patients’ dependence level, high fall risk, and disease diagnoses were variables associated with nursing needs (F = 73.49, P < 0.001) and nursing hours (F = 57.7, P < 0.001). Comparing the correlates of nursing needs and nursing hours revealed that, unlike nursing needs, nursing hours were not significantly associated with surgery and certain diagnoses.

CONCLUSION: This study confirmed the variables associated with nursing needs and nursing hours in acute hospitals; based on this, determining appropriate staffing levels, which is an important step in improving inpatients’ health outcomes, is necessary.

IMPLICATIONS FOR NURSING MANAGEMENT: In acute hospitals, an increased number of nurse staffing should be employed based on the number of newly hospitalized patients, patients with high dependence levels and specific diagnoses, and those at high risk of falling.

PMID:35420223 | DOI:10.1111/jonm.13634

J Vet Intern Med. 2022 Apr 14. doi: 10.1111/jvim.16416. Online ahead of print.

ABSTRACT

BACKGROUND: A recent study showed higher high-sensitivity cardiac troponin I (hs-cTnI) concentrations in healthy dogs eating grain-free (GF) compared to those eating grain-inclusive (GI) diets.

HYPOTHESIS/OBJECTIVES: Healthy dogs with subclinical cardiac abnormalities eating GF diets at baseline will show improvements in cardiac biomarkers and echocardiographic variables after diet change, whereas healthy dogs eating GI diets at baseline will not improve.

ANIMALS: Twenty healthy dogs with subclinical cardiac abnormalities (12 Golden Retrievers, 5 Doberman Pinschers, 3 Miniature Schnauzers).

METHODS: This prospective study included dogs with increased hs-cTnI or N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentrations, or echocardiographic abnormalities. Mixed modeling was used to evaluate echocardiographic, hs-cTnI, and NT-proBNP differences between groups (GF or GI diet at baseline) over time (1 y after diet change).

RESULTS: Ten GF and 10 GI dogs were evaluated. There were statistically significant time: group interactions for hs-cTnI (P = .02) and normalized left ventricular internal systolic diameter (LVIDsN; P = .02), with GF dogs showing larger decreases in these variables than GI dogs. Median (range) hs-cTnI (ng/mL) for GF dogs was 0.141 (0.012-0.224) at baseline and 0.092 (0.044-0.137) at 1 y, and for GI dogs was 0.051 (0.016-0.195) at baseline and 0.060 (0.022-0.280) at 1 y. Median LVIDsN for GF dogs was 1.01 (0.70-1.30) at baseline and 0.87 (0.79-1.24) at 1 y, and for GI dogs was 1.05 (0.84-1.21) at baseline and 1.10 (0.85-1.28) at 1 y.

CONCLUSIONS AND CLINICAL IMPORTANCE: Decreased hs-cTnI and LVIDsN in GF dogs after diet change supports reversibility of these subclinical myocardial abnormalities.

PMID:35420218 | DOI:10.1111/jvim.16416

J Am Geriatr Soc. 2022 Apr 14. doi: 10.1111/jgs.17799. Online ahead of print.

ABSTRACT

BACKGROUND: The medication-related death of a hospitalized older adult elucidated the inappropriateness of medication default doses in our electronic health record (EHR) for older adults. In response, we created and implemented the Geriatric Prescribing Context (GPC), an EHR-based set of age-specific dose and frequency defaults for patients 75 years and older, in July 2017. Inpatient medication orders aligned with GPC defaults and showed significant dose decreases at one year for nine of ten most commonly used medications. This follow-up investigation examined GPC alignment of dose and frequency over the 42-month time period after its implementation.

METHODS: Order data for the ten most commonly used medications at OHSU Hospital were collected retrospectively from July 2016 through December 2020. We used Statistical Process Control charts to assess the proportion of medication orders aligning with the GPC’s recommendations. Signals of special cause were evaluated to identify time periods when shifts in process averages likely occurred and suspected shifts were assessed using binomial proportion tests. We used RStudio (RStudio, Inc., version 1.2.5001) and Microsoft Excel (2016) to perform statistical analyses and control charts, respectively.

RESULTS: The preimplementation phase of all medications displayed no special causes. After significant initial improvement in 2017, control charts revealed three different patterns of performance. Eight medications maintained the initial improvement with one medication displaying a second significant improvement at a later date. Two medications showed a subsequent decline in performance not statistically different from baseline. Overall, eight of the ten medications were prescribed at more age-friendly doses and frequencies compared to baseline after 42 months.

CONCLUSIONS: The GPC is an effective method to support safer prescribing for hospitalized older patients, but long-term impacts may be medication-specific. Further investigation is needed to ensure appropriate prescribing across drug classes and understand the GPC’s impact on patient outcomes like adverse drug events.

PMID:35420159 | DOI:10.1111/jgs.17799

Tijdschr Psychiatr. 2022;64(2):94-100.

ABSTRACT

BACKGROUND: Leukemia is the most common pediatric malignancy. Acute lymphoblastic leukemia (ALL) is the most commonly observed subtype.

AIM: To assess cognitive functioning in children and adolescents with ALL post-treatment: chemotherapy-only (CT-only) or in combination with radiation therapy (CTRT). METHODS We searched in PubMed and PsycINFO (OvidSP). Relevant data were analyzed using statistical program Comprehensive Meta-Analysis (version 2).

RESULTS: 44 studies were included in the overall meta-analysis with a total of 5059 patients. A weighted mean IQ of 100.1 (95% CI 99.1-101.0) was found overall after ALL treatment. In subanalyses, we found for CT-only a weighted mean IQ of 100.7 (95% CI: 99.5-101.9) and for CTRT-treatment a weighted mean IQ of 98.2 (95%100.7 (95% CI: 96.3-100.3). There was no significant difference from the normative control (mean: 100.0; SD: 15).

CONCLUSION: No significant cognitive sequelae were shown in childhood survivors of leukemia who were exposed to either CT-only or CTRT therapy. Prospective studies are needed with inclusion of pre-and post-treatment IQ measurements, ideally compared to age and socio-economic status matched control groups.

PMID:35420152

Cardiovasc Res. 2022 Apr 14:cvac042. doi: 10.1093/cvr/cvac053. Online ahead of print.

ABSTRACT

AIMS: The British Heart Foundation’s (BHF) annual statistical compendium is a comprehensive source of accessible epidemiological data in relation to cardiovascular disease (CVD) in the UK. Using datasets with multiple years of data from the compendium we have analysed trends in mortality, morbidity, and treatment for CVD within the UK.

METHODS AND RESULTS: CVD mortality in the UK has consistently declined over recent decades, from 1,045 deaths per 100,000 in 1969, shortly after the BHF was founded, to 255 per 100,000 in 2019. Despite this remarkable improvement, inequalities in CVD mortality persist between the UK nations, for example in 2019 the death rate in Scotland was 326 deaths per 100,000 compared with 246 per 100,000 in England. Improvements in CVD mortality have been paralleled by increased use of primary prevention medications (anti-hypertensives and statins) and interventional procedures. In recent years, progress in mortality outcomes has stalled, probably due to a combination of factors including a rise in risk factors such as obesity and diabetes. In terms of morbidity, CVD remains a significant burden in the UK, accounting for at least 1.18 million hospital admissions and reflect enormous economic burden of CVD, estimated at £19bn in the UK.

CONCLUSIONS: Our results highlight the importance of accessible and comprehensive statistics in relation to the burden of CVD and the value of the BHF’s annual compendium in drawing out conclusions and opportunities for future research. One key area is to improve is the data on which estimation of prevalence is based. There is also a need for ongoing work to better understand the root causes of disparity between socio-economic groups in relation to CVD. One important way to address this will be to improve consistency of reporting of CVD heath data across all nations of the UK. Understanding the causes will inform UK healthcare planning in addition to providing analytical insights that will be applicable in other countries.

PMID:35420124 | DOI:10.1093/cvr/cvac053

Org Biomol Chem. 2022 Apr 14. doi: 10.1039/d2ob00606e. Online ahead of print.

ABSTRACT

The Angiotensin Converting Enzyme 2 (ACE2) assists the regulation of blood pressure and is the main target of the coronaviruses responsible for SARS and COVID19. The catalytic function of ACE2 relies on the opening and closing motion of its peptidase domain (PD). In this study, we investigated the possibility of allosterically controlling the ACE2 PD functional dynamics. After confirming that ACE2 PD binding site opening-closing motion is dominant in characterizing its conformational landscape, we observed that few mutations in the viral receptor binding domain fragments were able to impart different effects on the binding site opening of ACE2 PD. This showed that binding to the solvent exposed area of ACE2 PD can effectively alter the conformational profile of the protein, and thus likely its catalytic function. Using a targeted machine learning model and relative entropy-based statistical analysis, we proposed the mechanism for the allosteric perturbation that regulates the ACE2 PD binding site dynamics at atomistic level. The key residues and the source of the allosteric regulation of ACE PD dynamics are also presented.

PMID:35420112 | DOI:10.1039/d2ob00606e

J Osteopath Med. 2022 Apr 14. doi: 10.1515/jom-2021-0267. Online ahead of print.

ABSTRACT

CONTEXT: Ehlers-Danlos syndromes (EDS) are disorders of connective tissue that lead to a wide range of clinical presentations. While we are beginning to understand the association between EDS and psychological manifestations, it is critical that we further elucidate the relationship between the two. Understanding the correlation between EDS and mental health will better ensure swift diagnosis and effective treatment for patients.

OBJECTIVES: This study aims to systematically examine and report the prevalence of psychiatric disorders in the EDS population.

METHODS: The PubMed database was searched on June 14, 2021 for articles published from January 2011 to June 2021. We included original, evidence-based, peer-reviewed journal articles in English that reported information on psychiatric disorders among EDS patients. Psychiatric disorders and psychological conditions were limited to those included in the “psychology” and “mental disorders” Medical Subject Headings (MeSH) search terms defined by the National Library of Medicine. Publications identified utilizing this search strategy by M.K. were imported into the Covidence system, where they first underwent a title and abstract screening process by three independent reviewers (M.K., K.L., H.G.). During the full-text review, two independent reviewers read the full text of the questionable articles to assess their eligibility for inclusion. Studies were excluded if they did not meet our target objective or if they were not in English or if they were opinion pieces, conference abstracts, or review articles. Data were extracted from the shortlisted studies by reviewers. During the data extraction phase, the quality and risk of publication bias were assessed by two independent reviewers utilizing the National Institutes of Health (NIH) Study Quality Assessment Tools. Any disagreements in study selection, data extraction, or quality assessment were adjudicated via discussion between the two reviewers, utilizing a third reviewer as a decider if necessary.

RESULTS: Out of 73 articles identified, there were no duplicates. A total of 73 records were screened, but only 40 articles were assessed in full text for eligibility. A total of 23 articles were ultimately included, which collectively discussed 12,298 participants. Ten (43.5%) of the included studies were cross-sectional in design, three (13.0%) were case reports, and three (13.0%) were retrospective chart reviews. The remaining seven (30.4%) articles were either case-control, cohort, qualitative, controlled observational, or validation studies. Twelve (52.2%) of the studies reported data on depression disorders, six of which reported prevalence data. Nine (39.1%) of the studies reported data on anxiety disorders, five of which reported prevalence data. Studies that reported nonprevalence data presented odds-ratio, mean scores on psychiatric evaluations, and other correlation statistics. Psychiatric disorders that were most reported in these articles were mood disorders (n=11), anxiety disorders (n=9), and neurodevelopmental disorders (n=7). Although the reports varied, the highest psychiatric prevalence reports in EDS patients involved language disorders (63.2%), attention-deficit/hyperactivity disorder (ADHD) (52.4%), anxiety (51.2%), learning disabilities (42.4%), and depression (30.2%).

CONCLUSIONS: Although mood disorders were cited in more articles, the highest reported prevalence was for language disorders and ADHD. This discrepancy highlights the importance of performing more research to better understand the relationship between EDS and psychiatric disorders.

PMID:35420002 | DOI:10.1515/jom-2021-0267

Pediatr Pulmonol. 2022 Apr 13. doi: 10.1002/ppul.25921. Online ahead of print.

ABSTRACT

OBJECTIVES: To describe the short- and medium-term repeatability of lung clearance index (LCI_2.5 ) in infants and calculate the number of patients needed to enrol in a study (N) using LCI_2.5 as a primary outcome.

METHODS: An 8-month follow-up observational study was employed for assessing short-term [coefficient of repeatability (CR) and intraclass correlation (ICC)] and medium-term repeatability (Bland-Altman method) of LCI_2.5 in infants with cystic fibrosis (CF) or recurrent wheeze (RW) measured by the nitrogen multiple-breath washout test (N₂ -MBW). Using these variability data, the N to reach 90% test power at the level of statistical significance (0.05) was calculated.

RESULTS: Forty infants with CF and 21 with RW were enrolled. Initial N₂ -MBW testing was successful in 33 and 17 patients, respectively. Follow-up data were available for 23 and 11 infants, respectively. Short-term repeatability of LCI_2.5 was high (CR = 1.10 and 1.04 in CF and RW patients, respectively; ICC = 0.88 and 0.83 in CF and RW patients, respectively). The between-subject standard deviation was <13% of the actual LCI_2.5 value. In clinically stable patients, LCI_2.5 did not significantly change during the 8-month follow-up. Mean LCI_2.5 change was -0.08 (1% of baseline) in CF and -0.05 (0.6%) in RW, with 95% limits of agreement being (-1.70; 1.53) in CF and (-1.51; 1.40) in RW patients. N = 23 infants if both intra-group differences of LCI_2.5 and minimal difference to be detected would be 2.0.

CONCLUSION: N₂ -MBW may be a reproducible tool with reasonable test power to detect differences in infant studies. This article is protected by copyright. All rights reserved.

PMID:35419996 | DOI:10.1002/ppul.25921

Transbound Emerg Dis. 2022 Apr 13. doi: 10.1111/tbed.14558. Online ahead of print.

ABSTRACT

Colistin is a critically important antimicrobial for human medicine, and colistin-resistant Escherichia coli are commonly found in poultry and poultry products in Southeast Asia. Here, we aim at disentangling the within-farm and outside-farm drivers of colistin resistance in small-scale chicken farms of the Mekong delta of Vietnam. Nineteen Vietnamese chicken farms were followed up along a whole production cycle, during which weekly antimicrobial use data were recorded. At the beginning, middle and end of each production cycle, commensal E. coli samples from birds were collected, pooled and tested for colistin resistance. Twelve models were fitted to the data using an Expectation-Maximization algorithm and compared. We further tested the spatial clustering of the occurrence of resistance importations from external sources using the local Moran’s I statistic. In the best model, colistin resistance in E. coli from chickens was found to be mostly affected by importations of resistance, and, to a lesser extent, by the use of antimicrobials in the last 1.73 weeks [0.00; 2.90], but not by the use of antimicrobials in day-olds, nor their colistin resistance carriage from hatchery. The occurrence of external source importations proved to be sometimes spatially clustered, suggesting a role of local environmental sources of colistin resistance. This article is protected by copyright. All rights reserved.

PMID:35419995 | DOI:10.1111/tbed.14558