bluuebunny/crossref_metadata_2025 huggingface dataset:
Burnout, professional fulfillment, sleep impairment, and self-compassion within an academic medical center pharmacy department
Authors: Raber Hanna , May Alisyn , Tingey Ben , Qeadan Fares , Morrow Ellen , Mullin Shantel , Nickman Nancy A , Tyler Linda S
Published: June 2022

Purpose

To examine the prevalence of burnout, professional fulfillment, sleep impairment, and self-compassion within an academic medical center pharmacy department across varying job titles and practice settings.

Methods

In fall 2019, pharmacy staff completed a REDCap-based survey that consisted of a validated instrument relating to burnout, professional fulfilment, sleep-related impairment, and self-compassion. Burnout was measured by both single-item and extended 10-item questions on the survey. Survey outcomes from each domain were compared between pharmacists and pharmacy technicians/interns, as well as among practice settings (inpatient, ambulatory care, and infrastructure).

Results

A total of 593 surveys were completed by pharmacy personnel, representing a preliminary response rate of 71.8% (593/826). A total of 505 survey responses were analyzed (235 [46.5%] for pharmacists and 270 [53.5%] for pharmacy technicians/interns). Inpatient pharmacists reported the highest level of burnout (50.7%), followed by ambulatory care pharmacists (29.3%) and those working in infrastructure (24.3%). Pharmacy technicians working in infrastructure reported the highest level of burnout (36.4%), followed by inpatient (30.8%) and ambulatory care (28.3%) pharmacy technicians. There was no association between job type or location and burnout according to both single-item and 10-item burnout measures. A higher rate of burnout, sleep impairment, and decreased self-compassion and a lower rate of professional fulfillment were observed for inpatient pharmacists compared to pharmacists in ambulatory care or infrastructure. Except for higher rates of reported professional fulfillment, a similar trend was observed for pharmacy technicians.

Conclusion

Burnout was reported across the pharmacy team regardless of practice site.
A protoxylem pathway to evolution of pith? An hypothesis based on the Early Devonian euphyllophyte Leptocentroxyla
Authors: Tomescu Alexandru M F , McQueen Camryn R
Published: June 2022

Background and Aims

The Early Devonian (Emsian, 400–395 Ma) tracheophyte Leptocentroxyla tetrarcha Bickner et Tomescu emend. Tomescu et McQueen combines plesiomorphic Psilophyton-type tracheid thickenings with xylem architecture intermediate between the plesiomorphic basal euphyllophyte haplosteles and the complex actinosteles of Middle Devonian euphyllophytes. We document xylem development in Leptocentroxyla based on anatomy and explore its implications, which may provide a window into the evolution of pith.

Methods

Leptocentroxyla is preserved by permineralization in the Battery Point Formation (Quebec, Canada). Serial sections obtained using the cellulose acetate peel technique document branching pattern, anatomy of trace divergence to appendages, protoxylem architecture, and variations in tracheid size and wall thickening patterns.

Key Results

Leptocentroxyla has opposite decussate pseudo-whorled branching and mesarch protoxylem, and represents the earliest instance of central histological differentiation in a euphyllophyte actinostele. Tracheids at the centre of xylem exhibit simplified Psilophyton-type wall thickenings and are similar in size (at the axis centre) or smaller than the surrounding metaxylem tracheids (at the centre of appendage traces).

Conclusions

The position and developmental attributes of the simplified Psilophyton-type tracheids suggest they may have been generated by the protoxylem developmental pathway. This supports the delayed and shortened protoxylem differentiation hypothesis, which explains the evolution of pith by (1) delay in the onset of differentiation and lengthening of cell growth duration in a central protoxylem strand; and (2) shortening of the interval of differentiation of those tracheids, leading to progressive simplification (and eventual loss) of secondary wall thickenings, and replacement of tracheids with a central parenchymatous area. NAC domain transcription factors and their interactions with abscisic acid may have provided the regulatory substrate for the developmental changes that led to the evolution of pith. These could have been orchestrated by selective pressures associated with the expansion of early vascular plants into water-stresses upland environments.
Contributory Etiologies to Cognitive Performance in Multimorbid Post-9/11 Veterans: The Deployment Trauma Phenotype
Authors: Kim Sahra , Currao Alyssa , Bernstein John , Fonda Jennifer R , Fortier Catherine B
Published: June 2022

Objective

This study examined cognitive functioning in post-9/11 Veterans with the deployment trauma phenotype (DTP), comprised of co-occurring diagnoses of depressive disorder (major depressive disorder and or persistent depressive disorder/dysthymia), posttraumatic stress disorder (PTSD), and mild traumatic brain injury (mTBI), using objective neuropsychological measures.

Method

Participants included a cross-sectional sample of 399 post-9/11 Veterans who completed clinical interviews and neuropsychological tests as part of a larger study at VA Boston Healthcare System. Confirmatory factor analysis identified four cognitive domains: attention, cognitive control/processing speed, episodic memory, and cognitive flexibility. Veterans with DTP and its constituent diagnoses in isolation, two-way diagnostic combinations, and no constituent diagnoses were compared.

Results

Veterans with DTP had a twofold increased prevalence for below average performance in cognitive control/processing speed compared with those with no constituent diagnoses (prevalence ratios [PRs] = 2.04; 95% confidence interval [CI]: 1.03–4.05). The PTSD + depressive disorder group also had a twofold increased prevalence for below average performance in episodic memory (PR = 2.16; 95% CI: 1.05–4.43).

Conclusions

The deployment trauma phenotype is associated with clinically significant decrease in cognitive control/processing speed in post-9/11 Veterans. Comorbid PTSD and depressive disorder negatively impacted performances in episodic memory. Mild TBI alone showed no cognitive deficits. Clinical interventions should target psychiatric symptoms with a transdiagnostic approach to address this multimorbid population.
PCfun: a hybrid computational framework for systematic characterization of protein complex function
Authors: Sharma Varun S , Fossati Andrea , Ciuffa Rodolfo , Buljan Marija , Williams Evan G , Chen Zhen , Shao Wenguang , Pedrioli Patrick G A , Purcell Anthony W , Martínez María Rodríguez , Song Jiangning , Manica Matteo , Aebersold Ruedi , Li Chen
Published: June 2022

In molecular biology, it is a general assumption that the ensemble of expressed molecules, their activities and interactions determine biological function, cellular states and phenotypes. Stable protein complexes—or macromolecular machines—are, in turn, the key functional entities mediating and modulating most biological processes. Although identifying protein complexes and their subunit composition can now be done inexpensively and at scale, determining their function remains challenging and labor intensive. This study describes Protein Complex Function predictor (PCfun), the first computational framework for the systematic annotation of protein complex functions using Gene Ontology (GO) terms. PCfun is built upon a word embedding using natural language processing techniques based on 1 million open access PubMed Central articles. Specifically, PCfun leverages two approaches for accurately identifying protein complex function, including: (i) an unsupervised approach that obtains the nearest neighbor (NN) GO term word vectors for a protein complex query vector and (ii) a supervised approach using Random Forest (RF) models trained specifically for recovering the GO terms of protein complex queries described in the CORUM protein complex database. PCfun consolidates both approaches by performing a hypergeometric statistical test to enrich the top NN GO terms within the child terms of the GO terms predicted by the RF models. The documentation and implementation of the PCfun package are available at https://github.com/sharmavaruns/PCfun. We anticipate that PCfun will serve as a useful tool and novel paradigm for the large-scale characterization of protein complex function.
P-smoother: efficient PBWT smoothing of large haplotype panels
Authors: Yue William , Naseri Ardalan , Wang Victor , Shakya Pramesh , Zhang Shaojie , Zhi Degui
Published: June 2022

Motivation

As large haplotype panels become increasingly available, efficient string matching algorithms such as positional Burrows-Wheeler transformation (PBWT) are promising for identifying shared haplotypes. However, recent mutations and genotyping errors create occasional mismatches, presenting challenges for exact haplotype matching. Previous solutions are based on probabilistic models or seed-and-extension algorithms that passively tolerate mismatches.

Results

Here, we propose a PBWT-based smoothing algorithm, P-smoother, to actively ‘correct’ these mismatches and thus ‘smooth’ the panel. P-smoother runs a bidirectional PBWT-based panel scanning that flips mismatching alleles based on the overall haplotype matching context, which we call the IBD (identical-by-descent) prior. In a simulated panel with 4000 haplotypes and a 0.2% error rate, we show it can reliably correct 85% of errors. As a result, PBWT algorithms running over the smoothed panel can identify more pairwise IBD segments than that over the unsmoothed panel. Most strikingly, a PBWT-cluster algorithm running over the smoothed panel, which we call PS-cluster, achieves state-of-the-art performance for identifying multiway IBD segments, a challenging problem in the computational community for years. We also showed that PS-cluster is adequately efficient for UK Biobank data. Therefore, P-smoother opens up new possibilities for efficient error-tolerating algorithms for biobank-scale haplotype panels.

Availability and implementation

Source code is available at github.com/ZhiGroup/P-smoother.
A rarefaction-without-resampling extension of PERMANOVA for testing presence–absence associations in the microbiome
Authors: Hu Yi-Juan , Satten Glen A
Published: June 2022

Motivation

PERMANOVA is currently the most commonly used method for testing community-level hypotheses about microbiome associations with covariates of interest. PERMANOVA can test for associations that result from changes in which taxa are present or absent by using the Jaccard or unweighted UniFrac distance. However, such presence–absence analyses face a unique challenge: confounding by library size (total sample read count), which occurs when library size is associated with covariates in the analysis. It is known that rarefaction (subsampling to a common library size) controls this bias but at the potential costs of information loss and the introduction of a stochastic component into the analysis.

Results

Here, we develop a non-stochastic approach to PERMANOVA presence–absence analyses that aggregates information over all potential rarefaction replicates without actual resampling, when the Jaccard or unweighted UniFrac distance is used. We compare this new approach to three possible ways of aggregating PERMANOVA over multiple rarefactions obtained from resampling: averaging the distance matrix, averaging the (element-wise) squared distance matrix and averaging the F-statistic. Our simulations indicate that our non-stochastic approach is robust to confounding by library size and outperforms each of the stochastic resampling approaches. We also show that, when overdispersion is low, averaging the (element-wise) squared distance outperforms averaging the unsquared distance, currently implemented in the R package vegan. We illustrate our methods using an analysis of data on inflammatory bowel disease in which samples from case participants have systematically smaller library sizes than samples from control participants.

Availability and implementation

We have implemented all the approaches described above, including the function for calculating the analytical average of the squared or unsquared distance matrix, in our R package LDM, which is available on GitHub at https://github.com/yijuanhu/LDM.

Supplementary information

Supplementary data are available at Bioinformatics online.
PrISM: precision for integrative structural models
Authors: Ullanat Varun , Kasukurthi Nikhil , Viswanath Shruthi
Published: June 2022

Motivation

A single-precision value is currently reported for an integrative model. However, precision may vary for different regions of an integrative model owing to varying amounts of input information.

Results

We develop PrISM (Precision for Integrative Structural Models) to efficiently identify high- and low-precision regions for integrative models.

Availability and implementation

PrISM is written in Python and available under the GNU General Public License v3.0 at https://github.com/isblab/prism; benchmark data used in this paper are available at doi:10.5281/zenodo.6241200.

Supplementary information

Supplementary data are available at Bioinformatics online.
Role of right temporoparietal junction for counterfactual evaluation of partner’s decision in ultimatum game
Authors: Ogawa Akitoshi , Asano Saki , Osada Takahiro , Tanaka Masaki , Tochigi Reia , Kamagata Koji , Aoki Shigeki , Konishi Seiki
Published: June 2022

Humans assess the distributions of resources based on their aversion to unfairness. If a partner distributes in an unfair manner even though the partner had a less unfair distribution option, a recipient will believe that the partner should have chosen the counterfactual option. In this study, we investigated the neural basis for fairness evaluation of actual and counterfactual options in the ultimatum game. In this task, a partner chose one distribution option out of two options, and a participant accepted or rejected the option. The behavioral results showed that the acceptance rate was influenced by counterfactual evaluation (CE), among others, as defined by the difference of monetary amount between the actual and counterfactual options. The functional magnetic resonance imaging results showed that CE was associated with the right ventral angular gyrus (vAG) that provided one of convergent inputs to the supramarginal gyrus related to decision utility, which reflects gross preferences for the distribution options. Furthermore, inhibitory repetitive transcranial magnetic stimulation administered to the right vAG reduced the behavioral component associated with CE. These results suggest that our acceptance/rejection of distribution options relies on multiple processes (monetary amount, disadvantageous inequity, and CE) and that the right vAG causally contributes to CE.
Effects of contraction bias on the decision process in the macaque prefrontal cortex
Authors: Benozzo Danilo , Ferrucci Lorenzo , Genovesio Aldo
Published: June 2022

Our representation of magnitudes such as time, distance, and size is not always veridical because it is affected by multiple biases. From a Bayesian perspective, estimation errors are considered to be the result of an optimization mechanism for the behavior in a noisy environment by integrating previous experience with the incoming sensory information. One influence of the distribution of past stimuli on perceptual decisions is represented by the regression toward the mean, a type of contraction bias. Using a spatial discrimination task with 2 stimuli presented sequentially at different distances from the center, we show that this bias is also present in macaques when comparing the magnitude of 2 distances. We found that the contraction of the first stimulus magnitude toward the center of the distribution accounted for some of the changes in performance, even more so than the effect of difficulty related to the ratio between stimulus magnitudes. At the neural level in the dorsolateral prefrontal cortex, the coding of the decision after the presentation of the second stimulus reflected the effect of the contraction bias on the discriminability of the stimuli at the behavioral level.
Delayed Recognition of Coronavirus Disease 2019 (COVID-19) in New York City: A Descriptive Analysis of COVID-19 Illness Prior to 29 February 2020
Authors: Keating Page , Sell Jessica , Chen Judy , Ackelsberg Joel , Wu Winfred , Tsoi Benjamin , Weiss Don
Published: June 2022

Background

On 30 January 2020, COVID-19 was declared a Public Health Emergency of International Concern (PHEIC) by the World Health Organization. Almost a month later, on 29 February 2020, the first case in New York City (NYC) was diagnosed.

Methods

Three hundred sixty persons with COVID-19–like illness were reported to the NYC Department of Health and Mental Hygiene (DOHMH) before 29 February, but 37 of these tested negative and 237 were never tested for severe acute respiratory syndrome coronavirus 2. Records of 86 persons with confirmed COVID-19 and reported symptom onset prior to 29 February 2020 were reviewed by 4 physician-epidemiologists. Case-patients were classified as possible delayed recognition (PDR) of COVID-19 when upon medical review the reported onset date was believed to reflect the initial symptoms of COVID-19, or insufficient evidence to classify, when the onset could not be determined with confidence. Clinical and epidemiological factors collected by DOHMH and supplemented with emergency department records were analyzed.

Results

Thirty-nine PDR COVID-19 cases were identified. The majority had severe disease with 69% presenting to an emergency department within 2 weeks of symptom onset. The first PDR COVID-19 case had symptom onset on 28 January 2020. Only 7 of the 39 cases (18%) had traveled internationally within 14 days of onset (none to China).

Conclusions

COVID-19 was in NYC before being classified as a PHEIC, and eluded surveillance for another month. The delay in recognition limited mitigation efforts; by the time city- and statewide mandates were enacted, 16 and 22 days later, there was already widespread community transmission.
Sensitivity of Various Case Detection Algorithms for Community-based Tuberculosis Screening
Authors: Puma Daniela , Yuen Courtney M , Millones Ana K , Brooks Meredith B , Jimenez Judith , Calderon Roger I , Lecca Leonid , Becerra Mercedes C , Keshavjee Salmaan
Published: June 2022

Using data from 388 people diagnosed with tuberculosis through a community-based screening program in Lima, Peru, we estimated that cough screening followed by sputum smear microscopy would have detected only 23% of cases found using an algorithm of radiographic screening followed by rapid nucleic acid amplification testing and clinical evaluation.
Durability of Immune Responses After Boosting in Ad26.COV2.S-Primed Healthcare Workers
Authors: Sablerolles Roos S G , Rietdijk Wim J R , Goorhuis Abraham , Postma Douwe F , Visser Leo G , Schmitz Katharina S , Geers Daryl , Bogers Susanne , van Haren Eva , Koopmans Marion P G , Dalm Virgil A S H , Kootstra Neeltje A , Huckriede Anke L W , Akkerman Renate , Beukema Martin , Lafeber Melvin , van Baarle Debbie , de Vries Rory D , van der Kuy P Hugo M , GeurtsvanKessel Corine H ,   for the SWITCH Research Group
Published: June 2022

The emergence of SARS-CoV-2 variants raised questions regarding the durability of immune responses after homologous or heterologous boosters after Ad26.COV2.S-priming. We found that SARS-CoV-2–specific binding antibodies, neutralizing antibodies, and T cells are detectable 5 months after boosting, although waning of antibodies and limited cross-reactivity with Omicron BA.1 was observed.
Virologic and Immunologic Characterization of Coronavirus Disease 2019 Recrudescence After Nirmatrelvir/Ritonavir Treatment
Authors: Carlin Aaron F , Clark Alex E , Chaillon Antoine , Garretson Aaron F , Bray William , Porrachia Magali , Santos AsherLev T , Rana Tariq M , Smith Davey M
Published: June 2022

We isolated a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) BA.2 variant from a person with coronavirus disease 2019 recrudescence after nirmatrelvir/ritonavir treatment. Antiviral sensitivity and neutralizing antibody testing were performed with both parental SARS-CoV-2 and multiple variants of concern. We found that neither nirmatrelvir resistance nor absence of neutralizing immunity was a likely cause of the recrudescence.
Hospitalized Patients With Severe Coronavirus Disease 2019 During the Omicron Wave in Israel: Benefits of a Fourth Vaccine Dose
Authors: Brosh-Nissimov Tal , Hussein Khetam , Wiener-Well Yonit , Orenbuch-Harroch Efrat , Elbaz Meital , Lipman-Arens Shelly , Maor Yasmin , Yagel Yael , Chazan Bibiana , Hershman-Sarafov Mirit , Rahav Galia , Zimhony Oren , Zaidman Shimshovitz Adi , Chowers Michal
Published: June 2022

Background

Waning immunity and an increased incidence of coronavirus disease 2019 (COVID-19) during the Omicron outbreak led the Israeli Ministry of Health to recommend a fourth vaccine dose for high-risk individuals. In this study, we assessed its effect for hospitalized patients with severe breakthrough COVID-19.

Methods

In this multicenter cohort study of hospitalized adults with severe COVID-19 in Israel, from 15 to 31 January 2022, cases were divided according to the number of vaccinations received. Poor outcome was defined as mechanical ventilation or in-hospital death and was compared between 3- and 4-dose vaccinees using logistic regression.

Results

Included were 1049 patients, median age 80 years. Among them, 394 were unvaccinated, 386 and 88 had received 3 or 4 doses, respectively. The 3-dose group was older, included more males, and immunosuppressed patients but with similar outcomes, 49% vs 51% compared with unvaccinated patients (P = .72). Patients who received 4 doses were similarly older and immunosuppressed but had better outcomes compared with unvaccinated patients, 34% vs 51% (P < .01). We examined independent predictors for poor outcome in patients who received either 3 or 4 doses a median of 161 days or 14 days before diagnosis, respectively. Receipt of the fourth dose was associated with protection (odds ratio, 0.51; 95% confidence interval, .3–.87), as was remdesivir. Male sex, chronic renal failure, and dementia were associated with poor outcomes.

Conclusions

Among hospitalized patients with severe breakthrough COVID-19, a recent fourth dose was associated with significant protection against mechanical ventilation or death compared with 3 doses.
Optical coherence tomography-derived lipid core burden index and clinical outcomes: results from the CLIMA registry
Authors: Biccirè Flavio Giuseppe , Budassi Simone , Ozaki Yukio , Boi Alberto , Romagnoli Enrico , Di Pietro Riccardo , Bourantas Christos V , Marco Valeria , Paoletti Giulia , Debelak Caterina , Sammartini Emanuele , Versaci Francesco , Fabbiocchi Franco , Burzotta Francesco , Pastori Daniele , Crea Filippo , Arbustini Eloisa , Alfonso Fernando , Prati Francesco
Published: June 2022

Aims

The aim of this study was to assess the morphological characteristics and prognostic implications of the optical coherence tomography (OCT)-derived lipid core burden index (LCBI).

Methods and results

OCT-LCBI was assessed in 1003 patients with 1-year follow-up from the CLIMA multicentre registry using a validated software able to automatically obtain a maximum OCT-LCBI in 4 mm (maxOCT-LCBI4mm). Primary composite clinical endpoint included cardiac death, myocardial infarction, and target-vessel revascularization. A secondary analysis using clinical outcomes of CLIMA study was performed. Patients with a maxOCT-LCBI4mm ≥ 400 showed higher prevalence of fibrous cap thickness (FCT) <75 μm [odds ratio (OR) 1.43, 95% confidence interval (CI) 1.03–1.99; P = 0.034], lipid pool arc >180° (OR 3.93, 95%CI 2.97–5.21; P < 0.001), minimum lumen area <3.5 mm2 (OR 1.5, 95%CI 1.16–1.94; P = 0.002), macrophage infiltration (OR 2.38, 95%CI 1.81–3.13; P < 0.001), and intra-plaque intimal vasculature (OR 1.34, 95%CI 1.05–1.72; P = 0.021). A maxOCT-LCBI4mm ≥400 predicted the primary endpoint [adjusted hazard ratio (HR) 1.86, 95%CI 1.1–3.2; P = 0.019] as well as the CLIMA endpoint (HR 2.56, 95%CI 1.24–5.29; P = 0.011). Patients with high lipid content and thin FCT < 75 µm were at higher risk for adverse events (HR 4.88, 95%CI 2.44–9.72; P < 0.001).

Conclusions

A high maxOCT-LCBI4mm was related to poor outcome and vulnerable plaque features. This study represents a step further in the automated assessment of the coronary plaque risk profile.
Cost-effectiveness of clopidogrel vs. ticagrelor in patients of 70 years or older with non-ST-elevation acute coronary syndrome
Authors: van den Broek Wout W A , van Paassen Jacqueline G , Gimbel Marieke E , Deneer Vera H M , ten Berg Jurriën M , Vreman Rick A
Published: June 2022

Objective

The POPular AGE trial showed that clopidogrel significantly reduced bleeding risk compared with ticagrelor without any signs of an increase in thrombotic events. The aim of this analysis was to estimate the long-term cost-effectiveness of clopidogrel compared with ticagrelor in these patients aged 70 years or older with non-ST-elevation acute coronary syndrome (NSTE-ACS).

Methods and results

A 1-year decision tree based on the POPular AGE trial in combination with a lifelong Markov model was developed to compare clopidogrel with ticagrelor in terms of clinical outcomes, costs, and quality-adjusted life years (QALYs) in elderly patients (above 70 year) with NSTE-ACS. Cost-effectiveness was assessed from a Dutch healthcare system perspective. Events rates and utility data observed in the POPular AGE trial were combined with lifetime projections to evaluate costs and effects for a fictional cohort of 1000 patients. Treatment with clopidogrel instead of ticagrelor led to a cost saving of €1484 575 (€1485 per patient) and a decrease of 10.96 QALYs (0.011 QALY per patient) in the fictional cohort. In an alternative base case with equal distribution over health states in the first year, treatment with clopidogrel led to an increase in QALYs. In all scenario analyses, treatment with clopidogrel was cost-saving.

Conclusion

Clopidogrel is a cost-saving alternative to ticagrelor in elderly patients after NSTE-ACS, though regarding overall cost-effectiveness clopidogrel was not superior to ticagrelor, as it resulted in a small negative effect on QALYs. However, based on the results of the alternative base case and clinical outcomes of the POPular AGE trial, clopidogrel could be a reasonable alternative to ticagrelor for elderly NSTE-ACS patients with a higher bleeding risk.
Are non-invasive estimations of plasma volume an accurate measure of congestion in patients with chronic heart failure?
Authors: Cuthbert J J , Pellicori P , Rigby A S , Abel A A I , Kalvickbacka-Bennet A , Shah P , Kearsley J W , Kazmi S , Cleland J G F , Clark A L
Published: June 2022

Aims

We report associations between different formulae for estimating plasma volume status (PVS) and clinical and ultrasound markers of congestion in patients with chronic heart failure (CHF) enrolled in the Hull Lifelab registry.

Methods and results

Cohort 1 comprised patients with data on signs and symptoms at initial evaluation (n = 3505). Cohort 2 included patients with ultrasound assessment of congestion [lung B-line count, inferior vena cava (IVC) diameter, jugular vein distensibility (JVD) ratio] (N = 341). Two formulae for PVS were used: (a) Hakim (HPVS) and (b) Duarte (DPVS). Results were compared with clinical and ultrasound markers of congestion. Outcomes assessed were mortality and the composite of heart failure (HF) hospitalisation and all-cause mortality. In cohort 1, HPVS was associated with mortality [hazard ratio (HR) per unitary increase = 1.02 (1.01–1.03); P < 0.001]. In cohort 2, HPVS was associated with B-line count (HR) = 1.05 [95% confidence interval (CI) (1.01–1.08); P = 0.02] and DPVS with the composite outcome [HR = 1.26 (1.01–1.58); P = 0.04]. HPVS and DPVS were strongly related to haemoglobin concentration and HPVS to weight. After multivariable analysis, there were no strong or consistent associations between PVS and measures of congestion, severity of symptoms, or outcome. By contrast, log[NTproBNP] was strongly associated with all three.

Conclusion

Amongst patients with CHF, HPVS and DPVS are not strongly or consistently associated with clinical or ultrasound evidence of congestion, nor clinical outcomes after multivariable adjustment. They appear only to be surrogates of the variables from which they are calculated with no intrinsic clinical utility.
Trends in antibiotic prescribing in Dutch general practice and determinants of nonprudent antibiotic prescriptions
Authors: Janssen Manon W H , de Bont Eefje G P M , Hoebe Christian J P A , Cals Jochen W L , den Heijer Casper D J
Published: June 2022

Background

Antibiotic resistance is mainly driven by (incorrect) use of antibiotics. Most antibiotics are prescribed in family medicine. Therefore, regularly monitoring of antibiotic prescriptions and evaluation of their (non-) prudent use in primary care is warranted.

Objectives

The aim of this study was to determine time trends in antibiotic prescriptions by Dutch family physicians (FPs) and to identify determinants of nonprudent antibiotic prescriptions by Dutch FPs.

Methods

Retrospective study among 27 Dutch general practices from the Research Network Family Medicine Maastricht, from 2015 to 2019.

Results

In total 801,767 patient years were analysed. Antibiotic prescriptions mainly increased in patients aged 65+ while prescriptions mainly decreased in patients below 65 years. Nonprudent antibiotic prescriptions decreased from 2015 to 2019 with the highest percentage of decline found in skin infections (66.9% [2015] to 53.9% [2019]). Overall, higher likelihood of nonprudent antibiotic prescriptions was found among men (odds ratio [OR] 4.11, 95% confidence interval [CI]: 3.91–4.33), patients aged 80+ (OR 1.44, 95% CI: 1.03–2.01; reference category ≤17 years), patients with comedication (OR 1.24, 95% CI: 1.17–1.31), and patients in urban general practices (OR 1.47, 95% CI: 1.38–1.56).

Conclusions

Antibiotic prescriptions increased over time in the elderly aged categories. Although an overall decrease in nonprudent antibiotic prescriptions was established from 2015 to 2019, percentages of nonprudent prescriptions remained high for skin infections and respiratory tract infections. Additionally, men, elderly aged patients (80+), patients with comedication and patients in urban general practices were more likely to receive nonprudent antibiotic prescriptions. Our results will help FPs to prioritize optimalization of antibiotic prescriptions in family medicine.
Sexual Orientation and Psychosocial Factors in Terms of Loneliness and Subjective Well-Being in Later Life
Authors: Buczak-Stec Elżbieta , König Hans-Helmut , Hajek André
Published: June 2022

Background and Objectives

The aim of our study was to fill the gap in knowledge regarding the association between sexual orientation and psychosocial outcomes (loneliness and subjective well-being) based on nationally representative samples.

Research Design and Methods

Cross-sectional data collected in 2017 were taken from a nationally representative sample of individuals in the second half of life (>40 years) in Germany (n = 4,785, average age 66.4 years, standard deviation [SD]: 10.5 years). Outcomes were assessed using well-established tools (life satisfaction: Satisfaction with Life Scale; positive and negative affect: Positive and Negative Affect Schedule; loneliness: De Jong Gierveld Loneliness Scale). Sexual orientation was dichotomized (heterosexual; sexual minorities including gay/lesbian, bisexual, and other). Analyses were adjusted for socioeconomic factors, lifestyle-related factors, and health-related factors.

Results

In total, around 7.8% of respondents belonged to sexual minorities. Adjusted for various several socioeconomic, lifestyle-related and health-related covariates, linear regressions showed that sexual minority older adults reported higher loneliness scores (β = 0.07, p < .05), whereas sexual orientation was not associated with subjective well-being (life satisfaction, as well as positive and negative affect). Furthermore, our analysis showed that gender, age, marital status, and depressive symptoms were consistently associated with loneliness and subjective well-being.

Discussion and Implications

In accordance with minority stress theory, our study showed that sexual minority older adults report higher loneliness scores. This finding is important as loneliness has become widely acknowledged as a new geriatric giant, which could increase, for example, the risk of morbidity and mortality. Moreover, reducing loneliness is important for successful aging.
Exploring a relative harvest rate strategy for moderately data-limited fisheries management
Authors: Fischer Simon H , De Oliveira José A A , Mumford John D , Kell Laurence T
Published: June 2022

Moderately data-limited fisheries can be managed with simple empirical management procedures without analytical stock assessments. Often, control rules adjust advised catches by the trend of an abundance index. We explored an alternative approach where a relative harvest rate, defined by the catch relative to a biomass index, is used and the target level derived from analysing historical catch length data. This harvest rate rule was tested generically with management strategy evaluation. A genetic algorithm was deployed as an optimisation procedure to tune the parameters of the control rule to meet maximum sustainable yield and precautionary management objectives. Results indicated that this method could outperform trend-based strategies, particularly when optimised, achieving higher long-term yields while remaining precautionary. However, optimum harvest rate levels can be narrow and challenging to find because they depend on historical exploitation and life history characteristics. Misspecification of target levels can have a detrimental impact on management. Nevertheless, harvest rates appear to be a suitable management option for moderately data-limited resources, and their application has modest data requirements. Harvest rate strategies are especially suitable for stocks for which case-specific analyses can be conducted.
The Atlantic surfclam fishery and offshore wind energy development: 1. Model development and verification
Authors: Munroe Daphne M , Powell Eric N , Klinck John M , Scheld Andrew M , Borsetti Sarah , Beckensteiner Jennifer , Hofmann Eileen E
Published: June 2022

Competing pressures imposed by climate-related warming and offshore development have created a need for quantitative approaches that anticipate fisheries responses to these challenges. This study used a spatially explicit, ecological-economic agent-based model integrating dynamics associated with Atlantic surfclam stock biology, decision-making behavior of fishing vessel captains, and fishing fleet behavior to simulate stock biomass, and fishing vessel catch, effort and landings. Simulations were implemented using contemporary Atlantic surfclam stock distributions and characteristics of the surfclam fishing fleet. Simulated distribution of fishable surfclam biomass was determined by a spatially varying mortality rate, fishing by the fleet was controlled by captain decisions based on previous knowledge, information sharing, and the ability to search and find fishing grounds. Quantitative and qualitative evaluation of simulation results showed that this modeling approach sufficiently represents Atlantic surfclam fishery dynamics. A fishing simulation showed that the captain's decision-making and stock knowledge, and the distribution of fishing grounds relative to home ports controlled the landed catch. The approach used herein serves as the basis for future studies examining response of the Atlantic surfclam fishery to a nexus of simultaneous, complex natural and anthropogenic pressures, and provides a framework for similar models for other resources facing similar pressures.
The Atlantic surfclam fishery and offshore wind energy development: 2. Assessing economic impacts
Authors: Scheld Andrew M , Beckensteiner Jennifer , Munroe Daphne M , Powell Eric N , Borsetti Sarah , Hofmann Eileen E , Klinck John M
Published: June 2022

The Atlantic surfclam (Spisula solidissima) fishery generates approximately USD 30 million in landings revenues annually, distributed across ports throughout the US Mid-Atlantic and Northeast. Overlap between areas of Atlantic surfclam harvests and offshore wind energy leasing make the fishery vulnerable to exclusion and effort displacement as development expands in the region. An existing integrated bioeconomic agent-based model, including spatial dynamics in Atlantic surfclam stock biology, heterogeneous captain behaviour, and federal management processes, was extended to incorporate costs and revenues for fishing vessels and processors and used to evaluate the potential economic effects of offshore wind development on the Atlantic surfclam fishery. Fishing activity and economic outcomes were simulated under different offshore wind energy development scenarios that impose spatial restrictions on Atlantic surfclam vessel fishing and transiting behaviour. Decreases in the number of trips and shifts in the spatial distribution of fishing effort reduced revenues for Atlantic surfclam fishing vessels and processors by ∼3–15% and increased average fishing costs by < 1–5%,  with impacts varying across development scenarios and fishing ports. The modelling approach used in this analysis has potential for addressing additional questions surrounding sustainable ocean multi-use and further quantifying interactions between offshore wind energy development and commercial fisheries.
The impact of coronary artery bypass grafting added to aortic valve replacement on long-term outcomes in octogenarian patients: a reconstructed time-to-event meta-analysis
Authors: Gallingani Alan , D’Alessandro Stefano , Singh Gurmeet , Hernandez-Vaquero Daniel , Çelik Mevlüt , Ceccato Evelina , Nicolini Francesco , Formica Francesco
Published: June 2022

The long-term results in studies comparing octogenarian patients who received either isolated surgical aortic valve replacement (i-SAVR) or coronary artery bypass grafting (CABG) in addition to SAVR are still debated. We performed a reconstructed time-to-event data meta-analysis of studies comparing i-SAVR and CABG+SAVR to evaluate the impact of CABG and to analyse the time-varying effects on long-term outcome. We performed a systematic review of the literature from January 2000 through November 2021, including studies comparing i-SAVR and CABG+SAVR, which reported at least 3-year follow-up and that plotted Kaplan–Meier curves of overall survival. The primary endpoint was overall long-term survival; secondary endpoints were in-hospital/30-day mortality and postoperative outcomes. The pooled hazard ratio (HR) and odds ratio) with 95% confidence interval (CI) were calculated for primary and secondary endpoints, respectively. Random-effect model was used in all analyses. Sixteen retrospective studies were included (5382 patients, i-SAVR = 2568 and CABG+SAVR = 2814). I-SAVR showed a lower incidence of in-hospital mortality compared to CABG+SAVR (odds ratio = 0.73; 95% CI= 0.60–0.89; P = 0.002). Landmark analyses showed a significantly higher all-cause mortality within 1 year from surgery in CABG+SAVR (HR = 1.17; 95% CI = 1.01–1.36; P = 0.03); after 1 year, no significant difference was observed (HR = 0.95; 95% CI = 0.87–1.04; P = 0.35). Landmark analysis was confirmed by time-varying trend of HR. Late survival of octogenarians did not differ significantly between the 2 interventions. Interestingly, CABG added to SAVR was associated with both higher in-hospital and within 1-year mortality after surgery, whereas this difference was statistically non-significant at long-term follow-up.
Comparative effect of seven prophylactic locks to prevent biofilm biomass and viability in intravenous catheters
Authors: Austin Peter David , Stapleton Paul , Elia Marinos
Published: June 2022

Background

Patients requiring long-term intravenous access are at risk of intraluminal catheter bloodstream infection. ‘Prophylactic’ locks aim to limit this risk but there is uncertainty regarding the most effective lock.

Objectives

To develop a novel technique intended to replicate clinical procedures to compare the effectiveness of various ‘prophylactic’ locks against biofilm biomass (‘biomass’) formation and biofilm viability (‘viability’) of Escherichia coli and Staphylococcus epidermidis in intravenous catheters.

Methods

For 10 consecutive days 106 cfu/mL E. coli NCTC 10418 and S. epidermidis ATCC 12228 were separately cultured in single lumen 9.6 French silicone tunnelled and cuffed catheters. These were flushed with 0.9% w/v sodium chloride using a push–pause technique before and after instillation of seven ‘prophylactic’ locks (water, ethanol, sodium chloride, heparinized sodium chloride, citrate, taurolidine plus citrate, and taurolidine; each in triplicate) for 6 h daily. Intraluminal ‘biomass’ and ‘viability’ were quantified using crystal violet staining and flush culture, respectively.

Results

The reduction of ‘biomass’ and ‘viability’ depended on both agent and species. Citrate was least effective against E. coli ‘viability’ and ‘biomass’ but most effective against S. epidermidis ‘viability’, and taurolidine was most effective against E. coli ‘biomass’ and ‘viability’ but least effective against S. epidermidis ‘viability’. ‘Biomass’ and ‘viability’ were significantly correlated in E. coli between (r = 0.997, P < 0.001) and within (r = 0.754, P = 0.001) interventions, but not in S. epidermidis.

Conclusions

A novel technique found the effect of ‘prophylactic’ agents in reducing ‘biomass’ and ‘viability’ varied by species. The choice of agent depends on the most likely infecting organism.
Mortality risks associated with empirical antibiotic activity in Escherichia coli bacteraemia: an analysis of electronic health records
Authors: Yoon Chang Ho , Bartlett Sean , Stoesser Nicole , Pouwels Koen B , Jones Nicola , Crook Derrick W , Peto Tim E A , Walker A Sarah , Eyre David W
Published: June 2022

Background

Reported bacteraemia outcomes following inactive empirical antibiotics (based on in vitro testing) are conflicting, potentially reflecting heterogeneity in causative species, MIC breakpoints defining resistance/susceptibility, and times to rescue therapy.

Methods

We investigated adult inpatients with Escherichia coli bacteraemia at Oxford University Hospitals, UK, from 4 February 2014 to 30 June 2021 who were receiving empirical amoxicillin/clavulanate with/without other antibiotics. We used Cox regression to analyse 30 day all-cause mortality by in vitro amoxicillin/clavulanate susceptibility (activity) using the EUCAST resistance breakpoint (>8/2 mg/L), categorical MIC, and a higher resistance breakpoint (>32/2 mg/L), adjusting for other antibiotic activity and confounders including comorbidities, vital signs and blood tests.

Results

A total of 1720 E. coli bacteraemias (1626 patients) were treated with empirical amoxicillin/clavulanate. Thirty-day mortality was 193/1400 (14%) for any active baseline therapy and 52/320 (16%) for inactive baseline therapy (P = 0.17). With EUCAST breakpoints, there was no evidence that mortality differed for inactive versus active amoxicillin/clavulanate [adjusted HR (aHR) = 1.27 (95% CI 0.83–1.93); P = 0.28], nor of an association with active aminoglycoside (P = 0.93) or other active antibiotics (P = 0.18). Considering categorical amoxicillin/clavulanate MIC, MICs > 32/2 mg/L were associated with mortality [aHR = 1.85 versus MIC = 2/2 mg/L (95% CI 0.99–3.73); P = 0.054]. A higher resistance breakpoint (>32/2 mg/L) was independently associated with higher mortality [aHR = 1.82 (95% CI 1.07–3.10); P = 0.027], as were MICs > 32/2 mg/L with active empirical aminoglycosides [aHR = 2.34 (95% CI 1.40–3.89); P = 0.001], but not MICs > 32/2 mg/L with active non-aminoglycoside antibiotic(s) [aHR = 0.87 (95% CI 0.40–1.89); P = 0.72].

Conclusions

We found no evidence that EUCAST-defined amoxicillin/clavulanate resistance was associated with increased mortality, but a higher resistance breakpoint (MIC > 32/2 mg/L) was. Additional active baseline non-aminoglycoside antibiotics attenuated amoxicillin/clavulanate resistance-associated mortality, but aminoglycosides did not. Granular phenotyping and comparison with clinical outcomes may improve AMR breakpoints.
Taguchi Approach for Optimization of a Green Quantitative 1H-NMR Practice for Characterization of Levetiracetam and Brivaracetam in Pharmaceuticals
Authors: Mansour Noura M , El-Sherbiny Dina T , Ibrahim Fawzia A , El-Subbagh Hussein I
Published: June 2022

Background

Recently, quantitative nuclear magnetic resonance (qNMR) competes with separation techniques such as high performance liquid chromatography (HPLC) and capillary electrophoresis for quantification purposes when dealing with molecules that lack a chromophore.

Objective

The advantages of the proton nuclear magnetic resonance spectroscopy as a revolutionary quantitative analysis method were exploited aimed at simple and green assessment of two racetams, namely levetiracetam (LEV) and brivaracetam (BRV), as a new family of antiepileptic medications with a unique mechanism of action. The developed technique was effectively used to determine LEV in Keppra tablets and BRV in laboratory-prepared tablets without interfering with the ordinarily suspected excipients.

Method

A Taguchi approach was applied as a powerful and user-friendly statistical technique for optimization of the qH1NMR experimental design for both drugs. The optimum acquisition conditions were number of scans 32, pulse angle 20°, and relaxation delay of 40 s for LEV and number of scans 128, pulse angle 90°, and relaxation delay of 1 s for BRV. NMR spectra were obtained by means of phloroglucinol as an internal standard and dimethyl sulfoxide-d6 as a solvent.

Results

The diagnostic doublet of doublet quantitative signals at 4.3 and at 4.2 ppm were chosen to estimate LEV and BRV, respectively. The recovery of both drugs was quantified through the range of 0.1–12 mg/mL. The limits of detection were 0.013, 0.0013 and the limits of quantitation were 0.04, 0.0039 mg/mL for LEV and BRV correspondingly.

Conclusions

The suggested technique was fully validated according to ICH guidelines and proved to be an eco-friendly practice by means of three different assessment tools, including the green analytical procedures index, national environmental methods index, and analytical eco-scale. qH1NMR should be considered a green alternative for quantification and quality control assessment of pharmaceuticals.

Highlights

This research represents the first simple, quick, and green alternative method for determination of both racetams in their pharmaceuticals.