bluuebunny/crossref_metadata_2025 huggingface dataset:
Rare severe hypofibrinogenemia induced by tissue plasminogen activator in stroke patients
Authors: Huang Xuming , Cao Liming
Published: March 2021

Rationale:

Severe hypofibrinogenemia after intravenous thrombolysis (IVT) with recombinant tissue plasminogen activator (rt-PA) is rare and easily overlooked, but hypofibrinogenemia increases the risk of major bleeding. However, it is unclear when hypofibrinogenemia reaches the peak and when hypofibrinogenemia is resolved.

Patient concerns:

Case 1 was of a 66-year-old man who was hospitalized due to sudden onset of vague speech and right hemiplegia for 4 hours. Case 2 was of an 84-year-old woman who was hospitalized for sudden onset of left hemiplegia and vague speech for 4 hours. In case 1, fibrinogen levels decreased from normal values to <0.25 g/L within 4.5 hours after commencing IVT and returned to normal at 35 hours later. In case 2, fibrinogen levels decreased from 1.1 to <0.25 g/L within 2 hours after commencing IVT and normalized 36.5 hours later.

Diagnoses:

Both patients were diagnosed with rt-PA-related hypofibrinogenemia.

Interventions:

No antiplatelet or symptomatic treatment was administered during the period of hypofibrinogenemia.

Outcomes:

Fibrinogen levels gradually recovered. In case 1, the patient did not experience cerebral hemorrhage during hypofibrinogenemia. His symptoms improved significantly within 1 week. In case 2, repeat computed tomography revealed minor cerebral hemorrhage, but no deterioration in her condition was noted until she was discharged.

Lessons:

Rapid, severe, and prolonged hypofibrinogenemia may occur after IVT with rt-PA, which may increase the risk of massive hemorrhage and affect the related therapy. Prompt diagnosis of hypofibrinogenemia is important for preventing complications. We recommend checking the fibrinogen levels routinely after IVT. Fibrinogen replacement therapy and platelet transfusion are the main management routes for rt-PA-related symptomatic intracranial hemorrhage.
Assessment of blood consumption score for pediatrics predicts transfusion requirements for children with trauma
Authors: Komori Akira , Iriyama Hiroki , Aoki Makoto , Deshpande Gautam A. , Saitoh Daizoh , Naito Toshio , Abe Toshikazu
Published: March 2021

Although transfusion is a primary life-saving technique, the assessment of transfusion requirements in children with trauma at an early stage is challenging. We aimed to develop a scoring system for predicting transfusion requirements in children with trauma.

This was a case–control study that employed a nationwide registry of patients with trauma (Japan Trauma Data Bank) and included patients aged <16 years with blunt trauma between 2004 and 2015. An assessment of blood consumption score for pediatrics (ped-ABC score) was developed based on previous literatures and clinical relevance. One point was assigned for each of the following criteria: systolic blood pressure ≤90 mm Hg, heart rate ≥120/min, Glasgow coma scale (GCS) score <15, and positive focused assessment with sonography for trauma (FAST) scan. For sensitivity analysis, we assessed age-adjusted ped-ABC scores using cutoff points for different ages.

Among 5943 pediatric patients with trauma, 540 patients had transfusion within 24 hours after trauma. The in-hospital mortality rate was 2.6% (145/5615). The transfusion rate increased from 7.6% (430/5631) to 35.3% (110/312) in patients with systolic blood pressure ≤90 mm Hg (1 point), from 6.1% (276/4504) to 18.3% (264/1439) in patients with heart rate ≥120/min (1 point), from 4.1% (130/3198) to 14.9% (410/2745) in patients with disturbance of consciousness with GCS score <15 (1 point), and from 7.4% (400/5380) to 24.9% (140/563) in patients with positive FAST scan (1 point). Ped-ABC scores of 0, 1, 2, 3, and 4 points were associated with transfusion rates of 2.2% (48/2210), 7.5% (198/2628), 19.8% (181/912), 53.3% (88/165), and 89.3% (25/28), respectively. After age adjustment, c-statistic was 0.76 (95% confidence interval, 0.74–0.78).

The ped-ABC score using vital signs and FAST scan may be helpful in predicting the requirement for transfusion within 24 hours in children with trauma.
The semantic of a pandemic
Authors: Mapelli Massimo , Mantegazza Valentina , Agostoni Piergiuseppe
Published: March 2021

Rationale:

Northern Italy has been particularly hit by the current Covid-19 pandemic. Italian deceased patients have a mean age of 78.5 years and only 1.2% have no comorbidities. These data started a public debate whether patients die “with” or “from” Covid-19. If on one hand the public opinion has been persuaded to believe that Covid-19 infection has poor outcomes just in elderly and/or fragile subjects, on the other hand, hospitals are admitting an increasing number of healthy young patients needing semi-intensive or intensive care units.

Patient concerns:

At the end of March 2020, a 79-year-old patient (M.G.) was admitted to the emergency department of our hospital with a 5 days history of fever, dyspnea, and cough. He was known for hypertension and coronary artery disease with a previous coronary artery stenting. Both the comorbidities were carried out without complications and the patient was previously asymptomatic and in good health. At admission, he was febrile and showed signs of respiratory failure with hypoxia and hypocapnia at blood gas analysis.

Diagnosis:

The day after, he was tested for SARS-CoV-2 with a real-time reverse transcriptase-polymerase chain reaction assay of nasopharyngeal swab, which turned positive and a chest CT-Scan was consistent with the diagnosis of interstitial pneumonia.

Interventions:

He was treated with i.v. diuretics, paracetamol, prolonged noninvasive ventilation (CPAP), and empiric antibiotic therapy on top of his chronic treatment.

Outcomes:

A treatment with heparin and corticosteroids was started; however, he developed irreversible respiratory failure. Invasive ventilation was not considered appropriate due to his comorbidities, low chances of recovery, and intensive care unit overcrowding. The patient died 9 days after admission.

Lessons:

Health conditions that are most reported as risk factors are common cardiovascular diseases that can be managed in modern clinical practice. Through a brief illustrative clinical case, we would like to underline how Covid-19 can be per se the cause of death in patients that would otherwise have had an acceptable life expectancy.
Impacts of early insulin treatment vs glimepiride in diabetic patients with background metformin therapy
Authors: Yen Fu-Shun , Hsu Chih-Cheng , Su Yuan-Chih , Wei James Cheng-Chung , Hwu Chii-Min
Published: March 2021

Type 2 diabetes mellitus (T2DM) is a progressive disease. After metformin failure, the addition of insulin or sulfonylureas might increase the risk of hypoglycemia and cardiovascular (CV) morbidity. Here, the risk of all-cause mortality was compared between early insulin treatment and glimepiride use in T2DM patients with background metformin therapy.

We conducted a 9-year retrospective cohort study from the population-based National Health Insurance Research Database in Taiwan. A total of 2054 patients with T2DM under insulin or glimepiride treatment were enrolled during 2004 to 2012. Overall event rates of all-cause mortality were compared between 1027 insulin users and 1027 matched glimepiride users.

After the propensity score matching, the mortality rates were 72.5 and 4.42 per 1000 person-years for insulin users and glimepiride users. The adjusted hazard ratio of mortality was 14.47 (95% CI: 8.64–24.24; P value <.001) as insulin compared with glimepiride users. The insulin users had significantly higher risk of CV death (adjusted hazard ratio 7.95, 95% CI 1.65–38.3, P = .01) and noncardiovascular death (adjusted hazard ratio 14.9, 95% CI 8.4–26.3, P < .001).

The nationwide study demonstrated that metformin plus insulin therapy was associated with higher risk of all-cause mortality.
Differences in gut microbiota between allergic rhinitis, atopic dermatitis, and skin urticaria
Authors: Su Yu-Jih , Luo Sheng-Dean , Hsu Chung-Yuan , Kuo Ho-Chang
Published: March 2021

Introduction.

Several forms of allergy have been clinically presented, including, among others, atopic dermatitis (eczema), urticaria (hives), and allergic rhinitis (rhinitis). As their detailed pathogenesis continues to be researched, we aimed in the current study to compare gut microbiota differences between eczema, hives, and rhinitis patients.

Methods.

We enrolled 19 eczemas, nine hives, and 11 allergic rhinitis patients in this study. Fecal samples were examined using 16S ribosomal ribonucleic acid amplicon sequencing, followed by bioinformatics and statistical analyses. We compared microbiota in dermatitis (eczema), chronic urticaria (hives), and allergic rhinitis (rhinitis).

Results.

All clinical data were similar between the subgroups. The microbiota results indicated that Bacteroidales species were found in skin allergies, both urticaria and eczema, when compared to rhinitis. The microbiota differs substantially between those patients with atopic dermatitis (eczema), chronic urticaria (hives), and allergic rhinitis (rhinitis), thus indicating that the gut-skin and gut-nose axes exist. Gut flora colonies differ significantly between skin allergy and nose allergy. Bacteroidales species could be a clinical link between gut flora and skin allergy; of those, Bacteroids Plebeius DSM 17135 is significantly associated with the urticaria (hives) subgroup.Conclusion. Our results demonstrated high intra-group homogeneous and high inter-group heterogeneous microbiota. The clinical symptoms of eczema, hives, and rhinitis can all be linked to specific microbiota in the current study. In this pilot study, the Ruminococcaceae and Bacteroidales species are associated with allergic disease, in line with several previous published articles, and the abundance of Firmicutes Phylum is representative of intestinal dysbiosis. In the future, a larger cohort and thorough biochemical studies are needed for confirmation.
Clinical Practice Patterns in Nonsyndromic Craniosynostosis: A Review of Continuous Certification Tracer Data From the American Board of Plastic Surgery
Authors: Yuksel Selcen S. , Kearney Aaron M. , Taub Peter J. , Gosain Arun K.
Published: March 2021

Since 2003, the American Board of Plastic Surgery has collected data on 20 plastic surgery operations as part of the Maintenance of Certification process. The goal of this study was to describe national trends in craniosynostosis repair as they relate to Evidence-Based Medicine (EBM) articles published during this timeframe. Cumulative tracer data for nonsyndromic craniosynostosis were reviewed from 2006 to March 2020, and compared with EBM articles published in Plastic and Reconstructive Surgery. Topics were categorized as:

As of March 2020, 940 cases of nonsyndromic craniosynostosis had been entered. The median age at the time of surgery was 8 months (range, 1–204 months). Practice patterns from 2006 through 2013 were compared with those between 2013 and 2020. The most common surgical technique from 2006 through 2013 was anterior regional cranioplasty, and from 2013 to 2020 was orbital rim advancement. Differences in practice between these time periods included an increase in patients with asymptomatic clinical presentation (27% versus 42%, P < 0.001) and presentation with papilledema (1% versus 4%, P = 0.003). Use of preoperative MRI significantly increased (1% versus 6%, P < 0.001). Significant changes were noted in surgical technique and methods of fixation. By examining the American Board of Plastic Surgery tracer data, the authors can describe national trends in presentation, imaging, and surgical techniques for non -syndromic craniosynostosis repair over a 14-year period.
“Looks Can be Deceptive” – Radicular Cyst Mimicking a Developmental Origin Cyst
Authors: Khan Imran , Ansari Mohammad Irfan , Mansoori Shahnaz , Saalim Mohd.
Published: March 2021

Cysts of the jaws are not rare, among them the radicular cyst being the most common. It is an inflammatory type of odontogenic cyst forming as a consequence of a long-standing sequel of pulpal necrosis. In contrast to its usual location of occurrence (ie, the maxilla), herewith we report a case of successful management of a 45 year old female patient with a large radiolucent lesion in the left mandibular posterior region with a mandibular ramus extension. The pathology which was strongly presenting as a developmental variety of odontogenic cyst radiographically, was diagnosed as a radicular cyst after histopathological confirmation. To the authors best of knowledge radicular cyst extending into the mandibular ramus is extremely rare and has never been reported previously.
Insecticide resistance governed by gut symbiosis in a rice pest,
Cletus punctiger,
under laboratory conditions
Authors: Ishigami Kota , Jang Seonghan , Itoh Hideomi , Kikuchi Yoshitomo
Published: March 2021

Resistance to toxins in insects is generally thought of as their own genetic trait, but recent studies have revealed that gut microorganisms could mediate resistance by detoxifying phytotoxins and man-made insecticides. By laboratory experiments, we here discovered a striking example of gut symbiont-mediated insecticide resistance in a serious rice pest,
Cletus punctiger
. The rice bug horizontally acquired fenitrothion-degrading
Burkholderia
through oral infection and housed it in midgut crypts. Fenitrothion-degradation test revealed that the gut-colonizing
Burkholderia
retains a high degrading activity of the organophosphate compound in the insect gut. This gut symbiosis remarkably increased resistance against fenitrothion treatment in the host rice bug. Considering that many stinkbug pests are associated with soil-derived
Burkholderia
, our finding strongly supports that a number of stinkbug species could gain resistance against insecticide simply by acquiring insecticide-degrading gut bacteria.
Dark extinction: the problem of unknown historical extinctions
Authors: Boehm Mannfred M. A. , Cronk Quentin C. B.
Published: March 2021

The extinction of species before they are discovered and named (dark extinction, DE) is widely inferred as a significant part of species loss in the ‘pre-taxonomic’ period (approx. 1500–1800 CE) and, to some extent, in the ‘taxonomic period’ (approx. 1800–present) as well. The discovery of oceanic islands and other pristine habitats by European navigators and the consequent introduction of destructive mammals, such as rats and goats, started a process of anthropogenic extinction. Much ecosystem change happened before systematic scientific recording, so has led to DE. Statistical methods are available to robustly estimate DE in the ‘taxonomic period’. For the ‘pre-taxonomic period’, simple extrapolation can be used. The application of these techniques to world birds, for example, suggests that approximately 56 DEs occurred in the ‘taxonomic period’ (1800–present) and approximately 180 in the ‘pre-taxonomic period’ (1500–1800). Targeting collection activities in extinction hotspots, to make sure organisms are represented in collections before their extinction, is one way of reducing the number of extinct species without a physical record (providing that collection efforts do not themselves contribute to species extinction).
Basil Lythgoe. 18 August 1913—18 April 2009
Authors: Jones J. C.
Published: March 2021

Basil Lythgoe was distinguished as an organic chemist. He began his career at the University of Manchester, where he had studied for his undergraduate and PhD degrees, before moving to University of Cambridge. During this period he collaborated with Alexander Todd on the structural elucidation and total synthesis of the natural nucleosides, and was also noted for his investigation of the structure of the natural substance macrozamin. In 1953 he moved to the chair of organic chemistry at the University of Leeds, running a research group from which several graduate students went on to academic careers of the highest distinction. At Leeds he worked on the structure of the alkaloid taxine 1 and calciferol, among other natural substances. Lythgoe's work was characterized by a combination of insight and high experimental skill.
Devendra Lal. 14 February 1929—1 December 2012
Authors: Goswami J. N. , Macdougall J. D.
Published: March 2021

Devendra Lal was an Indian nuclear physicist who began his career studying particle physics while a student at the Tata Institute of Fundamental Research (TIFR) in Bombay, using tracks in nuclear emulsions to study cosmic ray particles and their interactions. He soon moved on to the search for radionuclides produced in the atmosphere by cosmic ray bombardment, independently (with colleagues) discovering radioisotopes of Be, P and Si and using them as geophysical tracers for atmospheric, meteorological and oceanographic processes. His career revolved principally around multiple aspects of cosmic rays, employing theory and experiment to examine their flux, chemical composition and energy spectrum, both at present and in the past through (for example) studies of particle tracks in the minerals of meteorites and lunar samples. He played a major role in developing approaches for the use of terrestrial cosmic-ray-produced isotopes as dating tools and tracers for a wide range of Earth processes, from biological cycles in the ocean to landscape evolution and ice ablation in the Antarctic. At various stages of his career Lal was professor at TIFR and led the geophysics group there, was professor and director of the Physical Research Laboratory in Ahmedabad, India, and was professor at the Scripps Institution of Oceanography, University of California San Diego. He was elected fellow of numerous scientific organizations and academies internationally, and was the recipient of many scientific awards and prizes.
Superstatistical modelling of protein diffusion dynamics in bacteria
Authors: Itto Yuichi , Beck Christian
Published: March 2021

A recent experiment (Sadoon AA, Wang Y. 2018
Phys. Rev. E
98
, 042411. (
doi:10.1103/PhysRevE.98.042411
)) has revealed that nucleoid-associated proteins (i.e. DNA-binding proteins) exhibit highly heterogeneous diffusion processes in bacteria where not only the diffusion constant but also the anomalous diffusion exponent fluctuates for the various proteins. The distribution of displacements of such proteins is observed to take a
q
-Gaussian form, which decays as a power law. Here, a statistical model is developed for the diffusive motion of the proteins within the bacterium, based on a superstatistics with two variables. This model hierarchically takes into account the joint fluctuations of both the anomalous diffusion exponents and the diffusion constants. A fractional Brownian motion is discussed as a possible local model. Good agreement with the experimental data is obtained.
Unity in bronze: German universities and the 250th anniversary of the Royal Society
Authors: Jöns Heike , Heffernan Michael , Bond Dean W.
Published: March 2021

This essay explains the emergence of a new era in global science and politics through increasing scientific nationalism in the years leading up to World War I. Based upon original archival research, we examine how the cultural geopolitics of international scientific jubilees triggered a major change in the self-representation of Prussian and non-Prussian German universities from delivering individual congratulatory addresses to the demonstration of unity through one joint address and present. The analysis focuses on the first centenary of the Royal Frederick University in Kristiania and the quincentenary of the University of St Andrews, both held in 1911, before discussing how all 21 German universities agreed to convey their felicitations with one voice—as
Universitates Germaniae
—and one address—an inscribed bronze votive tablet—to the Royal Society in London on the occasion of its 250th anniversary as a chartered institution in 1912. We argue that in the context of growing imperial and economic rivalry between European nation-states, the politicization of these jubilees reinforced scientific nationalism and encouraged a unified appearance of German universities overseas, no less than 41 years after the constitution of the German Empire. By analysing changing material, practical, and imaginative resource ensembles in science and politics, we reveal how the geographical imagination of national unity materialized in the German universities’ use of bronze tablets for conveying academic appreciation and geopolitical messages in London, and at the Groningen tercentenary in 1914, and thereby heralded a new era characterized by a national university system, an escalation of scientific nationalism, and global wars.
‘Out of a greate laborinth of errors’: Lunar astronomy in London before Kepler
Authors: Włodarczyk Jarosław
Published: March 2021

Johannes Kepler is considered to be the first scholar to have offered an adequate description of heavenly phenomena observed on the Moon's sky. Kepler outlined his ideas in his
Somnium
(
The Dream
), written originally in 1609, and subsequently printed in the years 1630/34. Kepler's lunar astronomy was to expose the absurdity of the arguments that the geocentric theatre of heavenly phenomena proves that the Earth remains motionless. In this paper, I argue that at the turn of the seventeenth century the idea of the sky observed from the Moon's surface was explored in cosmological discourse far more often than it has been assumed so far. My argument derives from the manuscript treatise
Astrostereon
(1603) authored by an English astrologer and physician, Edward Gresham. Writing for the same purpose as Kepler but several years earlier, Gresham laid down the foundation of lunar astronomy. I also demonstrate the uses of lunar astronomy in astrological almanacs printed in London at the time when Kepler's ideas were not widely known.
From infection to cancer: how DNA tumour viruses alter host cell central carbon and lipid metabolism
Authors: Magon Kamini L. , Parish Joanna L.
Published: March 2021

Infections cause 13% of all cancers globally, and DNA tumour viruses account for almost 60% of these cancers. All viruses are obligate intracellular parasites and hijack host cell functions to replicate and complete their life cycles to produce progeny virions. While many aspects of viral manipulation of host cells have been studied, how DNA tumour viruses manipulate host cell metabolism and whether metabolic alterations in the virus life cycle contribute to carcinogenesis are not well understood. In this review, we compare the differences in central carbon and fatty acid metabolism in host cells following infection, oncogenic transformation, and virus-driven cancer of DNA tumour viruses including: Epstein–Barr virus, hepatitis B virus, human papillomavirus, Kaposi's sarcoma-associated herpesvirus and Merkel cell polyomavirus.
On the Environmental Determinants of COVID-19 Seasonality
Authors: Choi Yeon-Woo , Tuel Alexandre , Eltahir Elfatih A. B.
Published: March 2021

Viral respiratory diseases (VRDs), such as influenza and COVID-19, are thought to spread faster over winter than during summer. It has been previously argued that cold and dry conditions were more conducive to the transmission of VRD than warm and humid climates, although this relationship appears restricted to temperate regions, and the causal relationship is not well understood. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing COVID-19 has emerged as a serious global public health problem after the first COVID-19 reports in Wuhan, China, in late 2019. It is still unclear whether this novel respiratory disease will ultimately prove to be a seasonal endemic disease. Here, we suggest that Air Drying Capacity (ADC; an atmospheric state-variable known to control the fate/evolution of the virus-laden droplets) and ultraviolet radiation (UV) are probable environmental determinants in shaping the transmission of COVID-19 at the seasonal time scale. These variables, unlike temperature and humidity, provide a physically-based framework consistent with the apparent seasonal variability in COVID-19 prevalence across a broad range of climates (e.g., Germany and India). Since this disease is known to be influenced by the compounding effect of social, biological, and environmental determinants, this study does not claim that these environmental determinants exclusively shape the seasonality of COVID-19. However, we argue that ADC and UV play a significant role in COVID-19 dynamics at the seasonal scale. These findings could help guide the development of a sound adaptation strategy against the pandemic over the coming seasons.

Plain Language Summary

There is growing scientific interest in the potential seasonality of COVID-19 and its links to climate variables. This study aims to determine whether four environmental variables, namely temperature, humidity, Air Drying Capacity (ADC), and ultraviolet radiation (UV), are probable environmental determinants for the observed seasonal dynamics of COVID-19 prevalence, based on extensive country-level data spanning the first year of the pandemic. Although the influence of socio-economic factors may be dominant, we here suggest that ADC and UV are key environmental determinants of COVID-19 and can potentially affect the transmission and seasonality of the disease across a wide range of climates.

Key Points

The seasonality of COVID-19 appears to follow seasonality of some environmental variables.

Seasonality of air drying capacity and ultraviolet radiation consistently match seasonality of COVID-19, across climatic zones.

Seasonality of air humidity and temperature, match seasonality of COVID-19 in temperate climates, but not in tropical monsoon climates.
Elevated Neutrophil to Lymphocyte Ratio Predicts In-hospital Mortality Among Stroke Patients in a Metropolitan hospital in Australia, Universal Value-added measure in Stroke Care
Authors: Wijeratne Tissa , Sales Carmela , Karimi Leila , Jakovljevic Mihajlo
Published: March 2021

Neutrophil counts (innate immunity) and lymphocyte counts (adaptive immunity) are common markers of inflammation in the context of acute stroke, and Neutrophil lymphocyte ratio (NLR) is likely to be expected to predict the post-stroke outcome.

This study aimed to explore the predictive value of NLR to predict the very early mortality during the acute hospital admission (death within the first week of hospital stay) as this has management implications for the ongoing investigations, family discussions and resource allocation. This the first such study attempting at exploring the role of NLR in hyperacute in-patient mortality in the world to the best of our knowledge.

This retrospective study included 120 patients (60 acute stroke patients who died within the first week of the hospital stay and 60 age, sex-matched controls who were discharged within two weeks of the hospital admission, alive. We reviewed the total white cell counts of these patients (first 72 hours of the hospital admission) and NLR was calculated manually. While there was no statistically significant difference between mean neutrophil counts and mean lymphocyte counts between the two cohorts [neutrophil counts (mean, SD), 8.52(3.20) in the death cohort, 6.48(2.20) among survivors and lymphocyte (mean, SD), 1.83(1.48) in the death cohort,1.66 (0.69) among survivors], there was a statistically significant difference in NLR between the two cohorts. NLR (mean, SD) was 6.51 (4.98) in the death cohort while the survivors had mean NLR of 4.64 with an SD 2.90 with a p-value of 0.048. Hypertension, diabetes, atrial fibrillation, previous vascular events were common in both groups indicating the value of exploring the evidence of background compromised vascular system and metabolic syndrome and bringing the systems biology approach to the management of stroke.
A multicentre point prevalence survey of patterns and quality of antibiotic prescribing in Indonesian hospitals
Authors: Limato Ralalicia , Nelwan Erni J. , Mudia Manzilina , Brabander Justin de , Guterres Helio , Enty Enty , Mauleti Ifael Y. , Mayasari Maria , Firmansyah Iman , Hizrani May , Hamers Raph L.
Published: March 2021

Synopsis

Background

Antibiotic misuse and overuse are a major driver of antimicrobial resistance, but systematic data in Indonesia are scarce.

Objectives

To evaluate patterns and quality indicators of antibiotic prescribing in six acute-care hospitals in Jakarta, Indonesia.

Methods

We conducted a hospital-wide point prevalence survey (PPS) between March and August 2019, using Global-PPS and WHO-PPS protocols. The analysis focused on antibacterials for systemic use (antibiotics).

Results

Of 1602 inpatients, 993 (62.0%) received ≥1 antimicrobials. Of 1666 antimicrobial prescriptions, 1273 (76.4%) were antibiotics. Most common reasons for prescribing were pneumonia (27.7%), skin and soft tissue infections (8.3%), gastrointestinal prophylaxis (7.9%), and gastrointestinal infections (5.4%). The most common indication was community-acquired infection (42.6%), followed by surgical prophylaxis (22.6%), hospital-acquired infection (18.5%), medical prophylaxis (9.6%), unknown (4.6%) and other indications (2.1%). The most prescribed antibiotic classes were third-generation cephalosporins (44.3%), fluoroquinolones (13.5%), carbapenems (7.4%), penicillins with B-lactamase inhibitor (6.8%) and aminoglycosides (6.0%). According to the WHO AWaRe classification, Watch antibiotics accounted for 67.4%, followed by 28.0% Access, 2.4% Reserve, and 2.2% Unclassified. Reason for prescribing, stop/review date and planned duration were poorly documented. Hospital antibiotic guidelines were not available for 28.1% of prescriptions, and guideline compliance was 52.2% (478/915). Parenteral administration was high (85.1%). Targeted (non-empirical) prescriptions comprised 8.1% (44/542) for community-acquired infections and 26.8% (63/235) for hospital-acquired infections.

Conclusions

Our data indicate a high rate of parenteral, empiric use of broad-spectrum antibiotics in Indonesian hospitals, coupled with poor documentation and guideline adherence. The findings suggest important areas for antimicrobial stewardship interventions.
Exposure-response analysis of the association of maternal smoking and use of electronic cigarettes (vaping) in relation to preterm birth and small-for-gestational-age in a national US sample, 2016-2018
Authors: Wang Xi , Lee Nora L , Burstyn Igor
Published: March 2021

We aimed to estimate exposure-response associations between smoking or vaping, and preterm and small-for-gestational age (SGA) births. We included 99,201 mothers who delivered live singletons in 2016-2018 from the Pregnancy Risk Assessment Monitoring System. We created exposure categories based on participants’ self-reported average number of cigarettes smoked per day and vaping frequency. Dual users in late pregnancy were a heterogeneous group: 36% heavily smoked and occasionally vaped; 29% lightly smoked and frequently vaped; 19% lightly smoked and frequently vaped; and 15% both heavily smoked and frequently vaped. While dual users who heavily smoked and occasionally vaped had the highest adjusted OR for SGA (3.4, 95% CI 1.7-6.6), all the dual users were on average at about twice the odds of having SGA than non-users. While the risks of preterm birth were higher among sole light smokers (adjusted OR 1.3, 95% CI 1.1-1.5) and sole heavy smokers (adjusted OR 1.4. 95 CI 1.2-1.8) than non-users, the adjusted odds of preterm births for dual users were not noticeably higher than those of non-users, unless they were also heavy smokers. Excess of preterm births among heavy vapers was suggested. Among younger non-Hispanic white women (where vaping is most common), only excess risk of SGA, not preterm, with vaping was apparent. Relative to non-users, both smoking and vaping during pregnancy appear to increase risk of SGA, but excess risk of preterm births appears to be primarily attributable to smoking alone. Higher levels of exposure tended to confer more risk.

Highlights

No observable change in prevalence of vaping during pregnancy from 2016 to 2018

Both smoking and vaping during pregnancy appear to increase risk of SGA births

Excess risk of preterm births appears to be primarily attributable to smoking alone
Maternal psychiatric diagnosis and comorbidities around pregnancy
Authors: Khachadourian Vahe , Kodesh Arad , Levine Stephen Z. , Lin Emma , Buxbaum Joseph D. , Bergink Veerle , Sandin Sven , Reichenberg Abraham , Janecka Magdalena
Published: March 2021

IMPORTANCE

Comorbidity between mental and physical health is a frequent problem, resulting in greater morbidity than the sum of the effects of individual diseases. Despite pervasive physiological and behavioral changes during pregnancy, the pattern of comorbidities among pregnant women is not well-understood.

OBJECTIVE

Systematically examine the associations between mental and physical diagnoses around pregnancy.

DESIGN, SETTING, PARTICIPANTS

Population-based sample, containing all children born between January 1st, 1997 and December 31st, 2008 within a health maintenance organization (HMO) in Israel. Cohort children were linked to their mothers’ health information, creating mother-child dyads.

MAIN OUTCOMES AND MEASURES

The primary outcome was any ICD-9 mental health diagnosis within the pregnancy period or the preceding 12 months. The secondary outcomes were specific ICD-9 mental health diagnoses. Exposures were all ICD-9 physical (non-mental) health diagnoses received during the exposure period. We used logistic regression to test the risk of physical health diagnoses in pregnant women associated with mental health diagnoses. The covariates for this study included maternal age, birth year, socioeconomic status and total number of ICD-9 diagnoses during the exposure period.

RESULTS

The analytical sample included 76,783 mother-child dyads, with 30,084 unique mothers. The mean age at birth was 29.8 years, with 4.4% of mothers diagnosed with a mental health disorder during the pregnancy period. Of the 18 major ICD-9 diagnostic categories, 10 were positively associated with mental health disorders, including ICD categories of e.g., symptoms, signs, and ill-defined conditions (OR=1.69; 95% CI=1.50, 1.89), musculoskeletal (OR=1.33; 95% CI=1.22,1.45) and digestive system diseases (OR=1.25; 95% CI=1.15, 1.37). Comorbidity between mental and physical health diagnoses was higher than that observed between various physical health diagnoses. Associations between physical health diagnoses and specific mental health conditions were consistent with the results of the general mental health and physical health comorbidity.

CONCLUSION AND RELEVANCE

We observed that associations between maternal diagnoses and mental health stand out from the general pattern of comorbidity between non-mental health diseases. The high co-occurrence of mental health and physical health diagnoses has implications for diagnoses and management of morbidity among pregnant women, with potential impact on pregnancy and child health outcomes.
A mixed methods study of seasonal influenza vaccine hesitancy in adults with chronic respiratory conditions
Authors: Williams Lynn , Deakin Karen , Gallant Allyson , Rasmussen Susan , Young David , Cogan Nicola
Published: March 2021

Background

Seasonal influenza vaccination is recommended for patients with chronic respiratory conditions, but uptake is suboptimal. We undertook a comprehensive mixed methods study in order to examine the barriers and enablers to influenza vaccination in patients with chronic respiratory conditions.

Methods

Mixed methods including a survey (n=429) which assessed socio-demographics and the psychological factors associated with vaccine uptake (i.e. confidence, complacency, constraints, calculation and collective responsibility) with binary logistic regression analysis. We also undertook focus groups and interviews (n=59) to further explore barriers and enablers to uptake using thematic analysis.

Results

The survey analysis identified that older participants were more likely to accept the vaccine, as were those with higher perceptions of collective responsibility around vaccination, lower levels of complacency, and lower levels of constraints. Thematic analysis showed that concerns over vaccine side effects, lack of tailored information and knowledge, and a lack of trust and rapport with healthcare professionals were key barriers. In contrast, the importance of feeling protected, acceptance of being part of an at-risk group, and feeling a reduced sense of vulnerability after vaccination were seen as key enablers.

Conclusions

Our findings showed that the decision to accept a vaccine against influenza is influenced by multiple sociodemographic and psychological factors. Future interventions should provide clear and transparent information about side effects and be tailored to patients with chronic respiratory conditions. Interactions between patients and their healthcare providers have a particularly important role to play in helping patients address their concerns and feel confident in vaccination.
COVID-19 Mortality in California Based on Death Certificates: Disproportionate Impacts Across Racial/Ethnic Groups and Nativity
Authors: Garcia Erika , Eckel Sandrah P. , Chen Zhanghua , Li Kenan , Gilliland Frank D.
Published: March 2021

Purpose

To examine characteristics of coronavirus disease 2019 (COVID-19) decedents in California (CA) and evaluate for disproportionate mortality across race/ethnicity and ethnicity/nativity.

Methods

COVID-19 deaths were identified from death certificates. Age-adjusted mortality rate ratios (MRR) were compared across race/ethnicity. Proportionate mortality rates (PMR) were compared across race/ethnicity and by ethnicity/nativity.

Results

We identified 10,200 COVID-19 deaths in CA occurring February 1 through July 31, 2020. Decedents tended to be older, male, Hispanic, foreign-born, and have lower educational attainment. MRR indicated elevated COVID-19 morality rates among Asian/Pacific Islander, Black, and Hispanic groups compared with the White group, with Black and Hispanic groups having the highest MRR at 2.75 (95%CI:2.54-2.97) and 4.18 (95%CI: 3.99-4.37), respectively. Disparities were larger at younger ages. Similar results were observed with PMR, which remained in analyses stratified by education. Elevated PMR were observed in all ethnicity/nativity groups, especially foreign-born Hispanic individuals, relative to U.S.-born non-Hispanic individuals, were generally larger at younger ages, and persisted after stratifying by education.

Conclusions

Differential COVID-19 mortality was observed in California across racial/ethnic groups and by ethnicity/nativity groups with evidence of greater disparities among younger age groups. Identifying COVID-19 disparities is an initial step towards mitigating disease impacts in vulnerable communities.
Massive Open Online Course (MOOC) Opportunities on Health Education (HE) during of mandatory social isolation context
Authors: Dolores-Maldonado Gandy , Cañari-Casaño Jorge L. , Montero-Romainville Rosalia , Málaga Germán
Published: March 2021

Background

Routine care for prevention and health promotion has reduced significantly due to the Covid-19 pandemic and mandatory social isolation measures. In this context, it is necessary to identify and describe Massive Open Online Courses (MOOCs) that provide opportunities for health education, promotion, and prevention aimed at the general population. The study is a systematic review of MOOCs on health education, health promotion, and prevention for the general population in a pandemic context.

Methods

We developed a search for MOOC courses aimed at the general population on health education, health promotion, and prevention in different MOOC available platforms. We executed a descriptive analysis of the main characteristics of the selected MOOCs.

Results

There were 117 MOOCs chosen on Health education, promotion, and prevention for the general population. Coursera (40.3%) was the platform that offered the highest quantity of MOOCs; more than half of MOOCs language was in English (52.9%). The median duration time in hours of the selected MOOCs was 11 (IR 6-15). The predominant themes were “Health promotion” (43%) and “Food and nutrition” (31%), and the origin was mainly from Europe (37.8%).

Conclusions

MOOCs offerings in Health Education (HE) is diverse, predominantly in English, of European origin, and in health promotion issues. This study opens an opportunity to multiply initiatives in different territories, considering other languages and topics more akin to each territorial reality, allowing it to be a more equitable learning opportunity in times of pandemic and compulsory social isolation.

FUNDING

None.
Aging-induced isoDGR-modified fibronectin activates monocytic and endothelial cells to promote atherosclerosis
Authors: Park Jung Eun , JebaMercy Gnanasekaran , Pazhanchamy Kalailingam , Guo Xue , Ngan SoFong Cam , Kang Liou Ken Cheng , Lynn Soe EinSi , Ng Ser Sue , Meng Wei , Lim Su Chi , Leow Melvin Khee-Shing , Richards A Mark , Pennington Daniel J , de Kleijn Dominique P.V. , Sorokin Vitaly , Ho Hee Hwa , McCarthy Neil E. , Sze Siu Kwan
Published: March 2021

Background and Aims

Aging is the primary risk factor for cardiovascular disease (CVD), but the mechanisms underlying age-linked atherosclerosis remain unclear. We previously observed that long-lived vascular matrix proteins can acquire ‘gain-of-function’ isoDGR motifs that might play a role in atherosclerotic pathology.

Methods

IsoDGR-specific mAb were generated and used for ELISA-based measurement of motif levels in plasma samples from patients with coronary artery diseases (CAD) and non-CAD controls. Functional consequences of isoDGR accumulation in age-damaged fibronectin were determined by bioassay for capacity to activate monocytes, macrophages, and endothelial cells (signalling activity, pro-inflammatory cytokine expression, and recruitment/adhesion potential). Mice deficient in the isoDGR repair enzyme PCMT1 were used to assess motif distribution and macrophage localisationin vivo.

Results

IsoDGR-modified fibronectin and fibrinogen levels in patient plasma were significantly enhanced in CAD and further associated with smoking status. Functional assays demonstrated that isoDGR-modified fibronectin activated both monocytes and macrophages via integrin receptor ‘outside in’ signalling, triggering an ERK:AP-1 cascade and expression of pro-inflammatory cytokines MCP-1 and TNFα to drive additional recruitment of circulating leukocytes. IsoDGR-modified fibronectin also induced endothelial cell expression of integrin β1 to further enhance cellular adhesion and matrix deposition. Analysis of murine aortic tissues confirmed accumulation of isoDGR-modified proteins co-localised with CD68+ macrophagesin vivo.

Conclusions

Age-damaged fibronectin features isoDGR motifs that increase binding to integrins on the surface of monocytes, macrophages, and endothelial cells. Subsequent activation of ‘outside-in’ signalling elicits a range of potent cytokines and chemokines that drive additional leukocyte recruitment to the developing atherosclerotic matrix.

Graphical Abstract

Highlights

IsoDGR-modified plasma proteins are associated with CAD.

IsoDGR binding to integrin receptors on monocytes, macrophage, and endothelial cells promotes ‘outside-in’ signalling, monocyte infiltration, and endothelial binding.

IsoDGR-modified fibronectin may initiate vascular inflammation in atherosclerotic CVD.
Impact of COVID-19 pre-test probability on positive predictive value of high cycle threshold SARS-CoV-2 real-time reverse transcription PCR test results
Authors: Gubbay Jonathan B. , Rilkoff Heather , Kristjanson Heather L. , Forbes Jessica D. , Murti Michelle , Eshaghi AliReza , Broukhanski George , Corbeil Antoine , Fittipaldi Nahuel , Hopkins Jessica P. , Kristjanson Erik , Kus Julianne V. , Macdonald Liane , Majury Anna , Mallo Gustavo V , Mazzulli Tony , Melano Roberto G. , Olsha Romy , Perusini Stephen J. , Tran Vanessa , Allen Vanessa G , Patel Samir N
Published: March 2021

Background

Performance characteristics of SARS-CoV-2 nucleic acid detection assays are understudied within contexts of low pre-test probability, including screening asymptomatic persons without epidemiological links to confirmed cases, or asymptomatic surveillance testing. SARS-CoV-2 detection without symptoms may represent resolved infection with persistent RNA shedding, presymptomatic or asymptomatic infection, or a false positive test. This study assessed clinical specificity of SARS-CoV-2 real-time reverse transcription polymerase chain reaction (rRT-PCR) assays by retesting positive specimens from five pre-test probability groups ranging from high to low with an alternate assay.

Materials and Methods

A total of 122 rRT-PCR positive specimens collected from unique patients between March and July 2020 were retested using a laboratory-developed nested RT-PCR assay targeting the RNA-dependent RNA polymerase (RdRp) gene followed by Sanger sequencing.

Results

Significantly less positive results in the lowest pre-test probability group (facilities with institution-wide screening having ≤ 3 positive asymptomatic cases) were reproduced with the nested RdRp gene RT-PCR assay than in all other groups combined (5/32, 15·6% vs 61/90, 68%; p <0·0001), and in each subgroup with higher pre-test probability (individual subgroup range 50·0% to 85·0%).

Conclusions

A higher proportion of false-positive test results are likely with lower pre-test probability. Positive SARS-CoV-2 PCR results should be interpreted within the context of patient history, clinical setting, known exposure, and estimated community disease prevalence. Large-scale SARS-CoV-2 screening testing initiatives among low pre-test probability populations should be evaluated thoroughly prior to implementation given the risk of false positives and consequent potential for harm at the individual and population level.
Structural basis for the hyperthermostability of an archaeal glutaminase induced by post-translational succinimide formation
Authors: Dongre Aparna Vilas , Das Sudip , Bellur Asutosh , Kumar Sanjeev , Chandrashekarmath Anusha , Karmakar Tarak , Balaram Padmanabhan , Balasubramanian Sundaram , Balaram Hemalatha
Published: March 2021

Stability of proteins from hyperthermophiles enabled by reduction of conformational flexibility is realized through various mechanisms. Presence of a stable, hydrolysis-resistant succinimide arising from cyclization of the side chains of aspartyl/asparaginyl residues with backbone amide -NH of the succeeding residue would restrain the torsion angle Ψ. Here, we describe the crystal structure ofMethanocaldococcus jannaschiiglutamine amidotransferase (MjGATase) and address the mechanism of a succinimide-induced increased thermostability using molecular dynamics simulations. This study reveals the interplay of negatively charged electrostatic shield and n→π* interactions in preventing succinimide hydrolysis. The stable succinimidyl residue induces formation of a ‘conformational-lock’, reducing protein flexibility. Protein destabilization upon replacement with the Φ-restricted prolyl residue highlights the specificity of the conformationally restrained succinimidyl residue in imparting hyperthermostability. The conservation of succinimide-forming tripeptide sequence (E(N/D)(E/D)) in a group of archaeal GATases suggests an adaptation of this otherwise detrimental post-translational modification as an inducer of thermostability.