bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of nintedanib on acute exacerbations of fibrosing interstitial lung diseases: a national database study in Japan
Authors: Urushiyama Hirokazu , Jo Taisuke , Hasegawa Wakae , Yokoyama Akira , Ando Takahiro , Sakamoto Yukiyo , Kumazawa Ryosuke , Uda Kazuaki , Michihata Nobuaki , Awano Nobuyasu , Hiroki Matsui , Fushimi Kiyohide , Yasunaga Hideo , Nagase Takahide
Published: October 2022

Background

Acute exacerbation is a life-threatening event in patients with fibrosing interstitial lung diseases (ILDs). Although nintedanib reduces acute exacerbation incidence, its effectiveness during acute exacerbation is unclear.

Methods

Using data from the Diagnosis Procedure Combination database (September 2015–March 2020) in Japan, we identified patients with fibrosing ILDs who received intravenous injection of high-dose corticosteroid within 3 days post-admission and analysed their first hospitalisation. We performed overlap propensity score weighting to compare in-hospital outcomes between patients who received nintedanib within 14 days post-admission and those who did not. The primary and secondary outcomes were in-hospital mortality and length of hospitalisation in the patients discharged alive, respectively.

Results

Among the 6235 identified patients, 353 patients received nintedanib within 14 days post-admission. In-hospital mortality occurred in 13.7% and 6.0% patients in the control (n=5882) and nintedanib-treated (n=353) patients, respectively. The mean length of hospitalisation was 39.9 and 30.4 days in the control and nintedanib-treated patients, respectively. After overlap propensity score weighting, nintedanib treatment was significantly associated with lower in-hospital mortality in the adjusted cohort (OR 0.43, 95% CI 0.27–0.70; p=0.001). The mean length of hospitalisation in nintedanib-treated patients (30.7 days) was significantly shorter than that in the control group (37.5 days; p<0.001).

Conclusions

Nintedanib initiation during acute exacerbation was significantly associated with a lower risk of in-hospital death and shorter length of hospitalisation in patients with fibrosing ILDs. Our results elucidate the potential role of nintedanib in the treatment of acute exacerbation in patients with fibrosing ILDs. Further prospective studies are warranted.
The demographics, clinical characteristics and quality of life of patients with chronic cough from the Isala Cough Clinic in the Netherlands
Authors: van den Berg Jan Willem K. , Baxter Carl A. , Edens Mireille A. , Patberg Kornelis W. , van der Velden Hester , Weijerse Arjan , Salomonsson Stina
Published: October 2022

Introduction

Chronic cough affects ∼10% of the population and adversely impacts quality of life. This retrospective observational cohort study aimed to identify the demographics, clinical characteristics and quality of life of the chronic cough population in a Dutch chronic cough clinic, at baseline and following treatment at 6 months. Patients were categorised based on the underlying phenotype and response to treatment.

Methods

Retrospective data on 2397 patients who were diagnosed according to standard guidelines of the American College of Chest Physicians were analysed. Quality of life was capturedviathe Leicester Cough Questionnaire, the Cough Numeric Rating Scale and the Hospital Anxiety and Depression Scale.

Results

Mean patient age was 59 years; 62.5% of the patients were female; and 69.1% had at least one underlying phenotype associated with chronic cough. Of the latter, 52.1% had bronchial hyperresponsiveness/airflow limitation, 33.3% had airway reflux and 20.1% had upper airway cough syndrome. 46% of patients with a phenotype, and 51% without, experienced no improvement in their quality of life or still had significant cough remaining after 6 months. Of patients with available quality-of-life data, 37.5% were categorised as having refractory chronic cough, and 9.5% were categorised as unexplained chronic cough.

Discussion

This study highlights the poor quality-of-life outcomes in patients with chronic cough, despite interventions to treat underlying conditions, and indicates a need to manage chronic cough irrespective of phenotype.
Arterial remodelling in smokers and in patients with small airway disease and COPD: implications for lung physiology and early origins of pulmonary hypertension
Authors: Bhattarai Prem , Lu Wenying , Gaikwad Archana Vijay , Dey Surajit , Chia Collin , Larby Josie , Haug Greg , Hardikar Ashutosh , Williams Andrew , Kaur Singhera Gurpreet , Hackett Tillie-Louise , Eapen Mathew Suji , Sohal Sukhwinder Singh
Published: October 2022

Introduction

Pulmonary vascular remodelling in chronic obstructive pulmonary disease (COPD) has detrimental consequences for lung physiology. The aim of our study was to provide a comprehensive size-based morphometric quantification of pulmonary arterial remodelling in smokers and in patients with small airway disease (SAD) or COPD.

Method

Movat's pentachrome staining was performed on lung resections for 46 subjects: 12 never-smoker normal controls (NC), six normal lung function smokers (NLFS), nine patients with SAD, nine patients with mild-to-moderate COPD who were current smokers (COPD-CS) and 10 patients with mild-to-moderate COPD who were ex-smokers (COPD-ES). Following a size-based classification of pulmonary arteries, image analysis software was used to measure their number, total wall thickness, individual layer thickness and elastin percentage.

Results

All pathological groups showed decreased numbers of pulmonary arteries compared with the NC group in all artery sizes. Arterial wall thickness was greater in NLFS and COPD-CS than in NC. Thickness in COPD-ES was decreased compared with COPD-CS. Intimal thickness was greater in all pathological groups in all arterial sizes than in the NC group. Medial thickness was also greater in small and medium arteries. Intimal thickness of larger arteries in COPD-CS correlated negatively to forced expiratory volume in 1 s/forced vital capacity (FVC) % and forced expiratory flow at 25–75% of FVC. Elastin deposition in small arteries was greatest in COPD-CS. Intimal elastin deposition had a more negative correlation with intimal thickness in NLFS and SAD than in COPD-CS.

Conclusion

Smoking, SAD and mild-to-moderate COPD are associated with pruning and a decrease in the number of pulmonary arteries, increased wall thickness and variable elastin deposition. These changes were associated with worse airway obstruction.
Genome-resolved analyses show an extensive diversification in key aerobic hydrocarbon-degrading enzymes across bacteria and archaea
Authors: Somee Maryam Rezaei , Amoozegar Mohammad Ali , Dastgheib Seyed Mohammad Mehdi , Shavandi Mahmoud , Maman Leila Ghanbari , Bertilsson Stefan , Mehrshad Maliheh
Published: October 2022

Background

Hydrocarbons (HCs) are organic compounds composed solely of carbon and hydrogen that are mainly accumulated in oil reservoirs. As the introduction of all classes of hydrocarbons including crude oil and oil products into the environment has increased significantly, oil pollution has become a global ecological problem. However, our perception of pathways for biotic degradation of major HCs and key enzymes in these bioconversion processes has mainly been based on cultured microbes and is biased by uneven taxonomic representation. Here we used Annotree to provide a gene-centric view of the aerobic degradation ability of aliphatic and aromatic HCs in 23,446 genomes from 123 bacterial and 14 archaeal phyla. 

Results

Apart from the widespread genetic potential for HC degradation in Proteobacteria, Actinobacteriota, Bacteroidota, and Firmicutes, genomes from an additional 18 bacterial and 3 archaeal phyla also hosted key HC degrading enzymes. Among these, such degradation potential has not been previously reported for representatives in the phyla UBA8248, Tectomicrobia, SAR324, and Eremiobacterota. Genomes containing whole pathways for complete degradation of HCs were only detected in Proteobacteria and Actinobacteriota. Except for several members of Crenarchaeota, Halobacterota, and Nanoarchaeota that have tmoA, ladA, and alkB/M key genes, respectively, representatives of archaeal genomes made a small contribution to HC degradation. None of the screened archaeal genomes coded for complete HC degradation pathways studied here; however, they contribute significantly to peripheral routes of HC degradation with bacteria.

Conclusion

Phylogeny reconstruction showed that the reservoir of key aerobic hydrocarbon-degrading enzymes in Bacteria and Archaea undergoes extensive diversification via gene duplication and horizontal gene transfer. This diversification could potentially enable microbes to rapidly adapt to novel and manufactured HCs that reach the environment.
The MBS microbial rapid detection system for rapid detection of major pathogenic bacteria in feed: comparison with plate counting method
Authors: Jiang Linlin , Zhang Beibei , Liu Shuitao , Zhu Lianqin , Zhu Fenghua
Published: October 2022

The current methods for detecting pathogenic bacteria in feed require high technique and take a long time. The Micro Biological Survey (MBS) rapid detection system is a simple, economical and rapid microbial detection method. The purpose of this experiment was to compare the detection ofEscherichia coli(E. coli),Salmonella,Staphylococcus aureus(S. aureus),Listeria monocytogenes(LM), coliform (COLI) and total viable count (TVC) in feed by the MBS rapid microbial detection system and plate counting method (PCM). The results showed that the limit of quantitation, recovery rate and coefficient of variation of the MBS microbial rapid detection system are better than the plate counting method. When detecting the pathogenic bacteria content in artificially contaminated feed, the MBS rapid microbial detection system was positively correlated with the PCM. When the MBS microbial rapid detection system and PCM were used to detect the collected real feed samples, there was no significant difference in the detection results of the two methods in most of the feed samples. In summary, the MBS microbial rapid detection system is the most convenient and rapid detection method and is suitable for promotion and application in production lines.
Population-based pattern of medication use and prevalence of polypharmacy among patients with cardiovascular diseases: results of the Pars cohort study from Iran
Authors: Mohsenzadeh Pooran , Ardekani Ali , Poustchi Hossein , Mohammadi Zahra , Abdipour Mehrian Seyed Reza , Bazrafshan Drissi Hamed , Rahimian Zahra , Taherifard Erfan , Nabavizadeh Ali , kamalipour Alireza , Mesgarpour Bita , Malekzadeh Fatemeh , Molavi Vardanjani Hossein
Published: October 2022

Background

Polypharmacy in patients with cardiovascular diseases (CVDs) has been linked to several adverse outcomes. This study aimed to investigate the pattern of medication use and prevalence of polypharmacy among CVDs patients in Iran.

Method

We used the baseline data of the Pars cohort study (PCS). The participants were asked to bring their medication bags; then, the medications were classified using the Anatomical Therapeutic Chemical classification. Polypharmacy was defined as using five or more medications concurrently. Poisson regression modeling was applied. The adjusted prevalence ratios (PR) and its 95% confidence interval (CI) were estimated.

Results

Totally, 9262 participants were enrolled in the PCS, of whom 961 had CVDs. The prevalence of polypharmacy in participants with and without CVDs was 38.9% and 7.1%, respectively. The highest prevalence of polypharmacy (51.5%) was among obese patients. Abnormal waist-hip ratio (PR: 2.79; 95% CI 1.57–4.94), high socioeconomic status (PR: 1.65; 95% CI 1.07–2.54), tobacco-smoking (PR: 1.35; 95% CI 1.00–1.81), patients with more than three co-morbidities (PR: 1.41; 95% CI 1.30–1.53), high physical activity (PR: 0.66; 95% CI 0.45–0.95), use of opiate ever (PR: 0.46; 95% CI 0.26–0.82), and healthy overweight subjects (PR: 0.22; 95% CI 0.12–0.39) were associated with polypharmacy. Cardiovascular drugs (76.1%), drugs acting on blood and blood-forming organs (50.4%), and alimentary tract and metabolism drugs (33.9%) were the most frequently used drugs. Agents acting on the renin-angiotensin system were the mostly used cardiovascular system drugs among men and those above 60 years old, while beta-blocking agents were mostly prevalent among cardiovascular system drugs in women with CVDs.

Conclusion

Given the high prevalence of polypharmacy among CVDs patients, and subsequent complications, programs to educate both physicians and patients to prevent this issue is crucial.
Red blood cell distribution width predicts gastrointestinal bleeding after coronary artery bypass grafting
Authors: Liao Ying , Zhang Rongting , Shi Shanshan , Lin Xueqin , Wang Yani , Wang Yun , Chen Weihua , Zhao Yukun , Bao Kunming , Zhang Kaijun , Chen Liling , Fang Yong
Published: October 2022

Background

Red blood cell distribution width (RDW) is highly associated with adverse clinical outcomes in many diseases. The present study aimed to evaluate the relationship between RDW and gastrointestinal bleeding (GIB) after isolated coronary artery bypass grafting (CABG).

Methods

This was a retrospective observational study that included 4473 patients who received CABG, and all the data were extracted from the Medical Information Mart for Intensive Care III database. Data collected included patient demographics, associated comorbid illnesses, laboratory parameters, and medications. The receiver operating characteristic (ROC) curve was used to determine the best cutoff value of RDW for the diagnosis of GIB. Multivariable logistic regression analysis was used to analyze the relationship between RDW and GIB.

Results

The incidence of GIB in patients receiving CABG was 1.1%. Quartile analyses showed a significant increase in GIB incidence at the fourth RDW quartile (> 14.3%; P < 0.001). The ROC curve analysis revealed that an RDW level > 14.1% measured on admission had 59.6% sensitivity and 69.4% specificity in predicting GIB after CABG. After adjustment for confounders, high RDW was still associated with an increased risk of GIB in patients with CABG (odds ratio = 2.83, 95% confidence interval 1.46–5.51, P = 0.002).

Conclusions

Our study indicates that the elevated RDW level is associated with an increased risk of GIB after CABG, and it can be an independent predictor of GIB. The introduction of RDW to study GIB enriches the diagnosis method of GIB and ensures the rapid and accurate diagnosis of GIB.
Outcomes improvement despite continuous visits of severely injured patients during the COVID-19 outbreak: experience at a regional trauma centre in South Korea
Authors: Kang Sooyeon , Park Ji Eun , Ko Ji Wool , Kim Myoung Jun , Choi Young Un , Shim Hongjin , Bae Keum Seok , Kim Kwangmin
Published: October 2022

Background

Understanding the changes in characteristics of patients who visited trauma centres during the coronavirus disease 2019 (COVID-19) pandemic is important to facilitate aneffective response. This retrospective study was conducted to analyse differences in the characteristics and outcomes of patients who visited our trauma centre between pre-COVID-19 and COVID-19 eras.

Methods

Medical data of trauma patients enrolled in the Korean trauma database from 1 January 2018 to 31 August 2021 were collected. The number of trauma centre visits, patient characteristics, factors associated with in-hospital intervention, and outcomes werecompared between patients in the two time periods. Propensity score matching was performed to analyse the outcomes in patients with similar characteristics and severitybetween patients in the two time periods.

Results

The number of emergency department (ED) trauma service visits reduced in the COVID-19 era. Based on the mean age, the patients were older in the COVID-19 era. Abbreviated injury scale (AIS) 1, AIS3, AIS5, and injury severity score (ISS) were higher in the COVID-19 era. The proportion of motor vehicle collisions decreased, whereas falls increased during the COVID-19 era. Ambulance transportation, admission to the general ward, and time from injury to ED visit significantly increased. Patient outcomes, such as hospital length of stay (LOS), intensive care unit (ICU) LOS, and duration of mechanical ventilation improved, while injury severity worsened during the COVID-19 era. After adjusting for patient characteristics and severity, similar findings were observed.

Conclusion

The small reduction in the number of trauma patients and visits by patients who hadhigher ISS during the COVID-19 pandemic highlights the importance of maintaining trauma service capacity and capability during the pandemic. A nationwide or nationalmulticentre study will be more meaningful to examine the impact of the COVID-19 outbreak on the changes in trauma patterns, volume, and patient outcomes.
Anti-cholinergic drug burden in patients with dementia increases after hospital admission: a multicentre cross-sectional study
Authors: Hook Annabelle , Randall Jessica L. , Grubb Carla M. , Ellis Natalie , Wellington Jack , Hemmad Aayushi , Zerdelis Agisilaos , Winnett Andrew R. D. , Geers Benjamin D. W. , Sykes Bethany , Auty Charlotte N. , Vinchenzo Cecilia , Thorburn Christiane E. , Asogbon Daniella , Granger Emily , Boagey Heather , Raphael Juliet , Patel Kajal , Bhargava Kartik , Dolley Mary-Kate M. , Maden Matthew J. , Shah Mehdin M. , Lee Qao M. , Vaidya Ratnaraj , Sehdev Simran , Barai Sneha , Roche Sophie , Khalid Uzair , Codling David A. , Harrison Judith R.
Published: October 2022

Background

Anticholinergic medications are drugs that block cholinergic transmission, either as their primary therapeutic action or as a secondary effect. Patients with dementia may be particularly sensitive to the central effects of anticholinergic drugs. Anticholinergics also antagonise the effects of the main dementia treatment, cholinesterase inhibitors. Our study aimed to investigate anticholinergic prescribing for dementia patients in UK acute hospitals before and after admission.

Methods

We included 352 patients with dementia from 17 UK hospital sites in 2019. They were all inpatients on surgical, medical or Care of the Elderly wards. Information about each patient’s medications were collected using a standardised form, and the anticholinergic drug burden of each patient was calculated with an evidence-based online calculator. Wilcoxon’s rank test was used to look at the correlation between two subgroups upon admission and discharge.

Results

On admission to hospital, 37.8% of patients had an anticholinergic burden score ≥ 1 and 5.68% ≥3. On discharge, 43.2% of patients with an anticholinergic burden score ≥ 1 and 9.1% ≥3. The increase in scores was statistically significant (p = 0.001). Psychotropics were the most common group of anticholinergic medications prescribed at discharge. Of those patients taking cholinesterase inhibitors, 44.9% were also prescribed anticholinergic medications.

Conclusions

Our cross-sectional, multicentre study found that people with dementia are commonly prescribed anticholinergic medications, even if concurrently taking cholinesterase inhibitors, and are significantly more likely to be discharged from hospital with a higher anticholinergic burden than on admission.
Changes in lifestyles, cognitive impairment, quality of life and activity day living after combined use of smartphone and smartband technology: a randomized clinical trial (EVIDENT-Age study)
Authors: Recio-Rodríguez José I. , Gonzalez-Sanchez Susana , Tamayo-Morales Olaya , Gómez-Marcos Manuel A. , Garcia-Ortiz Luis , Niño-Martín Virtudes , Lugones-Sanchez Cristina , Rodriguez-Sanchez Emiliano
Published: October 2022

Background

The aim of this study was to assess the efficacy of the combined use of smartphone and smartband technology for 3-months alongside brief lifestyle counselling, versus counselling alone, in increasing physical activity. As secondary objectives, the effects of the intervention on dietary habits, body composition, quality of life, level of functionality and cognitive performance were assessed.

Methods

This study employed a randomized clinical trial of two-parallel groups design – control group (CG) and intervention group (IG). The study was conducted in 3 Spanish health-centres between October 2018-February 2020. Eligible participants were people of both sexes and aged between 65–80 years attending the health-centres with a score ≥ 24 points on the Mini-Mental State Examination. Key variables included physical activity, dietary pattern, body composition, cognitive performance, level of functionality and quality of life. All variables were measured at baseline and after 3-months. Both groups received a brief nutritional and physical activity advice. Intervention group participants were instructed to use a smartphone application for a period of 3-months. This application integrates information on physical activity received from a fitness bracelet and self-reported information on the patient’s daily nutritional composition.

Results

The study population comprised 160 participants (IG = 81, CG = 79), with a mean age of 70.8 ± 4.0 years (61.3% women). No difference was found in the primary and secondary outcomes analyzed (physical activity (steps/min -0.4 (-1.0 to 0.2) p = 0.174), and dietary habits (Mediterranean diet score 0.0 (-0.6 to 0.6) p = 0.956) that could be attributed to either group after an ANCOVA test. A difference attributable to the intervention was observed in the total Clock test score (0.7 (0.1 to 1.2) p = 0.018.

Conclusions

In a sample of people over 65 years of age, the combined use of the EVIDENT 3 smartphone app and an activity tracking bracelet for 3-months did not result in lifestyles changes related to the amount and level of physical activity or the eating habits, compared to brief lifestyle advice. Other clinical parameters were not changed either, although at the cognitive level, a slight improvement was observed in the score on the Clock test assessing a variety of cognitive functions such as memory.

Trial registration

The study was registered in ClinicalTrials.gov Identifier: NCT03574480. Date of trial Registration 02/07/2018.
Brain magnetic resonance imaging findings among children with epilepsy in two urban hospital settings, Kampala-Uganda: a descriptive study
Authors: Apolot Denise , Erem Geoffrey , Nassanga Rita , Kiggundu Daniel , Tumusiime Crescent Max , Teu Anneth , Mugisha Alex Mwesigwa , Sebunya Robert
Published: October 2022

Background

Epilepsy is one of the most common neurological conditions in children worldwide. Its presentation is heterogeneous, with diverse underlying aetiology, clinical presentation, and prognosis. Structural brain abnormalities are among the recognized causes of epilepsy. Brain Magnetic Resonance Imaging (MRI) is the imaging modality of choice for epilepsy workup.

We aimed to determine the prevalence and describe the structural abnormalities identified in the brain MRI studies performed on children with epilepsy from two urban hospitals in Kampala, Uganda.

Methods

This was a cross-sectional descriptive study performed at two urban hospital MRI centres. The study population was 147 children aged 1 day to 17 years with confirmed epilepsy. Brain MRI was performed for each child and a questionnaire was used to collect clinical data.

Results

The prevalence of structural abnormalities among children with epilepsy was 74.15% (109 out of 147). Of these, 68.81% were male, and the rest were female. Among these, the majority, 40.14% (59 of 144) were aged 1 month to 4 years. Acquired structural brain abnormalities were the commonest at 69.22% with hippocampal sclerosis (HS) leading while disorders of cortical development were the most common congenital causes.

An abnormal electroencephalogram (EEG) was significant for brain MRI abnormalities among children with epilepsy with 95% of participants with an abnormal EEG study having epileptogenic structural abnormalities detected in their brain MRI studies.

Conclusion and recommendation

Two-thirds of children with epilepsy had structural brain abnormalities. Abnormal activity in the EEG study was found to positively correlate with abnormal brain MRI findings. As such, EEG study should be considered where possible before MRI studies as a determinant for children with epilepsy who will be having imaging studies done in the Ugandan setting.
Evaluating the potential implications of canadian front-of-pack labelling regulations in generic and branded food composition databases
Authors: Mulligan Christine , Lee Jennifer J. , Vergeer Laura , Ahmed Mavra , L’Abbé Mary R.
Published: October 2022

Background

Canada proposed the implementation of mandatory front-of-pack (FOP) labelling regulations, whereby foods meeting or exceeding thresholds for nutrients-of-concern (i.e., total sugars, saturated fat, sodium) must display a ‘high-in’ FOP symbol (FOP). The objective of the study was to evaluate the potential implications of the proposed regulations using Canadian generic and branded food composition databases.

Methods

A generic food composition database of products consumed by Canadians, Canadian Nutrient File (CNF) 2015 (n = 3,677), and a branded food composition database of packaged foods and beverages, Food Label Information Program (FLIP) 2017 (n = 17,521), were used to evaluate the number and proportion of foods that would display a FOP symbol based on the details of the proposed FOP labelling regulations published in 2018.

Results

Overall, 35.5% (n = 1,306) of products in CNF 2015 and 63.9% (n = 11,193) of products in FLIP 2017 would display a FOP symbol for at least one nutrient-of-concern exceeding proposed thresholds. Soups, Combination Dishes, and Desserts categories in CNF 2015 and Combination dishes, Soups, and Meats categories in FLIP 2017 would have the highest proportion of products that would display a FOP symbol. Although displaying a FOP symbol for one nutrient was most common in both CNF 2015 (n = 992; 27.0%) and FLIP 2017 (n = 7,296, 41.6%), the number (i.e., 0–3) and type (i.e., saturated fat, sodium, total sugar) of nutrients displayed varied by food category.

Conclusion

While the generic database, containing both packaged and unpackaged foods, revealed a low prevalence of foods that would display a FOP symbol, the branded database showed that the proposed FOP labelling regulations would identify over 60% of packaged foods with excess contents of nutrients-of-concern. Considering the high prevalence of packaged foods in Canada that would meet or exceed the thresholds of nutrients-of-concern, the proposed FOP labelling regulations should be implemented in a timely manner to help consumers easily identify foods high in nutrients-of-concern and encourage manufacturer-driven product reformulations.
The interRAI CHESS scale is comparable to the palliative performance scale in predicting 90-day mortality in a palliative home care population
Authors: Williams Nicole , Hermans Kirsten , Cohen Joachim , Declercq Anja , Jakda Ahmed , Downar James , Guthrie Dawn M. , Hirdes John P.
Published: October 2022

Background

Prognostic accuracy is important throughout all stages of the illness trajectory as it has implications for the timing of important conversations and decisions around care. Physicians often tend to over-estimate prognosis and may under-recognize palliative care (PC) needs. It is therefore essential that all relevant stakeholders have as much information available to them as possible when estimating prognosis.

Aims

The current study examined whether the interRAI Changes in Health, End-Stage Disease, Signs and Symptoms (CHESS) Scale is a good predictor of mortality in a known PC population and to see how it compares to the Palliative Performance Scale (PPS) in predicting 90-day mortality.

Methods

This retrospective cohort study used data from 2011 to 2018 on 80,261 unique individuals receiving palliative home care and assessed with both the interRAI Palliative Care instrument and the PPS. Logistic regression models were used to evaluate the relationship between the main outcome, 90-day mortality and were then replicated for a secondary outcome examining the number of nursing visits. Comparison of survival time was examined using Kaplan-Meier survival curves.

Results

The CHESS Scale was an acceptable predictor of 90-day mortality (c-statistic = 0.68; p < 0.0001) and was associated with the number of nursing days (c = 0.61; p < 0.0001) and had comparable performance to the PPS (c = 0.69; p < 0.0001). The CHESS Scale performed slightly better than the PPS in predicting 90-day mortality when combined with other interRAI PC items (c = 0.72; p < 0.0001).

Conclusion

The interRAI CHESS Scale is an additional decision-support tool available to clinicians that can be used alongside the PPS when estimating prognosis. This additional information can assist with the development of care plans, discussions, and referrals to specialist PC teams.
Comparative satisfaction and effectiveness of virtual simulation and usual supervised work for postpartum hemorrhage management: a crossover randomized controlled trial
Authors: Voillequin Sandrine , Rozenberg P. , Letutour K. , Rousseau A.
Published: October 2022

Background

Because virtual simulation promotes learning and cognitive skill development, it may be useful for teaching students to manage postpartum hemorrhage (PPH) and its complex decision algorithm.

Objective

This study aimed to compare the satisfaction and effectiveness of virtual simulation with usual supervised work in producing knowledge and satisfaction.

Methods

This two-center two-stage crossover randomized controlled trial included student midwives. One group underwent the virtual simulation intervention in the first period (January 2018) and the usual supervised classroom work in the second (May 2018); the other group followed the reverse chronology. Satisfaction was the primary outcome. The secondary outcome was knowledge of the PPH management algorithm, assessed by responses to a case vignette after each intervention session.

Results

The virtual simulation -supervised work (VS-SW) chronology was allocated to 48 students, and its inverse (SW-VS) to 47; Satisfaction was significantly higher for the virtual simulation for its overall grade (6.8 vs. 6.1, P = 0.009), engagingness (very good 82.1% vs. 24.3%, P < 0.001), and ease of use (very good 77.9% vs. 46.1%, P < 0.001). Knowledge did not differ between the two groups (respectively, 89.5% versus 83.5%, P = 0.3).

Conclusion

Satisfaction is higher with virtual simulation without lowering knowledge scores, which argues for the use of such innovative teaching strategies. This could lead to an increase in students’ motivation to learn.
Routine use of DHIS2 data: a scoping review
Authors: Byrne Elaine , Sæbø Johan Ivar
Published: October 2022

Background

In regard to health service planning and delivery, the use of information at different levels in the health system is vital, ranging from the influencing of policy to the programming of action to the ensuring of evidence-informed practices. However, neither ownership of, nor access to, good quality data guarantees actual use of these data. For information to be used, relevant data need to be collected, processed and analysed in an accessible format. This problem of underused data, and indeed the absence of data use entirely, is widespread and has been evident for decades.

The DHIS2 software platform supports routine health management for an estimated 2.4 billion people, in over 70 countries worldwide. It is by far the largest and most widespread software for this purpose and adopts a holistic, socio-technical approach to development and implementation. Given this approach, and the rapid and extensive scaling of DHIS2, we questioned whether or not there has been a parallel increase in the scaling of improved information use. To date, there has been no rigorous review of the documentation on how exactly DHIS2 data is routinely being used for decision-making and subsequent programming of action. This scoping review addresses this review gap.

Methods

The five-stage approach of Arksey and O’Malley progressed by Levac et al. and Peters was followed. Three databases (PubMed, Web of Science and Embase) were searched, along with relevant conference proceedings and postgraduate theses. In total, over 500 documents were reviewed and data from 19 documents were extracted.

Results

Overall, DHIS2 data are being used but there are few detailed descriptions of this usage in peer reviewed or grey literature. We find that, commonly, there exists a centralised versus decentralised pattern of use in terms of access to data and the reporting of data ‘up’ in the system. We also find that the different conceptualisations of data use and how data use is conceptualised are not made explicit.

Conclusions

We conclude with some suggestions for a way forward, namely: i) the need to document in more detail and share how data are being used, ii) the need to investigate how data were created and who uses such data, iii) the need to design systems based on work practices, and in tandem develop and promote forums in which ‘conversations’ around data can take place.
Lineage-specific, fast-evolving GATA-like gene regulates zygotic gene activation to promote endoderm specification and pattern formation in the Theridiidae spider
Authors: Iwasaki-Yokozawa Sawa , Nanjo Ryota , Akiyama-Oda Yasuko , Oda Hiroki
Published: October 2022

Background

The process of early development varies across the species-rich phylum Arthropoda. Owing to the limited research strategies for dissecting lineage-specific processes of development in arthropods, little is known about the variations in early arthropod development at molecular resolution. The Theridiidae spider, Parasteatoda tepidariorum, has its genome sequenced and could potentially contribute to dissecting early embryonic processes.

Results

We present genome-wide identification of candidate genes that exhibit locally restricted expression in germ disc forming stage embryos of P. tepidariorum, based on comparative transcriptomes of isolated cells from different regions of the embryo. A subsequent pilot screen by parental RNA interference identifies three genes required for body axis formation. One of them is a GATA-like gene that has been fast evolving after duplication and divergence from a canonical GATA family gene. This gene is designated fuchi nashi (fuchi) after its knockdown phenotypes, where the cell movement toward the formation of a germ disc was reversed. fuchi expression occurs in cells outside a forming germ disc and persists in the endoderm. Transcriptome and chromatin accessibility analyses of fuchi pRNAi embryos suggest that early fuchi activity regulates chromatin state and zygotic gene activation to promote endoderm specification and pattern formation. We also show that there are many uncharacterized genes regulated by fuchi.

Conclusions

Our genome-based research using an arthropod phylogenetically distant from Drosophila identifies a lineage-specific, fast-evolving gene with key developmental roles in one of the earliest, genome-wide regulatory events, and allows for molecular exploration of the developmental variations in early arthropod embryos.
Research on the equity of health resource allocation in TCM hospitals in China based on the Gini coefficient and agglomeration degree: 2009–2018
Authors: Dai Guolin , Li Ruifeng , Ma Shuang
Published: October 2022

Background

The demographical and geographical distributions of health resources are important aspects of healthcare access. Few studies have been published on health resource allocation in TCM hospitals in China despite public equity concerns.

Methods

This article uses the Gini coefficient and agglomeration degree to analyze the health resources of TCM hospitals in China according to demographic and geographic configuration conditions in order to study the equity of the health resources of TCM from 2009 to 2018.

Results

From 2009 to 2018, all regions of the TCM health resources per ten thousand people and per ten thousand square kilometers showed overall upward trends. The overall equity of the health resource allocations of TCM hospitals in China tended to improve year by year. However, there were still great differences among regions. Generally, the equity of physical resource allocation was better than the equity of human resource allocation. Additionally, the equity of health resources in TCM hospitals allocated by population was better than it was by geographic region.

Conclusions

It is necessary to further optimize the structure of TCM resource allocation, and enhance the equity of resource allocation among different regions.
Histopathologically TMA-like distribution of multiple organ thromboses following the initial dose of the BNT162b2 mRNA vaccine (Comirnaty, Pfizer/BioNTech): an autopsy case report
Authors: Kaimori Ryo , Nishida Haruto , Uchida Tomohisa , Tamura Mari , Kuroki Kohji , Murata Kumi , Hatakeyama Kinta , Ikeda Yoshihiko , Amemiya Kisaki , Nishizono Akira , Daa Tsutomu , Mori Shinjiro
Published: October 2022

Background

Coronavirus disease 2019 (COVID-19) has spread worldwide. Vaccination is now recommended as one of the effective countermeasures to control the pandemic or prevent the worsening of symptoms. However, its adverse effects have been attracting attention. Here, we report an autopsy case of multiple thromboses after receiving the first dose of the BNT162b2 mRNA vaccine (Comirnaty, Pfizer/BioNTech) in an elderly woman.

Case presentation

A 72-year-old woman with a history of diffuse large B-cell lymphoma in the stomach and hyperthyroidism received the first dose of the BNT162b2 mRNA vaccine and died 2 days later. The autopsy revealed multiple microthrombi in the heart, brain, liver, kidneys, and adrenal glands. The thrombi were CD61 and CD42b positive and were located in the blood vessels primarily in the pericardial aspect of the myocardium and subcapsular region of the adrenal glands; their diameters were approximately 5–40 μm. Macroscopically, a characteristic myocardial haemorrhage was observed, and the histopathology of the characteristic thrombus distribution, which differed from that of haemolytic uraemic syndrome and disseminated intravascular coagulation, suggested that the underlying pathophysiology may have been similar to that of thrombotic microangiopathy (TMA).

Conclusion

This is the first report on a post-mortem case of multiple thromboses after the BNT162b2 mRNA vaccine. The component thrombus and characteristic distribution of the thrombi were similar to those of TMA, which differs completely from haemolytic uraemic syndrome or disseminated intravascular coagulation, after vaccination. Although rare, it is important to consider that fatal adverse reactions may occur after vaccination and that it is vital to conduct careful follow-up.
T-cells in human trigeminal ganglia express canonical tissue-resident memory T-cell markers
Authors: Unger Peter-Paul A. , Oja Anna E. , Khemai-Mehraban Tamana , Ouwendijk Werner J. D. , Hombrink Pleun , Verjans Georges M. G. M.
Published: October 2022

Background

Trigeminal ganglia (TG) neurons are the main site of lifelong latent herpes simplex virus type 1 (HSV-1) infection. T-cells in ganglia contribute to long-term control of latent HSV-1 infection, but it is unclear whether these cells are bona fide tissue-resident memory T-cells (TRM). We optimized the processing of human post-mortem nervous tissue to accurately phenotype T-cells in human TG ex vivo and in situ.

Methods

Peripheral blood mononuclear cells (PBMC; 5 blood donors) were incubated with several commercial tissue digestion enzyme preparations to determine off-target effect on simultaneous detection of 15 specific T-cell subset markers by flow cytometry. Next, optimized enzymatic digestion was applied to ex vivo phenotype T-cells in paired PBMC, normal appearing white matter (NAWM) and TG of 8 deceased brain donors obtained < 9 h post-mortem by flow cytometry. Finally, the phenotypic and functional markers, and spatial orientation of T-cells in relation to neuronal somata, were determined in TG tissue sections of five HSV-1-latently infected individuals by multiparametric in situ analysis.

Results

Collagenase IV digestion of human nervous tissue was most optimal to obtain high numbers of viable T-cells without disrupting marker surface expression. Compared to blood, majority T-cells in paired NAWM and TG were effector memory T-cells expressing the canonical TRM markers CD69, CXCR6 and the immune checkpoint marker PD1, and about half co-expressed CD103. A trend of relatively higher TRM frequencies were detected in TG of latently HSV-1-infected compared to HSV-1 naïve individuals. Subsequent in situ analysis of latently HSV-1-infected TG showed the presence of cytotoxic T-cells (TIA-1+), which occasionally showed features of proliferation (KI-67+) and activation (CD137+), but without signs of degranulation (CD107a+) nor damage (TUNEL+) of TG cells. Whereas majority T-cells expressed PD-1, traits of T-cell senescence (p16INK4a+) were not detected.

Conclusions

The human TG represents an immunocompetent environment in which both CD4 and CD8 TRM are established and retained. Based on our study insights, we advocate for TRM-targeted vaccine strategies to bolster local HSV-1-specific T-cell immunity, not only at the site of recurrent infection but also at the site of HSV-1 latency.
Mitochondrial dysfunction in microglia: a novel perspective for pathogenesis of Alzheimer’s disease
Authors: Li Yun , Xia Xiaohuan , Wang Yi , Zheng Jialin C.
Published: October 2022

Alzheimer's disease (AD) is the most common neurodegenerative disease in the elderly globally. Emerging evidence has demonstrated microglia-driven neuroinflammation as a key contributor to the onset and progression of AD, however, the mechanisms that mediate neuroinflammation remain largely unknown. Recent studies have suggested mitochondrial dysfunction including mitochondrial DNA (mtDNA) damage, metabolic defects, and quality control (QC) disorders precedes microglial activation and subsequent neuroinflammation. Therefore, an in-depth understanding of the relationship between mitochondrial dysfunction and microglial activation in AD is important to unveil the pathogenesis of AD and develop effective approaches for early AD diagnosis and treatment. In this review, we summarized current progress in the roles of mtDNA, mitochondrial metabolism, mitochondrial QC changes in microglial activation in AD, and provide comprehensive thoughts for targeting microglial mitochondria as potential therapeutic strategies of AD.
A cross-sectional survey on the early impact of COVID-19 on the uptake of decentralised trial methods in the conduct of clinical trials
Authors: Suman Arnela , van Es Jasmijn , Gardarsdottir Helga , Grobbee Diederick E. , Hawkins Kimberly , Heath Megan A. , Mackenzie Isla S. , van Thiel Ghislaine , Zuidgeest Mira G. P. ,   on behalf of the Trials@Home Consortium
Published: October 2022

Background

The COVID-19 pandemic significantly impacted the conduct of clinical trials through delay, interruption or cancellation. Decentralised methods in clinical trials could help to continue trials during a pandemic. This paper presents the results of an exploratory study conducted early in the pandemic to gain insight into and describe the experiences of organisations involved in clinical trials, with regard to the impact of COVID-19 on the conduct of trials, and the adoption of decentralised methods prior to, and as mitigation for the impact, of COVID-19.

Methods

A survey with 11 open-ended and four multiple choice questions was conducted in June 2020 among member organisations of the public-private “Trials@Home” consortium. The survey investigated (1) the impact and challenges of COVID-19 on the continuation of ongoing clinical trials, (2) the adoption of decentralised methods in clinical trials prior to and as a mitigation strategy for COVID-19, (3) the challenges of conducting clinical trials during COVID-19, (4) the expected permanency of COVID-19-driven changes to the adoption of decentralised methods in clinical trials, and (5) lessons learned from conducting clinical trials during the COVID-19 pandemic. A thematic, inductive analysis of open survey questions was performed, complemented with descriptive statistics (frequencies and distributions).

Results

The survey had a response rate of 81%. All organisations included in the analysis (n = 18) implemented (some) decentralised methods in their clinical trials prior to COVID-19, and 15 (83%) implemented decentralised methods as mitigation for COVID-19. Decentralised methods for IMP supply, patient-health care provider interaction and communication, clinic visits and source document verification were used more often as mitigation strategies than they were used prior to COVID-19. Many respondents expect to maintain those decentralised methods they implemented during COVID-19 in ongoing trials, as well as implement them in future trials.

Conclusions

Decentralised methods are a widely implemented mitigation strategy for trial conduct in the face of the COVID-19 pandemic. The results of this survey show that there is an interest to continue the use of decentralised methods in future trials, but important points of attention have been identified that need solutions to help guide the transition from the traditional trial model to a more decentralised trial model.
Examining evidence of time-dependent treatment effects: an illustration using regression methods
Authors: Jachno Kim M. , Heritier Stephane , Woods Robyn L. , Mahady Suzanne , Chan Andrew , Tonkin Andrew , Murray Anne , McNeil John J. , Wolfe Rory
Published: October 2022

Background

For the design and analysis of clinical trials with time-to-event outcomes, the Cox proportional hazards model and the logrank test have been the cornerstone methods for many decades. Increasingly, the key assumption of proportionality—or time-fixed effects—that underpins these methods has been called into question. The availability of novel therapies with new mechanisms of action and clinical trials of longer duration mean that non-proportional hazards are now more frequently encountered.

Methods

We compared several regression-based methods to model time-dependent treatment effects. For illustration purposes, we used selected endpoints from a large, community-based clinical trial of low dose daily aspirin in older persons. Relative and absolute estimands were defined, and analyses were conducted in all participants. Additional exploratory analyses were undertaken by selected subgroups of interest using interaction terms in the regression models.

Discussion

In the trial with median 4.7 years follow-up, we found evidence for non-proportionality and a time-dependent treatment effect of aspirin on cancer mortality not previously reported in trial findings. We also found some evidence of time-dependence to an aspirin by age interaction for major adverse cardiovascular events. For other endpoints, time-fixed treatment effect estimates were confirmed as appropriate.

Conclusions

The consideration of treatment effects using both absolute and relative estimands enhanced clinical insights into potential dynamic treatment effects. We recommend these analytical approaches as an adjunct to primary analyses to fully explore findings from clinical trials.