bluuebunny/crossref_metadata_2025 huggingface dataset:
Hyperspectral retinal imaging in mouse models of proteinopathies identifies disease‐specific signatures
Authors: De Groef Lies , Veys Lien , Hadoux Xavier , Vandenabeele Marjan , Lemmens Sophie , Serneels Lutgarde , Theunis Jan , De Strooper Bart , Stalmans Ingeborg , van Wijngaarden Peter , Moons Lieve
Published: January 2022

Purpose

Previous research in the AppNL‐G‐F mouse has shown that hyperspectral retinal imaging (HSRI) can be used to quantify retinal amyloid burden in the preclinical stages of Alzheimer’s disease (AD) [1]. This underscores its potential as an imaging biomarker for AD diagnosis and monitoring. One prerequisite for the rational implementation of HSRI as a biomarker, however, is a better understanding of the pathological correlate of the HSRI signature. In this follow‐up study, we explored HSRI signatures in different proteinopathies and identified the pathological features underlying the observed HSRI results.

Methods

Retinal tissues were collected from mouse models with amyloid, tau and alpha‐synuclein overexpression/aggregation for ex vivo HSRI (Snapscan, Imec) [1]. HSRI was complemented with optical coherence tomography and electroretinograms (prior to HSRI) and immunohistochemistry and molecular studies of protein aggregation (after HSRI).

Results

While all protein aggregates led to HSRI changes in the 450–600 nm range, distinct signatures were observed for amyloid, tau and alpha‐synuclein. Furthermore, the observed HSRI changes correlated with levels of the protein oligomerization and aggregation. Diverging patterns of retinal dysfunction/degeneration were observed in the different mouse models, illustrating the varied impacts of these protein aggregates on retinal structure and function.

Conclusions

HSRI may be used to quantify retinal amyloid, tau and alpha‐synuclein, underscoring its potential as a biomarker for diagnosis and disease monitoring. Moreover, our data suggest that amyloid, tau and alpha‐synuclein accumulation lead to distinct HSRI signatures, thus adding further evidence that HSRI may have utility in the diagnosis and stratification of proteinopathies associated with the most common forms of neurodegenerative diseases.

Bibliograph

Vandenabeele et al. (2021) Acta Neuropathol Commun 9(1):6.
QR‐421a RNA therapy in retinitis pigmentosa due to mutations in USH2A: Stellar trial Phase[AP1] 1b/2 interim results
Authors: Audo Isabelle , Birch David G. , Thiran Jayasundera K. , Meunier Isabelle , Huckfeldt Rachel M. , Koenekoop Robert K. , Yang Paul , de Cock Edouard P. M. , Dahler Ellen C. , Taylor John , Shams Naveed , Girach Aniz
Published: January 2022

Purpose

To report Phase 1b/2 interim results of QR‐421a RNA therapy promoting USH2A exon 13 skipping. USH2A exon 13 mutations lead to non‐syndromic Retinitis Pigmentosa & Usher syndrome type 2.

Methods

Stellar (NCT03780257) is a 24‐month, multicenter Phase 1b/2 single‐dose trial assessing 3 dose levels (50, 100, 200 μg) of QR‐421a in patients aged ≥18 years with biallelic USH2A pathogenic mutations with at least one in exon 13. Cohorts 1 & 2 included subjects randomized to sham‐procedure or QR‐421a. Primary endpoints: frequency & severity of adverse events (AEs). Secondary endpoints: change in best‐corrected visual acuity (BCVA), static perimetry & ellipsoid zone [EZ] area.

Results

20 subjects were enrolled, 14 received QR‐421a & 6 received sham. Response to QR‐421a was similar for all doses. No serious AE or inflammation was observed. Two subjects had worsening of pre‐existing conditions: one with cataracts (not treatment‐related) & one with cystoid macular edema (being managed with standard care). BCVA stabilization was observed in QR‐421a‐treated eyes (TE), versus a decline in untreated eyes (UE). At week 48, mean BCVA benefit was 6.0 & 9.3 letters in all QR‐421a‐treated & advanced subjects (n = 6; baseline BCVA of <70 letters) respectively. No BCVA benefit was observed in sham‐treated eyes (SE). Mean change from baseline of the EZ‐area was +15.0% in TE, –26.4% in UE, & –12.5% in SE at week 24. For static perimetry at week 12, the mean number of locations (loci) that improved by ≥7 dB compared to baseline was 9.2 loci versus 6.1 loci in TE versus UE in all QR‐421a‐treated subjects & 12.9 loci versus 6.9 loci in early moderate‐stage subjects (n = 8; baseline BCVA of ≥70 letters). SE responded similarly to UE.

Conclusions

QR‐421a was well tolerated & demonstrated evidence of disease stabilization in visual acuity, & improvements in retinal sensitivity & retinal structural imaging data. An open‐label extension trial & 2 Phase 2/3 trials are planned.
Sclerochoroidal calcification associated to breast cancer and parathyroid adenoma
Authors: Boned‐Murillo Ana , Dolores Diaz Maria , El Bakkali Ismael Bakkali , Pérez Rivasés Guillermo , Cisneros Pablo , Núñez Moscarda Eva Josefina , Orejudo Derivas Marta , Ascaso Francisco , Honrubia Grijalbo Ana
Published: January 2022

Purpose

Sclerochoroidal calcification (SCC) is an unusual and poorly recognized ocular condition which is usually presented as an incidental finding in asymptomatic individuals. An exhaustive diagnosis is required as it may be commonly misdiagnosed such as choroidal osteoma, choroidal metastasis, amelanotic choroidal nevus, or lymphoma. It is commonly idiopathic but ophthalmologists should be aware of the possible association with severe ocular trauma and chronic intraocular inflammation, or with abnormal calcium‐phosphorus metabolism

Methods

We report the case of a 78‐year‐old woman with a medical history of breast cancer treated with quadrantectomy followed by adjuvant chemotherapy and radiotherapy, and Letrozole (aromatase inhibitors) for 3 years, which was discontinued when a hypercalcaemia and primary hyperparathyroidism (PHPT) related to a parathyroid adenoma. Oncological follow‐up was negative until during a routine examination prior to a right eye cataract intervention, dilated fundus examination revealed bilateral multiple asymptomatic yellow placoid lesions

Results

The patient's best‐corrected visual acuity (BCVA) was 20/20 in the right and left eye. Tomography–computed tomography (OCT‐scan), Magnetic resonance imaging (MRI) and Positron emission tomography–computed tomography (18‐FDG PET‐TC) revealed diffuse calcification in the choroid plexus bilaterally as well as calcification in the posterior aspect of both globes with no changes in metabolism at these levels. A SCC secondary to hypercalcaemia and PHPT related to a parathyroid adenoma was diagnosed. She was referred to endocrinology specialist to rule out systemic conditions. As the patient stills refusing surgery, she was treated with Cinacalcet (a calcimimetic) with regular follow‐up in the endocrinology clinic. Dilated fundus examination and OCT are performed periodically. For the time being, the patient remains asymptomatic and the lesion stays stable.

Conclusions

All patients with SCC should be tested for underlying systemic disorders involving abnormal calcium‐phosphorus metabolism to avoid complication or unwarranted intervention resulting from the misdiagnosed as a malignant tumor. Periodic ophthalmology studies are required as well to rule out possible complications.
Correlation between imaging morphological findings and laboratory biomarkers in patients with retinal vein occlusion
Authors: Kazantzis Dimitrios , Theodossiadis Panagiotis , Kroupis Christos , Chatziralli Irini
Published: January 2022

Purpose

To investigate the potential association between peripheral blood biomarkers and morphological characteristics of retinal imaging in patients with retinal vein occlusion (RVO).

Methods

Participants in this cross‐sectional observational study were 65 consecutive patients (65 eyes) with treatment naïve RVO, who underwent spectral‐domain optical coherence tomography (SD‐OCT) and fundus fluorescein angiography (FFA). In addition, peripheral blood samples were taken to evaluate full blood count and biochemical parameters. Correlation between imaging characteristics and laboratory parameters was examined.

Results

Eyes with subretinal fluid presented significantly higher neutrophil‐to‐lymphocyte ratio (p = 0.028). Hyperreflective foci on SD‐OCT were found to be associated with higher triglycerides (p = 0.024). Presence of cysts on SD‐OCT was associated with significantly higher triglycerides (p = 0.010). Central subfield thickness (CST) higher than 464 μm was associated with higher lymphocyte count (p = 0.016) and higher urea (p = 0.015). No significant associations were found between laboratory parameters and intraretinal fluid, ellipsoid zone and external limiting membrane condition, epiretinal membrane and macular ischemia.

Conclusions

Specific imaging morphological characteristics were found to be associated with laboratory parameters in patients with RVO. These findings may scrutinize the pathophysiology of RVO and its correlation with the development of specific clinical signs, while they could guide individualized treatment.
Patient opinion on the monitoring of their wet age‐related macular degeneration during coronavirus disease 2019 pandemic and on the importance of telemedicine
Authors: Tsiropoulos Georgios N. , Vallée Rodolphe , Calci Coraline , Gallo Castro Daniela , Ambresin Aude
Published: January 2022

Purpose

To present the patients’ view on the monitoring of their wet Age‐related Macular Degeneration (wet AMD) during Coronavirus disease 2019 (COVID‐19), and the impact that telemedicine could have on it.

Methods

Wet AMD patients of Swiss Visio Montchoisi and RétinElysée (Lausanne, Switzerland), who had intravitreal anti‐Vascular Endothelial Growth Factor (anti‐VEGF) injections before and after the first period of the Swiss confinement due to COVID‐19, completed two questionnaires. The first evaluated their view on their adherence to their scheduled injections during the confinement, and on the future use of telemedicine. The second, adapted from National Eye Institute Visual Function Questionnaire‐25, evaluated their opinion on their visual function during the confinement.

Results

From a total of 130 patients, 8.5% responded they did not respect their assigned injection interval during the confinement (group 1), while 91.5% responded they did (group 2). The majority of group 1 (37.5%) responded they did not attend their scheduled visit to avoid using public transportation. The majority of group 2 (78.7%) considered the continuation of their treatment more important than the risk of contracting COVID‐19. Before the lockdown, patients of group 2 had more need for help from others than the patients of group 1 (p = 0.02). In a future lockdown, 36.3% of group 1 and 8.7% of group 2 would prefer remote monitoring of their wet AMD via telemedicine (p = 0.02), 54.5% and 86.9% would prefer to visit the clinic (p = 0.02), while 9% and 4.3% would avoid the visit, respectively. 70% of group 1 and 33.6% of group 2 would rather use the telemedicine application in their home than visit a telemedicine center (p = 0.04).

Conclusions

Despite our availability to provide continuous intravitreal anti‐VEGF injections during the COVID‐19 confinement, many wet AMD patients did not receive their scheduled treatment. In similar future circumstances, most patients would prefer to visit the clinic. The patients of group 1 would prefer remote monitoring of their AMD via telemedicine at a higher rate than the patients of group 2.

Bibliography

Visual Function Questionnaire 25. https://www.nei.nih.gov/learn‐about‐eye‐health/resources‐for‐health‐educators/outreach‐materials/visual‐function‐questionnaire‐25
Outcomes following cataract surgery in patients with age‐related macular degeneration
Authors: Kumar Aneeta , Shalchi Zaid
Published: January 2022

Purpose

Cataract and age‐related macular degeneration (AMD) can occur concomitantly in the elderly population. AMD is often considered a poor prognostic factor for visual outcomes after cataract surgery. We wanted to investigate the outcomes of cataract surgery in patients with AMD.

Methods

We retrospectively analysed pre‐ and post‐operative visual acuity and refraction results for all adult patients who underwent phacoemulsification cataract surgery between February 2009 to May 2021 at a local hospital trust in the National Health Service (NHS), UK. Data collection was done through the Medisoft electronic medical record (Heidelberg Engineering, Leeds, UK). Statistical tests were conducted using paired and unpaired Student t‐tests, and p < 0.05 was considered significant.

Results

In total, we included 27 357 eyes undergoing cataract surgery in our analysis, of which 1653 had AMD. Patients with AMD underwent cataract surgery at an older age compared to those without AMD (82.2 years vs 74.6 years, p < 0.0001). Pre‐operatively, eyes with AMD tended to be more hypermetropic than healthy eyes and underwent a more substantial change in refractive power following surgery (p < 0.0001). Overall, visual acuity improved for patients post‐operatively, but patients with AMD had poorer improvement in visual acuity than patients with no ocular co‐pathology (LogMAR −0.17 versus −0.29, p < 0.0001). Notably, 23% of patients with AMD had poorer visual acuity post‐operatively, compared to only 10% in patients without any pathology (p < 0.0001).

Conclusions

Patients with AMD undergoing cataract surgery showed an improvement in visual acuity, although this improvement is less than in eyes with no co‐pathology. This data will help counsel AMD patients considering cataract surgery.
Comparison of quantitative self‐monitoring metamorphopsia measurements tools in myopic choroidal neovascularization (mCNV)
Authors: Hoffmann Laura , Mueller Susanne , Hatz Katja
Published: January 2022

Purpose

To assess the reproducibility and reliability of two self‐monitoring metamorphopsia devices (Alleye, Oculocare medical Inc. and AMD – A Metamorphopsia Detector software (MI), app4eyes GmbH & Co. KG, Germany) for detection of disease activity and inactivity in myopic choroidal neovascularization (mCNV).

Methods

Participants with foveal mCNV were followed over 12 months undergoing a standardized refraction protocol, metamorphopsia assessment, Spectral Domain Optical Coherence Tomography (SD‐OCT) and fundus autofluorescence (FAF) at baseline, 6 months, 12 months and additional individual visits. Disease activity and morphologic parameters were graded based on their location in an Early Treatment of Diabetic Retinopathy (ETDRS) grid overlay. Intraclass correlation coefficients (ICC) between inactive visits were calculated to assess repeatability. Scores of inactive and active visits were compared intra‐individually using paired t‐tests.

Results

Twenty‐one (21) eyes performing a total of 202 tests were included. Disease activity was observed in 14 eyes. ICC between inactive visits were excellent for both devices (0.98; 0.97). Mean difference between the active and inactive scores was more pronounced for the MI with 117.80 ± 231.57 (p = 0.079) than the Alleye score with 0.362 ± 17.16 (p = 0.938) considering all locations. Mean deviation from the mean inactive score was higher for both scores when disease activity was located in the central 1mm (128.70 ± 272.94; p = 0.195 for the MI and −4.42 ± 14.01; p = 0.372 for the Alleye score) compared to in the central 6 mm (70.67 ± 155.16; p = 0.513, respectively 1.43 ± 11.82; p = 0.853).

Conclusions

Both devices yielded reproducible scores for disease inactivity. Disease activity was better captured by the MI especially if subfoveally located. Hence, self‐monitoring devices may complement diagnostic management of mCNV. Data from larger cohorts including home monitoring are warranted.
Results of pars plana vitrectomy with inferior retinotomy in inferior rhegmatogenous retinal detachments with inferior retinal breaks and proliferative vitreoretinopathy grades B or C
Authors: Machado Soares Ricardo , Da Silva Fernandes Joana , Ferreira Catartina , Sousa Neves Filipe , Sepúlveda Paula , Bilhoto Miguel
Published: January 2022

Purpose

To report the surgical outcomes of pars plana vitrectomy (PPV) with inferior retinotomy without the need for scleral buckling in primary inferior rhegmatogenous retinal detachment (RRD) with inferior retinal breaks and Proliferative vitreoretinopathy (PVR) grades B or C.

Methods

Retrospective, consecutive series, single‐center study of patients that underwent PPV with inferior retinotomy for primary inferior RRD with inferior retinal breaks (4:00 to 8:00 clock hours) and PVR grades B or C. Data were obtained from patients’ medical records from October 2014 to November 2020. The primary outcomes of the study were retinal reattachment and visual acuity improvement. Data collected before and after surgery was compared between groups using chi‐square analysis and paired samples t‐test. The resulting p‐values significance level was set at p = 0.05.

Results

Thirty‐two patients (32 eyes) met the inclusion criteria. PVR in stage B was present in 19 patients and stage C in 13 patients. Macula‐off RRD was diagnosed in 25 patients while the other 7 patients had RRD with the macula attached. Regarding primary outcomes, 31 out of 32 (97%) patients achieved retinal reattachment with no differences between PVR groups (p = 0.406). The best‐corrected visual acuity (BCVA) improved significantly in eyes with macula‐off RRD at presentation (p < 0.001). Although macula‐attached RRD eyes had higher final BCVA, its improvement was not statistically significant (p = 0.370). Besides one retinal redetachment, no other significant complications were reported after surgery.

Conclusions

Inferior retinal breaks are associated with surgical failure following PPV for inferior RRD repair, especially if advanced PVR is present. Our results suggest that, in these less common and more challenging cases, PPV with an inferior retinotomy is associated with very favorable anatomic and visual outcomes.
Clinical features of patients with PEVAC in University Hospital of Canarias
Authors: Tapia Quijada Hugo E. , Falcon Roca Rocio , Sanchez Garcia Mariel
Published: January 2022

Purpose

To investigate the clinical characteristics of Perifoveal Exudative Vascular Anomalous Complex (PEVAC) patients diagnosed in the University Hospital of Canarias.

Methods

This retrospective study included 7 eyes (of 7 patients) diagnosed with PEVAC. We reviewed the demographic characteristics. All of our patients had undergone a complete ophtalmological examination including color retinography, autofluorescence, Optical Coherence Tomography (OCT), fluorescein angiography(FA) and OCT‐Angiography (OCTA). We also reviewed the follow‐up information.

Results

Of our 7 patients, 3 were women and 4 were men. The average age and standard deviation were 71.0 +‐12.8 years. Average visual acuity was 0.54 + −0.24.

Of our 7 patients, 4 had no remarkable comorbidities, 2 had age‐related macular degeneration and the resting patient had myopic degeneration. PEVAC presented as a big isolated perifoveal aneurysm. On OCT PEVAC appeared as a round hyperreflective lesion, typically surrounded by intraretinal cystic spaces. FA showed a well defined hyperfluorescent lesion with variable leakage. OCTA revealed that the isolated aneurysmatic lesion was located in the superficial capillary plexus in 2 cases; in the deep capillary plexus in 4 cases and in one cases it seemed to be in the intermediate plexus. In 5 cases, there was only subtle exudation that did not require treatment, remaining stable during follow‐up. In two cases, exudation was greater, so we treated them with anti‐VEGF, with partial response.

Conclusions

PEVAC is an aneurysmatic isolated perifoveal abnormality that can occur in patients with or without retinal disease. PEVAC did not respond to anti‐VEGF therapy.

Bibliography

Querques G, Kuhn D, Massamba N, Leveziel N, Querques L, Souied EH. Perifoveal Exudative Vascular Anomalous Complex. J Fr Ophtalmol 2011; 34(8): 559.e1–4.

Sacconi R, Freund KB, Yannuzzi LA, Dolz‐Marco R, Souied E, Capuano V, et al. The Expanded Spectrum of Perifoveal Exudative Vascular Anomalous Complex. Am J Ophthalmol 2017; 184:137–146.

Mrejen S,Le HM,Nghiem‐Buffet S,Tabary S,Quentel G,Cohen SY. Insights into Perifoveal Exudative Vascular Anomalous Complex. Retina 2020;40(1):80–86.
Measures to assess a warning vaccination level in a stochastic SIV model with imperfect vaccine
Authors: Gamboa Maria , Lopez‐Herrero Mariajesus
Published: January 2022

A stochastic Markovian Susceptible‐Infectious‐Susceptible (SIS) model, with infection reintroduction is considered to represent the evolution of an epidemic process within a finite population. Disease is assumed to be a contact disease whose effect can be prevented by a vaccine. Before the epidemic process emerges, individuals got vaccinated to assure that the population is protected by herd immunity. In consequence, we formulate the model by adding a new compartment for vaccine protected individuals. The administered vaccine is not a perfect one and consequently it fails in a proportion of vaccinated individuals that are not protected against the vaccine preventable communicable disease. Hence, while the infectious process is in progress, the initial vaccine coverage declines and herd immunity could be lost. A threshold on the size of the vaccinated group is included as a warning measure on the protection of the community. Our objective is to define and study random characteristics, depending on the vaccination eligible group, that could advise health authorities when to launch a new vaccination program to recover the initial immunity level.
Una historia todavía verde. El periodismo ambiental en Colombia
Authors: Vallejo Mejía Maryluz
Published: January 2022

El voluminoso caudal que ofrece la historia del periodismo en Colombia para comprender el país desde otras orillas ideológicas y disciplinares se enriquece con la historia de sus afluentes: las especialidades periodísticas que se caracterizan por la calidad de sus fuentes. De este modo, el periodismo ambiental abreva en las ciencias naturales y de allí el origen de sus padres fundadores, como el botánico de sotana Enrique Pérez Arbeláez, quien hizo de su columna de El Tiempo un púlpito para la defensa del ambiente desde finales de los años treinta hasta su muerte en 1972, año de la primera Cumbre de la Tierra de Estocolmo. Cruzados de esa causa, así como jalonadores de las políticas ambientales, fueron los periodistas Daniel Samper Pizano y Alberto Donadio, de la Unidad Investigativa de El Tiempo, al igual que colegas de El Espectador y las revistas Alternativa y Semana, que demostraron cómo detrás de las imágenes de postal de esta Colombia magia salvaje hay intereses políticos y económicos, además de redes criminales empeñadas en acabar con un patrimonio no renovable de la humanidad. Una historia todavía verde recoge esta tradición, pero también las voces de las nuevas generaciones de periodistas que están convencidas de la necesidad de reducir la huella ecológica ante la alarmante crisis climática actual.
Accounting for the Lombard effect in estimating the probability of detection in passive acoustic surveys: Applications for single sensor mitigation and monitoring
Authors: Palmer K. J. , Wu Gi-Mick , Clark Christopher , Klinck Holger
Published: January 2022

The detection range of calling animals is commonly described by the passive sonar equations. However, the sonar equations do not account for interactions between source and ambient sound level, i.e., the Lombard effect. This behavior has the potential to introduce non-linearities into the sonar equations and result in incorrectly predicted detection ranges. Here, we investigate the relationship between ambient sound and effective detection ranges for North Atlantic right whales (Eubalaena glacialis) in Cape Cod Bay, MA, USA using a sparse array of acoustic recorders. Generalized estimating equations were used to model the probability that a call was detected as a function of distance between the calling animal and the sensor and the ambient sound level. The model suggests a non-linear relationship between ambient sound levels and the probability of detecting a call. Comparing the non-linear model to the linearized version of the same model resulted in 12 to 25% increases in the effective detection range. We also found evidence of the Lombard effect suggesting that it is the most plausible cause for the non-linearity in the relationship. Finally, we suggest a simple modification to the sonar equation for estimating detection probability for single sensor monitoring applications.
Evidence for Multiple Subpopulations of Herpesvirus-Latently Infected Cells
Authors: Landis Justin T. , Tuck Ryan , Pan Yue , Mosso Carson N. , Eason Anthony B. , Moorad Razia , Marron J. Stephen , Dittmer Dirk P.
Published: January 2022

Latency is the defining characteristic of the
Herpesviridae
and central to the tumorigenesis phenotype of Kaposi’s sarcoma-associated herpesvirus (KSHV). KSHV-driven primary effusion lymphomas (PEL) rapidly develop resistance to therapy, suggesting tumor instability and plasticity.
Efficacy and safety of first-line osimertinib treatment and postprogression patterns of care in patients with epidermal growth factor receptor activating mutation-positive advanced non-small cell lung cancer (Reiwa study): study protocol of a multicentre, real-world observational study
Authors: Watanabe Kageaki , Yoh Kiyotaka , Hosomi Yukio , Usui Kazuhiro , Naka Go , Kishi Kazuma , Uemura Kohei , Ohashi Yasuo , Kunitoh Hideo
Published: January 2022

Introduction

Osimertinib, a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), is widely used as the first-line treatment for EGFR mutation-positive non-small cell lung cancer (NSCLC). Nevertheless, most cases ultimately acquire resistance to osimertinib, and no effective treatment has been currently established for cases having progressive disease (PD) with osimertinib. In clinical practice, EGFR-TKI therapy could be continued beyond response evaluation criteria in solid tumours (RECIST)-defined PD cases when they are clinically stable. Currently, the progression pattern of osimertinib and criteria for identifying patients who might benefit from osimertinib beyond PD are unknown. In addition, the efficacy and safety of osimertinib as the first-line treatment in real-world clinical practice remain unclear in Japan. This multicentre study was designed to evaluate the real-world data on first-line osimertinib and its post-treatment.

Methods and analysis

The study enrols patients with EGFR mutation-positive, advanced or recurrent NSCLC who received EGFR-TKI as the first-line therapy after 1 September 2018, from October 2019 to August 2020, and those started on osimertinib will be followed up until August 2022. We will evaluate the efficacy and safety of the first-line osimertinib treatment, adherence to it, progression patterns on RECIST PD and subsequent treatment.

Ethics and dissemination

All participating patients will provide written informed consent before entering the study. The protocol, amendments and patients’ informed consent forms will be approved before study commencement by the institutional review board or independent ethics committee at each participation site (Lead Ethics Committee; Japan Red Cross Medical Center (26 April 2019, order number 976)). Patients will be anonymised before registration into the study and their anonymised data will be collected from the case report form. The results of this study will be presented at the national and international conferences and submitted for publication.

Trial registration number

UMIN000038683.
SLEEP: intervention with weighted blankets for children with attention deficit hyperactivity disorder (ADHD) and sleep problems: study protocol for a randomised control trial
Authors: Larsson Ingrid , Aili Katarina , Nygren Jens M , Johansson Pia , Jarbin Håkan , Svedberg Petra
Published: January 2022

Introduction and objectives

Children with attention deficit hyperactivity disorder (ADHD) have an increased risk of sleep problems. Weighted blankets are one possible non-pharmacological intervention for these problems in this group of children. However, the effectiveness of weighted blankets is insufficiently investigated. This study aims to investigate the effectiveness of weighted blankets in terms of sleep, health-related outcomes and cost-effectiveness as well as to explore children’s and parents’ experiences of a sleep intervention with weighted blankets.

Methods and analysis

This study is a randomised placebo-controlled crossover trial comparing the effect of weighted fibre blankets (active) with fibre blankets without weight (control). Children aged 6–13 years, recently diagnosed with uncomplicated ADHD with verified sleep problems, were included in the study. The study period is 4 weeks for each condition, respectively, and then an 8-week follow-up. A total of 100 children diagnosed with ADHD and sleep problems will enter the study. The primary outcomes are sleep and cost per quality-adjusted life years. The secondary outcomes are health-related quality of life, ADHD symptoms, psychological distress and anxiety. Interviews with a subsample of the participating children and parents will be conducted for exploring the experiences of the intervention.

Ethics and dissemination

Ethical approval of the trial has been obtained from the Swedish Ethical Review Authority (number 2019–-2158) and conforms to the principles outlined in the Declaration of Helsinki (WMA, 2013). Results will be reported as presentations at peer-review conferences, in articles in peer-review journals and meetings with healthcare providers.

Trial registration number

NCT04180189.
Prognostic impact of albumin-bilirubin score on the prediction of in-hospital mortality in patients with heart failure: a retrospective cohort study
Authors: Han Su , Wang Chuanhe , Tong Fei , Li Ying , Li Zhichao , Sun Zhaoqing , Sun Zhijun
Published: January 2022

Objectives

Liver dysfunction is prevalent in patients with heart failure (HF) and can lead to poor prognosis. The albumin-bilirubin (ALBI) score is considered as an effective and convenient scoring system for assessing liver function. We analysed the correlation between ALBI and in-hospital mortality in patients with HF.

Design

A retrospective cohort study.

Setting and participants

A total of 9749 patients with HF (from January 2013 to December 2018) was enrolled and retrospectively analysed.

Main outcome measures

The main outcome is in-hospital mortality.

Results

ALBI score was calculated using the formula (log10 bilirubin [umol/L] * 0.66) + (albumin [g/L] * −0.085), and analysed as a continuous variable as well as according to three categories. Following adjustment for multivariate analysis, patients which occurred in-hospital death was remarkably elevated in tertile 3 group (ALBI ≥2.27) (OR 1.671, 95% CI 1.228 to 2.274, p=0.001), relative to the other two groups (tertile 1: ≤2.59; tertile 2: −2.59 to −2.27). Considering ALBI score as a continuous variable, the in-hospital mortality among patients with HF increased by 8.2% for every 0.1-point increase in ALBI score (OR 1.082; 95% CI 1.052 to 1.114; p<0.001). The ALBI score for predicting in-hospital mortality under C-statistic was 0.650 (95% CI 0.641 to 0.660, p<0.001) and the cut-off value of ALBI score was −2.32 with a specificity of 0.630 and a sensitivity of 0.632. Moreover, ALBI score can enhance the predictive potential of NT-pro-BNP (NT-pro-BNP +ALBI vs NT-pro-BNP: C-statistic: z=1.990, p=0.0467; net reclassification improvement=0.4012, p<0.001; integrated discrimination improvement=0.0082, p<0.001).

Conclusions

In patients with HF, the ALBI score was an independent prognosticator of in-hospital mortality. The predictive significance of NT-proBNP +ALBI score was superior to NT-proBNP, and ALBI score can enhance the predictive potential of NT-proBNP.
Significance of the dissection of common hepatic arterial lymph nodes in patients with oesophageal carcinoma: a multicentre retrospective study
Authors: He Huang-He , Hao Zhexue , Li Zhuoyi , Cheng Fei , Fu Junhui , Wang Wei , He Jiaxi , Luo Jinhua , He Jianxing
Published: January 2022

Objectives

To explore the significance of intraoperative common hepatic arterial lymph node dissection in patients with ooesophageal squamous carcinoma (ESCC) without coeliac trunk lymph node metastasis indicated by abdominal enhanced CT.

Methods

Patients aged 18–75 years who underwent oesophagectomy in three medical centres from June 2012 to June 2015, for whom R0 resection was completed and lymph node metastasis in the abdominal trunk was not identified before the operation were retrospectively analysed. The effects of the application value of common hepatic arterial lymph node dissection on survival were evaluated in patients with ESCC without coeliac trunk lymph node metastasis indicated by preoperative CT. According to the eighth version ofAmerican Joint Committee on Cancer (AJCC)/Union for International Cancer Control (UICC) staging, we selected patients with a Pathological Tumor Node Metastasis (pTNM) stage ranging from IA to IVA for analysis.

Results

Among the 816 qualified patients, 577 did not have coeliac trunk lymph node metastasis based on preoperative abdominal enhanced CT, and common hepatic arterial lymph node dissection was performed during the operation (observation group). Two hundred and thirty-nine preoperative CT examinations indicated no coeliac trunk lymph node metastasis, and common hepatic arterial lymph node dissection was not performed during the operation (control group). A multifactor Cox proportional hazards model showed no risk factors for overall survival (OS) (adjusted HR (HRadj)=0.91; p=0.404) or disease-free survival (DFS) (HRadj=0.86; p=0.179), regardless of whether common hepatic arterial lymph node dissection was performed. For patients with positive left gastric arterial lymph node metastasis, a multifactor Cox proportional hazards model indicated that common hepatic arterial lymph node dissection was a risk factor for OS (HRadj=0.63; p=0.035) and DFS (HRadj=0.58; p=0.026).

Conclusions

For patients with ESCC without celiac trunk metastasis indicated by abdominal enhanced CT, common hepatic arterial lymph node dissection conferred no survival benefits. However, for patients with left gastric arterial lymph node metastasis, common hepatic arterial lymph node dissection was beneficial.
Feasibility of an individualised, task-oriented, video-supported home exercise programme for arm function in patients in the subacute phase after stroke: protocol of a randomised controlled pilot study
Authors: Wanner Miriam , Schönherr Gudrun , Kiechl Stefan , Knoflach Michael , Müller Christoph , Seebacher Barbara
Published: January 2022

Introduction

Stroke rehabilitation guidelines suggest a high-frequency task-oriented training at high intensity. A targeted and self-paced daily training with intermittent supervision is recommended to improve patients’ self-management and functional output. So far, there is conflicting evidence concerning the most effective home-training delivery method.

Methods and analysis

The purpose of this pilot study is to compare the feasibility and preliminary effects of task-oriented home-exercises in patients in the subacute stage after stroke. Twenty-four patients will be randomised (1:1) to a Video group (a) or Paper group (b) of an individualised, task-oriented home-training (50 min, 6×/week, for 4 weeks) based on Wulf and Lewthwaite’s Optimizing Performance Through Intrinsic Motivation and Attention for Learning theory of motor learning. Patient-relevant goals will be identified using Goal Attainment Scaling and exercises progressively adapted. Semistructured interviews and a logbook will be used to monitor adherence, arm use and acceptability. Primary outcome will be the feasibility of the methods and a full-scale trial employing predefined feasibility criteria (recruitment, retention and adherence rates, patients’ satisfaction with the home-exercise programme and their progress, affected hand use and acceptance of the intervention). Assessed at baseline, post intervention and 4-week follow-up, secondary outcomes include self-perceived hand and arm use, actual upper extremity function and dexterity, hand strength, independence in activities of daily living and health-related quality of life. Interview data will be analysed using qualitative content analysis. Medians (ranges) will be reported for ordinal data, means (SD) for continuous and frequency (percentage) for nominal data.

Ethics and dissemination

This study follows the Standard Protocol Items: Recommendations for Interventional Trials-Patient-Reported Outcome (PRO) Extension guideline. Ethical approval was received from the Ethics Committee of the Medical University of Innsbruck, Austria (1304/2020). Written informed consent will be obtained from all participants prior to data collection. Study results will be disseminated to participating patients, patient organisations, via the clinic’s homepage, relevant conferences and peer-reviewed journals.

Trial registration number

DRKS-ID: DRKS00023395.

Study protocol, second revision, 5 December 2021.
Smoking-related behaviour changes among Korean men after the 2015 tobacco price increase: assessing the implications for the tobacco endgame using a reconstructed retrospective cohort study
Authors: Kim Seulgi , Cho Sung-il
Published: January 2022

Objectives

To examine the effect of Korea’s 2015 tax policy, discuss its effectiveness and limitations and present future directions for tax policy in the context of the tobacco endgame.

Design

A retrospectively reconstructed cohort study.

Setting

Korea, August 2014–October 2015.

Participants

The study examined 41,605 male smokers aged 19 years and older who participated in the 2015 Korea Community Health Survey.

Measures and analysis

Binary and multinomial logistic regression was used to assess the impact of the tax policy on smoking-related behaviour. We adjusted for demographic and health-related variables.

Results

Among 41,605 men who were smokers in 2014, 15,499 (35.85%, weighted) reported being affected by the price increase. Of all smokers, 1,772 (3.96%, weighted) reported quitting smoking because of the tobacco price increase. Others reduced their smoking amount (n=9,714, 22.48%, weighted) or made other changes such as switching brands (n=4,013, 9.41%, weighted). An additional 2,401 smokers (5.72%, weighted) quit smoking for reasons other than the tobacco price increase. Compared with those in the highest quintile of household income, the odds that those in the lowest quintile quit smoking due to the price increase were almost twice as high (OR=1.98, 95% CI 1.54 to 2.54).

Conclusions

Korea’s 2015 tobacco price increase affected a significant number of smokers within a year, especially in the lowest income group, inducing some to quit or reduce their smoking amount. However, more smokers quit for reasons independent of the price change. Tax policy can effectively reduce smoking, but needs to be combined with other policies for optimal results.
Lessons learned on the experienced facilitators and barriers of implementing a tailored VBHC model in a Dutch university hospital from a perspective of physicians and nurses
Authors: Lansdaal Dane , van Nassau Femke , van der Steen Marije , Bruijne Martine de , Smeulers Marian
Published: January 2022

Objective

This study aims to obtain insight into experienced facilitators and barriers of implementing a tailored value-based healthcare (VBHC) model in a Dutch university hospital from a perspective of physicians and nurses.

Method

A descriptive qualitative study with 12 physicians, nurses and managers of seven different care pathways who were involved in the implementation of a tailored VBHC methodology was conducted. Thematic content analysis was used to analyse the data guided by all factors of the Consolidated Framework for Implementation Research (CFIR).

Findings

The method designed for the implementation of a tailored VBHC methodology was appointed as a structured guide for the process. Throughout the implementation process, leadership and team dynamics were considered as important for the implementation to succeed. Also, sharing experiences with other value teams and the cooperation with external Information Technology (IT) teams in the hospital was mentioned as desirable. The involvement of patients, that is part of the VBHC methodology, was considered useful in the decision-making and improvement of the care process because it gave better insights in topics that are important for patients. The time-consuming nature of the implementation process was named as barrier to the VBHC methodology. On top of that, the shaping of the involvement of patients and the ongoing changes in departments were established as difficult. Finally, working with the Electronic Health Records and acquiring the necessary digital skills were considered to be often forgotten and, thus, hindering implementation.

Conclusion

Clinical Healthcare organisations implementing a tailored VBHC methodology will benefit from the use of a structured implementation methodology, a well-led strong team and cooperation with (external) teams and patients. However, shaping patient involvement, alignment with other departments and attention to digitisation were seen as a most important concerns in implementation and require further attention.
Health impact of work stressors and psychosocial perceptions among French hospital workers during the COVID-19 outbreak: a cross-sectional survey
Authors: Lucas David , Brient Sandrine , Eveillard Bisi Moriamo , Gressier Annabelle , LeGrand Tanguy , Pougnet Richard , Dewitte Jean-Dominique , Loddé Brice
Published: January 2022

Objective

To compare global health, mental health impact of work stressors and psychosocial perception of healthcare workers (HCWs) and non-HCWs in a hospital after the first peak of the COVID-19 outbreak in France.

Methods

A validated version of the SATIN (Santé Au Travail Inrs université Nancy 2)questionnaire with adapted scoring was used to collect data on health and impact of work stressors. This questionnaire was sent to all workers at a hospital in July 2020 and was self-administered online. In a multinomial regression model, we included HCW status, age, gender and front-line worker status as covariates.

Results

Data from a total of 1405 participants were included. We found that being an HCW, male and front-line worker was a risk factor for negative perception of work demand (OR 7.35, 95% CI 4.2 to 11.47; OR 2.55, 95% CI 1.11 to 5.89; OR 1.78, 95% CI 1.04 to 3.06). Being an HCW was a predictive factor for stress (OR 1.47, 95% CI 1.04 to 2.08), poor global health (OR 1.71, 95% CI 1.14 to 2.55) and negative perception of work activity environment (OR 1.9, 95% CI 1.3 to 2.8).

Conclusion

We have shown that all HCWs suffered from some health impact shortly after the first peak of the COVID-19 outbreak. We underline some stressors with high impact, including work demand, work abilities and organisational context, and emphasise the need for risk management.
Modern contraceptive use among adolescent girls and young women in Benin: a mixed-methods study
Authors: Ahissou Noudéhouénou Crédo Adelphe , Benova Lenka , Delvaux Thérèse , Gryseels Charlotte , Dossou Jean-Paul , Goufodji Sourou , Kanhonou Lydie , Boyi Christelle , Vigan Armelle , Peeters Koen , Sato Miho , Matsui Mitsuaki
Published: January 2022

Objectives

The study aimed to assess the determinants of modern contraceptive method use among young women in Benin.

Design

A mixed-methods design.

Setting and participants

We used the Benin 2017–2018 Demographic and Health Survey datasets for quantitative analysis. Data collection was conducted using multiple-cluster sampling method and through household survey. Qualitative part was conducted in the city of Allada, one of the Fon cultural capitals in Benin. The participants were purposively selected.

Outcomes

Contraceptive prevalence rate, unmet need for modern method and percentage of demand satisfied by a modern method for currently married and sexually active unmarried women were measured in the quantitative part. Access barriers and utilisation of modern methods were assessed in the qualitative part.

Results

Overall, 8.5% (95% CI 7.7% to 9.5%) among young women ages 15–24 were using modern contraceptives and 13% (12.1% to 14.0%) among women ages 25 or more. Women 15–24 had a higher unmet need, and a lower demand satisfied by modern contraceptive methods compared with women ages 25 or more. 60.8% (56.9% to 64.7%) of all unmarried young women had unmet need for modern contraceptives. Young women were more likely to use male condoms which they obtain mainly from for-profit outlets, pharmacies and relatives. The factors associated with demand satisfied by a modern method were literacy, being unmarried, knowing a greater number of modern contraceptive methods and experiencing barriers in access to health services. On the other hand, the qualitative study found that barriers to using modern methods include community norms about pre-marital sexual intercourse, perceptions about young women’s fertility, spousal consent and the use of non-modern contraceptives.

Conclusion

Contraceptive use is low among young women in Benin. The use of modern contraceptives is influenced by sociodemographic factors and social norms. Appropriate interventions might promote comprehensive sexuality education, increase community engagement, provide youth-friendly services and address gender inequalities.
Informal caregiver support needs and burden: a survey in Lithuania
Authors: Biliunaite Ieva , Kazlauskas Evaldas , Sanderman Robbert , Andersson Gerhard
Published: January 2022

Introduction

A demand for informal care exists worldwide. Lithuania presents an interesting case example where the need for the informal care is increasing, but relatively little research has been conducted documenting caregivers’ experiences and needs.

Objectives

The main objective of this study was to investigate Lithuanian informal caregiver characteristics, support needs and burden. In addition, the impact of the COVID-19 on the caregiver’s and care receiver’s well-being was investigated.

Methods

The study was conducted online between May and September 2020. Informal caregivers and individuals with informal caregiving experiences were invited to participate in the survey. The survey questionnaire comprised 38 multiple-choice items including participant demographic characteristics, availability of the support, support needs, well-being and the impact of the COVID-19 pandemic. In addition, caregiver burden was assessed with the 24-item Caregiver Burden Inventory (CBI).

Results

A total of 226 individuals completed the survey. Most of the participants were women (87.6%). Almost half of the participants (48.7%) were not receiving any support, and a total of 73.9% expressed a need to receive more professional support. Participants were found to experience high burden on the CBI (M=50.21, SD=15.63). Women were found to be significantly more burdened than men (p=0.011). Even though many participants experienced psychological problems (55.8%), only 2.2% were receiving any psychological support. Finally, majority of the participants did not experience any changes in their own (63.7%) or the well-being of their care receiver (68.1%) due to the COVID-19 pandemic.

Conclusion

Most of the participants were identified as intensive caregivers experiencing a high burden. A majority did not experience changes in their well-being due to COVID-19. We propose several recommendations for increasing accessibility and availability of support for informal caregivers in Lithuania based on the study findings.