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Background/Aim. Corneal cross-linking (CXL) treatment shows the best results in stabilizing the cornea and stopping the progress of the ectatic process. The aim of the study was to assess the impact of CXL on the keratoconus regarding higher-order aberrations (HOAs) and potential improvement of visual function. Methods. In 19 patients, a standard epithelium-off CXL was performed with an energy density of three mW/cm2 for half an hour. The cornea was examined by Pentacam topography before CXL and one and six months after CXL. Best-corrected visual acuity (BCVA), topographic data, and aberrations were collected. Results. A significant reduction in vertical coma was observed from preoperative -1.03 ? 1.89 to -0.74 ? 1.73 (p = 0.004) six months after CXL, and in spherical aberration from preoperative -0.22 ? 1.05 to -0.08 ? 1.13 (p = 0.002) six months after CXL. Root mean square (RMS) HOAs six months after CXL also significantly reduced from 2.31 ? 1.82 to 2.26 ? 1.84 six months after CXL (p = 0.001). BCVA improved from preoperative 0.43 ? 0.15 to 0.71 ? 0.19 six months after surgery (p < 0.001). Conclusion. CXL is a very potent treatment method for keratoconus, which significantly reduces certain corneal wavefront aberrations, especially vertical coma, spherical aberration, and RMS, and leads to a significant improvement in visual acuity.

Objective: Many older adults (aged 75+) continue cancer screening despite guidelines suggesting they should not. Using mixed-methods, we examined psychosocial and clinical factors associated with continued breast/prostate screening. Methods: We conducted an online, scenario-based, randomized study in Australia with participants aged 65+ years. The primary outcome was screening intention (10-point scale, dichotomized: low (1-5) and high (6-10)). We also measured demographic, psychosocial, and age-related clinical variables. Participants provided reason/s for their screening intentions in free-text. Results: 271 eligible participants completed the survey (aged 65-90 years, 71% adequate health literacy). Those who reported higher cancer anxiety, were men, screened more recently, had family history of breast/ prostate cancer and were independent in activities of daily living, were more likely to intend to continue screening. Commonly reported reasons for intending to continue screening were grouped into six themes: routine adherence, the value of knowing, positive screening attitudes, perceived susceptibility, benefits focus, and needing reassurance. Conclusions: Psychosocial factors may drive continued cancer screening in older adults and undermine efforts to promote informed decision-making. Practice implications: When communicating benefits and harms of cancer screening to older adults, both clinical and psychosocial factors should be discussed to support informed decision-making. (c) 2021 Elsevier B.V. All rights reserved.

Using machine learning techniques to build representations from biomedical data can help us understand the latent biological mechanism of action and lead to important discoveries. Recent developments in single-cell RNA-sequencing protocols have allowed measuring gene expression for individual cells in a population, thus opening up the possibility of finding answers to biomedical questions about cell differentiation. In this paper, we explore unsupervised generative neural methods, based on the variational autoencoder, that can model cell differentiation by building meaningful representations from the high dimensional and complex gene expression data. We use disentanglement methods based on information theory to improve the data representation and achieve better separation of the biological factors of variation in the gene expression data. In addition, we use a graph autoencoder consisting of graph convolutional layers to predict relationships between single-cells. Based on these models, we develop a computational framework that consists of methods for identifying the cell types in the dataset, finding driver genes for the differentiation process and obtaining a better understanding of relationships between cells. We illustrate our methods on datasets from multiple species and also from different sequencing technologies.

Limited studies at the beginning of the COVID-19 pandemic found GPs have been negatively affected by increased workload, reduced income and major concerns about staff and patient safety. This study aimed to investigate the challenges of COVID-19 in general practice 1 year since it was declared a pandemic. A national cross-sectional online survey was conducted in March 2021 of a convenience sample of 295 Australian GPs attending an online educational webcast. Twenty-five multipart and free-text questions collected information regarding GPs’ main COVID-19-related issues and concerns, including COVID-19 vaccines, useful sources of information, information needs and their perceived role as GPs in COVID-19 management. Descriptive statistics were calculated for all quantitative variables. Content analysis was used to analyse text data from open-ended questions. Of the 596 eligible attendees of the online educational webcast, 295 completed the survey (49.5% response rate). One year since COVID-19 was declared a pandemic, GPs still have concerns regarding patients ignoring prescreening and presenting with flu-like symptoms, the safety of their colleagues and family and catching COVID-19 themselves, as well as concerns about the effect of the pandemic on their patients and patients delaying essential care for non-COVID-19 conditions. More education and resources about vaccines was identified as the top information need, which will assist with what GPs’ perceived to be their key roles in managing the COVID-19 pandemic, namely educating the public, correcting misunderstandings and providing the COVID-19 vaccine. These findings highlight gaps in communication and information, particularly regarding COVID-19 vaccines. GPs need high-quality information and resources to support them in undertaking complex risk communication with their patients.

Background Single-cell RNA sequencing (scRNA-Seq) experiments are gaining ground to study the molecular processes that drive normal development as well as the onset of different pathologies. Finding an effective and efficient low-dimensional representation of the data is one of the most important steps in the downstream analysis of scRNA-Seq data, as it could provide a better identification of known or putatively novel cell-types. Another step that still poses a challenge is the integration of different scRNA-Seq datasets. Though standard computational pipelines to gain knowledge from scRNA-Seq data exist, a further improvement could be achieved by means of machine learning approaches. Results Autoencoders (AEs) have been effectively used to capture the non-linearities among gene interactions of scRNA-Seq data, so that the deployment of AE-based tools might represent the way forward in this context. We introduce here scAEspy, a unifying tool that embodies: (1) four of the most advanced AEs, (2) two novel AEs that we developed on purpose, (3) different loss functions. We show that scAEspy can be coupled with various batch-effect removal tools to integrate data by different scRNA-Seq platforms, in order to better identify the cell-types. We benchmarked scAEspy against the most used batch-effect removal tools, showing that our AE-based strategies outperform the existing solutions. Conclusions scAEspy is a user-friendly tool that enables using the most recent and promising AEs to analyse scRNA-Seq data by only setting up two user-defined parameters. Thanks to its modularity, scAEspy can be easily extended to accommodate new AEs to further improve the downstream analysis of scRNA-Seq data. Considering the relevant results we achieved, scAEspy can be considered as a starting point to build a more comprehensive toolkit designed to integrate multi single-cell omics.

Aspiration during swallow may have devastating consequences in COPD. It is known that COPD can impair swallow efficiency and safety [1–3] and a better understanding of how patients with COPD swallow is essential to inform preventative strategies. To date, no studies have examined swallow of large liquid volumes representative of everyday fast-paced drinking in an ample number of patients with COPD. In this letter we detail swallow patterns evaluated by videofluoroscopy in patients with COPD, with and without evidence of aspiration., Few studies have examined swallow of large liquid volumes representative of everyday drinking in COPD. Swallow by cup-drinking was evaluated in COPD using videofluoroscopy. Slower swallow was linked to aspiration indicating altered swallow habits in COPD. https://bit.ly/3wpdnO3

Malignant rhabdoid tumors (MRT) represent a very rare group of tumors in infants that have an aggressive clinical behavior, are refractory to therapy, and have a high mortality rate. We present two cases that demonstrate the importance of early diagnosis for further treatment. The first case was a 4 and a half month old boy that presented with an enlarged liver and was treated as hepatoblastoma with metastatic changes in the lung parenchyma after the diagnosis. The second case was a female neonate presenting with hardening on the right side of the abdomen which was treated as MRT of the liver after radiological and clinical evaluation. In both cases, the initial histopathologic diagnosis was hepatoblastoma, but later analyses confirmed the diagnosis of MRT. From our experience, imaging findings can be a valuable tool in directing further evaluation since even histopathologic differentiation from the small cell undifferentiated hepatoblastoma is a real challenge.

BACKGROUND/OBJECTIVES To compare the Australian Dietary Guideline Index (DGI-2013) and the Pyramid-based Mediterranean Diet Score (pyrMDS) as measures of diet quality in an ethnically diverse group of older men. SUBJECTS/METHODS Seven hundred and ninety-four older men aged ≥75 participated in wave 3 (2012-2013) of the Concord Health and Ageing in Men Project. Dietary intake was assessed using a validated diet history questionnaire. Ethnicity was based on self-reported country of birth and categorised as Australian-born (418 men), Italian or Greek migrants (188), and other migrants (188). Incident cardiovascular outcomes until March 2018 were measured using the composite of major adverse cardiovascular events (MACE), which comprises all-cause mortality, acute myocardial infarction, congestive cardiac failure, coronary revascularisation and/or ischaemic stroke. Ability to predict incident cardiovascular outcomes and all-cause mortality were compared between standardised DGI-2013 pyrMDS scores by comparison of hazard ratios, discrimination (Harrell's C-statistic) and calibration (calibration plots). RESULTS Italian and Greek migrant men had significantly lower DGI-2013 scores (91.7 vs. 93.9; p = 0.01) but significantly higher pyrMDS scores (8.8 vs. 8.2; p

Issues addressedTo investigate whether culturally and linguistically diverse communities in Western Sydney have experienced any positive effects during the COVID-19 pandemic, and if so, what these were.MethodsA cross–sectional survey with ten language groups was conducted from 21stMarch to 9thJuly 2021 in Sydney, Australia. Participants were recruited through bilingual multicultural health staff and health care interpreter service staff and answered a question, ‘In your life, have you experienced any positive effects from the COVID-19 pandemic?’ Differences were explored by demographic variables. Free–text responses were thematically coded using the Content Analysis method.Results707 people completed the survey, aged 18 to >70, 49% males and 51% females. Only 161 (23%) of those surveyed reported any positive impacts. There were significant differences in the proportion of those who reported positives based on age (p=0.004), gender (p=0.013), language (p=0.003), health literacy (p=0.014), English language proficiency (p=0.003), education (p=ConclusionsFrom 21st March to July 9th, 2021, few surveyed participants reported finding any positives because of the COVID–19 pandemic. This finding is in stark contrast to related research in Australia in a population dominated by adults with English as their first language, carried out in June 2020, in which many more people experienced positives.So whatThe needs of people from culturally and linguistically diverse backgrounds must inform future responses to community crises to facilitate an equitable effect of any collateral positives that may arise.

Background The acute sickness response to infection is a stereotyped set of illness manifestations initiated by proinflammatory signals in the periphery but mediated centrally. P2RX7 is a highly polymorphic gene encoding an ATP-gated cationic pore, widely expressed on immune cells and the brain, and regulating the NLRP3 inflammasome, as well as diverse neural functions. Methods Associations between P2RX7 genotype, pore activity, and illness manifestations were examined in a cohort with acute viral and bacterial infections (n = 484). Genotyping of 12 P2RX7 function-modifying single-nucleotide polymorphisms (SNPs) was used to identify haplotypes and diplotypes. Leucocyte pore activity was measured by uptake of the fluorescent dye, YO-PRO-1, and by ATP-induced interleukin-1β (IL-1β) release. Associations were sought with scores describing the symptom domains, or endophenotypes, derived from principal components analysis. Results Among the 12 SNPs, a 4-SNP haplotype block with 5 variants was found in 99.5% of the subjects. These haplotypes and diplotypes were closely associated with variations in pore activity and IL-1β production. Homozygous diplotypes were associated with overall illness severity as well as fatigue, pain, and mood disturbances. Conclusions P2RX7 signaling plays a significant role in the acute sickness response to infection, likely acting in both the immune system and the brain.

Key Points Question What is the association of individuals’ preferences for more or less health care with knowledge about prostate cancer overdiagnosis and informed choice? Findings In this survey study of 2993 men in Australia, higher scores on the Medical Maximizing-Minimizing Scale, indicating stronger preferences for more health care, were associated with reduced relative risk of making an informed choice, having adequate conceptual and correct numerical knowledge of prostate cancer screening outcomes, and correct understanding of overdiagnosis. Meaning These findings may help clinicians to better tailor discussions with patients about low-value care, such as prostate cancer screening, for which benefit is uncertain., This survey examines the association of preferences for more or less health care with informed choice among men in Australia eligible for prostate-specific antigen screening., Importance Understanding personal factors that influence diverse responses to health care information, such as preferences for more or less health care, might be beneficial to more effective communication and better involvement in health care choices. Objective To determine whether individuals’ preferences for more or less health care are associated with informed choice and understanding of overdiagnosis in routine prostate cancer screening and to examine associations among preferences, educational status, and health literacy. Design, Setting, and Participants This survey study included a community-based sample of men in Australia aged 45 to 60 years eligible for prostate-specific antigen (PSA) screening, recruited via an international social research company. Survey data were collected online from June 27 to July 26, 2018. Data were analyzed in April 2020. Exposures Participants were randomized to 1 of 2 versions of an online decision aid (full-length or abbreviated) about PSA screening and completed an online survey that included a measure of preference for more or less health care, the Medical Maximizer-Minimizer Scale (MMS), in which higher score indicates preference for more health care. Main Outcomes and Measures The primary outcome was informed choice; knowledge, attitudes, and intentions about screening for prostate cancer were also measured. Results Of 3722 participants who began the survey, 2993 (80.4%) completed it (mean [SD] age, 52.15 [6.65] years). Stronger preferences for more heath care were observed in those without tertiary education (mean difference, 0.15; 95% CI, 0.09-0.22; P

IntroductionShared decision making is as an essential principle for cardiovascular disease (CVD) prevention, where asymptomatic people are considering lifelong medication and lifestyle changes. This project aimed to develop and evaluate the first literacy-sensitive CVD prevention decision aid (DA) developed for people with low health literacy, and investigate the impact of literacy-sensitive design and heart age.MethodsWe developed the standard DA based on international standards. The literacy-sensitive version included simple language, supporting images, white space and a lifestyle action plan. A randomised trial included 859 people aged 45-74 using a 3 (DA: standard, literacy-sensitive, control) x 2 (heart age: heart age + percentage risk, percentage risk only) factorial design, with outcomes including prevention intentions/behaviours, gist/verbatim knowledge of risk, credibility, emotional response and decisional conflict. We iteratively improved the literacy-sensitive version based on end user testing interviews with 20 people with varying health literacy levels.ResultsImmediately post-intervention (n=859), there were no differences between the DA groups on any outcome. The heart age group was less likely to have a positive emotional response, perceived the message as less credible, and had higher gist/verbatim knowledge of heart age risk but not percentage risk. After 4 weeks (n=596), the DA groups had better gist knowledge of percentage risk than control. The literacy-sensitive decision aid group had higher fruit consumption, and the standard decision aid group had better verbatim knowledge of percentage risk. Verbatim knowledge was higher for heart age than percentage risk amongst those who received both.DiscussionThe literacy-sensitive DA resulted in increased knowledge and lifestyle change for participants with varying health literacy levels and CVD risk results. Adding heart age did not increase lifestyle change intentions or behaviour but did affect psychological outcomes, consistent with previous findings.MeSH TermsHealth Literacy, Cardiovascular Diseases, Decision Making (Shared), Life Style, Decision Support Techniques

Background: Serbia has an intermediate estimated prevalence of chronic hepatitis C (CHC) infection, approximately 1.13%, with hepatitis C remaining one of the leading causes of liver-related morbidity and mortality in Serbia with impaired quality of life and overwhelming cost of treating its complications As the availability of new treatment options and resources for screening remains limited, micro-elimination of CHC becomes a top priority. Methods: Review of the available published data related to the clinical and epidemiological situation of the hepatitis C infection in Serbia, including the unpublished data from the databases of four major reference centres in Serbia (Clinical Center Serbia, Clinical Center Niš, Clinical Center Vojvodina and Clinical Center Kragujevac). Results: Currently in Serbia, micro-elimination appears to be realistic in the patients with haemophilia, who represent a small, well-defined subpopulation, under constant monitoring by the healthcare system. Other feasible targets for micro-elimination of CHC infection in Serbia are patients on hemodialysis, prisoners and people who inject drugs. Conclusions: Micro-elimination is feasible in Serbia, especially in the subpopulation of patients with haemophilia. This may represent an initial step towards achieving the WHO objective to eliminate hepatitis C infection by 2030.

ObjectiveFrom December 2017, the Australian National Cervical Screening Program commenced 5 yearly primary human papillomavirus (HPV) screening; one of the first high-income countries to implement primary HPV screening. This study aimed to examine the psychosocial impact of self-reporting testing HPV positive in a sample of women screened since the renewal of the programme.MethodsWomen in Australia aged 25–74 years who reported participating in cervical screening since December 2017 were recruited through an online market research company to complete a cross-sectional survey. The primary outcomes were anxiety and general distress.Results1004 women completed the online survey; 80.9% reported testing HPV negative (HPV−), 6.5% reported testing HPV positive (HPV+) and 12.9% did not know/remember their test result. Women who reported testing HPV+ had significantly poorer psychological outcomes on a range of measures. Those who reported testing HPV+ had higher anxiety scores (53.03 vs 43.58 out of 80, pConclusionsReceipt of an HPV+ test result was associated with high levels of anxiety and distress, which reached clinical significance. Further work is needed to understand whether distress and concern could be reduced by ensuring all women receive high-quality standardised information with their results or by other interventions.

Paper description: Papillary thyroid carcinoma (PTC), usually curable, sometimes progresses to aggressive forms. Analysis of molecular alterations is helpful in predicting disease course and therapy decisions. BRAF gene mutations and epidermal growth factor receptor (EGFR) overexpression are associated with advanced stages of malignancy in several human cancers. We report that in PTC, when present as a single alteration, BRAFV600E mutation or EGFR overexpression both correlate with adverse clinical parameters and their simultaneous presence significantly enhances the frequency of lymph metastases and local tumor invasion. The coexistence of BRAFV600E mutation and EGFR overexpression identifies high risk patients as candidates for more serious treatment. Abstract: Papillary thyroid carcinoma (PTC) generally has a good prognosis, but in a subset of patients it progresses to aggressive forms. Analysis of molecular alterations in relation to clinical phenotype may help in risk stratification of patients by predicting tumor aggressiveness. We analyzed the expression profiles of epidermal growth factor receptor (EGFR) using immunohistochemistry and the presence of BRAF(V600E) mutation by mutant allele-specific PCR in PTC tissue samples (n=92) in relation to clinicopathological parameters. BRAFV600E was detected in 46.7% of patients and correlated with the presence of lymph node metastasis (LNM, p=0.035) and extrathyroid invasion (EI, p

Background: Adult education targeting health literacy (HL) may bring added value in the form of improved health. Objective: This study evaluated the effects of a HL program as part of an adult education curriculum for adults with low literacy and numeracy. Methods: This was a partial-cluster randomized controlled trial among 308 adults enrolled in basic education programs in Australia. Of the 308 participants, 141 (46%) were randomized to either the standard program (language, literacy, and numeracy [LLN]), or the HL intervention (LLN with embedded health content); the remainder ( n = 167) were allocated to standard intervention programs by the education provider at the class level. The main outcomes were functional HL, self-reported confidence, patient activation, generic HL (ie, HLQ, health knowledge, and self-reported health behavior). Data were collected at baseline, immediately after, and at 6 months post-intervention. Key Results: Of the 308 participants, 71% had limited literacy and 60% spoke a language other than English at home. Both interventions benefited participants, with improvements from baseline to immediate follow up on individual-level functional HL (e.g., reading a thermometer; HL group 18.4% vs. standard group 7.2%; p = .001), confidence (HL group 0.34 vs. standard group 0.06; p = .014) and health literacy questionnaire (HLQ) subscales. At 6 months, improvements in confidence ( p < .001) and some HLQ measures were retained. A consistent pattern of increased improvement in the HL program was observed compared to the standard program, although only some measures reached statistical significance: reading a food label (HL group 6.03/10 correct vs. standard group 5.49/10 correct; p = .022); confidence ( p = .008); ability to actively manage health (HLQ) ( p = .017), and health knowledge at 6 months (HL group 68% vs. standard group 60% correct, p = .052). HL participants reported being more likely to share course information and rated the program more useful to understand their health. Conclusions: Improving language, literacy, and numeracy generally has potential public health benefits that are retained at 6 months. Integrating health content adds further value to adult basic learning, is feasible, and potentially scalable. [ HLRP: Health Literacy Research and Practice . 2019;3(Suppl.):S42–S57.] Plain Language Summary: We compared the effect of an adult education-based health literacy (HL) program versus a standard language, literacy, and numeracy program on students' HL skills and psychosocial outcomes. Although students in both trial arms improved their skills, students in the HL program had better outcomes with higher HL, greater confidence, and higher health knowledge scores at 6 months.

Background: The aim of the study is to investigate whether the circadian IOP rhythm can be influenced by combined cataract surgery with high frequency deep sclerotomy (HFDS) and whether intraocular pressure (IOP) can be significantly reduced by HFDS. Methods: In our study 10 patients were included, in whom 24 h IOP monitoring was installed before and after HFDS/cataract surgery using a Triggerfish. HFDS is a minimally invasive glaucoma surgery (MIGS). Results: After performed HFDS combined with cataract surgery, the IOP was reduced from 27.7 ± 2.11 mmHg to 14.4 ± 2.59 mmHg, which is highly significant (p &lt, 0.001). The contact lens sensor (CLS) cosinor analysis pre- and postoperatively showed that the circadian rhythm is not influenced by the surgery, i.e., the circadian IOP rhythm did not show significant differences before and after surgery. Conclusions: HFDS combined with cataract surgery is a potent surgical method that can significantly reduce the IOP. However, the circadian rhythm cannot be changed by the surgery. The acrophase remained during the night in all patients.

The power density of femtosecond lasers and exposure time to the tissue are crucial for a successful procedure in terms of safety and precision. The reduction of the pulse duration allows reducing the quantity of the energy to be delivered to the tissue for disruption with strongly diminished mechanical and thermal collateral damage. The cutting effect of ultra-short pulses is very precise, minimally traumatic, safe, and predictable. Future developments will lead to further energy reductions to achieve optical breakdowns. However, the pulse length cannot be shortened arbitrarily because below 100 fs nonlinear effects can change the process in an unfavorable way. Compared to manual-conventional cataract surgery, femtosecond laser-assisted cataract surgery (FLACS) shows many advantages in clinical application, especially with regard to precision and tissue protection. The femtosecond laser has become particularly important and has made the overall procedure safer when we deal with complex cataract cases such as subluxated lenses. We provide an overview of the evolution of femtosecond laser technology for use in refractive and cataract surgeries. This article describes the advantages of available laser platforms with ultrashort pulses and mainly focuses on the technical and physical backgrounds of ophthalmic surgery technologies.

Background: Presbyopia treatment in pseudophakic patients with a monofocal IOL is challenging. This study investigates the refractive results of femto-PresbyLASIK and analyzes presbyopia treatment in pseudophakic eyes. Methods: 14 patients with 28 pseudophakic eyes were treated with femto-PresbyLASIK. The dominant eye was targeted at a distance and the non-dominant eye at −0.5 D. The presbyopic algorithm creates a steepness in the cornea center by using an excimer laser that leads to corneal multifocality. Results: 6 months after surgery a refraction of −0.11 ± 0.13 D (p = 0.001), an uncorrected distance visual acuity of 0.05 ± 1.0 logMAR (p &lt, 0.001) and an uncorrected near visual acuity of 0.15 ± 0.89 logMAR (p = 0.001) were achieved in the dominant eye. For the non-dominant eye, the refraction was −0.28 ± 0.22 D (p = 0.002), the uncorrected distance of visual acuity was 0.1 ± 1.49 logMAR, and the uncorrected near visual acuity was 0.11 ± 0.80 logMAR (p &lt, 0.001). Spherical aberrations (Z400) were reduced by 0.21–0.3 µm in 32% of eyes, and by 0.31–0.4 µm in 26% of eyes. Conclusion: By steepening the central cornea while maintaining spherical aberrations within acceptable limits, PresbyLASIK created a corneal multifocality that safely improved near vision in both eyes. Thus, femto-PresbyLASIK can be used to treat presbyopia in pseudophakic eyes without performing intraocular surgery.

BACKGROUND It is known that pterygia above a certain size cause astigmatism and other aberrations of the human cornea and thus impair the quality of vision. Exclusive Sr-/Ytt-90 beta irradiation is a highly effective treatment for primary pterygia. The aim of this retrospective study is to determine the extent to which higher order corneal aberrations are affected by this treatment. METHODS Evaluation of corneal topographies and wavefront aberration data of 20 primary pterygia patients generated before and at different points in time in the first year after irradiation. Additionally, the size of the pterygium was measured. RESULTS The study showed a significant increase in coma and triple leaf aberrations in pterygia with a horizontal length of 2 mm and more. It was also found that a pterygium size greater than 2 mm significantly induces astigmatism. Both phenomena reduce visual quality. In none of the patients could a pterygium recurrence be detected after irradiation. CONCLUSIONS If the pterygium size is less than 2 mm, early exclusive Sr/Ytt-90 beta irradiation can be recommended. If the size is more than 2 mm, a pterygium excision 6 months after beta irradiation can be discussed.

Issue addressed To investigate whether Australians have experienced any positive effects during the COVID‐19 pandemic. Methods National online longitudinal survey. As part of a June 2020 survey, participants (n = 1370) were asked ‘In your life, have you experienced any positive effects from the COVID‐19 pandemic’ (yes/no) and also completed the World Health Organisation‐Five well‐being index. Differences were explored by demographic variables. Free‐text responses were thematically coded. Results Nine hundred sixty participants (70%) reported experiencing at least one positive effect during the COVID‐19 pandemic. Living with others (P = .045) and employment situation (P

Rationale Swallow may be compromised in COPD leading to aspiration and adverse respiratory consequences. However, prevalence and consequences of detectable aspiration in stable COPD are not known. Objectives We tested the hypothesis that a significant number of patients with stable COPD will have detectable aspiration during swallow (prandial aspiration) and that they would experience more frequent severe acute exacerbations of COPD (AECOPD) over the subsequent 12 months. Methods Patients (n=151) with verified and stable COPD of all severities were recruited at a tertiary care hospital. Videofluoroscopy was conducted to evaluate aspiration using Rosenbek's scale for penetration–aspiration during 100-mL cup drinking. AECOPD was documented as moderate (antibiotics and/or corticosteroid treatment) or severe (emergency department admission or hospitalisation) over the ensuing 12 months. Measurements and main results Aspiration was observed in 30 out of 151 patients (19.9%, 18 males, 12 females; mean age 72.4 years). Patients with aspiration had more overall AECOPD events (3.03 versus 2 per patient; p=0.022) and severe AECOPD episodes (0.87 versus 0.39; p=0.032). Severe AECOPD occurred in more patients with aspiration (50% of patients versus 18.2%; OR 4.5, CI 1.9–10.5; p=0.001) and with silent aspiration (36.7% versus 18.2%; OR 2.6, CI 1.1–6.2; p=0.045). Aspiration was related to a shorter exacerbation-free period during the 12-month follow-up period (p=0.038). Conclusions Prandial aspiration is detectable in a subset of patients with COPD and was predictive of subsequent severe AECOPD. Studies to examine if the association is causal are essential to direct strategies aimed at prevention of aspiration and AECOPD., This study demonstrates that prandial aspiration occurs in ∼20% of patients with stable COPD and portends severe COPD exacerbations over the next 12 months https://bit.ly/2Tx5btj

Objective To investigate framing of active surveillance as a management option for cervical intraepithelial neoplasia (CIN)2 in women of childbearing age. Methods We conducted a between-subjects factorial (2 × 2) randomised experiment. Women aged 25–40 living in Australia were presented with the same hypothetical pathway of testing human papillomavirus (HPV)-positive, high-grade cytology and a diagnosis of CIN2, through an online survey. They were randomised to one of four groups to evaluate the effects of (i) framing (method of explaining resolution of abnormal cells) and (ii) inclusion of an overtreatment statement (included versus not). Primary outcome was management choice following the scenario: active surveillance or surgery. Results 1638 women were randomised. Overall, preference for active surveillance was high (78.9%; n = 1293/1638). There was no effect of framing or providing overtreatment information, or their interaction, on management choice. After adjusting for intervention received, age, education, and other model covariates, participants were more likely to choose active surveillance over surgery if they had not already had children, had plans for children in the future, had no family history of cancer, had no history of endometriosis, had adequate health literacy, and more trust in their GP. Participants were less likely to choose active surveillance over surgery if they were more predisposed to seek health care for minor problems. Conclusions Although we found no framing effect across the four conditions, we found a high level of preference for active surveillance with associations of increased preference that accord with the desire to minimise potential risks of CIN2 treatment on obstetric outcomes. These are valuable data for future clinical trials of active surveillance for management of CIN2 in younger women of childbearing age. Trial registration Australian New Zealand Clinical Trials Registry (ACTRN12618002043213, 20/12/2018, prior to participant enrolment).

Femtosecond laser-assisted cataract surgery has the potential to make critical steps of cataract surgery easier and safer, and reduce endothelial cell loss, thus, improving postoperative outcomes. This study compared FLACS with the conventional method in terms of endothelial cells behavior, clinical outcomes, and capsulotomy precision. Methods: In a single-center, randomized controlled study, 130 patients with cataracta senilis received FLACS or conventional cataract surgery. Results: A significant endothelial cell loss was observed postoperatively, compared to the preoperative values in both groups. The endothelial cell counts was significantly better in the FLACS group in cataract grade 2 (p = 0.048) patients, compared to conventionally at 4 weeks. The effective phaco time was notably shorter in grade 2 of the FLACS group (p = 0.007) compared to the conventional. However, no statistically significant differences were found for the whole sample, including all cataract grades, due to the overall cataract density in the FLACS group being significantly higher (2.60 ± 0.58, p &lt, 0.001) as compared to conventional methods (2.23 ± 0.42). Conclusions: Low energy FLACS provides a better result compared to endothelial cell loss, size, and shape variations, as well as in effective phaco time within certain cataract grade subgroups. A complete comparison between two groups was not possible because of the higher cataract grade in the FLACS. FLACS displayed a positive effect on endothelial cell preservation and was proven to be much more precise.

Phacoemulsification is a widely used surgical method in cataract surgery with a high energy ultrasound source. The viscoelastic is considered to be tissue protective. The aim of this study is to investigate during surgery the impact of using viscoelastic versus no viscoelastic on clinical outcomes, potential complications and effect on endothelial cell density. The study group included 64 patients, who were subjected to phacoemulsification using balanced salt solution (BSS). Control group consisted of 62 patients, who underwent phacoemulsification using Hyaloronic acid 1% Healon 1%. Student’s t-test was applied for statistical analysis. The simulations of temperature changes during phacoemulsification were performed by COMSOL Multiphysics software. In the BSS group, a mean endothelial cell loss (ECL) of 4.5% was measured one month postoperatively, while in the Healon group ECL was 5.3%. Data analysis showed no significant difference in ECL between the groups (Student’s t-test, p = 0.8). No significant difference was observed in endothelial cell morphology and IOP between the two groups pre- and postoperatively (all p &gt, 0.05). The modeling of thermo fluid dynamics showed that the heating of the cornea is slightly less when Healon was used as irrigation fluid. The phacoemulsification technique can be performed by an experienced surgeon with viscoelastics or continuous anterior chamber (AC) irrigation on the same level of safety regarding endothelial cell damage, providing equally satisfying clinical outcomes.

BackgroundCOVID-19 testing and contact tracing has been crucial in Australia’s prevention strategy. However, testing for COVID-19 is far from optimal, and behavioural barriers are unknown. Study 1 aimed to identify the range of barriers to testing. Study 2 aimed to estimate prevalence in a nationally relevant sample to target interventions.MethodsStudy 1: National longitudinal COVID-19 survey from April-November 2020. Testing barriers were included in the June survey (n=1369). Open responses were coded using the COM-B framework (capability-opportunity-motivation). Study 2: Barriers from Study 1 were presented to a new nationally representative sample in November to estimate prevalence (n=2869). Barrier prevalence was analysed by health literacy level using Chi square tests.ResultsStudy 1: 49% strongly agreed to get tested for symptoms, and 69% would self-isolate. Concern about pain was the top barrier from a provided list (11%), but 32 additional barriers were identified from open responses and coded to the COM-B framework. Study 2: The most prevalent barriers were motivation issues (e.g. don’t believe symptoms are COVID-19: 28%, few local cases: 18%). Capability issues were also common (e.g. not sure symptoms are bad enough: 19%, not sure whether symptoms need testing: 15%). Many barriers were more prevalent amongst people with low compared to high health literacy, including motivation (preference to self isolate: 21% vs 12%, pain: 15% vs 9%) and capability (not sure symptom needs testing: 12% vs 8%, not sure how to test:11% vs 4%).ConclusionEven in a health system with free and widespread access to COVID-19 testing, motivation and capability barriers were prevalent issues, particularly for people with lower health literacy. This study highlights the important of diagnosing behaviour barriers to target public health interventions for COVID-19 and future pandemics.

Background In response to the COVID-19 pandemic, telehealth has rapidly been adopted to deliver health care services around the world. To date, studies have not compared people’s experiences with telehealth services during the pandemic in Australia to their experiences with traditional in-person visits. Objective This study aimed to compare participants’ perceptions of telehealth consults to their perceptions of traditional in-person visits and investigate whether people believe that telehealth services would be useful after the pandemic. Methods A national, cross-sectional, community survey was conducted between June 5 and June 12, 2020 in Australia. In total, 1369 participants who were aged ≥18 years and lived in Australia were recruited via targeted advertisements on social media (ie, Facebook and Instagram). Participants responded to survey questions about their telehealth experience, which included a free-text response option. A generalized linear model was used to estimate the adjusted relative risks of having a poorer telehealth experience than a traditional in-person visit experience. Content analysis was performed to determine the reasons why telehealth experiences were worse than traditional in-person visit experiences. Results Of the 596 telehealth users, the majority of respondents (n=369, 61.9%) stated that their telehealth experience was “just as good as” or “better than” their traditional in-person medical appointment experience. On average, respondents perceived that telehealth would be moderately useful to very useful for medical appointments after the COVID-19 pandemic ends (mean 3.67, SD 1.1). Being male (P=.007), having a history of both depression and anxiety (P=.016), and lower patient activation scores (ie, individuals’ willingness to take on the role of managing their health/health care) (P=.036) were significantly associated with a poor telehealth experience. In total, 6 overarching themes were identified from free-text responses for why participants’ telehealth experiences were poorer than their traditional in-person medical appointment experiences, as follows: communication is not as effective, limitations with technology, issues with obtaining prescriptions and pathology results, reduced confidence in their doctor, additional burden for complex care, and inability to be physically examined. Conclusions Based on our sample’s responses, telehealth appointment experiences were comparable to traditional in-person medical appointment experiences. Telehealth may be worthwhile as a mode of health care delivery while the pandemic continues, and it may continue to be worthwhile after the pandemic.

Background Low health literacy is associated with poorer health outcomes. A key strategy to address health literacy is a universal precautions approach, which recommends using health-literate design for all health interventions, not just those targeting people with low health literacy. This approach has advantages: Health literacy assessment and tailoring are not required. However, action plans may be more effective when tailored by health literacy. This study evaluated the impact of health literacy and action plan type on unhealthy snacking for people who have high BMI or type 2 diabetes (Aim 1) and the most effective method of action plan allocation (Aim 2). Methods and findings We performed a 2-stage randomised controlled trial in Australia between 14 February and 6 June 2019. In total, 1,769 participants (mean age: 49.8 years [SD = 11.7]; 56.1% female [n = 992]; mean BMI: 32.9 kg/m2 [SD = 8.7]; 29.6% self-reported type 2 diabetes [n = 523]) were randomised to 1 of 3 allocation methods (random, health literacy screening, or participant selection) and 1 of 2 action plans to reduce unhealthy snacking (standard versus literacy-sensitive). Regression analysis evaluated the impact of health literacy (Newest Vital Sign [NVS]), allocation method, and action plan on reduction in self-reported serves of unhealthy snacks (primary outcome) at 4-week follow-up. Secondary outcomes were perceived extent of unhealthy snacking, difficulty using the plans, habit strength, and action control. Analyses controlled for age, level of education, language spoken at home, diabetes status, baseline habit strength, and baseline self-reported serves of unhealthy snacks. Average NVS score was 3.6 out of 6 (SD = 2.0). Participants reported consuming 25.0 serves of snacks on average per week at baseline (SD = 28.0). Regarding Aim 1, 398 participants in the random allocation arm completed follow-up (67.7%). On average, people scoring 1 SD below the mean for health literacy consumed 10.0 fewer serves per week using the literacy-sensitive action plan compared to the standard action plan (95% CI: 0.05 to 19.5; p = 0.039), whereas those scoring 1 SD above the mean consumed 3.0 fewer serves using the standard action plan compared to the literacy-sensitive action plan (95% CI: −6.3 to 12.2; p = 0.529), although this difference did not reach statistical significance. In addition, we observed a non-significant action plan × health literacy (NVS) interaction (b = −3.25; 95% CI: −6.55 to 0.05; p = 0.054). Regarding Aim 2, 1,177 participants across the 3 allocation method arms completed follow-up (66.5%). There was no effect of allocation method on reduction of unhealthy snacking, including no effect of health literacy screening compared to participant selection (b = 1.79; 95% CI: −0.16 to 3.73; p = 0.067). Key limitations include low–moderate retention, use of a single-occasion self-reported primary outcome, and reporting of a number of extreme, yet plausible, snacking scores, which rendered interpretation more challenging. Adverse events were not assessed. Conclusions In our study we observed nominal improvements in effectiveness of action plans tailored to health literacy; however, these improvements did not reach statistical significance, and the costs associated with such strategies compared with universal precautions need further investigation. This study highlights the importance of considering differential effects of health literacy on intervention effectiveness. Trial registration Australia and New Zealand Clinical Trial Registry ACTRN12618001409268., In a randomized trial, Julie Ayre and colleagues investigate the role of health literacy in the effectiveness of action plans to reduce unhealthy snacking in Australian individuals with overweight/obese BMI and/or type 2 diabetes., Author summary Why was this study done? Health literacy is increasingly recognised as an important contributor to health outcomes. Most health literacy interventions aim to make information easier to understand, but few behaviour change strategies address health literacy issues explicitly, and few studies have investigated the effect of an individual’s health literacy on behaviour change strategies. This study aimed to evaluate (1) the effects of health literacy and literacy-sensitive design on the effectiveness of action plans to reduce unhealthy snacking and (2) the most effective method of allocating an action plan. What did the researchers do and find? In total, 1,769 participants were randomised to 1 of 3 allocation methods (random, health literacy screening, participant selection) and 1 of 2 action plans to reduce unhealthy snacking (standard versus literacy-sensitive), with follow-up after 4 weeks. The literacy-sensitive action plan may be more effective for participants with low/moderate health literacy. We observed that the standard action plan may reduce snack consumption for those with high health literacy; however, the interaction between health literacy and action plan did not reach statistical significance. We did not find evidence suggesting that allocation method had a significant effect on reported snacking behaviour. What do these findings mean? There may be a benefit to tailoring action plans to individual health literacy, particularly for those with lower health literacy. However, this benefit did not reach statistical significance and should be weighed against the cost of tailoring compared to providing everyone with the same (literacy-sensitive) intervention (universal precautions approach). Future research should continue to investigate how health literacy and literacy-sensitive designs impact on intervention effectiveness.

ObjectivesIt is unclear how people with hypertension are responding to the COVID-19 pandemic given their increased risk, and whether targeted public health strategies are needed.DesignThis retrospective case-control study compared people with hypertension to matched healthy controls during COVID-19 lockdown, to determine whether they have higher risk perceptions, anxiety and prevention intentions.MethodsBaseline data from a national survey were collected in April 2020 during COVID-19 lockdown. Of 4362 baseline participants, 466 people reported hypertension with no other chronic conditions, and were randomly matched to healthy controls with similar age, gender, education and health literacy. A subset (n=1369) was followed-up at 2 months after restrictions eased, including 147 participants with hypertension only. Risk perceptions, prevention intentions and anxiety were measured.ResultsAt baseline, perceived seriousness was high for both hypertension and control groups. The hypertension group had higher anxiety than controls; and were more willing to have the influenza vaccine. At follow-up, these differences were no longer present in the longitudinal sub-sample. Perceived seriousness and anxiety had decreased, but vaccine intentions for both influenza and COVID-19 remained high (>80%).ConclusionsAnxiety was above normal levels during the COVID-19 lockdown. This was higher in the hypertension group, who also had higher vaccination intentions. Locations with prolonged restrictions may require targeted mental health screening for vulnerable groups. Despite a decrease in perceived risk and anxiety after 2 months of lockdown restrictions, vaccination intentions for both influenza and COVID-19 remained high, which is encouraging for future prevention of COVID-19.

Background People with intellectual disability (ID) have multiple and complex health needs, more frequent healthcare episodes, and experience poorer health outcomes. Research conducted two decades ago showed that medical professionals were lacking in the knowledge and skills required to address the complex needs of this patient group. The aim of the current study was to determine whether Australian undergraduate medical schools that offer ID health education content had changed the amount and nature of such teaching over this period. Methods Identical or equivalent questionnaire items were compared across eight Australian medical schools that participated in curricula audits conducted in 1995 (referred to as T1) and 2013/14 (T2). The audits were of the nature of the ID content, methods used to teach it, and who taught it. Results There was no significant difference in the number of hours of compulsory ID content offered to medical students at T2 (total = 158.3 h; median = 2.8 h per ID unit) compared with T1 (total = 171 h; median = 2.5 h). At T2 compared with T1, units with ID content taught in the area of general practice had increased (2 units; 3.6% to 7 units; 16.3%), while decreases were seen in paediatrics (22 units; 40.0% to 10 units; 23.3%) and psychiatry (10 units; 18.2% to 4 units; 9.3%). The number of schools using problem- and/or enquiry-based learning rose to six at T2 from one at T1. Inclusive teaching practices (people with ID develop or deliver content) in compulsory/elective units had increased at T2 (10 units; 23.3%) compared with T1 (6 units; 10.9%), but direct clinical contact with people with ID had decreased (29 units; 52.7% to 11 units; 25.6%). Conclusions Overall, little progress has been made to address the gaps in ID education for medical students identified from an audit conducted in 1995. Renewal of ID content in medical curricula is indicated as a key element in efforts to improve workforce capacity in this area and reduce barriers to care, with the aim of reversing the poor health outcomes currently seen for this group.

ObjectivesTo determine how participants perceived telehealth consults in comparison to traditional in-person visits, and to investigate whether people believe that telehealth services would be useful beyond the pandemic.DesignA national cross-sectional community survey.ParticipantsAustralian adults aged 18 years and over (n=1369).Main outcome measuresTelehealth experiences.ResultsOf the 596 telehealth users, the majority of respondents (62%) rated their telehealth experience as “just as good” or “better” than a traditional in-person medical appointment. On average, respondents perceived that telehealth would be moderately to very useful for medical appointments after the COVID-19 pandemic is over (M=3.67 out of 5, SD=1.1). Being male (p=0.007), having a history of both depression and anxiety (p=0.037), or lower patient activation (individuals’ willingness to take on the role of managing their health/healthcare) (p=0.037) were associated with a poorer telehealth experience. Six overarching themes were identified from free-text responses of why telehealth experience was poorer than a traditional in-person medical appointment: communication is not as effective; limitations with technology; issues with obtaining prescriptions and pathology; reduced confidence in doctor; additional burden for complex care; and inability to be physically examined.ConclusionsTelehealth appointments were reported to be comparable to traditional in-person medical appointments by most of our sample. Telehealth should continue to be offered as a mode of healthcare delivery while the pandemic continues and may be worthwhile beyond the pandemic.The knownThe COVID-19 pandemic has resulted in an increase in telehealth services.The newThe majority of telehealth users (62%) perceived their experience to be just as good or better than traditional in-person medical care; and that telehealth would be at least somewhat useful beyond the pandemic.Having a history of both depression and anxiety was associated with a poorer telehealth experience and in-person visits were frequently preferred over telehealth visits for mental health appointments.The implicationTelehealth should continue to be offered while the COVID-19 pandemic continues and may be worthwhile beyond the pandemic, however, telehealth may be less effective for mental health services.

Background: Inflammation and oxidative stress in COPD alters proteasis/antiproteasis balance. Matrix metalloproteinase -9 (MMP-9) has a significant role in augmentation of inflammatory process, matrix turnover and lung repair. Aim: of this study was to assess serum levels of MMP-9 and tissue inhibitor of metalloproteinase -1 (TIMP-1) and its association with lung function and clinical parameters. We hypothesized that elevated levels of MMP-9 will be identified in patients with most pronounced impairment of lung function, increased burden of symptoms and more frequent acute exacerbations in COPD patients (AECOPD). Methods: We measured serum levels of MMP-9, TIMP-1 and ratio MMP-9/TIMP-1 in group of 98 COPD participants and 47 healthy controls. In COPD group pulmonary function tests (post-bronchodilator spirometry, single breath diffusion capacity for carbon monoxide (CO) and body pletismography) were performed. Symptoms were assessed by Modified Medical Research Council (mMRC) scale and COPD Assessment Test (CAT). All moderate to severe COPD exacerbations in previous year were recorded. Results: Subjects with COPD had significantly higher serum MMP-9, TIMP-1 and MMP-9 / TIMP-1 ratio compared to healthy control (p Conclusion: These results may indicate the possible role of MMP-9 in the pathophysiology of airway remodeling in COPD.

Background Conflicting evidence exists regarding the association of socioeconomic status (SES) with mortality among older people and little is known about the mechanisms underlying this association. We investigated the association of SES with mortality among older Australian men. We also investigated potential mediating effects of health-related behaviours in SES-mortality associations. Methods We used data from a prospective population-based cohort (the Concord Health and Aging in Men Project), in Sydney, Australia. The main outcomes were all-cause and cause-specific mortality. Educational attainment, occupational position, source of income, housing tenure, and a cumulative SES score were assessed at baseline. Longitudinally assessed alcohol consumption, smoking, physical activity, and body mass index were investigated as potential mediators. Associations were quantified using Cox regression. Results We evaluated 1527 men (mean age: 77.4 ± 5.5 years). During a mean follow-up time of 9.0 years, 783 deaths occurred. For deaths from all causes, the adjusted hazard ratio (HR) for the lowest tertile of cumulative SES score versus the highest tertile was 1.44 (95% CI 1.21 to 1.70); the corresponding sub-HRs were 1.35 (0.96 to 1.89) for cardiovascular disease (CVD) mortality; 1.58 (1.15 to 2.18) for cancer mortality, and 1.86 (1.36 to 2.56) for non-CVD, non-cancer mortality. SES-mortality associations were attenuated by 11–25% after adjustment for mediating health-related behaviours. Conclusion Low SES is associated with increased mortality in older Australian men and health-related behaviours accounted for less than one-fourth of these associations. Further research is needed to fully understand the mechanisms underlying SES inequalities in mortality among older people.

Background Among older people, the extent to which psychosocial factors explain socioeconomic inequalities in mortality is debated. We aimed to investigate the potential mediating effect of psychosocial factors on socioeconomic inequalities in mortality. Methods We used data from a prospective population-based cohort (the Concord Health and Ageing in Men Project; baseline recruitment in 2005–2007), in Sydney, Australia. The main outcomes were all-cause and cause-specific mortality. Socioeconomic status (SES; educational attainment, occupational position, source of income, housing tenure, and a cumulative SES score) was assessed at baseline. Measures of structural and functional social support, as well as depressive and anxiety symptoms were assessed three times during follow-ups. Associations were quantified using Cox regression. Mediation was calculated using “change-in-estimate method”. Results 1522 men (mean age at baseline: 77·4 ± 5·5 years) were included in the analyses with a mean (SD) follow-up time of 9·0 (3·6) years for all-cause and 8·0 (2·8) years for cause-specific mortality. At baseline, psychosocial measures displayed marked social patterning. Being unmarried, living alone, low social interactions, and elevated depressive symptoms were associated with higher risk of all-cause and cardiovascular disease (CVD) mortality. Psychosocial factors explained 35% of SES inequalities in all-cause mortality, 29% in CVD mortality, 12% in cancer mortality, and 39% in non-CVD, non-cancer mortality. Conclusion Psychosocial factors may account for up to one-third of SES inequalities in deaths from all and specific causes (except cancer mortality). Our findings suggest that interventional studies targeting social relationships and/or psychological distress in older men aiming to reduce socioeconomic inequalities in mortality are warranted.

International audience; Recent developments in the understanding of the relationship between the microbiota and its host have provided evidence regarding the therapeutic potential of selected microorganisms to prevent or treat disease. According to Directive 2001/83/EC, in the European Union (EU), any product intended to prevent or treat disease is defined as a medicinal product and requires a marketing authorization by competent authorities prior to commercialization. Even if the pharmaceutical regulatory framework is harmonized at the EU level, obtaining marketing authorisations for medicinal products remains very challenging for Live Biotherapeutic Products (LBPs). Compared to other medicinal products currently on the market, safety assessment of LBPs represents a real challenge because of their specific characteristics and mode of action. Indeed, LBPs are not intended to reach the systemic circulation targeting distant organs, tissues, or receptors, but rather exert their effect through direct interactions with the complex native microbiota and/or the modulation of complex host-microbiota relation, indirectly leading to distant biological effects within the host. Hence, developers must rely on a thorough risk analysis, and pharmaceutical guidelines for other biological products should be taken into account in order to design relevant non-clinical and clinical development programmes. Here we aim at providing a roadmap for a risk analysis that takes into account the specificities of LBPs. We describe the different risks associated with these products and their interactions with the patient. Then, from that risk assessment, we propose solutions to design non-clinical programmes and First in Human (FIH) early clinical trials appropriate to assess LBP safety.

Objective: Mental health problems among medical students have been widely reported, but the predisposing and perpetuating factors and biological concomitants are poorly understood. Adopting a biopsychosocial approach, we studied well-being in a group of Australian medical students, focusing on sleep, autonomic and immune mechanisms, as well as mental, social and physical well-being, health-related behaviours, and daily functioning. Methods: Fourth-year medical students ( N = 151) completed comprehensive assessments, including laboratory-based and nocturnal autonomic monitoring via ambulatory bioharness, a psychiatric diagnostic interview, and questionnaires assessing sleep quality and psychosocial and physical well-being. A blood sample was taken to quantify the inflammatory marker C-reactive protein. Sleep, mood and activity was additionally monitored daily for 7 days. Results: A sizable minority of students reported diminished physical, mental and psychosocial well-being. We also found concerning levels of sleep disturbance and social and occupational impairment in a subset of students. The strong co-occurrence of problems across symptom domains supported a biopsychosocial interdependence of health and well-being states. Maladaptive coping behaviours were apparent, notably hazardous alcohol consumption, which was associated with a clinically significant elevation in C-reactive protein levels (> 3 mg/L). We documented, for the first time, significantly diminished nocturnal heart rate variability in medical students with a mental health diagnosis. Nocturnal heart rate variability was strongly associated with sleep quality, daytime autonomic stress reactivity, as well as occupational and social functioning. Conclusion: Well-being is a multifaceted phenomenon firmly interlinked with sleep, autonomic and immune function, health behaviours and functional outcomes. Our novel findings supported a key role for nocturnal autonomic function in promoting sleep quality and mental well-being. Interventions could focus on sleep hygiene and health behaviours as a buffer for well-being and teach more adaptive strategies for coping with the stresses of medical training.

The text offers a reappraisal of Walter Benjamin’s Theses on the Philosophy of History (Über den Begriff der Geschichte; ‘On the Concept of History’) from the perspective of global politics today and its similarities with the socio-economic and political situation in Europe and the Americas during the 1920s and 30s; more specifically, the impact of crises on the erosion of trust in liberal representative democracy and the concomitant rise of mostly rightwing populist movements and their strongmen leaders, aided to a significant degree by the media, ‘old’ and ‘new’ alike. The purpose of the text is to draw lessons from Benjamin’s vision of materialist historiography for our current political predicament. Predmet teksta jeste preispitivanje teza O shvatanju istorije (Über den Begriff der Geschichte) Valtera Benjamina iz ugla globalne politike danas i sličnosti sa društveno-ekonomskim i političkim stanjem u Evropi i Americi 20-ih i 30-ih godina 20. veka; preciznije, u članku se raspravlja o uplivu kriza i gubitka poverenja u liberalnu predstavničku demokratiju, kao i pratećeg uspona uglavnom desničarskih populističkih političkih pokreta i njihovih autoritarnih vođa, uz znatnu pomoć medija, i „starih“ i „novih“. Cilj teksta je da ponudi određene pouke iz Benjaminove vizije materijalističke istoriografije radi uspešnijeg nošenja s našim trenutnim političkim (ne)prilikama.

Background/Aim. The era of direct-acting antiviral (DAA) regimen in the treatment of chronic hepatitis C virus (HCV) started in 2011. The aim of this study was to assess the antiviral efficacy and safety of DAA regimen, ombitasvir (OBV)/paritaprevir (PTV)/ritonavir (r) + dasabuvir (DSV) + ribavirin (RBV), in patients with chronic HCV infection, genotype 1. Methods. The real-life data were collected. The study was multicentric and included seven infectious diseases and hepatology departments in Serbia. A total of 21 patients were enrolled in the OBV/PTV/r + DSV + RBV early access program, 20 of which were previously treated with pegylated interferon + RBV, while 1 was treatment-naive. All patients received the adequate doses of these antiviral drugs. RBV was not given to the patients with HCV genotype 1b infection according to the therapeutic protocol. For the majority of patient, the treatment duration lasted for 12 weeks. For the patients with liver cirrhosis, who were infected with HCV genotype 1a, the duration of treatment was 24 weeks. Viremia was assessed at four points in time: at baseline, 4 weeks after the treatment beginning (rapid viral response, RVR), 12 or 24 weeks after the treatment beginning (end of treatment response ? ETR) and 12 weeks after the end of treatment (sustained viral response ? SVR). SVR, as a confirmation of the absence of HCV was considered as endpoint of successful treatment. Results. Complete RVR, ETR and SVR were achieved in 64.71%, 85.71% and 95.24% of the patients, respectively. Only 3 patients had mild adverse effects which did not required dose reduction. Conclusion. The treatment of the patients with a chronic HCV infection with OBV/PTV/r + DSV + RBV resulted in excellent antiviral activity and tolerability.

People with intellectual disabilities (ID) experience high rates of mental health problems, particularly during the period of transition to adulthood. It is therefore important that the transition from child- to adult-oriented health services for people with ID is well managed to ensure appropriate orientation to ongoing adult mental health care. The purpose of this paper is to summarise the impact and experience of transition to adult mental health care for people with ID and those who support them, as well as issues related to current policy and practice in this area. Several opportunities for improvement are identified in the broad areas of policy, service structure and organisation, research and workforce capacity. Enhancements in these areas will lead to improved outcomes for young people with ID transitioning from child- to adult-oriented mental health care.

We have evaluated the clinical significance of deregulated expression of β-catenin and epidermal growth factor receptor (EGFR) during papillary thyroid carcinoma (PTC) progression. Immunohistochemical expression of β-catenin and EGFR was analyzed in 104 archival tissues of PTC and 19 matched lymph node metastases (LNMs). β-catenin (39/104, 37.5%) and EGFR (58/104, 55.7%) were co-expressed and co-localized in primary PTCs (p .0001), which was confirmed by double immunofluorescent staining. The high expression of each molecule, as well as their high cytosolic co-expression, correlated with adverse clinicopathological features of the patients (p .05). High expression of the proteins did not associate with the presence of BRAFV600E mutation (p .05), tested by mutant allele-specific PCR amplification. Although nuclear localization of β-catenin was found in a subset of PTC patients (16/104, 15.4%), no β-catenin mutations were found in exon 3 of the CTNNB1 gene (screened by PCR in combination with denaturing gradient gel electrophoresis and confirmed by next generation sequencing). Cases with additional nuclear β-catenin staining showed strong association with high EGFR expression (15/16, 93.7%), the presence of capsule invasion (12/16, 81.25%) and regional LNM (9/16, 52.3%). In corresponding LNMs, β-catenin and EGFR expressions were maintained at high levels or further increased. Co-expression of high levels of β-catenin and EGFR in association with clinicopathological features implicates their clinical utility in risk stratification of PTC patients, and supports the possibility of crosstalk between Wnt/β-catenin and EGFR signaling during PTC progression.

Epidermal growth factor receptor (EGFR) and its downstream effector, focal adhesion kinase (FAK), have been shown to be overexpressed frequently in human malignancies and implicated in tumour aggressiveness. We aimed to investigate the relationship between EGFR and FAK expression and their possible correlation with the clinical phenotype of patients with papillary thyroid carcinoma (PTC). Expression profiles of EGFR and FAK were analysed in PTC tissue samples (n = 104) by immunohistochemistry and Western blotting. Additionally, EGFR and FAK were immunohistochemically analysed in 20 primary tumours paired with their metastatic tissue in lymph nodes. High expression of EGFR and FAK was found in 55.77% and 57.69% cases, respectively, with a strong positive association between them (P

Purpose: Papillary thyroid carcinoma (PTC) has a strong propensity to metastasize to regional lymph nodes which increases the risk of local-regional relapse and affects the course of the disease. Molecular pathogenesis of lymph node metastasis (LNM) is not yet fully understood. Survivin, a multifunctionale molecule involved in apoptosis, proliferation and angiogenesis, and vascular endothelial growth factor-C (VEGF-C) are suggested to be implicated in lymphatic metastases of human malignancies. Materials and Methods: Expression of survivin and VEGF-C was examined by immunohistochemistry and Western blot in 75 cases of PTCs in relation to their LNM status. Additionally, survivin and VEGF-C were immunohistochemically analyzed in 15 primary PTCs paired with their metastatic tissue in lymph nodes. Results: High expression of survivin and VEGF-C was found in 62.7% and 64.0% cases, respectively, with a positive correlation to each other (Spearman's correlation co-efficient = 0.878, P < 0.001). Expression levels of both proteins were significantly higher in patients with LNM than in those without LNM (P < 0.001). The rate of concomitant high expression of survivin and VEGF-C in patients with LNM involvement was 88.9% (P < 0.01). Metastatic tissue in lymph nodes expressed survivin and VEGF-C at the same high extent as their primary tumors. Conclusion: Concomitant high expression of survivin and VEGF-C is closely associated with LNM status of PTC patients, which suggests their cooperation in the metastatic process. Evaluation of survivin and VEGF-C expression could be clinically significant in predicting the metastatic potential of PTC and subsequent treatment and follow-up of these patients.

Importance Decisions for older adults (aged ≥65 years) and their clinicians about whether to continue to screen for cancer are not easy. Many older adults who are frail or have limited life expectancy or comorbidities continue to be screened for cancer despite guidelines suggesting they should not; furthermore, many older adults have limited knowledge of the potential harms of continuing to be screened. Objective To summarize the patient-reported factors associated with older adults' decisions regarding screening for breast, prostate, colorectal, and cervical cancer. Evidence review Studies were identified by searching databases from January 2000 to June 2020 and were independently assessed for inclusion by 2 authors. Data extraction and risk of bias assessment were independently conducted by 2 authors, and then all decisions were cross-checked and discussed where necessary. Data analysis was performed from September to December 2020. Findings The search yielded 2475 records, of which 21 unique studies were included. Nine studies were quantitative, 8 were qualitative, and 4 used mixed method designs. Of the 21 studies, 17 were conducted in the US, and 10 of 21 assessed breast cancer screening decisions only. Factors associated with decision-making were synthesized into 5 categories: demographic, health and clinical, psychological, physician, and social and system. Commonly identified factors associated with the decision to undergo screening included personal or family history of cancer, positive screening attitudes, routine or habit, to gain knowledge, friends, and a physician's recommendation. Factors associated with the decision to forgo screening included being older, negative screening attitudes, and desire not to know about cancer. Some factors had varying associations, including insurance coverage, living in a nursing home, prior screening experience, health problems, limited life expectancy, perceived cancer risk, risks of screening, family, and a physician's recommendation to stop. Conclusions and relevance Although guidelines suggest incorporating life expectancy and health status to inform older adults' cancer screening decisions, older adults' ingrained beliefs about screening may run counter to these concepts. Communication strategies are needed that support older adults to make informed cancer screening decisions by addressing underlying screening beliefs in context with their perceived and actual risk of developing cancer.

Background With population ageing a significant concern, modifiable factors contributing to healthy ageing must be identified. Autonomic responding reflected by heart rate variability (HRV) has well-established links to general health and wellbeing in younger populations; but has yet to be explored in older individuals. Methods Forty-five healthy participants (49–82 years old) completed questionnaires about sleep and physical and psychological health. Autonomic activity was measured during rest and whilst completing a computerised battery of cognitive tasks. Participants then wore an ambulatory heart rate monitor overnight, and recorded their sleep and physical activity for one week. HRV parameters reflecting cardiac vagal tone were derived from electrocardiograph recordings. Results Age and resting HRV were not related; however a positive association was identified between higher HRV in the 2 h prior to sleep and older age. Higher resting HRV, older age, and better sleep quality significantly predicted psychological wellbeing; and fewer somatic and physical health symptoms and older age predicted better average sleep quality ratings. Older age and poorer general health were significant predictors of cognitive performance deficits. Conclusion These findings suggest that an age-related decline in HRV is not inevitable. Longitudinal designs exploring within-individual changes in cardiac vagal tone are required to better understand the factors contributing to healthy ageing.

STUDY OBJECTIVES: Physiological dearousal characterized by an increase in parasympathetic nervous system activity is important for good-quality sleep. Previous research shows that nocturnal parasympathetic activity (reflected by heart rate variability [HRV]) is diminished in individuals with chronic fatigue syndrome (CFS), suggesting hypervigilant sleep. This study investigated differences in nocturnal autonomic activity across sleep stages and explored the association of parasympathetic activity with sleep quality and self-reported physical and psychological wellbeing in individuals with CFS. METHODS: Twenty-four patients with medically diagnosed CFS, and 24 matched healthy control individuals participated. Electroencephalography and HRV were recorded during sleep in participants’ homes using a minimally invasive ambulatory device. Questionnaires were used to measure self-reported wellbeing and sleep quality. RESULTS: Sleep architecture in patients with CFS differed from that of control participants in slower sleep onset, more awakenings, and a larger proportion of time spent in slow-wave sleep (SWS). Linear mixed-model analyses controlling for age revealed that HRV reflecting parasympathetic activity (normalized high frequency power) was reduced in patients with CFS compared to control participants, particularly during deeper stages of sleep. Poorer self-reported wellbeing and sleep quality was associated with reduced parasympathetic signaling during deeper sleep, but not during wake before sleep, rapid eye movement sleep, or with the proportion of time spent in SWS. CONCLUSIONS: Autonomic hypervigilance during the deeper, recuperative stages of sleep is associated with poor quality sleep and self-reported wellbeing. Causal links need to be confirmed but provide potential intervention opportunities for the core symptom of unrefreshing sleep in CFS. CITATION: Fatt SJ, Beilharz JE, Joubert M, et al. Parasympathetic activity is reduced during slow-wave sleep, but not resting wakefulness, in patients with chronic fatigue syndrome. J Clin Sleep Med. 2020;16(1):19–28.

Background: The efficiency and safety of primary open-angle glaucoma with high-frequency deep sclerotomy (HFDS) combined with cataract surgery has to be investigated. Methods: Right after cataract surgery, HFDS was performed ab interno in 205 consecutive patients with open angle glaucoma. HFDS was performed with a custom-made high-frequency disSection 19 G probe (abee tip 0.3 &times, 1 mm, Oertli Switzerland). The bipolar current with a frequency of 500 kHz is applied. The nasal sclera was penetrated repetitively six times through the trabecular meshwork and consecutively through Schlemm&rsquo, s canal. Every time, a pocket of 0.3 mm high and 0.6 mm width was created. Results: Mean preoperative intraocular pressure (IOP) was 24.5 &plusmn, 2.1 mmHg (range 21 to 48 mmHg). After 48 months, the follow up average IOP was 15.0 &plusmn, 1.7 mmHg (range 10 to 20 mmHg). Postoperative IOP has been significantly reduced compared to preoperative IOP for all studied cases (p &lt, 0.001). After 48 months, the target IOP less than 21 mmHg reached in 84.9%. No serious complications were observed during the surgical procedure itself and in the postoperative period. Conclusions: HFDS is a minimally invasive procedure. It is a safe and efficacious surgical technique for lowering IOP combined with cataract surgery.