Publications by authors named "Paul Mitchell"

1,191 Publications

  • Page 1 of 1

Workplace noise exposure and the prevalence and 10-year incidence of age-related hearing loss.

PLoS One 2021 30;16(7):e0255356. Epub 2021 Jul 30.

Centre for Vision Research, Department of Ophthalmology and Westmead Institute for Medical Research, University of Sydney, NSW, Australia.

There is paucity of population-based data on occupational noise exposure and risk of age-related hearing loss. Therefore, we assessed cross-sectional and longitudinal associations of past workplace noise exposure with hearing loss in older adults. At baseline, 1923 participants aged 50+ years with audiological and occupational noise exposure data included for analysis. The pure-tone average of frequencies 0.5, 1.0, 2.0 and 4.0 kHz (PTA0.5-4KHz) >25 dB HL in the better ear, established the presence of hearing loss. Participants reported exposure to workplace noise, and the severity and duration of this exposure. Prior occupational noise exposure was associated with a 2-fold increased odds of moderate-to-severe hearing loss: multivariable-adjusted OR 2.35 (95% CI 1.45-3.79). Exposure to workplace noise for >10 years increased the odds of having any hearing loss (OR 2.39, 95% CI 1.37-4.19) and moderate-to-severe hearing loss (OR 6.80, 95% CI 2.97-15.60). Among participants reporting past workplace noise exposure at baseline the 10-year incidence of hearing loss was 35.5% versus 29.1% in those who had no workplace noise exposure. Workplace noise exposure was associated with a greater risk of incident hearing loss during the 10-year follow-up: multivariable-adjusted OR 1.39 (95% CI 1.13-1.71). Prior occupational noise exposure was not associated with hearing loss progression. Workplace noise exposure increased the risk of incident hearing loss in older adults. Our findings underscore the importance of preventive measures which diminish noise exposure in the workplace, which could potentially contribute towards reducing the burden of hearing loss in later life.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0255356PLOS
July 2021

Do ethnic patients report longer lung cancer intervals than Anglo-Australian patients?: Findings from a prospective, observational cohort study.

Eur J Cancer Care (Engl) 2021 Jul 26:e13492. Epub 2021 Jul 26.

Department of General Practice and Centre for Cancer Research, Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Melbourne, Victoria, Australia.

Objective: Lung cancer patients from ethnic minorities have poorer outcomes than their Caucasian counterparts. We compared lung cancer intervals between culturally and linguistically diverse (CALD) and Anglo-Australian patients to identify ethnic disparities.

Methods: This was a prospective, observational cohort study comprising a patient survey and reviews of patients' hospital and general practice records. Across three states, 577 (407 Anglo-Australian and 170 CALD) patients were recruited and their hospital records reviewed. The survey was returned by 189 (135 Anglo-Australian and 54 CALD) patients, and a review was completed by general practitioners (GPs) of 99 (76 Anglo-Australian and 23 CALD) patients. Survival and Cox regression analyses were conducted.

Results: CALD patients had longer hospital diagnostic interval [median 30 days, 95% confidence interval (CI) 26-34] than Anglo-Australian patients (median 17, 95% CI 14-20), p = 0.005, hazard ratio (HR) = 1.32 (95% CI 1.09-1.60). This difference persisted after relevant factors were taken into consideration, adjusted HR = 1.26 (95% CI 1.03-1.54, p = 0.022). CALD patients also reported longer prehospital intervals; however, these differences were not statistically significant.

Conclusion: Target interventions need to be developed to address ethnic disparity in hospital diagnostic interval.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/ecc.13492DOI Listing
July 2021

Choroidal nevi in children: prevalence, age of onset, and progression.

J AAPOS 2021 Jul 13. Epub 2021 Jul 13.

Centre for Vision Research, Department of Ophthalmology (Westmead Hospital), The Westmead Institute for Medical Research, University of Sydney, Sydney, Australia.

Purpose: To determine the age of onset and prevalence of choroidal nevi in children.

Methods: In this cross-sectional study, the fundus photographs of a pooled sample of children 6 months to 18 years of age with 6-year longitudinal follow-up who participated in the Sydney Paediatric Eye Disease Study, Sydney Myopia Study, and the Sydney Adolescent Vascular Eye Disease Study were reviewed. Prevalence by age, clinical features, and longitudinal follow-up assessment was undertaken.

Results: Of 7,059 children, 48 children with a choroidal nevus were identified. Prevalence increased with age: <6 years, 0.47%; 6 years, 0.63%; 12 years, 1.06%; 18 years, 1.79%. Nevus was unilateral in all cases (100%), and the majority were melanotic (46, 96%). Most (36 [75%]) were irregular in shape, with ill-defined margins (45 [94%]). All identified nevi were posterior to the equator. All nevi were small, with the average largest basal diameter of 1.6 mm (range, 0.5-3.2) and were not associated with secondary changes (drusen, orange pigment, subretinal fluid). The majority (18/31 [58%]) of nevi remained stable, with 5 of 31 (16%) demonstrating subtle growth (minimum of 600 μm). Four new-onset nevi were documented. Malignant transformation was not observed in any of the nevi.

Conclusions: In our study cohort, the prevalence of choroidal nevi increased with age up to 18 years. The distribution and prevalence of choroidal melanocytic lesions reported herein can be used for designing population-based studies in children that incorporate emerging imaging technologies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jaapos.2021.03.012DOI Listing
July 2021

A Retrospective Review of Primary Percutaneous Endoscopic Gastrostomy and Laparoscopic Gastrostomy Tube Placement.

J Pediatr Gastroenterol Nutr 2021 Jul 9. Epub 2021 Jul 9.

Division of Gastroenterology & Nutrition, Boston Children's Hospital, Boston, MA Clinical Research Center, Boston Children's Hospital, Boston, MA Department of General Surgery, Johns Hopkins All Children's Hospital, St. Petersburg, FL Information Services, Boston Children's Hospital, Boston, MA.

Objectives: The laparoscopic-assisted gastrostomy tube placement (LAP) has increasingly become the preferred method for placing gastrostomy tubes in infants and children. The goal of this retrospective review was to examine our institutional experiences with our transition from the percutaneous endoscopic gastrostomy (PEG) procedure to LAP technique.

Methods: All patients undergoing primary PEG or LAP gastrostomy at Boston Children's Hospital between January 2010 and June 2015 were identified. The primary aim was to compare complication rates within the first 6 months after tube placement; differences in total hospital procedural costs, hospital resource utilization, and postoperative gastroesophageal reflux disease were examined.

Results: 987 patients (442 PEG and 545 LAP gastrostomy tubes) were included. No differences in total complications within 6 months were seen. Patients undergoing PEG placement had more gastrostomy related complications (PEG 30 [6.7%] versus LAP 13 [2.4%], p = 0.0007) and cellulitis (PEG 23 [5.1%] versus LAP 2 [0.4%], p = 0.03) within the first week of placement. Patients undergoing LAP procedures had more granulation tissue episodes (PEG 19 [4.4%] versus LAP 107 [19.8%], p = 0.005). No differences in emergency room visits, hospital readmissions, or postoperative gastroesophageal reflux disease were seen, although transition to a gastrojejunal tube was higher in patients undergoing LAP procedure (PEG 20 patients [4.6%] versus LAP 51 patients [9.5%], p = 0.0008).

Conclusions: Total complications were similar between patients undergoing PEG versus LAP gastrostomy tube placement. Patients with the PEG procedure had more complications within the first week of placement versus patients with the LAP procedure had more granulation skin complications.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MPG.0000000000003236DOI Listing
July 2021

Gene Set Enrichment Analyses Identify Pathways Involved in Genetic Risk for Diabetic Retinopathy.

Am J Ophthalmol 2021 Jun 21. Epub 2021 Jun 21.

Department of Ophthalmology, Harvard Medical School, Massachusetts Eye and Ear Infirmary, Boston, MA; Broad Institute of Harvard and MIT, Cambridge, MA.

Purpose: To identify functionally related genes associated with diabetic retinopathy (DR) risk using gene set enrichment analyses (GSEA) applied to genome-wide association study (GWAS) meta-analyses.

Methods: We analyzed DR GWAS meta-analyses performed on 3,246 Europeans and 2,611 African Americans with type 2 diabetes. Gene sets relevant to five key DR pathophysiology processes were investigated: tissue injury, vascular events, metabolic events and glial dysregulation, neuronal dysfunction, and inflammation. Keywords relevant to these processes were queried in four pathway and ontology databases. Two GSEA methods, Meta-Analysis Gene set Enrichment of variaNT Associations (MAGENTA) and Multi-marker Analysis of GenoMic Annotation (MAGMA) were used. Gene sets were defined to be enriched for gene associations with DR if the P value corrected for multiple testing (Pcorr) was <.05.

Results: Five gene sets were significantly enriched for multiple modest genetic associations with DR in one method (MAGENTA or MAGMA) and also at least nominally significant (uncorrected P <.05) in the other method. These pathways were regulation of the lipid catabolic process (2-fold enrichment, Pcorr=.014); nitric oxide biosynthesis (1.92-fold enrichment, Pcorr=.022); lipid digestion, mobilization and transport (1.6-fold enrichment, P=.032); apoptosis (1.53-fold enrichment, P=.041); and retinal ganglion cell degeneration (2-fold enrichment, Pcorr=.049). The interferon gamma (IFNG) gene, previously implicated in DR by protein-protein interactions in our GWAS, was among the top ranked genes in the nitric oxide pathway (best variant P=.0001).

Conclusions: These GSEA indicate that variants in genes involved in oxidative stress, lipid transport and catabolism and cell degeneration are enriched for genes associated with DR risk.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ajo.2021.06.014DOI Listing
June 2021

Investigation of the mechanisms of VEGF-mediated compensatory lung growth: the role of the VEGF heparin-binding domain.

Sci Rep 2021 Jun 4;11(1):11827. Epub 2021 Jun 4.

Vascular Biology Program, Boston Children's Hospital, Harvard Medical School, Boston, MA, 02115, USA.

Morbidity and mortality for neonates with congenital diaphragmatic hernia-associated pulmonary hypoplasia remains high. These patients may be deficient in vascular endothelial growth factor (VEGF). Our lab previously established that exogenous VEGF164 accelerates compensatory lung growth (CLG) after left pneumonectomy in a murine model. We aimed to further investigate VEGF-mediated CLG by examining the role of the heparin-binding domain (HBD). Eight-week-old, male, C57BL/6J mice underwent left pneumonectomy, followed by post-operative and daily intraperitoneal injections of equimolar VEGF164 or VEGF120, which lacks the HBD. Isovolumetric saline was used as a control. VEGF164 significantly increased lung volume, total lung capacity, and alveolarization, while VEGF120 did not. Treadmill exercise tolerance testing (TETT) demonstrated improved functional outcomes post-pneumonectomy with VEGF164 treatment. In lung protein analysis, VEGF treatment modulated downstream angiogenic signaling. Activation of epithelial growth factor receptor and pulmonary cell proliferation was also upregulated. Human microvascular lung endothelial cells (HMVEC-L) treated with VEGF demonstrated decreased potency of VEGFR2 activation with VEGF121 treatment compared to VEGF165 treatment. Taken together, these data indicate that the VEGF HBD contributes to angiogenic and proliferative signaling, is required for accelerated compensatory lung growth, and improves functional outcomes in a murine CLG model.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-021-91127-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8178332PMC
June 2021

Defining Nonadherence and Nonpersistence to Anti-Vascular Endothelial Growth Factor Therapies in Neovascular Age-Related Macular Degeneration.

JAMA Ophthalmol 2021 07;139(7):769-776

Division of Ophthalmology, Tel Aviv Sourasky Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.

Importance: Poor adherence or persistence to treatment can be a barrier to optimizing clinical practice (real-world) outcomes to intravitreal injection therapy in patients with neovascular age-related macular degeneration (nAMD). Currently, there is a lack of consensus on the definition and classification of adherence specific to this context.

Objective: To describe the development and validation of terminology on patient nonadherence and nonpersistence to anti-vascular endothelial growth factor therapy.

Design, Setting, And Participants: Following a systematic review of currently used terminology in the literature, a subcommittee panel of retinal experts developed a set of definitions and classification for validation. Definitions were restricted to use in patients with nAMD requiring intravitreal anti-vascular endothelial growth factor therapy. Validation by the full nAMD Barometer Leadership Coalition was established using a modified Delphi approach, with predetermined mean scores of 7.5 or more signifying consensus. Subsequent endorsement of the definitions was provided from a second set of retinal experts, with more than 50% members agreeing or strongly agreeing with all definitions.

Main Outcomes And Measures: Development of consensus definitions for the terms adherence and persistence and a classification system for the factors associated with treatment nonadherence or nonpersistence in patients with nAMD.

Results: Nonadherence was defined as missing 2 or more treatment or monitoring visits over a period of 12 months, with a visit considered missed if it exceeded more than 2 weeks from the recommended date. Nonpersistence was defined by nonattendance or an appointment not scheduled within the last 6 months. The additional terms planned discontinuation and transfer of care were also established. Reasons for treatment nonadherence and nonpersistence were classified into 6 dimensions: (1) patient associated, (2) condition associated, (3) therapy associated, (4) health system and health care team associated, (5) social/economic, and (6) other, with subcategories specific to treatment for nAMD.

Conclusions And Relevance: This classification system provides a framework for assessing treatment nonadherence and nonpersistence over time and across different health settings in the treatment of nAMD with current intravitreal anti-vascular endothelial growth factor treatments. This may have additional importance, given the potential association of the coronavirus pandemic on adherence to treatment in patients with nAMD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1001/jamaophthalmol.2021.1660DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8176386PMC
July 2021

Excess mortality and undertreatment in elderly lung cancer patients: treatment nihilism in the modern era?

ERJ Open Res 2021 Apr 24;7(2). Epub 2021 May 24.

Dept of Respiratory Medicine, The Alfred Hospital, Melbourne, Australia.

Treatment of elderly patients with lung cancer is significantly hindered by concerns about treatment tolerability, toxicity and limited clinical trial data in the elderly; potentially giving rise to treatment nihilism amongst clinicians. This study aims to describe survival in elderly patients with lung cancer and explore potential causes for excess mortality. Patients diagnosed with lung cancer in the Victorian Lung Cancer Registry between 2011-2018 were analysed (n=3481). Patients were age-categorised and compared using Cox-regression modelling to determine mortality risk, after adjusting for confounding. Probability of being offered cancer treatments was also determined, further stratified by disease stage. The eldest patients (≥80 years old) had significantly shorter median survival compared with younger age groups (<60 years: 2.0 years; 60-69 years: 1.5 years; 70-79 years: 1.6 years; ≥80 years: 1.0 years; p<0.001). Amongst those diagnosed with stage 1 or 2 lung cancer, there was no significant difference in adjusted-mortality between age groups. However, in those diagnosed with stage 3 or 4 disease, the eldest patients had an increased adjusted-mortality risk of 28% compared with patients younger than 60 years old (p=0.005), associated with markedly reduced probability of cancer treatment, after controlling for sex, performance status, comorbidities and histology type (OR 0.24, compared with <60 years old strata; p<0.001). Compared to younger patients, older patients with advanced-stage lung cancer have a disproportionately higher risk of mortality and lower likelihood of receiving cancer treatments, even when performance status and comorbidity are equivalent. These healthcare inequities could be indicative of widespread treatment nihilism towards elderly patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1183/23120541.00393-2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8141829PMC
April 2021

Challenges in developing capability measures for children and young people for use in the economic evaluation of health and care interventions.

Health Econ 2021 May 25. Epub 2021 May 25.

Health Economics Bristol (HEB), Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.

Methods for measuring outcomes suitable for economic evaluations of health and care interventions have primarily focused on adults. The validity of such methods for children and young people is questionable in areas including the outcome domains measured and how they are measured and valued, with most existing measures narrowly focusing on health. Novel methods for assessing benefits beyond health by focusing on a person's capability have also concentrated on adults to date. This paper aims to set out the rationale for capability measures in children and young people. It argues for the need to expand the evaluative space beyond health functioning towards broader capabilities, with children and young people playing an integral role in capability measure development. Drawing from existing literature, specific challenges related to the identification, measurement, and valuation of capabilities in children and young people are also discussed. Finally, the practical implications for conducting economic evaluation when measuring and valuing capabilities at different stages across the life-course are illustrated. We develop an alternative framework based on conceiving capabilities as evolving across the life-course. This framework may also be helpful in thinking about how to model health outcomes across the life-course.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/hec.4363DOI Listing
May 2021

The Future Burden of Head and Neck Cancers Attributable to Modifiable Behaviors in Australia: A Pooled Cohort Study.

Cancer Epidemiol Biomarkers Prev 2021 May 21. Epub 2021 May 21.

Centre for Big Data Research in Health, University of New South Wales, Sydney, Australia.

Background: Estimates of future burden of cancer attributable to current modifiable causal exposures can guide cancer prevention. We quantified future head and neck cancer burden in Australia attributable to individual and joint causal exposures, and assessed whether these burdens differ between population subgroups.

Methods: We estimated the strength of the associations between exposures and head and neck cancer using adjusted proportional hazards models from pooled data from seven Australian cohorts ( = 367,058) linked to national cancer and death registries and estimated exposure prevalence from the 2017 to 2018 Australian National Health Survey. We calculated population attributable fractions (PAF) with 95% confidence intervals (CI), accounting for competing risk of death, and compared PAFs for population subgroups.

Results: Contemporary levels of current and former smoking contribute 30.6% (95% CI, 22.7%-37.8%), alcohol consumption exceeding two standard drinks per day 12.9% (95% CI, 7.6%-17.9%), and these exposures jointly 38.5% (95% CI, 31.1%-45.0%) to the future head and neck cancer burden. Alcohol-attributable burden is triple and smoking-attributable burden is double for men compared with women. Smoking-attributable burden is also at least double for those consuming more than two alcoholic drinks daily or doing less than 150 minutes of moderate or 75 minutes of vigorous activity weekly, and for those aged under 65 years, unmarried, with low or intermediate educational attainment or lower socioeconomic status, compared with their counterparts.

Conclusions: Two-fifths of head and neck cancers in Australia are preventable by investment in tobacco and alcohol control.

Impact: Targeting men and other identified high-burden subgroups can help to reduce head and neck cancer burden disparities.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1158/1055-9965.EPI-21-0003DOI Listing
May 2021

Enlargement of Geographic Atrophy From First Diagnosis to End of Life.

JAMA Ophthalmol 2021 Jul;139(7):743-750

Department of Ophthalmology, Erasmus University Medical Center, Rotterdam, the Netherlands.

Importance: Treatments for geographic atrophy (GA), a late stage of age-related macular degeneration (AMD), are currently under development. Understanding the natural course is needed for optimal trial design. Although enlargement rates of GA and visual acuity (VA) in the short term are known from clinical studies, knowledge of enlargement in the long term, life expectancy, and visual course is lacking.

Objective: To determine long-term enlargement of GA.

Design, Setting, And Participants: In this study, participant data were collected from 4 population-based cohort studies, with up to 25 years of follow-up and eye examinations at 5-year intervals: the Rotterdam Study cohorts 1, 2, and 3 and the Blue Mountains Eye Study. Data were collected from 1990 to 2015, and data were analyzed from January 2019 to November 2020.

Main Outcomes And Measures: Area of GA was measured pixel by pixel using all available imaging. Area enlargement and enlargement of the square root-transformed area, time until GA reached the central fovea, and time until death were assessed, and best-corrected VA, smoking status, macular lesions according to the Three Continent AMD Consortium classification, a modified version of the Wisconsin age-related maculopathy grading system, and AMD genetic variants were covariates in Spearman, Pearson, or Mann-Whitney analyses.

Results: Of 171 included patients, 106 (62.0%) were female, and the mean (SD) age at inclusion was 82.6 (7.1) years. A total of 147 of 242 eyes with GA (60.7%) were newly diagnosed in our study. The mean area of GA at first presentation was 3.74 mm2 (95% CI, 3.11-4.67). Enlargement rate varied widely between persons (0.02 to 4.05 mm2 per year), with a mean of 1.09 mm2 per year (95% CI, 0.89-1.30). Stage of AMD in the other eye was correlated with GA enlargement (Spearman ρ = 0.34; P = .01). Foveal involvement was already present in incident GA in 55 of 147 eyes (37.4%); 23 of 42 eyes (55%) developed this after a mean (range) period of 5.6 (3-12) years, and foveal involvement did not develop before death in 11 of 42 eyes (26%). After first diagnosis, 121 of 171 patients with GA (70.8%) died after a mean (SD) period of 6.4 (5.4) years. Visual function was visually impaired (less than 20/63) in 47 of 107 patients (43.9%) at last visit before death.

Conclusions And Relevance: In this study, enlargement of GA appeared to be highly variable in the general population. More than one-third of incident GA was foveal at first presentation; those with extrafoveal GA developed foveal GA after a mean of 5.6 years. Future intervention trials should focus on recruiting those patients who have a high chance of severe visual decline within their life expectancy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1001/jamaophthalmol.2021.1407DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8138753PMC
July 2021

Dietary flavonoids are associated with longitudinal treatment outcomes in neovascular age-related macular degeneration.

Eur J Nutr 2021 May 19. Epub 2021 May 19.

Centre for Vision Research, Department of Ophthalmology and The Westmead Institute for Medical Research, The University of Sydney, Sydney, Australia.

Purpose: To assess whether dietary intake of flavonoids are associated with longitudinal treatment outcomes of patients with neovascular age-related macular degeneration (nAMD).

Methods: 547 participants with nAMD were recruited at baseline, 494 were followed-up after receiving 12 months of anti-vascular endothelial growth factor (anti-VEGF) therapy. Baseline dietary intake of flavonoids was determined using a validated food frequency questionnaire. At follow-up, presence of intra-retinal and sub-retinal fluid (IRF and SRF), retinal pigment epithelium detachment and measurements of central macular thickness (CMT) were recorded from optical coherence tomography scans. Visual acuity (VA) was documented using LogMAR charts.

Results: Participants in the first tertile of intake of the flavonol quercetin, and the flavan-3-ols epigallocatechin-3-gallate and epigallocatechin had significantly worse vision than participants in the third tertile-multivariable-adjusted least square (LS) mean VA: 14.68 vs. 19.53 (p = 0.04); 14.06 vs. 18.89 (p = 0.04); 13.86 vs. 18.86 (p = 0.03), respectively. Participants in the first compared to the third tertile of flavan-3-ol, epigallocatechin-3-gallate and epigallocatechin intake all had a twofold higher risk of IRF, multivariable-adjusted p trend of: 0.03, 0.01 and 0.02, respectively. The first vs. the third tertile of tea intake had significantly worse vision (LS mean VA: 13.49 vs. 19.04, p = 0.02), increased risk of IRF (OR 2.13, 95% CI 1.18-3.85) and greater mean CMT (279.59 μm vs. 256.52 μm, p = 0.04).

Conclusions: Higher intakes of dietary flavonoids, specifically flavonols and flavan-3-ols, could be associated with better long-term treatment outcomes in nAMD patients receiving anti-VEGF therapy. Confirmation of these associations in interventional studies could result in promising new therapeutic approaches to the treatment of nAMD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00394-021-02582-4DOI Listing
May 2021

Tackling osteoporosis and fragility fractures in Singapore.

Ann Acad Med Singap 2021 04;50(4):291-293

Osteoporosis and Bone Metabolism Unit, Department of Endocrinology, Singapore General Hospital, Singapore.

View Article and Find Full Text PDF

Download full-text PDF

Source
April 2021

Measuring capability wellbeing in adults at different stages of life for use in economic evaluation of health and care interventions: a qualitative investigation in people requiring kidney care.

Qual Life Res 2021 May 11. Epub 2021 May 11.

Health Economics Bristol (HEB), Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.

Purpose: Capability wellbeing measures, such as the ICECAP measures, have been proposed for use in economic evaluations to capture broader outcomes of health and care interventions. The ICECAP measures have been developed to reflect capabilities at different stages of life. Some patient groups include patients of different ages and at different stages of life, so it is not always apparent which ICECAP measure is most relevant. This study explores the impact of age and life stage on completion, where both ICECAP-A and ICECAP-O were completed by the same patient.

Methods: A think-aloud study, and an associated semi-structured interview were conducted with people receiving kidney care as a renal outpatient, kidney transplant outpatient, or through receiving facility-based haemodialysis. Qualitative analysis focused on (1) differences in responses across measures by individuals, where attributes had conceptual overlap, (2) key factors in self-reported capability levels, and (3) measure preference.

Results: Thirty participants were included in the study, with a mix of older and younger adults. Attributes with similar wording across measures produced similar responses compared to attributes where wording differed. Age and health were key factors for self-reported capability levels. ICECAP-A was slightly preferred overall, including by older adults.

Conclusion: This study suggests use of ICECAP-A in patients with certain chronic health conditions that include a mix of adults across the life course. This study highlights the importance of considering the stage of life when using capability measures and in economic evaluations of health and care interventions more generally.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11136-021-02851-zDOI Listing
May 2021

Effect of ECG-gating Retinal Photographs on Retinal Vessel Caliber Measurements in Subjects with and without Type 2 Diabetes.

Curr Eye Res 2021 May 26:1-9. Epub 2021 May 26.

Department of Cardiology, Westmead Hospital, Sydney, Australia.

: Retinal vessel caliber is an independent risk marker of cardiovascular disease risk. However, variable mechanical delays in capturing retinal photographs and cardiac cycle-induced retinal vascular changes have been shown to reduce the accuracy of retinal vessel caliber measurements, but this has only ever been investigated in healthy subjects. This cross-sectional study is the first study to investigate this issue in type 2 diabetes. The aim of this study was to determine whether ECG-gating retinal photographs reduce the variability in retinal arteriolar and venular caliber measurements in controls and type 2 diabetes.: Fifteen controls and 15 patients with type 2 diabetes were arbitrarily recruited from Westmead Hospital, Sydney, Australia. A mydriatic fundoscope connected to our novel ECG synchronization unit captured 10 ECG-gated (at the QRS) and 10 ungated digital retinal photographs of the left eye in a randomized fashion, blinded to study participants. Two independent reviewers used an in-house semi-automated software to grade single cross-sectional vessel diameters across photographs, between 900 and 1800 microns from the optic disc edge. The coefficient of variation compared caliber variability between retinal arterioles and venules.: Our ECG synchronization unit reported the smallest time delay (33.1 ± 48.4 ms) in image capture known in the literature. All 30 participants demonstrated a higher reduction in retinal arteriolar (ungated: 1.02, 95%CI 0.88-1.17% vs ECG-gated: 0.39, 95%CI 0.29-0.49%, < .0001) than venular (ungated 0.62, 95%CI 0.53-0.73% vs ECG-gated: 0.26, 95%CI 0.19-0.35%, < .0001) coefficient of variation by ECG-gating photographs. Intra-observer repeatability and inter-observer reproducibility analysis reported high interclass correlation coefficients ranging from 0.80 to 0.86 and 0.80 to 0.93 respectively.: ECG-gating photographs at the QRS are recommended for retinal vessel caliber analysis in controls and patients with type 2 diabetes as they refine measurements.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/02713683.2021.1927112DOI Listing
May 2021

Non-ICGA treatment criteria for Suboptimal Anti-VEGF Response for Polypoidal Choroidal Vasculopathy: APOIS PCV Workgroup Report 2.

Ophthalmol Retina 2021 Apr 16. Epub 2021 Apr 16.

Department of Ophthalmology and Visual Sciences The Chinese University of Hong Kong Hong Kong Eye Hospital, Hong Kong.

Purpose: To develop and validate OCT and color fundus photography (CFP) criteria in differentiating polypoidal choroidal vasculopathy (PCV) from typical neovascular age-related macular degeneration (nAMD) in eyes with suboptimal response to anti-vascular endothelial growth factor (VEGF) monotherapy and to determine whether OCT alone can be used to guide photodynamic therapy (PDT) treatment.

Design: Clinical study evaluating diagnostic accuracy.

Participants: Patients with nAMD who received 3-month anti-VEGF monotherapy but had persistent activity defined as subretinal fluid or intraretinal fluid at month 3 assessments.

Methods: In phase 1, international retina experts evaluated OCT and CFP of eyes with nAMD to identify the presence or absence of features due to PCV. The performance of individual and combinations of these features were compared with ICGA. In phase 2, these criteria were applied to an independent image set to assess generalizability. In a separate exercise, retinal experts drew proposed PDT treatment spots using only OCT and near-infrared (NIR) images in eyes with PCV and persistent activity. The location and size of proposed spot were compared with ICGA to determine the extent of coverage of polypoidal lesions (PLs) and branching neovascular network (BNN).

Main Outcome Measures: Sensitivity and specificity of CFP and OCT criteria to differentiate PCV from nAMD and accuracy of coverage of OCT-guided PDT compared with ICGA.

Results: In eyes with persistent activity, the combination of 3 non-ICGA-based criteria (sharp-peaked pigment epithelial detachment [PED], subretinal pigment epithelium [RPE] ring-like lesion, and orange nodule) to detect PCV showed good agreement compared with ICGA, with an area under the receiver operating characteristic curve of 0.85. Validation using both an independent image set and assessors achieved an accuracy of 0.77. Compared with ICGA, the OCT-guided PDT treatment spot covered 100% of PL and 90% of the BNN.

Conclusions: In nAMD eyes with persistent activity, OCT and CFP can differentiate PCV from typical nAMD, which may allow the option of adjunct PDT treatment. Furthermore, OCT alone can be used to plan adjunct PDT treatment without the need for ICGA, with consistent and complete coverage of PL.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.oret.2021.04.002DOI Listing
April 2021

Non-responsive celiac disease in children on a gluten free diet.

World J Gastroenterol 2021 Apr;27(13):1311-1320

Division of Gastroenterology, Hepatology and Nutrition, Boston Children's Hospital, Boston, MA 02115, United States.

Background: Non-responsive celiac disease (NRCD) is defined as the persistence of symptoms in individuals with celiac disease (CeD) despite being on a gluten-free diet (GFD). There is scant literature about NRCD in the pediatric population.

Aim: To determine the incidence, clinical characteristics and underlying causes of NRCD in children.

Methods: Retrospective cohort study performed at Boston Children's Hospital (BCH). Children < 18 years diagnosed with CeD by positive serology and duodenal biopsies compatible with Marsh III histology between 2008 and 2012 were identified in the BCH's Celiac Disease Program database. Medical records were longitudinally reviewed from the time of diagnosis through September 2015. NRCD was defined as persistent symptoms at 6 mo after the initiation of a GFD and causes of NRCD as well as symptom evolution were detailed. The children without symptoms at 6 mo (responders) were compared with the NRCD group. Additionally, presenting signs and symptoms at the time of diagnosis of CeD among the responders and NRCD patients were collected and compared to identify any potential predictors for NRCD at 6 mo of GFD therapy.

Results: Six hundred and sixteen children were included. Ninety-one (15%) met criteria for NRCD. Most were female (77%). Abdominal pain [odds ratio (OR) 1.8 95% confidence interval (CI) 1.1-2.9], constipation (OR 3.1 95%CI 1.9-4.9) and absence of abdominal distension (OR for abdominal distension 0.4 95%CI 0.1-0.98) at diagnosis were associated with NRCD. NRCD was attributed to a wide variety of diagnoses with gluten exposure (30%) and constipation (20%) being the most common causes. Other causes for NRCD included lactose intolerance (9%), gastroesophageal reflux (8%), functional abdominal pain (7%), irritable bowel syndrome (3%), depression/anxiety (3%), eosinophilic esophagitis (2%), food allergy (1%), eating disorder (1%), gastric ulcer with (1%), lymphocytic colitis (1%), aerophagia (1%) and undetermined (13%). 64% of children with NRCD improved on follow-up.

Conclusion: NRCD after ≥ 6 mo GFD is frequent among children, especially females, and is associated with initial presenting symptoms of constipation and/or abdominal pain. Gluten exposure is the most frequent cause.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3748/wjg.v27.i13.1311DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8015304PMC
April 2021

Packet Flow Based Reinforcement Learning MAC Protocol for Underwater Acoustic Sensor Networks.

Sensors (Basel) 2021 Mar 24;21(7). Epub 2021 Mar 24.

Department of Electronic Engineering, University of York, York YO10 5DD, UK.

Medium access control (MAC) is one of the key requirements in underwater acoustic sensor networks (UASNs). For a MAC protocol to provide its basic function of efficient sharing of channel access, the highly dynamic underwater environment demands MAC protocols to be adaptive as well. Q-learning is one of the promising techniques employed in intelligent MAC protocol solutions, however, due to the long propagation delay, the performance of this approach is severely limited by reliance on an explicit reward signal to function. In this paper, we propose a restructured and a modified two stage Q-learning process to extract an implicit reward signal for a novel MAC protocol: Packet flow ALOHA with Q-learning (ALOHA-QUPAF). Based on a simulated pipeline monitoring chain network, results show that the protocol outperforms both ALOHA-Q and framed ALOHA by at least 13% and 148% in all simulated scenarios, respectively.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/s21072284DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8037887PMC
March 2021

EFFICACY AND SAFETY OF INTRAVITREAL AFLIBERCEPT USING A TREAT-AND-EXTEND REGIMEN FOR NEOVASCULAR AGE-RELATED MACULAR DEGENERATION: THE ARIES STUDY.

Retina 2021 Mar 22. Epub 2021 Mar 22.

University of Sydney (Westmead Institute for Medical Research), Sydney, NSW, Australia; Department of Ophthalmology, University of Bonn, Bonn, Germany; Moorfields Eye Hospital, London, United Kingdom; Department of Ophthalmology, University of Padova, Padova, Italy; Department d'Ophtalmologie, Hôpital Intercommunal de Creteil, Creteil, France; Bayer Consumer Care, AG, Pharmaceuticals, Switzerland; Bayer AG, Berlin, Germany; Department for Ophthalmology, Inselspital, University Hospital, University of Bern, Bern, Switzerland.

Purpose: Treating neovascular age-related macular degeneration (nAMD) with intravitreal aflibercept (IVT-AFL) treat-and-extend (T&E) can reduce treatment burden. ARIES assessed whether IVT-AFL early-start T&E was noninferior (NI) to late-start T&E.

Methods: A randomized, open-label, Phase 3b/4 study that included treatment-naïve patients aged ≥50 years with best-corrected visual acuity (BCVA) 73-25 Early Treatment Diabetic Retinopathy Study letters and active choroidal neovascularization secondary to AMD. Patients received 2mg IVT-AFL at Week (W)0, W4, W8, and W16. At W16 patients were randomized 1:1 to early-start (2W interval adjustments) or late-start T&E (8W intervals until W48 then 2W interval adjustments). Primary endpoint: BCVA change from randomization to W104.

Results: 271 patients were randomized. Mean (standard deviation [SD]) BCVA at baseline was 60.2 (12.1; early-T&E) and 61.3 (10.8; late-T&E) letters. Mean (SD) BCVA change (W16-104) was -2.1 (11.4) vs -0.4 (8.4) letters (early- vs late-T&E; least-squares mean difference: -2.0; 95% CI: -4.75 to 0.71; P=0.0162 for NI); +4.3 (13.4) vs +7.9 (11.9) letters (W0-104). Mean (SD) number of injections was 12.0 (2.3) vs 13.0 (1.8). From baseline to W104, 93.4% and 96.2% maintained BCVA; mean (SD) central retinal thickness change was -161.6 (135.6) µm and -158.6 (125.1) µm. Last injection interval (W104) was ≥12W for 47.2% and 51.9% of patients.

Conclusion: Outcomes were similar between patients with nAMD treated with an IVT-AFL early- or late-T&E regimen following initial dosing, with one injection difference over 2 years.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/IAE.0000000000003128DOI Listing
March 2021

Referral for disease-related visual impairment using retinal photograph-based deep learning: a proof-of-concept, model development study.

Lancet Digit Health 2021 01;3(1):e29-e40

Singapore Eye Research Institute, Singapore National Eye Centre, Singapore; Duke-NUS Medical School, Singapore; Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore. Electronic address:

Background: In current approaches to vision screening in the community, a simple and efficient process is needed to identify individuals who should be referred to tertiary eye care centres for vision loss related to eye diseases. The emergence of deep learning technology offers new opportunities to revolutionise this clinical referral pathway. We aimed to assess the performance of a newly developed deep learning algorithm for detection of disease-related visual impairment.

Methods: In this proof-of-concept study, using retinal fundus images from 15 175 eyes with complete data related to best-corrected visual acuity or pinhole visual acuity from the Singapore Epidemiology of Eye Diseases Study, we first developed a single-modality deep learning algorithm based on retinal photographs alone for detection of any disease-related visual impairment (defined as eyes from patients with major eye diseases and best-corrected visual acuity of <20/40), and moderate or worse disease-related visual impairment (eyes with disease and best-corrected visual acuity of <20/60). After development of the algorithm, we tested it internally, using a new set of 3803 eyes from the Singapore Epidemiology of Eye Diseases Study. We then tested it externally using three population-based studies (the Beijing Eye study [6239 eyes], Central India Eye and Medical study [6526 eyes], and Blue Mountains Eye Study [2002 eyes]), and two clinical studies (the Chinese University of Hong Kong's Sight Threatening Diabetic Retinopathy study [971 eyes] and the Outram Polyclinic Study [1225 eyes]). The algorithm's performance in each dataset was assessed on the basis of the area under the receiver operating characteristic curve (AUC).

Findings: In the internal test dataset, the AUC for detection of any disease-related visual impairment was 94·2% (95% CI 93·0-95·3; sensitivity 90·7% [87·0-93·6]; specificity 86·8% [85·6-87·9]). The AUC for moderate or worse disease-related visual impairment was 93·9% (95% CI 92·2-95·6; sensitivity 94·6% [89·6-97·6]; specificity 81·3% [80·0-82·5]). Across the five external test datasets (16 993 eyes), the algorithm achieved AUCs ranging between 86·6% (83·4-89·7; sensitivity 87·5% [80·7-92·5]; specificity 70·0% [66·7-73·1]) and 93·6% (92·4-94·8; sensitivity 87·8% [84·1-90·9]; specificity 87·1% [86·2-88·0]) for any disease-related visual impairment, and the AUCs for moderate or worse disease-related visual impairment ranged between 85·9% (81·8-90·1; sensitivity 84·7% [73·0-92·8]; specificity 74·4% [71·4-77·2]) and 93·5% (91·7-95·3; sensitivity 90·3% [84·2-94·6]; specificity 84·2% [83·2-85·1]).

Interpretation: This proof-of-concept study shows the potential of a single-modality, function-focused tool in identifying visual impairment related to major eye diseases, providing more timely and pinpointed referral of patients with disease-related visual impairment from the community to tertiary eye hospitals.

Funding: National Medical Research Council, Singapore.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/S2589-7500(20)30271-5DOI Listing
January 2021

Changes in Added Sugar Intake and Body Weight in a Cohort of Older Australians: A Secondary Analysis of the Blue Mountains Eye Study.

Front Nutr 2021 1;8:629815. Epub 2021 Mar 1.

Sydney School of Health Sciences, Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia.

The evidence regarding the association between added sugar (AS) intake and obesity remains inconsistent. The aim of this study was to investigate the association between changes in the percentage of energy intake from AS (EAS%) and changes in body weight in a cohort study of older Australians during 15 years of follow-up. In addition, associations were assessed according to whether EAS% intake was provided from beverage or non-beverage sources. Data were analyzed from the participants of the Blue Mountains Eye Study Cohort. Dietary data were collected at baseline (1992-94) and three five-yearly intervals using a 145-item food frequency questionnaire. Participants' body weight was measured at each time point. Five-yearly changes in EAS% intake and body weight were calculated ( = 1,713 at baseline). A generalized estimating equation (GEE) model was used to examine the relationship between the overall five-yearly changes in EAS% intake and body weight, adjusted for dietary and lifestyle variables. In each time interval, the EAS% intake decreased by ~5% in the lowest quartile (Q1) and increased by ~5% in the highest quartile (Q4). The mean (SD) body weight change in Q1 and Q4 were 1.24 (8.10) kg and 1.57 (7.50) kg (first time interval), 0.08 (6.86) kg and -0.19 (5.63) kg (second time interval), and -1.22 (5.16) kg and -0.37 (5.47) kg (third time interval), respectively. In GEE analyses, the overall five-yearly change in EAS% intake was not significantly associated with body weight change ( = 0.837). Furthermore, no significant associations were observed between changes in EAS% intake from either beverage or non-beverage sources and changes in body weight ( = 0.621 and = 0.626). The findings of this older Australian cohort do not support the association between changes in EAS% intake and body weight, regardless of AS food sources (beverage or non-beverage).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fnut.2021.629815DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7957007PMC
March 2021

A multi-ethnic genome-wide association study implicates collagen matrix integrity and cell differentiation pathways in keratoconus.

Commun Biol 2021 03 1;4(1):266. Epub 2021 Mar 1.

Institute for Translational Genomics and Population Sciences, The Lundquist Institute for Biomedical Innovation (formerly Los Angeles Biomedical Research Institute) at Harbor-UCLA Medical Center; Department of Pediatrics, Harbor-UCLA Medical Center, Torrance, CA, USA.

Keratoconus is characterised by reduced rigidity of the cornea with distortion and focal thinning that causes blurred vision, however, the pathogenetic mechanisms are unknown. It can lead to severe visual morbidity in children and young adults and is a common indication for corneal transplantation worldwide. Here we report the first large scale genome-wide association study of keratoconus including 4,669 cases and 116,547 controls. We have identified significant association with 36 genomic loci that, for the first time, implicate both dysregulation of corneal collagen matrix integrity and cell differentiation pathways as primary disease-causing mechanisms. The results also suggest pleiotropy, with some disease mechanisms shared with other corneal diseases, such as Fuchs endothelial corneal dystrophy. The common variants associated with keratoconus explain 12.5% of the genetic variance, which shows potential for the future development of a diagnostic test to detect susceptibility to disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s42003-021-01784-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7921564PMC
March 2021

Genome-wide meta-analysis identifies 127 open-angle glaucoma loci with consistent effect across ancestries.

Nat Commun 2021 02 24;12(1):1258. Epub 2021 Feb 24.

Faculty of Medicine, University of Southampton, Southampton, UK.

Primary open-angle glaucoma (POAG), is a heritable common cause of blindness world-wide. To identify risk loci, we conduct a large multi-ethnic meta-analysis of genome-wide association studies on a total of 34,179 cases and 349,321 controls, identifying 44 previously unreported risk loci and confirming 83 loci that were previously known. The majority of loci have broadly consistent effects across European, Asian and African ancestries. Cross-ancestry data improve fine-mapping of causal variants for several loci. Integration of multiple lines of genetic evidence support the functional relevance of the identified POAG risk loci and highlight potential contributions of several genes to POAG pathogenesis, including SVEP1, RERE, VCAM1, ZNF638, CLIC5, SLC2A12, YAP1, MXRA5, and SMAD6. Several drug compounds targeting POAG risk genes may be potential glaucoma therapeutic candidates.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41467-020-20851-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7904932PMC
February 2021

Retinal Vasculature Fractal and Stroke Mortality.

Stroke 2021 Apr 22;52(4):1276-1282. Epub 2021 Feb 22.

Centre for Vision Research, Westmead Institute for Medical Research, University of Sydney, Australia (G.L., B.G., A.J.W., G.B.M., P.M.).

Background And Purpose: Fractal analysis is a method of quantifying the branching complexity and density of the retinal vessels. We hypothesized that reduced fractal dimension, signifying a sparser vascular network, is associated with long-term stroke mortality.

Methods: We examined the relationship of fractal dimension and stroke mortality in a prospective, population-based cohort of 3143 participants aged 49 years or older. Fractal dimension was measured from digitized fundus photographs using a computer-automated method. Stroke mortality was documented from Australian National Death Index records. We defined reduced fractal dimension as values in the lowest quartile.

Results: Over 12 years, there were 132 (4.2%) stroke-related deaths. Stroke-related mortality was higher in participants with reduced fractal dimension (lowest quartile) compared with the highest quartile (7.7% versus 1.3%, <0.01). After controlling for age, gender, smoking, blood pressure, history of stroke, and other factors, participants with reduced fractal dimension had higher stroke mortality (hazard ratio, 2.42 [95% CI, 1.15-5.07], lowest versus highest quartile). When modeled as a continuous variable, reduced fractal dimension was associated with increased stroke mortality (multivariable-adjusted hazard ratio, 1.26 [95% CI, 1.06-1.51], per SD decrease).

Conclusions: Reduced retinal vascular fractal dimension is independently associated with 12-year stroke mortality. Reduced fractal dimension may indicate cerebral tissue hypoxia and increased risk of stroke.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1161/STROKEAHA.120.031886DOI Listing
April 2021

Efficacy and safety of intravitreal aflibercept for polypoidal choroidal vasculopathy: 96-week outcomes in the Japanese subgroup of the PLANET study.

Jpn J Ophthalmol 2021 May 20;65(3):344-353. Epub 2021 Jan 20.

Department of Ophthalmology, Kyushu University, Fukuoka, Japan.

Purpose: To evaluate the efficacy and safety of intravitreal aflibercept (IVT-AFL) versus IVT-AFL plus rescue photodynamic therapy (IVT-AFL + rPDT) in the subgroup of Japanese patients with polypoidal choroidal vasculopathy (PCV) enrolled in the PLANET study.

Study Design: A 96-week, double-masked, sham-controlled phase-3b/4 randomized clinical trial conducted at multiple centers from May 2014 to August 2016.

Patients And Methods: Patients with PCV (BCVA 73-24 ETDRS letters [20/40-20/320 Snellen]) received 3 initial monthly doses of IVT-AFL 2 mg. At week 12, the patients were randomly assigned 1:1 to IVT-AFL + sham PDT or IVT-AFL + rPDT. Patients not requiring rescue received IVT-AFL every 8 weeks; those requiring rescue received IVT-AFL monthly plus sham/active PDT. Following week 52, the treatment intervals could be extended > 8 weeks.

Results: The baseline demographics for the 159 Japanese patients were balanced. At week 96, the mean BCVA change was + 9.7 (IVT-AFL) versus + 9.5 letters (IVT-AFL + rPDT) (least-squares mean difference of - 0.3; 95% CI, - 3.7 to 3.1); the mean central subfield thickness reduction was - 148.0 µm versus - 145.9 µm. Overall, 17.1% of the patients required rescue PDT. At week 96, 25.0% (IVT-AFL) and 37.9% (IVT-AFL + rPDT) of the patients had complete polyp regression; 84.1% (IVT-AFL) and 88.4% (IVT-AFL + rPDT) of the patients had no evidence of active polyps. The mean number of injections (weeks 52-96) were 4.6 (IVT-AFL) and 4.5 (IVT-AFL + rPDT). Overall, 36.0% (IVT-AFL) and 33.8% (IVT-AFL + rPDT) of the patients experienced ocular treatment-emergent adverse events.

Conclusion: IVT-AFL monotherapy was efficacious for the treatment of Japanese patients with PCV, and the addition of rescue PDT did not show additional benefits.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10384-020-00805-5DOI Listing
May 2021

Perspectives of people with late age-related macular degeneration on mental health and mental wellbeing programmes: a qualitative study.

Ophthalmic Physiol Opt 2021 03 11;41(2):255-265. Epub 2021 Jan 11.

Centre for Vision Research, Department of Ophthalmology, The Westmead Institute for Medical Research, The University of Sydney, Sydney, Australia.

Purpose: People with age-related macular degeneration (AMD) experience high rates of depression, but rarely engage in or have access to tailored mental wellbeing programmes. This qualitative study investigated the perspectives of those primarily with late AMD on mental health and mental wellbeing programmes.

Methods: Twenty-eight people with late AMD in at least one eye, and one person with early AMD in both eyes, aged 56-87 years (mean age 78 years) attending a private eye clinic between December 2019 and January 2020 in Sydney, New South Wales, Australia, participated. Individual semi-structured interviews were conducted and analysed deductively using content analysis, following the individual level factors for health promotion interventions in the behaviour change wheel: Capability (Physical & Psychological), Opportunity (Physical & Social), and Motivation (Reflective & Automatic).

Results: Six major themes were identified: Capability: (1) Impact of vision loss on mobility and leisure pursuits; (2) Adjustment to living with vision loss; Opportunity: (3) Program considerations for those with AMD; (4) Stigma and self-perception of vision loss and mental health; Motivation: (5) Accumulation of vision-related issues as a barrier to participation; (6) Examples of others living with vision loss. General personal factors relevant to delivery of a programme in this age group were also identified: Comorbidities; Limitations using technology; Isolation; Financial concerns and Beliefs that undesired effects of aging are inevitable.

Conclusions: Complex individual, environmental and social factors influence the perspectives of people with late AMD on mental health, and potential participation in mental wellbeing programmes. These factors should be considered when developing and implementing mental wellbeing programmes to improve the emotional and functional rehabilitation outcomes for people with AMD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/opo.12779DOI Listing
March 2021

Comparison of Aerodigestive and Nonaerodigestive Provider Responses to Clinical Case Vignettes.

J Pediatr 2021 May 30;232:166-175.e2. Epub 2020 Dec 30.

Aerodigestive Center, Center for Motility and Functional Gastrointestinal Disorders, Division of Gastroenterology, Hepatology and Nutrition, Boston Children's Hospital, Boston, MA. Electronic address:

Objective: To evaluate differences in practice patterns between aerodigestive and nonaerodigestive providers in pediatric gastroenterology when diagnosing and treating common aerodigestive complaints.

Study Design: A questionnaire comprised of clinical vignettes with multiple-choice questions was distributed to both aerodigestive and nonaerodigestive pediatric gastroenterologists. Vignettes focused on management of commonly encountered general gastroenterology and aerodigestive issues, such as gastroesophageal (GE) reflux, aspiration, and feeding difficulties. Tests of equal proportions were used to compare rates of testing and empiric therapy within and across groups. Multivariate analysis was used to assess differences in response rates between aerodigestive and nonaerodigestive providers.

Results: A total of 88 pediatric gastroenterologists from 18 institutions completed the questionnaire. There were 35 aerodigestive gastroenterology providers and 53 nonaerodigestive gastroenterology providers. The nonaerodigestive group included 31 general gastroenterologists and 22 providers with self-identified subspecialty gastroenterology expertise. Aerodigestive specialists were more likely than nonaerodigestive gastroenterologists to pursue testing over empiric therapy in cases involving isolated respiratory symptoms (P < .05); aerodigestive providers were more likely to recommend pH-impedance testing, videofluoroscopic swallow studies, and upper gastrointestinal barium study (P < .05 for each test) depending on the referring physician. For vignettes involving infant GE reflux, both groups chose empiric treatments more frequently than testing (P < .001), although aerodigestive providers were more likely than nonaerodigestive providers to pursue testing like upper gastrointestinal barium studies (P < .05).

Conclusions: Although some practice patterns were similar between groups, aerodigestive providers pursued more testing than nonaerodigestive providers in several clinical scenarios including infants with respiratory symptoms and GE reflux.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jpeds.2020.12.067DOI Listing
May 2021

A novel tool to assess the quality of RWE to guide the management of retinal disease.

Acta Ophthalmol 2020 Dec 28. Epub 2020 Dec 28.

CHU Bordeaux, Service d'Ophtalmologie, France.

Despite the growing importance of real-world evidence (RWE) for guiding clinical decisions in retinal disease, there is currently no widely used guidance available for assessing the quality and relevance of RWE studies in ophthalmology. This paper summarizes the development of a user-friendly tool that facilitates assessment of the quality of available RWE for neovascular age-related macular degeneration (nAMD), diabetic macular oedema (DME) and retinal vein occlusion (RVO). A literature search was conducted to identify tools developed to assess the quality of RWE, in order to identify the most appropriate framework on which to base this tool. The Good Research for Comparative Effectiveness (GRACE) guidelines was chosen for this purpose as it is designed to assess the quality of observational studies and has been extensively validated, including demonstration of strong sensitivity and specificity. The GRACE guidelines were adapted to develop a straightforward tabular tool that allows simple assessment and comparison of the quality of published evidence in retinal disease for researchers and physicians alike, and includes guidance on treatment details, outcome measures, study population, and controlling for bias. The newly developed tool provides a simple method to support assessment of the strength of evidence and certainty of conclusions drawn from RWE in retinal disease, to ensure clinical decision-making is influenced by the highest quality evidence.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/aos.14698DOI Listing
December 2020
-->