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1.
Int J Cancer ; 2021 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-34847246

RESUMO

Thyroid cancer incidence and the prevalence of overweight and obesity are increasing, but the future thyroid cancer burden attributable to contemporary levels of overweight and obesity has not been evaluated before. We quantified this burden in Australia, and assessed whether the overweight/obesity-attributable burden differed by sex or other population subgroupings. We estimated the strength of the associations of overweight and obesity with thyroid cancer with adjusted proportional hazards models using pooled data from seven Australian cohorts (N=367,058) with 431 thyroid cancer cases ascertained from linked national cancer registry data during a maximum 22-year follow-up. We combined these estimates with nationally representative 2017-2018 estimates of overweight and obesity prevalence to estimate Population Attributable Fractions (PAFs) of future thyroid cancers attributable to overweight and obesity, accounting for competing risk of death, and compared PAFs for population subgroups. Contemporary levels of overweight and obesity explain 18.6% (95%CI=5.2%-30.2%), and obesity alone 13.7% (95%CI=5.2%-21.4%), of the future thyroid cancer burden. The obesity-attributable thyroid cancer burden is 21.4% (95%CI=2.8%-36.5%) for men and 10.1% (95%CI=0.8%-18.6%) for women. Were the currently obese overweight instead, 9.9% (95%CI=1.0%-18.1%) of thyroid cancers could be avoided. The relative overweight/obesity-attributable burden is higher for those consuming on average more than two alcoholic drinks per day (63.4%) and for those who are not married/co-habiting (33.2%). In conclusion, avoiding excess weight, especially obesity, should be a priority for thyroid cancer prevention. Further studies, with findings stratified by tumour size, may reveal the potential role of overdiagnosis in our results. This article is protected by copyright. All rights reserved.

2.
Nutrients ; 13(11)2021 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-34836381

RESUMO

Tinnitus is the phantom perception of sound in the ears or head that increases in prevalence as age increases. With strong evidence supporting the benefits of dietary fibre for vascular health and hearing loss, intake of dietary fibre may also have a role in the prevention of tinnitus symptoms. This longitudinal study aims to determine the association between the intake of dietary fibre and other carbohydrate nutrition variables including glycaemic index (GI), glycaemic load (GL) and total carbohydrate intakes, and incident tinnitus over 10 years. Of the 1730 participants (aged ≥50 years) from the Blue Mountains Hearing Study with complete baseline data on tinnitus symptoms and carbohydrate intakes, 536 (31%) cases of tinnitus were identified and excluded from further incidence analysis. Dietary data were collected using a validated semi-quantitative food frequency questionnaire to determine intakes of total dietary fibre and fibre contributions from cereals, vegetables, and fruit. A purpose-built database based on Australian GI values was used to calculate mean GI. Lower versus higher intakes of fruit fibre (≤3.6 g/day vs. >3.6 g/day) and cereal fibre (≤4.2 g/day vs. >4.2 g/day) were significantly associated with a 65% (HR = 1.65; 95% CI: 1.15-2.36) and 54% (HR = 1.54; 95% CI: 1.07-2.22) increased risk of developing tinnitus over 10 years, respectively. Associations between intake of other carbohydrate nutrients and incident tinnitus were mostly non-significant. In summary, our study showed modest associations between intake of dietary fibre and incident tinnitus. The protective effects of fibre, particularly insoluble fibre, could underlie observed associations by reducing the risk of tinnitus via vascular risk factors such as cardiovascular disease. Further longitudinal studies evaluating different types and sources of fibre and tinnitus risk are needed to confirm our study findings.

3.
Artigo em Inglês | MEDLINE | ID: mdl-34839342

RESUMO

PURPOSE: Review and provide consensus recommendations on use of treat-and-extend (T&E) regimens for neovascular age-related macular degeneration (nAMD) and polypoidal choroidal vasculopathy (PCV) management with relevance for clinicians in the Asia-Pacific region. METHODS: A systematic search of MEDLINE, EMBASE, and Cochrane databases, and abstract databases of the Asia-Pacific Vitreo-retina Society, European Society of Retina Specialists, American Academy of Ophthalmology, and Controversies in Ophthalmology: Asia-Australia congresses, was conducted to assess evidence for T&E regimens in nAMD. Only studies with ≥100 study eyes were included. An expert panel reviewed the results and key factors potentially influencing the use of T&E regimens in nAMD and PCV, and subsequently formed consensus recommendations for their application in the Asia-Pacific region. RESULTS: Twenty-seven studies were included. Studies demonstrated that T&E regimens with aflibercept, ranibizumab, or bevacizumab in nAMD, and with aflibercept in PCV, were efficacious and safe. The recommendation for T&E is, after ≥3 consecutive monthly loading doses, treatment intervals can be extended by 2 to 4 weeks up to 12 to 16 weeks. When disease activity recurs, the recommendation is to reinject and shorten intervals by 2 to 4 weeks until fluid resolution, after which treatment intervals can again be extended. Intraretinal fluid should be treated until resolved; however, persistent minimal subretinal fluid after consecutive treatments may be tolerated with treatment intervals maintained or extended if the clinical condition is stable. CONCLUSIONS: T&E regimens are efficacious and safe for nAMD and PCV, can reduce the number of visits, and minimize the overall burden for clinicians and patients.

4.
J AAPOS ; 2021 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-34728382

RESUMO

PURPOSE: To investigate prevalence and age of onset of choroidal melanocytic lesions (other than nevi) in pediatric patients. METHODS: The pooled data of participants 6 months to 18 years of age in the Sydney Paediatric Eye Disease Study, the Sydney Myopia Study, and the Sydney Adolescent Vascular Eye Disease Study were reviewed retrospectively to identify children with choroidal melanocytic lesions. The clinical features and prevalence by age were assessed. RESULTS: From the pooled sample of 5,533 unique children, 39 cases of focal melanocytic aggregates and 22 cases of choroidal melanocytosis were identified, with overall prevalence of 0.70% and 0.40%, respectively. There was a statistically significant trend toward increased prevalence with increasing age. Both focal melanocytic aggregates and choroidal melanocytosis tended to be bilateral (100% and 86% respectively), brown in color, and temporally located in all cases. Amelanotic variants were not identified. Focal melanocytic aggregates were small (0.15-0.5 mm), whereas choroidal melanocytosis varied in size (5.0-20 mm). All focal melanocytic aggregates were characteristically located 4-5 mm temporal to the center of the fovea and were associated with linear nervelike (11 [28%]) or tortuous vessel like structure (10 [26%]). CONCLUSIONS: In this study, pooled data from large population studies revealed morphologic patterns of choroidal melanocytic lesions, other than nevus, that correlate with described clinical appearance in adults. The association of focal melanocytic aggregates with nervelike structure supports their embryologic origin along the migration path of uveal melanocytes.

5.
J Crohns Colitis ; 2021 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-34788420

RESUMO

BACKGROUND: Children with inflammatory bowel disease (IBD) are disproportionally affected by recurrent Clostridioides difficile infection (rCDI). Although fecal microbiota transplantation (FMT) has been used with good efficacy in adults with IBD, little is known about outcomes associated with FMT in pediatric IBD. METHODS: We performed a retrospective review of FMT at 20 pediatric centers in the United States (US) from March 2012-March 2020. Children with and without IBD were compared to determine differences in the efficacy of FMT for rCDI. In addition, children with IBD with and without a successful outcome were compared to determine predictors of success. Safety data and IBD-specific outcomes were obtained. RESULTS: A total of 396 pediatric patients, including 148 with IBD, were included. Children with IBD were no less likely to have a successful first FMT then the non-IBD affected cohort (76% vs 81%, P=0.17). Among children with IBD, patients were more likely to have a successful FMT if they received FMT with fresh stool (P=0.03), were without diarrhea prior to FMT (P=0.03), or had a shorter time from rCDI diagnosis until FMT (P=0.04). Children with a failed FMT were more likely to have clinically active IBD post-FMT (P=0.002) and 19 (13%) patients had an IBD-related hospitalization in the 3 month follow-up. CONCLUSIONS: Based on the findings from this large US multi-center cohort, the efficacy of FMT for the treatment of rCDI did not differ in children with IBD. Failed FMT among children with IBD was possibly related to the presence of clinically active IBD.

6.
Br J Ophthalmol ; 2021 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-34607789

RESUMO

AIMS: To report the 6-year incidence of optical coherence tomography (OCT)-derived age-related changes in drusen volume and related systemic and ocular associations. METHODS: Chinese adults aged 40 years and older were assessed at baseline and 6 years with colour fundus photography (CFP) and spectral domain (SD) OCT. CFPs were graded for age-related macular degeneration (AMD) features and drusen volume was generated using commercially available automated software. RESULTS: A total of 4172 eyes of 2580 participants (mean age 58.12±9.03 years; 51.12% women) had baseline and 6-year follow-up CFP for grading, of these, 2130 eyes of 1305 participants had gradable SD-OCT images, available for analysis. Based on CFP grading, 136 (3.39%) participants developed incident early AMD and 10 (0.25%) late AMD. Concurrently, retinal pigment epithelial-Bruch's membrane (RPE-BrC) volumes decreased, remained stable and increased in 6.8%, 78.5% and 14.7%, respectively, over 6 years. In eyes where RPE-BrC volumes were >0 mm3 at baseline, this was associated with two-fold higher prevalence rate of any AMD at baseline (p<0.001). Multivariable analysis showed that when compared with eyes where RPE-BrC volume was unchanged, volume decrease was significantly associated with older age (OR=1.30; p<0.001), smoking (OR=2.21; p=0.001) and chronic kidney disease (OR=3.4, p=0.008), while increase was associated with older age (OR=1.36; p<0.001) and hypertension (OR=1.43; p=0.016). CONCLUSION: AMD incidence detected at 6 years on CFP and correlated OCT-derived drusen volume measurement change is low. Older age and some systemic risk factors are associated with drusen volume change, and our data provide new insights into relationship between systemic risk factors and outer retinal morphology in Asian eyes.

7.
Am J Ophthalmol ; 2021 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-34695401

RESUMO

PURPOSE: To investigate the impact of physical activity (PA) on the incidence or progression of age-related macular degeneration (AMD) in the general population. DESIGN: Meta-analysis of longitudinal cohort studies. METHODS: We included a total of 14,630 adults with no or early AMD at baseline from seven population-based studies and examined associations of PA with AMD incidence and progression using multi-state models (MSM) per study and subsequent random effects meta-analysis. Age effects were assessed using meta-regression. MAIN OUTCOME MEASURE: Hazard ratio (HR) for incident early or progression to late AMD. RESULTS: At baseline, mean age ranged from 60.7± 6.9 to 76.4 ± 4.3 years and prevalence of early AMD was 7.7%, ranging from 3.6 to 16.9% between cohorts. During follow-up, 1461 and 189 events occurred for early and late AMD, respectively. In meta-analyses, no or low to moderate PA (high PA as reference) was associated with an increased risk for incident early AMD (HR 1.19; 95%CI=[1.01, 1.40]; p=0.04), but not for late AMD. In subsequent meta-regression, we found no association of age with the effect of PA on incident AMD. CONCLUSIONS: Our study suggests high levels of PA to be protective for the development of early AMD across several population-based cohort studies. Our results establish PA as a modifiable risk factor for AMD and inform further AMD prevention strategies to reduce its public health impact.

8.
FASEB J ; 35(10): e21850, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34569654

RESUMO

Children with hypoplastic lung disease associated with congenital diaphragmatic hernia (CDH) continue to suffer significant morbidity and mortality secondary to progressive pulmonary disease. Recently published work from our lab demonstrated the potential of Roxadustat (FG-4592), a prolyl hydroxylase inhibitor, as a treatment for CDH-associated pulmonary hypoplasia. Treatment with Roxadustat led to significantly accelerated compensatory lung growth (CLG) through downregulation of pigment epithelium-derived factor (PEDF), an anti-angiogenic factor, rather than upregulation of vascular endothelial growth factor (VEGF). PEDF and its role in pulmonary development is a largely unexplored field. In this study, we sought to further evaluate the role of PEDF in accelerating CLG. PEDF-deficient mice demonstrated significantly increased lung volume, total lung capacity, and alveolarization compared to wild type controls following left pneumonectomy without increased VEGF expression. Furthermore, Roxadustat administration in PEDF-deficient mice did not further accelerate CLG. Human microvascular endothelial lung cells (HMVEC-L) and human pulmonary alveolar epithelial cells (HPAEC) similarly demonstrated decreased PEDF expression with Roxadustat administration. Additionally, downregulation of PEDF in Roxadustat-treated HMVEC-L and HPAEC, a previously unreported finding, speaks to the potential translatability of Roxadustat from small animal studies. Taken together, these findings further suggest that PEDF downregulation is the primary mechanism by which Roxadustat accelerates CLG. More importantly, these data highlight the critical role PEDF may have in pulmonary growth and development, a previously unexplored field.


Assuntos
Células Endoteliais/citologia , Células Epiteliais/citologia , Proteínas do Olho/fisiologia , Glicina/análogos & derivados , Isoquinolinas/farmacologia , Pulmão/crescimento & desenvolvimento , Fatores de Crescimento Neural/fisiologia , Serpinas/fisiologia , Animais , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Glicina/farmacologia , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout
9.
BMJ Open ; 11(9): e048658, 2021 09 08.
Artigo em Inglês | MEDLINE | ID: mdl-34497082

RESUMO

OBJECTIVES: We aimed to analyse the degree of carer burden and depressive symptoms in family carers of persons with age-related macular degeneration (AMD) and explore the factors independently associated with carer burden and depressive symptoms. METHODS: Cross-sectional study using self-administered and interviewer-administered surveys, involving 96 family carer-care recipient pairs. Participants were identified from tertiary ophthalmology clinics in Sydney, Australia, as well as the Macular Disease Foundation of Australia database. Logistic regression, Pearson and Spearman correlation analyses were used to investigate associations of explanatory factors (family caregiving experience, carer fatigue, carer quality of life and care-recipient level of dependency) with study outcomes-carer burden and depressive symptoms. RESULTS: Over one in two family carers reported experiencing mild or moderate-severe burden. More than one in five and more than one in three family carers experienced depressive symptoms and substantial fatigue, respectively. High level of care-recipient dependency was associated with greater odds of moderate-severe and mild carer burden, multivariable-adjusted OR 8.42 (95% CI 1.88 to 37.60) and OR 4.26 (95% CI 1.35 to 13.43), respectively. High levels of fatigue were associated with threefold greater odds of the carer experiencing depressive symptoms, multivariable-adjusted OR 3.47 (95% CI 1.00 to 12.05). CONCLUSIONS: A substantial degree of morbidity is observed in family carers during the caregiving experience for patients with AMD. Level of dependency on the family carer and fatigue were independently associated with family carer burden and depressive symptoms. TRIAL REGISTRATION NUMBER: The trial registration number is ACTRN12616001461482. The results presented in this paper are Pre-results stage.


Assuntos
Cuidadores , Degeneração Macular , Estudos Transversais , Depressão/epidemiologia , Humanos , Qualidade de Vida
10.
Clin Exp Ophthalmol ; 2021 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-34378302

RESUMO

BACKGROUND: The prevalence of myopia is increasing globally including in Europe and parts of Asia but Australian data are lacking. This study aim described the change in myopia prevalence in middle-aged Australian adults over approximately a 20-year period. METHODS: Two contemporary Western Australian studies (conducted in mid-late 2010s): the coastal-regional Busselton Healthy Ageing Study (BHAS) and the urban Gen1 of the Raine Study (G1RS) were compared to two earlier studies (early-mid 1990s) in Australia: the urban Blue Mountains Eye Study (BMES) and urban/regional Melbourne Visual Impairment Project (MVIP). Refractive error was measured by autorefraction, vertometry, or subjective refraction. Participants (49-70 years) of European descent without self-reported/diagnosed cataract, corneal disease, or refractive or corneal surgery were included. RESULTS: After exclusions, data were available from 2217, 1760, 700, 2987 and 756 participants from BMES, urban MVIP, regional MVIP, BHAS, and G1RS, respectively. The mean age ranged from 57.1 ± 4.6 years in the G1RS to 60.1 ± 6.0 years in the BMES; 44-48% of participants were male. When stratified by location, the contemporary urban G1RS cohort had a higher age-standardised myopia prevalence than the urban MVIP and BMES cohorts (29.2%, 16.4%, and 23.9%, p < 0.001). The contemporary coastal-regional BHAS had a higher age-standardised myopia prevalence than the regional MVIP cohort (19.4% vs. 13.8%, p = 0.001). CONCLUSIONS: We report an increase in myopia prevalence in older adults in Australia born after World War ll compared to cohorts born before, accounting for urban/regional location. The prevalence of myopia remains relatively low in middle-aged Australian adults.

11.
J Clin Oncol ; 39(30): 3391-3402, 2021 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-34339292

RESUMO

PURPOSE: Non-small-cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 20 insertion (Exon20ins) mutations exhibits inherent resistance to approved tyrosine kinase inhibitors. Amivantamab, an EGFR-MET bispecific antibody with immune cell-directing activity, binds to each receptor's extracellular domain, bypassing resistance at the tyrosine kinase inhibitor binding site. METHODS: CHRYSALIS is a phase I, open-label, dose-escalation, and dose-expansion study, which included a population with EGFR Exon20ins NSCLC. The primary end points were dose-limiting toxicity and overall response rate. We report findings from the postplatinum EGFR Exon20ins NSCLC population treated at the recommended phase II dose of 1,050 mg amivantamab (1,400 mg, ≥ 80 kg) given once weekly for the first 4 weeks and then once every 2 weeks starting at week 5. RESULTS: In the efficacy population (n = 81), the median age was 62 years (range, 42-84 years); 40 patients (49%) were Asian, and the median number of previous lines of therapy was two (range, 1-7). The overall response rate was 40% (95% CI, 29 to 51), including three complete responses, with a median duration of response of 11.1 months (95% CI, 6.9 to not reached). The median progression-free survival was 8.3 months (95% CI, 6.5 to 10.9). In the safety population (n = 114), the most common adverse events were rash in 98 patients (86%), infusion-related reactions in 75 (66%), and paronychia in 51 (45%). The most common grade 3-4 adverse events were hypokalemia in six patients (5%) and rash, pulmonary embolism, diarrhea, and neutropenia in four (4%) each. Treatment-related dose reductions and discontinuations were reported in 13% and 4% of patients, respectively. CONCLUSION: Amivantamab, via its novel mechanism of action, yielded robust and durable responses with tolerable safety in patients with EGFR Exon20ins mutations after progression on platinum-based chemotherapy.

12.
Br J Ophthalmol ; 2021 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-34433549

RESUMO

AIM: To evaluate the effectiveness of dexamethasone intravitreal implant 0.7 mg (DEX; Ozurdex) monotherapy in the patient subgroup of the AUSSIEDEX study with treatment-naïve diabetic macular oedema (DME). METHODS: The open-label, prospective, phase 4, real-world study included pseudophakic eyes and phakic eyes scheduled for cataract surgery that were treatment-naïve or non-responsive to antivascular endothelial growth factors. No eyes were excluded based on baseline best-corrected visual acuity (BCVA) or central subfield retinal thickness (CRT). After the initial DEX injection at the baseline visit, reinjection was permitted at ≥16-week intervals. Week-16 and week-52 visits were mandatory. Primary endpoints were changes in mean BCVA and CRT from baseline to 52 weeks. RESULTS: Of 200 eyes enrolled in the AUSSIEDEX study, 57 were treatment-naïve. Baseline mean BCVA was 58.8 letters and baseline mean CRT was 418.6 µm; changes in mean BCVA and CRT from baseline to 52 weeks in this subgroup were 3.4 letters (p=0.042) and -89.6 µm (p<0.001), respectively, with a mean 2.5 injections. The change in mean CRT from baseline was -55.8 µm at week 16 (p<0.001). The most common adverse event was increased intraocular pressure (IOP), with 20.0% of eyes requiring IOP-lowering medication. One patient was discontinued due to increased IOP. No eyes required filtration surgery. No serious, treatment-related ocular adverse events were reported. CONCLUSION: In this largest prospective, real-world study of DEX monotherapy for DME to date, DEX significantly improved CRT and BCVA at 52 weeks in treatment-naïve eyes, without new safety concerns, supporting DEX use in treatment-naïve DME. TRIAL REGISTRATION NUMBER: NCT02731911.

13.
J Pediatr Gastroenterol Nutr ; 73(2): 178-183, 2021 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-34402809

RESUMO

BACKGROUND: The revised ESPGHAN/NASPGHAN 2016 guideline on the diagnosis and management of Helicobacter pylori (H pylori) infection discourages a "test and treat" strategy. Instead, upper endoscopy (EGD) is recommended when a valid clinical indication is present. Likewise, new treatment recommendations for first-line therapies strongly encourage obtaining antimicrobial susceptibility before treatment. We conducted this study to assess the effect of revised guidelines on clinical practice at our center. METHODS: Retrospective chart review of patients with H pylori infection diagnosis either by serology, stool antigen test, urea breath test, or EGD at Boston Children's Hospital between January 2013 and July 2019. We compared demographic and clinical data between initial guideline and 2016 revision (January 2013 to November 2016) and period after revised guideline (December 2016 to July 2019). RESULTS: Two hundred and fifty-six patients were included. EGD was the initial diagnostic test in 49% (50/103, prerevised guideline) and in 52% (79/153, postrevised guideline). Biopsy culture was sent in 3% of patients for both periods (3/103 and 4/153, respectively). PPI-clarithromycin-amoxicillin triple therapy was the most common regimen in both periods. Clarithromycin use was lower in postrevised guideline period (P = 0.003) whereas the opposite was noted for metronidazole and tetracycline (P = 0.009 and P = 0.02, respectively). There was no significant difference in eradication rate between periods (86% vs 81%). CONCLUSIONS: Low adherence to the updated H pylori guideline recommendations was observed among pediatric gastroenterologists at our center with low use of gastric biopsy culture. The guideline revision was associated with avoidance of clarithromycin use as a second-line therapy, but no change in eradication rates. Future interventions should address the importance of obtaining gastric biopsy culture for antibiotic susceptibilities to guide therapy.


Assuntos
Gastroenterologistas , Infecções por Helicobacter , Helicobacter pylori , Amoxicilina/uso terapêutico , Antibacterianos/uso terapêutico , Criança , Claritromicina/uso terapêutico , Quimioterapia Combinada , Infecções por Helicobacter/diagnóstico , Infecções por Helicobacter/tratamento farmacológico , Humanos , Metronidazol/uso terapêutico , Inibidores da Bomba de Prótons/uso terapêutico , Estudos Retrospectivos
14.
Eur J Cancer Care (Engl) ; 30(6): e13492, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34312918

RESUMO

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.


Assuntos
Grupos Étnicos , Neoplasias Pulmonares , Austrália , Grupo com Ancestrais do Continente Europeu , Humanos , Estudos Prospectivos
15.
J AAPOS ; 25(4): 225.e1-225.e6, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34271212

RESUMO

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 5,533 children (7,059 examinations), 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.


Assuntos
Neoplasias da Coroide , Nevo , Neoplasias Cutâneas , Adolescente , Idade de Início , Criança , Neoplasias da Coroide/diagnóstico , Neoplasias da Coroide/epidemiologia , Estudos Transversais , Humanos , Nevo/epidemiologia , Prevalência
16.
J Pediatr Gastroenterol Nutr ; 73(5): 586-591, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34259651

RESUMO

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: Nine hundred and eighty-seven 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%] vs LAP 13 [2.4%], P = 0.0007) and cellulitis (PEG 23 [5.1%] vs 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%] vs 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%] vs 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.


Assuntos
Refluxo Gastroesofágico , Laparoscopia , Criança , Nutrição Enteral , Refluxo Gastroesofágico/etiologia , Gastrostomia/efeitos adversos , Humanos , Lactente , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos
17.
PLoS One ; 16(7): e0255356, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34329348

RESUMO

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.


Assuntos
Perda Auditiva Provocada por Ruído , Doenças Profissionais , Exposição Ocupacional/efeitos adversos , Idoso , Feminino , Seguimentos , Perda Auditiva Provocada por Ruído/epidemiologia , Perda Auditiva Provocada por Ruído/fisiopatologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Doenças Profissionais/epidemiologia , Doenças Profissionais/fisiopatologia
18.
Am J Ophthalmol ; 233: 111-123, 2021 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-34166655

RESUMO

To identify functionally related genes associated with diabetic retinopathy (DR) risk using gene set enrichment analyses applied to genome-wide association study meta-analyses. METHODS: We analyzed DR GWAS meta-analyses performed on 3246 Europeans and 2611 African Americans with type 2 diabetes. Gene sets relevant to 5 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 4 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 numerous 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.

19.
Sci Rep ; 11(1): 11827, 2021 06 04.
Artigo em Inglês | MEDLINE | ID: mdl-34088930

RESUMO

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.


Assuntos
Heparina/química , Pulmão/fisiopatologia , Fator A de Crescimento do Endotélio Vascular/metabolismo , Animais , Proliferação de Células , Desenho de Fármacos , Células Endoteliais/metabolismo , Teste de Esforço , Hematócrito , Humanos , Pulmão/metabolismo , Pulmão/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Microcirculação , Pneumonectomia , Domínios Proteicos , Transdução de Sinais , Fator A de Crescimento do Endotélio Vascular/química
20.
STAR Protoc ; 2(2): 100581, 2021 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-34151301

RESUMO

High cell viability and recovered cell concentration are typical quality control requirements for single-cell processing and quality data. This protocol describes procedures for sampling, live-cell biobanking, preprocessing for single-cell RNA sequencing, and analysis of fine-needle aspiration (FNA) samples of the skin. The minimally invasive nature of FNA collection is more accepted by patients and allows for frequent longitudinal sampling, resulting in high-quality single-cell sequencing data that capture cellular heterogeneity in clinical samples.

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