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Multiple breath washout (MBW) has successfully assessed the silent lung zone particularly in cystic fibrosis lung disease, however, it is limited to the communicating lung only. There are a number of different pulmonary function methods that can assess what is commonly referred to as trapped air, with varying approaches and sensitivity. Twenty-five people with cystic fibrosis (pwCF) underwent MBW, spirometry, body plethysmography, and spirometry-controlled computed tomography (spiro-CT) on the same day. PwCF also performed extensions to MBW that evaluate air trapping, including our novel extension (MBWShX), which reveals the extent of under-ventilated lung units (UVLU). Additionally, we used 2 previously established 5-breath methods that provide a volume of trapped gas (VTG). We used trapped air % from spiro-CT as the gold standard for comparison. UVLU derived from MBWShX showed the best agreement with trapped air %, both in terms of correlation (RS 0.89, P<0.0001) and sensitivity (79%). Bland-Altman analysis demonstrated a significant underestimation of the VTG by both 5-breath methods (-249ml [95%CI -10796; 580ml] and -203ml [95%CI -997;591ml], respectively). Parameters from both spirometry and body plethysmography were sub-optimal at assessing this pathophysiology. The parameters from MBWShX demonstrated the best relationship with spiro-CT and had the best sensitivity compared to the other pulmonary function methods assessed in this study. MBWShX shows promise to assess and monitor this critical pathophysiological feature, which has been shown to be a driver of lung disease progression in pwCF.
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This is a single arm, open label perioperative trial to assess the feasibility, pharmacokinetics and pharmacodynamics of treatment with safusidenib following biopsy, and prior to surgical resection in patients with IDH1 mutated glioma who have not received radiation therapy or chemotherapy. Fifteen participants will receive treatment in two parts. First, biopsy followed by one cycle (28 days) of safusidenib, an orally available, small molecular inhibitor of mutated IDH1, then maximal safe resection of the tumor (Part A). Second, after recovery from surgery, safusidenib until disease progression or unacceptable toxicity (Part B). This research will enable objective measurement of biological activity of safusidenib in patients with IDH1 mutated glioma. Anti-tumor activity will be assessed by progression free survival and time to next intervention.Clinical Trial Registration: NCT05577416 (ClinicalTrials.gov).
Adult low-grade gliomas (aLGG) are primary brain cancers, defined by mutations in IDH1 or IDH2. When the IDH gene becomes abnormal (mutated), production of a metabolite that causes cancer cells to grow is increased. These tumors grow slowly but invade the normal functioning brain, making them nearly impossible to cure. The current standard of care treatment includes surgery, followed by radiation therapy and chemotherapy, the timing of which depends on the risk of cancer regrowth. Some patients may be suitable for monitoring with MRI scans alone, however recurrences will inevitably occur. Recently developed targeted mutant IDH inhibitors for aLGG patients may be beneficial both at diagnosis and recurrence. Notably, early treatment prior to radiation therapy and chemotherapy delays growth of aLGG and the need for subsequent radiation therapy and chemotherapy. Nevertheless, most patients will eventually suffer further tumor growth and the optimal timing and sequencing of these therapies remains an area of active research. This research investigates the mutant IDH1 inhibitor safusidenib. The researchers are conducting an innovative clinical trial where patients with aLGG, who have not received radiation therapy or chemotherapy, are treated with safusidenib following a biopsy and prior to surgical removal of their tumor. In this study they investigate whether this trial design is safe and feasible, and how safusidenib works; with the goal to better understand the optimal use of IDH inhibitors for patients with aLGG.
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Description: New York State Department of Health (NYSDOH) recommends that all pregnant patients receive human immunodeficiency virus (HIV) screening during pregnancy. This study assessed the prevalence of repeat prenatal HIV testing and factors associated with receipt of the recommended tests. Methods: Data from the NYSDOH newborn screening program were used to randomly select pregnant persons without HIV who delivered a liveborn infant in 2017. Receipt of repeat testing was defined as an initial HIV test in the first or second trimesters and the final in the third trimester (relaxed); or an initial test in the first trimester and the final in the third trimester (strict). Relative risks (RRs) and 95% confidence intervals were calculated in bivariate analyses. Adjusted RRs were calculated to determine associations between demographic and clinical factors and receipt of repeat HIV testing. Results: The cohort included 2,225 individuals. Roughly one quarter (24%) received the recommended tests in the first or second and third trimesters and 17% received them in the first and third trimesters. Individuals who reported Hispanic or Asian race/ethnicities, had government-funded insurance, started prenatal care in the first trimester, delivered in New York City, or received prenatal hepatitis C virus screening were significantly more likely to receive repeat testing using either definition. Conclusions: Despite the benefits and cost-effectiveness, the prevalence of repeat prenatal HIV screening during the third trimester remains persistently low. Improved messaging and targeted education and resources to assist prenatal providers could reinforce the importance of repeat testing and reduce residual perinatal HIV transmission.
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BACKGROUND: Neutrophils are key contributors to chronic airway inflammation in cystic fibrosis (CF) lung disease, although airway and blood-based neutrophil markers are seldom used. The neutrophil-to-lymphocyte ratio (NLR) is an accessible biomarker, the clinical utility of which has not been adequately studied. OBJECTIVE: This study aimed to investigate the characteristics of the NLR in children with CF and its correlations with acute pulmonary exacerbations and spirometry. DESIGN: A previous study had collected clinical data from children with CF for a 3-year period between 2016 and 2021. Retrospectively, NLR values were categorised according to patients' clinical status during blood sample collection as 'stable', 'acute pulmonary exacerbation' or 'elective admission for chronic clinical concern'. MAIN OUTCOME MEASURES: Demographic characteristics associated with the NLR; changes in NLR values in relation to clinical status; relationship between NLR and lung function. RESULTS: 141 children with CF were included. NLR values during clinical stability were higher in females and increased with age. For children admitted for intravenous antibiotics, NLR values significantly increased from clinical stability (median (IQR)=1.13 (0.75-1.51)) to acute pulmonary exacerbations (median (IQR)=1.50 (0.96-2.65), p=0.001), but similar changes were not observed in elective admissions. The NLR was not associated with lung function. CONCLUSIONS: The NLR demonstrated associations with clinical status in children with CF with significant elevations during acute pulmonary exacerbations. While its utility as a single-marker measure is limited, monitoring the NLR over time may help identify periods of increased inflammation.
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BACKGROUND: Late HIV diagnosis is associated with a wide range of negative outcomes. The aim of this study was to identify the characteristics of individuals who received a concurrent diagnosis (CDX) in New York State (NYS) so that more effective interventions can be developed to encourage earlier testing among these populations. METHODS: The NYS HIV registry was used to identify people who received a CDX from 2016 to 2021. A CDX was a diagnosis that met the criteria for a stage 3 HIV infection within 30 days of the initial HIV diagnosis. Sex at birth, race/ethnicity, transmission risk group, age at diagnosis, region of residence at diagnosis, urbanicity of zip code of diagnosis, and type of diagnosing facility were used as covariates. Bivariate and multivariate risk ratios were calculated to quantify associations between CDX and covariates. RESULTS: There were 14,866 people newly diagnosed with HIV in NYS from 2016 to 2021, of which 19.0% had a CDX. Those with female sex at birth, history of injection drug use, or history of male-to-male sexual contact/history of injection drug use risk were less likely to have a CDX. Increased age, Asian race/ethnicity, residence outside of New York City, and diagnosis at inpatient facilities or emergency rooms were associated with an increased likelihood of a CDX. CONCLUSION: Populations with the highest proportions of CDX were ones that made up a small percentage of all new HIV diagnoses and may not be benefiting as much from current HIV prevention efforts. There are complex interactions between many factors including geographic and social characteristics that may lead to delayed diagnostic testing.
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Infecções por HIV , Humanos , Masculino , Feminino , New York/epidemiologia , Adulto , Infecções por HIV/diagnóstico , Infecções por HIV/epidemiologia , Pessoa de Meia-Idade , Adolescente , Adulto Jovem , Diagnóstico Tardio/estatística & dados numéricos , Síndrome da Imunodeficiência Adquirida/diagnóstico , Síndrome da Imunodeficiência Adquirida/epidemiologia , Fatores de RiscoAssuntos
Coinfecção , Fibrose Cística , Infecções por Pseudomonas , Pseudomonas aeruginosa , Infecções Estafilocócicas , Staphylococcus aureus , Fibrose Cística/complicações , Fibrose Cística/microbiologia , Humanos , Infecções por Pseudomonas/complicações , Coinfecção/microbiologia , Infecções Estafilocócicas/complicações , Masculino , Feminino , Adulto , Doença Crônica , CriançaRESUMO
BACKGROUND: The Russian invasion of Ukraine in February 2022 prompted many to provide mental health input, especially trauma management, to Ukrainian children and adolescents (C/A) exposed to it. METHODS: Rapid cascade training of 200 Ukrainian psychologists during 2022 to provide, in pairs, free of charge and without selection, TRT courses of 4-6, 90 min sessions online or face to face to C/A 7 to 23 years in Ukraine and those migrating abroad. CRIES-8 PTSD questionnaires were administered at the beginning and end of the courses during May-December 2022. Age, gender, their geographical war risk, and whether C/A had stayed or migrated elsewhere were collected. A CRIES-8 score of ≥17/40 defined likely PTSD. RESULTS: 3123 C/A completed an initial CRIES-8 questionnaire with matching demographics, 2737 a questionnaire at the end and 1798 both. At entry to TRT, likely PTSD was greater in females (65 %) than males (52 %, p < 0.001) declining with increasing age, particularly in males (p < 0.001). Migration had mixed effects and moving to lower war risk areas or abroad did not reduce PTSD risk. TRT benefited 68 % of C/A overall by reducing CRIES-8 from ≥17 to <17, the rate increasing the more experienced the TRT facilitators became (p < 0.0001). Online and face to face outcomes were the same. LIMITATIONS: The chaos of war prevented capture of all potential C/A questionnaires and long-term repeat testing not yet undertaken. CONCLUSIONS: Even in the chaos of war, effective mental health input can be rapidly and cheaply (c.50 USD/child) provided and should be encouraged.
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Autogestão , Transtornos de Estresse Pós-Traumáticos , Masculino , Criança , Feminino , Humanos , Adolescente , Transtornos de Estresse Pós-Traumáticos/terapia , Transtornos de Estresse Pós-Traumáticos/diagnóstico , Ucrânia , Saúde Mental , Federação RussaRESUMO
BACKGROUND: Demonstrating safety and efficacy of new medical treatments requires clinical trials but clinical trials are costly and may not provide value proportionate to their costs. As most health systems have limited resources, it is therefore important to identify the trials with the highest value. Tools exist to assess elements of a clinical trial such as statistical validity but are not wholistic in their valuation of a clinical trial. This study aims to develop a measure of clinical trials value and provide an online tool for clinical trial prioritisation. METHODS: A search of the academic and grey literature and stakeholder consultation was undertaken to identify a set of criteria to aid clinical trial valuation using multi-criteria decision analysis. Swing weighting and ranking exercises were used to calculate appropriate weights of each of the included criteria and to estimate the partial-value function for each underlying metric. The set of criteria and their respective weights were applied to the results of six different clinical trials to calculate their value. RESULTS: Seven criteria were identified: 'unmet need', 'size of target population', 'eligible participants can access the trial', 'patient outcomes', 'total trial cost', 'academic impact' and 'use of trial results'. The survey had 80 complete sets of responses (51% response rate). A trial designed to address an 'Unmet Need' was most commonly ranked as the most important with a weight of 24.4%, followed by trials demonstrating improved 'Patient Outcomes' with a weight of 21.2%. The value calculated for each trial allowed for their clear delineation and thus a final value ranking for each of the six trials. CONCLUSION: We confirmed that the use of the decision tool for valuing clinical trials is feasible and that the results are face valid based on the evaluation of six trials. A proof-of-concept applying this tool to a larger set of trials with an external validation is currently underway.
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BACKGROUND: Many clinical trials are conducted globally, creating challenges in deciding which trial outcomes deserve a clinician's focus and where to direct limited resources. Determining the 'value' of a clinical trial relative to others could be useful in this context. The aim of this study was to test a novel web-based application using multi-criteria decision analysis (MCDA) to rank clinical trial value. METHODS: The MCDA tool combines seven metrics: unmet need; target population size; access; outcomes; cost; academic impact and use of results. Clinical trials were ranked according to their calculated 'value' - meaning the importance or worth of a trial. We determined face validity of the app using a set of ten published Phase 3 neuro-oncology clinical trials. A survey of neuro-oncology clinicians asked them to rank the same ten clinical trials, and to rank the seven metrics in terms of importance. RESULTS: The two highest app-ranked trials were in concordance with that of the survey respondents, and consistent with the two studies that have had the most impact on routine clinical practice in neuro-oncology. Of the seven metrics, surveyed clinicians considered patient outcomes and unmet need to be the most important when determining clinical trial value. CONCLUSIONS: The metrics app was able to rank and produce a numerical 'value' for existing phase 3 neuro-oncology clinical trials. In the future, a related app to prospectively rank future trials at the startup stage could be developed to help centers determine which should be prioritized to be conducted at their site.
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Aplicativos Móveis , Neoplasias , Humanos , Técnicas de Apoio para a Decisão , Reprodutibilidade dos Testes , Ensaios Clínicos como AssuntoRESUMO
Background: There is an immunologic rationale to evaluate immunotherapy in the older glioblastoma population, who have been underrepresented in prior trials. The NUTMEG study evaluated the combination of nivolumab and temozolomide in patients with glioblastoma aged 65 years and older. Methods: NUTMEG was a multicenter 2:1 randomized phase II trial for patients with newly diagnosed glioblastoma aged 65 years and older. The experimental arm consisted of hypofractionated chemoradiation with temozolomide, then adjuvant nivolumab and temozolomide. The standard arm consisted of hypofractionated chemoradiation with temozolomide, then adjuvant temozolomide. The primary objective was to improve overall survival (OS) in the experimental arm. Results: A total of 103 participants were randomized, with 69 in the experimental arm and 34 in the standard arm. The median (range) age was 73 (65-88) years. After 37 months of follow-up, the median OS was 11.6 months (95% CI, 9.7-13.4) in the experimental arm and 11.8 months (95% CI, 8.3-14.8) in the standard arm. For the experimental arm relative to the standard arm, the OS hazard ratio was 0.85 (95% CI, 0.54-1.33). In the experimental arm, there were three grade 3 immune-related adverse events which resolved, with no unexpected serious adverse events. Conclusions: Due to insufficient evidence of benefit with nivolumab, the decision was made not to transition to a phase III trial. No new safety signals were identified with nivolumab. This complements the existing series of immunotherapy trials. Research is needed to identify biomarkers and new strategies including combinations.
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INTRODUCTION: Glioblastoma is the most common aggressive primary central nervous system cancer in adults characterised by uniformly poor survival. Despite maximal safe resection and postoperative radiotherapy with concurrent and adjuvant temozolomide-based chemotherapy, tumours inevitably recur. Imaging with O-(2-[18F]-fluoroethyl)-L-tyrosine (FET) positron emission tomography (PET) has the potential to impact adjuvant radiotherapy (RT) planning, distinguish between treatment-induced pseudoprogression versus tumour progression as well as prognostication. METHODS AND ANALYSIS: The FET-PET in Glioblastoma (FIG) study is a prospective, multicentre, non-randomised, phase II study across 10 Australian sites and will enrol up to 210 adults aged ≥18 years with newly diagnosed glioblastoma. FET-PET will be performed at up to three time points: (1) following initial surgery and prior to commencement of chemoradiation (FET-PET1); (2) 4 weeks following concurrent chemoradiation (FET-PET2); and (3) within 14 days of suspected clinical and/or radiological progression on MRI (performed at the time of clinical suspicion of tumour recurrence) (FET-PET3). The co-primary outcomes are: (1) to investigate how FET-PET versus standard MRI impacts RT volume delineation and (2) to determine the accuracy and management impact of FET-PET in distinguishing pseudoprogression from true tumour progression. The secondary outcomes are: (1) to investigate the relationships between FET-PET parameters (including dynamic uptake, tumour to background ratio, metabolic tumour volume) and progression-free survival and overall survival; (2) to assess the change in blood and tissue biomarkers determined by serum assay when comparing FET-PET data acquired prior to chemoradiation with other prognostic markers, looking at the relationships of FET-PET versus MRI-determined site/s of progressive disease post chemotherapy treatment with MRI and FET-PET imaging; and (3) to estimate the health economic impact of incorporating FET-PET into glioblastoma management and in the assessment of post-treatment pseudoprogression or recurrence/true progression. Exploratory outcomes include the correlation of multimodal imaging, blood and tumour biomarker analyses with patterns of failure and survival. ETHICS AND DISSEMINATION: The study protocol V.2.0 dated 20 November 2020 has been approved by a lead Human Research Ethics Committee (Austin Health, Victoria). Other clinical sites will provide oversight through local governance processes, including obtaining informed consent from suitable participants. The study will be conducted in accordance with the principles of the Declaration of Helsinki and Good Clinical Practice. Results of the FIG study (TROG 18.06) will be disseminated via relevant scientific and consumer forums and peer-reviewed publications. TRIAL REGISTRATION NUMBER: ANZCTR ACTRN12619001735145.
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Neoplasias Encefálicas , Ficus , Glioblastoma , Adulto , Humanos , Adolescente , Glioblastoma/diagnóstico por imagem , Glioblastoma/terapia , Glioblastoma/patologia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Tirosina , Estudos Prospectivos , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/terapia , Neoplasias Encefálicas/patologia , Recidiva Local de Neoplasia/diagnóstico por imagem , Austrália , Tomografia por Emissão de Pósitrons , Imageamento por Ressonância Magnética , Ensaios Clínicos Fase II como Assunto , Estudos Multicêntricos como AssuntoRESUMO
BACKGROUND: Handheld spirometry allows monitoring of lung function at home, of particular importance during the COVID-19 pandemic. Pediatric studies are unclear on whether values are interchangeable with traditional, clinic-based spirometry. We aimed to assess differences between contemporaneous, home (unsupervised) and clinic (supervised) spirometry and the variability of the former. The accuracy of the commercially available spirometer used in the study was also tested. METHODS: Data from participants in the Clinical Monitoring and Biomarkers to stratify severity and predict outcomes in children with cystic fibrosisc (CLIMB-CF) Study aged ≥ 6 years who had paired (±1 day) clinic and home forced expiratory volume in 1 s (FEV1 ) readings were analyzed. Variability during clinical stability over 6-months was assessed. Four devices from Vitalograph were tested using 1 and 3 L calibration syringes. RESULTS: Sixty-seven participants (median [interquartile range] age 10.7 [7.6-13.9] years) provided home and clinic FEV1 data pairs. The mean (SD) FEV1 % bias was 6.5% [±8.2%]) with wide limits of agreement (-9.6% to +22.7%); 76.2% of participants recorded lower results at home. Coefficient of variation of home FEV1 % during stable periods was 9.9%. Data from the testing of the handheld device used in CLIMB-CF showed a potential underread. CONCLUSION: In children and adolescents, home spirometry using hand-held equipment cannot be used interchangeably with clinic spirometry. Home spirometry is moderately variable during clinical stability. New handheld devices underread, particularly at lower volumes of potential clinical significance for smaller patients; this suggests that supervision does not account fully for the discrepancy. Opportunities should be taken to obtain dual device measurements in clinic, so that trend data from home can be utilized more accurately.
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COVID-19 , Fibrose Cística , Adolescente , Humanos , Criança , Fibrose Cística/diagnóstico , Pandemias , COVID-19/diagnóstico , Espirometria , Volume Expiratório ForçadoRESUMO
BACKGROUND: The COVID-19 pandemic led to an increase in the number of deaths among all populations, including people with diagnosed HIV (PWDH). The aim of this study was to analyze the top causes of death (COD) among PWDH before the start of the COVID-19 pandemic, during the start of the COVID-19 pandemic, and a year later; to determine changes in the leading COD among PWDH; and to determine whether the historical trend of decreasing deaths related to HIV continued through the pandemic. METHODS: To examine mortality among PWDH in New York State (NYS), records for PWDH who died from 2015 to 2021 were extracted from the NYS HIV registry and Vital Statistics Death Data. RESULTS: The number of deaths among PWDH in NYS increased 32% from 2019 to 2020 and continued in 2021. COVID-19 was one of the most common underlying COD among PWDH in 2020. In 2021, COVID-19-related deaths decreased while HIV and diseases of the circulatory system remained the top COD. HIV listed as either the underlying or contributing COD showed a consistent downward trend in the percentage of HIV-related deaths among PWDH, from 45% in 2015 to 32% in 2021. CONCLUSIONS: There was a large increase in deaths among PWDH in 2020, with a substantial percentage related to COVID-19. However, even with the introduction of COVID-19 in 2020, the percentage of deaths related to HIV-one of the goals of the Ending the Epidemic Initiative in NYS-continued to decrease.
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COVID-19 , Infecções por HIV , Humanos , Infecções por HIV/epidemiologia , Pandemias , HIV , Causas de Morte , MortalidadeRESUMO
BACKGROUND: Olutasidenib (FT-2102) is a highly potent, orally bioavailable, brain-penetrant and selective inhibitor of mutant isocitrate dehydrogenase 1 (IDH1). The aim of the study was to determine the safety and clinical activity of olutasidenib in patients with relapsed/refractory gliomas harboring an IDH1R132X mutation. METHODS: This was an open-label, multicenter, nonrandomized, phase Ib/II clinical trial. Eligible patients (≥18 years) had histologically confirmed IDH1R132X-mutated glioma that relapsed or progressed on or following standard therapy and had measurable disease. Patients received olutasidenib, 150 mg orally twice daily (BID) in continuous 28-day cycles. The primary endpoints were dose-limiting toxicities (DLTs) (cycle 1) and safety in phase I and objective response rate using the Modified Response Assessment in Neuro-Oncology criteria in phase II. RESULTS: Twenty-six patients were enrolled and followed for a median 15.1 months (7.3â19.4). No DLTs were observed in the single-agent glioma cohort and the pharmacokinetic relationship supported olutasidenib 150 mg BID as the recommended phase II dose. In the response-evaluable population, disease control rate (objective response plus stable disease) was 48%. Two (8%) patients demonstrated a best response of partial response and eight (32%) had stable disease for at least 4 months. Grade 3â4 adverse events (≥10%) included alanine aminotransferase increased and aspartate aminotransferase increased (three [12%], each). CONCLUSIONS: Olutasidenib 150 mg BID was well tolerated in patients with relapsed/refractory gliomas harboring an IDH1R132X mutation and demonstrated preliminary evidence of clinical activity in this heavily pretreated population.
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Glioma , Quinolinas , Humanos , Piridinas , Glioma/tratamento farmacológico , Glioma/genética , Isocitrato Desidrogenase/genéticaRESUMO
BACKGROUND: Aspergillus fumigatus (Af) infection is associated with poor lung health in chronic suppurative lung diseases but often goes undetected. We hypothesised that inhibition of Af growth by Pseudomonas aeruginosa (Pa) increases the frequency of false-negative Af culture in co-infected people. Using a substantial group of cystic fibrosis (CF) airway samples, we assessed the relationship between Af and bacterial pathogens, additionally comparing fungal culture with next-generation sequencing. METHODS: Frequency of co-culture was assessed for 44,554 sputum/BAL cultures, from 1,367 CF patients between the years 2010-2020. In a subgroup, Internal Transcribed Spacer-2 (ITS2) fungal sequencing was used to determine sequencing-positive, culture-negative (S+/C-) rates. RESULTS: Pa+ samples were nearly 40% less likely (P<0.0001) than Pa- samples to culture Af, an effect that was also seen with some other Gram-negative isolates. This impact varied with Pa density and appeared to be moderated by Staphylococcus aureus co-infection. Sequencing identified Af-S+/C- for 40.1% of tested sputa. Samples with Pa had higher rates of Af-S+/C- (49.3%) than those without (35.7%; RR 1.38 [1.02-1.93], P<0.05). Af-S+/C- rate was not changed by other common bacterial infections. Pa did not affect the S+/C- rates of Candida, Exophiala or Scedosporium. CONCLUSIONS: Pa/ Af co-positive cultures are less common than expected in CF. Our findings suggest an Af-positive culture is less likely in the presence of Pa. Interpretation of negative cultures should be cautious, particularly in Pa-positive samples, and a companion molecular diagnostic could be useful. Further work investigating mechanisms, alternative detection techniques and other chronic suppurative lung diseases is needed.
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Aspergilose , Fibrose Cística , Infecções Estafilocócicas , Humanos , Fibrose Cística/complicações , Fibrose Cística/diagnóstico , Fibrose Cística/epidemiologia , Aspergillus , Aspergilose/microbiologia , Pulmão , Infecções Estafilocócicas/complicações , Bactérias , Pseudomonas aeruginosaRESUMO
BACKGROUND: Glioma accounts for approximately 80% of malignant adult brain cancer and its most common subtype, glioblastoma, has one of the lowest 5-year cancer survivals. Fifty risk-associated variants within 34 glioma genetic risk regions have been found by genome-wide association studies (GWAS) with a sex difference reported for 8q24.21 region. We conducted an Australian GWAS by glioma subtype and sex. METHODS: We analyzed genome-wide data from the Australian Genomics and Clinical Outcomes of Glioma (AGOG) consortium for 7 573 692 single nucleotide polymorphisms (SNPs) for 560 glioma cases and 2237 controls of European ancestry. Cases were classified as glioblastoma, non-glioblastoma, astrocytoma or oligodendroglioma. Logistic regression analysis was used to assess the associations of SNPs with glioma risk by subtype and by sex. RESULTS: We replicated the previously reported glioma risk associations in the regions of 2q33.3 C2orf80, 2q37.3 D2HGDH, 5p15.33 TERT, 7p11.2 EGFR, 8q24.21 CCDC26, 9p21.3 CDKN2BAS, 11q21 MAML2, 11q23.3 PHLDB1, 15q24.2 ETFA, 16p13.3 RHBDF1, 16p13.3 LMF1, 17p13.1 TP53, 20q13.33 RTEL, and 20q13.33 GMEB2 (P < .05). We also replicated the previously reported sex difference at 8q24.21 CCDC26 (P = .0024) with the association being nominally significant for both sexes (P < .05). CONCLUSIONS: Our study supports a stronger female risk association for the region 8q24.21 CCDC26 and highlights the importance of analyzing glioma GWAS by sex. A better understanding of sex differences could provide biological insight into the cause of glioma with implications for prevention, risk prediction and treatment.
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Neoplasias Encefálicas , Glioblastoma , Glioma , Feminino , Humanos , Adulto , Masculino , Estudo de Associação Genômica Ampla , Predisposição Genética para Doença , Austrália , Glioma/genética , Neoplasias Encefálicas/genética , Glioblastoma/genética , Polimorfismo de Nucleotídeo Único , Estudos de Casos e Controles , Proteínas do Tecido Nervoso , Peptídeos e Proteínas de Sinalização Intracelular/genéticaRESUMO
BACKGROUND: Real-world data (RWD) is increasingly being embraced as an invaluable source of information to address clinical and policy-relevant questions that are unlikely to ever be answered by clinical trials. However, the largely unrealised potential of RWD is the value to be gained by supporting prospective studies and translational research. Here we describe the design and implementation of an Australian brain cancer registry, BRAIN, which is pursuing these opportunities. METHODS: BRAIN was designed by a panel of clinicians in conjunction with BIOGRID to capture comprehensive clinical data on patients diagnosed with brain tumours from diagnosis through treatment to recurrence or death. Extensive internal and external testing was undertaken, followed by implementation at multiple sites across Victoria and Tasmania. RESULTS: Between February 2021 and December 2021, a total of 350 new patients from 10 sites, including one private and two regional, were entered into BRAIN. Additionally, BRAIN supports the world's first registry trial in neuro-oncology, EX-TEM, addressing the optimal duration of post-radiation temozolomide; and BioBRAIN, a dedicated brain tumour translational program providing a pipeline for biospecimen collection matched with linked clinical data. CONCLUSIONS: Here we report on the first data collection effort in brain tumours for Australia, which we believe to be unique worldwide given the number of sites and patients involved and the extent to which the registry resource is being leveraged to support clinical and translational research. Further directions such as passive data flow and data linkages, use of artificial intelligence and inclusion of patient-entered data are being explored.
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Inteligência Artificial , Neoplasias Encefálicas , Neoplasias Encefálicas/epidemiologia , Neoplasias Encefálicas/terapia , Coleta de Dados , Humanos , Estudos Prospectivos , Sistema de Registros , VitóriaRESUMO
OBJECTIVES: The purpose of this study was to compare the American Society of Echocardiography (ASE) algorithm for assessing mitral regurgitation (MR) to cardiac magnetic resonance (CMR) and left ventricular (LV) remodeling following mitral intervention. BACKGROUND: The ASE recommends integrating multiple echocardiographic parameters for assessing MR. The ASE guidelines include an algorithm that weighs the parameters and highlights those considered indicative of definitely mild or definitely severe MR. METHODS: We prospectively enrolled 152 (age 62 ± 13 years; 59% male) patients with degenerative MR who underwent ASE algorithm-guided echocardiographic and CMR grading of MR severity. Using the ASE algorithm, patients were graded as definitely mild, grade I, grade II, grade III, grade IV, or definitely severe MR. CMR MR volume was graded as mild (<30 mL), grade II moderate (30-44 mL), grade III moderate (45-59 mL), or severe (≥60 mL). A subgroup of 63 patients underwent successful mitral intervention, of whom 48 had postintervention CMR. RESULTS: Only 52% of patients with definitely severe MR by the ASE algorithm had severe MR by CMR, and 10% had mild MR by CMR. There was an increase in post mitral intervention LV reverse remodeling with worsening MR severity using CMR (P < 0.0001) but not the ASE algorithm (P = 0.07). Severe MR by CMR was an independent predictor of post mitral intervention LV reverse remodeling and definitely severe MR by the ASE algorithm was not. CONCLUSIONS: In patients with degenerative MR, agreement between CMR and the ASE algorithm was suboptimal. Severe MR by CMR was an independent predictor of post mitral intervention LV reverse remodeling, whereas definitely severe MR by the ASE algorithm was not. These findings suggest an important role for CMR in surgical decision making in degenerative MR. (Comparison Study of Echocardiography and Cardiovascular Magnetic Resonance Imaging in the Assessment of Mitral and Aortic Regurgitation; NCT04038879).
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Insuficiência da Valva Mitral , Idoso , Algoritmos , Ecocardiografia , Feminino , Humanos , Imageamento por Ressonância Magnética , Espectroscopia de Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Índice de Gravidade de Doença , Estados Unidos , Remodelação VentricularRESUMO
PURPOSE: High-grade disease accounts for ~ 70% of all glioma, and has a high mortality rate. Few modifiable exposures are known to be related to glioma risk or mortality. METHODS: We examined associations between lifetime physical activity and physical activity at different ages (15-18 years, 19-29 years, 30-39 years, last 10 years) with the risk of glioma diagnosis, using data from a hospital-based family case-control study (495 cases; 371 controls). We followed up cases over a median of 25 months to examine whether physical activity was associated with all-cause mortality. Physical activity and potential confounders were assessed by self-administered questionnaire. We examined associations between physical activity (metabolic equivalent [MET]-h/wk) and glioma risk using unconditional logistic regression and with all-cause mortality in cases using Cox regression. RESULTS: We noted a reduced risk of glioma for the highest (≥ 47 MET-h/wk) versus lowest (< 24 METh/wk) category of physical activity for lifetime activity (OR = 0.58, 95% CI: 0.38-0.89) and at 15-18 years (OR = 0.57, 95% CI: 0.39-0.83). We did not observe any association between physical activity and all-cause mortality (HR for lifetime physical activity = 0.91, 95% CI: 0.64-1.29). CONCLUSION: Our findings are consistent with previous research that suggested physical activity during adolescence might be protective against glioma. Engaging in physical activity during adolescence has many health benefits; this health behavior may also offer protection against glioma.
Assuntos
Exercício Físico , Glioma , Adolescente , Estudos de Casos e Controles , Seguimentos , Glioma/epidemiologia , Humanos , Fatores de RiscoRESUMO
In children with very severe cerebral palsy, an adversarial legal process for medical negligence, when liability is admitted, requires an estimate of life expectancy. Medical experts using the same cohort data and the same clinical facts can produce quite different life expectancies, leading to arguments in legal conferences and courts. The issues that commonly arise include between-country comparisons, projected and therapy-induced advanced life expectancies, and the contribution of epilepsy, scoliosis, and especially cognition to life expectancy. In this review, these factors are discussed from an arithmetic, statistical, and medical viewpoint to initiate debate on the issue, including whether median survival should be advocated.