Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 781
Filtrar
1.
Int J Cancer ; 2020 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-33038275

RESUMO

Obesity is a risk factor for several major cancers. Associations of weight change in middle adulthood with cancer risk, however, are less clear. We examined the association of change in weight and body mass index (BMI) category during middle adulthood with 42 cancers, using multivariable Cox proportional hazards models in the European Prospective Investigation into Cancer and Nutrition cohort. Of 241 323 participants (31% men), 20% lost and 32% gained weight (>0.4 to 5.0 kg/year) during 6.9 years (average). During 8.0 years of follow-up after the second weight assessment, 20 960 incident cancers were ascertained. Independent of baseline BMI, weight gain (per one kg/year increment) was positively associated with cancer of the corpus uteri (hazard ratio HR = 1.14; 95% confidence interval: 1.05-1.23). Compared to stable weight (+/-0.4 kg/year), weight gain (>0.4 to 5.0 kg/year) was positively associated with cancers of the gallbladder and bile ducts (HR = 1.41; 1.01-1.96), post-menopausal breast (HR = 1.08, 1.00-1.16) and thyroid (HR = 1.40; 1.04-1.90). Compared to maintaining normal weight, maintaining overweight or obese BMI (World Health Organization categories) was positively associated with most obesity-related cancers. Compared to maintaining the baseline BMI category, weight gain to a higher BMI category was positively associated with cancers of the post-menopausal breast (HR = 1.19; 1.06-1.33), ovary (HR = 1.40; 1.04-1.91), corpus uteri (HR = 1.42; 1.06-1.91), kidney (HR = 1.80; 1.20-2.68) and pancreas in men (HR = 1.81; 1.11-2.95). Losing weight to a lower BMI category, however, was inversely associated with cancers of the corpus uteri (HR = 0.40; 0.23-0.69) and colon (HR = 0.69; 0.52-0.92). Our findings support avoiding weight gain and encouraging weight loss in middle adulthood.

2.
Int J Cancer ; 2020 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-33038280

RESUMO

Obesity is considered a chronic inflammatory state characterised by continued secretion of adipokines and cytokines. Experimental and epidemiological evidence indicates that circulating adipokines may be associated with the development of obesity-related cancers, but it is unclear if these associations are causal or confounded. We examined potential causal associations of specific adipokines [adiponectin, leptin, soluble leptin receptor (sOB-R), and plasminogen activator inhibitor-1 (PAI-1)] with five obesity-related cancers (colorectal, pancreatic, renal cell carcinoma, ovarian, and endometrial) using Mendelian randomization (MR) methods. We used summary-level data from large genetic consortia for 114 530 cancer cases and 245 284 controls. We constructed genetic instruments using 18 genetic variants for adiponectin, 2 for leptin, and 4 for both sOB-R and PAI-1 (P-value for inclusion<5 ˟ 10-8 ). Causal estimates were obtained using two-sample MR methods. In the inverse-variance weighted models, we found an inverse association between adiponectin and risk of colorectal cancer [odds ratio (OR) per 1 µg/mL increment in adiponectin concentration: 0.90 (95% confidence interval [CI]: 0.84-0.97); P: 0.01]; but, evidence of horizontal pleiotropy was detected and the association was not present when this was taken into consideration. No association was found for adiponectin and risks of pancreatic cancer, renal cell carcinoma, ovarian cancer, and endometrial cancer. Leptin, sOB-R and PAI-1 were also similarly unrelated to risk of obesity-related cancers. Despite the large sample size, our MR analyses do not support causal effects of circulating adiponectin, leptin, sOB-R, and PAI-1 concentrations on the development of five obesity-related cancers. This article is protected by copyright. All rights reserved.

3.
J Biol Chem ; 2020 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-33028632

RESUMO

The molecular mechanisms of reduced frataxin (FXN) expression in Friedreich's ataxia (FRDA) are linked to epigenetic modification of the FXN locus caused by the disease-associated GAA expansion. Here, we identify that SUV4-20 histone methyltransferases, specifically SUV4-20 H1, play an important role in the regulation of FXN expression and represent a novel therapeutic target. Using a human FXN-GAA-Luciferase repeat expansion genomic DNA reporter model of FRDA, we screened the Structural Genomics Consortium epigenetic probe collection. We found that pharmacological inhibition of the SUV4-20 methyltransferases by the tool compound A-196 increased the expression of FXN by approximately 1.5-fold in the reporter cell line. In several FRDA cell lines and patient-derived primary peripheral blood mononuclear cells A-196 increased FXN expression by up to 2-fold, an effect not seen in wild-type cells. SUV4-20 inhibition was accompanied by a reduction in H4K20me2 and H4K20me3 and an increase in H4K20me1, but only modest (1.4-7.8%) perturbation in genome-wide expression was observed. Finally, based on the structural activity relationship and crystal structure of A-196, novel small molecule A-196 analogues were synthesized and shown to give a 20-fold increase in potency for increasing FXN expression. Overall, our results suggest that histone methylation is important in the regulation of FXN expression, and highlight SUV4-20 H1 as a potential novel therapeutic target for FRDA.

4.
J Surg Educ ; 2020 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-33077417

RESUMO

OBJECTIVE: Laparoscopic simulation is widely used in surgical training. However, the impact of training on performance is difficult to assess. Observation is time-intensive and subjective. SurgTrac laparoscopic box-trainer instrument tracking software provides continuous, automated, real-time, objective performance feedback. We used this data to assess the relationship between task attempts and performance. We assessed whether improvement in performance with repetition could be modeled in learning curves that might be used for benchmarking. DESIGN: Anonymized SurgTrac data for performances undertaken between 10/2016 and 05/2019 were retrospectively extracted. The thread transfer task, a basic instrument handling task, was assessed. Task duration and instrument-based metrics were analyzed; total distance travelled by instrument tips, average speed, average acceleration, and the ratio of movements between the left and right hands. Curve estimation regression was used to assess the relationship between attempt number and metrics for pooled data across the entire cohort of users and amongst individual users with ≥50 attempts. Threshold for significance p = 0.05. SETTING: SurgTrac has generated the largest available database of performances in box trainer simulated tasks with 64,000 activities performed by over 1450 users in 77 countries to date. PARTICIPANTS: Data was derived from the unselected world-wide cohort of SurgTrac users. No participants were excluded. RESULTS: Five hundred seventy-eight users performed 13,027 attempts in the thread transfer task. Across the entire cohort, SurgTrac performance metrics were significantly associated with attempt number. Task duration and total distance decreased with attempt number. This benefit persisted across 100 attempts. Ambidexterity increased with attempt number. Individual candidate performance improved in line with predicted learning curves for better performing candidates. CONCLUSIONS: We analyzed the largest database of simulated laparoscopic task performances. Performance improves with practice. Using learning curves derived from peer-group performances as benchmarks, users may be regularly and objectively assessed to support personalization of training.

5.
Nutr J ; 19(1): 108, 2020 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-32988395

RESUMO

BACKGROUND AND OBJECTIVES: Flavonoids are the most important group of polyphenols with well-known beneficial effects on health. However; the association of intake of total flavonoid or their subclasses with all-cause or cause-specific mortality is not fully understood. The present study aims to evaluate the association between intake of total flavonoid, flavonoid subclasses, and total and cause-specific mortality in a developing country. METHODS: A total number of 49,173 participants from the Golestan cohort study, who completed a validated food frequency questionnaire at recruitment, were followed from 2004 till 2018. Phenol-Explorer database was applied to estimate dietary intakes of total flavonoid and different flavonoid subclasses. Associations were examined using adjusted Cox proportional hazards models. RESULTS: During a mean follow-up of 10.63 years, 5104 deaths were reported. After adjusting for several potential confounders, the hazard ratios (HRs) of all-cause mortality for the highest versus the lowest quintile of dietary flavanones, flavones, isoflavonoids, and dihydrochalcones were 0.81 (95% confidence interval = 0.73-0.89), 0.83(0.76-0.92), 0.88(0.80-0.96) and 0.83(0.77-0.90), respectively. However, there was no association between total flavonoid intake or other flavonoid subclasses with all-cause mortality. In cause-specific mortality analyses, flavanones and flavones intakes were inversely associated with CVD mortality [HRs: 0.86(0.73-1.00) and 0.85(0.72-1.00)] and isoflavonoids and dihydrochalcones were the only flavonoid subclasses that showed a protective association against cancer mortality [HR: 0.82(0.68-0.98)]. CONCLUSION: The results of our study suggest that certain subclasses of flavonoids can reduce all-cause mortality and mortality rate from CVD and cancer.

6.
J Neurosurg ; : 1-6, 2020 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-32898843

RESUMO

OBJECTIVE: The Glasgow Coma Scale (GCS) is used for the assessment of impaired consciousness; however, it is not always possible to test each component, most commonly the verbal component. This affects the derivation of the GCS sum score, which has a role in systems for predicting patient outcome. Imputation of missing scores does not add extra information, but it does allow use of tools for predicting outcome that require complete data. The authors devised a simple and practical tool to employ when verbal component data are missing. They then assessed the tool's utility by application to the GCS-Pupils plus age plus CT findings (GCS-PA CT) prognostic model. METHODS: The authors inspected data from the International Mission for Prognosis and Analysis of Clinical Trials in Traumatic Brain Injury (IMPACT) cohort to characterize the frequency of missing verbal scores. The authors identified a single verbal score to impute for each eye and motor combined sum (EM) score from distributions of verbal scores in a published database of 54,069 patients. The effectiveness of the imputed verbal score was assessed using a dataset containing information from the IMPACT and Corticosteroid Randomisation After Significant Head Injury (CRASH) databases. The authors compared the performance of the prognostic model using actual verbal scores with the performance using imputed verbal scores and assessed the information yield using Nagelkerke's R2 statistic. RESULTS: Verbal data were most commonly missing in patients with no eye opening and with a motor score of 4 or less. The "simple" imputation model that was developed performed as well as a more complex model involving distinct combinations of eye and motor scores. The imputation model consisted of the following: EM scores 2-6, add 1; EM score 7, add 2; EM score 8 or 9, add 4; and EM score 10, add 5 to provide the GCS sum score. Modeling without information about the verbal score reduced the R2 from 32.1% to 31.4% and from 34.9% to 34.0% for predictions of death and favorable outcome at 6 months, respectively, compared with using full verbal score information. CONCLUSIONS: This strategy is particularly valuable for imputation in clinical practice, enabling clinicians to make a rapid and reliable determination of the GCS sum score when the verbal component is not testable. This will support clinical communication and decisions based on estimates of injury severity as well as enable estimation of prognosis. The authors suggest that external validation of their imputation strategy and the performance of the GCS-PA charts should be undertaken in other clinical populations.

7.
Front Med ; 2020 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-32889700

RESUMO

Although genome-wide association studies have identified more than eighty genetic variants associated with non-small cell lung cancer (NSCLC) risk, biological mechanisms of these variants remain largely unknown. By integrating a large-scale genotype data of 15 581 lung adenocarcinoma (AD) cases, 8350 squamous cell carcinoma (SqCC) cases, and 27 355 controls, as well as multiple transcriptome and epigenomic databases, we conducted histology-specific meta-analyses and functional annotations of both reported and novel susceptibility variants. We identified 3064 credible risk variants for NSCLC, which were overrepresented in enhancer-like and promoter-like histone modification peaks as well as DNase I hypersensitive sites. Transcription factor enrichment analysis revealed that USF1 was AD-specific while CREB1 was SqCC-specific. Functional annotation and gene-based analysis implicated 894 target genes, including 274 specifics for AD and 123 for SqCC, which were overrepresented in somatic driver genes (ER = 1.95, P = 0.005). Pathway enrichment analysis and Gene-Set Enrichment Analysis revealed that AD genes were primarily involved in immune-related pathways, while SqCC genes were homologous recombination deficiency related. Our results illustrate the molecular basis of both well-studied and new susceptibility loci of NSCLC, providing not only novel insights into the genetic heterogeneity between AD and SqCC but also a set of plausible gene targets for post-GWAS functional experiments.

8.
Int J Cancer ; 2020 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-32914876

RESUMO

At the time of cancer diagnosis, body mass index (BMI) is inversely correlated with lung cancer risk, which may reflect reverse causality and confounding due to smoking behavior. We used two-sample univariable and multivariable Mendelian randomization (MR) to estimate causal relationships of BMI and smoking behaviors on lung cancer and histological subtypes based on an aggregated genome-wide association studies (GWASs) analysis of lung cancer in 29 266 cases and 56 450 controls. We observed a positive causal effect for high BMI on occurrence of small-cell lung cancer (odds ratio (OR) = 1.60, 95% confidence interval (CI) = 1.24-2.06, P = 2.70 × 10-4 ). After adjustment of smoking behaviors using multivariable Mendelian randomization (MVMR), a direct causal effect on small cell lung cancer (ORMVMR = 1.28, 95% CI = 1.06-1.55, PMVMR = .011), and an inverse effect on lung adenocarcinoma (ORMVMR = 0.86, 95% CI = 0.77-0.96, PMVMR = .008) were observed. A weak increased risk of lung squamous cell carcinoma was observed for higher BMI in univariable Mendelian randomization (UVMR) analysis (ORUVMR = 1.19, 95% CI = 1.01-1.40, PUVMR = .036), but this effect disappeared after adjustment of smoking (ORMVMR = 1.02, 95% CI = 0.90-1.16, PMVMR = .746). These results highlight the histology-specific impact of BMI on lung carcinogenesis and imply mediator role of smoking behaviors in the association between BMI and lung cancer.

9.
Genet Epidemiol ; 2020 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-32924180

RESUMO

Clinical trial results have recently demonstrated that inhibiting inflammation by targeting the interleukin-1ß pathway can offer a significant reduction in lung cancer incidence and mortality, highlighting a pressing and unmet need to understand the benefits of inflammation-focused lung cancer therapies at the genetic level. While numerous genome-wide association studies (GWAS) have explored the genetic etiology of lung cancer, there remains a large gap between the type of information that may be gleaned from an association study and the depth of understanding necessary to explain and drive translational findings. Thus, in this study we jointly model and integrate extensive multiomics data sources, utilizing a total of 40 genome-wide functional annotations that augment previously published results from the International Lung Cancer Consortium (ILCCO) GWAS, to prioritize and characterize single nucleotide polymorphisms (SNPs) that increase risk of squamous cell lung cancer through the inflammatory and immune responses. Our work bridges the gap between correlative analysis and translational follow-up research, refining GWAS association measures in an interpretable and systematic manner. In particular, reanalysis of the ILCCO data highlights the impact of highly associated SNPs from nuclear factor-κB signaling pathway genes as well as major histocompatibility complex mediated variation in immune responses. One consequence of prioritizing likely functional SNPs is the pruning of variants that might be selected for follow-up work by over an order of magnitude, from potentially tens of thousands to hundreds. The strategies we introduce provide informative and interpretable approaches for incorporating extensive genome-wide annotation data in analysis of genetic association studies.

10.
BMC Cancer ; 20(1): 856, 2020 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-32894098

RESUMO

BACKGROUND: Germline copy number variants (CNVs) increase risk for many diseases, yet detection of CNVs and quantifying their contribution to disease risk in large-scale studies is challenging due to biological and technical sources of heterogeneity that vary across the genome within and between samples. METHODS: We developed an approach called CNPBayes to identify latent batch effects in genome-wide association studies involving copy number, to provide probabilistic estimates of integer copy number across the estimated batches, and to fully integrate the copy number uncertainty in the association model for disease. RESULTS: Applying a hidden Markov model (HMM) to identify CNVs in a large multi-site Pancreatic Cancer Case Control study (PanC4) of 7598 participants, we found CNV inference was highly sensitive to technical noise that varied appreciably among participants. Applying CNPBayes to this dataset, we found that the major sources of technical variation were linked to sample processing by the centralized laboratory and not the individual study sites. Modeling the latent batch effects at each CNV region hierarchically, we developed probabilistic estimates of copy number that were directly incorporated in a Bayesian regression model for pancreatic cancer risk. Candidate associations aided by this approach include deletions of 8q24 near regulatory elements of the tumor oncogene MYC and of Tumor Suppressor Candidate 3 (TUSC3). CONCLUSIONS: Laboratory effects may not account for the major sources of technical variation in genome-wide association studies. This study provides a robust Bayesian inferential framework for identifying latent batch effects, estimating copy number, and evaluating the role of copy number in heritable diseases.

11.
Int J Cancer ; 2020 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-32895947

RESUMO

Scant evidence exists to support the association of opium use with head and neck cancer, limited to the larynx and oral cavity. In a multicenter case-control study-Iran Opium and Cancer study, we recruited 633 cases of head and neck squamous cell carcinoma (HNSCC) (254 lip and oral cavity, 54 pharynx, 327 larynx and 28 other subsites within the head and neck) and 3065 frequency-matched controls from April 2016 to April 2019. Odds ratios (ORs) for opium use and 95% confidence intervals (95% CIs) were obtained using mixed-effects logistic regression because of heterogeneity among centers. The adjusted OR (95% CI) for regular opium use was 3.76 (2.96-4.79) for all HNSCC combined. Strong dose-response effects were observed by frequency or amount of use, and duration of use. Regular opium uses significantly increased the risk of HNSCC of the pharynx, larynx and other subsites within the head and neck with OR (95% CI) of 2.90 (1.40-6.02), 6.55 (4.69-9.13) and 5.95 (2.41-14.71), respectively. The observed associations were significant even among never tobacco smokers (including cigarette and water-pipe smoking). Moreover, by the multiplicative interaction scale, the effect of opium use could be varied by cigarette smoking on HNSCC, 8.16 (6.20-10.74). For the first time, the current study showed opium users have an increased risk of several anatomic subsites of HNSCC.

12.
PLoS One ; 15(9): e0232644, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32877430

RESUMO

When trying to identify new potential therapeutic protein targets, access to data and knowledge is increasingly important. In a field where new resources and data sources become available every day, it is crucial to be able to take a step back and look at the wider picture in order to identify potential drug targets. While this task is routinely performed by bespoke literature searches, it is often time-consuming and lacks uniformity when comparing multiple targets at one time. To address this challenge, we developed TargetDB, a tool that aggregates public information available on given target(s) (links to disease, safety, 3D structures, ligandability, novelty, etc.) and assembles it in an easy to read output ready for the researcher to analyze. In addition, we developed a target scoring system based on the desirable attributes of good therapeutic targets and machine learning classification system to categorize novel targets as having promising or challenging tractrability. In this manuscript, we present the methodology used to develop TargetDB as well as test cases.

13.
Artigo em Inglês | MEDLINE | ID: mdl-32967863

RESUMO

BACKGROUND: Whether circulating polyunsaturated fatty acid (PUFA) levels are associated with pancreatic cancer risk is uncertain. Mendelian randomization (MR) represents a study design using genetic instruments to better characterize the relationship between exposure and outcome. METHODS: We utilized data from genome-wide association studies within the Pancreatic Cancer Cohort Consortium and Pancreatic Cancer Case-Control Consortium, involving approximately 9,269 cases and 12,530 controls of European descent, to evaluate associations between pancreatic cancer risk and genetically predicted plasma n-6 PUFA levels. Conventional MR analyses were performed using individual-level and summary-level data. RESULTS: Using genetic instruments, we did not find evidence of associations between genetically predicted plasma n-6 PUFA levels and pancreatic cancer risk [estimates per one SD increase in each PUFA-specific weighted genetic score using summary statistics: linoleic acid odds ratio (OR) = 1.00, 95% confidence interval (CI) = 0.98-1.02; arachidonic acid OR = 1.00, 95% CI = 0.99-1.01; and dihomo-gamma-linolenic acid OR = 0.95, 95% CI = 0.87-1.02]. The OR estimates remained virtually unchanged after adjustment for covariates, using individual-level data or summary statistics, or stratification by age and sex. CONCLUSIONS: Our results suggest that variations of genetically determined plasma n-6 PUFA levels are not associated with pancreatic cancer risk. IMPACT: These results suggest that modifying n-6 PUFA levels through food sources or supplementation may not influence risk of pancreatic cancer.

14.
Nat Rev Clin Oncol ; 2020 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-32973296

RESUMO

Despite improvements in the understanding of cancer causation, much remains unknown regarding the mechanisms by which genomic and non-genomic factors initiate carcinogenesis, drive cell invasion and metastasis, and enable cancer to develop. Technological advances have enabled the analysis of whole genomes, comprising thousands of tumours across populations worldwide, with the aim of identifying mutation signatures associated with particular tumour types. Large collaborative efforts have resulted in the identification and improved understanding of causal factors, and have shed light on new opportunities to prevent cancer. In this new era in cancer genomics, discoveries from studies conducted on an international scale can inform evidence-based strategies in cancer control along the cancer care continuum, from prevention to treatment. In this Review, we present the relevant history and emerging frontiers of cancer genetics and genomics from the perspective of global cancer prevention. We highlight the importance of local context in the adoption of new technologies and emergent evidence, with illustrative examples from worldwide. We emphasize the challenges in implementing important genomic findings in clinical settings with disparate resource availability and present a conceptual framework for the translation of such findings into clinical practice, and evidence-based policies in order to maximize the utility for a population.

15.
J Hepatol ; 2020 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-32976865

RESUMO

Advanced liver disease presents a significant worldwide health and economic burden and accounts for 3.5% of global mortality. When liver disease progresses to organ failure the only effective treatment is liver transplantation which requires lifelong immune suppression and brings associated risks. Furthermore, the shortage in suitable donor organs means patients may die waiting for a suitable transplant organ. Cell therapies have made their way from animal studies to a small number of early clinical trials. Here we discuss the current state of cell therapies for liver disease and the mechanism underpinning their actions to repair liver tissue or rebuild functional parenchyma, cellular therapies that are on the clinical horizon and challenges to be overcome before routine clinical use is a possibility.

16.
Cochrane Database Syst Rev ; 9: CD013564, 2020 09 04.
Artigo em Inglês | MEDLINE | ID: mdl-32901926

RESUMO

BACKGROUND: Brain tumours are recognised as one of the most difficult cancers to diagnose because presenting symptoms, such as headache, cognitive symptoms, and seizures, may be more commonly attributable to other, more benign conditions. Interventions to reduce the time to diagnosis of brain tumours include national awareness initiatives, expedited pathways, and protocols to diagnose brain tumours, based on a person's presenting symptoms and signs; and interventions to reduce waiting times for brain imaging pathways. If such interventions reduce the time to diagnosis, it may make it less likely that people experience clinical deterioration, and different treatment options may be available. OBJECTIVES: To systematically evaluate evidence on the effectiveness of interventions that may influence: symptomatic participants to present early (shortening the patient interval), thresholds for primary care referral (shortening the primary care interval), and time to imaging diagnosis (shortening the secondary care interval and diagnostic interval). To produce a brief economic commentary, summarising the economic evaluations relevant to these interventions. SEARCH METHODS: For evidence on effectiveness, we searched CENTRAL, MEDLINE, and Embase from January 2000 to January 2020; Clinicaltrials.gov to May 2020, and conference proceedings from 2014 to 2018. For economic evidence, we searched the UK National Health Services Economic Evaluation Database from 2000 to December 2014. SELECTION CRITERIA: We planned to include studies evaluating any active intervention that may influence the diagnostic pathway, e.g. clinical guidelines, direct access imaging, public health campaigns, educational initiatives, and other interventions that might lead to early identification of primary brain tumours. We planned to include randomised and non-randomised comparative studies. Included studies would include people of any age, with a presentation that might suggest a brain tumour. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed titles identified by the search strategy, and the full texts of potentially eligible studies. We resolved discrepancies through discussion or, if required, by consulting another review author. MAIN RESULTS: We did not identify any studies for inclusion in this review. We excluded 115 studies. The main reason for exclusion of potentially eligible intervention studies was their study design, due to a lack of control groups. We found no economic evidence to inform a brief economic commentary on this topic. AUTHORS' CONCLUSIONS: In this version of the review, we did not identify any studies that met the review inclusion criteria for either effectiveness or cost-effectiveness. Therefore, there is no evidence from good quality studies on the best strategies to reduce the time to diagnosis of brain tumours, despite the prioritisation of research on early diagnosis by the James Lind Alliance in 2015. This review highlights the need for research in this area.

17.
Artigo em Inglês | MEDLINE | ID: mdl-32936433

RESUMO

Both intravenous thrombolysis (IVT) and mechanical thrombectomy (MT) are evidence-based treatments for acute ischemic stroke (AIS) in selected cases. Recanalization may occur following IVT without the necessity of further interventions or requiring a subsequent MT procedure. IVT prior to MT (bridging-therapy) may be associated with benefits or hazards. We studied the retrieved clot area and degree of recanalization in patients undergoing MT or bridging-therapy for whom it was possible to collect thrombus material. We collected mechanically extracted thrombi from 550 AIS patients from four International stroke centers. Patients were grouped according to the administration (or not) of IVT before thrombectomy and the mechanical thrombectomy approach used. We assessed the number of passes for clot removal and the mTICI (modified Treatment In Cerebral Ischemia) score to define revascularization outcome. Gross photos of each clot were taken and the clot area was measured with ImageJ software. The non-parametric Kruskal-Wallis test was used for statistical analysis. 255 patients (46.4%) were treated with bridging-therapy while 295 (53.6%) underwent MT alone. By analysing retrieved clot area, we found that clots from patients treated with bridging-therapy were significantly smaller compared to those from patients that underwent MT alone (H1 = 10.155 p = 0.001*). There was no difference between bridging-therapy and MT alone in terms of number of passes or final mTICI score. Bridging-therapy was associated with significantly smaller retrieved clot area compared to MT alone but it did not influence revascularization outcome.

18.
Int J Epidemiol ; 2020 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-32810213

RESUMO

BACKGROUND: Many diabetic individuals use prescription and non-prescription opioids and opiates. We aimed to investigate the joint effect of diabetes and opiate use on all-cause and cause-specific mortality. METHODS: Golestan Cohort study is a prospective population-based study in Iran. A total of 50 045 people-aged 40-75, 28 811 women, 8487 opiate users, 3548 diabetic patients-were followed during a median of 11.1 years, with over 99% success follow-up. Hazard ratio and 95% confidence intervals (HRs, 95% CIs), and preventable death attributable to each risk factor, were calculated. RESULTS: After 533 309 person-years, 7060 deaths occurred: 4178 (10.8%) of non-diabetic non-opiate users, 757 (25.3%) diabetic non-users, 1906 (24.0%) non-diabetic opiate users and 219 (39.8%) diabetic opiate users. Compared with non-diabetic non-users, HRs (95% CIs) for all-cause mortality were 2.17 (2.00-2.35) in diabetic non-opiate users, 1.63 (1.53-1.74) in non-diabetic opiate users and 2.76 (2.40-3.17) in diabetic opiate users. Among those who both had diabetes and used opiates, 63.8% (95% CI: 58.3%-68.5%) of all deaths were attributable to these risk factors, compared with 53.9% (95% CI: 50%-57.4%) in people who only had diabetes and 38.7% (95% CI: 34.6%-42.5%) in non-diabetic opiate users. Diabetes was more strongly associated with cardiovascular than cancer mortality. The risk of early mortality in known cases of diabetes did not depend on whether they started opiate use before or after their diagnosis. CONCLUSIONS: Using opiates is detrimental to the health of diabetic patients. Public awareness about the health effects of opiates, and improvement of diabetes care especially among individuals with or at risk of opiate use, are necessary.

19.
Br J Cancer ; 2020 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-32830199

RESUMO

BACKGROUND: Alcohol is a well-established risk factor for head and neck cancer (HNC). This study aims to explore the effect of alcohol intensity and duration, as joint continuous exposures, on HNC risk. METHODS: Data from 26 case-control studies in the INHANCE Consortium were used, including never and current drinkers who drunk ≤10 drinks/day for ≤54 years (24234 controls, 4085 oral cavity, 3359 oropharyngeal, 983 hypopharyngeal and 3340 laryngeal cancers). The dose-response relationship between the risk and the joint exposure to drinking intensity and duration was investigated through bivariate regression spline models, adjusting for potential confounders, including tobacco smoking. RESULTS: For all subsites, cancer risk steeply increased with increasing drinks/day, with no appreciable threshold effect at lower intensities. For each intensity level, the risk of oral cavity, hypopharyngeal and laryngeal cancers did not vary according to years of drinking, suggesting no effect of duration. For oropharyngeal cancer, the risk increased with durations up to 28 years, flattening thereafter. The risk peaked at the higher levels of intensity and duration for all subsites (odds ratio = 7.95 for oral cavity, 12.86 for oropharynx, 24.96 for hypopharynx and 6.60 for larynx). CONCLUSIONS: Present results further encourage the reduction of alcohol intensity to mitigate HNC risk.

20.
ChemMedChem ; 2020 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-32812371

RESUMO

Combined photochemical arylation, "nuisance effect" (SN Ar) reaction sequences have been employed in the design of small arrays for immediate deployment in medium-throughput X-ray protein-ligand structure determination. Reactions were deliberately allowed to run "out of control" in terms of selectivity; for example the ortho-arylation of 2-phenylpyridine gave five products resulting from mono- and bisarylations combined with SN Ar processes. As a result, a number of crystallographic hits against NUDT7, a key peroxisomal CoA ester hydrolase, have been identified.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA