66 research outputs found

    Genomic landscape and actionable mutations of brain metastases derived from non–small cell lung cancer: A systematic review

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    Background Brain metastases derived from non–small cell lung cancer (NSCLC) represent a significant clinical problem. We aim to characterize the genomic landscape of brain metastases derived from NSCLC and assess clinical actionability. Methods We searched Embase, MEDLINE, Web of Science, and BIOSIS from inception to 18/19 May 2022. We extracted information on patient demographics, smoking status, genomic data, matched primary NSCLC, and programmed cell death ligand 1 expression. Results We found 72 included papers and data on 2346 patients. The most frequently mutated genes from our data were EGFR (n = 559), TP53 (n = 331), KRAS (n = 328), CDKN2A (n = 97), and STK11 (n = 72). Common missense mutations included EGFR L858R (n = 80) and KRAS G12C (n = 17). Brain metastases of ever versus never smokers had differing missense mutations in TP53 and EGFR, except for L858R and T790M in EGFR, which were seen in both subgroups. Of the top 10 frequently mutated genes that had primary NSCLC data, we found 37% of the specific mutations assessed to be discordant between the primary NSCLC and brain metastases. Conclusions To our knowledge, this is the first systematic review to describe the genomic landscape of brain metastases derived from NSCLC. These results provide a comprehensive outline of frequently mutated genes and missense mutations that could be clinically actionable. These data also provide evidence of differing genomic landscapes between ever versus never smokers and primary NSCLC compared to the BM. This information could have important consequences for the selection and development of targeted drugs for these patients

    A systematic review of techniques and effects of self-help interventions for tinnitus: application of taxonomies from health psychology

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    Objective: Self-help interventions are followed by people independently with minimal or no therapist contact. This review aims to assess the effectiveness of self-help interventions for adults with chronic tinnitus and systematically identify the self-help techniques used. Design: Systematic review and application of health psychology taxonomies. Electronic database searches were conducted, supplemented by citation searching and hand-searching of key journals. Prospective controlled trials, which used measures of tinnitus distress, functional management, anxiety, depression, and quality of life, were included. Michie et al’s behaviour change techniques (BCTs) taxonomy and Taylor et al’s PRISMS taxonomy of self-management components were applied to describe interventions. Study sample: Five studies were included, providing low-to-moderate levels of evidence. Results: Randomized controlled trial studies were too few and heterogeneous for meta-analysis to be performed. Studies comparing self-help interventions to therapist-guided interventions and assessing non tinnitus-specific psychosocial outcomes and functional management were lacking. Fifteen BCTs and eight self-management components were identified across interventions. Conclusions: A lack of high-quality and homogeneous studies meant that confident conclusions could not be drawn regarding the efficacy of self-help interventions for tinnitus. Better reporting and categorization of intervention techniques is needed for replication in research and practice and to facilitate understanding of intervention mechanisms

    Omega-3 polyunsaturated fatty acids: Their potential role in blood pressure prevention and management

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    Omega-3 polyunsaturated fatty acids (PUFAs) from fish and fish oils appear to protect against coronary heart disease: their dietary intake is in fact inversely associated to cardiovascular disease morbidity/mortality in population studies. Recent evidence suggests that at least part of their heart protective effect is mediated by a relatively small but significant decrease in blood pressure level. In fact, omega-3 PUFAs exhibit wide-ranging biological actions that include regulating both vasomotor tone and renal sodium excretion, partly competing with omega-6 PUFAs for common metabolic enzymes and thereby decreasing the production of vasocostrincting rather than vasodilating and anti-inflammatory eicosanoids. PUFAs also reduce angiotensin-converting enzyme (ACE) activity, angiotensin II formation, TGF-beta expression, enhance eNO generation and activate the parasympathetic nervous system. The final result is improved vasodilation and arterial compliance of both small and large arteries. Preliminary clinical trials involving dyslipidemic patients, diabetics and elderly subjects, as well as normotensive and hypertensive subjects confirm this working hypothesis. Future research will clarify if PUFA supplementation could improve the antihypertensive action of specific blood pressure lowering drug classes and of statins

    The risk of deterioration in GCS13-15 patients with traumatic brain injury identified by CT imaging : a systematic review and meta-analysis

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    The optimal management of mild traumatic brain injury (TBI) patients with injuries identified by computed tomography (CT) brain scan is unclear. Some guidelines recommend hospital admission for an observation period of at least 24 h. Others argue that selected lower-risk patients can be discharged from the Emergency Department (ED). The objective of our review and meta-analysis was to estimate the risk of death, neurosurgical intervention, and clinical deterioration in mild TBI patients with injuries identified by CT brain scan, and assess which patient factors affect the risk of these outcomes. A systematic review and meta-analysis adhering to PRISMA standards of protocol and reporting were conducted. Study selection was performed by two independent reviewers. Meta-analysis using a random effects model was undertaken to estimate pooled risks for: clinical deterioration, neurosurgical intervention, and death. Meta-regression was used to explore between-study variation in outcome estimates using study population characteristics. Forty-nine primary studies and five reviews were identified that met the inclusion criteria. The estimated pooled risk for the outcomes of interest were: clinical deterioration 11.7% (95% confidence interval [CI]: 11.7%-15.8%), neurosurgical intervention 3.5% (95% CI: 2.2%-4.9%), and death 1.4% (95% CI: 0.8%-2.2%). Twenty-one studies presented within-study estimates of the effect of patient factors. Meta-regression of study characteristics and pooling of within-study estimates of risk factor effect found the following factors significantly affected the risk for adverse outcomes: age, initial Glasgow Coma Scale (GCS), type of injury, and anti-coagulation. The generalizability of many studies was limited due to population selection. Mild TBI patients with injuries identified by CT brain scan have a small but clinically important risk for serious adverse outcomes. This review has identified several prognostic factors; research is needed to derive and validate a usable clinical decision rule so that low-risk patients can be safely discharged from the ED

    Low-value clinical practices in adult traumatic brain injury : an umbrella review

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    Despite numerous interventions and treatment options, the outcomes of traumatic brain injury (TBI) have improved little over the last 3 decades, which raises concern about the value of care in this patient population. We aimed to synthesize the evidence on 14 potentially low-value clinical practices in TBI care. Using umbrella review methodology, we identified systematic reviews evaluating the effectiveness of 14 potentially low-value practices in adults with acute TBI. We present data on methodological quality (Assessing the Methodological Quality of Systematic Reviews), reported effect sizes, and credibility of evidence (I to IV). The only clinical practice with evidence of benefit was therapeutic hypothermia (credibility of evidence II to IV). However, the most recent meta-analysis on hypothermia based on high-quality trials suggested harm (credibility of evidence IV). Meta-analyses on platelet transfusion for patients on antiplatelet therapy were all consistent with harm but were statistically non-significant. For the following practices, effect estimates were consistently close to the null: computed tomography (CT) in adults with mild TBI who are low-risk on a validated clinical decision rule; repeat CT in adults with mild TBI on anticoagulant therapy with no clinical deterioration; antibiotic prophylaxis for external ventricular drain placement; and decompressive craniectomy for refractory intracranial hypertension. We identified five clinical practices with evidence of lack of benefit or harm. However, evidence could not be considered to be strong for any clinical practice as effect measures were imprecise and heterogeneous, systematic reviews were often of low quality, and most included studies had a high risk of bias
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