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1.
Br J Cancer ; 130(12): 1916-1920, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38658782

ABSTRACT

BACKGROUND: Treatment options for pre-treated patients with metastatic triple-negative breast cancer (mTNBC) remain limited. This is the first study to assess the real-world safety and efficacy of sacituzumab govitecan (SG) in the UK. METHODS: Data was retrospectively collected from 16 tertiary UK cancer centres. Pts had a diagnosis of mTNBC, received at least two prior lines of treatment (with at least one being in the metastatic setting) and received at least one dose of SG. RESULTS: 132 pts were included. Median age was 56 years (28-91). All patients were ECOG performance status (PS) 0-3 (PS0; 39, PS1; 76, PS2; 16, PS3;1). 75% (99/132) of pts had visceral metastases including 18% (24/132) of pts with CNS disease. Median PFS (mPFS) was 5.2 months (95% CI 4.5-6.6) with a median OS (mOS) of 8.7 months (95% CI 6.8-NA). The most common adverse events (AEs) were fatigue (all grade; 82%, G3/4; 14%), neutropenia (all grade; 55%, G3/4; 29%), diarrhoea (all grade; 58%, G3/4, 15%), and nausea (all grade; 38%, G3/4; 3%). SG dose reduction was required in 54% of pts. CONCLUSION: This study supports significant anti-tumour activity in heavily pre-treated pts with mTNBC. Toxicity data aligns with clinical trial experience.


Subject(s)
Antibodies, Monoclonal, Humanized , Camptothecin , Triple Negative Breast Neoplasms , Humans , Triple Negative Breast Neoplasms/drug therapy , Triple Negative Breast Neoplasms/pathology , Middle Aged , Female , Aged , Antibodies, Monoclonal, Humanized/therapeutic use , Antibodies, Monoclonal, Humanized/adverse effects , Antibodies, Monoclonal, Humanized/administration & dosage , Adult , United Kingdom/epidemiology , Camptothecin/analogs & derivatives , Camptothecin/therapeutic use , Camptothecin/adverse effects , Camptothecin/administration & dosage , Retrospective Studies , Aged, 80 and over , Neoplasm Metastasis , Immunoconjugates
2.
Oncoimmunology ; 12(1): 2275846, 2023.
Article in English | MEDLINE | ID: mdl-38025838

ABSTRACT

Based upon results of the KEYNOTE-522 trial and following approval by regulatory authorities, the addition of pembrolizumab to chemotherapy is now the standard-of-care for the treatment of early triple-negative breast cancer (eTNBC) (Clinical stage II-III). Pembrolizumab is a programmed cell death protein 1 monoclonal antibody, known to cause immune-related adverse events (irAEs) in a significant subset of patients. Real-world data on incidence, type and treatment strategies of irAEs in the setting of eTNBC treatment are sparse. In this multicenterretrospective analysis, we characterized real-world incidence of irAEs and treatment outcomes such as pathological complete response (pCR) from the combination of pembrolizumab and chemotherapy as neoadjuvant treatment for eTNBC. We found a rate of irAEs of all grades of 63.9% and of 20% for irAEs of grade 3 or higher. In the overall population, a pCR rate of 57.1% was observed. The emergence of irAEs correlated significantly with pCR (72.2% versus 30.8%; p =.03). Discontinuation of neoadjuvant chemotherapy before week 12 correlated significantly with a lower pCR rate. To our knowledge, this is the first study evaluating the real-world efficacy and safety of a neoadjuvant combination of chemotherapy and pembrolizumab in eTNBC, demonstrating a significant correlation between irAEs and pCR. Early discontinuation of neoadjuvant therapy due to AEs resulted in a lower pCR rate.


Subject(s)
Triple Negative Breast Neoplasms , Humans , Triple Negative Breast Neoplasms/drug therapy , Antibodies, Monoclonal, Humanized/adverse effects , Antibodies, Monoclonal , Treatment Outcome
3.
Sci Rep ; 13(1): 11327, 2023 07 25.
Article in English | MEDLINE | ID: mdl-37491478

ABSTRACT

Patients with cancer are at increased risk of hospitalisation and mortality following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. However, the SARS-CoV-2 phenotype evolution in patients with cancer since 2020 has not previously been described. We therefore evaluated SARS-CoV-2 on a UK populationscale from 01/11/2020-31/08/2022, assessing case-outcome rates of hospital assessment(s), intensive care admission and mortality. We observed that the SARS-CoV-2 disease phenotype has become less severe in patients with cancer and the non-cancer population. Case-hospitalisation rates for patients with cancer dropped from 30.58% in early 2021 to 7.45% in 2022 while case-mortality rates decreased from 20.53% to 3.25%. However, the risk of hospitalisation and mortality remains 2.10x and 2.54x higher in patients with cancer, respectively. Overall, the SARS-CoV-2 disease phenotype is less severe in 2022 compared to 2020 but patients with cancer remain at higher risk than the non-cancer population. Patients with cancer must therefore be empowered to live more normal lives, to see loved ones and families, while also being safeguarded with expanded measures to reduce the risk of transmission.


Subject(s)
COVID-19 , Neoplasms , Humans , Male , Female , Case-Control Studies , Treatment Outcome , Neoplasms/complications , Neoplasms/epidemiology , COVID-19/complications , COVID-19/epidemiology , England/epidemiology , Adolescent , Young Adult , Adult , Middle Aged , Aged , Aged, 80 and over
4.
Children (Basel) ; 10(4)2023 Apr 20.
Article in English | MEDLINE | ID: mdl-37190001

ABSTRACT

The aim of this insights paper is to propose how the theory of ecological dynamics may invite re-consideration of how sport scientists could support performance, learning and development of children and youth in sports programmes. We seek to outline why learning should be individualised and contextualised, based on the specific needs of learners, such as children and youth, women and disabled athletes in sport. Case examples from individual and team sports are presented to illustrate how constraints can be designed to enrich interactions of children and youth with different performance environments, based on integrating principles of specificity and generality in learning and development. These case examples suggest how a collaborative effort by sport scientists and coaches in children and youth sport may be undertaken in a department of methodology to enrich learning and performance.

5.
iScience ; 26(6): 106848, 2023 Jun 16.
Article in English | MEDLINE | ID: mdl-37250804

ABSTRACT

Preclinical and genetic studies suggest that impaired glucose-dependent insulinotropic polypeptide receptor (GIPR) signaling worsens glycemic control. The relationship between GIPR signaling and the risk of cancers influenced by impaired glucose homeostasis is unclear. We examined the association of a variant in GIPR, rs1800437 (E354Q), shown to impair long-term GIPR signaling and lower circulating glucose-dependent insulinotropic peptide concentrations, with risk of 6 cancers influenced by impaired glucose homeostasis (breast, colorectal, endometrial, lung, pancreatic, and renal) in up to 235,698 cases and 333,932 controls. Each copy of E354Q was associated with a higher risk of overall and luminal A-like breast cancer and this association was consistent in replication and colocalization analyses. E354Q was also associated with higher postprandial glucose concentrations but diminished insulin secretion and lower testosterone concentrations. Our human genetics analysis suggests an adverse effect of the GIPR E354Q variant on breast cancer risk, supporting further evaluation of GIPR signaling in breast cancer prevention.

6.
JAMA Oncol ; 9(2): 188-196, 2023 02 01.
Article in English | MEDLINE | ID: mdl-36547970

ABSTRACT

Importance: Accurate identification of patient groups with the lowest level of protection following COVID-19 vaccination is important to better target resources and interventions for the most vulnerable populations. It is not known whether SARS-CoV-2 antibody testing has clinical utility for high-risk groups, such as people with cancer. Objective: To evaluate whether spike protein antibody vaccine response (COV-S) following COVID-19 vaccination is associated with the risk of SARS-CoV-2 breakthrough infection or hospitalization among patients with cancer. Design, Setting, and Participants: This was a population-based cross-sectional study of patients with cancer from the UK as part of the National COVID Cancer Antibody Survey. Adults with a known or reported cancer diagnosis who had completed their primary SARS-CoV-2 vaccination schedule were included. This analysis ran from September 1, 2021, to March 4, 2022, a period covering the expansion of the UK's third-dose vaccination booster program. Interventions: Anti-SARS-CoV-2 COV-S antibody test (Elecsys; Roche). Main Outcomes and Measures: Odds of SARS-CoV-2 breakthrough infection and COVID-19 hospitalization. Results: The evaluation comprised 4249 antibody test results from 3555 patients with cancer and 294 230 test results from 225 272 individuals in the noncancer population. The overall cohort of 228 827 individuals (patients with cancer and the noncancer population) comprised 298 479 antibody tests. The median age of the cohort was in the age band of 40 and 49 years and included 182 741 test results (61.22%) from women and 115 737 (38.78%) from men. There were 279 721 tests (93.72%) taken by individuals identifying as White or White British. Patients with cancer were more likely to have undetectable anti-S antibody responses than the general population (199 of 4249 test results [4.68%] vs 376 of 294 230 [0.13%]; P < .001). Patients with leukemia or lymphoma had the lowest antibody titers. In the cancer cohort, following multivariable correction, patients who had an undetectable antibody response were at much greater risk for SARS-CoV-2 breakthrough infection (odds ratio [OR], 3.05; 95% CI, 1.96-4.72; P < .001) and SARS-CoV-2-related hospitalization (OR, 6.48; 95% CI, 3.31-12.67; P < .001) than individuals who had a positive antibody response. Conclusions and Relevance: The findings of this cross-sectional study suggest that COV-S antibody testing allows the identification of patients with cancer who have the lowest level of antibody-derived protection from COVID-19. This study supports larger evaluations of SARS-CoV-2 antibody testing. Prevention of SARS-CoV-2 transmission to patients with cancer should be prioritized to minimize impact on cancer treatments and maximize quality of life for individuals with cancer during the ongoing pandemic.


Subject(s)
COVID-19 , Neoplasms , Vaccines , Female , Adult , Male , Humans , Middle Aged , COVID-19 Vaccines , Spike Glycoprotein, Coronavirus , Cross-Sectional Studies , Antibody Formation , Quality of Life , COVID-19/epidemiology , COVID-19/prevention & control , SARS-CoV-2 , Neoplasms/epidemiology , Antibodies, Viral , Delivery of Health Care
7.
Eur J Cancer ; 175: 1-10, 2022 11.
Article in English | MEDLINE | ID: mdl-36084618

ABSTRACT

PURPOSE: People living with cancer and haematological malignancies are at an increased risk of hospitalisation and death following infection with acute respiratory syndrome coronavirus 2. Coronavirus third dose vaccine boosters are proposed to boost waning immune responses in immunocompromised individuals and increase coronavirus protection; however, their effectiveness has not yet been systematically evaluated. METHODS: This study is a population-scale real-world evaluation of the United Kingdom's third dose vaccine booster programme for cancer patients from 8th December 2020 to 7th December 2021. The cancer cohort comprises individuals from Public Health England's national cancer dataset, excluding individuals less than 18 years. A test-negative case-control design was used to assess the third dose booster vaccine effectiveness. Multivariable logistic regression models were fitted to compare risk in the cancer cohort relative to the general population. RESULTS: The cancer cohort comprised of 2,258,553 tests from 361,098 individuals. Third dose boosters were evaluated by reference to 87,039,743 polymerase chain reaction coronavirus tests. Vaccine effectiveness against breakthrough infections, symptomatic infections, coronavirus hospitalisation and death in cancer patients were 59.1%, 62.8%, 80.5% and 94.5%, respectively. Lower vaccine effectiveness was associated with a cancer diagnosis within 12 months, lymphoma, recent systemic anti-cancer therapy (SACT) or radiotherapy. Patients with lymphoma had low levels of protection from symptomatic disease. In spite of third dose boosters, following multivariable adjustment, individuals with cancer remain at an increased risk of coronavirus hospitalisation and death compared to the population control (OR 3.38, 3.01, respectively. p < 0.001 for both). CONCLUSIONS: Third dose boosters are effective for most individuals with cancer, increasing protection from coronavirus. However, their effectiveness is heterogenous and lower than the general population. Many patients with cancer will remain at the increased risk of coronavirus infections even after 3 doses. In the case of patients with lymphoma, there is a particularly strong disparity of vaccine effectiveness against breakthrough infection and severe disease. Breakthrough infections will disrupt cancer care and treatment with potentially adverse consequences on survival outcomes. The data support the role of vaccine boosters in preventing severe disease, and further pharmacological intervention to prevent transmission and aid viral clearance to limit the disruption of cancer care as the delivery of care continues to evolve during the coronavirus pandemic.


Subject(s)
COVID-19 , Neoplasms , COVID-19/epidemiology , COVID-19/prevention & control , Hospitalization , Humans , Pandemics , Vaccination , Vaccine Efficacy
8.
Lancet Oncol ; 23(6): 748-757, 2022 06.
Article in English | MEDLINE | ID: mdl-35617989

ABSTRACT

BACKGROUND: People with cancer are at increased risk of hospitalisation and death following infection with SARS-CoV-2. Therefore, we aimed to conduct one of the first evaluations of vaccine effectiveness against breakthrough SARS-CoV-2 infections in patients with cancer at a population level. METHODS: In this population-based test-negative case-control study of the UK Coronavirus Cancer Evaluation Project (UKCCEP), we extracted data from the UKCCEP registry on all SARS-CoV-2 PCR test results (from the Second Generation Surveillance System), vaccination records (from the National Immunisation Management Service), patient demographics, and cancer records from England, UK, from Dec 8, 2020, to Oct 15, 2021. Adults (aged ≥18 years) with cancer in the UKCCEP registry were identified via Public Health England's Rapid Cancer Registration Dataset between Jan 1, 2018, and April 30, 2021, and comprised the cancer cohort. We constructed a control population cohort from adults with PCR tests in the UKCCEP registry who were not contained within the Rapid Cancer Registration Dataset. The coprimary endpoints were overall vaccine effectiveness against breakthrough infections after the second dose (positive PCR COVID-19 test) and vaccine effectiveness against breakthrough infections at 3-6 months after the second dose in the cancer cohort and control population. FINDINGS: The cancer cohort comprised 377 194 individuals, of whom 42 882 had breakthrough SARS-CoV-2 infections. The control population consisted of 28 010 955 individuals, of whom 5 748 708 had SARS-CoV-2 breakthrough infections. Overall vaccine effectiveness was 69·8% (95% CI 69·8-69·9) in the control population and 65·5% (65·1-65·9) in the cancer cohort. Vaccine effectiveness at 3-6 months was lower in the cancer cohort (47·0%, 46·3-47·6) than in the control population (61·4%, 61·4-61·5). INTERPRETATION: COVID-19 vaccination is effective for individuals with cancer, conferring varying levels of protection against breakthrough infections. However, vaccine effectiveness is lower in patients with cancer than in the general population. COVID-19 vaccination for patients with cancer should be used in conjunction with non-pharmacological strategies and community-based antiviral treatment programmes to reduce the risk that COVID-19 poses to patients with cancer. FUNDING: University of Oxford, University of Southampton, University of Birmingham, Department of Health and Social Care, and Blood Cancer UK.


Subject(s)
COVID-19 , Neoplasms , Viral Vaccines , Adolescent , Adult , COVID-19/epidemiology , COVID-19/prevention & control , COVID-19 Vaccines , Case-Control Studies , Humans , Neoplasms/epidemiology , SARS-CoV-2 , Vaccine Efficacy
9.
Sci Rep ; 12(1): 1463, 2022 01 27.
Article in English | MEDLINE | ID: mdl-35087170

ABSTRACT

The Rho GTPase family consists of 20 genes encoding intracellular signalling proteins that influence cytoskeletal dynamics, cell migration and cell cycle progression. They are implicated in breast cancer progression but their role in breast cancer aetiology is unknown. As aberrant Rho GTPase activity could be associated with breast cancer, we aimed to determine the potential for a causal role of Rho GTPase gene expression in breast cancer risk, using two-sample Mendelian randomization (MR). MR was undertaken in 122,977 breast cancer cases and 105,974 controls, including 69,501 estrogen receptor positive (ER+) cases and 105,974 controls, and 21,468 ER negative (ER-) cases and 105,974 controls. Single nucleotide polymorphisms (SNPs) underlying expression quantitative trait loci (eQTLs) obtained from normal breast tissue, breast cancer tissue and blood were used as genetic instruments for Rho GTPase expression. As a sensitivity analysis, we undertook co-localisation to examine whether findings reflected shared causal variants or genomic confounding. We identified genetic instruments for 14 of the 20 human Rho GTPases. Using eQTLs obtained from normal breast tissue and normal blood, we identified evidence of a causal role of RHOD in overall and ER+ breast cancers (overall breast cancer: odds ratio (OR) per standard deviation (SD) increase in expression level 1.06; (95% confidence interval (CI) 1.03, 1.09; P = 5.65 × 10-5) and OR 1.22 (95% CI 1.11, 1.35; P = 5.22 × 10-5) in normal breast tissue and blood respectively). There was a consistent direction of association for ER- breast cancer, although the effect-estimate was imprecisely estimated. Using eQTLs from breast cancer tissue and normal blood there was some evidence that CDC42 was negatively associated with overall and ER + breast cancer risk. The evidence from colocalization analyses strongly supported our MR results particularly for RHOD. Our study suggests a potential causal role of increased RHOD gene expression, and, although the evidence is weaker, a potential protective role for CDC42 gene expression, in overall and ER+ breast cancers. These finding warrant validation in independent samples and further biological investigation to assess whether they may be suitable targets for drug targeting.


Subject(s)
Breast Neoplasms/epidemiology , Genetic Predisposition to Disease , rho GTP-Binding Proteins/genetics , Breast/pathology , Breast Neoplasms/genetics , Breast Neoplasms/pathology , Case-Control Studies , Female , Gene Expression Regulation, Neoplastic , Genome-Wide Association Study , Humans , Mendelian Randomization Analysis , Odds Ratio , Polymorphism, Single Nucleotide , Protective Factors , Quantitative Trait Loci , Risk Factors , cdc42 GTP-Binding Protein/genetics
10.
Am J Surg ; 223(1): 146-150, 2022 Jan.
Article in English | MEDLINE | ID: mdl-34340862

ABSTRACT

BACKGROUND: Enoxaparin is the recommended agent for deep vein thrombosis (DVT) chemoprophylaxis in trauma patients. Current literature suggests weight-based dosing is superior to standard dosing for adequate chemoprophylaxis. Literature regarding the use of weight-based enoxaparin in the setting of traumatic brain injury (TBI) however is limited. METHODS: A retrospective analysis of adult trauma patients admitted between January 1, 2018 to February 28, 2019 was performed. Sixty-six patients with TBI receiving weight-based enoxaparin met inclusion criteria. Incidence of intracranial hemorrhage (ICH) expansion was the primary endpoint. Newly diagnosed venous thromboembolism (VTE) and death were secondary endpoints. RESULTS: Two patients, out of sixty-six, had progression of their TBI requiring surgical intervention. Newly diagnosed VTE occurred in one patient. No deaths were due to ICH expansion or VTE. CONCLUSIONS: Use of weight-based enoxaparin dosing in the setting of TBI shows promise without an increased incidence of ICH expansion when compared to other studies. Level of Evidence and Study Type: Level IV, Therapeutic.


Subject(s)
Anticoagulants/administration & dosage , Brain Injuries, Traumatic/complications , Enoxaparin/administration & dosage , Intracranial Hemorrhages/epidemiology , Venous Thrombosis/prevention & control , Adult , Aged , Anticoagulants/adverse effects , Body Weight , Brain Injuries, Traumatic/blood , Brain Injuries, Traumatic/drug therapy , Drug Dosage Calculations , Enoxaparin/adverse effects , Female , Humans , Incidence , Intracranial Hemorrhages/chemically induced , Male , Middle Aged , Retrospective Studies , Venous Thrombosis/epidemiology , Venous Thrombosis/etiology
11.
Pharmacotherapy ; 41(6): 508-514, 2021 06.
Article in English | MEDLINE | ID: mdl-33864688

ABSTRACT

STUDY OBJECTIVE: The purpose of this study was to evaluate the utility of routine anti-Xa peak monitoring for trauma patients initiated on weight-based enoxaparin for venous thromboembolism (VTE) prophylaxis and identify patient populations where monitoring is necessary. DESIGN: Retrospective study. SETTING: Augusta University (AU) Medical Center in Augusta, Georgia, a level 1 trauma center. PATIENTS: Adult patients admitted to the trauma surgery service requiring chemical VTE prophylaxis. INTERVENTION: At least three consecutive doses of enoxaparin 0.5 mg/kg subcutaneously every 12 hour for VTE prophylaxis prior to an anti-Xa peak as the initial chemical VTE prophylaxis strategy. MEASUREMENTS: The primary end point was the percentage of patients who achieved goal anti-Xa peak of 0.2-0.6 unit/ml. The incidence of newly diagnosed VTE and clinically significant bleeding were assessed as secondary end points. MAIN RESULTS: From January 1, 2018, through February 28, 2019, 300 patients met inclusion criteria. Anti-Xa peaks were within goal in 91% of all patients, 7.7% were below goal, and 1.3% were above goal. For patients who did not meet the goal, dose adjustments were made in 70.4% of patients. New levels were obtained in 73.7% of those patients, and all repeat levels was within goal. Clinically significant bleeding occurred in 5.3% of patients. Newly diagnosed VTE occurred in 1.7% of patients. CONCLUSIONS: The use of initial weight-based enoxaparin dosing in trauma patients routinely achieved the prespecified target anti-Xa goal. In conclusion, anti-Xa levels are not necessary for routine monitoring of weight-based enoxaparin for VTE prophylaxis in trauma patients. Incidence of clinically significant bleeding and newly diagnosed VTE were similar to previous studies.


Subject(s)
Enoxaparin , Venous Thromboembolism , Wounds and Injuries , Adult , Anticoagulants/administration & dosage , Anticoagulants/adverse effects , Enoxaparin/administration & dosage , Enoxaparin/adverse effects , Factor Xa Inhibitors , Goals , Hemorrhage/chemically induced , Hemorrhage/epidemiology , Heparin, Low-Molecular-Weight , Humans , Retrospective Studies , Venous Thromboembolism/epidemiology , Venous Thromboembolism/prevention & control , Wounds and Injuries/drug therapy
12.
Aust Econ Rev ; 54(1): 5-18, 2021 Mar.
Article in English | MEDLINE | ID: mdl-33821015

ABSTRACT

This article summarises developments in the Australian economy in 2020. It describes the economic growth and labour market ramifications associated with COVID-19, and the fiscal and monetary policies implemented to help counter its effects. COVID-19 has resulted in considerable slack in an economy that was weak pre-pandemic. While current policies are appropriately focused on stimulating demand and supporting employment, existing challenges such as weak growth in productivity, gross domestic product and real wages are also likely to remain relevant post-pandemic.

13.
RSC Adv ; 10(20): 11907-11917, 2020 Mar 19.
Article in English | MEDLINE | ID: mdl-35496617

ABSTRACT

Vehicle gas is often compressed to about 200 bar at the refueling station prior to charging to the vehicle's tank. If a high amount of oil is carried over to the gas, it may cause damage to the vehicles; it is therefore necessary to accurately measure oil carryover. In this paper, three analytical methods for accurate quantification of the oil content are presented whereby two methods are based on gas chromatography and one on FTIR. To better evaluate the level of complexity of the matrix, 10 different compressor oils in use at different refueling stations were initially collected and analysed with GC and FTIR to identify their analytical traces. The GC traces could be divided into three different profiles: oils exhibiting some well resolved peaks, oils exhibiting globally unresolved peaks with some dominant peaks on top of the hump and oils exhibiting globally unresolved peaks. After selection of three oils; one oil from each type, the three methods were evaluated with regards to the detection and quantification limits, the working range, precision, trueness and robustness. The evaluation of the three measurement methods demonstrated that any of these three methods presented were suitable for the quantification of compressor oil for samples. The FTIR method and the GC/MS method both resulted in measurement uncertainties close to 20% rel. while the GC/FID method resulted in a higher measurement uncertainty (U = 30% rel.).

15.
Crit Rev Oncol Hematol ; 122: 150-156, 2018 Feb.
Article in English | MEDLINE | ID: mdl-29458783

ABSTRACT

IMPORTANCE: The identification of anaplastic lymphoma kinase (ALK) rearrangements in 2-5% of non-small cell lung cancer (NSCLC) patients led to the rapid clinical development of its oral tyrosine kinase inhibitor (TKI). Crizotinib was the first ALK inhibitor approved and utilised in the treatment of ALK+ NSCLC patients in the second line setting first and subsequently in the first line one. Since then many other ALK inhibitors have been developed (ceritinib, alectinib, brigatinib, lorlatinib,etc) and the treatment paradigm of these patients has considerably drifted. The questions regarding their treatment at progression remains unanswered at the moment. OBJECTIVE: Our review clarifies what it is the state of the art in the treatment of ALK rearranged NSCLC patients, highlights the mechanisms of primary and secondary resistance mutations and suggests a treatment algorithm based on specific primary resistance or acquired mutations. EVIDENCE REVIEW: Studies that enrolled ALK+ NSCLC patients with locally advance or metastatic disease receiving treatment with ALK inhibitor, first or second line, were identified using electronic databases (MEDLINE, EMBASE, and Cochrane library). Trials were excluded if they were phase 1, enrolled less than 10 patients. FINDING: Overall 1942 patients were included in our review. It confirms the role and the efficacy in first line of Alectinib but it highlights also that all the ALK inhibitors could play a crucial role during the patients' journey. Identifying the different mutations and utilising the most active ALK inhibitor depending on the "up-to-date" driven mutation is the way forward in the management of those patients. CONCLUSIONS AND RELEVANCE: the review shows the rapid drifting in the management of ALK+ NSCLC patients and the importance of fully understanding and acknowledging the role of the resistance mutation, primary or acquired. We strongly advocate a comprehensive genomic approach in the management of ALK+ NSCLC patients who develop resistance mutations that are still targetable by a different ALK inhibitor.


Subject(s)
Antineoplastic Agents/pharmacology , Carcinoma, Non-Small-Cell Lung/drug therapy , Lung Neoplasms/drug therapy , Precision Medicine/methods , Protein Kinase Inhibitors/pharmacology , Anaplastic Lymphoma Kinase , Antineoplastic Agents/therapeutic use , Carcinoma, Non-Small-Cell Lung/enzymology , Carcinoma, Non-Small-Cell Lung/genetics , Drug Resistance, Neoplasm , Humans , Lung Neoplasms/enzymology , Lung Neoplasms/genetics , Protein Kinase Inhibitors/therapeutic use , Randomized Controlled Trials as Topic , Receptor Protein-Tyrosine Kinases/antagonists & inhibitors , Receptor Protein-Tyrosine Kinases/genetics
16.
Br J Cancer ; 114(7): 731-6, 2016 Mar 29.
Article in English | MEDLINE | ID: mdl-26954715

ABSTRACT

BACKGROUND: International guidelines, including NICE, recommend using the 21-gene Recurrence Score assay for guiding adjuvant treatment decisions in ER+, HER2-negative early breast cancer (BC). We investigated the impact of adding this assay to standard pathological tests on clinicians'/patients' treatment decisions and on patients' decisional conflict in the United Kingdom. METHODS: In this prospective multicentre study, eligibility criteria included: ER+ HER2-negative BC (N0/Nmic for patients ⩽50 years; ⩽3 positive lymph nodes for patients >50 years) and being fit for chemotherapy. Physicians'/patients' treatment choices and patients' decisional conflict were recorded pre- and post testing. RESULTS: The analysis included 137 patients. Overall, adjuvant treatment recommendations changed in 40.7% of patients, with the direction of the change consistent with the Recurrence Score results (net decrease in chemotherapy recommendation rate in low Recurrence Score patients and net increase in high Recurrence Score patients). Patients' choices were generally consistent with physicians' recommendations. Post-testing, patients' decisional conflict decreased significantly (P<0.0001). In the 67 patients meeting the NICE criteria for testing, the recommendation change rate was 49.3%. CONCLUSIONS: Recurrence Score testing significantly influenced treatment recommendations overall and in the subgroup of patients meeting the NICE criteria, suggesting that this test could substantially alter treatment patterns in the United Kingdom.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Biomarkers, Tumor/genetics , Breast Neoplasms/genetics , Gene Expression Profiling , Neoplasm Recurrence, Local/genetics , Patient Care Planning , Receptors, Estrogen/metabolism , Adult , Aged , Aged, 80 and over , Breast Neoplasms/drug therapy , Breast Neoplasms/metabolism , Breast Neoplasms/pathology , Chemotherapy, Adjuvant , Decision Making , Decision Support Techniques , Female , Follow-Up Studies , Humans , Middle Aged , Neoplasm Grading , Neoplasm Invasiveness , Neoplasm Recurrence, Local/drug therapy , Neoplasm Recurrence, Local/metabolism , Neoplasm Recurrence, Local/pathology , Neoplasm Staging , Prognosis , Prospective Studies , United Kingdom
17.
Int J Occup Environ Health ; 21(1): 14-22, 2015.
Article in English | MEDLINE | ID: mdl-25335826

ABSTRACT

BACKGROUND: The woodworking industry represents an important cause of occupational noise-induced hearing loss (NIHL), a significant yet underappreciated problem in many developing countries. OBJECTIVES: To describe the prevalence of occupational NIHL among woodworkers in Nepal and measure noise levels at workplaces. METHODS: We conducted a cross-sectional study with 124 woodworkers (88 carpenters, 36 sawyers), recruited through convenience sampling from 26 workplaces. Pure-tone audiometry between the frequencies 0·5 and 8 kHz ascertained participants' hearing status, and noise readings were taken at selected workplaces. RESULTS: In all, 31% of carpenters and 44% of sawyers met criteria for NIHL, with 7 and 17% meeting World Health Organization (WHO) criteria for hearing impairment (HI), respectively. Noise levels at various workplaces ranged from 71·2 to 93·9 dBA. CONCLUSIONS: Woodworkers in Nepal are at risk of occupational NIHL. As the industry develops, this problem will likely become more extensive, highlighting the need for workplace interventions and additional research.


Subject(s)
Hearing Loss, Noise-Induced/epidemiology , Noise, Occupational/adverse effects , Occupational Diseases/epidemiology , Occupational Exposure , Adolescent , Adult , Aged , Aged, 80 and over , Audiometry, Pure-Tone , Cross-Sectional Studies , Hearing Loss, Noise-Induced/etiology , Humans , Male , Middle Aged , Nepal/epidemiology , Noise, Occupational/statistics & numerical data , Occupational Diseases/etiology , Pilot Projects , Prevalence , Young Adult
19.
J Med Syst ; 37(3): 9936, 2013 Jun.
Article in English | MEDLINE | ID: mdl-23526127

ABSTRACT

Smartphones are becoming increasingly common in both personal and professional spheres. These devices have many features which can be successfully harnessed in healthcare, including rapid access to information, instant communication and improved organisation. In particular, the smartphone's potential as an educational tool is an area which is starting to gain recognition, with a number of institutions providing the device to medical students. However, before more universities follow suit, a better understanding of students' ownership, usage and attitudes relating to smartphones is required. We therefore distributed a questionnaire to clinical medical students at the University of Birmingham, UK, which aimed to fill these gaps in knowledge. Data were obtained from 361 participants, representing a response rate of 32%. Fifty-nine per cent of students owned a smartphone; 37% of these reported using the device to support their learning. Generally students were positive towards the concept of smartphones as future educational aids, with 84% believing the devices would be useful or very useful. However, 64% thought smartphones would be too costly to implement and 62% felt such technology was not in the medical school's interest. Themes which emerged upon analysis of free text supported general findings, with students also mentioning issues such as potential for unprofessional behaviour and dependence upon smartphones. In conclusion, it appears most medical students believe a smartphone would be a useful addition to their education, although financial barriers must be overcome before the device is more universally accepted.


Subject(s)
Smartphone , Students, Medical , Cell Phone , Communication , Humans , Surveys and Questionnaires
20.
Health Estate ; 66(10): 76-8, 2012 Nov.
Article in English | MEDLINE | ID: mdl-23193930

ABSTRACT

High quality architecture and extensive stakeholder consultations have transformed the delivery of Laboratory Medicine within Sheffield Teaching Hospitals NHS Foundation Trust (NHSFT), explains Tim Robinson, senior architect at Race Cottam Associates, the architects on a scheme that has seen laboratory services from across the city consolidated within one modern, spacious, well-lit, and well-equipped building that should provide an extremely positive, 'future-proofed' working environment for staff.


Subject(s)
Facility Design and Construction/standards , Laboratories, Hospital , England , Facility Design and Construction/methods
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