RESUMO
BACKGROUND: There are few data on international variation in chemotherapy use, despite it being a key treatment type for some patients with cancer. Here, we aimed to examine the presence and size of such variation. METHODS: This population-based study used data from Norway, the four UK nations (England, Northern Ireland, Scotland, and Wales), eight Canadian provinces (Alberta, British Columbia, Manitoba, Newfoundland and Labrador, Nova Scotia, Ontario, Prince Edward Island, and Saskatchewan), and two Australian states (New South Wales and Victoria). Patients aged 15-99 years diagnosed with cancer in eight different sites (oesophageal, stomach, colon, rectal, liver, pancreatic, lung, or ovarian cancer), with no other primary cancer diagnosis occurring from within the 5 years before to 1 year after the index cancer diagnosis or during the study period were included in the study. We examined variation in chemotherapy use from 31 days before to 365 days after diagnosis and time to its initiation, alongside related variation in patient group differences. Information was obtained from cancer registry records linked to clinical or patient management system data or hospital administration data. Random-effects meta-analyses quantified interjurisdictional variation using 95% prediction intervals (95% PIs). FINDINGS: Between Jan 1, 2012, and Dec 31, 2017, of 893â461 patients with a new diagnosis of one of the studied cancers, 111â569 (12·5%) did not meet the inclusion criteria, and 781â892 were included in the analysis. There was large interjurisdictional variation in chemotherapy use for all studied cancers, with wide 95% PIs: 47·5 to 81·2 (pooled estimate 66·4%) for ovarian cancer, 34·9 to 59·8 (47·2%) for oesophageal cancer, 22·3 to 62·3 (40·8%) for rectal cancer, 25·7 to 55·5 (39·6%) for stomach cancer, 17·2 to 56·3 (34·1%) for pancreatic cancer, 17·9 to 49·0 (31·4%) for lung cancer, 18·6 to 43·8 (29·7%) for colon cancer, and 3·5 to 50·7 (16·1%) for liver cancer. For patients with stage 3 colon cancer, the interjurisdictional variation was greater than that for all patients with colon cancer (95% PI 38·5 to 78·4; 60·1%). Patients aged 85-99 years had 20-times lower odds of chemotherapy use than those aged 65-74 years, with very large interjurisdictional variation in this age difference (odds ratio 0·05; 95% PI 0·01 to 0·19). There was large variation in median time to first chemotherapy (from diagnosis date) by cancer site, with substantial interjurisdictional variation, particularly for rectal cancer (95% PI -15·5 to 193·9 days; pooled estimate 89·2 days). Patients aged 85-99 years had slightly shorter median time to first chemotherapy compared with those aged 65-74 years, consistently between jurisdictions (-3·7 days, 95% PI -7·6 to 0·1). INTERPRETATION: Large variation in use and time to chemotherapy initiation were observed between the participating jurisdictions, alongside large and variable age group differences in chemotherapy use. To guide efforts to improve patient outcomes, the underlying reasons for these patterns need to be established. FUNDING: International Cancer Benchmarking Partnership (funded by the Canadian Partnership Against Cancer, Cancer Council Victoria, Cancer Institute New South Wales, Cancer Research UK, Danish Cancer Society, National Cancer Registry Ireland, The Cancer Society of New Zealand, National Health Service England, Norwegian Cancer Society, Public Health Agency Northern Ireland on behalf of the Northern Ireland Cancer Registry, DG Health and Social Care Scottish Government, Western Australia Department of Health, and Public Health Wales NHS Trust).
Assuntos
Neoplasias do Colo , Neoplasias Ovarianas , Neoplasias Retais , Feminino , Humanos , Benchmarking , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/epidemiologia , Fígado , Pulmão , Ontário/epidemiologia , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/epidemiologia , Medicina Estatal , Estômago , Vitória , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , MasculinoRESUMO
BACKGROUND: There is little evidence on variation in radiotherapy use in different countries, although it is a key treatment modality for some patients with cancer. Here we aimed to examine such variation. METHODS: This population-based study used data from Norway, the four UK nations (England, Northern Ireland, Scotland, and Wales), nine Canadian provinces (Alberta, British Columbia, Manitoba, New Brunswick, Newfoundland and Labrador, Nova Scotia, Ontario, Prince Edward Island, and Saskatchewan), and two Australian states (New South Wales and Victoria). Patients aged 15-99 years diagnosed with cancer in eight different sites (oesophageal, stomach, colon, rectal, liver, pancreatic, lung, or ovarian cancer), with no other primary cancer diagnosis occurring within the 5 years before to 1 year after the index cancer diagnosis or during the study period were included in the study. We examined variation in radiotherapy use from 31 days before to 365 days after diagnosis and time to its initiation, alongside related variation in patient group differences. Information was obtained from cancer registry records linked to clinical or patient management system data, or hospital administration data. Random-effects meta-analyses quantified interjurisdictional variation using 95% prediction intervals (95% PIs). FINDINGS: Between Jan 1, 2012, and Dec 31, 2017, of 902â312 patients with a new diagnosis of one of the studied cancers, 115â357 (12·8%) did not meet inclusion criteria, and 786,955 were included in the analysis. There was large interjurisdictional variation in radiotherapy use, with wide 95% PIs: 17·8 to 82·4 (pooled estimate 50·2%) for oesophageal cancer, 35·5 to 55·2 (45·2%) for rectal cancer, 28·6 to 54·0 (40·6%) for lung cancer, and 4·6 to 53·6 (19·0%) for stomach cancer. For patients with stage 2-3 rectal cancer, interjurisdictional variation was greater than that for all patients with rectal cancer (95% PI 37·0 to 84·6; pooled estimate 64·2%). Radiotherapy use was infrequent but variable in patients with pancreatic (95% PI 1·7 to 16·5%), liver (1·8 to 11·2%), colon (1·6 to 5·0%), and ovarian (0·8 to 7·6%) cancer. Patients aged 85-99 years had three-times lower odds of radiotherapy use than those aged 65-74 years, with substantial interjurisdictional variation in this age difference (odds ratio [OR] 0·38; 95% PI 0·20-0·73). Women had slightly lower odds of radiotherapy use than men (OR 0·88, 95% PI 0·77-1·01). There was large variation in median time to first radiotherapy (from diagnosis date) by cancer site, with substantial interjurisdictional variation (eg, oesophageal 95% PI 11·3 days to 112·8 days; pooled estimate 62·0 days; rectal 95% PI 34·7 days to 77·3 days; pooled estimate 56·0 days). Older patients had shorter median time to radiotherapy with appreciable interjurisdictional variation (-9·5 days in patients aged 85-99 years vs 65-74 years, 95% PI -26·4 to 7·4). INTERPRETATION: Large interjurisdictional variation in both use and time to radiotherapy initiation were observed, alongside large and variable age differences. To guide efforts to improve patient outcomes, underlying reasons for these differences need to be established. FUNDING: International Cancer Benchmarking Partnership (funded by the Canadian Partnership Against Cancer, Cancer Council Victoria, Cancer Institute New South Wales, Cancer Research UK, Danish Cancer Society, National Cancer Registry Ireland, The Cancer Society of New Zealand, National Health Service England, Norwegian Cancer Society, Public Health Agency Northern Ireland on behalf of the Northern Ireland Cancer Registry, DG Health and Social Care Scottish Government, Western Australia Department of Health, and Public Health Wales NHS Trust).
Assuntos
Neoplasias Ovarianas , Neoplasias Retais , Feminino , Humanos , Masculino , Benchmarking , Colo , Fígado , Pulmão , Ontário/epidemiologia , Medicina Estatal , Estômago , Vitória , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou maisRESUMO
BACKGROUND: Identifying patients presenting with nonspecific abdominal symptoms who have underlying cancer is a challenge. Common blood tests are widely used to investigate these symptoms in primary care, but their predictive value for detecting cancer in this context is unknown. We quantify the predictive value of 19 abnormal blood test results for detecting underlying cancer in patients presenting with 2 nonspecific abdominal symptoms. METHODS AND FINDINGS: Using data from the UK Clinical Practice Research Datalink (CPRD) linked to the National Cancer Registry, Hospital Episode Statistics and Index of Multiple Deprivation, we conducted a population-based cohort study of patients aged ≥30 presenting to English general practice with abdominal pain or bloating between January 2007 and October 2016. Positive and negative predictive values (PPV and NPV), sensitivity, and specificity for cancer diagnosis (overall and by cancer site) were calculated for 19 abnormal blood test results co-occurring in primary care within 3 months of abdominal pain or bloating presentations. A total of 9,427/425,549 (2.2%) patients with abdominal pain and 1,148/52,321 (2.2%) with abdominal bloating were diagnosed with cancer within 12 months post-presentation. For both symptoms, in both males and females aged ≥60, the PPV for cancer exceeded the 3% risk threshold used by the UK National Institute for Health and Care Excellence for recommending urgent specialist cancer referral. Concurrent blood tests were performed in two thirds of all patients (64% with abdominal pain and 70% with bloating). In patients aged 30 to 59, several blood abnormalities updated a patient's cancer risk to above the 3% threshold: For example, in females aged 50 to 59 with abdominal bloating, pre-blood test cancer risk of 1.6% increased to: 10% with raised ferritin, 9% with low albumin, 8% with raised platelets, 6% with raised inflammatory markers, and 4% with anaemia. Compared to risk assessment solely based on presenting symptom, age and sex, for every 1,000 patients with abdominal bloating, assessment incorporating information from blood test results would result in 63 additional urgent suspected cancer referrals and would identify 3 extra cancer patients through this route (a 16% relative increase in cancer diagnosis yield). Study limitations include reliance on completeness of coding of symptoms in primary care records and possible variation in PPVs if extrapolated to healthcare settings with higher or lower rates of blood test use. CONCLUSIONS: In patients consulting with nonspecific abdominal symptoms, the assessment of cancer risk based on symptoms, age and sex alone can be substantially enhanced by considering additional information from common blood test results. Male and female patients aged ≥60 presenting to primary care with abdominal pain or bloating warrant consideration for urgent cancer referral or investigation. Further cancer assessment should also be considered in patients aged 30 to 59 with concurrent blood test abnormalities. This approach can detect additional patients with underlying cancer through expedited referral routes and can guide decisions on specialist referrals and investigation strategies for different cancer sites.
Assuntos
Dor Abdominal , Testes Hematológicos , Neoplasias , Valor Preditivo dos Testes , Atenção Primária à Saúde , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Neoplasias/diagnóstico , Neoplasias/epidemiologia , Neoplasias/sangue , Inglaterra/epidemiologia , Dor Abdominal/diagnóstico , Dor Abdominal/etiologia , Idoso , Adulto , Estudos de Coortes , Detecção Precoce de Câncer/métodos , Idoso de 80 Anos ou maisRESUMO
We report ultrabroadband two-dimensional electronic spectroscopy (2D ES) measurements obtained in the pump-probe geometry using conventional optics. A phase-stabilized Michelson interferometer provides the pump-pulse delay interval, τ1, necessary to obtain the excitation-frequency dimension. Spectral resolution of the probe beam provides the detection-frequency dimension, ω3. The interferometer incorporates active phase stabilization via a piezo stage and feedback from interference of a continuous-wave reference laser detected in quadrature. To demonstrate the method, we measured a well-characterized laser dye sample and obtained the known peak structure. The vibronic peaks are modulated as a function of the waiting time, τ2, by vibrational wave packets. The interferometer simplifies ultrabroadband 2D ES measurements and analysis.
RESUMO
BACKGROUND: Patients with multiple conditions present a growing challenge for healthcare provision. Measures of multimorbidity may support clinical management, healthcare resource allocation and accounting for the health of participants in purpose-designed cohorts. The recently developed Cambridge Multimorbidity scores (CMS) have the potential to achieve these aims using primary care records, however, they have not yet been validated outside of their development cohort. METHODS: The CMS, developed in the Clinical Research Practice Dataset (CPRD), were validated in UK Biobank participants whose data is not available in CPRD (the cohort used for CMS development) with available primary care records (n = 111,898). This required mapping of the 37 pre-existing conditions used in the CMS to the coding frameworks used by UK Biobank data providers. We used calibration plots and measures of discrimination to validate the CMS for two of the three outcomes used in the development study (death and primary care consultation rate) and explored variation by age and sex. We also examined the predictive ability of the CMS for the outcome of cancer diagnosis. The results were compared to an unweighted count score of the 37 pre-existing conditions. RESULTS: For all three outcomes considered, the CMS were poorly calibrated in UK Biobank. We observed a similar discriminative ability for the outcome of primary care consultation rate to that reported in the development study (C-index: 0.67 (95%CI:0.66-0.68) for both, 5-year follow-up); however, we report lower discrimination for the outcome of death than the development study (0.69 (0.68-0.70) and 0.89 (0.88-0.90) respectively). Discrimination for cancer diagnosis was adequate (0.64 (0.63-0.65)). The CMS performs favourably to the unweighted count score for death, but not for the outcomes of primary care consultation rate or cancer diagnosis. CONCLUSIONS: In the UK Biobank, CMS discriminates reasonably for the outcomes of death, primary care consultation rate and cancer diagnosis and may be a valuable resource for clinicians, public health professionals and data scientists. However, recalibration will be required to make accurate predictions when cohort composition and risk levels differ substantially from the development cohort. The generated resources (including codelists for the conditions and code for CMS implementation in UK Biobank) are available online.
Assuntos
Bancos de Espécimes Biológicos , Neoplasias , Humanos , Multimorbidade , Biobanco do Reino Unido , Neoplasias/diagnóstico , Neoplasias/epidemiologia , Neoplasias/terapia , Reino UnidoRESUMO
Researchers and research funders aiming to improve diagnosis seek to identify if, when, where, and how earlier diagnosis is possible. This has led to the propagation of research studies using a wide range of methodologies and data sources to explore diagnostic processes. Many such studies use electronic health record data and focus on cancer diagnosis. Based on this literature, we propose a taxonomy to guide the design and support the synthesis of early diagnosis research, focusing on five key questions: Do healthcare use patterns suggest earlier diagnosis could be possible? How does the diagnostic process begin? How do patients progress from presentation to diagnosis? How long does the diagnostic process take? Could anything have been done differently to reach the correct diagnosis sooner? We define families of diagnostic research study designs addressing each of these questions and appraise their unique or complementary contributions and limitations. We identify three further questions on relationships between the families and their relevance for examining patient group inequalities, supported with examples from the cancer literature. Although exemplified through cancer as a disease model, we recognise the framework is also applicable to non-neoplastic disease. The proposed framework can guide future study design and research funding prioritisation.
Assuntos
Detecção Precoce de Câncer , Neoplasias , Humanos , Previsões , Neoplasias/diagnósticoRESUMO
Aggregates of conjugated organic molecules (i.e., dyes) may exhibit relatively large one- and two-exciton interaction energies, which has motivated theoretical studies on their potential use in quantum information science (QIS). In practice, one way of realizing large one- and two-exciton interaction energies is by maximizing the transition dipole moment (µ) and difference static dipole moment (Δd) of the constituent dyes. In this work, we characterized the electronic structure and excited-state dynamics of monomers and aggregates of four asymmetric polymethine dyes templated via DNA. Using steady-state and time-resolved absorption and fluorescence spectroscopy along with quantum-chemical calculations, we found the asymmetric polymethine dye monomers exhibited a large µ, an appreciable Δd, and a long excited-state lifetime (τp). We formed dimers of all four dyes and observed that one dye, Dy 754, displayed the strongest propensity for aggregation and exciton delocalization. Motivated by these results, we undertook a more comprehensive survey of Dy 754 dimer and tetramer aggregates using steady-state absorption and circular dichroism spectroscopy. Modeling these spectra revealed an appreciable excitonic hopping parameter (J). Lastly, we used femtosecond transient absorption spectroscopy to characterize τp of the dimer and tetramer, which we observed to be exceedingly short. This work revealed that asymmetric polymethine dyes exhibited µ, Δd, monomer τp, and J values promising for QIS; however, further work is needed to overcome excited-state quenching and achieve long aggregate τp.
RESUMO
Molecular (dye) aggregates are a materials platform of interest in light harvesting, organic optoelectronics, and nanoscale computing, including quantum information science (QIS). Strong excitonic interactions between dyes are key to their use in QIS; critically, properties of the individual dyes govern the extent of these interactions. In this work, the electronic structure and excited-state dynamics of a series of indolenine-based squaraine dyes incorporating dimethylamino (electron donating) and/or nitro (electron withdrawing) substituents, so-called asymmetric dyes, were characterized. The dyes were covalently tethered to DNA Holliday junctions to suppress aggregation and permit characterization of their monomer photophysics. A combination of density functional theory and steady-state absorption spectroscopy shows that the difference static dipole moment (Δd) successively increases with the addition of these substituents while simultaneously maintaining a large transition dipole moment (µ). Steady-state fluorescence and time-resolved absorption and fluorescence spectroscopies uncover a significant nonradiative decay pathway in the asymmetrically substituted dyes that drastically reduces their excited-state lifetime (τ). This work indicates that Δd can indeed be increased by functionalizing dyes with electron donating and withdrawing substituents and that, in certain classes of dyes such as these asymmetric squaraines, strategies may be needed to ensure long τ, e.g., by rigidifying the π-conjugated network.
RESUMO
DNA is a re-configurable, biological information-storage unit, and much remains to be learned about its heterogeneous structural dynamics. For example, while it is known that molecular dyes templated onto DNA exhibit increased photostability, the mechanism by which the structural dynamics of DNA affect the dye photophysics remains unknown. Here, we use femtosecond, two-dimensional electronic spectroscopy measurements of a cyanine dye, Cy5, to probe local conformations in samples of single-stranded DNA (ssDNA-Cy5), double-stranded DNA (dsDNA-Cy5), and Holliday junction DNA (HJ-DNA-Cy5). A line shape analysis of the 2D spectra reveals a strong excitation-emission correlation present in only the dsDNA-Cy5 complex, which is a signature of inhomogeneous broadening. Molecular dynamics simulations support the conclusion that this inhomogeneous broadening arises from a nearly degenerate conformer found only in the dsDNA-Cy5 complex. These insights will support future studies on DNA's structural heterogeneity.
Assuntos
Corantes Fluorescentes , Quinolinas , Corantes Fluorescentes/química , DNA/química , Carbocianinas/química , DNA de Cadeia SimplesRESUMO
BACKGROUND: Greater understanding of international cancer survival differences is needed. We aimed to identify predictors and consequences of cancer diagnosis through emergency presentation in different international jurisdictions in six high-income countries. METHODS: Using a federated analysis model, in this cross-sectional population-based study, we analysed cancer registration and linked hospital admissions data from 14 jurisdictions in six countries (Australia, Canada, Denmark, New Zealand, Norway, and the UK), including patients with primary diagnosis of invasive oesophageal, stomach, colon, rectal, liver, pancreatic, lung, or ovarian cancer during study periods from Jan 1, 2012, to Dec 31, 2017. Data were collected on cancer site, age group, sex, year of diagnosis, and stage at diagnosis. Emergency presentation was defined as diagnosis of cancer within 30 days after an emergency hospital admission. Using logistic regression, we examined variables associated with emergency presentation and associations between emergency presentation and short-term mortality. We meta-analysed estimates across jurisdictions and explored jurisdiction-level associations between cancer survival and the percentage of patients diagnosed as emergencies. FINDINGS: In 857 068 patients across 14 jurisdictions, considering all of the eight cancer sites together, the percentage of diagnoses through emergency presentation ranged from 24·0% (9165 of 38 212 patients) to 42·5% (12 238 of 28 794 patients). There was consistently large variation in the percentage of emergency presentations by cancer site across jurisdictions. Pancreatic cancer diagnoses had the highest percentage of emergency presentations on average overall (46·1% [30 972 of 67 173 patients]), with the jurisdictional range being 34·1% (1083 of 3172 patients) to 60·4% (1317 of 2182 patients). Rectal cancer had the lowest percentage of emergency presentations on average overall (12·1% [10 051 of 83 325 patients]), with a jurisdictional range of 9·1% (403 of 4438 patients) to 19·8% (643 of 3247 patients). Across the jurisdictions, older age (ie, 75-84 years and 85 years or older, compared with younger patients) and advanced stage at diagnosis compared with non-advanced stage were consistently associated with increased emergency presentation risk, with the percentage of emergency presentations being highest in the oldest age group (85 years or older) for 110 (98%) of 112 jurisdiction-cancer site strata, and in the most advanced (distant spread) stage category for 98 (97%) of 101 jurisdiction-cancer site strata with available information. Across the jurisdictions, and despite heterogeneity in association size (I2=93%), emergency presenters consistently had substantially greater risk of 12-month mortality than non-emergency presenters (odds ratio >1·9 for 112 [100%] of 112 jurisdiction-cancer site strata, with the minimum lower bound of the related 95% CIs being 1·26). There were negative associations between jurisdiction-level percentage of emergency presentations and jurisdiction-level 1-year survival for colon, stomach, lung, liver, pancreatic, and ovarian cancer, with a 10% increase in percentage of emergency presentations in a jurisdiction being associated with a decrease in 1-year net survival of between 2·5% (95% CI 0·28-4·7) and 7·0% (1·2-13·0). INTERPRETATION: Internationally, notable proportions of patients with cancer are diagnosed through emergency presentation. Specific types of cancer, older age, and advanced stage at diagnosis are consistently associated with an increased risk of emergency presentation, which strongly predicts worse prognosis and probably contributes to international differences in cancer survival. Monitoring emergency presentations, and identifying and acting on contributing behavioural and health-care factors, is a global priority for cancer control. FUNDING: Canadian Partnership Against Cancer; Cancer Council Victoria; Cancer Institute New South Wales; Cancer Research UK; Danish Cancer Society; National Cancer Registry Ireland; The Cancer Society of New Zealand; National Health Service England; Norwegian Cancer Society; Public Health Agency Northern Ireland, on behalf of the Northern Ireland Cancer Registry; the Scottish Government; Western Australia Department of Health; and Wales Cancer Network.
Assuntos
Neoplasias Ovarianas , Neoplasias Retais , Idoso de 80 Anos ou mais , Benchmarking , Canadá , Estudos Transversais , Feminino , Hospitais , Humanos , Prognóstico , Fatores de Risco , Medicina Estatal , VitóriaRESUMO
Molecular aggregates are of interest to a broad range of fields including light harvesting, organic optoelectronics, and nanoscale computing. In molecular aggregates, nonradiative decay pathways may emerge that were not present in the constituent molecules. Such nonradiative decay pathways may include singlet fission, excimer relaxation, and symmetry-breaking charge transfer. Singlet fission, sometimes referred to as excitation multiplication, is of great interest to the fields of energy conversion and quantum information. For example, endothermic singlet fission, which avoids energy loss, has been observed in covalently bound, linear perylene trimers and tetramers. In this work, the electronic structure and excited-state dynamics of dimers of a perylene derivative templated using DNA were investigated. Specifically, DNA Holliday junctions were used to template the aggregation of two perylene molecules covalently linked to a modified uracil nucleobase through an ethynyl group. The perylenes were templated in the form of monomer, transverse dimer, and adjacent dimer configurations. The electronic structure of the perylene monomers and dimers were characterized via steady-state absorption and fluorescence spectroscopy. Initial insights into their excited-state dynamics were gleaned from relative fluorescence intensity measurements, which indicated that a new nonradiative decay pathway emerges in the dimers. Femtosecond visible transient absorption spectroscopy was subsequently used to elucidate the excited-state dynamics. A new excited-state absorption feature grows in on the tens of picosecond timescale in the dimers, which is attributed to the formation of perylene anions and cations resulting from symmetry-breaking charge transfer. Given the close proximity required for symmetry-breaking charge transfer, the results shed promising light on the prospect of singlet fission in DNA-templated molecular aggregates.
Assuntos
Perileno , DNA , DNA Cruciforme , Imidas/química , UracilaRESUMO
OBJECTIVE: To evaluate the relationship between hospital volume and intermediate- and long-term patient survival for patients undergoing nephrectomy for renal cell carcinoma (RCC). PATIENTS AND METHODS: Adult patients with RCC treated with nephrectomy between 2000 and 2010 were identified from the English Hospital Episode Statistics database and National Cancer Data Repository. Patients with nodal or metastatic disease were excluded. Hospitals were categorised into low- (LV; <20 cases/year), medium- (20-39 cases/year) and high-volume (HV; ≥40 cases/year), based on annual cases of RCC nephrectomy. Multivariable Cox regression analyses were used to calculate hazard ratios (HRs) for all-cause mortality by hospital volume, adjusting for patient, tumour and surgical characteristics. We assessed conditional survival over three follow-up periods: short (30 days to 1 year), intermediate (1-3 years) and long (3-5 years). We additionally explored whether associations between volume and outcomes varied by tumour stage. RESULTS: A total of 12 912 patients were included. Patients in HV hospitals had a 34% reduction in mortality risks up to 1 year compared to those in LV hospitals (HR 0.66, 95% confidence interval 0.53-0.83; P < 0.01). Assuming causality, treatment in HV hospitals was associated with one fewer death in every 71 patients treated. Benefit of nephrectomy centralisation did not change with higher T stage (P = 0.17). No significant association between hospital volume and survival was observed beyond the first year. CONCLUSIONS: Nephrectomy for RCC in HV hospitals was associated with improved survival for up to 1 year after treatment. Our results contribute new insights regarding the value of nephrectomy centralisation.
Assuntos
Carcinoma de Células Renais/mortalidade , Carcinoma de Células Renais/cirurgia , Hospitais com Alto Volume de Atendimentos , Hospitais com Baixo Volume de Atendimentos , Neoplasias Renais/mortalidade , Neoplasias Renais/cirurgia , Nefrectomia , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Humanos , Pessoa de Meia-Idade , Taxa de Sobrevida , Fatores de Tempo , Adulto JovemRESUMO
Compared with experimental spectra, calculations for conjugated phenyl and thiophene oligomers tend to overestimate the ground state Raman intensities of higher-frequency vibrations (1200-1800 cm-1) relative to the intensities at lower frequencies (<1200 cm-1). The discrepancy was observed in previous benchmarking work that examined the method dependence of the calculated Raman spectra for a series of aromatic molecules. This paper further investigates the nature of the discrepancy by examining the role of anharmonic corrections and the dependence of the calculated Raman spectra on the inter-ring torsion angle for the representative molecules biphenyl (BP), 2-phenylthiophene (PT), and 2,2'-bithiophene (BT). Perturbative anharmonic corrections to the spectra calculated using density functional theory (DFT) provide only slightly better agreement with experiment. On the other hand, calculations at larger torsion angles give up to 30% improvement in the relative Raman intensities compared with the spectra calculated at the optimized geometries. The torsion-angle dependence of the Raman intensities is most pronounced for delocalized C-C and C-S stretching modes, and less pronounced for bending and ring distortion modes that do not involve inter-ring stretching. Higher-level calculations using the coupled cluster with single, double, and perturbative triple excitations [CCSD(T)] method indicate that DFT underestimates the energy barrier for torsion isomerization at small angles, and it overestimates the barriers at large angles, thus predicting minimum geometries at torsion angles that are too small. Therefore, the results suggest that the discrepancy in relative Raman intensities may be related to an overestimation of inter-ring conjugation by DFT, which also tends to favor geometries that are too planar.
RESUMO
BACKGROUND: Lung cancer 5-year survival has doubled over 15 years. Although the risk of second primary cancer is recognised, quantification over time is lacking. We describe the incidence of second and higher order smoking-related primary cancers in lung cancer survivors, identifying high-incidence groups and how incidence changes over time from first diagnosis. METHODS: Data on smoking-related primary cancers (lung, laryngeal, head and neck, oesophageal squamous cell carcinoma and bladder) diagnosed in England between 2000 and 2014 were obtained from Public Health England National Cancer Registration and Analysis Service. We calculated absolute incidence rates and standardised incidence rate ratios, both overall and for various subgroups of second primary cancer for up to 10 years from the initial diagnosis of lung cancer, using Poisson regression. RESULTS: Elevated incidence of smoking-related second primary cancer persists for at least 10 years from first lung cancer diagnosis with those aged 50 and 79 at first diagnosis at particularly high risk. The most frequent type of second malignancy was lung cancer although the highest standardised incidence rate ratios were for oesophageal squamous cell carcinoma (2.4) and laryngeal cancers (2.8) and consistently higher in women than in men. Over the last decade, the incidence of second primary lung cancer has doubled. CONCLUSION: Lung cancer survivors have increased the incidence of subsequent lung, laryngeal, head and neck and oesophageal squamous cell carcinoma for at least a decade from the first diagnosis. Consideration should be given to increasing routine follow-up from 5 years to 10 years for those at highest risk, alongside surveillance for other smoking-related cancers.
Assuntos
Neoplasias de Cabeça e Pescoço/epidemiologia , Neoplasias Pulmonares/epidemiologia , Segunda Neoplasia Primária/epidemiologia , Fumar/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Inglaterra/epidemiologia , Feminino , Seguimentos , Neoplasias de Cabeça e Pescoço/etiologia , Humanos , Incidência , Neoplasias Pulmonares/etiologia , Masculino , Pessoa de Meia-Idade , Segunda Neoplasia Primária/etiologia , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Fumar/epidemiologia , Taxa de Sobrevida/tendências , Fatores de TempoRESUMO
Femtosecond stimulated Raman scattering (FSRS) is a spectroscopic technique that probes the structural dynamics of molecules. The technique typically relies on an electronic resonance condition to increase signal strength or enhance species selectivity, giving a Raman enhancement that is vibrational-mode-specific and depends on the character of the resonant electronic state. The resonance condition is complicated for molecules already in an excited electronic state and also for systems where multiple electronic states are resonant or nearly resonant with the Raman excitation energy, both of which are often the case for FSRS. This paper examines the excitation wavelength dependence of the FSRS spectrum for the lowest triplet state of 2-phenylthiophene (PT). Except for an overall increase of the signal strength due to the resonance condition, the relative intensities of most Raman bands are relatively insensitive to the excitation wavelength, and the spectrum is remarkably similar to the calculated off-resonance spectrum obtained by neglecting the resonance condition. On the other hand, calculated resonance Raman spectra using a gradient approximation to simulate the resonance condition correctly predict the excitation wavelength dependence for a few modes but overestimate the relative enhancement of others. The weak wavelength dependence of the triplet spectrum of PT contrasts the case of the singlet FSRS spectrum for the same molecule. We attribute this discrepancy to a combination of homogeneous broadening, overlapping TN â T1 transitions, and possibly vibronic coupling among states in the triplet manifold. This work highlights important limitations in using standard approaches to simulate excited-state resonance Raman spectra.
RESUMO
BACKGROUND: statistics comparing the stage at diagnosis of geographically defined populations of cancer patients are increasingly used in public reporting to monitor geographical inequalities but may be confounded by patient case mix. We explore the impact of case-mix adjustment on a publicly reported measure of early stage at diagnosis in England. METHODS: We analyzed data used for publicly reported statistics about the stage of patients diagnosed with 1 of 11 solid tumours in 2015 in England, including information on cancer site (bladder, breast, colon, rectum, kidney, lung, melanoma, non-Hodgkin lymphoma, ovarian, prostate, endometrial), age, gender, income deprivation and population-based commissioning organization. We investigated how cancer site and other patient characteristics influence organizational comparisons and attainment of early-stage targets (≥60% of all cases diagnosed in TNM stages I-II). RESULTS: Adjusting for patient case mix reduced between-organization variance by more than 50%, resulting in appreciable discordance in organizational ranks (Kendall's tau = 0.53), with 18% (37/207) of organizations being reclassified as meeting/failing the early-stage target due to case mix. CONCLUSION: Summary statistics on stage of cancer diagnosis for geographical populations currently used as public health surveillance tools to monitor organizational inequalities need to account for patient sociodemographic characteristics and cancer site case mix.
Assuntos
Estadiamento de Neoplasias , Saúde Pública , Risco Ajustado , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Inglaterra , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Saúde Pública/estatística & dados numéricos , Sistema de Registros , Fatores SocioeconômicosRESUMO
Purpose: Meningiomas are the commonest predominantly non-malignant brain tumour in adults. The use of surgery appears to be increasing, and outcomes are thought to be good, but whole nation data for England is scarce. The aim of this report is to examine the epidemiology of patients operated for cranial and spinal meningioma in England, and to assess associations between outcomes and gender, age, meningioma site (cranial or spinal), and grade.Material and methods: A search strategy encompassing all patients coded with cranial and spinal meningioma treated between January 1999 and December 2013 was obtained from data linkage between the National Cancer Registration and Analysis Service and Hospital Episode Statistics for England.Results: 25,694 patients were diagnosed with meningioma in England between 1999 and 2013, in whom 24,302 were cranial and 1392 spinal. Of these patients, 14,229 (60%) cranial and 1188 (85%) spinal meningioma received surgery. Of those operated on 70.1% were women, and, where the tumour grade was recorded, 79.5% were WHO grade I, 18.4% grade II, and 2.1% grade III. Five and ten year net survival rates for surgically treated cranial meningiomas were respectively 90% and 81% for those with WHO grade I, 80% and 63% for grade II, and 30% and 15% for WHO grade III tumours. Overall survival after surgery is better in women, younger adults, and people with spinal or lower grade meningiomas. Outcomes have improved over the time period examined.Conclusion: The outcome for patients with meningioma is good and is improving. However, there remains a significant mortality related to the disease process.
Assuntos
Neoplasias Encefálicas/epidemiologia , Neoplasias Encefálicas/cirurgia , Meningioma/epidemiologia , Meningioma/cirurgia , Neoplasias da Coluna Vertebral/epidemiologia , Neoplasias da Coluna Vertebral/cirurgia , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Neoplasias Encefálicas/patologia , Criança , Pré-Escolar , Inglaterra/epidemiologia , Feminino , Humanos , Lactente , Masculino , Meningioma/patologia , Pessoa de Meia-Idade , Gradação de Tumores , Procedimentos Neurocirúrgicos , Sistema de Registros , Estudos Retrospectivos , Fatores Sexuais , Neoplasias da Coluna Vertebral/patologia , Taxa de Sobrevida , Resultado do Tratamento , Adulto JovemRESUMO
OBJECTIVE: To describe the temporal trends in nephrectomy practice and outcomes for English patients with renal cell carcinoma (RCC). PATIENTS AND METHODS: Adult RCC nephrectomy patients treated between 2000 and 2010 were identified in the National Cancer Data Repository and Hospital Episode Statistics, and followed-up until date of death or 31 December 2015 (n = 30 763). We estimated the annual frequency for each nephrectomy type, the hospital and surgeon numbers and their case volumes. We analysed short-term surgical outcomes, as well as 1- and 5-year relative survivals. RESULTS: Annual RCC nephrectomy number increased by 66% during the study period. Hospital number decreased by 24%, whilst the median annual hospital volume increased from 10 to 23 (P < 0.01). Surgeon number increased by 27% (P < 0.01), doubling the median consultant number per hospital. The proportion of minimally invasive surgery (MIS) nephrectomies rose from 1% to 46%, whilst the proportion of nephron-sparing surgeries (NSS) increased from 5% to 16%, with 29% of all T1 disease treated with partial nephrectomy in 2010 (P < 0.01). The 30-day mortality rate halved from 2.4% to 1.1% and 90-day mortality decreased from 4.9% to 2.6% (P < 0.01). The 1-year relative survival rate increased from 86.9% to 93.4%, whilst the 5-year relative survival rate rose from 68.2% to 81.2% (P < 0.01). Improvements were most notable in patients aged ≥65 years and those with T3 and T4 disease. CONCLUSIONS: Surgical RCC management has changed considerably with nephrectomy centralisation and increased NSS and MIS. In parallel, we observed significant improvements in short- and long-term survival particularly for elderly patients and those with locally advanced disease.
Assuntos
Atenção à Saúde/estatística & dados numéricos , Neoplasias Renais/cirurgia , Nefrectomia/estatística & dados numéricos , Tratamentos com Preservação do Órgão/estatística & dados numéricos , Idoso , Inglaterra/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Néfrons , Padrões de Prática Médica/estatística & dados numéricos , Estudos Retrospectivos , Análise de Sobrevida , Fatores de Tempo , Resultado do TratamentoRESUMO
Femtosecond stimulated Raman scattering (FSRS) measurements typically probe the structural dynamics of a molecule in the first electronically excited state, S1. While these measurements often rely on an electronic resonance condition to increase signal strength or enhance species selectivity, the effects of the resonance condition are usually neglected. However, mode-specific enhancements of the vibrational transitions in an FSRS spectrum contain detailed information about the resonant (upper) electronic state. Analogous to ground-state resonance Raman spectroscopy, the relative intensities of the Raman bands reveal displacements of the upper potential energy surface due to changes in the bonding pattern upon S n â S1 electronic excitation, and therefore provide a sensitive probe of the ultrafast dynamics in the higher-lying state, S n. Raman gain profiles from the wavelength-dependent FSRS spectrum of the model compound 2,5-diphenylthiophene (DPT) reveal several modes with large displacement in the upper potential energy surface, including strong enhancement of a delocalized C-S-C stretching and ring deformation mode. The experimental results provide a benchmark for comparison with calculated spectra using time-dependent density functional theory (TD-DFT) and equation-of-motion coupled-cluster theory with single and double excitations (EOM-CCSD), where the calculations are based on the time-dependent formalism for resonance Raman spectroscopy. The simulated spectra are obtained from S1-S n transition strengths and the energy gradients of the upper (S n) potential energy surfaces along the S1 normal mode coordinates. The experimental results provide a stringent test of the computational approach, and indicate important limitations based on the level of theory and basis set. This work provides a foundation for making more accurate assignments of resonance-enhanced excited-state Raman spectra, as well as extracting novel information about higher-lying excited states in the transient absorption spectrum of a molecule.