Publications

2021
Lee SF, Redondo Sánchez D, Sánchez M{\'ıa-J, Gelaye B, Chiang CL, Wong IOL, Cheung DST, Luque-Fernandez MA. Trends in gender of authors of original research in oncology among major medical journals: a retrospective bibliometric study [Internet]. BMJ Open 2021;11(10) Publisher's VersionAbstract
Objective We evaluated the temporal trend in gender ratios of first and last authors in the field of oncological research published in major general medical and oncology journals and examined the gender pattern in coauthorship.Design We conducted a retrospective study in PubMed using the R package RISmed. We retrieved original research articles published in four general medical journals and six oncology specialty journals. These journals were selected based on their impact factors and popularity among oncologists. We identified the names of first and last authors from 1 January 2002 to 31 December 2019. The gender of the authors was identified and validated using the Gender API database (https://gender-api.com/).Primary and secondary outcome measures The percentages of first and last authors by gender and the gender ratios (male to female) and temporal trends in gender ratios of first and last authors were determined.Results We identified 34 624 research articles, in which 32 452 had the gender of both first and last authors identified. Among these 11 650 (33.6%) had women as the first author and 7908 (22.8%) as the last author, respectively. The proportion of female first and last authors increased from 26.6% and 16.2% in 2002, to 32.9% and 27.5% in 2019, respectively. However, the gender ratio (male to female) of first and last authors decreased by 1.5% and 2.6% per year, respectively, which were statistically significant (first author: incidence rate ratio (IRR) 0.98, 95% CI 0.97 to 1.00; last author: IRR 0.97, 95% CI 0.96 to 0.99). Male first and last authorship was the most common combination. Male–female and female–female pairs increased by 2.0% and 5.0%, respectively (IRR 1.02, 95% CI 1.01 to 1.03 and IRR 1.05, 95% CI 1.04 to 1.06, respectively).Conclusions The continued under-representation of women means that more efforts to address parity for advancement of women in academic oncology are needed.Data are available in a public, open access repository.
e046618.full_.pdf
Niksic M, Redondo-Sanchez D, Chang Y-L, RODRIGUEZ-BARRANCO MIGUEL, Exposito-Hernandez J, Marcos-Gragera R, Oliva-Poch E, Bosch-Barrera J, Sanchez M-J, Luque-Fernandez MA. The role of multimorbidity in short-term mortality of lung cancer patients in Spain: a population-based cohort study. BMC Cancer 2021;21(1):1048.Abstract
Chronic diseases often occur simultaneously and tend to be associated with adverse health outcomes, but limited research has been undertaken to understand their role in lung cancer mortality. Therefore, this study aims to describe the prevalence and patterns of having one (comorbidity) or ≥ 2 chronic diseases (multimorbidity) among lung cancer patients in Spain, and to examine the association between comorbidity or multimorbidity and short-term mortality risk at six months after cancer diagnosis. In this population-based cohort study, data were drawn from two Spanish population-based cancer registries, Girona and Granada, and electronic health records. We identified 1259 adult lung cancer patients, diagnosed from 1st January 2011 to 31st December 2012. We identified the most common patterns of individual comorbidities and their pairwise correlations. We used a flexible parametric modelling approach to assess the overall short-term mortality risk 6 months after cancer diagnosis by levels of comorbidity after adjusting for age, sex, smoking status, province of residence, surgery, cancer stage, histology, and body mass index. We found high prevalence of comorbidity in lung cancer patients, especially among the elderly, men, those diagnosed with advanced-stage tumours, smokers, and obese patients. The most frequent comorbidities were chronic obstructive pulmonary disease (36.6%), diabetes (20.7%) and heart failure (16.8%). The strongest pairwise correlation was the combination of heart failure with renal disease (r = 0.20, p < 0.01), and heart failure with diabetes (r = 0.16, p < 0.01). Patients with either one or two or more comorbidities had 40% higher overall mortality risk than those without comorbidities (aHR for comorbidity: 1.4, 95%CI: 1.1–1.7; aHR for multimorbidity: 1.4, 95%CI: 1.1–1.8), when relevant confounding factors were considered. The presence of comorbid diseases, rather than the number of comorbidities, was associated with increasing the risk of short-term lung cancer mortality in Spain. Comorbidity was a consistent and independent predictor of mortality among lung cancer patients, six months after diagnosis. The most common comorbid conditions were age-, obesity- and tobacco-related diseases. Our findings highlight the need to develop targeted preventive interventions and more personalised clinical guidelines to address the needs of lung cancer patients with one or more comorbidities in Spain.
Lee SF, Evens AM, Ng AK, Luque-Fernandez M-A. Socioeconomic inequalities in treatment and relative survival among patients with diffuse large B-cell lymphoma: a Hong Kong population-based study [Internet]. Scientific Reports 2021;11(1):17950. Publisher's VersionAbstract
The influence of socioeconomic status (SES) on access to standard chemotherapy and/or monoclonal antibody therapy, and associated secular trends, relative survival, and excess mortality, among diffuse large B-cell lymphoma (DLBCL) patients is not clear. We conducted a Hong Kong population-based cohort study and identified adult patients with histologically diagnosed DLBCL between 2000 and 2018. We examined the association of SES levels with the odds and the secular trends of receipt of chemotherapy and/or rituximab. Additionally, we estimated the long-term relative survival by SES utilizing Hong Kong life tables. Among 4017 patients with DLBCL, 2363 (58.8%) patients received both chemotherapy and rituximab and 740 (18.4%) patients received chemotherapy alone, while 1612 (40.1%) and 914 (22.8%) patients received no rituximab or chemotherapy, respectively. On multivariable analysis, low SES was associated with lesser use of chemotherapy (odd ratio $[$OR$]$ 0.44; 95% CI 0.34–0.57) and rituximab (OR 0.41; 95% CI 0.32–0.52). The socioeconomic disparity for either treatment showed no secular trend of change. Additionally, patients with low SES showed increased excess mortality, with a hazard ratio of 2.34 (95% CI 1.67–3.28). Improving survival outcomes for patients with DLBCL requires provision of best available medical care and securing access to treatment regardless of patients'SES.
Smith MJ, Luque-Fernandez MA, Belot A, Quartagno M, Bonaventure A, Majano SB, Rachet B, Njagi EN. Investigating the inequalities in route to diagnosis amongst patients with diffuse large B-cell or follicular lymphoma in England [Internet]. British Journal of Cancer 2021; Publisher's VersionAbstract
Diagnostic delay is associated with lower chances of cancer survival. Underlying comorbidities are known to affect the timely diagnosis of cancer. Diffuse large B-cell (DLBCL) and follicular lymphomas (FL) are primarily diagnosed amongst older patients, who are more likely to have comorbidities. Characteristics of clinical commissioning groups (CCG) are also known to impact diagnostic delay. We assess the association between comorbidities and diagnostic delay amongst patients with DLBCL or FL in England during 2005–2013.
Redondo-Sánchez D, Marcos-Gragera R, Carulla M, Lopez de Munain A, Sabater Gregori C, Jimenez Chillarón R, Guevara M, Nuñez O, Fernández-Navarro P, Sánchez M-J, Luque-Fernandez MA. Lung, Breast and Colorectal Cancer Incidence by Socioeconomic Status in Spain: A Population-Based Multilevel Study [Internet]. Cancers 2021;13(11) Publisher's VersionAbstract
Socioeconomic inequalities in cancer incidence are not well documented in southern Europe. We aim to study the association between socioeconomic status (SES) and colorectal, lung, and breast cancer incidence in Spain. We conducted a multilevel study using data from Spanish population-based cancer registries, including incident cases diagnosed for the period 2010–2013 in nine Spanish provinces. We used Poisson mixed-effects models, including the census tract as a random intercept, to derive cancer incidence rate ratios by SES, adjusted for age and calendar year. Male adults with the lowest SES, compared to those with the highest SES, showed weak evidence of being at increased risk of lung cancer (risk ratio (RR): 1.18, 95% CI: 0.94–1.46) but showed moderate evidence of being at reduced risk of colorectal cancer (RR: 0.84, 95% CI: 0.74–0.97). Female adults with the lowest SES, compared to those with the highest SES, showed strong evidence of lower breast cancer incidence with 24% decreased risk (RR: 0.76, 95% CI: 0.68–0.85). Among females, we did not find evidence of an association between SES and lung or colorectal cancer. The associations found between SES and cancer incidence in Spain are consistent with those obtained in other European countries.
Lee SF, Nikšić M, Rachet B, Sanchez M-J, Luque-Fernandez MA. Socioeconomic Inequalities and Ethnicity Are Associated with a Positive COVID-19 Test among Cancer Patients in the UK Biobank Cohort [Internet]. Cancers 2021;13(7) Publisher's VersionAbstract
We explored the role of socioeconomic inequalities in COVID-19 incidence among cancer patients during the first wave of the pandemic. We conducted a case-control study within the UK Biobank cohort linked to the COVID-19 tests results available from 16 March 2020 until 23 August 2020. The main exposure variable was socioeconomic status, assessed using the Townsend Deprivation Index. Among 18,917 participants with an incident malignancy in the UK Biobank cohort, 89 tested positive for COVID-19. The overall COVID-19 incidence was 4.7 cases per 1000 incident cancer patients (95%CI 3.8–5.8). Compared with the least deprived cancer patients, those living in the most deprived areas had an almost three times higher risk of testing positive (RR 2.6, 95%CI 1.1–5.8). Other independent risk factors were ethnic minority background, obesity, unemployment, smoking, and being diagnosed with a haematological cancer for less than five years. A consistent pattern of socioeconomic inequalities in COVID-19 among incident cancer patients in the UK highlights the need to prioritise the cancer patients living in the most deprived areas in vaccination planning. This socio-demographic profiling of vulnerable cancer patients at increased risk of infection can inform prevention strategies and policy improvements for the coming pandemic waves.
Bouvier A-M, Jooste V, Sanchez-Perez MJ, Bento MJ, Rodrigues JR, Marcos-Gragera R, Carmona-Garcia MC, Luque-Fernandez MA, Minicozzi P, Bouvier V, Innos K, Sant M, Eycken LV, Henau K, Grozeva T, Valerianova Z, Innos K, Mägi M, Bouvier V, Launoy G, Robaszkiewicz M, Bouvier AM, Jooste V, Babaev V, Katalinic A, Ólafsdóttir EJ, Tryggvadóttir L, Amati C, Baili P, Bonfarnuzzo S, Margutti C, Meneghini E, Minicozzi P, Moretti G, Sant M, Cirilli C, Carrozzi G, Spata E, Tumino R, Rossi PG, Vicentini M, Stracci F, Bianconi F, Contiero P, Tagliabue G, Kycler W, Oko M, Macek P, Smok-Kalwat J, Bielska-Lasota M, Kycler W, Oko M, Bento MJ, Rodrigues J, Mayer-da-Silva A, Miranda A, Primic-Žakelj M, Jarm K, Almar E, Mateos A, Bidaurrazaga J, De La Cruz M, Alberich C, Torrella-Ramos A, García JMD, Marcos-Navarro AI, Carmona-Garcia C, Marcos-Gragera R, Luque-Fernandez MA, Sánchez-Pérez MJ, Ardanaz E, Guevara M, Bouchardy C, Fournier E. Differences in the management and survival of metastatic colorectal cancer in Europe. A population-based study [Internet]. Digestive and Liver Disease 2021; Publisher's VersionAbstract
Background The management regarding metastatic colorectal cancer throughout Europe is not well known. Aims To draw a European comparison of the management and prognosis of metastatic colorectal cancers. Methods Factors associated with chemotherapy administration were identified through logistic regressions. Net survival was estimated and crude probabilities of death related to cancer and other causes using a flexible cumulative hazard model. Results Among the 13 227 patients with colorectal cancer diagnosed between 2010 and 2013 in cancer registries from 10 European countries, 3140 were metastatic. 62% of metastatic patients received chemotherapy. Compared to Spain, the related adjusted odds ratios ranged from 0.7 to 4.0 (P<0.001) according to country. The 3-year net survival by country ranged between 16% and 37%. The survival gap between countries diminished from 21% to 10% when adjusting for chemotherapy, age and sex. Geographical differences in the crude probability of death related to cancer were large for patients <70 or ≥80 years at diagnosis. Conclusion Heterogeneity in the application of European guidelines partly explain these differences. General health between populations, accessibility to a reference centre, or provision of health care could also be involved. Further population-based studies are warranted to disentangle between these possible explanations.
Abdollahpour I, Nedjat S, Almasi-Hashiani A, Nazemipour M, Mansournia MA, Luque-Fernandez MA. Estimating the Marginal Causal Effect and Potential Impact of Waterpipe Smoking on Multiple Sclerosis Using Targeted Maximum Likelihood Estimation Method: a Large Population-Based Incident Case-Control Study [Internet]. American Journal of Epidemiology 2021; Publisher's VersionAbstract
There are few if any reports regarding the role of lifetime waterpipe smoking in multiple sclerosis (MS) etiology. The authors investigated the association between waterpipe and MS, adjusted for confounders. This was a population-based incident case-control study conducted in Tehran, Iran. Cases (n=547) were 15–50-year-old patients identified from the Iranian Multiple Sclerosis Society between 2013 and 2015. Population-based controls (n=1057) were 15–50-year old recruited by random digit telephone dialing. A double robust estimator method known as targeted maximum likelihood estimator (TMLE) was used to estimate the marginal risk ratio and odds ratio between waterpipe and MS. The both estimated RR and OR was 1.70 (95% CI: 1.34, 2.17). The population attributable fraction was 21.4% (95% CI: 4.0%, 38.8%). Subject to the limitations of case-control studies in interpreting associations causally, this study suggests that waterpipe use, or its strongly related but undetermined factors, increases the risk of MS. Further epidemiological studies including nested case-control studies are needed to confirm these results.
2020
Smith MJ, Maringe C, Rachet B, Mansournia MA, Zivich PN, Cole SR, Luque-Fernandez MA. Tutorial: Introduction to computational causal inference using reproducible Stata, R and Python code [Internet]. https://arxiv.org/abs/2012.09920 2020;2020(December-2020) Publisher's VersionAbstract
The purpose of many health studies is to estimate the effect of an exposure on an outcome. It is not always ethical to assign an exposure to individuals in randomised controlled trials, instead observational data and appropriate study design must be used. There are major challenges with observational studies, one of which is confounding that can lead to biased estimates of the causal effects. Controlling for confounding is commonly performed by simple adjustment for measured confounders; although, often this is not enough. Recent advances in the field of causal inference have dealt with confounding by building on classical standardisation methods. However, these recent advances have progressed quickly with a relative paucity of computational-oriented applied tutorials contributing to some confusion in the use of these methods among applied researchers. In this tutorial, we show the computational implementation of different causal inference estimators from a historical perspective where different estimators were developed to overcome the limitations of the previous one. Furthermore, we also briefly introduce the potential outcomes framework, illustrate the use of different methods using an illustration from the health care setting, and most importantly, we provide reproducible and commented code in Stata, R and Python for researchers to apply in their own observational study. The code can be accessed at https://github.com/migariane/TutorialCausalInferenceEstimators
2012.09920.pdf
Cano-Ibáñez N, Martínez-Galiano JM, Luque-Fernández MA, Martín-Peláez S, Bueno-Cavanillas A, Delgado-Rodríguez M. Maternal Dietary Patterns during Pregnancy and Their Association with Gestational Weight Gain and Nutrient Adequacy [Internet]. International Journal of Environmental Research and Public Health 2020, Vol. 17, Page 7908 2020;17(21):7908. Publisher's VersionAbstract
Several epidemiologic studies have shown an association between Gestational Weight Gain (GWG) and offspring complications. The GWG is directly linked to maternal dietary intake and women’s nutritional status during pregnancy. The aim of this study was (1) to assess, in a sample of Spanish pregnant women, the association between maternal dietary patterns and GWG and (2) to assess maternal dietary patterns and nutrient adequate intake according to GWG. A retrospective study was conducted in a sample of 503 adult pregnant women in five hospitals in Eastern Andalusia (Spain). Data on demographic characteristics, anthropometric values, and dietary intake were collected from clinical records by trained midwives. Usual food intake was gathered through a validated Food Frequency Questionnaire (FFQ), and dietary patterns were obtained by principal component analysis. Nutrient adequacy was defined according to European dietary intake recommendations for pregnant women. Regression models adjusted by confounding factors were constructed to study the association between maternal dietary pattern and GWG, and maternal dietary patterns and nutritional adequacy. A negative association was found between GWG and the Mediterranean dietary pattern (crude β = −0.06, 95% CI: −0.11, −0.04). Independent of maternal dietary pattern, nutrient adequacy of dietary fiber, vitamin B9, D, E, and iodine was related to a Mediterranean dietary pattern (p \textless 0.05). A Mediterranean dietary pattern is related to lower GWG and better nutrient adequacy. The promotion of healthy dietary behavior consistent with the general advice promoted by the Mediterranean Diet (based on legumes, vegetables, nuts, olive oil, and whole cereals) will offer healthful, sustainable, and practical strategies to control GWG and ensure adequate nutrient intake during pregnancy.
Lee SF, Luque-Fernandez MA, Chen YH, Catalano PJ, Chiang CL, Wan EY-F, Wong IC-K, Chen MH, Ng AK. Doxorubicin and subsequent risk of cardiovascular diseases among survivors of diffuse large B-cell lymphoma in Hong Kong [Internet]. Blood Advances 2020;4(20):5107-5117. Publisher's VersionAbstract
Evidence regarding the dose-related impact of doxorubicin on subsequent cardiovascular diseases (CVDs) in Asian patients with diffuse large B-cell lymphoma (DLBCL) without preexisting CVDs is lacking. From a territory-wide electronic database in Hong Kong, we identified adults who were diagnosed with DLBCL and treated with chemotherapy between 2000 and 2018. We evaluated the patients for incident CVDs (including ischemic heart disease, heart failure, and cardiomyopathy). We evaluated the cause-specific cumulative incidence (csCI) of CVD with levels of doxorubicin exposure by using flexible parametric competing risk analysis and adjusting for demographics, comorbidities, therapeutic exposure, cardiovascular risk factors, and lifestyle factors. Controls were age- and sex-matched to DLBCL patients. We analyzed 2600 patients and 13 000 controls. The adjusted cause-specific hazard ratio (HR) for CVD in patients treated with ġt;500 mg doxorubicin compared with non-doxorubicin regimens was 2.65 (95\% confidence interval [CI], 1.23-5.74; P = .013). The 5-, 10-, and 15-year csCIs were 8.2\%, 11.3\%, and 12.8\% in patients vs 3.1\%, 4.4\%, and 5.2\% in controls, respectively. Hypertension (HR, 6.20; 95\% CI, 0.79-48.44; P = .082) and use of aspirin/angiotensin-converting enzyme inhibitor/beta-blocker at baseline (HR, 2.13-4.63; P \< .001 to .002) might confer a higher risk of subsequent CVDs. In this Hong Kong population-based study, doxorubicin exposure (absolute dose ġt;500 mg), together with hypertension or baseline use of medication for cardiovascular risk factors, was found to be associated with an increase in csCIs of CVDs. Tailoring therapeutic strategies to underlying CVD risk factors and risk-adapted monitoring and follow-up of susceptible DLBCL patients are advisable.
Nuñez O, Barranco MR, Fernández-Navarro P, Sanchez DR, Luque-Fernandez MA, Santamaría MP, Sánchez M-J. Deprivation gap in colorectal cancer survival attributable to stage at diagnosis: A population-based study in Spain [Internet]. Cancer Epidemiology 2020;68:101794. Publisher's VersionAbstract
Objective Socioeconomic inequalities in colorectal cancer (CRC) survival are a major concern of the Spanish public health system. If these inequalities were mainly due to differences in stage at diagnosis, population-based screening programs might reduce them substantially. We aimed to determine to what extent adverse stage distribution contributed to survival inequalities in a Spanish region before the implementation of a CRC screening program. Methods We analyzed data from a population-based cohort study that included all patients living in a region of southern Spain with CRC diagnosed between 2004 and 2013. The European Deprivation Index was used to assign each patient a socioeconomic level based on their area of residence. The role of tumor stage in survival disparities between socioeconomic groups was assessed using a causal mediation analysis. Results A total of 2802 men and 1957 women were included in the study. For men, the adjusted difference in deaths between the most deprived and the most affluent areas was 131 deaths per 1000 person-years by the first year after diagnosis. Of these deaths, 42 (per 1000 person-years) were attributable to differences in stage at diagnosis. No socioeconomic disparities in survival were detected among female patients. Conclusions In this study, we mainly detected socioeconomic disparities in short term survival of male patients. More than two thirds of these inequalities could not be attributed to differences in stage at diagnosis. Our results suggest that in addition to a screening program, other public health interventions are necessary to reduce the deprivation gap in survival.
Luque-Fernandez MA, Redondo-Sanchez D, RODRIGUEZ-BARRANCO MIGUEL, Yoe-Ling C-C, Salamanca-Fernandez E, Nunez O, Fernandez-Navarro P, Pollan M, Sanchez M-J. Socioeconomic Inequalities in Colorectal Cancer Survival in Southern Spain: A Multilevel Population-Based Cohort Study [Internet]. Clinical Epidemiology 2020;Volume 12:797–806. Publisher's VersionAbstract
Background: Colorectal cancer (CRC) is the most frequently diagnosed cancer in Spain. Socioeconomic inequalities in cancer survival are not documented in Spain. We aim to study the association of socioeconomic inequalities with overall mortality and survival among CRC patients in southern Spain.
Methods: We conducted a multilevel population-based cohort study, including CRC cases for the period 2011– 2013. The study time-to-event outcome was death, and the primary exposure was CRC patients’ socioeconomic status assessed by the Spanish deprivation index at the census tract level. We used a mixed-effects flexible hazard model, including census tract as a random intercept, to derive overall survival estimates by deprivation.
Results: Among 3589 CRC patients and 12,148 person-years at risk (pyr), 964 patients died before the end of the follow-up. Mortality by deprivation showed the highest mortality rate for the most deprived group (96.2 per 1000 pyr, 95% CI: 84.0– 110.2). After adjusting for sex, age, cancer stage, and the area of residence, the most deprived had a 60% higher excess mortality risk than the less deprived group (excess mortality risk ratio: 1.6, 95% CI: 1.1– 2.3).
Conclusions: We found a consistent association between deprivation and CRC excess mortality and survival. The reasons behind these inequalities need further investigation in order to improve equality cancer outcomes in all social groups.

Keywords: socioeconomic inequalities, colorectal cancer, survival, population-based epidemiology, epidemiological methods, multilevel
Luque-Fernández MÁ, Redondo-Sánchez D, Fernández P, Salamanca-Fernández E, Marcos-Gragera R, Guevara M, Carulla Aresté M, Jiménez R, Núñez O, Sabater C, López de Munain Marqués A, Chirlaque MD, Mateos A, Rodríguez-Barranco M, Espín Balbino J, Pollán M, Sánchez M-J. Protocolo del Estudio Poblacional Multinivel de las Desigualdades Socioeconómicas en la Distribución Geográfica de la Incidencia, la Mortalidad y la Supervivencia Neta del Cáncer en España: Estudio DESOCANES. Gaceta Sanitaria 2020;Abstract
La incidencia y la mortalidad brindan información sobre la carga de la morbilidad del cáncer y los años potenciales de vida perdidos debido al cáncer. Se ha desarrollado el Índice de Privación (IP) como una medida estandarizada para medir la privación socioeconómica en España a nivel de sección censal. Además, se puede combinar la información del IP con variables ecológicas poblacionales y los datos de los Estudios Europeos de Alta Resolución en Cáncer. El objetivo de este estudio es caracterizar las desigualdades socioeconómicas en la incidencia, el exceso de mortalidad, la mortalidad prematura y la supervivencia neta para tres de los cánceres más incidentes (pulmón, colon-recto y mama) en España usando el IP. Este estudio nacional multinivel de base poblacional evaluará el impacto de las desigualdades socioeconómicas. Se usarán el análisis espacial, la modelización multinivel, la supervivencia neta y la evaluación del impacto económico. Los resultados serán útiles para el apoyo a la toma de decisiones y la planificación y la gestión de intervenciones en salud pública destinadas a reducir el impacto de las desigualdades socioeconómicas en el diagnóstico y el pronóstico de los pacientes de cáncer en España. ER
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Pazos M, Biarnes M, Blasco-Alberto A, Dyrda A, Luque-Fernandez MA, Gómez A, Mora C, Milla E, Muniesa JM, Anton A, Diaz-Aleman VT. SD-OCT peripapillary nerve fibre layer and ganglion cell complex parameters in glaucoma: principal component analysis [Internet]. British Journal of Ophthalmology 2020; Publisher's VersionAbstract
{Background/aims To identify objective glaucoma-related structural features based on peripapillary (p) and macular (m) spectral domain optical coherence tomography (SD-OCT) parameters and assess their discriminative ability between healthy and glaucoma patients.Methods Two hundred and sixty eyes (91 controls and 169 glaucoma) were included in this prospective study. After a complete examination, all participants underwent the posterior pole and the peripapillary retinal nerve fibre layer (pRNFL) protocols of the Spectralis SD-OCT. Principal component analysis (PCA), a data reduction method, was applied to identify and characterise the main information provided by the ganglion cell complex (GCC). The discriminative ability between healthy and glaucomatous eyes of the first principal components (PCs) was compared with that of conventional SD-OCT parameters (pRNFL, macular RNFL (mRNFL), macular ganglion cell layer (mGCL)and macular inner plexiform layer (mIPL)) using 10-fold cross-validated areas under the curve (AUC).Results The first PC explained 58% of the total information contained in the GCC and the pRNFL parameters and was the result of a general combination of almost all variables studied (diffuse distribution). Other PCs were driven mainly by pRNFL and mRNFL measurements. PCs and pRNFL had similar AUC (0.95 vs 0.96
Lee SF, Luk H, Wong A, Ng CK, Wong FCS, Luque-Fernandez MA. Prediction model for short-term mortality after palliative radiotherapy for patients having advanced cancer: a cohort study from routine electronic medical data [Internet]. Scientific Reports 2020;10(1):5779. Publisher's VersionAbstract
{We developed a predictive score system for 30-day mortality after palliative radiotherapy by using predictors from routine electronic medical record. Patients with metastatic cancer receiving first course palliative radiotherapy from 1 July, 2007 to 31 December, 2017 were identified. 30-day mortality odds ratios and probabilities of the death predictive score were obtained using multivariable logistic regression model. Overall, 5,795 patients participated. Median follow-up was 39.6 months (range, 24.5–69.3) for all surviving patients. 5,290 patients died over a median 110 days, of whom 995 (17.2%) died within 30 days of radiotherapy commencement. The most important mortality predictors were primary lung cancer (odds ratio: 1.73, 95% confidence interval: 1.47–2.04) and log peripheral blood neutrophil lymphocyte ratio (odds ratio: 1.71, 95% confidence interval: 1.52–1.92). The developed predictive scoring system had 10 predictor variables and 20 points. The cross-validated area under curve was 0.81 (95% confidence interval: 0.79–0.82). The calibration suggested a reasonably good fit for the model (likelihood-ratio statistic: 2.81
Luque-Fernandez MA, Gonçalves K, Salamanca-Fernández E, Redondo-Sanchez D, Lee SF, Rodríguez-Barranco M, Carmona-García MC, Marcos-Gragera R, Sánchez M-J. Multimorbidity and short-term overall mortality among colorectal cancer patients in Spain: A population-based cohort study [Internet]. European Journal of Cancer 2020;129:4 - 14. Publisher's VersionAbstract
Background Numerous studies have analysed the effect of comorbidity on cancer outcomes, but evidence on the association between multimorbidity and short-term mortality among colorectal cancer patients is limited. We aimed to assess this association and the most frequent patterns of multimorbidity associated with a higher short-term mortality risk among colorectal cancer patients in Spain. Methods Data were obtained from two Spanish population-based cancer registries and electronic health records. We estimated the unadjusted cumulative incidence of death by comorbidity status at 6 months and 1 year. We used a flexible parametric model to derive the excess mortality hazard ratios (HRs) for multimorbidity after adjusting for sex, age at diagnosis, cancer stage and treatment. We estimated the adjusted cumulative incidence of death by comorbidity status and identified multimorbidity patterns. Results Among the study participants, 1,048 cases were diagnosed with cancers of the colon and rectum, 2 cases with cancer of the anus with overlapping sites of the rectum and 11 cases with anal adenocarcinomas but treated as colorectal cancer patients. Among 1,061 colorectal cancer patients, 171 (16.2%) died before 6 months, 246 (23.3%) died before the 1-year follow-up, and 324 (30.5%) had multimorbidity. Patients with multimorbidity had two times higher mortality risk than those without comorbidities at 6 months (adjusted HR: 2.04; 95% confidence interval [CI]: 1.30–3.20, p = 0.002). The most frequent multimorbidity pattern was congestive heart failure + diabetes. However, patients with rheumatologic disease + diabetes had two times higher 1-year mortality risk than those without comorbidities (HR: 2.23; 95% CI: 1.23–4.07, p = 0.008). Conclusions Multimorbidity was a strong independent predictor of short-term mortality at 6 months and 1 year among the colorectal cancer patients in Spain. The identified multimorbidity pattern was consistent. Our findings might help identify patients at a higher risk for poor cancer and treatment outcomes.
Ma D, Luque-Fernandez MA, Bogdanet D, Desoye G, Dunne F, Halperin JA. Plasma Glycated CD59 Predicts Early Gestational Diabetes and Large for Gestational Age Newborns. The Journal of Clinical Endocrinology & Metabolism 2020;Abstract
Gestational diabetes mellitus (GDM) diagnosed in early pregnancy is a health care challenge because it increases the risk of adverse outcomes. Plasma glycated CD59 (pGCD59) is an emerging biomarker for diabetes and GDM. The aim of this study was to assess the performance of pGCD59 as a biomarker of early GDM and its association with delivering a large for gestational age (LGA) infant.Study: Blood levels of pGCD59Â were measured in samples from 693 obese women (BMI >29) undergoing a 75g, 2-hour oral glucose tolerance test (OGTT) at <20 weeks gestation in the DALI study: the main analyses included 486 subjects who had normal glucose tolerance throughout the pregnancy, 207 who met criteria for GDM at <20 weeks and 77 diagnosed with GDM at pregnancy week 24-28.Reference tests: 75g, 2-hour OGTT adjudicated based on IADPSG criteria.Index test: pGCD59 ELISA.Primary aim: To assess the performance of pGCD59 to identify women with GDM in early pregnancy (GDM<20).Secondary aim: To assess the association of pGCD59 with LGA and potentially others adverse neonatal outcomes linked to GDM. Mean pGCD59 levels were significantly higher (p-value <0.001) in women with GDM<20 (3.9 ±1.1 SPU) than in those without (2.7 ±0.7 SPU). pGCD59 accurately identified GDM in early pregnancy with an AUC ROC curves of 0.86 (95% CI: 0.83-0.90). One unit increase in maternal pGCD59 level was associated with 36% increased odds of delivering a large for gestational age (LGA) infant (odds ratio for LGA vs non-LGA infant: 1.4; 95%CI: 1.1-1.8; p-value: 0.016). Our results indicate that pGCD59 is a simple and accurate biomarker for detection of GDM in early pregnancy and risk assessment of LGA.
Fowler H, Belot A, Ellis L, Maringe C, Luque-Fernandez MA, Njagi EN, Navani N, Sarfati D, Rachet B. Comorbidity prevalence among cancer patients: a population-based cohort study of four cancers [Internet]. BMC Cancer 2020;20(1):2. Publisher's VersionAbstract
The presence of comorbidity affects the care of cancer patients, many of whom are living with multiple comorbidities. The prevalence of cancer comorbidity, beyond summary metrics, is not well known. This study aims to estimate the prevalence of comorbid conditions among cancer patients in England, and describe the association between cancer comorbidity and socio-economic position, using population-based electronic health records.
Luque-Fernandez MA, Redondo-Sanchez D, Lee SF, Rodriguez-Barranco M, Carmona-Garcia M, Marcos-Gragera R, Sanchez MJ. Multimorbidity by Patient and Tumor Factors and Time-to-Surgery Among Colorectal Cancer Patients in Spain : A Population-Based Study. Clinical Epidemiology 2020;2020:12:31-40.Abstract

Background: Cancer treatment and outcomes can be influenced by tumor characteristics, patient overall health status, and comorbidities. While previous studies have analyzed the influence of comorbidity on cancer outcomes, limited information is available regarding factors associated with the increased prevalence of comorbidities and multimorbidity among patients with colorectal cancer in Spain.

Patients and Methods: This cross-sectional study obtained data from all colorectal cancer cases diagnosed in two Spanish provinces in 2011 from two population-based cancer registries and electronic health records. We calculated the prevalence of comorbidities according to patient and tumor factors, identified factors associated with an increased prevalence of comorbidity and multimorbidity, analyzed the association between comorbidities and time-to-surgery, and developed an interactive web application (https://comcor.netlify.com/).

Results: The most common comorbidities were diabetes (23.6%), chronic obstructive pulmonary disease (17.2%), and congestive heart failure (14.5%). Among all comorbidities, 52% of patients were diagnosed at more advanced stages (stage III/IV). Patients with advanced age, restricted performance status or who were disabled, obese, and smokers had a higher prevalence of multimorbidity. Patients with multimorbidity had a longer time-to-surgery than those without comorbidity (17 days, 95% confidence interval: 3– 29 days).

Conclusion: We identified a consistent pattern of factors associated with a higher prevalence of comorbidities and multimorbidity at diagnosis and an increased time-to-surgery among patients with colorectal cancer with multimorbidity in Spain. This pattern may provide insights for further etiological and preventive research and help to identify patients at a higher risk for poorer cancer outcomes and suboptimal treatment.

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