[Impact of days elapsed from the onset of symptoms to hospitalization in COVID-19 in-hospital mortality: Time matters]. / Impacto de los días transcurridos desde el inicio de los síntomas hasta la hospitalización en la mortalidad hospitalaria por COVID-19: el tiempo importa.

Background: COVID-19 shows different clinical and pathophysiological stages over time. Theeffect of days elapsed from the onset of symptoms (DEOS) to hospitalization on COVID-19prognostic factors remains uncertain. We analyzed the impact on mortality of DEOS to hospital-ization and how other independent prognostic factors perform when taking this time elapsedinto account. Methods: This retrospective, nationwide cohort study, included patients with confirmed COVID-19 from February 20th and May 6th, 2020. The data was collected in a standardized online datacapture registry. Univariate and multivariate COX-regression were performed in the generalcohort and the final multivariate model was subjected to a sensitivity analysis in an earlypresenting (EP; < 5 DEOS) and late presenting (LP; ≥5 DEOS) group. Results: 7915 COVID-19 patients were included in the analysis, 2324 in the EP and 5591 in theLP group. DEOS to hospitalization was an independent prognostic factor of in-hospital mortalityin the multivariate Cox regression model along with other 9 variables. Each DEOS incrementaccounted for a 4.3% mortality risk reduction (HR 0.957; 95% CI 0.93---0.98). Regarding variationsin other mortality predictors in the sensitivity analysis, the Charlson Comorbidity Index onlyremained significant in the EP group while D-dimer only remained significant in the LP group. Conclusion: When caring for COVID-19 patients, DEOS to hospitalization should be consideredas their need for early hospitalization confers a higher risk of mortality. Different prognosticfactors vary over time and should be studied within a fixed timeframe of the disease.

[Persistent COVID-19 syndrome. A narrative review]. / Síndrome de COVID-19 persistente. Una revisión narrativa.

As the coronavirus-2019 disease (COVID-19) pandemic, caused by the infection with severe acute respiratory syndrome (SARS-CoV-2) coronavirus type 2, has progressed, persistent COVID-19 syndrome is an increasingly recognized problem on which a significant volume of medical literature is developing. Symptoms may be persistent or appear, after an asymptomatic period, weeks or months after the initial infection. The clinical picture is as markedly heterogeneous and multisystemic as in the acute phase, so multidisciplinary management is required. In addition, their appearance is not related to the severity of the initial infection, so they can affect both mild patients, even asymptomatic, and seriously ill patients who have required hospitalization. Although it can affect people of any age, it is more common in middle-aged women. The sequelae can generate a high impact on the quality of life, and in the work and social environment. The objective of this paper is to review persistent COVID-19 syndrome, to know its clinical manifestations and the strategies for the management and follow-up of these patients.

[Clinical characteristics and risk factors for mortality upon admission in patients with heart failure hospitalized due to COVID-19 in Spain]. / Características clínicas y factores de riesgo de mortalidad al ingreso en pacientes con insuficiencia cardíaca hospitalizados por COVID-19 en España.

Background: There are few studies on patients with heart failure (HF) hospitalized for COVID-19. Our aim is to describe the clinical characteristics of patients with HF hospitalized for COVID-19 and identify risk factors for in-hospital mortality upon admission. Methods: We conducted a retrospective, multicenter study in patients with HF hospitalized for COVID-19 in 150 Spanish hospitals (SEMI-COVID-19 Registry). A multivariate logistic regression analysis was performed to identify admission risk factors associated with in-hospital mortality. Results: A total of 1,718 patients were analyzed (56.5% men; median age 81.4 years). The overall case fatality rate was 47.6% (n=819). The independent risk factors at admission for in-hospital mortality were: age (adjusted odds ratio [AOR]: 1.03; 95% confidence interval [95%CI]: 1.02-1.05; p< .001); severe dependence (AOR: 1.62; 95%CI: 1.19-2.20; p=.002); tachycardia (AOR: 1.01; 95%CI: 1.00-1.01; p=.004); and high C-reactive protein (AOR: 1.004; 95%CI:1.002-1.004; p< .001), LDH (AOR: 1.001; 95%CI: 1.001-1.002; p< .001), and serum creatinine levels (AOR: 1.35; 95%CI: 1.18-1.54; p< .001). Conclusions: Patients with HF hospitalized for COVID-19 have a high in-hospital mortality rate. Some simple clinical and laboratory tests can help to identify patients with a worse prognosis.

[Derivation and validation of a risk score for admission to the Intensive Care Unit in patients with COVID-19]. / Derivación y validación de una puntuación de riesgo de ingreso en la Unidad de Cuidados Intensivos para pacientes con COVID-19.

BACKGROUND: This work aims to identify and validate a risk scale for admission to intensive care units (ICU) in hospitalized patients with coronavirus disease 2019 (COVID-19). METHODS: We created a derivation rule and a validation rule for ICU admission using data from a national registry of a cohort of patients with confirmed SARS-CoV-2 infection who were admitted between March and August 2020 (n = 16,298). We analyzed the available demographic, clinical, radiological, and laboratory variables recorded at hospital admission. We evaluated the performance of the risk score by estimating the area under the receiver operating characteristic curve (AUROC). Using the ß coefficients of the regression model, we developed a score (0 to 100 points) associated with ICU admission. RESULTS: The mean age of the patients was 67 years; 57% were men. A total of 1,420 (8.7%) patients were admitted to the ICU. The variables independently associated with ICU admission were age, dyspnea, Charlson Comorbidity Index score, neutrophil-to-lymphocyte ratio, lactate dehydrogenase levels, and presence of diffuse infiltrates on a chest X-ray. The model showed an AUROC of 0.780 (CI: 0.763-0.797) in the derivation cohort and an AUROC of 0.734 (CI: 0.708-0.761) in the validation cohort. A score of greater than 75 points was associated with a more than 30% probability of ICU admission while a score of less than 50 points reduced the likelihood of ICU admission to 15%. CONCLUSION: A simple prediction score was a useful tool for forecasting the probability of ICU admission with a high degree of precision.

Executive summary: Updates to the dietary treatment of prediabetes and type 2 diabetes mellitus. / Resumen ejecutivo: actualización en el tratamiento dietético de la prediabetes y la diabetes mellitus tipo 2.

Adequate lifestyle changes significantly reduce the cardiovascular risk factors associated with prediabetes and type 2 diabetes mellitus. Therefore, healthy eating habits, regular physical activity, abstaining from using tobacco, and good sleep hygiene are recommended for managing these conditions. There is solid evidence that diets that are plant-based; low in saturated fatty acids, cholesterol, and sodium; and high in fiber, potassium, and unsaturated fatty acids are beneficial and reduce the expression of cardiovascular risk factors in these subjects. In view of the foregoing, the Mediterranean diet, the DASH diet, a low-carbohydrate diet, and a vegan-vegetarian diet are of note. Additionally, the relationship between nutrition and these metabolic pathologies is fundamental in targeting efforts to prevent weight gain, reducing excess weight in the case of individuals with overweight or obesity, and personalizing treatment to promote patient empowerment. This document is the executive summary of an updated review that includes the main recommendations for improving dietary nutritional quality in people with prediabetes or type 2 diabetes mellitus. The full review is available on the webpages of the Spanish Society of Arteriosclerosis, the Spanish Diabetes Society, and the Spanish Society of Internal Medicine.

Recommendations on the comprehensive, multidimensional assessment of hospitalized elderly people. Position of the Spanish Society of Internal Medicine. / Recomendaciones sobre la valoración integral y multidimensional del anciano hospitalizado. Posicionamiento de la Sociedad Española de Medicina Interna.

This position paper describes the most relevant and essential aspects of a comprehensive, multidimensional assessment of hospitalized elderly people. The change in demographic patterns and the epidemiological profiles of diseases makes it necessary for internal medicine departments to adapt in order to take into account the vulnerabilities of the elderly in this context. A comprehensive, multidimensional assessment and the multidisciplinary development of a care plan during hospitalization can have an impact in terms of preventing mortality, disability, and institutionalization at discharge. It is necessary for all internists to acquire skills to improve the hospitalization experience in the elderly and obtain better health outcomes in our patients. This document has been developed by the Focus Group on Aging and the Polypathological and Advanced Age Working Group and endorsed by the Spanish Society of Internal Medicine.

Medical treatment of type 2 diabetes mellitus: Recommendations of the Diabetes, Obesity and Nutrition Group of the Spanish Society of Internal Medicine. / Tratamiento médico de la diabetes mellitus tipo 2: recomendaciones del Grupo de Diabetes, Obesidad y Nutrición de la Sociedad Española de Medicina Interna.

Type 2 diabetes mellitus is a major health problem with high prevalence, morbidity and mortality, and its medical treatment is growing in complexity due to patients' diverse clinical conditions. This article presents a consensus document by the Diabetes, Obesity and Nutrition Group of the Spanish Society of Internal Medicine, with recommendations for the medical treatment of type 2 diabetes mellitus. The main objective of this article is to facilitate the therapeutic decision-making process to improve the care of patients with diabetes. The document prioritises treatments with cardiovascular benefits, especially those that benefit patients with heart and renal failure.

[Solving one of the pieces of the puzzle: COVID-19 and type 2 diabetes]. / Resolviendo una de las piezas del puzle: COVID-19 y diabetes tipo 2.

The emergence of the COVID-19 pandemic represents an enormous challenge. Given the considerable presence of type 2 diabetes mellitus in the current population, the pandemic is a health issue that requires an effort to provide better responses to our patients who are more vulnerable to the onset of infection and who are candidates for presenting more severe symptoms. This document attempts to address the relationship between COVID-19 infection and type 2 diabetes mellitus. To this end, we will briefly analyse whether the epidemiological data support this association and, subsequently, go in depth on the pathophysiological mechanisms that might connect the 2 diseases.

Obesity is a chronic disease. Positioning statement of the Diabetes, Obesity and Nutrition Workgroup of the Spanish Society of Internal Medicine (SEMI) for an approach centred on individuals with obesity. / La obesidad es una enfermedad crónica. Posicionamiento del grupo de trabajo de Diabetes, Obesidad y Nutrición de la Sociedad Española de Medicina Interna (SEMI) por un abordaje centrado en la persona con obesidad.

INTRODUCTION: Obesity is a chronic, complex and multifactorial metabolic disease involved in the development of chronic noncommunicable diseases such as type 2 diabetes mellitus, cardiovascular disease and cancer. The care of individuals with obesity is an essential part of the holistic approach provided by internal medicine to patients. MATERIAL AND METHODS: Between September 2019 and January 2020, we distributed an online survey to the members of the Spanish Society of Internal Medicine. We prepared a Strengths, Weaknesses, Opportunities, and Threats analysis using the responses and, using the nominal group technique, developed the recommendations. RESULTS: We obtained 599 responses. The respondents mean age was 44.4±11 years, and 52.1% were women. Some 91.8% of the internists evaluate their patients to rule out the comorbidities associated with obesity, mainly type 2 diabetes mellitus (96.2%), cardiovascular disease (88.9%) and obesity-associated hypoventilation syndrome (73%), among others. Some 79.9% provided indications on lifestyle changes. Some 64.1% and 74.9% of the respondents knew the indications for the drugs and bariatric surgery, respectively. Some 93.8% and 83% of the respondents considered obesity and excess weight a chronic disease, and 88.7% considered it a disease of specific interest to internists, who should take an active and leading role in its treatment (85.3%). CONCLUSIONS: The objective of the present document is to determine the degree of understanding and sensitivity of internists regarding the management of obesity and to develop a consensus of recommendations for the Spanish Society of Internal Medicine based on the scientific evidence and the opinion of its members.

Use of antihyperglycaemic therapy with cardiovascular benefit in patients with type 2 diabetes who require hospitalisation: A cross-sectional study. / Uso de terapia antihiperglucemiante con beneficio cardiovascular en pacientes con diabetes tipo 2 que requieren hospitalización: un estudio transversal.

OBJECTIVE: To evaluate the use of therapy with cardiovascular benefit in patients with type 2 diabetes mellitus admitted to internal medicine departments. METHODS: One day, cross-sectional study of patients with type 2 diabetes mellitus hospitalised in internal medicine departments. We recorded demographic and anthropometric variables, laboratory data and use of antihyperglycaemic drugs. The endpoint was the proportion and determinants of the use of sodium-glucose cotransporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP1-RA). RESULTS: We included 928 patients belonging to 74 hospitals, with a mean age of 78.9 years (SD, 10.86 years), 50% of whom were men. A total of 557 (60%) patients had ischaemic heart disease, 189 (20.4%) had cerebrovascular disease, 293 (31.6%) had heart failure, 274 (29.5%) had chronic kidney disease, and 129 (13.9%) had peripheral arterial disease. Prior to their hospital admission, the patients were taking sulfonylureas (5.7%), biguanides (49.1%), alpha-glucosidase inhibitors (0.2%), pioglitazone (0%), dipeptidyl peptidase 4 inhibitors (39%), SGLT2i (5.8%), GLP1-RA (2.6%) and basal insulin analogues (24%). An age over 75 years was the main determinant for not taking SGLT2i (adjusted OR, 0.28; 95% CI 0.10-0.74; P=.039) or GLP1-RA (adjusted OR, 0.09; 95% CI 0.02-0.46; P=.006). DISCUSSION: A large proportion of elderly patients with type 2 diabetes mellitus at very high cardiovascular risk are not treated with antihyperglycemic drugs with proven cardiovascular benefit. The most commonly used drugs were metformin and DPP4i. There is room for improvement in the treatment of this very high-risk population.

[Clinical characteristics of patients hospitalized with COVID-19 in Spain: Results from the SEMI-COVID-19 Registry]. / Características clínicas de los pacientes hospitalizados con COVID-19 en España: resultados del Registro SEMI-COVID-19.

BACKGROUND: Spain has been one of the countries most affected by the COVID-19 pandemic. OBJECTIVE: To create a registry of patients with COVID-19 hospitalized in Spain, in order to improve our knowledge of the clinical, diagnostic, therapeutic, and prognostic aspects of this disease. METHODS: A multicentre retrospective cohort study, including consecutive patients hospitalized with confirmed COVID-19 throughout Spain. Epidemiological and clinical data, additional tests at admission and at seven days, treatments administered, and progress at 30 days of hospitalization were collected from electronic medical records. RESULTS: Up to June 30th 2020, 15,111 patients from 150 hospitals were included. Their median age was 69.4 years (range: 18-102 years) and 57.2% were male. Prevalences of hypertension, dyslipidemia, and diabetes mellitus were 50.9%, 39.7%, and 19.4%, respectively. The most frequent symptoms were fever (84.2%) and cough (73.5%). High values of ferritin (73.5%), lactate dehydrogenase (73.9%), and D-dimer (63.8%), as well as lymphopenia (52.8%), were frequent. The most used antiviral drugs were hydroxychloroquine (85.6%) and lopinavir/ritonavir (61.4%); 33.1% developed respiratory distress. Overall mortality rate was 21.0%, with a marked increase with age (50-59 years: 4.7%, 60-69 years: 10.5%, 70-79 years: 26.9%, ≥ 80 years: 46.0%). CONCLUSIONS: The SEMI-COVID-19 Network provides data on the clinical characteristics of patients with COVID-19 hospitalized in Spain. Patients with COVID-19 hospitalized in Spain are mostly severe cases, as one in three patients developed respiratory distress and one in five patients died. These findings confirm a close relationship between advanced age and mortality.

Recommendations of the Spanish-Portuguese Internal Medicine services in the fight against climate change and environmental degradation.

Facing the severity of the impact of climate change and environmental degradation on human health, 32 Internal Medicine societies, colleges, and associations of 29 Spanish and Portuguese-speaking countries issue a consensus document in which they call for the implication of doctors and all health professionals in the global fight against the causes of these changes. This commitment requires the cooperation of health-related organizations, elaboration and implementation of good environmental sustainability practices, greater awareness of professionals and population, promotion of education and research in this area, increasing climate resilience and environmental sustainability of health systems, combating inequalities and protecting the most vulnerable populations, adopting behaviors that protect the environment, and claiming Internal Medicine as a core specialty for empowerment of the health system to respond to these challenges.

Applications to augment patient care for Internal Medicine specialists: a position paper from the EFIM working group on telemedicine, innovative technologies & digital health.

Telemedicine applications present virtually limitless prospects for innovating and enhancing established and new models of patient care in the field of Internal Medicine. Although there is a wide range of innovative technological solutions in Europe, there are overarching elements associated with such technologies when applied to the practices of Internal Medicine specialists. The European Federation of Internal Medicine (EFIM) strongly advocates for active leadership and influence from the Internal Medicine societies and specialist physicians across Europe in the development and application of telemedicine and digital technologies in healthcare. This position paper's conclusions were drawn via Delphi method, which was developed collaboratively from July 2021 to December 2023. The panel, consisting of experts in clinical medicine, public health, health economics and statistics, assessed various aspects related to telemedicine. Participants assigned scores on a Likert scale reflecting perceived value and potential risks. The findings were consolidated in a comprehensive checklist aligning with relevant literature and a SWOT analysis. Specifically, key issues that need to be addressed include promoting the professional development of e-health competencies in the healthcare and medical workforce, using educational campaigns to promote digital literacy among patients and caregivers, designing and implementing telemedicine applications tailored to local conditions and needs and considering the ethical and legal contexts under which these applications are employed. Importantly, there is currently no consensus on care models or standardized protocols among European Internal Medicine specialists regarding the utilization of telemedicine. This position paper aims to outline the opportunities and challenges associated with the application of telemedicine in Internal Medical practice in Europe.

Characteristics of hospitalized patients with hypercalcemia in the province of Malaga: a longitudinal, retrospective, multicenter study.

BACKGROUND AND OBJECTIVE: There are limited studies analyzing hypercalcemia in hospitalized patients. Our objectives were to describe the clinical characteristics of hospitalized patients with hypercalcemia, estimate its prevalence in the hospital setting, analyze the rate of correction of hypercalcemia, and identify prognostic variables. MATERIALS AND METHODS: Observational, longitudinal, retrospective, and bicentric study. Adult patients admitted to two hospitals in Málaga (2014-2018) with a diagnosis of hypercalcemia were included. The minimum follow-up was 2 years or until death. RESULTS: A total of 205 patients with hypercalcemia were included (incidence: 0.13%). The mean age (SD) was 68.2 (13.1) years, with a predominance of males (55.1%). The median (IQR) serum calcium at admission was 13.1 (11.8-14.6) mg/dl. The most common etiologies were neoplasms (75.1%), primary hyperparathyroidism, and medications (both 8.8%). The median (IQR) follow-up period was 5.1 (1.7-60.3) weeks. The most commonly used treatments were fluid therapy (86.8%), loop diuretics (70.9%), bisphosphonates (60.7%), and glucocorticoids (46.2%). The rate of correction of hypercalcemia was 65.2%, with a median (IQR) of 6 (3-10) days. The mortality rate was 81.5%. The median (95% CI) survival was 5.1 (3-7.3) weeks. Factors associated with higher mortality were advanced age, neoplastic etiology, serum calcium at admission, and failure to correct hypercalcemia. CONCLUSIONS: Hypercalcemia in hospitalized patients is mainly due to neoplastic processes and is associated with high mortality. We observed a low rate of adherence to recommendations for the management of hypercalcemia.

Competences of internal medicine specialists for the management of patients with multimorbidity. EFIM multimorbidity working group position paper.

Patients with multimorbidity increasingly impact healthcare systems, both in primary care and in hospitals. This is particularly true in Internal Medicine. This population associates with higher mortality rates, polypharmacy, hospital readmissions, post-discharge syndrome, anxiety, depression, accelerated age-related functional decline, and development of geriatric syndromes, amongst others. Internists and Hospitalists, in one of their roles as Generalists, are increasingly asked to attend to these patients, both in their own Departments as well as in surgical areas. The management of polypathology and multimorbidity, however, is often complex, and requires specific clinical skills and corresponding experience. In addition, patients' needs, health-care environment, and routines have changed, so emerging and re-emerging specific competences and approaches are required to offer the best coordinated, continuous, and comprehensive integrated care to these populations, to achieve optimal health outcomes and satisfaction of patients, their relatives, and staff. This position paper proposes a set of emerging and re-emerging competences for internal medicine specialists, which are needed to optimally address multimorbidity now and in the future.

Assessment of long-term cognitive dysfunction in older patients who undergo heart surgery.

INTRODUCTION: Older patients are more likely to have cognitive dysfunction, and a great proportion of patients undergone surgical procedures are older adults. Postoperative cognitive dysfunction (POCD) has been shown as a consistent complication after major surgical procedures such as heart surgery. AIM: To determine the presence of long-term POCD in ≥65-year-old patients undergoing coronary artery bypass grafting and aortic valve replacement, and to establish related risk factors. METHODS: We prospectively and sequentially included 44 patients with coronary disease and aortic stenosis scheduled for heart surgery. Follow-up of all patients was standardized and a neurocognitive evaluation were performed preoperatively and at 1, 6 and 12 months after surgery. RESULTS: Patients experienced a significantly postoperative cognitive dysfunction (33.5%, 63.4% and 38.9% at 1, 6 and 12 months, respectively) from baseline (20.5%). Patient-associated aspects such as age (p<0.01), history of smoking (p<0.01), arterial hypertension (p=0.022), diabetes mellitus (p=0.024), heart failure (p=0.036) and preoperative cognitive dysfunction (p<0.01), and surgery-associated aspects such as EuroSCORE (p<0.01) and operation time (p<0.01) were identified as related risk factors. CONCLUSIONS: Older patients who underwent heart surgery had long-term POCD. Both patient- and surgery-related risk factors were established as related risk factors. These findings suggest that the prevalence of cognitive dysfunction after cardiac surgery in older patients could be related to a possible progression to dementia. In addition, many of the risk factors identified may be modifiable but in practice, these patients are not attended to for their possible cognitive impairment.

The impact of frailty on intra-hospital survival in older patients with COVID-19 infection: the importance of early identification. SEMI-COVID National Registry.

BACKGROUND: Emerging evidence suggests that frailty may be a significant predictor of poor outcomes in older individuals hospitalized due to COVID-19. This study aims to determine the prognostic value of frailty on intrahospital patient survival. METHODS: This observational, multicenter, nationwide study included patients aged 70 years and older who were hospitalized due to COVID-19 in Spain between March 1 and December 31, 2020. Patient data were obtained from the SEMI-COVID-19 Registry of the Spanish Society of Internal Medicine. Frailty was assessed using the Clinical Frailty Scale. The primary outcome was hospital survival. Cox proportional hazards models were used to assess predictors of survival. RESULTS: A total of 1,878 participants (52% men and 48% women) were included, with 1,351 (71.9%) survivors and 527 (28.1%) non-survivors. The non-survivor group had higher mean age (83.5 vs. 81 years), comorbidities (6.3 vs. 5.3 points on the Charlson index), degree of dependency (26.8% vs. 12.4% severely dependent patients), and frailty (34.5% vs. 14.7% severely frail patients) compared to survivors. However, there were no differences in terms of sex. Our results demonstrate that a moderate-severe degree of frailty is the primary factor independently associated with shorter survival [HR 2.344 (1.437-3.823; p<0.001) for CFS 5-6 and 3.694 (2.155-6.330; p<0.001) for CFS 7-9]. CONCLUSION: Frailty is the main predictor of adverse outcomes in older patients with COVID-19. The utilization of tools such as the Clinical Frailty Scale is crucial for early detection in this population.

Impact of days elapsed from the onset of symptoms to hospitalization in COVID-19 in-hospital mortality: time matters.

BACKGROUND: COVID-19 shows different clinical and pathophysiological stages over time. The effect of days elapsed from the onset of symptoms (DEOS) to hospitalization on COVID-19 prognostic factors remains uncertain. We analyzed the impact on mortality of DEOS to hospitalization and how other independent prognostic factors perform when taking this time elapsed into account. METHODS: This retrospective, nationwide cohort study, included patients with confirmed COVID-19 from February 20th and May 6th, 2020. The data was collected in a standardized online data capture registry. Univariate and multivariate COX-regression were performed in the general cohort and the final multivariate model was subjected to a sensitivity analysis in an early presenting (EP; <5 DEOS) and late presenting (LP; ≥5 DEOS) group. RESULTS: 7915 COVID-19 patients were included in the analysis, 2324 in the EP and 5591 in the LP group. DEOS to hospitalization was an independent prognostic factor of in-hospital mortality in the multivariate Cox regression model along with other 9 variables. Each DEOS increment accounted for a 4.3% mortality risk reduction (HR 0.957; 95% CI 0.93-0.98). Regarding variations in other mortality predictors in the sensitivity analysis, the Charlson Comorbidity Index only remained significant in the EP group while D-dimer only remained significant in the LP group. CONCLUSION: When caring for COVID-19 patients, DEOS to hospitalization should be considered as their need for early hospitalization confers a higher risk of mortality. Different prognostic factors vary over time and should be studied within a fixed timeframe of the disease.