Lifting COVID-19 mitigation measures in Spain (May-June 2020).

Introduction: The state of alarm was declared in Spain due to the COVID-19 epidemic on March 14, 2020, and established population confinement measures. The objective is to describe the process of lifting these mitigation measures. Methods: The Plan for the Transition to a New Normality, approved on April 28, contained four sequential phases with progressive increase in socio-economic activities and population mobility. In parallel, a new strategy for early diagnosis, surveillance and control was implemented. A bilateral decision mechanism was established between the Spanish Government and the autonomous communities (AC), guided by a set of qualitative and quantitative indicators capturing the epidemiological situation and core capacities. The territorial units were established ad-hoc and could be from Basic Health Zones to entire AC. Results: The process run from May 4 to June 21, 2020. AC implemented plans for reinforcement of core capacities. Incidence decreased from a median (50% of territories) of 7.4 per 100,000 in 7 days at the beginning to 2.5 at the end. Median PCR testing increased from 53% to 89% of suspected cases and PCR total capacity from 4.5 to 9.8 per 1000 inhabitants weekly; positivity rate decreased from 3.5% to 1.8%. Median proportion of cases with traced contacts increased from 82% to 100%. Conclusion: Systematic data collection, analysis, and interterritorial dialogue allowed adequate process control. The epidemiological situation improved but, mostly, the process entailed a great reinforcement of core response capacities nation-wide, under common criteria. Maintaining and further reinforcing capacities remained crucial for responding to future waves.

Introducción: El 14 de marzo de 2020 España declaró el estado de alarma por la pandemia por COVID-19 incluyendo medidas de confinamiento. El objetivo es describir el proceso de desescalada de estas medidas. Métodos: Un plan de transición hacia una nueva normalidad, del 28 de abril, incluía 4 fases secuenciales incrementando progresivamente las actividades socioeconómicas y la movilidad. Concomitantemente, se implementó una nueva estrategia de diagnóstico precoz, vigilancia y control. Se estableció un mecanismo de decisión bilateral entre Gobierno central y comunidades autónomas (CCAA), guiado por un panel de indicadores cualitativos y cuantitativos de la situación epidemiológica y las capacidades básicas. Las unidades territoriales evaluadas comprendían desde zonas básicas de salud hasta CCAA. Resultados: El proceso se extendió del 4 de mayo al 21 de junio y se asoció a planes de refuerzo de las capacidades en las CCAA. La incidencia disminuyó de una mediana inicial de 7,4 por 100.000 en 7 días a 2,5 al final del proceso. La mediana de pruebas PCR aumentó del 53% al 89% de los casos sospechosos, y la capacidad total de 4,5 a 9,8 pruebas semanales por 1.000 habitantes; la positividad disminuyó del 3,5% al 1,8%. La mediana de casos con contactos trazados aumentó del 82% al 100%. Conclusión: La recogida y análisis sistemático de información y el diálogo interterritorial logaron un adecuado control del proceso. La situación epidemiológica mejoró, pero sobre todo, se aumentaron las capacidades, en todo el país y con criterios comunes, cuyo mantenimiento y refuerzo fue clave en olas sucesivas.

Trends in stroke mortality in La Rioja (Spain) from 1999 to 2022.

INTRODUCTION: Stroke mortality has declined in recent decades, but there appears to be a slowdown in the decline in recent years. We analyze the trends in stroke mortality in La Rioja (Spain) for the period 1999-2022. METHODS: We evaluated stroke mortality using statistical data from the mortality registry of La Rioja (Spain). We adjusted the rates by age and sex and analyzed both overall strokes and subtypes: hemorrhagic and ischemic. To analyze the trend in mortality rates we constructed joinpoint regression models, with associated annual percentage change (APC) RESULTS: Age-standardized stroke mortality declined between 1999 and 2022: females from 98.0 to 29.2 per 100 000; males, from 131.6 to 44.8 per 100 000. We found a decrease in overall stroke mortality in all age groups, except those under 65 years old. Ischemic stroke mortality showed declines in the first decade (APC: 7.3%, CI95%: 4.1-19.1%) and increases in the second decade (APC: 1.6%, CI95%: -1.6-11.7%) among men. In women, the rates declined between 2018 and 2022(APC: -6.6%, CI95%: -5.1-30.6%) after an increase between 2015 and 2017 (APC: 23.5%, CI95%: -20.2-38.3%). For hemorrhagic stroke, we found a consistent rate of decline throughout the entire time period in men (APC: 2.4%, CI95%: 0.9 a 4.0%). In women, rates increased during the period 1999-2009(APC: 1.9%, CI95%: -2.1-22.8%) and decreased 2010-2022 (APC: 6.5%, CI95%: 4.0-25.6%). CONCLUSIONS: Stroke mortality rates have decreased, more so for haemorrhagic than ischaemic strokes.

CCL5 Levels Predict Stroke Volume Growth in Acute Ischemic Stroke and Significantly Diminish in Hemorrhagic Stroke Patients.

Stroke remains an important health challenge. Here, we study whether circulating chemokine (C-C motif) ligand 5 (CCL5) levels may predict clinical outcomes for stroke patients. A total of 100 consecutive stroke patients (36 acute ischemic and 64 hemorrhagic) were admitted to the stroke unit. Clinical history data and monitoring parameters were recorded. Blood serum was collected at days 0, 1, and hospital discharge to measure CCL5 levels by ELISA. Infarct or hemorrhagic volume, neurological severity (NIHSS), and functional prognosis (mRankin scale) were measured as clinical outcomes. CCL5 levels were lower in patients with hemorrhagic stroke than in patients with acute ischemic stroke. No differences were found between females and males in both types of stroke. Ischemic stroke patients whose infarct volume grew had lower CCL5 levels at day 0. Levels of CCL5 in ischemic and hemorrhagic patients were not associated with more severe symptoms/worse prognosis (NIHSS > 3; mRankin > 2) at admission or at 3 months. CCL5 could be used as a diagnostic marker to distinguish between ischemic and hemorrhagic strokes. Furthermore, CCL5 levels could predict the infarct volume outcomes in ischemic patients.

Trends in Guillain-Barré syndrome mortality in Spain from 1999 to 2013.

BACKGROUND: Guillain-Barré syndrome (GBS) is a rare disease that consists of a group of neuropathic conditions. Very few epidemiological studies of GBS have been carried out in Spain. The aim of this study was to determine the trends in GBS mortality in the total population of Spain for the period 1999 to 2013. METHODS: Data on GBS deaths were drawn from the National Statistics Institute of Spain. Crude and overall age-standardised GBS mortality rates were calculated and joinpoint regression models were used to describe trend changes. Mean age of deceased by GBS each year was also assessed. RESULTS: The overall age-standardised GBS mortality rate was 0.71 per million in 1999 and 0.40 in 2013. It was higher in men, 1.08 vs. 0.42 in 1999 and 0.48 vs. 0.35 in 2013. There was a statistically significant decrease in mortality during the study period. All the age-standardised mortality rates decreased (overall and by gender) from 1999 to 2013. The mean age at death increased with time, from 73 years in 1999 to 77 years in 2013. CONCLUSIONS: GBS mortality has improved in Spain during the last 15 years. The age of death has risen and the mortality rate has decreased.

Validation of diagnosis of aplastic anaemia in La Rioja (Spain) by International Classification of Diseases codes for case ascertainment for the Spanish National Rare Diseases Registry.

OBJECTIVE: To analyse the validity of diagnosis of aplastic anaemia (AA) by International Classification of Diseases codes in hospital discharge data (MBDS) and the mortality registry (MR) of La Rioja to detect cases to be included in the Spanish National Rare Diseases Registry. METHODS: International Classification of Diseases (ICD) codes were used to detect AA cases during the period 2007-2012 from two administrative databases: the MBDS and the MR of La Rioja (Spain). Medical records of population selected by merging both databases were used to confirm true AA cases. The annual mean incidence rate of AA was calculated using confirmed incident cases. RESULTS: By merging both databases, 62 hypothetical AA incident patients were detected during the period 2007-2012. The medical records of the 89% of them could be revised, and they confirmed that only the 15% of the patients actually suffered AA. The annual mean AA incidence in La Rioja was 4.17 per million inhabitants (6.23 per million, males; 2.10 per million, females). CONCLUSIONS: The MBDS and the MR are not in themselves sufficient to ascertain AA cases in La Rioja and medical records should be reviewed to confirm true AA cases to be included in the Spanish National Rare Diseases Registry.

Validity of procalcitonin for the diagnosis of bacterial infection in elderly patients.

INTRODUCTION: PCT has been consolidated as a key tool in the diagnosis of bacterial infections in general population. Few studies have been conducted to determine the applicability of this test in elderly patients. METHODS: Study of validity of PCT on elderly patients. Two groups were formed; the first group was formed by patients aged 75 years or older, under bacterial infection criteria and PCT on the initial Lab test. The second group was formed by patients aged 75 years or older with any noninfectious disease; these patients were asked PCT in the initial Lab test. Sensitivity, specificity, positive and negative likelihood ratio were calculated. RESULTS: 161 patients were included, 95 with probable bacterial infection and 66 without infection. Patients with probable bacterial infection criteria, 72% of them had PCT >0.5 ng/mL. Patients without infection, 8% of the patients had PCT >0.5 ng/mL. Sensitivity and specificity of PCT to bacterial infection with the cutoff value of 0.5 ng/mL was 72% and 92%, respectively. CONCLUSION: PCT can be used in elderly patients to diagnose bacterial infections because it has proved good sensitivity and high specificity.

Validity of discharge diagnoses in the surveillance of stroke.

BACKGROUND: Hospital administrative data have been suggested as a valuable cost-effective tool for providing information about the stroke burden. Nevertheless, the choice of the diagnosis codes has been a critical issue in the development of case ascertainment algorithms. METHODS: In this study, the Minimum Basic Data Set administrative database was used to analyze the accuracy of different ICD-9-CM algorithms based on the neurologist's clinical judgement as the 'gold standard'. RESULTS: The most accurate algorithm observed in our study involved the selection of ICD-9-CM codes 430-438 in the primary diagnosis. It yielded a sensitivity of 96.1%, a specificity of 87.5% and a positive predictive value of 82.5%. CONCLUSIONS: The Minimum Basic Data Set is a valuable source to evaluate stroke frequency when using an accurate algorithm to select events.

Hospital discharges and mortality registries: 2 complementary databases for the epidemiological surveillance of stroke.

BACKGROUND: Stroke is a public health concern and the availability of a stroke registry would provide valuable information. Administrative hospital data and mortality registries have been previously suggested as suitable sources of information. The aim of this study was to evaluate the utility of merging data from a hospital discharge database and the mortality registry (MR) to estimate the incidence of stroke in La Rioja, Spain. METHODS: A cross-sectional study about events of stroke occurred in our region in 2009 was carried out. Patients were selected among those registered in the discharge hospital database and in the MR, using the International Classification of Diseases. The databases were merged to detect duplicated occurrences and to estimate the number of cases identified by each source. Characteristics of the study population were analyzed and crude- and age-adjusted incidence rates were assessed. RESULTS: Using both databases, 1133 stroke events were detected, 153 (13.5%) representing coincident or recurrent cases. A total of 980 incident stroke cases were obtained, 150 provided by the MR (15.3%) and 830 by the hospital discharge database (84.7%). Incidence of stroke was similar in men than in women, the ischemic stroke being the major type. Most of the study population (66%) were older than 74 years. Crude incidence rate was 304.6 per 100,000, and age-adjusted rates were 171.1 per 100,000 (adjusted to the European population) and 107.9 per 100,000 (adjusted to the World population). CONCLUSIONS: Considering both the Minimum Basic Data Set and the MR as data sources appears advisable to build a stroke registry to evaluate the incidence and to perform epidemiological surveillance of stroke.

Trends in suicide mortality in Spain from 1998 to 2021 and its relationship with the COVID-19 pandemic: A joinpoint regression analysis.

In the European Union, a rate of 11.9 cases per 100,000 was estimated in 2019.In Spain, suicide is the leading cause of external death. Social crises can have an impact on suicide rates. We analyzed changes in suicide mortality trends in Spain following the COVID-19 pandemic. We used statistical data from the National Institute of Statistics of Spain (1998-2021). We calculated age-specific rates, age and sex-adjusted rates, and analyzed trends and changes using joinpoint-regression models. Rates decrease in both sexes at the ages of 65 and older. In women, they increase in the ages of 1-29 years and 45-59 years. In men, they decrease in the ages of 15-39 years. Among women, age-adjusted rates remained stable between 1998 and 2021, with a non-significant annual decrease of 0.4 %. Among men, there was a significant annual decrease of 0.7 %. The years 2020 and 2021 had 8 % higher mortality compared to the two years prior to the COVID-19 pandemic. Suicide mortality in Spain slightly decreased among men and remained stable among women between 1998 and 2021, but there seems to be an increase following the COVID-19 pandemic.

Lifting COVID-19 mitigation measures in Spain (May-June 2020).

INTRODUCTION: The state of alarm was declared in Spain due to the COVID-19 epidemic on March 14, 2020, and established population confinement measures. The objective is to describe the process of lifting these mitigation measures. METHODS: The Plan for the Transition to a New Normality, approved on April 28, contained four sequential phases with progressive increase in socio-economic activities and population mobility. In parallel, a new strategy for early diagnosis, surveillance and control was implemented. A bilateral decision mechanism was established between the Spanish Government and the autonomous communities (AC), guided by a set of qualitative and quantitative indicators capturing the epidemiological situation and core capacities. The territorial units were established ad-hoc and could be from Basic Health Zones to entire AC. RESULTS: The process run from May 4 to June 21, 2020. AC implemented plans for reinforcement of core capacities. Incidence decreased from a median (50% of territories) of 7.4 per 100,000 in 7 days at the beginning to 2.5 at the end. Median PCR testing increased from 53% to 89% of suspected cases and PCR total capacity from 4.5 to 9.8 per 1000 inhabitants weekly; positivity rate decreased from 3.5% to 1.8%. Median proportion of cases with traced contacts increased from 82% to 100%. CONCLUSION: Systematic data collection, analysis, and interterritorial dialogue allowed adequate process control. The epidemiological situation improved but, mostly, the process entailed a great reinforcement of core response capacities nation-wide, under common criteria. Maintaining and further reinforcing capacities remained crucial for responding to future waves.

Prognostic and Predictive Biomarkers in Patients with Locally Advanced Rectal Cancer (LARC) Treated with Preoperative Chemoradiotherapy.

Neoadjuvant chemoradiotherapy (CRT) is one of the standards of care in locally advanced rectal cancer (LARC). This retrospective study examines clinical, analytical, and pathological parameters collected from 77 patients with locally advanced (cT3-4 or cN+) rectal carcinoma diagnosed between 2007 and 2017 at our institution that were treated with preoperative CRT and surgery. In the prognosis analysis, lower hemoglobin levels (p = 0.008), lower lymphocyte/monocyte ratio (LMR) (p = 0.011), and higher platelet/lymphocyte ratio (PLR) (p = 0.029) in the second determination (Hb2, LMR2 and PLR2) were associated with the relapse group. The number of positive nodes after surgery (N+) showed a statistically significant association with relapse (p = 0.012). KRAS mutations were associated with a worse prognosis for 5 years progression-free and overall survival (p = 0.005 and 0.022; respectively). We propose a prognostic model based on four parameters (number of positive lymph nodes after surgery, hemoglobin levels, LMR, and PLR after neoadjuvant therapy) that can be a useful tool to estimate relapse risk. Moreover, bilirubin could be a useful parameter to predict the response to neoadjuvant CRT.

Cancer Survival in Adults in Spain: A Population-Based Study of the Spanish Network of Cancer Registries (REDECAN).

The assessment of cancer survival at the population level is essential for monitoring progress in cancer control. We aimed to assess cancer survival and its trends in adults in Spain. Individual records of 601,250 adults with primary cancer diagnosed during 2002-2013 and followed up to 2015 were included from 13 population-based cancer registries. We estimated net survival up to five years after diagnosis and analyzed absolute changes between 2002-2007 and 2008-2013. Estimates were age-standardized. Analyses were performed for 29 cancer groups, by age and sex. Overall, age-standardized five-year net survival was higher in women (61.7%, 95% CI 61.4-62.1%) than in men (55.3%, 95% CI 55.0-55.6%), and ranged by cancer from 7.2% (pancreas) to 89.6% (prostate) in men, and from 10.0% (pancreas) to 93.1% (thyroid) in women in the last period. Survival declined with age, showing different patterns by cancer. Between both periods, age-standardized five-year net survival increased overall by 3.3% (95% CI 3.0-3.7%) in men and 2.5% (95% CI 2.0-3.0%) in women, and for most cancer groups. Improvements were greater in patients younger than 75 years than in older patients. Chronic myeloid leukemia and myeloma showed the largest increases. Among the most common malignancies, the greatest absolute increases in survival were observed for colon (5.0%, 95% CI 4.0-6.0%) and rectal cancers (4.5%, 95% CI 3.2-5.9%). Survival improved even for some cancers with poor prognosis (pancreas, esophagus, lung, liver, and brain cancer). Further investigation of possible sociodemographic inequalities is warranted. This study contributes to the evaluation of cancer control and health services' effectiveness.

[Surveillance of rare diseases in Spain: Spanish Registry of Rare Diseases (ReeR).] / Vigilancia de las enfermedades raras en España: el Registro Estatal de Enfermedades Raras (ReeR).

Traditionally, epidemiological surveillance has focused on infectious diseases, but the concept of Public Health surveillance, introduced in Spain with the Law 33/2011, is broader and includes chronic diseases. Health strategies for these diseases need epidemiological information to improve understanding of socio-health needs and to facilitate the efficient management of resources. The European Union defines rare diseases (RD) as those that, being life-threatening or chronically debilitating, have a prevalence of less than 5 cases per 10,000 inhabitants. The RD Strategy of the National Health System, approved in 2009 and updated in 2014, recommends the development of regional registries of rare diseases (RAER), in addition to a national registry. The REpIER and Spain-RDR projects of the Institute of Health Carlos III (ISCIII) promoted the creation and regulation of 94% of the RAER. After more than 10 years of initiatives and work to improve the knowledge of RD's epidemiology in Spain, it was possible to implement the Spanish Registry of Rare Diseases (ReeR) in 2015, becoming one of the first population surveillance systems for chronic diseases of state scope. The ReeR procedures manual is the result of consensus between the RAER, the Ministry of Health, the ISCIII and the patient associations. The participatory methodology used for the implementation and launching of ReeR is considered an added value. The information system implemented will allow improving knowledge about the prevalence and distribution of RD in Spain.

Tradicionalmente la vigilancia epidemiológica se ha centrado en enfermedades transmisibles, pero el concepto de vigilancia en Salud Pública, incorporado en España con la Ley 33/2011, es más amplio e incluye las enfermedades crónicas. Las estrategias de salud para estas enfermedades necesitan disponer de información epidemiológica para mejorar el conocimiento de las necesidades sociosanitarias y facilitar la gestión eficiente de recursos. La Unión Europea define las enfermedades raras (ER) como aquellas que, con peligro de muerte o invalidez crónica, presentan una prevalencia inferior a 5 casos por cada 10.000 habitantes. La Estrategia en ER del Sistema Nacional de Salud, aprobada en 2009 y actualizada en 2014, recomienda desarrollar registros autonómicos de enfermedades raras (RAER) y uno estatal. Los proyectos REpIER y Spain-RDR del Instituto de Salud Carlos III (ISCIII) impulsaron la creación y regulación del 94% de los RAER; y tras más de 10 años de iniciativas y trabajos para mejorar el conocimiento de la epidemiología de las ER en España, se logró implementar el Registro Estatal de Enfermedades Raras (ReeR) en 2015, convirtiéndose en uno de los primeros sistemas de vigilancia poblacional de enfermedades crónicas de ámbito estatal. El manual de procedimientos del ReeR es el resultado del consenso entre los RAER, Ministerio de Sanidad, ISCIII y asociaciones de pacientes. La metodología participativa empleada para la implementación y puesta en funcionamiento del ReeR es considerada un valor añadido. El sistema de información implementado va a permitir mejorar el conocimiento sobre la prevalencia y distribución de las ER en España.

Education and information needs for physicians about rare diseases in Spain.

BACKGROUND: Rare diseases are a priority objective for public health systems. Given its complexity, late and misdiagnoses occur very often which causes mental and physical burden for patients and family. This would be caused, in part, for unprepared clinicians in this field. The aim of this study was to report the training needs and the perceived shortcomings of Spanish physicians of the public health system in the diagnosis, treatment and monitoring of patients with rare diseases. METHODS: We used a descriptive cross-sectional study through an "ad hoc" survey of 26 questions was completed by 132 primary care physicians and 37 specialists during April and May 2018. RESULTS: Less than a third of the physicians had received training in rare disease during their undergraduate or postgraduate years, and for hospital professionals, they received more training in the postgraduate period. CONCLUSION: Primary care physicians and specialists showed low training level in rare diseases. An academical and continuous program on rare disease, as well as, multidisciplinary units and high quality practice guidelines are necessary to help to prevention and support clinical decisions and improve quality of care of patients and families.

Duplex mapping of 2036 primary varicose veins.

OBJECTIVE: To produce a comprehensive anatomical and hemodynamic ultrasound scan mapping of the whole limb in patients with primary varicose veins (VVs). DESIGN: An analysis of venous duplex scans performed on patients referred for treatment of primary VVs. METHODS: A total of 2036 limbs were evaluated, looking for the origin of VVs in the saphenous systems and in the perforating vein (PV) systems, as well as for the presence of non-saphenous reflux. RESULTS: The sapheno-femoral junction (SFJ) of the great saphenous vein (GSV) was involved in 1330 limbs (65.3%). We have noted that finding reflux in the groin does not imply that it originates at that point necessarily, as reflux from the pelvis or abdominal wall can also cause primary VVs (SFJ reflux, 41.9% and competent SFJ with reflux from proximal veins, 35.4%). We also noted that analyzing only the presence of reflux in the SFJ of the GSV would miss 10.9% of limbs of reflux in the SFJ of the anterior accessory GSV. In 237 limbs (11.6%), reflux was observed in the popliteal fossa. In the PV system, we distinguished those PVs with retrograde flow that acted as an origin of the VVs, and other PVs that acted as re-entry points. Based on this difference, the location identified as the most frequent origin of VVs in the PV system was the thigh, specifically in the group of PVs of the medial thigh of the femoral canal, with 85 PVs with a total of 238 incompetent PVs identified. Pure non-saphenous reflux was observed in 162 limbs (8%). CONCLUSION: The assumption that the origin of VVs would be exclusively in the sapheno-femoral or sapheno-popliteal junction, is a mistaken attitude and a comprehensive duplex scan mapping is recommended.

Gender differences for frailty in HIV-infected patients on stable antiretroviral therapy and with an undetectable viral load.

BACKGROUND: Patients with HIV infection suffer from accelerated aging. In this context, frailty could be a relevant problem that aggravates the quality of life (QoL) and morbi-mortality of these patients. Our objective was to determine the prevalence of frailty and pre-frailty in HIV-infected patients in our cohort as well as their risk factors and QoL. METHODS: This was a prospective cross-sectional study of HIV-infected people aged ≥18 years on a stable antiretroviral regimen (ART) ≥1 year. Frailty was defined by ≥3 of 5 Fried's criteria: weight loss, low physical activity, exhaustion, weak grip strength and slow walking time. Variables related to sociodemographics, HIV infection, comorbidities, polypharmacy, and QoL were evaluated. Independent predictors of frailty were evaluated using collinearity in a multivariate logistic regression analyses (backward stepwise elimination). RESULTS: The 248 people studied has a mean age of 49 years, 63.7% were male, and 81% were Caucasian. The prevalence of pre-frailty and fragility was 39.1% and 4.4%, respectively. The main route of HIV acquisition was heterosexual (47.2%). At the inclusion time 26.6% of the patients had AIDS events, 60.9% were anti-HCV negative, and 91.5% had HIV RNA <50 copies/mL (84.3% for ≥1 year); 10.9% had >2 comorbidities, and 13.3% were receiving >5 non-HIV drugs. Frailty patients had a higher age (p 0.006), more sensitive deficits (visual or auditory) (p 0.002), a greater number of falls during the previous year (p 0.0001), a higher Charlson comorbidity index (p 0.001), and a higher VACS index (p 0.001). All comorbidities, excluding bone and liver, were significantly more frequent in fragile patients. The presence of >2 comorbidities and treatment with >5 drugs not related to HIV they were also more frequent in frail patienst (p 0.0001 and p 0.004, respectively). Independent predictors of pre-frailty/frailty in the multivariable analysis differ in men (VACS index, C-reactive protein [CRP], and falls) and women (CRP, AIDS, and menopause). Patients with pre-frailty/frailty had some indicator of a lower QoL. CONCLUSION: Factors associated with pre-frailty/frailty in HIV-infected patients differ by gender, which should be considered when establishing measures for prevention. The role of menopause in the risk of pre-frailty/frailty warrants further investigations.

Battle of Thermopylae: 300 Spartans (natural killer cells plus obinutuzumab) versus the immortal warriors (chronic lymphocytic leukemia cells) of Xerxes' army.

AIM: To analyze the effects of subcutaneous or intravenous rituximab + lymphokine-activated killer cells, obinutuzumab or ibrutinib on natural killer (NK) cell levels in chronic lymphocytic leukemia and follicular lymphoma patients. PATIENTS & METHODS: The distribution of peripheral blood NK cells of 31 patients was analyzed by flow cytometry. RESULTS: We detected a decrease of NK cells in peripheral blood below normal range after obinutuzumab treatment. During maintenance treatment with subcutaneous rituximab, an NK cell reduction was less pronounced than after intravenous rituximab treatment, despite lymphokine-activated killer cell infusions. CONCLUSION: After one dose of obinutuzumab, each NK cell in peripheral blood destroys 25 leukemic cells.

Impact of variations in blood pressure with orthostatism on mortality: the HOMO study.

OBJECTIVE: The aim of this study was to determine the impact of orthostatic hypotension (OH) and orthostatic hypertension (OHT) on all-cause mortality. PATIENTS AND METHODS: A total of, 1176 adults from the community over 18 years of age were included in this ambispective study. The mean follow-up was 9.4 years. OH and OHT were defined as a decrease or an increase, respectively, in systolic blood pressure (BP) of at least 20 mmHg and/or diastolic BP of at least 10 mmHg from sitting to standing position at 1 and/or 3 min after standing. The impact of systolic or diastolic OH and systolic or diastolic OHT at 1 and 3 min after standing was also analyzed separately. RESULTS: In total, 135 individuals died during the follow-up. Neither OH [hazard ratio (HR) 1.23; 95% confidence interval (CI): 0.72-2.10] nor OHT (HR 0.90; 95% CI: 0.59-1.38) was associated with all-cause mortality in the adjusted models. In contrast, systolic OHT at 3 min (HR 2.31; 95% CI: 1.14-4.68) was independently associated with global mortality. CONCLUSION: Systolic OHT at 3 min is associated with all-cause mortality. The determination of this parameter could add valuable prognostic information during the routine examination of patients.

[Disease registries in the epidemiological researching of rare diseases in Spain]. / Los registros de enfermedades en la investigacion epidemiológica de las enfermedades raras en España.

BACKGROUND: The use of tools such as disease registries poses a problem in the case of rare diseases. This study is aimed at describing the current situation concerning rare disease registries in Spain. METHODS: The information provided by two Spanish health registries directories prepared by the Spanish Health Assessment Technologies Agencies are employed, a descriptive cross-sectional study being conducted. The registries identified in these directories has been classified as: (1) "Specific rare diseases" (2) "Unspecific but with information on rare disease and (3) "Non-informative regarding rare diseases". RESULTS: The 2000 directory listed 82 registries, 15.8% of which were classified under Group 1, whilst a total of 107 registries, 16.8% in Group 1, were identified in the 2005 review. The main health registries in Group 2, by topic, were: cancer, mortality, psychiatry and nephrology. No general rare disease registries were found in the directories. CONCLUSIONS: Although few in number, health registries do exist in Spain including information on rare diseases. Areas have been identified by topic lacking registries and also information systems or registries unidentified in the sources used. Continuing efforts must be made to improve the information available on rare diseases.