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.

Effectiveness of influenza vaccine against laboratory-confirmed influenza, in the late 2011-2012 season in Spain, among population targeted for vaccination.

BACKGROUND: In Spain, the influenza vaccine effectiveness (VE) was estimated in the last three seasons using the observational study cycEVA conducted in the frame of the existing Spanish Influenza Sentinel Surveillance System. The objective of the study was to estimate influenza vaccine effectiveness (VE) against medically attended, laboratory-confirmed influenza-like illness (ILI) among the target groups for vaccination in Spain in the 2011-2012 season. We also studied influenza VE in the early (weeks 52/2011-7/2012) and late (weeks 8-14/2012) phases of the epidemic and according to time since vaccination. METHODS: Medically attended patients with ILI were systematically swabbed to collect information on exposure, laboratory outcome and confounding factors. Patients belonging to target groups for vaccination and who were swabbed <8 days after symptom onset were included. Cases tested positive for influenza and controls tested negative for any influenza virus. To examine the effect of a late season, analyses were performed according to the phase of the season and according to the time between vaccination and symptoms onset. RESULTS: The overall adjusted influenza VE against A(H3N2) was 45% (95% CI, 0-69). The estimated influenza VE was 52% (95% CI, -3 to 78), 40% (95% CI, -40 to 74) and 22% (95% CI, -135 to 74) at 3.5 months, 3.5-4 months, and >4 months, respectively, since vaccination. A decrease in VE with time since vaccination was only observed in individuals aged ≥ 65 years. Regarding the phase of the season, decreasing point estimates were only observed in the early phase, whereas very low or null estimates were obtained in the late phase for the shortest time interval. CONCLUSIONS: The 2011-2012 influenza vaccine showed a low-to-moderate protective effect against medically attended, laboratory-confirmed influenza in the target groups for vaccination, in a late season and with a limited match between the vaccine and circulating strains. The suggested decrease in influenza VE with time since vaccination was mostly observed in the elderly population. The decreasing protective effect of the vaccine in the late part of the season could be related to waning vaccine protection because no viral changes were identified throughout the season.

Assessment of Human SARS CoV-2-Specific T-Cell Responses Elicited In Vitro by New Computationally Designed mRNA Immunogens (COVARNA).

The COVID-19 pandemic has brought significant changes and advances in the field of vaccination, including the implementation and widespread use of encapsidated mRNA vaccines in general healthcare practice. Here, we present two new mRNAs expressing antigenic parts of the SARS-CoV-2 spike protein and provide data supporting their functionality. The first mRNA, called RBD-mRNA, encodes a trimeric form of the virus spike protein receptor binding domain (RBD). The other mRNA, termed T-mRNA, codes for the relevant HLA I and II spike epitopes. The two mRNAs (COVARNA mRNAs) were designed to be used for delivery to cells in combination, with the RBD-mRNA being the primary source of antigen and the T-mRNA working as an enhancer of immunogenicity by supporting CD4 and CD8 T-cell activation. This innovative approach substantially differs from other available mRNA vaccines, which are largely directed to antibody production by the entire spike protein. In this study, we first show that both mRNAs are functionally transfected into human antigen-presenting cells (APCs). We obtained peripheral blood mononuclear cell (PBMC) samples from three groups of voluntary donors differing in their immunity against SARS-CoV-2: non-infected (naïve), infected-recovered (convalescent), and vaccinated. Using an established method of co-culturing autologous human dendritic cells (hDCs) with T-cells, we detected proliferation and cytokine secretion, thus demonstrating the ability of the COVARNA mRNAs to activate T-cells in an antigen-specific way. Interestingly, important differences in the intensity of the response between the infected-recovered (convalescent) and vaccinated donors were observed, with the levels of T-cell proliferation and cytokine secretion (IFNγ, IL-2R, and IL-13) being higher in the vaccinated group. In summary, our data support the further study of these mRNAs as a combined approach for future use as a vaccine.

Safety and immunogenicity of the protein-based PHH-1V compared to BNT162b2 as a heterologous SARS-CoV-2 booster vaccine in adults vaccinated against COVID-19: a multicentre, randomised, double-blind, non-inferiority phase IIb trial.

Background: A SARS-CoV-2 protein-based heterodimer vaccine, PHH-1V, has been shown to be safe and well-tolerated in healthy young adults in a first-in-human, Phase I/IIa study dose-escalation trial. Here, we report the interim results of the Phase IIb HH-2, where the immunogenicity and safety of a heterologous booster with PHH-1V is assessed versus a homologous booster with BNT162b2 at 14, 28 and 98 days after vaccine administration. Methods: The HH-2 study is an ongoing multicentre, randomised, active-controlled, double-blind, non-inferiority Phase IIb trial, where participants 18 years or older who had received two doses of BNT162b2 were randomly assigned in a 2:1 ratio to receive a booster dose of vaccine-either heterologous (PHH-1V group) or homologous (BNT162b2 group)-in 10 centres in Spain. Eligible subjects were allocated to treatment stratified by age group (18-64 versus ≥65 years) with approximately 10% of the sample enrolled in the older age group. The primary endpoints were humoral immunogenicity measured by changes in levels of neutralizing antibodies (PBNA) against the ancestral Wuhan-Hu-1 strain after the PHH-1V or the BNT162b2 boost, and the safety and tolerability of PHH-1V as a boost. The secondary endpoints were to compare changes in levels of neutralizing antibodies against different variants of SARS-CoV-2 and the T-cell responses towards the SARS-CoV-2 spike glycoprotein peptides. The exploratory endpoint was to assess the number of subjects with SARS-CoV-2 infections ≥14 days after PHH-1V booster. This study is ongoing and is registered with ClinicalTrials.gov, NCT05142553. Findings: From 15 November 2021, 782 adults were randomly assigned to PHH-1V (n = 522) or BNT162b2 (n = 260) boost vaccine groups. The geometric mean titre (GMT) ratio of neutralizing antibodies on days 14, 28 and 98, shown as BNT162b2 active control versus PHH-1V, was, respectively, 1.68 (p < 0.0001), 1.31 (p = 0.0007) and 0.86 (p = 0.40) for the ancestral Wuhan-Hu-1 strain; 0.62 (p < 0.0001), 0.65 (p < 0.0001) and 0.56 (p = 0.003) for the Beta variant; 1.01 (p = 0.92), 0.88 (p = 0.11) and 0.52 (p = 0.0003) for the Delta variant; and 0.59 (p ≤ 0.0001), 0.66 (p < 0.0001) and 0.57 (p = 0.0028) for the Omicron BA.1 variant. Additionally, PHH-1V as a booster dose induced a significant increase of CD4+ and CD8+ T-cells expressing IFN-γ on day 14. There were 458 participants who experienced at least one adverse event (89.3%) in the PHH-1V and 238 (94.4%) in the BNT162b2 group. The most frequent adverse events were injection site pain (79.7% and 89.3%), fatigue (27.5% and 42.1%) and headache (31.2 and 40.1%) for the PHH-1V and the BNT162b2 groups, respectively. A total of 52 COVID-19 cases occurred from day 14 post-vaccination (10.14%) for the PHH-1V group and 30 (11.90%) for the BNT162b2 group (p = 0.45), and none of the subjects developed severe COVID-19. Interpretation: Our interim results from the Phase IIb HH-2 trial show that PHH-1V as a heterologous booster vaccine, when compared to BNT162b2, although it does not reach a non-inferior neutralizing antibody response against the Wuhan-Hu-1 strain at days 14 and 28 after vaccination, it does so at day 98. PHH-1V as a heterologous booster elicits a superior neutralizing antibody response against the previous circulating Beta and the currently circulating Omicron BA.1 SARS-CoV-2 variants in all time points assessed, and for the Delta variant on day 98 as well. Moreover, the PHH-1V boost also induces a strong and balanced T-cell response. Concerning the safety profile, subjects in the PHH-1V group report significantly fewer adverse events than those in the BNT162b2 group, most of mild intensity, and both vaccine groups present comparable COVID-19 breakthrough cases, none of them severe. Funding: HIPRA SCIENTIFIC, S.L.U.

Factors associated with childhood obesity in Spain. The OBICE study: a case-control study based on sentinel networks.

OBJECTIVE: To estimate the association strength of dietary behaviour and sedentary habits in relation to childhood obesity in Spain. DESIGN: A matched case-control study was carried out using data collected by sentinel network paediatricians in general practices. SETTING: Five Spanish autonomous communities. SUBJECTS: Cases were 437 children (2-14 years old) with BMI >95th percentile according to Spanish reference tables. Controls were 751 children (2-14 years old; two paired per case) with BMI <84th percentile. Data were collected in two phases: individual (questionnaires filled in by sentinel paediatricians) and family (self-administered questionnaires filled in a family environment). Crude OR and adjusted OR (ORc and adj OR) for the given variables were calculated using a simple and multiple conditional logistic regression analysis. RESULTS: The factors with the greatest effect on obesity were family history of obesity: both parents (adj OR = 11.2), mother but not father (adj OR = 9.1), father but not mother (adj OR = 6.1), siblings (adj OR = 2.7); and eating between meals (adj OR = 2.5) and consumption of sweets and soft drinks >2 times/week (adj OR = 2.0). The highest protection effect was found for five meals per day (adj OR = 0.5), the regular consumption of breakfast (adj OR = 0.5) and for eating fruit for dessert (adj OR = 0.6). Factors related to sedentary habits did not appear as noteworthy. CONCLUSIONS: We have determined the association between certain dietary behaviour and family history with childhood obesity in several Spanish regions.

Using surveillance data to estimate pandemic vaccine effectiveness against laboratory confirmed influenza A(H1N1)2009 infection: two case-control studies, Spain, season 2009-2010.

BACKGROUND: Physicians of the Spanish Influenza Sentinel Surveillance System report and systematically swab patients attended to their practices for influenza-like illness (ILI). Within the surveillance system, some Spanish regions also participated in an observational study aiming at estimating influenza vaccine effectiveness (cycEVA study). During the season 2009-2010, we estimated pandemic influenza vaccine effectiveness using both the influenza surveillance data and the cycEVA study. METHODS: We conducted two case-control studies using the test-negative design, between weeks 48/2009 and 8/2010 of the pandemic season. The surveillance-based study included all swabbed patients in the sentinel surveillance system. The cycEVA study included swabbed patients from seven Spanish regions. Cases were laboratory-confirmed pandemic influenza A(H1N1)2009. Controls were ILI patients testing negative for any type of influenza. Variables collected in both studies included demographic data, vaccination status, laboratory results, chronic conditions, and pregnancy. Additionally, cycEVA questionnaire collected data on previous influenza vaccination, smoking, functional status, hospitalisations, visits to the general practitioners, and obesity. We used logistic regression to calculate adjusted odds ratios (OR), computing pandemic influenza vaccine effectiveness as (1-OR)*100. RESULTS: We included 331 cases and 995 controls in the surveillance-based study and 85 cases and 351 controls in the cycEVA study. We detected nine (2.7%) and two (2.4%) vaccine failures in the surveillance-based and cycEVA studies, respectively. Adjusting for variables collected in surveillance database and swabbing month, pandemic influenza vaccine effectiveness was 62% (95% confidence interval (CI): -5; 87). The cycEVA vaccine effectiveness was 64% (95%CI: -225; 96) when adjusting for common variables with the surveillance system and 75% (95%CI: -293; 98) adjusting for all variables collected. CONCLUSION: Point estimates of the pandemic influenza vaccine effectiveness suggested a protective effect of the pandemic vaccine against laboratory-confirmed influenza A(H1N1)2009 in the season 2009-2010. Both studies were limited by the low vaccine coverage and the late start of the vaccination campaign. Routine influenza surveillance provides reliable estimates and could be used for influenza vaccine effectiveness studies in future seasons taken into account the surveillance system limitations.

In the Era of mRNA Vaccines, Is There Any Hope for HIV Functional Cure?

Over 36 million people worldwide are infected with HIV. Antiretroviral therapy (ART) has proven to be highly effective to prevent HIV-1 transmission, clinical progression and death. Despite this success, the number of HIV-1 infected individuals continues increasing and ART should be taken for life. Therefore, there are two main priorities: the development of preventive vaccines to protect from HIV acquisition and achieve an efficient control of HIV infection in the absence of ART (functional cure). In this sense, in the last few years, there has been a broad interest in new and innovative approaches such as mRNA-based vaccines. RNA-based immunogens represent a promising alternative to conventional vaccines because of their high potency, capacity for rapid development and potential for low-cost manufacture and safe administration. Some mRNA-based vaccines platforms against infectious diseases have demonstrated encouraging results in animal models and humans. However, their application is still limited because the instability and inefficient in vivo delivery of mRNA. Immunogens, design, immunogenicity, chemical modifications on the molecule or the vaccine delivery methods are all crucial interventions for improvement. In this review we, will present the current knowledge and challenges in this research field. mRNA vaccines hold great promises as part of a combined strategy, for achieving HIV functional cure.

Feasibility of using monocyte-derived dendritic cells obtained from cryopreserved cells for DC-based vaccines.

The study of the effect of cryopreservation on the functionality of monocyte-derived dendritic cells (MDDCs) and dendritic cells (DCs) is essential for their use in different clinical applications such as DCs-based vaccines. Its full maturation and its optimal functionality are crucial for DCs based immunotherapy. In this study, we compared MDDCs derived from fresh and cryopreserved PBMCs in the aspects of phenotype and its effect on T cells at the level of proliferation and cytokine secretion. We pulsed MDDCs obtained from fresh and cryopreserved PBMCs with two different stimuli, CEF and SEA, and the expression maturation markers and cytokine secretion were analyzed. Our results showed that the cryopreservation had no effects in the phenotype of the MDDCs obtained, cell viability, maturation markers expression and/or cytokines secretion, independently whether MDDCs had been generated from fresh or cryopreserved PBMCs. Thus, this study suggests that the use of cryopreserved cells is a good method to keep the cells before use in immunotherapy, avoiding the variability within same individual due to severe blood draws. Even so, the interpretation and comparison of different results should be done considering the different cryopreservation techniques and assays, and their effects on PBMCs, specifically on MDDC and DC cells.

Risk of Severe COVID-19 Infection in Patients With Inflammatory Rheumatic Diseases.

OBJECTIVE: To describe the cohort of patients with inflammatory rheumatic diseases (IRD) hospitalized due to SARS-CoV-2 infection in the Ramón y Cajal Hospital, and to determine the increased risk of severe coronavirus disease 2019 (COVID-19) in patients with no IRD. METHODS: This is a retrospective single-center observational study of patients with IRD actively monitored in the Department of Rheumatology who were hospitalized due to COVID-19. RESULTS: Forty-one (1.8%) out of 2315 patients admitted due to severe SARS-CoV-2 pneumonia suffered from an IRD. The admission OR for patients with IRD was 1.91 against the general population, and it was considerably higher in patients with Sjögren syndrome, vasculitis, and systemic lupus erythematosus. Twenty-seven patients were receiving treatment for IRD with corticosteroids, 23 with conventional DMARDs, 12 with biologics (7 rituximab [RTX], 4 anti-tumor necrosis factor [anti-TNF], and 1 abatacept), and 1 with Janus kinase inhibitors. Ten deaths were registered among patients with IRD. A higher hospitalization rate and a higher number of deaths were observed in patients treated with RTX (OR 12.9) but not in patients treated with anti-TNF (OR 0.9). CONCLUSION: Patients with IRD, especially autoimmune diseases and patients treated with RTX, may be at higher risk of severe pneumonia due to SARS-CoV-2 compared to the general population. More studies are needed to analyze this association further in order to help manage these patients during the pandemic.

[Seroprevalence study of hepatitis B among orienteers]. / Estudio de seroprevalencia de hepatitis B en deportistas de orientación.

BACKGROUND AND OBJECTIVE: Our objectives were to detect asymptomatic cases involved in an outbreak of hepatitis B, to assess the seroprevalence of hepatitis B (HB) in orienteers and to establish recommendations. PATIENTS AND METHOD: One hundred sixteen orienteers who had competed in the categories involved in the previous outbreak as well as a stratified random sample of 166 of the remaining orienteers in other competition categories were included in a cross-sectional serological prevalence study. HB surface antigen (anti-HBs); total antibody to HB core antigen (total anti-HBc); HB surface antigen (Ag HBs); and antibody IgM to HB core antigen (anti-HBcIgM) along with the history of vaccination for hepatitis B were analyzed. The results were weighted. RESULTS: The seroprevalence of HB (total anti-HBc positive) was 6.7% (n=12, 95% CI 0.6-12.9). No case of acute HB or chronic infection was observed. All the serological markers were negative for 61.1% (n=64, 95% CI 46.3-75.6), and 31.5% (n=29, 95% CI 18.2-46.4) had markers of immunity due to vaccination. Among individuals under 25 years of age, 28.4% were unvaccinated, although they were covered by vaccination programs. CONCLUSION: Our results suggest that the seroprevalence of HB among orienteers is not different from the general population in Spain. However, it is necessary to reinforce the vaccination among adolescents and young adults. General recommendations for the prevention of HB were made to orienteering federations.

Analysis of Complete Remission in Systemic Lupus Erythematosus Patients Over a 32-Year Period.

OBJECTIVE: Systemic lupus erythematosus (SLE) is characterized by an unpredictable and fluctuating course. Although various methods have been developed to measure disease activity, there is still a lack of consensus about the optimal criteria for SLE remission. The principal aim of our study was to identify the number of lupus patients achieving a complete remission (implying that for 3 years there were no clinical or serologic features and no treatment with steroids and immunosuppressive drugs) in a single cohort of patients followed for a period of up to 32 years. In addition, we have identified patients in clinical but not serologic remission (known as serologically active, clinically quiescent disease [SACQ]) and vice versa. We were particularly interested to determine the factors associated with complete remission. METHODS: Eligible patients were followed up in the University College Hospital Lupus cohort from January 1978 until December 2010 for a period of at least 3 years. Complete remission was defined as a period of at least 3 years with clinical inactivity (British Isles Lupus Assessment Group scores of C, D, or E only) and laboratory remission (no antibodies to double-stranded DNA and normal complement C3 levels), and being off-treatment with corticosteroids and immunosuppressants. Antimalarial and nonsteroidal antiinflammatory drugs were allowed. RESULTS: Of 624 lupus patients at our hospital, a total of 532 patients met the strict inclusion criteria for the study. Of these 532 patients, 77 patients (14.5%) achieved complete remission for at least 3 years, and 23 (4.3%) achieved complete remission for a minimum period of 10 years. Ten of these 77 patients were subsequently lost to followup, and, interestingly, flares occurred subsequently in 15 of the 67 remaining patients (22.4%). Three patients relapsed after the tenth year of remission. Forty-five patients (8.5%) fulfilled the requirement for SACQ, and 66 patients (12.4%) achieved only serologic remission. CONCLUSION: Our study indicated that 14.5% of lupus patients achieved a complete remission for 3 years. However, flares may continue to occur beyond 10 years of remission. Long-term followup of SLE is therefore mandatory.

General knowledge and opinion of future health care and non-health care professionals on rare diseases.

RATIONALE, AIMS AND OBJECTIVES: The debate about whether to dedicate funds to rare diseases (RD) may hinge on the existence of a societal preference for prioritizing rarity. There are scarce studies about the interest of doctors and general society in RD. METHOD: Four groups of future health and non-health professionals were surveyed in a region of Spain to evaluate their opinion on RD. Questions of the study were organized into four groups: general knowledge on RD, prioritization of research of RD, willingness to assign resources to RD and real distribution of resources to RD. RESULTS: A total of 234 students were surveyed. The mean age of the whole study population was 24.0 years and the 83.3% were female. Only around 25% of the survey sample knew the definitions of RD and orphan drugs. Questions related to willingness to assign resources to RD did not reveal statistically significant differences between study groups. Seventy-three per cent considered that the majority of the budget should be used to treat common diseases. However, resident doctors recognized that they have neither experience nor time to diagnose and treat RD. CONCLUSION: Although resident doctors have a little more general knowledge on RD than other surveyed groups, health and non-health future professionals have a low general knowledge on this topic and none of them prioritized the assignment of funds to RD.

Knee hemarthros secondary to osteochondritis dissecans (König disease).

A case is presented of a hemarthrosis associated with osteochondritis dissecans in a young man who arrived in the Emergency unit due to tender and swelling of his right knee one hour after a slightly rotational gesture of the lower limb. Many years before the patient suffered a sports injury in the same knee, but it was never assessed. Radiography studies showed bone fragments inside the synovial capsule, and the joint aspiration was compatible with hemarthrosis. A review of the available information of this uncommon condition is also presented.

Induction of Cancer Cell Death by Hyaluronic Acid-Mediated Uptake of Cytochrome C.

Effective cancer treatment needs both, passive and active targeting approaches, to achieve highly specific drug delivery to the target cells while avoiding cytotoxicity to normal cells. Protein drugs are useful in this context because they can display excellent specificity and potency. However, their use in therapeutic formulations is limited due to their physical and chemical instability during storage and administration. Polysaccharides have been used to stabilize proteins during formulation and delivery. To accomplish both, stabilization and targeting simultaneously, the apoptosis-inducing protein cytochrome c (Cyt c) was modified with the polysaccharide hyaluronic acid (HA) because its corresponding receptor CD44 is overexpressed in many cancers. Cyt c-HA bioconjugates were formed using low and high molecular weight HA (8 kDa and 1 MDa) with a resultant Cyt c loading percentage of 4%. Circular dichroism and a cell-free caspase assay showed minor structural changes and high bioactivity (more than 80% caspase activation) of Cyt c, respectively, after bioconjugate formation. Two CD44-positive cancer cells lines, HeLa and A549 cells, and two CD44-negative normal cell lines, Huvec and NIH-3T3 cells, were incubated with the samples to assess selectivity and cytotoxicity. After 24 h of incubation with the samples, cancer cell viability was reduced at least 3-fold while CD44-negative control cell lines remained minimally affected. Fluorescence imaging confirmed selective internalization of the Cyt c-HA construct by CD44-positive cancer cell lines. These results demonstrate the development of a drug delivery system that incorporates passive and active targeting which is essential for cancer treatment.

Is it safe to perform joint infiltrations or aspirations in patients anticoagulated with acenocoumarol?

The purpose of this study is to determine the rate of bleeding complications in patient's anticoagulated with acenocoumarol according to the international normalized ratio (INR) coagulation index. A cross-sectional study was performed with 901 charts of patients who underwent arthrocentesis or joint infiltration between 2009 and 2013; the charts were grouped on the basis of having an INR higher or lower than 2.0 (268 and 633, respectively). Comparisons were performed in terms of rates of early or late bleeding complications. A 0.37% rate of early bleeding complications (< 24hours) was observed in the group of patients with INR<2 and 0.99% in the group of patients with INR≥2 (P=.47). Only one case of late complication was presented by bleeding between 24 hours and 30 days, in the group of patients with INR≥2. We conclude that oral anticoagulation with acenocoumarol at terapeutical doses does not increase the risk of bleeding joint punctures.

Record linkage between hospital discharges and mortality registries for motor neuron disease case ascertainment for the Spanish National Rare Diseases Registry.

Our objective was to analyse the coverage of hospital discharge data and the mortality registry (MR) of La Rioja to ascertain motor neuron disease (MND) cases to be included in the Spanish National Rare Diseases Registry. MND cases that occurred in La Rioja during the period 1996-2011 were selected from hospital discharge data and the MR by means of the International Classification of Diseases. Review of the medical histories was carried out to confirm the causes of death reported. Characteristics of the population with MND were analysed. A total of 133 patients with MND were detected in La Rioja during the period 1996-2011; 30.1% were only recorded in the hospital discharges data, 12.0% only in the MR, and 57.9% were recorded by both databases. Medical records revealed a miscoding of patients who had been diagnosed with progressive supranuclear palsy but were recorded in the MR with an MND code. In conclusion, the hospital discharges data and the MR appear to be complementary and are valuable databases for the Spanish National Rare Diseases Registry when MNDs are properly codified. Nevertheless, it would be advisable to corroborate the validity of the MR as data source since the miscoding of progressive supranuclear palsy has been corrected.

[Palliative and support care at home in primary care]. / Atención sanitaria paliativa y de soporte de los equipos de atención primaria en el domicilio.

OBJECTIVES: To estimate the proportion of people requiring palliative and support care at home in primary care and to describe their characteristics. METHODS: A descriptive study was carried out by five Spanish sentinel networks between October 2007 and March 2008 in 282,216 people attended by 218 general practitioners and nurses. Patients receiving comprehensive, active and continued care at home were included if the aim was not to prolong life but to achieve the best quality of life for the patient, the family and the carers. A standard form was used to collect data on age, sex, type of patient, underlying diseases and other variables related to the process. Crude and age-adjusted rates were estimated. RESULTS: Of the 400 men and 792 women registered, 12% were strictly terminal. The mean age was 82.4 years and was higher in patients with functional disability (82.9 years) than in terminally-ill patients (78.9 years) (p<0.01). The estimated prevalence was 422.3 per 100,000 inhabitants aged 14 years or more (95% CI: 398.7-447.0) and was much higher in women than in men (553.9 versus 287.3, p<0.01). The estimate for the entire Spanish population was 309.0 per 100,000 inhabitants (95% CI: 286.0-332.0). CONCLUSIONS: The prevalence of palliative and support care in Spain is around three cases per 1,000 inhabitants and is higher in elderly populations. More than 85% of patients needing palliative or support care have a life expectancy of over 6 months and thus represent the majority of persons using this type of medical and social support. The most susceptible groups are women and the oldest-old.

Cystic fibrosis mortality trends in Spain among infants and young children: 1981-2004.

UNLABELLED: This paper sought to analyse mortality trends among infants and young children who died with a diagnosis of cystic fibrosis (CF) in Spain, during the period 1981-2004. STUDY DESIGN: Descriptive observational study, using joinpoint regression models. PARTICIPANTS: Data on cystic fibrosis deaths were drawn from the National Statistics Institute (Instituto Nacional de Estadística), which collects data from all death certificates in Spain. During the period 1981-2004, overall CF mortality in Spain decreased by an annual average of 4% in both sexes. A breakdown by age showed that patients under 15 years registered a declining and those over 15 years a rising mortality rate over the study period. Mean and median age at death from CF increased with time, from a median of 4.4 years (males) and 3.8 years (females) in 1981 to 20.1 years (males) and 17.7 years (females) in 2004. The results of this study show that, as in other Western countries, CF is no longer a major cause of death in childhood, and that the challenge now lies in caring for adults who suffer from this disease. The fact that our study was descriptive meant that the reasons for the decrease in CF mortality in Spain could not be identified. Other authors have shown that this decrease is associated with improved treatment for pulmonary complications, better nutritional control and lung transplants.