Case report: Novel compound heterozygous IL1RN mutations as the likely cause of a lethal form of deficiency of interleukin-1 receptor antagonist.

Undiagnosed monogenic diseases represent a challenging group of human conditions highly suspicious to have a genetic origin, but without conclusive evidences about it. We identified two brothers born prematurely from a non-consanguineous healthy couple, with a neonatal-onset, chronic disease characterized by severe skin and bone inflammatory manifestations and a fatal outcome in infancy. We conducted DNA and mRNA analyses in the patients' healthy relatives to identify the genetic cause of the patients' disease. DNA analyses were performed by both Sanger and next-generation sequencing, which identified two novel heterozygous IL1RN variants: the intronic c.318 + 2T>G variant in the father and a ≈2,600-bp intragenic deletion in the mother. IL1RN mRNA production was markedly decreased in both progenitors when compared with healthy subjects. The mRNA sequencing performed in each parent identified two novel, truncated IL1RN transcripts. Additional experiments revealed a perfect intrafamilial phenotype-genotype segregation following an autosomal recessive inheritance pattern. The evidences shown here supported for the presence of two novel loss-of-function (LoF) IL1RN pathogenic variants in the analyzed family. Biallelic LoF variants at the IL1RN gene cause the deficiency of interleukin-1 receptor antagonist (DIRA), a monogenic autoinflammatory disease with marked similarities with the patients described here. Despite the non-availability of the patients' samples representing the main limitation of this study, the collected evidences strongly suggest that the patients described here suffered from a lethal form of DIRA likely due to a compound heterozygous genotype at IL1RN, thus providing a reliable genetic diagnosis based on the integration of old medical information with currently obtained genetic data.

Spanish cohort of VEXAS syndrome: clinical manifestations, outcome of treatments and novel evidences about UBA1 mosaicism.

BACKGROUND: The vacuoles, E1-enzyme, X linked, autoinflammatory and somatic (VEXAS) syndrome is an adult-onset autoinflammatory disease (AID) due to postzygotic UBA1 variants. OBJECTIVES: To investigate the presence of VEXAS syndrome among patients with adult-onset undiagnosed AID. Additional studies evaluated the mosaicism distribution and the circulating cytokines. METHODS: Gene analyses were performed by both Sanger and amplicon-based deep sequencing. Patients' data were collected from their medical charts. Cytokines were quantified by Luminex. RESULTS: Genetic analyses of enrolled patients (n=42) identified 30 patients carrying UBA1 pathogenic variants, with frequencies compatible for postzygotic variants. All patients were male individuals who presented with a late-onset disease (mean 67.5 years; median 67.0 years) characterised by cutaneous lesions (90%), fever (66.7%), pulmonary manifestations (66.7%) and arthritis (53.3%). Macrocytic anaemia and increased erythrocyte sedimentation rate and ferritin were the most relevant analytical abnormalities. Glucocorticoids ameliorated the inflammatory manifestations, but most patients became glucocorticoid-dependent. Positive responses were obtained when targeting the haematopoietic component of the disease with either decitabine or allogeneic haematopoietic stem cell transplantation. Additional analyses detected the UBA1 variants in both haematopoietic and non-haematopoietic tissues. Finally, analysis of circulating cytokines did not identify inflammatory mediators of the disease. CONCLUSION: Thirty patients with adult-onset AID were definitively diagnosed with VEXAS syndrome through genetic analyses. Despite minor interindividual differences, their main characteristics were in concordance with previous reports. We detected for the first time the UBA1 mosaicism in non-haematopoietic tissue, which questions the previous concept of myeloid-restricted mosaicism and may have conceptual consequences for the disease mechanisms.

Characterization of Novel Pathogenic Variants Leading to Caspase-8 Cleavage-Resistant RIPK1-Induced Autoinflammatory Syndrome.

Pathogenic RIPK1 variants have been described as the cause of two different inborn errors of immunity. Biallelic loss-of-function variants cause the recessively inherited RIPK1 deficiency, while monoallelic variants impairing the caspase-8-mediated RIPK1 cleavage provoke a novel autoinflammatory disease (AID) called cleavage-resistant RIPK1-induced autoinflammatory (CRIA) syndrome. The aim of this study was to characterize the pathogenicity of two novel RIPK1 variants located at the cleavage site of caspase-8 detected in patients with dominantly-inherited, early-onset undefined AID. RIPK1 genotyping was performed by Sanger and next-generation sequencing. Clinical and analytical data were collected from medical charts, and in silico and in vitro assays were performed to evaluate the functional consequences. Genetic analyses identified two novel heterozygous RIPK1 variants at the caspase-8 cleavage site (p.Leu321Arg and p.Asp324Gly), which displayed a perfect intrafamilial phenotype-genotype segregation following a dominant inheritance pattern. Structural analyses suggested that these variants disrupt the normal RIPK1 structure, probably making it less accessible to and/or less cleavable by caspase-8. In vitro experiments confirmed that the p.Leu321Arg and p.Asp324Gly RIPK1 variants were resistant to caspase-8-mediated cleavage and induced a constitutive activation of necroptotic pathway in a similar manner that previously characterized RIPK1 variants causing CRIA syndrome. All these results strongly supported the pathogenicity of the two novel RIPK1 variants and the diagnosis of CRIA syndrome in all enrolled patients. Moreover, the evidences here collected expand the phenotypic and genetic diversity of this recently described AID, and provide interesting data about effectiveness of treatments that may benefit future patients.

First Description of Late-Onset Autoinflammatory Disease Due to Somatic NLRC4 Mosaicism.

OBJECTIVE: Autoinflammatory diseases are inherited disorders of innate immunity that usually start during childhood. However, several recent reports have described an increasing number of patients with autoinflammatory disease starting in adulthood. This study was undertaken to investigate the underlying cause of a case of late-onset uncharacterized autoinflammatory disease. METHODS: Genetics studies were performed using Sanger sequencing and next-generation sequencing (NGS) methods. In silico, in vitro, and ex vivo analyses were performed to determine the functional consequences of the detected variant. RESULTS: We studied a 57-year-old woman who at the age of 47 years began to have recurrent episodes of fever, myalgias, arthralgias, diffuse abdominal pain, diarrhea, adenopathies, and systemic inflammation, which were relatively well controlled with anti-interleukin-1 (anti-IL-1) drugs. NGS analyses did not detect germline variants in any of the known autoinflammatory disease-associated genes, but they identified the p.Ser171Phe NLRC4 variant in unfractionated blood, with an allele fraction (2-4%) compatible with gene mosaicism. Structural modeling analyses suggested that this missense variant might favor the open, active conformation of the NLRC4 protein, and in vitro and ex vivo analyses confirmed its propensity to oligomerize and activate the NLRC4 inflammasome, with subsequent overproduction of IL-18. CONCLUSION: Our findings indicate that the postzygotic p.Ser171Phe NLRC4 variant is a plausible cause of the disease in the enrolled patient. Functional and structural studies clearly support, for the first time, its gain-of-function behavior, consistent with previously reported NLRC4 pathogenic variants. These novel findings should be considered in the diagnostic evaluation of patients with adult-onset uncharacterized autoinflammatory disease.

Admittances characteristics by sepsis in the Spanish internal medicine services between 2005 and 2015: mortality pattern.

BACKGROUND: Studies in recent years suggest an increase in the incidence of sepsis but a decrease in mortality. The aim of this study is to describe the characteristics of patients discharged after a sepsis episode from Spanish internal medicine services between 2005 and 2015. RESULTS: Since 2005, in which there were a total of 4,319 cases, sepsis hospitalizations has been consistently increasing yearly reaching a total of 25,820 cases in 2015. We observed that septic patients are older and with higher comorbidity than the general population admitted in Internal Medicine. On the other hand, we found a decreasing trend in the mortality rates of patients with sepsis in our series going from 35.7% in 2005 to 30.1% in 2015 (p < 0.005). DISCUSSION: In our study, a higher comorbidity at admission and developing complications during admittance, conditioned a higher probability of death due to sepsis. The variables that were associated with increased mortality risk were age, acute renal failure, acute respiratory failure, lactic acidosis, septic shock and chronic heart failure. CONCLUSION: As in other similar studies, we observed an increase in the hospitalizations by sepsis as a diagnosis at discharge during the study period in Internal Medicine services with a simultaneous decrease in mortality. Comorbidity at admission and complications during admittance condition mortality.

Novel evidences of atypical manifestations in cryopyrin-associated periodic syndromes.

OBJECTIVES: Cryopyrin-associated periodic syndromes (CAPS) usually start during infancy as an urticarial-like rash and a marked acute phase response, with additional manifestations appearing during its evolution. The aim of this study was to expand the clinical diversity of CAPS by the description of novel atypical features. METHODS: Clinical data were collected from patients' medical charts. Sanger sequencing analyzed NLRP3. Response to anti-IL-1 blockade was evaluated by clinical assessments and by measurements of laboratory parameters. RESULTS: Seventeen patients from two families (A and B), carrying the p.Ala439Thr and p.Arg260Trp NLRP3 mutations respectively, were enrolled. The disease was unexpectedly atypical in all members of Family A, with a 16-year-old asymptomatic carrier, and onset in adulthood associated with absence of skin lesions in four affected members. Surprisingly, one patient from each family suffered from severe haemorrhagic cystitis due to AA amyloidosis in the urinary bladder. Members of Family B displayed a classical phenotype, with two patients suffering from olfactive disorders. CONCLUSIONS: Our evidence suggests that CAPS may occasionally be presented as a late-onset, recurrent inflammatory disease without urticarial-like rash. In some patients, AA amyloidosis in strange locations like urinary bladder may complicate the clinical course. The response to IL-1 blockade in these atypical CAPS was similar to that described in classical forms. Consequently, we suggest that CAPS should be included in the differential diagnosis of adult patients with unexplained, recurrent inflammatory diseases, and once confirmed, the early initiation of anti-IL-1 blockade will probably prevent the development of life-threatening complications.

Prolonged length of stay in hospitalized internal medicine patients.

BACKGROUND: Targeting patients with prolonged hospitalizations may represent an effective strategy for reducing average hospital length of stay (LOS). OBJECTIVE: We sought to characterize predictors of prolonged hospitalization among internal medicine patients in an effort to guide future improvement efforts. DESIGN: We conducted a retrospective cohort study using administrative data of internal medicine patients from all hospitals of the Spanish Public Health Service between January 1st, 2005 and December 31st, 2013. Multivariable logistic regression was performed to assess the association between sociodemographic and clinical variables and prolonged LOS, defined as >30days. KEY RESULTS: Of 5,275,139 discharges, 166,470 (3.2%) had a prolonged LOS. Prolonged hospitalizations accounted for 17.4% of total inpatient days and contributed 0.5days to an average LOS of 9.8days during the study period. Prolonged hospitalizations were associated with younger age (odds ratio [OR]: 0.97 per 10-year increase in age, 95% confidence interval [CI]: 0.96-0.98) and male gender (OR 0.88 IC95% 0.87-0.89). Compared to patients without prolonged LOS, prolonged LOS patients were more likely to require a palliative care consult (OR: 2.48, 95% CI: 2.39-2.58), surgery (OR: 6.9 95% CI: 6.8-7.0); and be discharged to a post-acute-care facility (OR: 2.91, 95% CI: 2.86-2.95). CONCLUSIONS: Prolonged hospitalizations in a small proportion of patients were an important contributor to overall LOS and particularly affected complex hospital stays who were not discharged home.

The obesity paradox in stroke: impact on mortality and short-term readmission.

BACKGROUND: The aim of the present study was to assess the association of obesity with the mortality of hospitalized patients with acute stroke and the risk of readmission in less than 30 days. METHODS: A retrospective chart review of a cohort of consecutive patients admitted with stroke as the primary reason for discharge in Spain between January 1, 2005, and December 31, 2011, was performed. Patients with a diagnosis of obesity were identified. The mortality and readmittance indexes of obese patients were compared against the subpopulation without theses diagnosis. RESULTS: A total of 201,272 stroke admittances were analyzed, and 14,047 (7.0%) diagnosis of obesity were identified. In-hospital global mortality reached 14.9%, and readmittance risk was 5.9%. Obese patients showed a lower in-hospital mortality risk (odds ratio [OR], .71; 95% confidence interval [CI], .67-.76) and early readmittance risk (OR, .89; 95% CI, .82-.96) than the nonobese even after adjusting for possible confounding factors. CONCLUSIONS: Obesity in those hospitalized for stroke is associated with reduced in-hospital mortality risk and early readmittance.

Frequency of hypoglycemia and its impact on length of stay, mortality, and short-term readmission in patients with diabetes hospitalized in internal medicine wards.

OBJECTIVE: To evaluate whether hypoglycemia is associated with increases in length of stay (LOS), inpatient mortality, and readmission among patients with diabetes hospitalized in internal medicine wards. METHODS: A retrospective cohort study was carried out using the Basic Minimum Data Set registry of the Spanish National Health System, which contains clinical and administrative information for every patient discharged from system hospitals. The analysis included patients discharged between January 2005 and December 2010 and had a primary (i.e., reason for the admission) or secondary diagnosis of diabetes and a secondary diagnosis of hypoglycemia. The associations between hypoglycemia and the study outcomes (mortality, readmission, and LOS) were evaluated using multivariate and multilinear regression models that included age, sex, and the Charlson index as covariates. RESULTS: During the study period, 3,361,104 patients were admitted to internal medicine wards in the National Health System. Of these, 921,306 (27.4%) had diagnoses of diabetes, and among these patients, 46,408 (5%) had secondary hypoglycemia. A total of 4,754 (10.2%) patients with secondary hypoglycemia died during their hospital stays, compared with 83,508 (9.5%) patients without hypoglycemia. The multivariate/multilinear regression models demonstrated significant associations between the presence of secondary hypoglycemia and greater inpatient mortality (odds ratio [OR] 1.24, 95% confidence interval [CI] 1.20-1.28), a greater likelihood of readmission (OR 1.20, 95% CI 1.17-1.23), and an increased LOS (ß 1.24, 95% CI 1.15-1.35). CONCLUSION: Hypoglycemia in patients with diabetes hospitalized in internal medicine wards is associated with increases in the LOS, inpatient mortality, and early readmission.

Low prevalence of hyponatremia codification in departments of internal medicine and its prognostic implications.

OBJECTIVE: Hyponatremia is the most frequent ionic disorder among ambulatory and hospitalized populations. The aim of the study is to describe the profile of patients admitted to internal medicine departments of Spanish hospitals with a diagnostic codification of hyponatremia in their discharge sheets. METHODS: Data from the Minimum Basic Data Set (MBDS) of discharged patients from all departments of internal medicine (IM) of the Spanish National Health System (NHS) between 2007 and 2010 were analyzed to describe the profile of patients with diagnostic codification of hyponatremia. RESULTS: A total of 2,134,363 admittances were analyzed, identifying 31,933 (1.5%) with a diagnostic code of hyponatremia (18.3% as principal diagnosis and 81.7% as secondary diagnosis). Mortality among patients with codified hyponatremia was markedly higher than in patients without this condition (13.1% vs 9.8% [OR 1.38; 95% CI 1.33-1.41]). Hyponatremia codification was independently associated with a higher risk of readmission (OR 1.33 CI 95% 1.29-1.38). Average length of stay for patients with hyponatremia was 11.67 days (SD 13.01), compared to 9.84 days (SD 11.61) among the general population admitted to IM (p < 0.001). Mean cost per admission in the presence of codified hyponatremia was €4023 (SD €2531), compared to €3537 (SD €2858.02); p < 0.001. Hyponatremia was more prevalent among patients with the following conditions: dementia, chronic and acute renal failure, hepatic cirrhosis, pressure ulcers, heart failure, and depression. CONCLUSIONS: We found an extremely low prevalence of hyponatremia codification in our series (1.5%). Hyponatremia is underreported and undertreated although numerous studies have shown its devastating impact on hospital admittance. The first step in order to improve this situation is to raise awareness among physicians about a problem that despite its high prevalence is still overlooked.

The effects of increasing effective airway diameter on weaning from mechanical ventilation in tracheostomized patients: a randomized controlled trial.

PURPOSE: To determine the effects of deflating the tracheal cuff during disconnections from mechanical ventilation (MV) in tracheostomized patients. METHODS: This was a single-center, randomized trial conducted in a general ICU of a tertiary hospital with regional referral for trauma patients. Patients at high risk of aspiration based on the drink test were excluded. Critically ill tracheostomized patients were randomized to have the tracheal cuff deflated or not during spontaneous breathing trials. Weaning was protocolized on progressive T-tube trials, and patients were considered weaned after 24 consecutive hours disconnected from MV. The primary end point was time to definitive withdrawal of MV; secondary end points were ventilator-associated respiratory infection (pneumonia and/or tracheobronchitis) and swallowing function. Statistical analyses included Cox proportional risk models. RESULTS: We randomized 195 patients and 181 patients completed the study (94 patients with deflated cuff and 87 with inflated cuff). Variables independently related to weaning time in the multivariate analysis were tracheostomy-to-first MV disconnection time (HR 0.5, 95 % CI 0.3-0.8; p < 0.01) and cuff deflation (HR 2.2, 95 % CI 1.5-3; p < 0.01). Respiratory infection was lower in the deflated group (20 vs. 36 %; p = 0.02). Swallowing function improved more in the deflated group (31 vs. 22 %; p = 0.02). CONCLUSION: Under the conditions of our protocol, deflating the tracheal cuff in tracheostomized patients shortens weaning, reduces respiratory infections, and probably improves swallowing.

Hip fracture in hospitalized medical patients.

BACKGROUND: The aim of the present study is to analyze the incidence of hip fracture as a complication of admissions to internal medicine units in Spain. METHODS: We analyzed the clinical data of 2,134,363 adults who had been admitted to internal medicine wards. The main outcome was a diagnosis of hip fracture during hospitalization.Outcome measures included rates of in-hospital fractures, length of stay and cost. RESULTS: A total of 1127 (0.057%) admittances were coded with an in-hospital hip fracture. In hospital mortality rate was 27.9% vs 9.4%; p < 0.001, and the mean length of stay was significantly longer for patients with a hip fracture (20.7 days vs 9.8 days; p < 0.001). Cost were higher in hip-fracture patients (6927€ per hospitalization vs 3730€ in non fracture patients). Risk factors related to fracture were: increasing age by 10 years increments (OR 2.32 95% CI 2.11-2.56), female gender (OR 1.22 95% CI 1.08-1.37), admission from nursing home (OR 1.65 95% CI 1.27-2.12), dementia (1.55 OR 95% CI1.30-1.84), malnutrition (OR 2.50 95% CI 1.88-3.32), delirium (OR 1.57 95% CI 1.16-2.14), and anemia (OR 1.30 95%CI 1.12-1.49). CONCLUSIONS: In-hospital hip fracture notably increased mortality during hospitalization, doubling the mean length of stay and mean cost of admission. These are reasons enough to stress the importance of designing and applying multidisciplinary plans focused on reducing the incidence of hip fractures in hospitalized patients.

Nonagenarios en los servicios de Medicina Interna españoles / Nonagenarian patients admitted to Spanish Internal Medicine Hospital Departments

Objetivo. Describir el perfil demográfico y clínico de los pacientes nonagenarios ingresados en servicios de Medicina Interna en los hospitales españoles, y compararla con los pacientes más jóvenes. Métodos. Se identificaron a través del CMBD (Conjunto Mínimo Básico de Datos) a todos los pacientes con edad superior a los 90 años ingresados en servicios de Medicina Interna de los hospitales públicos españoles Servicio Nacional de Salud entre 2005 a 2008. Los datos se obtuvieron del alta hospitalaria. Para cada paciente se identificó un grupo de diagnóstico relacionado (GRD). Se utilizó el GRD versión 21.0. Comparamos este grupo de nonagenarios de personas adultas más jóvenes. Se utilizó el índice de comorbilidad de Charlson (ICC) como elemento comparativo. Todos los análisis estadísticos se realizaron con SPSS 14.0. Resultados. La muestra incluye 131.434 pacientes mayores de 90 años (6% del total de pacientes atendidos). Dos mil doscientos veintidós pacientes fueron más de 100 años. Eran mujeres un 45,3% de los pacientes menores de 90 años y un 67,3% los mayores de 90 años (p<0,001). Los 10 primeros GRD que figuran en el grupo de mayor edad incluyen 3 nuevas entidades que no se presenta en el más joven: edema pulmonar (GRD: 87), infección grave de las vías urinarias (GRD: 320) e infección severa del tracto respiratorio (GRD: 540). Los 5 primeros GRD por encima de 89 años fueron: neumonía/bronquitis (541): 11,9%, la insuficiencia cardiaca (127): 8,9%, trastornos del ritmo (544): 7,5%, edema pulmonar (87): 3,8%, y otras enfermedades respiratorias (89): 3,24%. La tasa de aparición de estas entidades fue superior a la encontrada en pacientes más jóvenes. Dentro del «top ten» solo la EPOC y la angina de pecho tenían una tasa mayor en el grupo más joven. La mortalidad hospitalaria fue del 9,1% en el grupo más joven y el 21,8% entre los nonagenarios (p<0,001). Si tomamos a cuenta solo las primeras 48 h después de la admisión, las proporciones fueron del 2,2 frente al 6% (p<0,001). El 78,2% de los pacientes nonagenarios volvieron a su domicilio tras el alta médica. Conclusiones. 1) El número de pacientes nonagenarios ingresados en los servicios hospitalarios de Medicina Interna es muy alto; 2) La tasa de las mujeres aumenta con la edad; 3) La lista de diagnósticos varía según la edad; 4) La mortalidad hospitalaria aumenta con la edad, tanto si tenemos en cuenta los 2 primeros días o el total de la estancia, y 5) Una mayoría de los nonagenarios regresan a su domicilio tras el alta (AU)

Objetive. To describe the demographic and clinical profile of nonagenarian patients admitted to Internal Medicine departments in Spanish hospitals, and to compare it with younger patients. Methods. We identified, through the MBDS (Basic Minimum Data Set), every patient older than 90 years admitted to Internal Medicine Departments of the Spanish National Health Service public hospitals between 2005- 2008. Hospital discharge data were obtained from the MBDS. A diagnosis-related group (DRG) was identified for every patient. The DRG 21.0 version was used. We compared this nonagenarian group with data of younger adult people. All centres submit this information to the Spanish Health Ministry. The Charlson Index (CCI) was used to determine comorbidity. All statistical analyses were performed using SPSS 14.0. Results. The sample included 131,434 patients over 90 years (6% of total patients admitted), with 2,222 patients being over 100 years. There were 45.3% female patients under 90 years, compared to 67.3% over 90 years (P<.001). The top ten DRGs listed in the older group included three new conditions not present in the younger one: pulmonary oedema (DRG: 87), severe urinary tract infection (DRG: 320), and severe respiratory tract infection (DRG: 540). The first 5 DRG were: pneumonia/bronchitis (541): 11.9%, heart failure (127): 8.9%, rhythm disorders (544): 7.5%, pulmonary oedema (87): 3.8%, and other respiratory diseases (89): 3.24%. In any case the incidence of these conditions was higher than those found in younger patients. Among this top ten, only COPD and angina had a higher rate in the younger group. The incidence of hospital deaths were 9.1% among the younger group, and 21.8% among the nonagenarians (P<.001). If only the first 48hours after admission are taken into account, the rates were 2.2% vs 6% (P<.001). The majority (78.2%) of nonagenarian patients return home after discharge Conclusions. 1) There are a high number of nonagenarians patients admitted in hospital Internal Medicine Departments; 2) The number of women increases with age; 3) List of diagnosis varies according with age; 4) Hospital death rates increase with age, both in first two days and total stay, and 5) The majority of these patients are able to return home after discharge(AU)

[Nonagenarian patients admitted to Spanish internal medicine hospital departments]. / Nonagenarios en los servicios de Medicina Interna españoles.

OBJECTIVE: To describe the demographic and clinical profile of nonagenarian patients admitted to Internal Medicine departments in Spanish hospitals, and to compare it with younger patients. METHODS: We identified, through the MBDS (Basic Minimum Data Set), every patient older than 90 years admitted to Internal Medicine Departments of the Spanish National Health Service public hospitals between 2005- 2008. Hospital discharge data were obtained from the MBDS. A diagnosis-related group (DRG) was identified for every patient. The DRG 21.0 version was used. We compared this nonagenarian group with data of younger adult people. All centres submit this information to the Spanish Health Ministry. The Charlson Index (CCI) was used to determine comorbidity. All statistical analyses were performed using SPSS 14.0. RESULTS: The sample included 131,434 patients over 90 years (6% of total patients admitted), with 2,222 patients being over 100 years. There were 45.3% female patients under 90 years, compared to 67.3% over 90 years (P<.001). The top ten DRGs listed in the older group included three new conditions not present in the younger one: pulmonary oedema (DRG: 87), severe urinary tract infection (DRG: 320), and severe respiratory tract infection (DRG: 540). The first 5 DRG were: pneumonia/bronchitis (541): 11.9%, heart failure (127): 8.9%, rhythm disorders (544): 7.5%, pulmonary oedema (87): 3.8%, and other respiratory diseases (89): 3.24%. In any case the incidence of these conditions was higher than those found in younger patients. Among this top ten, only COPD and angina had a higher rate in the younger group. The incidence of hospital deaths were 9.1% among the younger group, and 21.8% among the nonagenarians (P<.001). If only the first 48 hours after admission are taken into account, the rates were 2.2% vs 6% (P<.001). The majority (78.2%) of nonagenarian patients return home after discharge CONCLUSIONS: 1) There are a high number of nonagenarians patients admitted in hospital Internal Medicine Departments; 2) The number of women increases with age; 3) List of diagnosis varies according with age; 4) Hospital death rates increase with age, both in first two days and total stay, and 5) The majority of these patients are able to return home after discharge.

Predictive model of readmission to internal medicine wards.

OBJECTIVE: Prevention of readmission to hospital is considered an outstanding example of a cost-effective practice. Our aim was to derive and validate a clinically useful index to quantify the risk of readmission among patients discharged from Internal Medicine departments. METHODS: We analysed hospital Basic Minimum Data Sets (BMDS) recorded between 2006 and 2008 to determine patterns of rehospitalization. Multivariate statistical analysis of routinely collected data was used to develop an algorithm ('SEMI INDEX') to identify patients predicted to have the highest risk of readmission in the 30 days following discharge. The algorithm was developed by using data from admissions in 2006-2007, for four age subgroups. Coefficients for the most powerful and statistically significant variables were applied against episodes recorded in 2008 to validate the findings of the algorithm developed from the first sample. RESULTS: Of the 999,089 internal medicine admissions in Spain during 2006-2007, 12.4% were rehospitalized within 30 days. The key factors that predicted subsequent admission included male sex, length of stay, comorbidity of the patient, and some clinical conditions. There were small but relevant differences among the different age subgroups. CONCLUSIONS: Readmissions to Internal Medicine departments are prevalent (12.4%). The SEMI INDEX can be used to assess accurately the risk of readmission within 30 days after discharge.

Influencia de la obesidad y la desnutrición en la insuficiencia cardiaca aguda / Influence of obesity and malnutrition on acute heart failure

Introducción y objetivos. La obesidad es un factor independiente de riesgo de insuficiencia cardiaca; sin embargo, se ha demostrado que los pacientes obesos con insuficiencia cardiaca tienen mejor evolución, lo que se ha llamado «paradoja de la obesidad». Por otro lado, la desnutrición tiene un papel pronóstico negativo en la insuficiencia cardiaca. Métodos. Se analizaron los datos del Conjunto Mínimo Básico de Datos de los pacientes con diagnóstico de insuficiencia cardiaca dados de alta por todos los servicios de medicina interna del país en los años 2006-2008. Se identificó a los pacientes con diagnostico de obesidad y/o desnutrición y se comparó la tasa de mortalidad y reingresos de los pacientes con desnutrición u obesidad con los que no las tenían. Resultados. Se analizaron 370.983 ingresos por insuficiencia cardiaca; 41.127 (11,1%) tenían registrado un diagnóstico de obesidad y 4.105 (1,1%), de desnutrición. La mortalidad total fue del 12,9% y el riesgo de reingreso, del 16,4%. Los pacientes obesos presentaron menos riesgo de muerte durante el ingreso (odds ratio [OR]=0,65; intervalo de confianza del 95% [IC95%], 0,62-0,68) y de reingreso a los 30 días (OR=0,81; IC95%, 0,78-0,83) que los no obesos. Los pacientes con desnutrición tenían más riesgo de fallecer (OR=1,83; IC95%, 1,69-1,97) o reingresar (OR=1,39; IC95%, 1,29-1,51), incluso cuando se ajusta por posibles factores de confusión. Conclusiones. La desnutrición en los pacientes hospitalizados por insuficiencia cardiaca aumenta el riesgo de muerte durante el ingreso y la posibilidad de reingreso, mientras que la obesidad se comporta como un factor protector (AU)

Introduction and objectives. Obesity is an independent risk factor for the development of heart failure. Several recent studies have found better outcomes of heart failure for obese patients, an observation termed as the "obesity paradox". On the other hand, the negative effect of malnutrition on the evolution of heart failure has also been clearly established. Methods. Data from the Minimum Basic Data Set were analyzed for all patients discharged from all the departments of internal medicine in hospitals of the Spanish National Health System between the years 2006 and 2008. The information was limited to those patients with a primary or secondary diagnosis of heart failure. Patients with a diagnosis of obesity or malnutrition were identified. The mortality and readmission indexes of obese and malnourished patients were compared against the subpopulation without these diagnoses. Results. A total of 370 983 heart failure admittances were analyzed, with 41 127 (11.1%) diagnosed with obesity and 4105 (1.1%) with malnutrition. In-hospital global mortality reached 12.9% and the risk of readmission was 16.4%. Obese patients had a lower in-hospital mortality risk (odds ratio [OR]: 0.65, 95% confidence interval [95%CI]: 0.62-0.68) and early readmission risk (OR: 0.81, 95%CI: 0.78-0.83) than nonobese patients. Malnourished patients had a much higher risk of dying while in hospital (OR: 1.83 95%CI: 1.69-1.97) or of being readmitted within 30 days after discharge (OR: 1.39, 95%CI: 1.29-1.51), even after adjusting for possible confounding factors. Conclusions. Obesity in patients admitted for HF substantially reduces in-hospital mortality risk and the possibility of early readmission, whereas malnutrition is associated with important increases in in-hospital mortality and risk of readmission in the 30 days following discharge (AU)

Anemia in chronic obstructive pulmonary disease: a readmission prognosis factor.

OBJECTIVE: The prevalence of comorbid anemia in patients with COPD ranges from 7.5% to 34%. The aim of this study is to determine if anemia is a risk factor for readmission in COPD patients. METHODS: This study analyzed the hospital data of 289,077 adults with acute exacerbations of COPD admitted to the hospital at any public center in Spain, in 2006 and 2007. We calculated the prevalence of anemia and compared readmissions between COPD patients with and without anemia. Multiple regression analyses were carried out with the aim of determining the risk of readmission attributable to anemia, after the correction of possible confounding variables. RESULTS: Of the patients with COPD, 9.8% (n = 26,899) had a diagnosis of anemia. Anemic patients were older, more likely to be female and had a greater comorbidity burden than non-anemic individuals. Multiple regression modeling revealed that multiple independent factors were associated with an increased risk of readmission in persons with COPD. Anemia was one of the greatest risks: anemic patients had a 25% higher risk of readmission than non-anemic patients (odds ratio [OR], 1.25; 95% confidence interval [CI] 1.21-1.29). CONCLUSION: Utilizing an administrative database the authors found that anemia correlates independently with readmission in COPD patients. LIMITATIONS: This is a retrospective cohort study and thus subject to multiple forms of bias. Although spirometric evidence of COPD was not available, our case identification methods have been previously validated and found to be accurate in recognizing COPD.

Influence of obesity and malnutrition on acute heart failure.

INTRODUCTION AND OBJECTIVES: Obesity is an independent risk factor for the development of heart failure. Several recent studies have found better outcomes of heart failure for obese patients, an observation termed as the "obesity paradox." On the other hand, the negative effect of malnutrition on the evolution of heart failure has also been clearly established. METHODS: Data from the Minimum Basic Data Set were analyzed for all patients discharged from all the departments of internal medicine in hospitals of the Spanish National Health System between the years 2006 and 2008. The information was limited to those patients with a primary or secondary diagnosis of heart failure. Patients with a diagnosis of obesity or malnutrition were identified. The mortality and readmission indexes of obese and malnourished patients were compared against the subpopulation without these diagnoses. RESULTS: A total of 370,983 heart failure admittances were analyzed, with 41,127 (11.1%) diagnosed with obesity and 4105 (1.1%) with malnutrition. In-hospital global mortality reached 12.9% and the risk of readmission was 16.4%. Obese patients had a lower in-hospital mortality risk (odds ratio [OR]: 0.65, 95% confidence interval [95%CI]: 0.62-0.68) and early readmission risk (OR: 0.81, 95%CI: 0.78-0.83) than nonobese patients. Malnourished patients had a much higher risk of dying while in hospital (OR: 1.83 95%CI: 1.69-1.97) or of being readmitted within 30 days after discharge (OR: 1.39, 95%CI: 1.29-1.51), even after adjusting for possible confounding factors. CONCLUSIONS: Obesity in patients admitted for HF substantially reduces in-hospital mortality risk and the possibility of early readmission, whereas malnutrition is associated with important increases in in-hospital mortality and risk of readmission in the 30 days following discharge.