Cardiovascular risk in the elderly population of Spain. The EPICARDIAN risk score.

BACKGROUND AND OBJECTIVES: Cardiovascular risk estimation in people over 70 years of age is problematic. Most scores have been created based on cohorts of middle-aged people, with an underrepresentation of older adults. The predictive power of classical cardiovascular risk factors declines with age. The aim of this work is to develop a specific score for estimating cardiovascular risk among the elderly population in Spain. METHODS: This work is a population-based cohort established in 1995. SETTING: Three geographical areas of Spain (Madrid, Ávila, and Lugo). PARTICIPANTS: 3,729 people older than 64 years with no cardiovascular diseases (CVD) at baseline. MEASUREMENTS: Suspected fatal and nonfatal CVD (both coronary heart disease and stroke) were investigated annually and confirmed using the WHO-MONICA criteria. All participants were followed-up on until occurrence of a first CVD event, until death, or until December 31, 2015. RESULTS: Age was the strongest predictor of CVD at 10 years in both men and women. In men, variables associated with CVD were high blood pressure treatment (HR: 1.35; 95% CI: 1.067-1.710), diabetes (HR: 1.359; 95% CI: 0.997-1.852), and smoking (HR: 1.207; 95% CI: 0.945-1.541) and in women, the variables were smoking (HR: 1.881; 95% CI: 1.356-2.609) and diabetes (HR: 1.285; 95% CI: 0.967-1.707). Total cholesterol did not increase the risk of CVD in men or women. However, total cholesterol levels >200 mg/dL were inversely associated with 10-year risk of CVD in men and women. CONCLUSIONS: In elderly Spanish men, total CVD at 10 years is significantly increased by age, diabetes, and antihypertensive treatment and in elderly Spanish women by diabetes and smoking. Total cholesterol levels did not increase the risk of CVD, particularly in males.

[Pharmacological treatment in uncertainty times: Hydroxychloroquine/chloroquine use in the COVID-19 treatment]. / Tratamiento farmacológico en tiempos de incertidumbre: uso de la hidroxicloroquina/cloroquina en el tratamiento de COVID-19.

BACKGROUND AND OBJECTIVES: In this moments, of extreme gravity in which we find ourselves, and in the uncertainty face about the most effective treatment against COVID-19 disease and with the aim of find the evidence that support the chloroquine/hydroxychloroquine use recommendation to treat COVID-19 disease, a systematic review of published studies and RCT studies publishes until April 28, 2020 was carried out. MATERIAL AND METHODS: A systematic search was carried out in PubMed with the keywords COVID-19 and their synonyms and hydroxychloroquine/chloroquine. The data selection and extraction was elaborated by two researchers, independently. The results were discussed with a Primary Care physicians clinical group and the results were synthesized using GRADE methodology. RESULTS: A good quality systematic review was found that includes articles with a high risk of bias. And 8 EC launched that will produce results beyond May 2020. CONCLUSIONS: Although the conclusions of the systematic review generate a low confidence in the results, and the clinical variables that show benefit are intermediate variables, the side effects are acceptable and could be minimized with the use of QT lengthening risk tools, so it is could make a weak recommendation in favor of the use of chloroquine/hydroxychloroquine in patients with mild-moderate stage COVID-19.

[Do we adequately prescribe antiplatelet treatment to type 2 diabetic patients?]. / Antiagregamos adecuadamente a los pacientes diabéticos tipo 2?

OBJECTIVE: To estimate how many type 2 diabetic patients receive antiplatelet therapy according to the American Diabetes Association (ADA) guidelines on primary and secondary prevention. DESIGN: A descriptive, cross-sectional study based on information in medical records. A random sample of 170 type 2 diabetics seen in an urban Health Centre was studied. MEASUREMENTS: The data collected including, age, sex, antiplatelet therapy according to the ADA, antiplatelet therapy indicated, cardiovascular risk factors, cardiovascular disease, and other clinical parameters. RESULTS: Of the subjects analysed, 56.9% were males, and the mean age was 67.8 years. The majority of patients (71.2%) were on primary prevention, and 44.4% of the diabetics were receiving adequate antiplatelet therapy according to the ADA. Among the subjects on secondary prevention, 90.9% received adequate antiplatelet therapy, while only 25.7% of those on primary prevention received it, which was significant. The most used antiplatelet drug was acetylsalicylic acid (ASA). CONCLUSIONS: A large proportion of diabetes on primary prevention does not receive adequate antiplatelet therapy, according to the ADA. However, patients on secondary prevention receive sufficient antiplatelet treatment. The benefits of ASA in reducing cardiovascular disease are well documented in patients with cardiovascular disease. On the other hand, the role of antiplatelet therapy in diabetics on primary prevention is not clear and is the subject of discussion. From 2006 to 2011, the ADA has modified the recommendation level of primary prevention antiplatelet therapy, thus decreasing the percentage of patients that may be given antiplatelet therapy with ASA, to the extent that it increases the cardiovascular risk calculation required for its indication.

Nutritional state during COPD exacerbation: clinical and prognostic implications.

AIMS: To estimate the prevalence of malnutrition in chronic obstructive pulmonary disease (COPD) patients hospitalized for exacerbation and to evaluate its clinical and prognostic influence on the exacerbation. SUBJECTS/METHODS: The subjects were 78 consecutive patients with moderate-to-severe COPD who were admitted to hospital with a diagnosis of exacerbation. Nutritional status was assessed by means of body mass index (BMI), bioelectric impedance analysis and levels of plasmatic albumin. Previous spirometry, 6-min walk test, severity of the exacerbation, days of hospitalization and readmission in the following 3 months were also evaluated. RESULTS: Malnutrition [BMI <20 or fat-free mass (FFM) index

[Relationship between pulse pressure and clinical cardiovascular damage in elderly subjects of EPICARDIAN study]. / Relación entre presión de pulso y antecedente de enfermedad cardiovascular en ancianos de dos poblaciones pertenecientes al estudio EPICARDIAN.

INTRODUCTION: Arterial hypertension and aging are the main cardiovascular risk factors (CVRF) in the elderly population. Aging is associated with an increase in systolic blood pressure (SBP) levels and a decrease of diastolic blood pressure (DBP), due to increased large artery stiffness. Several epidemiological studies have demonstrated that pulse pressure (PP) is an independent risk factor, better than SBP, for overall, cardiovascular mortality, coronary heart disease and cerebrovascular, particularly in the elderly. OBJECTIVES: To determine the association of PP with clinical cardiovascular damage, in a population-based sample of Spanish elders subjects. To quantify the association between PP and the background of clinical cardiovascular damage. To determine which PP, SBP, DBP or mean arterial pressure (MAP) are better associated to the history of clinical cardiovascular damage. PATIENTS AND METHODS: The sample analyzed included individuals from the EPICARDIAN study in the areas of Lista district (Madrid) and Arévalo (Avila). The following CVRF of age, gender, hypertension, diabetes, dyslipidemia, obesity, abdominal obesity and smoking were considered. Clinical cardiovascular damage is defined as the personal background of stroke, myocardial infarction, angina pectoris and/or intermittent claudication. RESULTS: The sample included 2665 individuals, 56% women, mean age: 74 year-old; 74.3% were hypertensive, 55.6% had central obesity and 31.9% hypercholesterolemia. In the multivariate analysis, the PP was the BP parameter associated most to stroke, angina pectoris and intermittent claudication: OR, 1.015, (95% CI: 1.001-1.030), 1.029 (95% CI: 1.006-1.052) and 1.012 (95% CI: 1.002-1.023), respectively. CONCLUSIONS: In the elderly population studied, an elevated PP is the component of arterial pressure with the greatest association to the background of cardiovascular damage.

Osteoporosis increases the severity of cartilage damage in an experimental model of osteoarthritis in rabbits.

OBJECTIVE: To evaluate the effect of osteoporosis (OP) in cartilage damage developed in an experimental model of osteoarthritis (OA) in mature female rabbits in order to investigate the relationship between OP and OA. METHODS: OA was experimentally induced by anterior cruciate section and partial medial meniscectomy in the left knee of 12 rabbits. OP was experimentally induced prior to OA in six rabbits by bilateral ovariectomy (OVX) and systemic corticosteroid administration during 4 weeks. Knees were evaluated with high resolution magnetic resonance imaging (MRI) before knee surgery to rule out any detrimental effect of corticosteroids on cartilage. Gross and microscopic cartilage changes were assessed 16 weeks after surgery in bilateral knees. Left knees were considered osteoarthritic or osteoarthritic plus osteoporotic. Right knees were used as osteoporotic and healthy controls, respectively. Bone mineral density (BMD) was measured with dual energy X-ray absorptiometry (DXA) at the lumbar spine, global knee and subchondral knee bone, and its variations correlated with cartilage abnormalities. RESULTS: MRI before knee surgery disclosed no cartilage or bone abnormalities in any of the studied groups. OP increased the severity of cartilage abnormalities in experimental knee OA significantly (P<0.05). Cartilage damage was inversely correlated with BMD variations measured at the lumbar spine (r=-0.74; P=0.015). BMD changes in global and subchondral knee bone also showed a trend to correlate inversely with cartilage damage. CONCLUSIONS: Prior induction of OP increases the severity of cartilage damage in experimental OA. Increase in cartilage damage correlates with bone loss. These findings suggest a direct relationship between OP and OA.

Bone mineral measurements of subchondral and trabecular bone in healthy and osteoporotic rabbits.

INTRODUCTION: Experimental models of osteoporosis in rabbits are useful to investigate anabolic agents because this animal has a fast bone turnover with predominant remodelling over the modelling processes. For that purpose, it is necessary to characterize the densitometric values of each type of bony tissue. OBJECTIVE: To determine areal bone mass measurement in the spine and in trabecular, cortical and subchondral bone of the knee in healthy and osteoporotic rabbits. DESIGN: Bone mineral content and bone mineral density were measured in lumbar spine, global knee, and subchondral and cortical bone of the knee with dual energy X-ray absorptiometry using a Hologic QDR-1000/W densitometer in 29 skeletally mature female healthy New Zealand rabbits. Ten rabbits underwent triplicate scans for evaluation of the effect of repositioning. Osteoporosis was experimentally induced in 15 rabbits by bilateral ovariectomy and postoperative corticosteroid treatment for 4 weeks. Identical dual energy X-ray absorptiometry (DXA) studies were performed thereafter. RESULTS: Mean values of bone mineral content at the lumbar spine, global knee, subchondral bone and cortical tibial metaphysis were: 1934+/-217 mg, 878+/-83 mg, 149+/-14 mg and 29+/-7.0 mg, respectively. The mean values of bone mineral density at the same regions were: 298+/-24 mg/cm(2), 455+/-32 mg/cm(2), 617+/-60 mg/cm(2) and 678+/-163 mg/cm(2), respectively. Bone mineral content and bone density of healthy rabbits followed a normal distribution at the four skeletal regions studied. Precision after triplicate repositioning yielded a coefficient of variation ranging from 2.6% to 3.8%. The least significant change ranged between 7.3% and 10.7%. Bone mineral density measured at the four different skeletal regions correlated significantly. Bone mineral density in osteoporotic rabbits was significantly lower in the four regions studied than that in controls, rendering a T-score of, respectively, -2.0+/-1.1 in the lumbar spine, -2.2+/-2.1 in the global knee, -1.9+/-0.6 in the subchondral bone, and -5.7+/-3.1 in the cortical tibia (P<0.05). CONCLUSIONS: DXA is a reliable and precise method to evaluate the bone mass in rabbits. Our results also suggest that subchondral bone is a bone of mixed densitometric characteristics with marked cortical bone predominance.

[Cystic fibrosis in adults: inter- and intraobserver agreement for the Brasfield and Chrispin-Norman chest radiography scoring systems and correlation with clinical data and spirometry]. / Fibrosis quística en adultos: acuerdos inter e intraobservador para las escalas de puntuación de Brasfield y Chrispin-Norman en la radiografía de tórax y relación con datos clínicos y espirométricos.

OBJECTIVE: Most chest radiography scoring systems for patients with cystic fibrosis have been developed for children but are also used for adults. Our aim was to evaluate the intra- and interobserver variability of 2 radiographic scoring systems in adults with cystic fibrosis and to assess the correlation of these systems with clinical and spirometric parameters. PATIENTS AND METHODS: The chest x-rays of 24 adult patients with cystic fibrosis were compared using 2 scoring systems (Brasfield and Chrispin-Norman). The x-rays were scored by 2 radiologists and reevaluated 4 months later by 1 of the 2 observers. Intra- and interobserver agreement was assessed using the intraclass and Pearson's correlation coefficients. The radiographic scores were compared to lung function tests and other clinical data. RESULTS: Both intra- and interobserver agreement were high (r > or = 0.9 and the intraclass correlation coefficient > or = 0.85 with both systems for both samples). Both scoring systems correlated with spirometry results: forced expiratory volume in the first second (FEV1) (r = 0.64 and r = 0.55), FEV1% (r = 0.75 and r = 0.72), and the percentage of forced vital capacity in relation to the predicted value (r = 0.63 and r = 0.056). We found no association between scoring system and sex, age, or body mass index. CONCLUSIONS: Assessment of chest radiographs of adult patients with cystic fibrosis by the Brasfield and Chrispin-Norman scoring systems shows good intra- and interobserver agreement. Both systems correlate well with lung function variables, especially FEV1.

[Evaluation of referrals in primary care]. / Evaluación de la demanda derivada en atención primaria.

OBJECTIVE: To study the process of referral from primary care in a health area in Madrid. The second objective was to evaluate the trends in the referral process. DESIGN: Observational, descriptive and cross-sectional study. SETTING: Three urban health centers in the Area 2. PARTICIPANTS: All referrals made by 13 doctors during 3 consecutive weeks. The total number of visits attended were 6012. The study was realized between February 2002 and January 2003. MAIN MEASUREMENTS: Patient, doctor and referral characteristics on every referral. RESULTS: 349 referrals were studied. The rate of referral 5.8% (5.21-6.39). The referred patients, 65.5% women, medium age 50.6+/-21. The specialties that received more referrals are gynecologist, ophthalmology, dermatology, otorhinolaryngology, rehabilitation, orthopedic surgeon and general surgeon. The most common conditions referred, 25.6% of all referrals, are gynecologist check, blindness, other illnesses of subcutaneous cellular tissue, arthrosis, joint pain, diabetes, benign neoplasm of skin, depression and hypoacusis. 92.3% of the referrals were sent to the specialist center. 89.7% were normal (no urgent). The reason for referral was to accede to the patient's request in 18.3% of the referrals. CONCLUSIONS: The process of referral is similar to previous studies. Although people are more participative, have more information and the defensive medicine is increasing, the process of referral have not changed.

Pegylated interferon-alpha2a kinetics during experimental haemodialysis: impact of permeability and pore size of dialysers.

BACKGROUND: Therapeutics in end-stage renal disease (ESRD) patients undergoing haemodialysis (HD) has to consider potential drug clearance during the dialysis procedure. Pegylated interferon-alpha (PEG-IFN-alpha), a middle-size protein drug active against viral hepatitis, allows convenient once-weekly dosing due to prolonged plasma half-life. AIM: To investigate the impact of permeability and dialyser pore size on PEG-IFN-alpha blood levels during experimental HD. METHODS: Polymethylmetacrylate (PMMA) membrane 1.6 m2 dialysers with three different permeabilities/pore sizes were selected. RESULTS: A 40 kDa PEG-IFN-alpha2a (PEGASYS) was not cleared (< 5%) through low-flux/small pore size (25 A;B3A) and high-flux/middle-large pore size (60 A;BKP) dialysers, and was partially (approximately 15%) through intermediate permeability/large pore size (100 A;BKF) dialysers. In contrast, unmodified 17 kDa IFN-alpha2a(Roferon-A) was removed (65%-95%) through BKP or BKF, but not B3A, PMMA dialysers. Moreover, 12 kDa PEG-IFN-alpha2b(PegIntron) was cleared (40%-80%) through PMMA dialysers with pore sizes > or = 60 angstroms. When B3A or BKP were replaced every hour PEG-IFN-alpha2a plasma levels remained constant throughout three experimental-HD-sessions, but PEG-IFN-alpha2b was cleared partially every BKP replacement. Porosity differ among high-flux dialysers. Neither PEG-IFN-alpha2a nor PEG-IFN-alpha2b were removed after three HD sessions through (27/31/33 A) pore size polysulphone dialysers. Although PEG-IFN-alpha2a was not cleared through middle pore-size (43 A/AN69ST) polyacrylonitrile dialyser, PEG-IFN-alpha2b was partially removed. CONCLUSIONS: The pharmacokinetics of Peg-IFN-alpha may vary in a patient on dialysis.

[New procedure for the early detection and control of hospital malnutrition]. / Nuevo procedimiento para la detección precoz y control de la desnutrición hospitalaria.

The serious problem of hospital undernutrition is still being underestimated by medical staff of modern hospitals, despite its impact on clinical evolution and hospitalisation costs. The actual system used to detect undernutrition in hospitals depends on doctor's sensitivity and not even the 10% of the cases that require intervention are detected. The screening methods developed so far are not useful for daily clinical practice due to their low effectiveness/cost ratio. We present a screening method that allows an automatic daily assessment of nutritional status, of all inpatients that undergo routine analysis. The system is based on a computer application that compiles daily all patients' information available in hospital databases, through the internal network. It automatically assesses the nutritional status of patients taking into account laboratory information concerning albumin, total cholesterol and total lymphocyte count. This tool also provides diagnostic and patients data for physicians' usage. The screening method has been validated, obtaining a sensitivity of 92.3 and specificity of 85.0, considering only laboratory information. This is an efficient tool for early detection and permanent control of hospital undernutrition, with the suitable characteristics for these screening functions, such as its sensitivity, specificity, universality, economy and harmlessness, as well as a great versatility for undertaking a high number of studies regarding the hospital undernutrition problem. We trust that working with it we will obtain a remarkable welfare improvement as well as make aware to people in charge of Public Health of the magnitude of the undernutrition's derived consequences of hospital's in-patients, and after discharge.

CsA-based post-graft immunosuppression: the main factor for improving outcome of allografted patients with acquired aplastic anemia. A retrospective survey by the Spanish Group of Hematopoietic Transplantation.

A retrospective multicenter study was performed to assess the clinical results in patients with acquired aplastic anemia (AA) allografted over a 19 year period and to identify prognostic factors influencing survival. From April 1978 to December 1997, 176 patients were transplanted. Records from 160 receiving related matched bone marrow transplantation (BMT) were reviewed. Fifty-two percent of the patients were older than 20 years, 5% older than 40; 6.3% were untransfused at BMT and 56.2% had received prior treatments. Conditioning regimens were with chemotherapy in 43.7% of the procedures and with additional irradiation in 56.3%. Graft-versus-host disease (GVHD) prophylaxis was based on cyclosporin A (CsA) in 58.1% of the patients while methotrexate (MTX) was administered to 41.9%. Transplantation earlier on, a longer interval from diagnosis to BMT, GVHD prophylaxis with MTX, graft failure/rejection and acute severe GVHD were adverse factors for survival. The use of CsA emerged as the main factor for the improvement, inducing a significant decrease in graft failure/rejection rate and severe acute GVHD when compared with MTX alone. Radiation-containing regimens decreased the graft failure/rejection rate without improving survival due to the increased risk of acute GVHD. Age and number of transfusions pretransplant did not influence outcome. Survival achieved since 1991 is 79.79%, and graft failure and acute severe GVHD rates are 6.0% and 11.8%, respectively. In conclusion, CsA-based post-graft immunosuppression has been crucial in achieving improved survival in patients with acquired AA up to 40 years of age. Regardless of CsA use, further improvement in survival was apparent with time, probably due to better skills in patient care.

[Clinical predictors of long-term outcome of lithium prophylaxis in bipolar disorder]. / Factores predictores de respuesta al litio en pacientes bipolares en seguimiento a largo plazo.

INTRODUCTION: In spite of the frequent prophylactic use of lithium salts in affective disorders, few papers have been published about clinical outcome predictors in long-term follow-up. OBJECTIVE: To identify clinical predictors of long-term outcome in a sample of bipolar outpatients on lithium treatment. METHODS: An intervention study was conducted in a case series of all patients treated, at least for two years, at two Affective Disorders ambulatory Units. It was examined the association between two dependent outcome variables (presence vs absence of relapses and number of relapses/person/year) and the rest of clinical variables. RESULTS: 139 outpatients diagnosed of bipolar disorder were included in the sample. In each case, therapeutic lithium dosages were administered. Delay time to start treatment since the disorder has begun was the only variable useful to predict weakly outcome. The time spent without treatment and the association with other mood stabilizers or neuroleptics correlates with bad outcome. CONCLUSION: Whichever clinical characteristics of the sample may be, patients should be treated as soon as possible with lithium to get better outcome.

[Analysis of prognostic factors for mortality in bacteremia and fungemia at a university hospital. Experience of 10 years]. / Análisis de factores pronósticos de mortalidad de las bacteriemias y fungemias en un Hospital Universitario. Evolución en 10 años.

OBJECTIVE: The objective of this study was to determine the prognostic factors in relationship to evolution to death of bacteremia-fungemia (BF) episodes occurred in 1986 and to compare them with the results obtained ten years later in 1996. PATIENTS AND METHODS: Prospective study of all BF episodes observed at Hospital Universitario La Princesa, Madrid, during the 1985-1986 and 1996-1997 periods. The same definitions were used for the two study periods. The univariate analysis of results was performed with the chi square test and variables with statistical significance with p < 0.10 in the multivariate analysis with the logistic regression model. RESULTS: A total of 984 episodes were analyzed. There was an increased incidence per 1,000 admissions from 23.58 to 28.44. A change in the relationship of nosocomial acquisition (55.5%-42.6%) to community-acquired episodes (44.1%-57.4%) and an increase in gram-positive organisms (39%-48.6%) compared with gram-negative organisms (53.4%-41.8%) was observed. The organisms recovered most frequently in both periods were Escherichia coli and coagulase-negative Staphylococcus. An overall decrease of mortality rate from 26.2% down to 15.9% (OR: 4.52) was noted. Independent factors with poor prognosis in the first period included age over 60 years (OR: 4.52), underlying disease (OR: 2.79; more than one OR: 6.53), respiratory source (OR: 3.86), DIC (OR: 4.79), hypotension (OR: 3.19); as for the second period, the corresponding independent factors included age > 60 years (OR: 6.48), nosocomial acquisition (OR: 2.62), DIC (OR: 18.7), hypotension (OR: 3.07), and inadequate surgical treatment (OR: 7.61). CONCLUSIONS: In the last ten years the incidence of BF episodes has increased. In contrast, mortality rate has decreased. Factors with poor prognosis, including age > 60, DIC, and hypotension, still persist.

[A population-based study of need for changes and continuing rates of antihypertensive drugs]. / Análisis poblacional de la necesidad de cambios y tasas de continuidad de los diferentes fármacos antihipertensivos.

BACKGROUND: Antihypertensive drugs are frequently changed because of inefficacy and adverse effects. The aim of this study was to compare the incidence of changes of the new classes of drugs from the classical beta-blockers and diuretics. We also have calculated the probability of continuing with each class of drug. MATERIAL AND METHOD: Clinical reports of hypertensive patients of a general practice centre were examined. All changes of treatment and their causes were registered between october 1997 and september 1999. The incidences for global changes and also for intolerance and inefficacy changes were calculated for each drug. Relative risks for beta-blockers, diuretics, ACE inhibitors of anhidride carbonic enzyme and angiotensine II-receptor-antagonists were analized. The cumulated probability for continuing therapy was also studied. RESULTS: 27.6% out of 786 courses of treatment were changed, 51.4% due to intolerance and 29,8% due to inefficacy. The probability for continuing was 88% after 3 months, 81% after 6 months, 71% after one year and 54% after 2 years. The probability for discontinuing because of intolerance was higher in the first 3 months (51%), but afterwards it remained stable along the time. CONCLUSIONS: Antihypertensive drugs are discontinued more frequently than what it would be desirable and their continuing rates are low. Differences observed among each class of drugs are not argument enough for changing the general recommendation of using beta-blockers and diuretics as first choice drugs for initial treatment of hypertension.

[Effectiveness of lithium in the prophylaxis of affective disorders]. / Efectividad del litio en la profilaxis de las recaídas en pacientes con trastornos afectivos.

UNLABELLED: Lithium effectiveness in manic depressive illness is still controversial. Recent naturalistic trials on lithium effectiveness as a mood stabilizer offer poorer results than previous controlled studies. These previous studies have methodological deficiencies. OBJECTIVE: To determine the effectiveness of lithium treatment as a mood stabilizer under real clinical conditions. METHODOLOGY: An intervention study in a case series of all patients treated at least for two years at two Affective Disorders ambulatory Units was conducted to evaluate the incidence of episodes by year, before and during lithium therapy. RESULTS: 152 patients were included. (91% were bipolar patients). Most of them were in monotherapy. The average time of illness before lithium treatment was 13 years, and cases were followed up a media of 8 years. Only 33% of the sample had no relapses during lithium therapy. An average of 1.38 (+/- 2.89) episodes/person year was estimated previous to lithium therapy and was decreased to 0.35 (+/- 0.47) phases/person year during lithium therapy. CONCLUSIONS: Although the total absence of relapses is not attained in most of the patients, our results support the lithium effectiveness to reduce the relapses in bipolar patients.

Tuberculosis after hematopoietic stem cell transplantation: incidence, clinical characteristics and outcome. Spanish Group on Infectious Complications in Hematopoietic Transplantation.

A national survey of tuberculosis after hematopoietic stem cell transplant (SCT) was undertaken to study incidence, clinical presentation and outcome. Twenty confirmed cases were found among 8,013 patients (eight in 5,147 autologous and 12 in 2,866 allogeneic SCT). The estimated incidence in cases/10(5) patients/year (95% CI) was 101 (56.5-145) for the whole group, 71.1 (21.8-120) in autologous and 135.6 (58.9-212) in allogeneic transplants. Compared with the general population, tuberculosis was more frequent after allogeneic (RR 2.95) but not after autologous SCT. Tuberculosis after SCT is a late infection (median 324 days post transplant), predominately affects the lungs (80% of the cases), appears to respond well to treatment but has a high mortality (25%) in allogeneic recipients. It can also complicate the post-transplant management as antituberculosis drugs frequently decrease the serum levels of cyclosporine causing an aggravation of GVHD. Graft-versus-host disease, corticosteroid treatment and total body irradiation appear to be associated with tuberculosis in allogeneic recipients. No obvious factors were associated with tuberculosis in autologous transplants. Finally, we found that the published literature on tuberculosis after solid and SCT has overestimated its incidence due to the direct translation of tuberculosis frequency into incidence.

Stage, percentage of basophils at diagnosis, hematologic response within six months, cytogenetic response in the first year: the main prognostic variables affecting outcome in patients with chronic myeloid leukemia in chronic phase treated with interferon-alpha. Results of the CML89 trial of the Spanish Collaborative Group on interferon-alpha2a and CML.

BACKGROUND AND OBJECTIVE: Interferon-a (IFN) is increasingly being used as the drug of choice in chronic myeloid leukemia patients. The main objectives of the study were to study the influence of the classic prognostic variables and response to IFN, and to assess the influence of this response on the course of the disease and survival. DESIGN AND METHODS: Single arm, prospective, multicenter study, without a control group. Only Ph1-positive CML patients were included. The treatment scheme was biphasic: the patients first received standard chemotherapy and thereafter IFN-a2a was used as monotherapy, with a target dose of 9 MU/d/s.c. RESULTS: Twenty-one centers in Spain enrolled 132 patients (72 men, 60 women). The median dose of IFN given was 5.8 MU/d, and the median treatment duration was 431 days (range: 18-2,597). Seventy-two percent of patients obtained a hematologic response in the first six months of IFN treatment. Genetic response was obtained in 47% of the patients, and the response was major or complete in 27% and 19%, respectively. The median time to obtain this response was 7, 9, and 18 months for minimal, partial and complete genetic response, respectively. Multivariant analysis showed that only a higher percentage of basophils at diagnosis was associated with a worse hematologic response at six months (p=0.001) (OR: 1.23) and with a worse cytogenetic response in the first year of IFN therapy (p=0.018) (OR: 1.4). Over an observation period of 8 years, 35.6% of the patients died, and 85 (64.4%) remained alive. With a median follow-up of 42 months (3.7-98), the 6-year projected probabilities of survival and transformation-free survival were 0.61+/-0.07 vs. 0.54+/-0.07, respectively. Patients with Kantarjian's stage 3 disease or in a high-risk Sokal group had lower probabilities of survival, but these systems did not adequately discriminate in our series. Obtaining a complete hematologic response in the first six months of IFN therapy was favorable in terms of overall survival (p=0.05; HR=0.33). Cox's analysis demonstrated that obtaining a cytogenetic response in the first year was independently associated with better overall survival (p=0.04; HR=0.19) and better transformation-free survival (p=0.0035; HR=0.11). INTERPRETATION AND CONCLUSIONS: Nearly half of the patients obtained some degree of Philadelphia suppression, which was major in 27%, and complete in 19%. A higher percentage of basophils at diagnosis was the only variable associated with a lower probability of cytogenetic response. Obtaining a cytogenetic response during the first year of IFN treatment was a favorable and independent variable in terms of survival and transformation-free survival. Obtaining a major cytogenetic response during this period decreased the risk of transformation twenty times. Our results suggest that the effect of IFN on survival is independent of the classic prognostic variables.