Flow cytometry analysis with a new FITC-conjugated monoclonal antibody-3E12 for HLA-B*57:01 rapid screening in prevention of abacavir hypersensitivity in HIV-1-infected patients.

BACKGROUND: Rapid screening for the detection of HLA-B*57:01 in the prevention of abacavir hypersensitivity in HIV-1-infected patients is a hallmark for clinical services. OBJECTIVE: The aim of this work was to analyze the utility of flow cytometry with a new FITC-conjugated B-17 monoclonal antibody (mAb3E12) for HLA-B*57:01 screening in a Spanish cohort of 577 HIV-1+ individuals. METHODS: Cryopreserved peripheral blood mononuclear cell samples from HIV-1+ individuals were analyzed by flow cytometry with the mAb 3E12 that recognizes both HLA-B*57 and HLA-B*58 alleles (members of the group specificity, HLA-B17). Patients' DNA samples had been previously typed for HLA-B*57:01 with PCR-SSO or PCR-SSP and additional DNA sequencing (EPI Study). The results obtained by flow cytometry were compared with the results obtained by the DNA-PCR techniques. RESULTS: By flow cytometry, 46 samples (7.97%) were positive for HLA-B17, 530 (91.86%) were negative, and 1 (0.17%) was undetermined. All samples found negative by flow cytometry were negative for HLA-B*57:01 by DNA-PCR. Of the HLA-B17 positive samples, 31 (67.4%) were positive for HLA-B*57:01, 2 (3.25%) were positive for HLA-B*57:03, 11 (26.1%) were positive for HLA-B*58, and 2 (3.25%) were negative for both HLA-B*57 and HLA-B*58 antigens. The undetermined sample was negative for HLA-B*57 and HLA-B*58 alleles by DNA-PCR. CONCLUSIONS: This study shows that flow cytometry with mAb3E12 is a highly sensitive method (no false negatives) to implement prior to DNA-PCR analysis for rapid screening of HLA-B*57:01. Additional confirmation by molecular HLA typing method would be required in less than 10% of the cohort of HIV-1-infected individuals.

Cost minimization analysis of brolucizumab in the treatment of neovascular age-related macular degeneration.

INTRODUCTION: Brolucizumab is a novel anti-vascular endothelial growth factor (anti-VEGF) drug administered in a fixed regimen of 8 or 12 weeks which, in the HAWK and HARRIER studies, was shown not to be inferior to aflibercept with respect to the best corrected visual acuity, with a less burdensome treatment regimen. The aim of the analysis was to compare the direct healthcare costs of both anti-VEGF as a treatment in patients with neovascular age-related macular degeneration. MATERIAL AND METHODS: A cost minimization analysis was performed under a 25-year time horizon and considering the drug costs, administration, follow-up tests, and management of adverse events. Resource use was obtained from the related literature and validated by clinical experts. Various scenario analysis were carried out to check the robustness of the results. RESULTS: Brolucizumab resulted in a lower cost per patient compared with aflibercept, considering the number of injections derived from the HAWK and HARRIER studies. This result was maintained in the different scenarios analysed, except for the number of injections of the flexible aflibercept regimen of the ARIES study, since the lower discontinuation of treatment with brolucizumab implies maintaining the treatment of more patients. Considering the same discontinuation, brolucizumab maintained the results observed in the base case of the analysis. CONCLUSIONS: This study shows how the fixed administration regimen of brolucizumab can help reduce both healthcare and patients' burden.

Association of coronary calcification with prognosis of Covid-19 patients without known heart disease.

Risk factors that determine the severity of Covid-19 have not been fully elucidated. The aim of this study was to evaluate the role of coronary artery calcification (CAC) as a risk factor for death or mechanical ventilation (MV) of patients without known heart disease infected with Covid-19. We analyzed 283 consecutive in-patients with acute respiratory symptoms with chest computed tomography (chest-CT), without previous heart disease, and criteria for Covid-19 (RT-PCR positive and/or typical clinical and chest-CT findings). CAC was classified by the number of coronary segments affected as absent (0), mild (1-3), and severe calcification (more than 3). The association between CAC, CAC severity, and death or MV due to severe respiratory failure was assessed by logistic regression. The mean age was 58.7±15.7 years and 54.1% were men. Patients with CAC were older, more likely to have hypertension, and less likely to be obese. CAC was present in 75 patients (26.5%), of which 42 had a mild calcification and 33 had severe calcification, and was associated with death (OR=2.35, 95%CI: 1.01-5.48) or MV (OR=2.72, 95%CI: 1.20-6.20) adjusted for multiple confounders, with significant and increased odds ratio for the severe form of CAC (death: OR=3.70, 95%CI: 1.20-11.42; MV: OR=3.30, 95%CI: 1.09-9.95). We concluded that CAC was an independent risk factor for death or MV in Covid-19 patients without previous heart disease, particularly for those with severe calcification. CAC can be easily visualized on common chest-CT, widely used in evaluation of moderate to severe Covid-19.

Prevalence of HLA-B*5701 in HIV-infected patients in Spain (results of the EPI Study).

BACKGROUND: A hypersensitivity reaction (HSR) is associated with abacavir (ABC), a nucleoside reverse transcriptase inhibitor. Genetic association of ABC HSR with the presence of HLA-B*5701 has been demonstrated in PREDICT-1 study, showing a prevalence of 5.6% in HIV-infected population. However the prevalence of this allele in HIV-infected patients in Spain has not been established yet. METHOD: This is a cross-sectional epidemiological study that included 1,198 patients in 74 centers that serve the HIV-infected population of Spain. HLA-B*5701 was checked both in the hospital lab and one central lab, showing an overall prevalence of this allele of 6%. RESULTS: HLA-B*5701 was most prevalent in Caucasian population (6.5%). Concordance between the local and central lab was very high for positive and negative results (95.7% and 99.3%, respectively). CONCLUSION: These aspects define this test as a useful tool for the management of HIV-infected patients.

Detection of border disease virus in Mexican cattle.

The genus Pestivirus within Flaviviridae is comprised of four recognized species, namely, bovine viral diarrhoea virus 1 (BVDV-1), bovine viral diarrhoea virus 2 (BVDV-2), border disease virus (BDV) and classical swine fever virus (CSFV). BDV, while primarily infecting sheep and goats, has also been reported in cattle and wild animals. Infections of sheep and goats result in economic loss due to abortions and the birth of persistently infected animals that have poor production and reduced life expectancy. In this study, we report the detection of BDV in cattle serum collected as part of pestivirus surveillance programme from six regions of Mexico, where a 67.1% of BVDV seroprevalence was calculated previously. Phylogenetic analyses based on comparison of the 5'UTR region typed the Mexican strains as BDV-1. Border disease (BD) is listed as an exotic disease in Mexico, and the origin of BDV found in these cattle is unclear. This is the first identification of BDV in Mexican cattle.

[Oat-cell carcinoma of the esophagus: presentation of two cases and literature review]. / Carcinoma oat-cell de esófago: presentación de dos casos y actualización bibliográfica.

OBJECTIVE: Our objective is to contribute an updated view on a condition as rare as oat-cell carcinoma of the esophagus by reviewing the literature and reporting two recent patients seen in our department. MATERIAL AND METHOD: A retrospective study with a review of all medical records of patients seen in our ward and diagnosed with esophageal neoplasm for 6 years (January 2000 to December 2006). RESULTS: 249 cases of esophageal neoplasms were found, of them 106 were of squamous ancestry (42.6%), 141 were adenocarcinomas (56.6%), and 2 were oat-cell carcinomas (0.8%). Only in 45 (18%) was surgical resection feasible, 23 underwent palliative surgery (endoprostheses, gastrostomies, and jejunostomies not included) (9.3%), and the rest (181 cases, 72.7%) received derivative surgery or no surgery at all. CONCLUSIONS: We can affirm that this neoplasm is highly aggressive, displaying in practically all cases dissemination to other sites; this is a rare cancer that mainly affects men and whose clinical picture is similar to that of other malignancies involving the esophagus.

Association of coronary calcification with prognosis of Covid-19 patients without known heart disease

Risk factors that determine the severity of Covid-19 have not been fully elucidated. The aim of this study was to evaluate the role of coronary artery calcification (CAC) as a risk factor for death or mechanical ventilation (MV) of patients without known heart disease infected with Covid-19. We analyzed 283 consecutive in-patients with acute respiratory symptoms with chest computed tomography (chest-CT), without previous heart disease, and criteria for Covid-19 (RT-PCR positive and/or typical clinical and chest-CT findings). CAC was classified by the number of coronary segments affected as absent (0), mild (1-3), and severe calcification (more than 3). The association between CAC, CAC severity, and death or MV due to severe respiratory failure was assessed by logistic regression. The mean age was 58.7±15.7 years and 54.1% were men. Patients with CAC were older, more likely to have hypertension, and less likely to be obese. CAC was present in 75 patients (26.5%), of which 42 had a mild calcification and 33 had severe calcification, and was associated with death (OR=2.35, 95%CI: 1.01-5.48) or MV (OR=2.72, 95%CI: 1.20-6.20) adjusted for multiple confounders, with significant and increased odds ratio for the severe form of CAC (death: OR=3.70, 95%CI: 1.20-11.42; MV: OR=3.30, 95%CI: 1.09-9.95). We concluded that CAC was an independent risk factor for death or MV in Covid-19 patients without previous heart disease, particularly for those with severe calcification. CAC can be easily visualized on common chest-CT, widely used in evaluation of moderate to severe Covid-19.

Relationship of bacterioplankton production with primary production and respiration in a shallow estuarine system (Ria de Aveiro, NW Portugal).

The response of bacterial growth to phytoplankton production and planktonic respiration (RESP) variation was examined over different stations and dates in the shallow estuarine system Ria de Aveiro. The temporal and spatial profiles of bacterial productivity (2.7-744.2mg Cm(-3)d(-1)) did not coincide with those of primary production (PP) (0.2-19.1 g Cm(-3)d(-1)) and RESP (0.1-8.2 g Cm(-3) d(-1)). The bacterioplankton production/PP ratio varied differently, depending on the season and location. The heterotrophic zones, with the lowest values of PP, exhibited the most intense bacterial secondary production. Moreover, the variation of PP in the system was rather small when compared with that of bacterial secondary production. These suggest that, in a large extension of the lagoon and throughout the year, bacterioplankton growth is largely dependent on non-phytoplanktonic carbon sources. Benthic PP and/or allochtonous organic matter from land have a fundamental role in the dynamics of the planktonic compartment of the estuarine system.

Heparin in plasma samples causes nonspecific binding to histones on Western blots.

We observed an artifactual reactivity on Western blots when heparin was used as the anticoagulant in collected blood specimens. This nonspecific interaction was found to be due to immunoglobulin aggregates that bound to cellular proteins, in particular histones. Nonspecific interaction was not observed in fresh heparinized samples, but was present in samples frozen for long-term storage. Other anticoagulants such as EDTA, oxaloacetate and sodium citrate did not cause this nonspecific reactivity. Although adding heparin to serum could reproduce the nonspecific reactivity on Western blots, other immunological tests such as ELISA or indirect immunofluorescence were not affected by the use of heparinized plasma. Enzymatic digestion of heparinized samples with Heparinase I removed the artifactual reactivity, leaving specific antigen-antibody interactions unaffected. Therefore, we advise caution in the interpretation of Western blotting experiments when blood or other tissue fluid specimens are collected in heparin.

Peripheral neuropathy associated with treatment for multidrug-resistant tuberculosis.

OBJECTIVE: To review the incidence and management of peripheral neuropathy in patients receiving therapy for MDR-TB. METHODS: A case series with retrospective chart review of 75 patients who initiated individualized therapy for multidrug-resistant tuberculosis (MDR-TB) in Lima, Peru, between 1 August 1996 and 31 January 1999. RESULTS: All patients had confirmed MDR-TB and were receiving individualized therapy, comprised of an average of six drugs. Ten (13%) of these patients presented with symptoms of peripheral neuropathy, confirmed by electromyography. All symptoms were reported in the lower extremities, and all were sensory in nature. Median time to presentation from initiation of MDR-TB therapy was 9.1 months. No significant risk factors associated with development of peripheral neuropathy were identified. Management strategies depended on the severity of symptoms and included the treatment of contributing co-morbidities, medications for neuropathic pain, and adjustment of doses of possible offending agents. All patients responded to management; three patients were left with mild residual symptoms. Patients whose neuropathy resolved had symptoms for a median of 7 months. CONCLUSIONS: Peripheral neuropathy was encountered in 13% of our cohort of MDR-TB patients. The diagnosis of peripheral neuropathy can be based on clinical presentation alone, and effective management of this side-effect is possible without sacrificing MDR-TB treatment efficacy.

Occurrence of serious adverse effects in patients receiving community-based therapy for multidrug-resistant tuberculosis.

SETTING: A community-based treatment program for multidrug-resistant tuberculosis (MDR-TB) in an urban shantytown of Lima, Peru. OBJECTIVES: To ascertain the occurrence of serious adverse effects associated with therapy for MDR-TB in northern Lima, Peru, where therapy was individualized according to drug-susceptibility testing of patients' infecting strains and delivered through a community-based program. DESIGN: A retrospective record review of 60 patients who had received individualized therapy for MDR-TB between September 1996 and October 1998. RESULTS: Although adverse effects were common, they occurred less frequently than previously reported in the literature and were rarely life-threatening. Effects occurring most frequently in this population included: mild gastritis (100%), dermatological effects (43.3%), peripheral neuropathy (16.7%), depression (18.3%), and anxiety (11.7%). These effects never resulted in the discontinuation of anti-tuberculosis therapy, and only occasionally resulted in the suspension of an agent (11.7%). CONCLUSION: In young patients with little comorbid disease, multidrug, long-course regimens rarely caused life-threatening adverse effects. Common side effects may be managed successfully on an out-patient basis through a community-based treatment program in conjunction with MDR-TB experts, even in resource-poor settings. The very low rate of default in this cohort offers hope that strategies to manage the adverse effects may reduce the incidence of abandonment of therapy and increase rates of cure.

Short-Term Responses of the Natural Planktonic Bacterial Community to the Changing Water Properties in an Estuarine Environment: Ectoenzymatic Activity, Glucose Incorporation, and BiomassProduction.

The possibility that two principal bacterial communities expressing different levels of heterotrophic activity might coexist in an estuarine ecosystem (Ria de Aveiro, Portugal) and could quickly respond to tidal fluctuations of environmental factors was experimentally tested in diffusion chambers by swapping the dissolved components of the natural water between the two communities and comparing their reactivity against the unaltered controls. The results for ectoenzymatic activity (Leu-aminopeptidase and b-glucosidase), glucose incorporation and biomass production after transference of the marine bacterial community to brackish water showed maxima in the range of 241-384% of the control values. The opposite transference of the brackish-water bacterial community to marine water produced maximal decreases to 0.14-0.58% of the control values. In a reverse experiment, designed as the return to the initial conditions after 2 hours of the first exposure, the marine community rapidly re-acquired the characteristic low profile of activity. Contrastingly, the negative effects of 2 hours of exposure to marine water on the activity of the brackish water bacteria persisted, at least for 4 hours, after return to their own water. The apparent short-term irreversibility of the decline in activity of the brackish water bacteria when exposed to marine water, in parallel with the quick and reversible positive response of the marine water bacteria to the brackish water, suggests the development of two distinct bacterioplankton communities adapted to the environmental conditions prevailing at distinct sections of the estuary. The reactivity to environmental changes demonstrated by the two communities allows the prediction of estuarine profiles of bacterial activity steeper than those expected from the conservative transport of bacterial cells associated with tidal currents.

Loss of Estuarine Bacteria by Viral Infection and Predation in Microcosm Conditions.

The bacterioplankton density in Ria de Aveiro, a shallow estuarine ecosystem, varied in the broad range of 1.9-10.6 x 109 cells L-1. The range of values was about 2 times higher in brackish water than in marine water. At high tide bacterial abundance was 2-3 times lower than at low tide. The overall variation in virioplankton was in the range of 2.4-25.0 x 1010 particles L-1. Brackish water was about 2 times richer in viral particles than the marine water. Near low tide the virioplankton was 2-3 times higher that at high tide. Viral density followed the pattern of bacterial abundance (it explained 40% of virioplankton variation). The viruses to bacterium ratio varied, throughout tidal cycles, by a factor of about 10 establishing the range 4.7-55.6 (average 17.6). This ratio was rather similar in the two estuarine zones. We compared the effects of infection and predation on the control of bacterioplankton size in the two zones of the estuary. The approach to this question was conducted in experimental microcosms, set up in six combinations of plankton variables affecting the presence/absence of predators, virus-to-bacterium ratio (10-fold increase), virus-to-bacterium distance (2.2-fold increase), and bacterial growth rate. The results showed that predation was similar, in a percent basis, in marine (69%) and brackish water (73%). Viral infection was, however, higher in brackish water (59%) than in the marine water (36%). We conclude that the bacterioplankton along the salinity gradient evolves under biological pressures that are in different balance in the marine and brackish water zones. The effect of viral lysis on bacterial communities with enhanced growth (after yeast extract addition) was masked even when the initial ratio was 10-fold greater than in the natural samples. The high density of the virioplankton did not preclude the large and rapid increase in bacterial density. We suggest that the dynamics of the equilibrium between bacteria and viruses in the environment is driven to higher numerical levels during periods of intensive bacterial growth. On the contrary, at low bacterial growth rates the temporarily increased virus-to-bacterium ratio may drive the equilibrium to its lowest levels.

Factors Influencing Bacterial Production in a Shallow Estuarine System.

The bacterioplankton of the marine and brackish water zones of the complex system Ria de Aveiro was characterized as profiles of bacterial abundance and biomass productivity. During the warm season, total bacteria ranged from 0.2 to 8.5 x 109 cells L-1 and active bacteria number from 0.1 to 3.1 x 109 cells L-1. Total and active bacterial numbers were, on average, three times higher in brackish than in marine water. Bacterial productivity on different dates and different tides in the marine zone varied from 0.05 to 4.5 mg C L-1 h-1. Here the average productivity (1.1 mg C L-1 h-1) was 3.5 times less than in brackish water (average 3.8 mg C L-1 h-1; range 0.7-14.2 mg C L-1 h-1). Specific productivity varied from 0.05 to 2.61 fg C cell-1 h-1, a range that was similar throughout the ecosystem. However, specific productivity per active cell was 19% higher in brackish water. Bacterial production variation was best explained by the number of active bacteria, which, in turn, was highly associated with total bacterial number, temperature, and particulate organic carbon. In the marine zone, bacterial production was also influenced by depth and salinity. In the brackish zone, the set of independent variables explained a smaller percentage of bacterial production variation than in marine zone, suggesting greater importance of other variables. In the marine zone, and mainly near low tide, productivity was significantly higher (average 3.3 times) at the surface (down to 0.5 m) than in the deeper layers of the water column. This stratification of bacterial productivity was linked to the increased specific productivity per active cell, as no modification in the proportion of active cells in the population could be detected. The vertical profile of bacterial production in the deeper zone of this estuarine ecosystem, in which no clear salinity or thermal stratification occurs throughout the tidal cycle, seemed to reflect a biochemical stratification generated by increased phytoplankton exudation and/or by photochemical transformation of semilabile or recalcitrant organic compounds. Shallower water masses tend to blur this surface effect. The relative importance of photochemical transformation in the pattern of estuarine bacterial production will therefore tend to vary with the bathymetry of the system.

Acute buspirone abolishes the expression of behavioral dopaminergic supersensitivity in mice.

Previous studies have shown that rats withdrawn from long-term treatment with dopamine receptor blockers exhibit dopaminergic supersensitivity, which can be behaviorally evaluated by enhanced general activity observed in an open-field. Recently, it has been reported that co-treatment with the non-benzodiazepine anxiolytic buspirone attenuates the development of haloperidol-induced dopaminergic supersensitivity measured by open-field behavior of rats. The aims of the present study were: 1) to determine, as previously reported for rats, if mice withdrawn from long-term neuroleptic treatment would also develop dopaminergic supersensitivity using open-field behavior as an experimental paradigm, and 2) to examine if acute buspirone administration would attenuate the expression of this behavioral dopaminergic supersensitivity. Withdrawal from long-term haloperidol treatment (2.5 mg/kg, once daily, for 20 days) induced a significant (30%) increase in ambulation frequency (i.e., number of squares crossed in 5-min observation sessions) but did not modify rearing frequency or immobility duration in 3-month-old EPM-M1 male mice observed in the open-field apparatus. Acute intraperitoneal injection of buspirone (3.0 and 10 but not 1.0 mg/kg, 12-13 animals per group) 30 min before open-field exposure abolished the increase in locomotion frequency induced by haloperidol withdrawal. These data suggest that the open-field behavior of mice can be used to detect dopaminergic supersensitivity, whose expression is abolished by acute buspirone administration.

[Socioclinical and diagnostic characteristics of prostatism in Spain at the end of the 20th century]. / Características sociosanitarias y diagnósticas del paciente prostático en España a finales del siglo XX.

RATIONALE: To study sociodemographic characteristics and current diagnostic and therapeutic behaviour with Benign Prostate Hyperplasia (BPH) patients in Spain at the end of the 20th century. METHODS: Sociodemographic, clinical, therapeutic and quality of life (QoL) data from study ESECI-98, conducted in Spain (1998-1999) in patients with BPH. RESULTS: Nine hundred and forty nine patients were evaluable, with a mean (+/- SD) age of 65.6 (+/- 7.8) years, with concomitant diseases (40%), pain/discomfort (34%) and anxiety/depression (23%); QoL score (mean +/- SD) was 72.1 +/- 16.1 on a total possible score of 100. BPH diagnosis was based on symptoms (93%), digital rectal examination (93%) and abdomino-pelvic ultrasonography (76%). PSA was mentioned for the diagnosis of BPH in 54% of the patients and 77% were receiving pharmacological treatment (61% alpha-blockers) during less than 6 months (38%) or more than a year (35%). CONCLUSIONS: In this study the diagnosis of BPH was mainly based on symptoms, digital rectal examination and abdomino-pelvic ultrasonography. It is worth mentioning that PSA for the diagnosis of BPH, was used in a half of the total number of patients. Pharmacological therapy was used in 3 out of every 4 patients. Compared to a previous national study, there is a change on diagnosis and therapy of BPH.

Salvage therapy for multidrug-resistant tuberculosis.

Treatment of multidrug-resistant tuberculosis (MDR-TB), defined as Mycobacterium tuberculosis resistant to both isoniazid and rifampicin, is challenging under the best of circumstances, and particularly in resource-limited settings. For patients who remain persistently sputum-culture-positive despite therapy with second-line TB drugs, treatment options are limited, especially if disease is too advanced for resective surgery. Salvage therapy refers to the design of a regimen combining new and previously used drugs in a final effort to attain sputum conversion before declaring treatment to have failed. We retrospectively evaluated the outcomes of salvage therapy in 213 Peruvian patients. Salvage regimens included a median of two new drugs (range 1-6) and nine (range 5-13) total (new plus previously used) drugs. The most frequently used new drug was moxifloxacin, followed by capreomycin, amoxicillin-clavulanate, kanamycin and clarithromycin. Culture conversion occurred in 65 (30.5%) patients. Salvage regimens that included moxifloxacin were significantly more likely to be followed by culture conversion (OR 2.2; p 0.02). Later-generation fluoroquinolones such as moxifloxacin should be used in salvage therapy but also in the initial treatment of MDR-TB, if the best clinical strategy is to use the most effective drugs when the patient has the best chance for cure. New TB drugs are most likely to be initially used in salvage patients, in conditions similar to those described here. Close bacteriological monitoring of these patients will be essential, as useful information about the best way to use these new drugs can be gained from analysis of salvage therapy cohorts.

Burden of illness attributable to subclinical hypothyroidism in the Spanish population.

INTRODUCTION: Subclinical hypothyroidism (SH) has been associated recently to cardiovascular diseases. However, the loss of health it entails remains unknown. This study has assessed the burden of illness attributable to SH in Spain. PATIENTS AND METHODS: Based on the Spanish prevalence data found in international studies, a theoretical model was developed to estimate the Disability Adjusted Life Years (DALYs), Years of Life Lost (YLL) and Years Lost due to Disability (YLD) associated with SH. Prevalence of risk factors, coronary mortality risk and coronary event risk associated with SH were obtained from a review of the literature. An analysis was conducted according to the World Health Organization methodology approach for these studies, using official Spanish sources (hospital discharge records, minimum basic data set [MBDS], inpatient mortality records, etc. RESULTS: In Spain, approximately 2,767,124 people have SH, specifically 1,949,820 with levels of TSH between 4.5 and 6.9mIU/l (70.5%), 538,988 with levels between 7 and 9.9mIU/l (19.5%), and 278,317 between 10 and 19.9mIU/l (10%). These subjects suffer approximately 12,608 cardiac events and 1,388 deaths a year attributed to their SH. This represents 30,550 DALYs (13,124 YLL and 17,426 YLD). Between 1.6 and 7.3% of cardiovascular DALYs can be attributed to SH. CONCLUSION: SH is a silent disease which considerably increases the burden of disease. Evaluation of SH, at least in patients belonging to risk groups, could be cost-effective.

The prevalence of dysphonia, its association with immunomediated diseases and correlation with biochemical markers.

INTRODUCTION: Patients with autoimmune diseases may suffer from hoarseness and voice disorders because of anatomical and functional alterations. OBJECTIVES: To assess the prevalence of dysphonia in rheumatic patients and its impact on their quality of life (QOL). To analyze the association of voice disorders in patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and Sjögren syndrome (SS). To determine if voice disorders during the acute phase of these diseases are correlated with specific biochemical parameters. METHODS: Present an observational and transverse analytic study of 140 patients selected from February 2009 to January 2010. The subjects (80) were diagnosed with RA (44), SLE (32), and SS (4), and the control group (60) presented no voice disorders or rheumatic diseases. Patients were evaluated using the Voice Handicap Index (VHI) and a three items outcome scale (TIOS). A biochemical and C-reactive protein study was performed on 40 patients with a disease outbreak, measuring their complement, sedimentation velocity (VSG), and anti-DNA antibodies. RESULTS: The prevalence of dysphonia among the subjects was 32-38% as opposed to 5-8% in the control group. The rheumatic patients presented an odds ratio (OR) for dysphonia of 2.82 (VHI) and 5.04 (TIOS) when compared with healthy individuals (P<0.05). We found statistically significant differences in functional, physical, occupational, and emotional subscales of these tests. No significant differences were found when studying the biochemical parameters. A higher incidence of voice disorders (OR=3.07) was associated with SLE, followed by RA (OR=2.8; 95% CI). CONCLUSIONS: Systemic immunomediated diseases may associate voice disorders. Patients with SLE are those who develop these disorders more frequently. The biochemical parameters most affected during a crisis are VSG and anti-DNA antibodies.