Trends in tuberculosis notification and mortality and factors associated with treatment outcomes in Serbia, 2005 to 2015.

BackgroundPreviously a country with medium tuberculosis (TB) burden, Serbia almost reached a low TB burden during the period 2005 to 2015.AimThe aim of this study was to analyse the trends in notification rates and treatment success rates as well as to identify predictors of treatment outcomes.MethodsWe performed a trend analysis and logistic regression analysis of 17,441 TB cases registered from 2005 to 2015 in all health facilities in Serbia, to identify predictors of treatment success, loss to follow-up and mortality.ResultsFrom 2005 to 2015, TB notification rate and mortality in Serbia decreased but treatment success remained below the global target. Loss to follow-up was associated with retreatment (odds ratio (OR) = 2.38; 95% confidence interval (CI): 2.08-2.77), male sex (OR = 1.57; 95% CI: 1.39-1.79), age younger than 65 years (OR = 1.37; 95% CI: 1.20-1.51), lower education level (OR = 2.57; 95% CI: 1.74-3.80) and pulmonary TB (OR = 1.28; 95% CI: 1.06-1.56). Deaths were more frequent in retreatment cases (OR = 1.39; 95% CI: 1.12-1.61), male patients (OR = 1.34; 95% CI: 1.19-1.52), those 65 years and older (OR = 4.34; 95% CI: 4.00-5.00), those with lower education level (OR = 1.63; 95% CI: 1.14-2.33) and pulmonary TB (OR = 2.24; 95% CI: 1.78-2.83).ConclusionsSpecial interventions should be implemented to address groups at risk of poor treatment outcome.

HIV prevalence, knowledge and self-perceived risk of HIV infection among tuberculosis patients in Serbia.

OBJECTIVE: The aim of the study was to estimate the seroprevalence of HIV infection among TB patients, knowledge, self-perceived risks and testing practices related to HIV. METHODS: We performed cross-sectional study from 10 May to 15 July 2011. Cluster sampling method was used to select 27 hospitals where 289 TB patients were consecutively recruited. Descriptive statistics and multivariable logistic regression methods were used to identify the factors associated with correct comprehensive knowledge of HIV/AIDS. RESULTS: HIV prevalence among TB patients was 0.3%. Only 25.2% of the respondents presented comprehensive correct knowledge of HIV/AIDS. The percentage of correct answers to all questions related to knowledge about HIV/AIDS increases with educational status (χ2 = 5.42; p < 0.05) and decreases with the age of respondents (χ2 = 8.53; p > 0.05). The independent predictors of correct comprehensive knowledge were living without partner (OR = 4.45; CI = 1.59-12.95) and self-awareness of HIV risk (OR = 4.43; CI = 1.20-16.52). CONCLUSION: HIV prevalence among TB patients is higher than among general population in Serbia. The level of comprehensive correct knowledge of HIV/AIDS is low. There is a need for continuous implementation of public health strategy to successfully manage HIV and HIV/TB co-infection in Serbia.

ASSESSMENT OF THE ROLE OF PRIMARY HEALTH CARE IN TUBERCULOSIS CONTROL IN SERBIA.

INTRODUCTION: At the onset of the 21st century, tuberculosis is still a public health problem. Due to the implementation of tuberculosis control program in Serbia, there is no fear of an epidemic. Within the reform of the health care system, the service for pulmonary diseases is being restructured, calling for strengthening the role of primary health care. This study was aimed at analyzing the current role of primary health care in tuberculosis control. MATERIAL AND METHODS: A cross-sectional study was conducted between the 12th and 30th September, 2010. For evaluating the current role of primary health care in tuberculosis control, four questionnaires were designed based on the "Performance assessment questionnaire regarding TB control for use in PHC", Journal Brasileiro de Pneumologia, print version ISSN 1806-3713 (vol. 35, no 6, Sao Paulo, June 2009). The following methods were used to analyze the results: descriptive statistical analysis, Student's T-test, Fisher's analysis of variance. The reliability of the results was tested with Cronbach's alpha and factor analysis. The level of significance in all the methods bordered 0.05. RESULTS: Primary health care does not participate in tuberculosis control in line with the possibilities of the existing legal framework. Although the paper proves that tuberculosis notification rate is higher in the areas less covered by the pneumophysiological service, the role of primary health care does not differ from the areas fully covered. CONCLUSION: There is a need for strategic empowerment of the primary health care system to be actively involved in the diagnostics. treatment and follow up of tuberculosis in Serbia.

Relation of functional characteristics and serum alpha-1-antitrypsin (AAT) concentration in patients with PiMM phenotype and chronic obstructive pulmonary disease (COPD).

INTRODUCTION: The relation of AAT phenotype and COPD still raises lots of controversy. In this study we aimed to investigate relation lung function characteristics, AAT serum level and COPD in smoking and non smoking population. PATIENTS AND METHODS: This was a prospective non-randomized study in which we evaluated 45 patients with severe (stage IV) COPD. In all patients we determined AAT phenotype, serum AAT levels and lung function tests. We correlated findings in relation to the smoking status. RESULTS: All patients were MM type homozygotes. Serum AAT concentrations were within the reference values, amounting to 1.66g/l in smokers and 1.80g/l in nonsmokers. There was no significant correlation between serum AAT concentrations and lung function parameters. We have observed the higher mean values of ITGV, RV, TLC and RV/TLC in smokers and a statistically significant difference only in ITGV. CONCLUSION: All of the investigated patients with severe COPD were MM type homozygotes with normal plasma level of AAT. There was no significant correlation between the phenotype and severity of COPD. We did not find significant relation of plasma AAT level and lung function impairment.

The Serbian version of the Epworth Sleepiness Scale.

PURPOSE: The Epworth Sleepiness Scale (ESS) is extensively used for evaluating daytime sleepiness in patients with sleep apnea-hypopnea syndrome (SAHS). The aim of this study was to translate and validate the ESS in the Serbian language. METHODS: The Serbian version of the ESS (ESSs) was administered to 112 patients with symptoms of sleep disorder breathing referred to Sleep Center of the Institute for Pulmonary Diseases of Vojvodina, Sremska Kamenica, Serbia and 111 healthy controls. Test-retest reliability was tested in 19 healthy subjects. RESULTS: Patients referred to the Sleep center had significantly higher ESS scores compared to controls (9 vs. 4, p < 0.001). The difference was also present for each item separately, excluding item 5. The ESSs scores were significantly higher in patients with severe (median, 13.5; interquartile range (IQR), 10.3-17.8) compared to moderate (median, 9; IQR, 7.3-9.5; p = 0.005) and mild SAHS (median, 8; IQR, 5.5-9.7; p < 0.001). Item analysis demonstrated good internal consistency of the scale (Cronbach's alpha 0.88 in patients and 0.72 in healthy controls). Test-retest Spearman's correlation coefficient was 0.68 (p = 0.001). CONCLUSION: The Serbian version of the ESS demonstrated good internal consistency and test-retest reliability. The ESSs could be used for both clinical practice and research in Serbian population.

[Immunological assays in the diagnosis of tuberculosis infection at the beginning of 21st century].

A subject infected by tubercle bacilli may immediately develop the disease (primary tuberculosis), witch occurs in a few number of infected persons, or may overcome the primary infection (a latent carrier of the infection). Nowadays there are about two milliard people with a latent tubercular infection. About 10% of them will develop active tuberculosis during their lifetime. Detection of latent tuberculosis and its treatment decreases the risk of developing the active form of the disease. Until recently, the tuberculin test was a single screening method to identify the subjects with tubercular infection. In recent years, some novel in vitro tests to diagnose the tubercular infection have been designed. These tests measure the cell-mediated immune response quantifying the emission of interferon gamma by T cells in response to stimulation by Mycobacterium tuberculosis specific antigens. These tests are more sensitive and specific than the tuberculin skin test, but they are just an accessory tool, i.e., a link in the diagnostic chain of the tubercular infection.

Autofluorescence videobronchoscopy (AFI) for the assessment of tumor extension in lung cancer.

The major objective of our study was to determine the specificity and sensitivity of AFI videobronchoscopy vs. white light videobronchoscopy, in the assessment of lung cancer extent. Secondary objective was to investigate whether or not AFI can reveal greater extension of the tumor, and can it influence therapy making decision. Autofluorescence videobronchoscopy systems are new technology for visualization of bronchial mucosa, and the proper indications for such systems will be determined in the near future. In this prospective trial we have enrolled 27 patients with suspected lung cancer in whom we performed 108 diagnostic biopsies and 54 control biopsies. All patients underwent WL videobronchoscopy followed by Auto Fluorescence Imaging (AFI) examination of tracheobronchial tree. We were using videobronchoscope BF-F260 and EVIS LUCERA SPECTRUM processor unit. Overall specificity for AFI in the diagnostics of lung cancer was found to be 85%, sensitivity was 90%, positive predictive value (PPV) 78%, and negative predictive value (NPV) 94%. Specificity, sensitivity, PPV, and NPV for WL videobronchoscopy in lung cancer diagnostics were 54%, 64%, 51%, and 69%, respectively. Relative sensitivity ratio of AFI over WL videobronchoscopy, which is calculated to be 1.41, confirmed superiority of AFI in lung cancer diagnostics. We confirmed significant correlation between the greater extension of the tumor (assessed with AFI) and the therapeutical decision in lung cancer treatment (p = 0.01). Influence of AFI on therapeutical decision was significant (p = 0.034). AFI videobronchoscopy system yields significantly higher sensitivity and specificity for the assessment of lung cancer extent than WLB videobronchoscopy alone. It had shown to be able to influence therapeutic option for lung cancer treatment. Further studies are needed to evaluate and validate these results.

Autoantibodies in patients treated for active pulmonary tuberculosis.

The genesis of auto-immune antibodies directed against the own tissue antigens of a host may be due to the host's immune response to mycobacteria. The prospective study included 110 patients treated for active pulmonary tuberculosis and the control group of 60 healthy subjects, volontary blood donors. Applying the method of indirect immnunofluorescence and cryostat sections of rat organs and human larynx cancer epithelial cell line (HEp-2 cells), the prescence of the following autoantibodies in the serum of the examined patients was examined: anti,nclear (ANA), anticardiac (ACA), antimitochondrial (AMA), antiparietal (APA), anti smooth muscular (ASMA), antithyroidal (ATA), rheumnatoid factor (RF). These autoantibodies were determined in the course oftreatment and five years later. Low levels of some examined autoantibodies were detected in the serum of a number of the examined patients. No significant difference in the presence of the analysed antibodies was registered between the sexes. In the course of the treatment a reversible hyper-gammaglobulinemia developed, which was at least partially due to the presence of autoantibodies in the patients blood serum. Besides possibly involved mechanisms of molecular mimicry and polyclonal lymphocyte activation, the presence of antinuclear antibodies in the patient's serum is at least partially due to isoniazide treatment. The finding of other autoantibodies is nonspecific and not related to the mycobacterial infection or antituberculosis drug administration.

Differential diagnosis of tuberculous and malignant pleural effusions: what is the role of adenosine deaminase?

The objective of this study was to evaluate the utility of invasive and noninvasive diagnostic procedures in tuberculous pleurisy (TPE) in an area with intermediate incidence of tuberculosis. The aim was to determine the cutoff value for adenosine deaminase (ADA) and the sensitivity and specificity of ADA and evaluate pleural fluid cytology and pleural biopsy in the differential diagnosis of malignant and tuberculous pleurisy. The study included 121 patients. TPE was confirmed in 54 patients and malignant effusion in 67 patients. Criteria used for TPE diagnosis were positive cultures of effusion or biopsy specimen, tuberculous granulomas, or positive sputum cultures without other explanation for pleural effusion. Malignancy was diagnosed by either cytology or biopsy. The cutoff value of ADA in TPE was 49 U/L, sensitivity was 89.2%, specificity was 70.4%, positive predictive value (PPV) was 84.4%, and negative predictive value (NPV) was 78.4%. ADA activity below 16 U/L suggests that TPE is highly unlikely with sensitivity=38.5%, specificity=100%, PPV=100%, and NPV=57.4%. ADA effusion/serum ratio reached a cutoff in TPE of 1.7 (sensitivity=84.6%, specificity=72.2%, PPV=81.4%, NPV=71.4%). Sensitivity, specificity, PPV, and NPV of cytology evaluation for TPE are 72.2%, 70.1%, 66.1%, and 75.8%, respectively. Pleuroscopy-guided pleural biopsy had sensitivity=66.7%, specificity=100%, PPV=100%, and NPV=78.8%. In 27.8% of TPE cases, pleural fluid cultures were positive. There is no doubt that pleuroscopy-guided biopsy is of great value for TPE diagnosis; however, sensitivity and specificity of noninvasive tests, especially ADA, can help to distinguish between TB and malignancy.

[The role of physical rehabilitation in the treatment of exudative pleurisy]. / Uloga fizikalnog tretmana u lecenju eksudativnog pleuritisa.

INTRODUCTION: Exudates are due to a variety of diseases, the major and most common ones being tuberculosis, nonspecific inflammation and malignancy. They are usually treated conservatively, sometimes combined with surgery and physical treatment. Physical therapy includes positional exercises, breathing exercises and biostimulation. AIM OF THE STUDY: The study was aimed to find out the following: 1) Is lung function improved by physical therapy; 2) Can adhesions be diminished and mobility of the affected hemidiaphragm improved by physical treatment; 3) Is there a direct positive correlation between physical treatment and obtained improvement, or the same can be achieved in patients receiving medicamentous treatment only; 4) What are the effects of some factors we cannot influence (sex, age, effusion level, position of adhesions) on lung function and diaphragm mobility improvement, that is on the efficiency of physical treatment; 5) How do the factors we can influence (the time interval before initiating the treatment and its duration) affect improvement of the same lung function parameters, that is treatment efficacy? MATERIAL AND METHODS: Physical treatment of patients with exudative pleurisy was accomplished at the Department of Rehabilitation in our Institute and it consisted of directed breathing exercises and laser biostimulation. Its effects were examined in a group of 175 patients, who received both conservative and physical treatment, and results were compared with the control group patients, treated only conservatively (with antibiotics, antituberculotics, corticosteroids). RESULTS: Comparative analysis confirmed a significant improvement of lung function parameters (VC, FEV1, PEF) as well as of hemidiaphragm mobility on the affected side of the thorax in favour of the examined group. The severity of the lung function and diaphragm mobility impairments have been found to be in correlation with the localization of adhesions, whereas the degree of improvement correlated with the time interval before the treatment initiation, as well as with its duration. DISCUSSION AND CONCLUSION: The applied physical therapy resulted in: 1) significant improvement of all examined lung function parameters in the examined group, which was not registered in the control group; 2) significant improvement of the diaphragm mobility in general; 3) factors such as sex, age and effusion level have no effects on the physical treatment results; 4) treatment results are affected by the time interval passed before the treatment initiation and its duration, as well as the localization of adhesions; anterior adhesions affected lung function and diaphragm mobility least, posterior ones more, while the influence of lateral adhesions was most significant. It is finally concluded that physical treatment should necessarily be included in the treatment of exudative pleurisy.

[Laser biostimulation in the treatment of pleurisy]. / Laserska biostimulacija u lecenju pleuritisa.

INTRODUCTION: Low-intensity lasers have been utilized in medicine in two ways: for local stimulation and for stimulation of acupuncture points. Literature data reveal that this method has been indiscriminately applied in psychiatry, rheumatology, gynecology, dermatology, otorhinolaryngology, in diverse acute and chronic pains, inflammations, vascular disorders, angina pectoris, bronchial asthma. Most commonly reported clinical effects are analgesia, spasmolytic and anti-inflammatory effects, as well as faster wound and bone healing. MATERIAL AND METHODS: This prospective study analyses effects of laser biostimulation on patients with pleurisy. The analysis included 25 patients treated at the Institute of Lung Diseases in Sremska Kamenica during 2000, 2001 and 2002. Apart from conservative treatment, these patients were treated with laser biostimulation of acupuncture points and local region for ten days. During treatment, changes of present clinical signs, general symptoms, radiological findings, as well as changes of some relevant biochemical parameters were recorded. RESULTS: Results were compared with the control group which included the same number of patients, who differed from the examined group only by not being exposed to laser biostimulation. The examined group of patients with pleuritis presented with quicker resorption of pleural effusion, less pleural adhesions, more significant decrease of clinical symptoms, especially pain, as well as more significant increase of cortisol and immunoglobulin A and decrease of circulating immune complexes (CIC), leukocytes and sedimentation rate than the control group. DISCUSSION: Mechanisms of laser biostimulation in treatment of pleurisy were described in detail and the obtained results were correlated to those reported by other authors. CONCLUSION: 1. Patients with pleurisy undergoing laser stimulation presented with faster resorption of effusion and remission of the subjective symptoms, as well as significant decrease of biochemical acute inflammation parameters in the peripheral blood and therefore with faster recovery. 2. In patients with pleurisy laser treatment increases regenerative mechanisms of the pleural surface, thus decreasing the quantity of formed adhesions and resulting in better mobility of the diaphragm.

[Low power laser biostimulation in the treatment of bronchial asthma]. / Biostimulacija laserom niske snage u lecenju bronhijalne astme.

INTRODUCTION: Modern concept of acupuncture is based on the fact there are designated locations on the surface of human body, which are related to integrative systems of an organism by means of sensory nerves, correlating and synchronizing organ functioning, depending on external and internal conditions, by means of nervous and neurohumoral regulation of metabolic and regenerative processes, including also mobilisation of immunological, protective and antistress reactions. Apart from standard needle acupuncture, other methods of stimulating acupuncture points are also applied. Due to invention of low power lasers, irradiation laser acupuncture has been introduced into routine medical practice, characterised by painless and aseptic technique and outstanding clinical results. MATERIAL AND METHODS: The investigation was aimed at defining therapeutic effects of low power laser irradiation by stimulating acupuncture points or local treatment of asthma. A prospective analysis included 50 patients treated at the Institute of Pulmonary Diseases in Sremska Kamenica during 2000, 2001 and 2002. Together with conservative treatment of present disease, these patients were treated with laser stimulation of acupuncture points in duration of ten days. During treatment changes of functional respiratory parameters were recorded. Results were compared with those in the control group. The control group consisted of the same number of patients and differed from the examination group only by not using laser stimulation. RESULTS: Patients with bronchial asthma presented with significant improvement (p < 0000,5) of all estimated lung function parameters just 30 minutes after laser stimulation. Improvements achieved on the third and the tenth day of treatment were significantly higher (p < 0.001 to p < 0.00005) in the examination group in comparison with the control group. Further investigation confirmed that improvement of measured lung function parameters was significantly higher in younger patients, in patients whose disease lasted shorter, as well as in women. Patients with asthma, who were treated every three months for a one year period, presented with significantly lower frequency and intensity of attacks. DISCUSSION: The mechanism of laser stimulation activity in treatment of bronchial asthma is explained in detail, correlating our results to those obtained by other authors. CONCLUSIONS: A ten-day course of low-power laser stimulation of acupuncture points in patients with bronchial asthma improves both the lung function and gas exchange parameters. Positive effects of laser treatment in patients with bronchial asthma are achieved in a short time and they last long, for several weeks, even months. Successive laser stimulation in asthmatics prolongs periods of remission and decreases the severity of asthmatic attacks. Better positive effects of laser stimulation are achieved in younger asthmatics, in those with shorter disease history and in female patients. There is a negative correlation between effects of laser stimulation and patients' age and disease history. However, these characteristics do not affect response rate and speed but positive laser stimulation effects are achieved in a shorter period in female asthmatics.