Surveillance of adverse events in the treatment of drug-resistant tuberculosis: A global feasibility study.

The World Health Organization launched a global initiative, known as aDSM (active TB drug safety monitoring and management) to better describe the safety profile of new treatment regimens for drug-resistant tuberculosis (TB) in real-world settings. However, comprehensive surveillance is difficult to implement in several countries. The aim of the aDSM project is to demonstrate the feasibility of implementing national aDSM registers and to describe the type and the frequency of adverse events (AEs) associated with exposure to the new anti-TB drugs. Following a pilot study carried out in 2016, official involvement of TB reference centres/countries into the project was sought and cases treated with bedaquiline- and/or delamanid-containing regimens were consecutively recruited. AEs were prospectively collected ensuring potential attribution of the AE to a specific drug based on its known safety profile. A total of 309 cases were fully reported from 41 centres in 27 countries (65% males; 268 treated with bedaquiline, 20 with delamanid, and 21 with both drugs) out of an estimated 781 cases the participating countries had committed to report by the first quarter of 2019.

Tuberculosis in the Prisons in the Republic of Macedonia, 2008-2017.

BACKGROUND: Tuberculosis (TB) is a major health problem in penitentiary institutions (prisons), and its prevalence was reported to be multiple times higher compared to that of the general population. Conditions such as overcrowding, malnutrition and limited access to medical care which often exist in prisons increase the risk of reactivation, transmission and poor prognosis of tuberculosis disease among inmates. AIM: The main objective of this study was to present the epidemiological situation of TB in the prisons from 2008 till 2017 in the Republic of Macedonia (RM). PATIENTS AND METHODS: There are 13 different penitentiary institutions in the RM with a total capacity to house 2600 prisons inmates. Management of TB in the prisons is part of the National TB program in RM, and the Institute for Lung Diseases and Tuberculosis in Skopje is in charge of it. All prisoners with TB in the RM are registered in the Central Register for TB within this Institute. We use the data from the Central Register, and with the method of description, we present the epidemiological data and clinical characteristics of the prisoners about TB in prisons in RM for 10 years' period. RESULTS: From 2008 till 2017 there were 58 TB cases registered in prisons in total. The absolute number of TB cases in the prisons is not big, but the incidence rate is higher than 100/100,000 population, or several times bigger than in the general population (except in 2012 and 2016). In 2017 there were 10 TB cases registered in the prisons with an incidence rate of 323.9/100,000 population which is many times higher than in the general population in RM. The majority of inmates with TB were young men with risk factors for TB infection or TB disease before incarceration such as drug abuse, alcohol, smoking, but there was no association with HIV infection. The most of the patients diagnosed in prison were new cases (54), secondary TB due to reactivation from the latent TB infection or secondary TB due to the environment. From 2008-2017 there were 82.75% successfully treated TB cases in the prisons, and there were no cases of multi-drug resistant tuberculosis (MDR-TB). CONCLUSION: The results from our study showed that the TB control in the prisons in RM is good with satisfactory treatment outcome. On the other hand, the high incidence rate showed that the prisons in RM provide conditions for TB transmission and with other additional risk factors present place for high TB prevalence. The study findings can be used for planning more effective TB control interventions for the prison population in RM.

Evaluation of the Directly Observed Treatment's Acceptance by Tuberculosis Patients in the Republic of Macedonia.

BACKGROUND: Directly observed therapy (DOT) is a specific strategy endorsed by the World Health Organization in 1994 to improve adherence by requiring health workers, community volunteers or family members to observe and record tuberculosis (TB) patients for taking each dose. The implementation of DOT strategy in the National Tuberculosis Programme (NTP) in Macedonia was introduced in 2006 and was realised by 6 nurses engaged through the Project of Global Fund against HIV/AID and TB. AIM: This study aimed to evaluate how these visits conducted by the DOT nurses engaged through the GF were accepted by TB patients and to evaluate the impact on the treatment outcomes. PATIENTS AND METHODS: In this prospective study 105 TB patients who started treatment in 2016 and who were supposed to be visited by DOT nurses at their homes were included. All of these patients filled out a questionnaire compiled of 6 questions related to their opinion about the efficacy and usefulness of the visits managed by the nurses when they would come for check-ups at the Institute for Lung Diseases and Tuberculosis. The assessment of the efficacy of the work of DOT nurses was performed by analysis of the answers received by TB patients. The data were analysed with the method of description and was statistically prepared in the program SPSS for Windows, 17.0. RESULTS: The results from the analyses showed that the number of visited patients were not satisfied, because 29.52%% were never visited by a DOT nurse at their homes. A lot of patients (61.91%) were not willing to take medicines under the observed control by nurses. Those TB patients who were visited by DOT nurses thought that this type of visit is useful for them: they were satisfied by the attitude of the nurses during the visits, and they received enough explanations regarding TB. CONCLUSION: We can conclude that the DOT visits to TB patients are useful, contribute patients to complete the therapeutic regime without interruption, take care for every individual patient effectively, and protect the rest of society by preventing the development and spread of TB, including drug-resistant strains.

Practical Approach to Lung Health - Experience from the Republic of Macedonia.

BACKGROUND: Among the adults and children aged 5 yrs who attend PHC settings, 20-30% seeks to care for respiratory symptoms. Over 80-90% of the respiratory patients suffer from acute respiratory infections (ARI), followed by chronic obstructive pulmonary diseases (COPD), asthma, and less frequently with pneumonia and tuberculosis (TB). To improve the quality of care in patients who seek assistance for respiratory symptoms in PHC settings and the efficiency of respiratory service delivery within healthcare systems, WHO has designated several initiatives among which one is PAL (Practical Approach to Lung Health). PAL is an integrated and symptom-based approach focused on all priority respiratory illnesses encountered in PHC, including TB. Its patient-centred syndromic approach aims to improve the quality of diagnosis and treatment of respiratory illnesses in a PHC setting. AIM: To evaluate the short-term impact of PAL approach in improving the management of patients with the most frequent respiratory diseases by the GPs from PHC settings in the Republic of Macedonia. MATERIAL AND METHODS: A total of 588 GPs were educated for the most frequent respiratory diseases during the PAL training from 2013-2016. To evaluate the efficiency of GPs education from PHC settings, GPs fill in a form out of 69 questions for the patients enrolled before (baseline survey) and after PAL training (impact survey), and the results of the two surveys were compared. This analysis aimed to assess if the theoretical and practical skills obtained during the PAL training have been used in the routine practice of the GPs who attended the training and to what degree. RESULTS: Our results showed that in the impact study more patients with ARI (P < 0.000001) and more patients with COPD exacerbations were treated in the PHC settings (P < 0.000008). More patients suspected of asthma were referred to upper health level for diagnosis (P < 0.037). The comparison of the findings between the baseline and impact surveys suggest that training on PAL had an impact in decreasing drug prescription through a reduction in a prescription for antibiotics for ARI, COPD and asthma. Our study indicates that training on PAL is likely to increase the prescription of inhaled corticosteroids and tends to decrease the prescription of other formulation of these drugs (P < 0.0000001). The impact surveys showed that the patients with COPD and pneumonia in the PHC settings were better managed due to the more frequent use of CAT questionnaires and CURB test. And regarding TB cases, our study indicates that the GPs were more aware of this disease and were more willing to take part in the patient treatment follow-up (P < 0.000001). CONCLUSION: The results from this study showed that implementation of PAL approach for GPs from the PHC setting in our country have positive results (effect) in the management of patients with respiratory symptoms: it is likely to reduce prescribing for antibiotics, to increase the use of inhalation medication which is highly recommended in the management of asthma and COPD, and to decrease the referral of patients with chronic diseases to the upper health level. However, more experience is needed for long-term influence on the effects over the cost-effectiveness of respiratory care services and on strengthening the health care system.

Latent Tuberculosis Infection - Diagnosis and Treatment.

INTRODUCTION: Latent tuberculosis infection (LTBI) is defined as a state of persistent immune response to stimulation by Mycobacterium tuberculosis antigens without evidence of clinically manifested active tuberculosis (TB). Diagnosis and treatment for LTBI are important for TB, especially in high-risk populations. Tuberculin skin test (TST) and interferon-gamma release assays (IGRAs) are used to diagnose LTBI. AIM: The study aims to present the first results with IGRA test compared with TST in the screening of LTBI and the treatment results in the cases with LTBI in Macedonia. MATERIAL AND METHODS: In this study 73 cases diagnosed and treated with LTBI in 2016 were included. For diagnosis of LTBI, we used TST RT -23 5T.U. and commercial IGRA test such as QuantiFERON-TB Gold In-Tube (QFT-IT). RESULTS: Out of 73 cases with LTBI, 61.64% were men, and 38.36% were women. Among all age groups, the most frequent were cases between 5 and 14 years old (54.79%). Among the evaluated risk groups for LTBI, the most frequent were children household contacts with pulmonary TB cases (61-83.65%), followed by people living with HIV (9-12.33%) and only 3 cases with other medical reasons. Positive TST had 34 cases (46.57%) and positive IGRA test 25 cases (34.25%). Regarding the treatment regimes, we use two regimes: 50 cases (68.44%) received 6 months daily regime with Isoniazid, and 23 cases (31.51%) received 3 months daily regime with Isoniazid and Rifampicin. Treatment outcomes showed that the most patients completed treatment regimes: 55 (75.34%) and only 10 (13.09%) interrupted the treatment. CONCLUSION: Despite the progress made in the last few years, several challenges remain to be addressed for better management of LTBI which will contribute to strength TB control in the country.

Bcl-2 as a prognostic factor for survival in small-cell lung cancer.

BACKGROUND: The expression of Bcl-2 oncoprotein is associated with inhibition of apoptosis and prolonged cell survival. The purpose of this study was to investigate Bcl-2 protein expression in patients with small-cell lung cancer (SCLC) in order to see if it was related to clinicopathological features and to prognosis. MATERIALS AND METHODS: Forty patients with SCLC were stained immunohistochemically using specific monoclonal antibody (DAKO-Bcl-2, 124). Bcl-2 positivity was determined as detection of the oncoprotein in greater than 10% of neoplastic cells. RESULTS: Immunopositivity was present in 26 (60%) of SCLC patients. Twenty-three of 40 (57.5%) patients had limited disease at presentation, and 17 of 40 (42.5%) had extensive disease. There was not any correlation with Bcl-2 protein expression and clinicopathological parameters such as sex, age, smoking history and performance status. According to the extent of the disease, Bcl-2 expression was significantly higher in patients with extensive disease (p < 0.009). Bcl-2 expression was associated with significant shorter survival in patients with SCLC (Log Rank = -5.26; p = 0.00001). Cox regression analysis controlling for age, sex and tumor stage, confirmed that Bcl-2 expression (HR = 0.049 p < 0.0001) and N stage (HR = 0.152 p < 0.012) were an independent prognostic markers for poor prognosis. In CONCLUSION Bcl-2 oncoprotein was expressed in most cases of SCLC and its expression may have prognostic importance.