Objective: To evaluate the use of family members as supervisors of directly observed therapy (DOT) in patients with tuberculosis.Methods: This was a prospective descriptive study involving patients diagnosed with pulmonary tuberculosis. The sample comprised 98 patients. A standardized protocol was implemented in order to train the patient and their families. After the training, the patient was allowed to choose either a family member or a health care worker as a supervisor. Absolute and relative frequencies were used in descriptive data analysis. Results: A family member supervisor was chosen by 94 patients (96%). The cure rate was 99%. The partner was chosen by 49% of the patients, and other family members were chosen by 28%. The heath care team needed to take over DOT in 3% of the cases. Regular attendance at follow-up appointments was 67%. It was observed that 24% of the problems in this DOT model referred to the family supervisor forgetting to administer the medication or to the patient forgetting to take it; 39% of the patients forgot to take the medication for one day, and 31% forgot to take it for two days. There was change of supervisor in 9% of the sample, medication was lost by the patient sometime during treatment in 9%, and patient drug intolerance occurred in 8%. Conclusions: DOT supervised by a family member has proven an effective and low-cost technique. However, compliance is not due to one single factor but to the combination of strategies adopted: bus passes; educational measures and especially the individualized approach.

Keywords: Directly observed therapy; Tuberculosis; Patient compliance.

Objective: To determine treatment noncompliance rates among patients participating in a municipal tuberculosis control program and to identify the variables related to noncompliance depending on the type of treatment strategy used. Methods: A longitudinal non-concurrent cohort study was carried out involving two cohorts of patients participating in the Tuberculosis Control Program of the city of Carapicuíba, Brazil. The first cohort comprised 173 patients with tuberculosis treated from January 1, 2003 to December 31, 2003 using self administration of treatment, and the second comprised 187 patients with tuberculosis treated from July 1, 2004 to June 30, 2005 using the directly observed therapy, short-course strategy. Results: Noncompliance rates decreased from 13.3% (self administration of treatment) to 5.9% (directly observed therapy, short-course), a significant difference (p < 0.05). For the self administration of treatment strategy, the variables significantly associated with treatment noncompliance were as follows: being an unregistered worker (relative risk [RR] = 3.06); retreatment (RR = 2.73); alcoholism (RR = 3.10); and no investigation of contacts (RR = 8.94). For the directly observed therapy, short-course strategy, no variables were significantly associated with noncompliance. Conclusion: The directly observed therapy, short-course strategy decreased noncompliance rates and produced better treatment outcomes, even when the risk factors for noncompliance were the same.

Keywords: Tuberculosis; Self administration; Directly observed therapy; Treatment refusal.

Objective: To determine the compliance with tuberculosis treatment among patients enrolled the tuberculosis control program in the city of Carapicuíba, Brazil, before and after the implementation of the directly observed treatment, short-course (DOTS) strategy. Methods: A retrospective historical cohort study of operational aspects based on records of attendance and treatment evolution of patients in self-administered treatment (SAT) and of those submitted to DOTS. Monthly treatment outcome tables were created, and the probability of compliance with the treatment was calculated for both groups of patients. Results: A total of 360 patients with tuberculosis met the inclusion criteria: 173 (48.1%) in the SAT group; and 187 (51.9%) in the DOTS group. Treatment compliance was 6.1% higher in the DOTS group than in the SAT group. The proportion of patients completing the six months of treatment was 91.6% and 85.5% in the DOTS group and in the SAT group, respectively. Conclusions: The results of this study show that DOTS can be successfully implemented at primary health care clinics. In this population of patients, residents of a city with low incomes and a high burden of tuberculosis infection, DOTS was more effective than was SAT.

Keywords: Tuberculosis; Mycobacterium tuberculosis; Treatment outcome; Medication adherence.

Objective: The demanding nature and psychosocial burdens of directly observed treatment (DOT) have opened a path to alternative strategies such as video-observed therapy (VOT), which offers comparable treatment outcomes and patient satisfaction while potentially saving time and reducing costs. The objective of this study was to evaluate the perceptions and experiences of patients and health care professionals regarding DOT and other treatment strategies implemented in Portugal. Methods: Patients with a confirmed diagnosis of tuberculosis, treated at the Vila Nova de Gaia Outpatient Tuberculosis Centre in the last two years, were asked to complete a brief questionnaire, as were health care professionals working in the northern region of Portugal. Differences were analysed with chi-square tests, complemented by thematic analysis. Results: A total of 62 individuals completed the questionnaire: 29 health care professionals and 33 patients. There were significant differences between the two groups in their views regarding the impact of DOT on treatment outcomes, with health care professionals perceiving a higher degree of negative effects and patients expressing greater satisfaction. Long travel distances, transportation issues and high costs were some of the challenges mentioned by the patients. Significant differences were also found regarding the role DOT plays in ensuring treatment adherence, with patients emphasising personal responsibility and its importance in preventing loss to follow-up and strengthening relationships with health care professionals. Dose dispensing was favoured for its convenience in specific situations, and VOT was generally preferred to reduce constant travelling. Both parties raised some concerns. Conclusions: Existing discrepancies suggest a misalignment between patient experiences and health care provider perceptions, underscoring the need for enhanced communication and a more nuanced understanding of patient perspectives when designing and implementing different tuberculosis treatment adherence strategies.

Keywords: Treatment adherence and compliance; Directly observed therapy; Patient satisfaction; Tuberculosis.

Objective: To describe treatment outcomes (cure, noncompliance or death) after the implementation of the Directly Observed Treatment, Short-course (DOTS) strategy for tuberculosis control in the city of São José do Rio Preto, Brazil, between 1998 and 2003. Methods: A descriptive study, based on secondary data (National Case Registry database, Tuberculosis Epidemiology database, and the 'Black Book' Registry), was conducted using a specific instrument. The data were analyzed using descriptive statistics. Results: After the implementation of the DOTS strategy, there was a decrease in noncompliance and case detection rates as well as an increase in cure and death rates. The increase in the number of tuberculosis-related deaths might be attributable to three factors: the predominance of the disease in individuals over 50 years of age, tuberculosis/HIV co-infection, and the presence of accompanying diseases. Conclusion: The implementation of the DOTS strategy strengthened the decentralization of the tuberculosis control plans as well as the integration of the Basic Health Care Clinic teams with the Tuberculosis Control Program team. Political commitment of the administrator to tuberculosis control, in conjunction with the policy of benefits and incentives, is essential for the sustainability of the DOTS strategy.

Keywords: Tuberculosis; Epidemiology; Health services; Politics; Directly observed therapy.

Objective: To describe the epidemiological profile of tuberculosis cases reported among health care workers in the Tuberculosis Control Program of the Cassiano Antonio of Moraes University Hospital in Vitoria, Brazil. Methods: A retrospective descriptive study of secondary data was conducted between 2002 and 2006. Results: Twenty-five cases of health care workers with tuberculosis were reported: 8 in nursing technicians (32%); 4 in doctors (16%); 3 in nurses (12%); 2 in radiology technicians (8%) and 8 in professionals from other categories (32%). Of those 25 health care workers, 14 (56%) were male and 11 (44%) were female. The incidence of the disease was highest among those from 35 to 39 years of age. The predominant clinical presentation was extrapulmonary (12 cases, 48%), followed by pulmonary (11 cases, 44%) and a combination of the two (2 cases, 8%). Regarding comorbidities, AIDS, alcoholism and smoking, respectively, were present in 33.3% of the study population. Outcomes were as follows: 22 cases of cure (88%); 2 transfers (8%); and 1 death (4%). The proportion of health care workers diagnosed with tuberculosis in the period studied was 2.53%. Conclusions: The results show the need for heath care workers who work in the tuberculosis control program to fill out the field "professional occupation" on the tuberculosis case registry database reporting forms. In addition, this situation draws attention to the need to implement an occupational tuberculosis control program.

Keywords: Health profile; Tuberculosis/epidemiology; Health personnel; Prevalence.

Objective: To describe the factors associated with nonadherence to TB chemoprophylaxis in patients older than 15 years of age treated via referral TB control programs. Methods: A historical cohort study was carried out based on medical charts related to cases treated via referral TB control programs in the city of Vitória, Brazil, between 2002 and 2007. Cases of infection with Mycobacterium tuberculosis were stratified into two groups: health care workers (HCW group); and individuals who were not health care workers (NHCW group). Results: A total of 395 patients were included in the study: 35 in the HCW group and 360 in the NHCW group. The mean age in the HCW and NHCW groups was 34.8 and 32.4 years, respectively (p = 0.36). Of the 35 patients in the HCW group, 29 (82.9%) were female, compared with 180 (50.0%) of the 360 patients in the NHCW group. In the HCW and NHCW groups, respectively, 15 (42.9%) and 169 (46.9%) of the patients were contacts of TB cases. In addition, 9 (25.7%) and 157 (78.5%) the HCW and NHCW group patients, respectively, were HIV-infected. Nonadherence to chemoprophylaxis was 37.1% and 21.9% in the HCW and NHCW groups, respectively (p = 0.045). In the multivariate analysis, the factors associated with nonadherence were being a health care worker (OR = 8.60; 95% CI: 2.09-35.41), being HIV-infected (OR = 4.57; 95% CI: 1.2-17.5) and having had contact with a TB patient (OR = 2.65; 95% CI: 1.15-6.12). Conclusions: In order to improve adherence to TB chemoprophylaxis, new TB control program strategies are needed, especially for health care workers and HIV-infected patients.

Keywords: Tuberculosis; Chemoprevention; Isoniazid.

Objective: To compare clinical, radiological and laboratory aspects of household contacts, aged 15 or younger, of patients presenting a positive culture for Mycobacterium tuberculosis. Methods: This was a cohort study comparing children and adolescents (≤ 15 years of age) who were household contacts of TB cases presenting positive sputum smear and positive culture results (exposed group, n = 100) or negative sputum smear and positive culture results (unexposed group, n = 55). All of the contacts were evaluated via the TB control program of a university hospital in the city of Vitória, Brazil, between July of 2003 and December of 2006. Results: Of the 155 minors evaluated, 87 (56.1%) were female and 68 (43.9%) were male. Of those 155, 28 (18%) were aged 5 or younger, 62 (40%) were aged 5-9, and 65 (42%) were aged 10-15. Symptoms of the disease were found in 17 (17%) of the 100 contacts in the exposed group and in 9 (16%) of the 55 in the unexposed group (p = 0.86). Chest X-rays showed alterations in 20 (21%) and 2 (4%) of the contacts in the exposed and unexposed groups, respectively (RR = 6.9; p = 0.004). In the exposed and unexposed groups, respectively, 35 (38%) and 10 (18%) of the contacts presented positive results on the tuberculin skin test (RR = 2.8; p = 0.01). Of the 100 contacts in the exposed group, 5 (5%) were diagnosed with TB, which was not diagnosed in any of those in the unexposed group (p = 0.08). Conclusions: Although no significant difference was found between the two groups regarding the incidence of TB, it is of note that there is a greater risk of becoming infected with M. tuberculosis if the bacterial load of the index case is high.

Keywords: Tuberculosis; Mycobacterium tuberculosis; Tuberculosis, pulmonary; Child; Adolescent.

Objetivo: Descrever as taxas de cura, falência e abandono do tratamento da tuberculose com o esquema básico preconizado pelo Ministério da Saúde (tratamento com rifampicina, isoniazida, pirazinamida e etambutol por dois meses seguido de isoniazida e rifampicina por quatro meses) utilizando comprimidos em dose fixa combinada em regime autoadministrado e descrever os eventos adversos e seus possíveis impactos nos desfechos do tratamento. Métodos: Estudo descritivo utilizando dados coletados prospectivamente dos prontuários médicos de pacientes com tuberculose (idade ≥ 18 anos) tratados com o esquema básico em duas unidades básicas de saúde da região metropolitana de Goiânia, GO. Resultados: A amostra foi composta por 40 pacientes com tuberculose. A taxa de cura foi de 67,5%, a taxa de abandono foi de 17,5%, e não ocorreram casos de falência. Nessa amostra, 19 pacientes (47%) relataram reações adversas aos medicamentos. Essas foram leves e moderadas, respectivamente, em 87% e 13% dos casos. Em nenhum caso houve necessidade de mudança do esquema ou suspensão do tratamento. Conclusões: A taxa de cura do esquema básico com o uso de comprimidos em dose fixa combinada sob regime autoadministrado foi semelhante às taxas históricas do esquema anterior. A taxa de abandono, na amostra estudada, foi muito acima da taxa preconizada como adequada (até 5%).

Keywords: Tuberculose; Resultado de tratamento; Combinação de medicamentos.

Objective: To determine whether mobility therapy is associated with central or peripheral catheter-related adverse events in critically ill patients in an ICU in Brazil. Methods: A retrospective analysis of the daily medical records of patients admitted to the Clinical Emergency ICU of the University of São Paulo School of Medicine Hospital das Clínicas Central Institute between December of 2009 and April of 2011. In addition to the demographic and clinical characteristics of the patients, we collected data related to central venous catheters (CVCs), hemodialysis (HD) catheters and indwelling arterial catheters (IACs): insertion site; number of catheter days; and types of adverse events. We also characterized the mobility therapy provided. Results: Among the 275 patients evaluated, CVCs were used in 49%, HD catheters were used in 26%, and IACs were used in 29%. A total of 1,268 mobility therapy sessions were provided to patients while they had a catheter in place. Catheter-related adverse events occurred in 20 patients (a total of 22 adverse events): 32%, infection; 32%, obstruction; and 32%, accidental dislodgement. We found that mobility therapy was not significantly associated with any catheter-related adverse event, regardless of the type of catheter employed: CVC-OR = 0.8; 95% CI: 0.7-1.0; p = 0.14; HD catheter-OR = 1.04; 95% CI: 0.89-1.21; p = 0.56; or IAC-OR = 1.74; 95% CI: 0.94-3.23; p = 0.07. Conclusions: In critically ill patients, mobility therapy is not associated with the incidence of adverse events involving CVCs, HD catheters, or IACs.

Keywords: Physical therapy modalities; Intensive care units; Catheters; Early ambulation.

Objective: To develop a system for the molecular diagnosis of tuberculosis by polymerase chain reaction (PCR), constructing primers based on the difference in gene organization of the intergenic region of phospholipase C (plcB-plcC region), which differentiates Mycobacterium tuberculosis from other mycobacteria. Methods: A PCR product of the expected size (432 bp) was obtained from M. tuberculosis and M. africanum only. A total of 33 mycobacterial isolates and 273 clinical samples from patients suspected of having tuberculosis were examined. These were used in the comparative study of the PCR technique versus culture. Results: For PCR versus culture, the data showed 93.8% accuracy (p < 0.0001), 93.1% sensitivity (CI: 88.7-96.0), and 96.4% specificity (CI: 96.1-99.4). The Kappa value (0.82) shows that there was a near-perfect concordance between the two tests. Conclusion: The use of the plcB-plcC region in PCR amplification was found to be an important and reliable tool for the specific diagnosis of tuberculosis in the samples analyzed.

Keywords: Polymerase chain reaction; Diagnosis; Tuberculosis; Mycobacterium tuberculosis

Patients with obstructive lung disease often require ventilatory support via invasive or noninvasive mechanical ventilation, depending on the severity of the exacerbation. The use of inhaled bronchodilators can significantly reduce airway resistance, contributing to the improvement of respiratory mechanics and patient-ventilator synchrony. Although various studies have been published on this topic, little is known about the effectiveness of the bronchodilators routinely prescribed for patients on mechanical ventilation or about the deposition of those drugs throughout the lungs. The inhaled bronchodilators most commonly used in ICUs are beta adrenergic agonists and anticholinergics. Various factors might influence the effect of bronchodilators, including ventilation mode, position of the spacer in the circuit, tube size, formulation, drug dose, severity of the disease, and patient-ventilator synchrony. Knowledge of the pharmacological properties of bronchodilators and the appropriate techniques for their administration is fundamental to optimizing the treatment of these patients.

Keywords: Bronchial hyperreactivity; Drug delivery systems; Respiration, artificial.

Objective: To identify the determinants of tuberculosis-related variables in the various regions of Brazil and evaluate trends in those variables over the ten-year period preceding the end of the timeframe defined for the United Nations Millennium Development Goals (MDGs). Methods: This was an ecological analytical study in which we utilized eight national public databases to investigate the 716,971 new tuberculosis cases reported between 2006 and 2015. Results: Over the study period, there were slight reductions in the prevalence, incidence, and mortality associated with tuberculosis. Brazil did not reach the MDG for tuberculosis-related mortality. Among the performance indicators of tuberculosis control, there were improvements only in those related to treatment and treatment abandonment. In terms of the magnitude of tuberculosis, substantial regional differences were observed. The tuberculosis incidence rate was highest in the northern region, as were the annual mean temperature and relative air humidity. That region also had the second lowest human development index, primary health care (PHC) coverage, and number of hospitalizations for tuberculosis. The northeastern region had the highest PHC coverage, number of hospitalizations for primary care-sensitive conditions, and tuberculosis-related mortality rate. The southern region showed the smallest reductions in epidemiological indicators, together with the greatest increases in the frequency of treatment abandonment and retreatment. The central-west region showed the lowest overall magnitude of tuberculosis and better monitoring indicators. Conclusions: The situation related to tuberculosis differs among the five regions of Brazil. Those differences can make it difficult to control the disease in the country and could explain the fact that Brazil failed to reach the MDG for tuberculosis-related mortality. Tuberculosis control measures should be adapted to account for regional differences.

Keywords: Tuberculosis/epidemiology; Tuberculosis, pulmonary/epidemiology; Health status indicators; Social determinants of health; Healthcare disparities.

Despite the considerable efforts made in the fight against smoking in the last decades, there are still substantial numbers of people who, in full knowledge of the health hazards, begin smoking or continue smoking. Recent studies have focused on the genetic bases of the nicotine addiction. Various genetic polymorphisms have been associated with smoking. However, environmental factors have also been shown to play a role. In this review, we present some of the principal data collected in genetic studies of smoking behavior. The results obtained through this line of research will eventually aid clinicians in individualizing the type, dosage and duration of treatment for patients with nicotine dependence in accordance with the genotype of each smoker, thereby maximizing the efficacy of the proposed treatment regimen.

Keywords: Smoking; Tobacco use cessation; Nicotine; Tobacco use disorder

Objective: The PACIFIC trial established standard therapy for patients with unresectable stage III NSCLC who did not progress after platinum-based concurrent chemoradiation therapy. However, real-world data, particularly from Latin America, remain limited. The LACOG 0120 study aimed to evaluate the efficacy and safety of consolidation therapy with durvalumab in a real-world setting in Brazil. Methods: Patients with unresectable stage III NSCLC who received chemoradiotherapy followed by durvalumab consolidation therapy through an expanded access program were evaluated. The primary objective was to assess progression-free survival (PFS). Secondary endpoints included overall survival (OS), treatment compliance, and safety, with a focus on the incidence and severity of immune-mediated adverse events (NCT04948411). Results: Thirty-one patients from seven centers were evaluated. Median follow-up was 50.3 months (95% CI: 48.6–54.4). Median PFS was 9.9 months (95% CI: 7.3–52.4), with a 36 month-PFS of 34.5% (95% CI: 17.7–52.1). Median OS was 34.9 months (95% CI: 26.0–NR), and the 36 month-OS was 46.3% (95% CI: 25.7–64.6). Durvalumab was administered for a median of 17 cycles (10 to 24), with 45.2% of patients completing the planned therapy. The main reason for discontinuation was disease progression. Treatment-related adverse events of any grade occurred in 12 patients (38.7%), with grade 3 events reported in two (6.5%). Pneumonitis was observed in 4 patients (12.9%) – grade 3 in 1 patient. Conclusions: PFS was lower in this analysis compared to the PACIFIC trial; however, OS was similar, indicating comparable efficacy in a real-world setting among Brazilian patients with unresectable stage III NSCLC. No new safety concerns were identified.

Background: Knowledge of the rates of drug resistance is one of the pillars of tuberculosis control program evaluation. Data from low-resource countries are scarce and results are delayed due to the techniques employed. There is therefore an urgent need for evaluation of faster and less onerous testing methods. Objective: To compare the performance of rapid colorimetric assays for phenotyping that employ oxidationreduction indicators to determine the susceptibility profile of Mycobacterium tuberculosis with the gold-standard proportion method on Lowenstein-Jensen Medium. Method: We analyzed 166 M. tuberculosis strains of known susceptibility. Minimal inhibition concentrations for isoniazid and rifampicin were determined in microplates, using a liquid medium and Alamar Blue and tetrazolium bromide indicators. To measure agreement the Kappa value was used. Cutoff values between sensitive and resistant strains were defined as 0.2µg/mL and 1.0µg/mL for isoniazid and rifampicin, respectively. Results: There was 100% concordance between Alamar Blue and tetrazolium bromide methods in the determination of minimal inhibition concentrations. Agreement between the colorimetric method and the Lowenstein-Jensen was 95% for isoniazid and rifampicin. Using the colorimetric method, results were obtained within 7 days, in contrast to the 28 days required for the conventional method. Conclusions: Assays to determine minimal inhibition concentrations in liquid medium and employing oxidationreduction indicators proved to be rapid and inexpensive. This method has the potential to become a faster, alternative method for determining susceptibility of M. tuberculosis strains in developing countries.

Keywords: Mycobacterium tubercolis. Disease susceptibility. Isoniazid/therapeutic use. Rifampin/therapeutic use.

Objective: The objective of this study was to evaluate the applicability of a modified version of the Saint George's Respiratory Questionnaire. The version evaluated elicits "agree" and "do not agree", rather than "yes" and "no", responses. The intention is to facilitate the comprehension of double-negative questions and to promote better recollection of symptoms by patients by shortening their symptom histories from 12 months to 3 months. Methods: A total of 30 clinically stable patients with chronic obstructive pulmonary disease were evaluated. The Saint George's Respiratory Questionnaire and the modified version of the same were administered 15 days apart. Results: All of the patients presented health-related alterations in their quality of life. Comparing mean scores between the two questionnaires, the greatest difference was seen in the Symptoms domain. No significant differences were found in any of the remaining domains or in the total scores. In a subsequent analysis, significant correlations between the two questionnaires were found in all domains: Symptoms (r = 0.71; p < 0.001); Activity (r = 0.75; p < 0.001); Impact (r = 0.73; p < 0.001) and Total (r = 0.86; p < 0.001). Conclusion: The modified version of the Saint George's Respiratory Questionnaire is as effective as the original in gauging quality of life. However, various symptoms recollection time frames should be investigated in order to determine which would be the best time frame to employ in the analysis.

Keywords: Pulmonary disease, chronic obstructive; Quality of life; Reproducibility of results; Cross-cultural comparison; Questionnaires