Objective: To evaluate the evolution of clinical and epidemiological data, as well as data related to diagnosis, staging, treatment, and survival, among patients undergoing curative surgery for lung cancer at a tertiary referral center in the city of São Paulo, Brazil. Methods: This was a retrospective study of cases in the International Association for the Study of Lung Cancer database. We selected only cases of patients undergoing curative surgery between January of 2011 and April of 2018. We determined overall and disease-free survival at 36 months and compared the data between two periods (2011-2014 and 2015-2018). Results: Comparing the two periods (N = 437 cases), we observed trends toward increases in the number of female patients, as well as in the proportions of former smokers (44.09% vs. 53.59%), of patients diagnosed with adenocarcinoma (52.21% vs. 59.72%), and of patients diagnosed at an earlier pathological stage, together with a decrease in 30-day mortality (4.05% vs. 2.39%). There were significant increases in the proportions of cases diagnosed at an earlier clinical stage (p = 0.002) or incidentally (p = 0.003). Although lobectomy was the main surgical technique employed, there was a proportional increase in segmentectomies (2.67% vs. 7.11%; p = 0.026). Overall and disease-free survival rates were 79.4% (95% CI: 74.0-83.9%) and 75.1% (95% CI: 69.1-80.1%), respectively. The difference in overall survival between the periods lost statistical significance when adjusted for pathological stage, the only factor that affected survival (log-rank: p = 0.038 to p = 0.079). Conclusions: The clinical and epidemiological evolution presented in this study corroborates global trends. The decrease in 30-day mortality was probably due to better patient selection and improved surgical techniques.

Keywords: Lung neoplasms/surgery; Lung neoplasms/epidemiology; Lung neoplasms/therapy; Survival analysis; Thoracic surgery; Thoracic surgery, video-assisted.

Objective: To analyze the clinical characteristics and evolution of a group of patients with positive sputum cultures for multidrug-resistant (MDR) Mycobacterium tuberculosis and treated at a referral center in the city of Rio de Janeiro, Brazil. Methods: Based on the positive results in sputum cultures for MDR M. tuberculosis, 50 patients were selected, and their clinical data were obtained from the Brazilian Ministry of Health MDR-TB Database. The frequencies of noncompliance, relapses, failures and previous treatments for TB up to diagnosis of MDR-TB were compiled. The radiological patterns were classified as unilateral or bilateral, and with or without cavitation. Two years after the end of the standard treatment for MDR-TB, the outcome (cure, failure, noncompliance or death) for each patient was evaluated and reassessed every two years. The post-treatment follow-up period was eight years. Results: The mean number of previous treatments was 2.3 ± 0.9. The mean interval between the initial diagnosis and the development of MDR-TB was 2.0 ± 1.7 years. Two years after the initial treatment for MDR-TB, 2 patients had abandoned treatment, 8 had died, 18 had been cured, and 22 had presented treatment failure. The bivariate analysis showed that bilateral pulmonary involvement and cavitary pattern markedly reduced the chances for cure, with a relative risk of 1-0.6 (40%) and 1-0.7 (30%), respectively. At the end of the follow-up period, 2 patients had abandoned treatment, 9 had presented treatment failure, 17 had been cured, and 22 had died. Conclusions: Bilateral pulmonary involvement and cavity pattern greatly reduced the chances for cure of the patients with MDR-TB. Most patients who presented treatment failure died within the 8-year follow-up period.

Keywords: Tuberculosis, multidrug-resistant; Treatment outcome; Disease-free survival; Treatment refusal; Treatment failure.

Objective: The clinical, functional, radiological and genotypic descriptions of patients with an alpha-1 antitrypsin (A1AT) gene mutation in a referral center for COPD in Brazil. Methods: A cross-sectional study of patients with an A1AT gene mutation compatible with deficiency. We evaluated the A1AT dosage and genotypic, demographic, clinical, tomographic, and functional characteristics of these patients. Results: Among the 43 patients suspected of A1AT deficiency (A1ATD), the disease was confirmed by genotyping in 27 of them. The A1AT median dosage was 45 mg/dL, and 4 patients (15%) had a normal dosage. Median age was 54, 63% of the patients were male, and the respiratory symptoms started at the age of 40. The median FEV1 was 1.37L (43% predicted). Tomographic emphysema was found in 77.8% of the individuals. The emphysema was panlobular in 76% of them and 48% had lower lobe predominance. The frequency of bronchiectasis was 52% and the frequency of bronchial thickening was 81.5%. The most common genotype was Pi*ZZ in 40.7% of participants. The other genotypes found were: Pi*SZ (18.5%), PiM1Z (14.8%), Pi*M1S (7.4%), Pi*M2Z (3.7%), Pi*M1I (3.7%), Pi*ZMnichinan (3.7%), Pi*M3Plowell (3.7%), and Pi*SF (3.7%). We did not find any significant difference in age, smoking load, FEV1, or the presence of bronchiectasis between the groups with a normal and a reduced A1AT dosage, neither for 1 nor 2-allele mutation for A1ATD. Conclusions: Our patients presented a high frequency of emphysema, bronchiectasis and bronchial thickening, and early-beginning respiratory symptoms. The most frequent genotype was Pi*ZZ. Heterozygous genotypes and normal levels of A1AT also manifested significant lung disease.

Keywords: Alpha-1 antitrypsin; Emphysema; Alleles.

Background: Lung cancer is the leading cause of cancer-related death worldwide. Objective: To determine the time spent diagnosing, staging and surgically treating lung cancer in a university hospital. Method: Between January 1990 and December 1998, 69 (53 male, 16 female) patients were diagnosed with lung cancer and underwent surgery. The hospital records of these patients were reviewed to evaluate clinical and histological data, dates of outpatient visits, hospital admission, tests and procedures, as well as to determine if the patients were examined as inpatients or as outpatients. Results: The 15 patients investigated as outpatients were designated as group I, the 28 examined as both inpatients and outpatients as group II, and the 26 investigated as inpatients as group III. Age ranged from 43 to 79 years (mean ± SD; 61 ± 10). Of the 69 patients, 43 were smokers and 23 were ex-smokers. The mean time from onset of symptoms to the first outpatient visit was 110 days and 33 days from the first outpatient visit until diagnosis. There was a lapse of 25 days between diagnosis and surgery. The mean total elapsed time between the first outpatient visit and surgery was 58 days. The mean total time was 72 days for group I, 72 days for group II, and 35 days for group III (p < 0.01). There was no significant difference regarding total time in relation to the different stages of the disease (p = 0.16). Conclusions: The results show that patients waited too long before seeking medical assistance and that medical treatment of lung cancer was further delayed when patients were examined in an outpatient setting.

Keywords: Lung neoplasm/surgery. Disease progression.

Abstract Objective: To determine the rate of adherence to treatment with inhaled corticosteroids in patients with severe asthma, to identify predictive factors for adherence and to evaluate the relationship between adherence to treatment and parameters of clinical and functional response. Methods: Prospective cohort study of patients enrolled in the Program for the Control of Asthma and Allergic Rhinitis in the state of Bahia, Brazil. The study comprised 160 patients with severe asthma, monitored for 180 days in order to evaluate adherence (dependent variable) to the prescribed inhaled corticosteroid. Independent variables were assessed at baseline and for a six-month follow-up period by means of interviews and the completion of a standardized questionnaire. Patients recorded the missed doses in a diary. Results: Of the 160 patients, 158 completed the study. Adherence rate was 83.8%. Of the 158 patients, 112 (70.9%) were considered adherent (cut-off point: 80% of prescribed doses administered). There was a significant association between asthma control and adherence to treatment. Predictors of poor adherence were adverse effects, living far from the referral center, limited resources to pay for transportation and dose schedule. Other factors, such as depressive symptoms, religion and economic status, were not associated with poor adherence. Conclusions: Adherence to asthma treatment was high and was associated with the clinical response to treatment, in a sample of patients with severe asthma enrolled in a public program that provides free medication and the assistance of a multiprofessional specialized team in a referral center.

Keywords: Asthma; Directly observed therapy; Treatment outcome; Patient compliance; Pharmacy.

Objective: The purpose of this study was to assess performance in the Brazilian Lung Cancer Registry Database by using the parsimonious EuroLung risk models for morbidity and mortality. Methods: The EuroLung1 and EuroLung2 models were tested and evaluated through calibration (calibration plot, Brier score, and the Hosmer-Lemeshow test) and discrimination (ROC AUCs), in a national multicenter registry of 1,031 patients undergoing anatomic lung resection. Results: The evaluation of performance in Brazilian health care facilities utilizing risk-adjustment models, specifically EuroLung1 and EuroLung2, revealed substantial miscalibration, as evidenced by calibration plots and Hosmer-Lemeshow tests in both models. In terms of calibration, EuroLung1 exhibited a calibration plot with overlapping points, characterized by a slope of 1.11 and a Brier score of 0.15; the Hosmer-Lemeshow test yielded a statistically significant p-value of 0.015; and the corresponding ROC AUC was 0.678 (95% CI: 0.636-0.721). The EuroLung2 model displayed better calibration, featuring fewer overlapping points in the calibration plot, with a slope of 1.22, with acceptable discrimination, as indicated by a ROC AUC of 0.756 (95% CI: 0.670-0.842). Both models failed to accurately predict morbidity and mortality outcomes in this specific health care context. Conclusions: Discrepancies between the EuroLung model predictions and outcomes in Brazil underscore the need for model refinement and for a probe into inefficiencies in the Brazilian health care system. (Plataforma Brasil identifier: 16424413.2.1001.0065. [https://plataformabrasil.saude.gov.br/])

Keywords: Quality of health care; Models, statistical; Public health; Morbidity; Lung neoplasms.

Objective: To evaluate the risk factors for the development of tuberculosis and multidrug-resistant tuberculosis (MDR-TB) in patients treated at a tertiary referral hospital. Methods: This was a cross-sectional study based on data obtained from patients treated at the Júlia Kubitschek Hospital, located in the city of Belo Horizonte, Brazil, between October of 2012 and October of 2014. We evaluated sociodemographic, behavioral, clinical, and radiological variables. The outcome considered to identify associations between tuberculosis and the explanatory variables was the treatment prescribed. To evaluate the associations between MDR-TB and the same explanatory variables, the change in MDR-TB treatment was considered. Results: The factors associated with tuberculosis were alcoholism, comorbidities, pulmonary cavitations, and a radiological pattern suggestive of tuberculosis. Cavitation and previous treatment for tuberculosis were associated with MDR-TB. Conclusions: Despite the significant progress made in the fight against tuberculosis, there is a need for coordinated actions that include social protection measures and patient support.

Keywords: Tuberculosis; Risk factors; Tuberculosis, multidrug-resistant.

Objective: To determine the relative frequency of hypomagnesemia among patients with chronic airflow limitation treated as outpatients at a referral center in the northern part of the state of Paraná between 2000 and 2001, as well as to determine whether hypomagnesemia correlates with hypoxia, with other electrolyte disturbances and with the severity of airflow limitation. Methods: This was a descriptive study of the relative frequency of hypomagnesemia in 72 patients with chronic airflow limitation. All of the patients were submitted to blood tests to determine serum levels of magnesium and other electrolytes, as well as to staging of the underlying disease. Results: The prevalence of hypomagnesemia was 27.8%. The mean age was 65 ± 9.9 years, and there was a predominance of males. The mean forced expiratory volume in one second was 1.31 ± 0.52 L. Most of the patients (68.1%) were found to be in the advanced stages of the disease. Hypomagnesemia was not found to correlate with other electrolyte disturbances, hypoxemia or disease stage. Conclusion: The high frequency of patients in the advanced stages is likely attributable to the fact that the outpatient facility is a referral center for the region. Further studies should be conducted in order to determine the probable causes of this high prevalence of hypomagnesemia.

Keywords: Magnesium/blood; Pulmonary ventilation; Pulmonary disease, chronic obstructive; Respiratory insufficiency

Objective: To evaluate the use of inhaler devices by patients with severe asthma treated via the Programa para o Controle da Asma e Rinite Alérgica na Bahia (ProAR, Bahia State Asthma and Allergic Rhinitis Control Program), recording the frequency of their errors in performing key steps and the relationship between such errors and the lack of asthma control. Methods: A cross-sectional study involving 467 patients enrolled in the ProAR in the city of Salvador, Brazil. The devices evaluated were metered dose inhalers (MDIs), with or without a spacer, and dry powder inhalers (DPIs; Pulvinal® or Aerolizer®). For the assessment of the inhalation technique, a checklist was used; the patients were asked to demonstrate the technique so that an interviewer could observe all of the steps performed. For the assessment of asthma control, we used the 6-item asthma control questionnaire. Results: Most of the patients showed appropriate inhalation techniques when using the devices. When using an MDI, few patients made mistakes in the key step of "coordinating activation and inhalation" (5.2% and 9.1% with and without the use of a spacer, respectively). During Pulvinal® use, 39% of the patients did not inhale quickly and deeply, compared with only 5.8% during Aerolizer® use. Of the patients that made use of Aerolizer® alone, 71.3% appropriately performed all of the essential steps, and their asthma was controlled. Conclusions: Most of the patients in this sample, all of whom had been submitted to periodic checks of their inhalation technique (as part of the program), used the devices appropriately. Proper inhalation technique is associated with asthma symptom control.

Keywords: Asthma; Administration, inhalation; Metered dose inhalers; Dry powdered inhalers.

Objective: To assess the determining factors for Mycobacterium tuberculosis multidrug resistance at a referral center for infectious diseases in the state of Minas Gerais, Brazil. Methods: A retrospective case-control study was conducted using data collected from September of 2000 to January of 2004. During this period, 473 cultures presenting growth of M. tuberculosis, corresponding to 313 patients, were submitted to susceptibility tests at the Central Laboratory of Minas Gerais. Cases presenting resistance to at least rifampin and isoniazid were classified as cases of multidrug resistance and were selected for study. These cases were paired to control group cases of drug-susceptible tuberculosis at a ratio of 1:3. Clinical and demographic data were analyzed using univariate and multivariate analyses. Results: During the study period, 12 (3.83%) cases of multidrug-resistant tuberculosis were identified. In the univariate analysis, multidrug-resistant tuberculosis was found to be more common among male patients, as well as among those testing positive in the sputum smear microscopy, those with cavitations larger than 4 cm in diameter and those having been previously treated for tuberculosis (p = 0.10 for all). After the multivariate analysis, only previous treatment for tuberculosis remained statistically significant (p = 0.0374), with an odds ratio of 14.36 (1.96-176.46). Conclusion: In the present study, previous treatment for tuberculosis was found to be an independent risk factor for multidrug-resistant tuberculosis.

Keywords: Mycobacterium tuberculosis; Tuberculosis, multidrug-resistant; Tuberculosis; Microbial sensitivity tests; Risk factors

Objective: To describe the profile of patients with cystic fibrosis (CF). Methods: A prospective, cross-sectional study involving CF patients ≤ 18 years of age, evaluated between March and July of 2006 at a referral center in northeastern Brazil. Nutritional assessment was performed using Z scores for height/age (H/A), weight/age (W/A) and weight/height (W/H), as well as %weight/height (%W/H) and body composition measurements. Socioeconomic and clinical data were obtained. Results: Twenty-one patients were evaluated, 12 (57.1%) of whom were female. Mean age at diagnosis was 3.8 ± 3.9 years. The principal features at diagnosis were respiratory infection (85.7%), steatorrhea (66.7%) and nutritional deficit (47.6%). The mean Z scores for W/A, H/A and W/H were 0.73 ± 0.28, 0.34 ± 0.21 and 0.73 ± 0.35, respectively. Mean %W/H was 94.52 ± 1.58. The percentage of malnourished children assessed by Z score differed from that assessed by %W/H (nutritional deficit in 66.7% and 33.3%, respectively; p > 0.05). Socioeconomic status, clinical status and Shwachman score were better among well-nourished patients than among those classified as malnourished (p < 0.05 for Shwachman score). Conclusions: Normal nutritional status was identified based on nutritional indicators (W/A, H/A and W/H), whereas nutritional deficit was identified by assessing body composition. Socioeconomic factors proved favorable, especially maternal education and per capita income. Age at diagnosis was higher than that reported in the literature, although the Shwachman score and the incidence of respiratory infections demonstrated that the patients presented good clinical status.

Keywords: Cystic fibrosis; Nutritional assessment; Symptoms, clinical; Socioeconomic factors.

Objective: To describe our experience with video-assisted thoracic surgery (VATS) for anatomic pulmonary resection at a referral center for thoracic surgery in Brazil. Methods: All patients who underwent anatomic pulmonary resection by VATS between 2010 and 2015 were included. Clinical and pathological data, as well as postoperative complications, were analyzed. Results: A total of 117 pulmonary resections by VATS were performed, of which 98 were lobectomies and 19 were anatomic segmentectomies. The mean age of the patients was 63.6 years (range, 15-86 years). Females predominated (n = 69; 59%). The mean time to chest tube removal was 2.47 days, and the mean length of ICU stay was 1.88 days. The mean length of hospital stay was 4.48 days. Bleeding ≥ 400 mL occurred in 15 patients. Conversion to thoracotomy was required in 4 patients. Conclusions: Our results are similar to those published in major international studies, indicating that VATS is an important strategy for pulmonary resection. They also show that VATS can be safely performed with adequate training. This technique should be used more often for the treatment of lung diseases in Brazil.

Keywords: Lung neoplasms/therapy; Lung neoplasms/complications; Thoracic surgery, video-assisted.

Objective: To describe the occurrence of tuberculous uveitis (TBU) at a referral center in the state of Minas Gerais, Brazil. Methods: A total of 16 consecutive patients (≥15 years of age) who underwent diagnostic evaluation of uveitis between January of 2001 and July of 2004 at the Minas Gerais State Referral Center were selected for study. Demographic and clinical data, as well as data related to screening for toxoplasmosis, syphilis, and rheumatologic diseases, together with the results of tuberculin skin testing and HIV testing, were collected. Results: Of the16 patients evaluated, 11 (69%) were found to have TBU. A history of contact with pulmonary tuberculosis was reported by 8 (72%) of the 11 patients with TBU and by 1 (20%) of the 5 with non-TBU. Although the odds ratio for this association was 10.67 (95% CI: 0.59-398.66), the p value was borderline significant (p = 0.078). There was no difference between the patients with TBU and those with non-TBU in terms of the status of ocular inflammation or the tuberculin skin testing results. All of the patients were HIV negative and were monitored for two years. Conclusion: In this study, a history of contact with pulmonary tuberculosis proved to be useful in diagnosing TBU.

Keywords: Tuberculosis; Uveitis; Diagnosis; Brazil.

Objective: To estimate the rates of recurrence, cure, and treatment abandonment in patients with pulmonary tuberculosis treated with a four-drug fixed-dose combination (FDC) regimen, as well as to evaluate possible associated factors. Methods: This was a retrospective observational study involving 208 patients with a confirmed diagnosis of pulmonary tuberculosis enrolled in the Hospital Tuberculosis Control Program at the Institute for Thoracic Diseases, located in the city of Rio de Janeiro, Brazil. Between January of 2007 and October of 2010, the patients were treated with the rifampin-isoniazid-pyrazinamide (RHZ) regimen, whereas, between November of 2010 and June of 2013, the patients were treated with the rifampin-isoniazid-pyrazinamide-ethambutol FDC (RHZE/FDC) regimen. Data regarding tuberculosis recurrence and mortality in the patients studied were retrieved from the Brazilian Case Registry Database and the Brazilian Mortality Database, respectively. The follow-up period comprised two years after treatment completion. Results: The rates of cure, treatment abandonment, and death were 90.4%, 4.8%, and 4.8%, respectively. There were 7 cases of recurrence during the follow-up period. No significant differences in the recurrence rate were found between the RHZ and RHZE/FDC regimen groups (p = 0.13). We identified no factors associated with the occurrence of recurrence; nor were there any statistically significant differences between the treatment groups regarding adverse effects or rates of cure, treatment abandonment, or death. Conclusions: The adoption of the RHZE/FDC regimen produced no statistically significant differences in the rates of recurrence, cure, or treatment abandonment; nor did it have any effect on the occurrence of adverse effects, in comparison with the use of the RHZ regimen.

Keywords: Tuberculosis, pulmonary, Drug combinations; Recurrence.

Objective: In view of the relevance of co-infection with tuberculosis and human immunodeficiency virus, this study was designed to determine tuberculosis prevalence and identify factors related to tuberculosis in patients residing in a region in which both infections are highly prevalent. Methods: All patients treated during 1999 at the HIV/AIDS Clinic of the Universidade Federal do Rio Grande (Rio Grande Federal University) University Hospital were evaluated retrospectively, from the time of human immunodeficiency virus diagnosis, in terms of the incidence of tuberculosis and its relationship to sociodemographic, behavioral and immunological factors. Results: The sample included 204 patients, and tuberculosis prevalence was found to be 27%. The multivariate analysis showed a significant correlation between the development of tuberculosis and being of African descent (odds ratio: 4.76; 95% confidence interval: 1.93-11.72) and an inverse correlation between the development of tuberculosis and the TCD4+ lymphocyte count at the time of human immunodeficiency virus diagnosis (odds ratio: 0.995; 95% confidence interval: 0.993-0.997). When analyzed separately, other variables were found to be potential risk factors: being of the male gender (odds ratio: 2.49; 95% confidence interval: 1.15-5.39); and using illicit drugs (odds ratio: 2.1; 95% confidence interval: 1.02-4.31). Conclusion: The factors responsible for the development of tuberculosis among patients who are human immunodeficiency virus seropositive include immunological, socioeconomic and demographic factors. The high rate of tuberculosis prevalence among the seropositive patients underscores the urgent need to implement strategies that combine rapid identification and prompt treatment of individuals with active or latent infection, as well as of those with whom they have been in contact.

Keywords: HIV Infections/complications; AIDS-related opportunistic infections/complications; Tuberculosis/etiology; Tuberculosis/epidemiology

Objective: To determine the epidemiological profile of inpatients at a TB referral hospital. Methods: This was a descriptive, retrospective study of the medical charts of patients with TB hospitalized at the Hospital Estadual Santa Maria (HESM), in the city of Rio de Janeiro, Brazil, between January of 2002 and December of 2003. Data were collected using a standardized form. Results: Of the 451 patients included in the study, 313 (69.4%) had been referred to the HESM from health care clinics, and 302 (67.0%) were male. Most of the patients were in the 30-59  year age bracket, 443 (98.2%) lived in the greater metropolitan region of Rio de Janeiro, and 298 (66.1%) lived in the city of Rio de Janeiro itself. The most common reason for hospitalization was poor health status (in 237, 52.5%). The most common comorbidity was AIDS (in 137, 30.4%). The most common signs and symptoms at admission were weight loss, fever and productive cough. Sputum smear microscopy was positive in 122 (71.0%) of the patients presenting with productive cough at admission. Of the 212 patients being retreated, 156 (73.6%) reported noncompliance with previous treatment. Regarding the outcome, 273 (65.8%) of the patients were referred to municipal health care centers, 83 (18.4%) died, 44 (9.8%) were cured, and 27 (6%) were discharged against medical advice. Conclusions: Providing hospitals specializing in TB is relevant for TB control, especially in metropolitan regions. In addition to taking biosafety measures, these hospitals must be prepared to treat patients with TB-related comorbidities and social problems. This study has resulted in improvements at the HESM.

Keywords: Tuberculosis; Epidemiology; Hospitalization.

Objective: To compare smokers and never smokers in terms of the following: quality of life; BMI; hospitalizations; functionality; family history of mental disorder; tobacco-related diseases; depression; and psychoactive substance use. Methods: We evaluated 167 smokers enrolled in a smoking cessation program at the Londrina State University Referral Center for Understanding and Treating Smoking, together with 272 never-smoking blood donors. We employed the following instruments, all validated for use in Brazil: a structured questionnaire for the collection of sociodemographic data; the Alcohol, Smoking and Substance Involvement Screening Test; the World Health Organization Quality of Life Instrument, brief version (WHOQoL-BREF); and the Fagerström Test for Nicotine Dependence. We also applied diagnostic criteria for the investigation of depressive disorders. Results: The mean age of the smokers and never smokers was, respectively, 45 and 44 years. Females predominated in both groups. Smokers more often presented with impaired work/domestic functionality, hospitalizations, depressive disorders, smoking in the household, sedative use and a family history of mental disorders, as well as scoring lower in all domains of the WHOQoL-BREF. The mean age at smoking onset was lower for smokers with depression or using psychoactive substances than for smokers without such comorbidities. Diabetes, arterial hypertension, heart disease, respiratory disease and peptic ulcer were more common in smokers than in never smokers. The mean BMI was lower in the smokers than in the never smokers. Conclusions: This study suggests that, for smoking cessation programs, subgroups of smokers with specific characteristics (early age at smoking onset, tobacco-related diseases, depressive disorders and use of psychoactive substances) should be identified.

Keywords: Smoking; Depressive disorder; Smoking cessation; Tobacco use disorder.