The impact of smoking on tuberculosis treatment outcomes: a meta-analysis.

BACKGROUND: Cigarette smoking contributes to tuberculosis (TB) epidemiology. However, limited evidence exists on how smoking impacts TB treatment outcomes such as treatment loss to follow-up and culture conversion.METHODS: This meta-analysis assessed current evidence of the impact of active cigarette smoking on TB treatment outcomes. PubMed, Scopus, Embase, and the Cochrane Library were searched for English-language articles published from database inception through 2017. Articles addressing active pulmonary TB and cigarette smoking were identified and data abstracted. Smokers were defined as those who smoked every day or some days at the time of interview/diagnosis. Non-smokers did not smoke at the time of interview/diagnosis. Unfavorable outcomes included any outcome other than cure or completion of TB treatment. Three different data sets were examined: 8 articles addressing unfavorable treatment outcomes, 9 analyzing only treatment loss to follow-up, and 5 addressing delayed smear or culture conversion. Studies that had <20 subjects or that addressed only populations with comorbidities were excluded.RESULTS: We identified 1030 studies; 21 studies fulfilled the inclusion/exclusion criteria. Smokers had greater odds of unfavorable outcomes (pooled odds ratio [pOR] 1.23, 95%CI 1.14-1.33), delayed smear or culture conversion (pOR 1.55, 95%CI 1.04-2.07), and treatment loss to follow-up (pOR 1.35, 95%CI 1.21-1.50).CONCLUSION: Cigarette smoking is associated with negative treatment results and delayed conversion to negative smear or culture, suggesting smoking is an important factor for consideration in TB elimination efforts.

The California Multidrug-Resistant Tuberculosis Consult Service: a partnership of state and local programs.

Background: The US Centers for Disease Control and Prevention recommend expert consultation for multi-drug-resistant tuberculosis (MDR-TB) cases. In 2002, the California MDR-TB Service was created to provide expert MDR-TB consultations. We describe the characteristics, treatment outcomes and management of patients referred to the Service. Methods: Surveillance data were used for descriptive analysis of cases, with consultation during July 2002-December 2012. Clinical consultation data and modified World Health Organization indicators were used to assess the care and management of cases, with consultation from January 2009 to December 2012. Results: Of 339 MDR-TB patients, 140 received a consultation. The proportion of patients receiving a consultation increased from 12% in 2002 to 63% in 2012. There were 24 pre-extensively drug-resistant TB and 5 patients with extensively drug-resistant TB. The majority (n = 123, 88%) completed treatment, 5 (4%) died, 7 (5%) moved before treatment completion, 4 (3%) stopped treatment due to an adverse event and 1 (1%) had an unknown outcome. Indicator data showed that 86% underwent rapid molecular drug susceptibility testing, 98% received at least four drugs to which they had known or presumed susceptibility, and 93% culture converted within 6 months. Conclusions: Consultations with the MDR-TB Service increased over time. Results highlight successful treatment and indicator outcomes.

Contexte : Les Centers for Disease Control and Prevention des Etats Unis recommandent de consulter un expert en cas de tuberculose multirésistante (TB-MDR). En 2002, le California MDR-TB Service a été créé afin de fournir une consultation d'experts en TB-MDR. Nous décrivons les caractéristiques, les résultats du traitement et la prise en charge des patients référés vers ce service.Méthode : Les données de surveillance ont été utilisées pour une analyse descriptive des cas ayant eu une consultation entre juillet 2002 et décembre 2012. Les données de consultation clinique et les indicateurs modifiés de l'Organisation Mondiale de la Santé ont été utilisés afin d'évaluer la prise en charge des cas qui ont bénéficié d'une consultation entre janvier 2009 et décembre 2012.Résultats : Sur 339 patients TB-MDR, 140 ont bénéficié d'une consultation. Cette proportion est passée de 12% en 2002 à 63% en 2012. Il y a eu 24 patients TB pré-ultrarésistante et 5 patients TB ultrarésistante. La majorité (n = 123 ; 88%) a achevé le traitement, 5 (4%) sont décédés, 7 (5%) ont déménagé avant la fin du traitement, 4 (3%) ont arrêté le traitement à cause d'un effet secondaire et 1 (1%) a eu un résultat inconnu. Les indicateurs ont montré que 86% avaient bénéficié d'un test de pharmacosensibilité moléculaire rapide, que 98% avaient reçu au moins quatre médicaments avec une sensibilité connue ou présumée et que 93% ont eu une conversion de culture dans les 6 mois.Conclusion : Les consultations au service de TB-MDR ont augmenté dans le temps. Nous avons mis en lumière les bons résultats du traitement et des indicateurs.

Marco de referencia: Los Centros para el Control y la Prevención de Enfermedades de los Estados Unidos recomiendan que se recurra a la consulta con expertos en los casos de tuberculosis multirresistente (TB-MDR). En el 2002, se creó el California MDR-TB Service en California, con el objeto de proveer consultas de expertos en la materia. En el presente estudio se describen las características, los desenlaces terapéuticos y el tratamiento de los pacientes remitidos a este servicio.Métodos: Se utilizaron los datos de la vigilancia en el análisis descriptivo de los casos que consultaron el Servicio de julio del 2002 a diciembre del 2012. A partir de la base de datos de la consulta y los indicadores modificados de la Organización Mundial de la Salud se evaluó la atención y el tratamiento de los casos que consultaron de enero del 2009 a diciembre del 2012.Resultados: De los 339 pacientes con diagnóstico de TB-MDR, 140 obtuvieron la consulta de expertos. La proporción de pacientes con una consulta aumentó de un 12% en el 2002 al 63% en el 2012. Se atendieron 24 pacientes con TB pre-ultrarresistente y cinco pacientes con TB ultrarresistente. La mayoría completó el tratamiento (n = 123; 88%), 5 pacientes fallecieron (4%), 7 se mudaron antes de haber completado el tratamiento (5%), 4 interrumpieron el tratamiento debido a una reacción adversa (3%) y se desconoció el desenlace de 1 paciente (1%). Según los datos de los indicadores, en 86% de los casos se practicaron pruebas moleculares rápidas de sensibilidad a los medicamentos, el 98% de pacientes recibió como mínimo cuatro fármacos con sensibilidad confirmada o supuesta y el 93% de los pacientes había convertido el cultivo en un lapso de 6 meses.Conclusión: Las consultas al Servicio de expertos en TB-MDR han aumentado con el transcurso del tiempo. Los resultados del estudio ponen de manifiesto la eficacia del tratamiento y revelan indicadores de evolución muy favorables.

Characteristics and costs of multidrug-resistant tuberculosis in-patient care in the United States, 2005-2007.

OBJECTIVE: A population-based study of 135 multidrug-resistant tuberculosis (MDR-TB) patients reported to the Centers for Disease Control and Prevention (CDC) during 2005-2007 found 73% were hospitalized. We analyzed factors associated with hospitalization. METHODS: We assessed statistically significant multivariable associations with US in-patient TB diagnosis, frequency of hospitalization, length of hospital stay, and in-patient direct costs to the health care system. RESULTS: Of 98 hospitalized patients, 83 (85%) were foreign-born. Blacks, diabetics, or smokers were more likely, and patients with disseminated disease less likely, to receive their TB diagnosis while hospitalized. Patients aged ⩾65 years, those with the acquired immune-deficiency syndrome (AIDS), or with private insurance, were hospitalized more frequently. Excluding deaths, length of stay was greater for patients aged ⩾65 years, those with extensively drug-resistant TB (XDR-TB), those residing in Texas, those with AIDS, those who were unemployed, or those who had TB resistant to all first-line medications vs. others. Average hospitalization cost per XDR-TB patient (US$285 000) was 3.5 times that per MDR-TB patient (US$81 000), in 2010 dollars. Hospitalization episode costs for MDR-TB rank third highest and those for XDR-TB highest among the principal diagnoses. CONCLUSIONS: Hospitalization was common and remains a critical care component for patients who were older, had comorbidities, or required complex management due to XDR-TB. MDR-TB in-patient costs are among the highest for any disease.

Tuberculosis and diabetes mellitus in the Republic of Kiribati: a case-control study.

OBJECTIVES: To better inform local management of TB-diabetes collaborative activities, we aimed to determine the prevalence of diabetes among persons with and without TB and to determine the association between TB and diabetes in Kiribati, a Pacific Island nation. METHODS: We compared consecutively enrolled TB cases to a group of randomly selected community controls without evidence of TB. Diabetes was diagnosed by HbA1c, and clinical and demographic data were collected. A tuberculin skin test was administered to controls. The chi-square test was used to assess significance in differences between cases and controls. We also calculated an odds ratio, with 95% confidence intervals, for the odds of diabetes among cases relative to controls. Unweighted multivariate logistic regression was performed to adjust for the effects of age and sex. RESULTS: A total of 275 TB cases and 499 controls were enrolled. The diabetes prevalence in cases (101, 37%) was significantly greater than in controls (94, 19%) (adjusted odds ratio: 2.8; 95% CI 2.0-4.1). Fifty-five percent (108) of all diabetic diagnoses were new; this proportion was higher among controls (64.8%) than cases (46.5%). Five patients with TB were screened to detect one patient with diabetes. CONCLUSIONS: There is a strong association between TB and diabetes in Kiribati and bidirectional screening should be conducted in this setting.

Effect of diabetes on tuberculosis presentation and outcomes in Kiribati.

OBJECTIVES: To determine the association between diabetes and the clinical features and treatment outcomes of TB in Kiribati. METHODS: We enrolled consecutive patients with TB who presented from August 2010 to February 2012 and compared clinical features and TB treatment outcomes for patients with and without diabetes, as measured by haemoglobin A1c assay. Poor outcome was defined as death, default or treatment failure, and good outcome as treatment success or cure. RESULTS: Two hundred and seventy-five eligible persons with TB disease were enrolled; 101 (37%) had diabetes. TB patients with diabetes were more likely to have acid-fast bacilli (AFB) seen on sputum smear microscopy (RR: 1.3; 95% CI: 1.03-1.62). The risk of poor outcome did not differ between patients with or without diabetes (RR: 1.1; 95% CI: 0.5-2.7). CONCLUSION: TB patients with diabetes are more likely than those without to have sputum with AFB on microscopy. This could increase transmission in the community. Early detection of TB by screening patients with diabetes, and the converse, could be important public health interventions where diabetes and TB are prevalent.

Treatment for LTBI in contacts of MDR-TB patients, Federated States of Micronesia, 2009-2012.

SETTING: Few studies have shown the operational feasibility, safety, tolerability, or outcomes of multidrug-resistant latent tuberculous infection (MDR LTBI) treatment. After two simultaneous multidrug-resistant tuberculosis (MDR-TB) outbreaks in Chuuk, Federated States of Micronesia, infected contacts were offered a 12-month fluoroquinolone (FQ) based MDR LTBI treatment regimen. DESIGN: Between January 2009 and February 2012, 119 contacts of MDR-TB patients were followed using a prospective observational study design. After MDR-TB disease was excluded, 12 months of daily FQ-based preventive treatment of MDR LTBI was provided by directly observed therapy. RESULTS: Among the 119 infected contacts, 15 refused, while 104 began treatment for MDR LTBI. Of the 104 who initiated treatment, 93 (89%) completed treatment, while 4 contacts discontinued due to adverse effects. None of the 104 contacts who undertook MDR LTBI treatment of any duration developed MDR-TB disease; however, 3 of 15 contacts who refused and 15 unidentified contacts developed MDR-TB disease. CONCLUSION: Providing treatment for MDR LTBI can be accomplished in a resource-limited setting, and contributed to preventing MDR-TB disease. The Chuuk TB program implemented treatment of MDR LTBI with an 89% completion rate. The MDR LTBI regimens were safe and well tolerated, and no TB cases occurred among persons treated for MDR LTBI.

Surgical interventions for drug-resistant tuberculosis: a systematic review and meta-analysis.

BACKGROUND: With the emergence of multidrug-resistant (MDR-) and extensively drug-resistant tuberculosis (XDR-TB), surgery, which had been replaced by short-course chemotherapy, is again being considered a viable treatment option. OBJECTIVE: To assess the literature on the effectiveness of surgical interventions in the treatment of drug-resistant TB. METHODS: Medline, EMBASE, and PubMed were searched from 1975 to April 2012 in addition to hand searching reference lists, and the International Journal of Tuberculosis and Lung Disease. Potentially relevant studies were assessed according to pre-defined eligibility criteria: MDR- and XDR-TB patients undergoing surgical and non-surgical treatment. Treatment outcomes were extracted according to internationally accepted definitions and included in meta-analyses using random effects models. RESULTS: Summary meta-analysis of 24 comparison studies revealed a significant association between surgery and successful treatment compared to non-surgical interventions (OR 2.24, 95%CI 1.68-2.97). A meta-analysis from 23 single-arm studies demonstrated that respectively 92% (95%CI 88.1-95) and 87% (95%CI 83-91) of surgical patients achieved successful short- and long-term outcomes. Subgroup analyses showed that favorable surgical outcomes were associated with increased drug resistance in studies reporting surgical and non-surgical treatment outcomes. CONCLUSIONS: While the results suggest that surgical intervention is associated with successful treatment outcomes in patients with drug-resistant TB, there is insufficient evidence to recommend surgery plus chemotherapy over chemotherapy alone, to evaluate the potential harm from surgery and to determine the optimal conditions for surgery. Controlled studies are needed to better assess the effectiveness of surgery and to investigate other contextual issues.

Linezolid in the treatment of multidrug-resistant tuberculosis.

BACKGROUND: Linezolid is a new antibiotic with activity against Mycobacterium tuberculosis in vitro and in animal studies. Several small case series suggest that linezolid is poorly tolerated because of the side effects of anemia/thrombocytopenia and peripheral neuropathy. To characterize our clinical experience with linezolid, the California Department of Public Health Tuberculosis Control Branch's Multidrug-Resistant Tuberculosis (MDR-TB) Service reviewed cases in which the MDR-TB treatment regimens included linezolid therapy. METHODS: Record review was performed for 30 patients treated with linezolid as part of an MDR-TB regimen. Data were collected on clinical and microbiological characteristics, linezolid tolerability, and treatment outcomes. The dosage of linezolid was 600 mg daily. Vitamin B6 at a dosage of 50-100 mg daily was used to mitigate hematologic toxicity. RESULTS: During 2003-2007, 30 patients received linezolid for the treatment of MDR-TB. Patients had isolates resistant to a median of 5 drugs (range, 2-13 drugs). Of the 30 cases, 29 (97%) were pulmonary; of these 29, 21 (72%) had positive results of acid-fast bacilli smear, and 16 (55%) were cavitary. Culture conversion occurred in all pulmonary cases at a median of 7 weeks. At data censure (31 December 2008), 22 (73%) of 30 patients had successfully completed treatment. Five continued to receive treatment. There were no deaths. Three patients had a poor outcome, including 2 defaults and 1 treatment failure. Side effects occurred in 9 patients, including peripheral and optic neuropathy, anemia/thrombocytopenia, rash, and diarrhea. However, only 3 patients stopped linezolid treatment because of side effects. CONCLUSIONS: Linezolid was well tolerated, had low rates of discontinuation, and may have efficacy in the treatment of MDR-TB.

Yield of serial sputum specimen examinations in the diagnosis of pulmonary tuberculosis: a systematic review.

Current international tuberculosis (TB) guidelines recommend the microscopic examination of three sputum specimens for acid-fast bacilli in the evaluation of persons suspected of having pulmonary TB. We conducted a systematic review of studies that quantified the diagnostic yield of each of three sputum specimens. By searching multiple databases and sources, we identified a total of 37 eligible studies. The incremental yield in smear-positive results (in studies using all smear-positive cases as the denominator) and the increase in sensitivity (in studies that used all culture-positive cases as the denominator) of the third specimen were the main outcomes of interest. Although heterogeneity in study methods and results presented challenges for data synthesis, subgroup analyses suggest that the average incremental yield and/or the increase in sensitivity of examining a third specimen ranged between 2% and 5%. Reducing the recommended number of specimens examined from three to two (particularly to two specimens collected on the same day) could benefit TB control programs, and potentially increase case detection for several reasons. A number of operational research issues need to be addressed. Studies examining the most effective and efficient means to utilize current technologies for microscopic examination of sputum would be most useful if they followed an internationally coordinated and standardized approach, both to strengthen the country-specific evidence base and to permit comparison among studies.

Investigation of human contacts: a Mycobacterium bovis outbreak among cattle at a California dairy.

BACKGROUND: In May 2002, a Mycobacterium bovis outbreak occurred among cattle at a California dairy. We investigated to determine whether persons were infected after working with the cattle or drinking their raw milk. METHODS: We identified persons with potential contact with infected cattle, including dairy workers, their family members, and slaughterhouse workers. Persons were given a tuberculin skin test (TST), and their occupational and milk-drinking habits were recorded. RESULTS: Of 88 potential contacts, 78 (90%) were given a TST; 33 (43%) had positive TST results, of whom 32 were Mexican-born (RR 15.8, 95%CI 2.3-108.8). No persons had active tuberculosis. Eighteen (72%) dairy workers, 11 (27%) family members, and four (33%) slaughterhouse workers had positive TST results. After adjusting for Mexican-birth and age, dairy workers were no more likely to have positive TST results than others (adjusted RR 1.2, 95%CI 0.6-2.1). Forty-one (62%) dairy staff and their family members drank raw milk from the dairy; 21 (51%) had positive TST results and were Mexican-born. All 13 US-born raw milk drinkers had negative TST results. CONCLUSION: A high prevalence of positive TST results was documented among workers at the affected dairy, although results were not independently associated with contact with infected cattle or milk products. Further assessment of California dairy workers should be considered.

[Injury of the long thoracic nerve after LRA, which etiology? Clinical case]. / Danno del nervo toracico lungo dopo ALR: quale eziologia? Caso clinico.

The long thoracic nerve supplies the serratus magnus muscle. Its injury causes "winging" of the scapula and functional limitation of the upper limb. Such lesion is mostly due to chronic trauma, occasionally iatrogenic. This case report presents a case of serratus magnus muscle paralysis following an anesthetic block of the brachial plexus performed at the time of a minor orthopedic surgery of the wrist, in a young healthy woman who was a tennis player. The observed lesion seemed to have been caused by the anesthetic technique employed, but, at the same time, it is impossible to rule out, in the etiology of the disease, a role of other predisposing factors, such as the intense sport activity above mentioned, or of concurrent factors, such as an incorrect position in the immediate postoperative period.

A long term observation of antibody status to chicken anaemia virus in individual chickens of breeder flocks.

The antibody status to chicken anaemia virus (CAV) in four layer breeder flocks was evaluated. Sera were periodically collected from the same 17 to 20 individual chickens of each flock ranging in age from 10 to 63 weeks old. The neutralising and fluorescence antibody were detectable in individual chickens during the observation periods ranging from 13 to 44 weeks. A high prevalence of both neutralising and fluorescence antibodies was observed; however, the prevalence of fluorescence antibody in older chickens was lower than that of neutralising antibody. The geometric mean (GM) of neutralising antibody titres, after all the chickens examined had seroconverted in flocks 1, 2 and 4, ranged from 373.2 to 2940.6. In flock 1, the GM titre at 63 weeks old was significantly lower than that at 37 and 52 weeks old. In flock 4, the GM titre at 48 weeks old was significantly lower than that at 24 and 35 weeks old. In flock 2, the GM titre at more than 31 weeks old significantly increased compared with that at 25 weeks old; this tendency was not seen in the GM of the fluorescence antibody titres. The results indicate that immunity to CAV can last a long time in naturally infected individual chickens.