Treatment of drug-resistant tuberculosis

Lancelot Pinto1,2, Dick Menzies1,21Respiratory Epidemiology and Clinical Research Unit, Montreal Chest Institute, Montreal, QC, Canada; 2Department of Epidemiology and Biostatistics, McGill University, Montreal, QC, CanadaClinical question: What is the best approach to the treatment of drug-resistant tuberculosis (TB)?Results: Evidence-based treatment of drug-susceptible TB is the best means of preventing the development of drug-resistant disease. Suspecting the possibility of drug-resistant TB, and prompt detection of all forms of drug-resistant TB, not only multidrug-resistant and extensively drug-resistant TB, should be part of the algorithm for diagnosis and management of all patients with active TB.Implementation: Treatment of all forms of drug-resistant TB must be tailored to the specific form of resistance with appropriate and effective drug regimens.Keywords: drug-resistant tuberculosis, MDR-TB, treatmen

Development of a simple reliable radiographic scoring system to aid the diagnosis of pulmonary tuberculosis

Rationale: Chest radiography is sometimes the only method available for investigating patients with possible pulmonary tuberculosis (PTB) with negative sputum smears. However, interpretation of chest radiographs in this context lacks specificity for PTB, is subjective and is neither standardized nor reproducible. Efforts to improve the interpretation of chest radiography are warranted. Objectives To develop a scoring system to aid the diagnosis of PTB, using features recorded with the Chest Radiograph Reading and Recording System (CRRS). METHODS: Chest radiographs of outpatients with possible PTB, recruited over 3 years at clinics in South Africa were read by two independent readers using the CRRS method. Multivariate analysis was used to identify features significantly associated with culture-positive PTB. These were weighted and used to generate a score. RESULTS: 473 patients were included in the analysis. Large upper lobe opacities, cavities, unilateral pleural effusion and adenopathy were significantly associated with PTB, had high inter-reader reliability, and received 2, 2, 1 and 2 points, respectively in the final score. Using a cut-off of 2, scores below this threshold had a high negative predictive value (91.5%, 95%CI 87.1,94.7), but low positive predictive value (49.4%, 95%CI 42.9,55.9). Among the 382 TB suspects with negative sputum smears, 229 patients had scores <2; the score correctly ruled out active PTB in 214 of these patients (NPV 93.4%; 95%CI 89.4,96.3). The score had a suboptimal negative predictive value in HIV-infected patients (NPV 86.4, 95% CI 75,94). CONCLUSIONS: The proposed scoring system is simple, and reliably ruled out active PTB in smear-negative HIV-uninfected patients, thus potentially reducing the need for further tests in high burden settings. Validation studies are now required

Private patient perceptions about a public programme; what do private Indian tuberculosis patients really feel about directly observed treatment?

<p>Abstract</p> <p>Background</p> <p>India accounts for one-fifth of the global incident cases of tuberculosis(TB). The country presently has the world's largest directly observed treatment, short course (DOTS) programme, that has shown impressive results and covers almost 100% of the billion-plus Indian population. Despite such a successful programme, the majority of Indian patients with tuberculosis prefer private healthcare, although repeated audits of this sector have shown the quality to be poor.</p> <p>We aimed to ascertain the level of awareness and knowledge of private patients with tuberculosis attending our clinic at a tertiary private healthcare institute with regards to the DOTS programme, understanding the reasons behind their preference for private healthcare, and evaluating their perceptions and reasons for accepting or failing to accept directly observed therapy as a treatment option.</p> <p>Methods</p> <p>A structured interview schedule was administered to private patients with tuberculosis at the P.D. Hinduja Hospital and Medical Research Centre, Mumbai, India between January 2006 to November 2007.</p> <p>Results</p> <p>Only 30 of 200 patients (15%) were aware of the DOTS programme. After being explained what directly observed therapy was, 136 patients (68%) found this form of treatment unacceptable.183 patients (91.5%) preferred buying the drugs themselves to visiting a DOTS centre. 90 patients (45%) were not prepared to be observed while swallowing their TB drugs, finding it an intrusion of privacy.</p> <p>Conclusions</p> <p>Our study reveals a poor knowledge and awareness of the DOTS programme among the cohort of TB patients that we interviewed. The control of TB in India will undoubtedly benefit from more patients being attracted to and treated by the existing DOTS programmes. However, directly observed treatment, in its present form, is considered too rigid and intrusive and is unlikely to be accepted by a majority of patients seeking private healthcare. Novel strategies and more flexible options will have to be devised to ensure higher cure rates without compromising patient choice.</p

Chest radiograph scoring systems for the diagnosis of Active Pulmonary Tuberculosis

Background: Chest radiography is often the only tool available for the investigation of tuberculosis (TB) suspects with negative sputum smears, thus playing a crucial role in clinical decision-making. However, chest radiographs lack specificity for TB, and their interpretation is subjective and not standardized, and therefore not highly reproducible. Efforts to improve the interpretation of chest radiography are warranted, especially with the growing use of digital radiology.Objectives: To systematically review the literature on the use of scoring systems to aid the diagnosis of active pulmonary TB (PTB), and to derive a new, simple scoring system using features noted on the Chest Radiograph Reading and Recording System (CRRS), a tool designed for the documentation of radiographic abnormalities in epidemiological surveys for PTB.Methods: A systematic review of the literature was performed to assess the utility of chest radiograph scoring systems for the diagnosis of PTB, and to use this information to derive a scoring system using the CRRS. Chest radiographs of outpatients with suspected PTB, consecutively recruited over 3 years at clinics in South Africa, were read by two independent readers using CRRS. Multivariable analysis was used to identify features significantly associated with culture-positive PTB, and these were assigned weights and used to generate a composite score.Results: A systematic review of the literature identified 12 studies that used radiographic features as part of scoring systems for the diagnosis of PTB. Six of these were tested in smear-negative patients. There was no scoring system found that involved the exclusive use of radiographic features. Upper lobe infiltrates and cavities were the radiographic features most commonly associated with the disease. The sensitivities of the scoring systems were uniformly high, but all of them lacked specificity. For the study in South Africa, 473 patients were included in the analysis. Large upper lobe opacities, cavities, unilateral pleural effusion and adenopathy were significantly associated with culture-confirmed PTB, had high inter-reader reliability, and received 2, 2, 1 and 2 points, respectively in the final score. When applied to all TB suspects, using a cut-off of ≥ 2, the score had a high negative predictive value (92%, 95%CI 87,95). Among TB suspects with negative sputum smears, the score correctly ruled out active disease in 214 of 229 patients (NPV 93; 95%CI 89,96) Conclusions: Existing radiographic scoring systems for the diagnosis of PTB appear to be sensitive, but lack specificity. The scoring system derived from CRSS is a simple and reliable tool that may be useful for ruling out active PTB in smear-negative patients. Validation studies are needed to confirm these initial findings.Contexte: La radiographie thoracique est souvent le seul outil disponible pour le dépistage de la tuberculose (TB) chez les patients ayant des frottis d'expectoration négatifs, lui donnant ainsi un rôle crucial dans la prise de décision clinique. Toutefois, les radiographies thoraciques manquent de spécificité pour la tuberculose, et leur interprétation est subjective et non standardisée, et donc n'est pas très reproductible. Les efforts visant à améliorer l'interprétation de la radiographie pulmonaire sont justifiés, surtout vu l'utilisation croissante de la radiologie numérique.Objectifs: Les objectifs incluent une recherche systématique de la littérature sur l'utilisation des systèmes de notation pour aider le diagnostic de la tuberculose pulmonaire active (TBP), et d'en tirer un nouveau système de notation simple à partir du Chest Radiograph Reading and Recording System (CRRS) (Système de Lecture et Notation des radiographies thoraciques), un outil conçu pour la documentation des anomalies radiologiques dans les études épidémiologiques sur la TBP.Méthodes: Une recherche systématique de la littérature a été effectuée pour évaluer l'utilité des systèmes de notation des radiographies thoraciques pour le diagnostic de la TBP, et pour utiliser ces informations pour dériver un système de notation à partir du CRRS. Les radiographies thoraciques de patients ambulatoires suspects de TBP, recrutés consécutivement sur 3 ans dans des cliniques en Afrique du Sud, ont été lues par deux lecteurs indépendants en utilisant CRRS. Une analyse multivariée a été utilisée pour identifier les caractéristiques significativement associées à la TBP à culture positive, et ceux-ci ont reçu une importance respective et ont été utilisé pour générer un score composite.Résultats: Une recherche systématique de la littérature a identifié 12 études qui ont utilisé des systèmes de notation pour analyser les caractéristiques radiographiques dans le cours du diagnostic de la TBP. Six d'entre elles comprenaient seulement des patients à frottis négatif. Aucun système de notation ne comprenait l'usage exclusif des caractéristiques radiographiques. Des cavités et des infiltrats dans les lobes supérieurs étaient les caractéristiques radiographiques les plus couramment associées à la maladie. Les sensibilités des systèmes de notation étaient uniformément élevées, mais chacun d'eux manquait de spécificité.Dans l'étude en Afrique du Sud, 473 patients ont été inclus dans l'analyse. Les grandes opacités du lobe supérieur, les cavités, un épanchement pleural unilatéral ainsi que la présence d'adénopathie étaient significativement associés à la TBP confirmée par culture, avaient un haut taux de fiabilité entre lecteur, et ont reçu 2, 2, 1 et 2 points, respectivement dans le final. Lorsqu'appliqué à tous les cas suspects de tuberculose, en utilisant un seuil de ≥ 2, le score avait une forte valeur prédictive négative (92%, IC 95% 87-95). Parmi les suspects de TB à frottis négatifs, le score a correctement exclu la présence de maladie active dans 214 des 229 patients (VPN 93, 95% CI 89-96).Conclusions: Les systèmes actuels de notation radiographiques pour le diagnostic de TBP semblent être sensibles, mais manquent de spécificité. Le système de notation dérivée de la CRSS est un outil simple et fiable qui peut être utile pour exclure la TBP active chez les patients à frottis négatif. Des études de validation sont nécessaires pour confirmer ces premiers résultats

Tuberculosis Management by Private Practitioners in Mumbai, India: Has Anything Changed in Two Decades?

Setting: Mumbai, India. A study conducted in Mumbai two decades ago revealed the extent of inappropriate tuberculosis (TB) management practices of private practitioners. Over the years, India’s national TB programme has made significant progress in TB control. Efforts to engage private practitioners have also been made with several successful documented public-private mix initiatives in place. Objective: To study prescribing practices of private practitioners in the treatment of tuberculosis, two decades after a similar study conducted in the same geographical area revealed dismal results. Methods: Survey questionnaire administered to practicing general practitioners attending a continuing medical education programme. Results: The participating practitioners had never been approached or oriented by the local TB programme. Only 6 of the 106 respondents wrote a prescription with a correct drug regimen. 106 doctors prescribed 63 different drug regimens. There was tendency to over treat with more drugs for longer durations. Only 3 of the 106 respondents could write an appropriate prescription for treatment of multidrug-resistant TB. Conclusions: With a vast majority of private practitioners unable to provide a correct prescription for treating TB and not approached by the national TB programme, little seems to have changed over the years. Strategies to control TB throug

Emphysema detected on computed tomography and risk of lung cancer: a systematic review and meta-analysis.

BACKGROUND: Studies exploring the association between emphysema detected on chest computed tomography (CT) and lung cancer have yielded mixed results. Our objective was to systematically review the evidence for this association. METHODS: We searched MEDLINE, EMBASE and the Cochrane Library for the terms "lung cancer", "emphysema" and "computed tomography" without language restriction. Bibliographies were also reviewed and authors contacted for additional information. Human studies in which CTs were performed and assessed for emphysema and in which subjects were evaluated systematically for lung cancer were included. Qualitative synthesis of evidence was performed followed by pooling of effect estimates using a random-effects model. RESULTS: Of 187 citations, 7 were included in the qualitative synthesis and 5 in the meta-analysis. Three studies assessing emphysema visually observed an association with lung cancer, independent of smoking history and airflow obstruction. Three studies using densitometry to detect emphysema found no association with lung cancer. Another study directly comparing automated and visual emphysema detection techniques found only the latter to associate with lung cancer. Among 7368 subjects included in the meta-analysis, 2809 had emphysema on CT and 870 were diagnosed with lung cancer. The pooled adjusted odds ratio for lung cancer in the presence of emphysema on CT was 2.11 (95% CI 1.10-4.04); stratification by detection method yielded OR of 3.50 (95% CI 2.71-4.51) with visually detected emphysema and 1.16 (95% CI 0.48-2.81) with densitometric emphysema. CONCLUSION: Systematic literature review shows emphysema detected visually on CT to be independently associated with increased odds of lung cancer. This association did not hold with automated emphysema detection

Analysis of the physicians' prescriptions for MDR TB.^*

<p>*25 prescriptions were blank.</p

Genome-wide loss of heterozygosity analysis ofWT1-wild-type andWT1-mutant Wilms tumors

International audienceWilms tumor (WT) is genetically heterogeneous, and the one known WT gene, WT1 at 11p13, is altered in only a subset of WTs. Previous loss of heterozygosity (LOH) analyses have revealed the existence of additional putative WT genes at 11p15, 16q, and 1p, but these analyses examined only one or a handful of chromosomes or looked at LOH at only a few markers per chromosome. We conducted a genome-wide scan for LOH in WT by using 420 markers spaced at an average of 10 cM throughout the genome and analyzed the data for two genetically defined subsets of WTs: those with mutations in WT1 and those with no detectable WT1 alteration. Our findings indicated that the incidence of LOH throughout the genome was significantly lower in our group of WTs with WT1 mutations. In WT1–wild-type tumors, we observed the expected LOH at 11p, 16q, and 1p, and, in addition, we localized a previously unobserved region of LOH at 9q. Using additional 9q markers within this region of interest, we ublocalized the region of 9q LOH to the 12.2 Mb between D9S283 and a simple tandem repeat in BAC RP11-177I8, a region containing several potential tumor-suppressor genes. As a result, we have established for the first time that WT1-mutant and WT1–wild-type WTs differ significantly in their patterns of LOH throughout the genome, suggesting that the genomic regions showing LOH in WT1–wild-type tumors harbor genes whose expression is regulated by the pleiotropic effects of WT1. Our results implicate 9q22.2–q31.1 as a region containing such a gene