Diabetes characteristics and long-term management needs in diabetic TB patients.

BACKGROUND: Diabetes mellitus (DM) is common among patients with TB. We assessed DM characteristics and long-term needs of DM-TB patients after completing TB treatment.METHODS: Newly diagnosed TB patients with DM were recruited for screening in a randomised clinical trial evaluating a simple algorithm to improve glycaemic control during TB treatment. DM characteristics, lifestyle and medication were compared before and after TB treatment and 6 months later. Risk of cardiovascular disease (CVD), albuminuria and neuropathy were assessed after TB treatment.RESULTS: Of 218 TB-DM patients identified, 170 (78%) were followed up. Half were males, the mean age was 53 years, 26.5% were newly diagnosed DM. High glycated haemoglobin at TB diagnosis (median 11.2%) decreased during TB treatment (to 7.4% with intensified management and 8.4% with standard care), but this effect was lost 6 months later (9.3%). Hypertension and dyslipidemia contributed to a high 10-year CVD risk (32.9% at month 6 and 35.5% at month 12). Neuropathy (33.8%) and albuminuria (61.3%) were common. After TB treatment, few patients used CVD-mitigating drugs.CONCLUSION: DM in TB-DM patients is characterised by poor glycaemic control, high CVD risk, and nephropathy. TB treatment provides opportunities for better DM management, but effort is needed to improve long-term care.

Implementing the 4R and 9H regimens for TB preventive treatment in Indonesia.

BACKGROUND: The implementation of tuberculosis preventive treatment (TPT) is challenging especially in resource-limited settings. As part of a Phase 3 trial on TPT, we described our experience with the use of rifampicin for 4 months (4R) and isoniazid for 9 months (9H) in Indonesia.METHODS: In 2011-2017, children and adults with latent TB infection were randomised to either 4R or 9H and followed until 16 months after randomisation for children and 28 months for adults. The primary outcome was the treatment completion rate. Secondary outcomes were Grade 3-5 adverse events (AEs), active TB occurrence, and health costs.RESULTS: A total of 157 children and 860 adults were enrolled. The 4R treatment completion rate was significantly higher than that of 9H (78.7% vs. 65.5%), for a rate difference of 13.2% (95% CI 7.1-19.2). No Grade 3-5 AEs were reported in children; in adults, it was lower in 4R (0.4%) compared to 9H (2.8%). The incidence of active TB was lower with 4R than with 9H (0.09/100 person-year vs. 0.36/100 person-year) (rate difference: -0.36/100 person-year). The total cost per patient was lower for the 4R regimen than for the 9H regimen (USD151.9 vs. USD179.4 in adults and USD152.9 vs. USD206.5 in children)CONCLUSIONS: Completion and efficacy rates for 4R were better than for 9H. Compared to 9H, 4R was cheaper in all age groups, safer in adults and equally safe in children. The Indonesian TB program could benefit from these benefits of the 4R regimen.

Educational counselling of patients with combined TB and diabetes mellitus: a randomised trial.

SETTING: Newly diagnosed pulmonary TB with diabetes mellitus (DM) comorbidity attending clinics in Bandung City, Indonesia. OBJECTIVE: To describe the effect of educational counselling on patients' knowledge about TB (transmission, treatment, risk factors) and DM (symptoms, treatment, complications, healthy lifestyle), adherence to medication, and to assess characteristics associated with knowledge. DESIGN: All patients received counselling and were then randomised to either structured education on TB-DM, combined with clinical monitoring and medication adjustment (intervention arm), or routine care (control arm). Knowledge and adherence were assessed using a questionnaire. RESULTS: Baseline and 6-month questionnaires were available for 108 of 150 patients randomised (60/76 in the intervention arm and 48/74 in the control arm). Patients knew less about DM than about TB. There was no significant difference in the proportion with knowledge improvement at 6 months, both for TB (difference of differences 14%; P = 0.20) or for DM (10%; P = 0.39) between arms. Intervention arm patients were more likely to adhere to taking DM medication, with fewer patients reporting ever missing oral DM drugs than those in the control arm (23% vs. 48%; P = 0.03). Higher education level was associated with good knowledge of both TB and DM. CONCLUSIONS: Structured education did not clearly improve patients' knowledge. It was associated with better adherence to DM medication, but this could not be attributed to education alone. More efforts are needed to improve patients' knowledge, especially regarding DM.

CONTEXTE: Patients atteints de diabète sucré (DM) ayant récemment reçu un diagnostic de TB pulmonaire consultant dans les cliniques de la ville de Bandung, Indonésie. OBJECTIF: Décrire l'effet de conseils éducatifs sur les connaissances des patients en matière de TB (transmission, traitement, facteurs de risque), de DM (symptômes, traitement, complications, mode de vie sain) et d'observance thérapeutique, et évaluer les caractéristiques associées à ces connaissances. MÉTHODE: Tous les patients ont reçu des conseils et ont ensuite été randomisés dans l'un des deux groupes suivants : programme d'éducation structuré sur la TB-DM associé à un suivi clinique et à un ajustement thérapeutique (groupe d'intervention) ou prise en charge de routine (groupe témoin). Les connaissances et l'observance ont été évaluées par questionnaire. RÉSULTATS: Les questionnaires administrés à l'inclusion et à 6 mois étaient disponibles pour 108 des 150 patients randomisés (60/76 dans le groupe d'intervention et 48/74 dans le groupe témoin). Les connaissances des patients étaient moins bonnes sur le DM que sur la TB. Aucune différence significative n'a été observée entre les groupes dans la proportion de patients dont les connaissances s'étaient améliorées à 6 mois, tant pour la TB (différence des différences 14% ; P = 0,20) que pour le DM (10% ; P = 0,39). Les patients du groupe d'intervention étaient plus susceptibles d'observer correctement leur traitement antidiabétique. Moins de patients ont en effet rapporté avoir manqué une dose de leur traitement antidiabétique oral par rapport au groupe témoin (23% vs. 48% ; P = 0,03). Un niveau d'éducation plus élevé a été associé à de bonnes connaissances sur la TB et le DM. CONCLUSIONS: Le programme d'éducation structuré n'a pas amélioré de manière évidente les connaissances des patients. Ce programme a été associé à une meilleure observance du traitement antidiabétique, mais cela n'a pas pu être attribué au seul programme d'éducation. Davantage d'efforts sont nécessaires pour améliorer les connaissances des patients, notamment sur le DM.

A public health approach to increase treatment of latent TB among household contacts in Brazil.

SETTING: Two consecutive trials were conducted to evaluate the effectiveness of a public health approach to identify and correct problems in the care cascade for household contacts (HHCs) of TB patients in three Brazilian high TB incidence cities.METHODS: In the first trial, 12 clinics underwent standardised evaluation using questionnaires administered to TB patients, HHCs and healthcare workers, and analysis of the cascade of latent TB care among HHCs. Six clinics were then randomised to receive interventions to strengthen management of latent TB infection (LTBI), including in-service training provided by nurses, work process organisation and additional clinic-specific solutions. In the second trial, a similar but streamlined evaluation was conducted in two clinics, who then received initial and subsequent intensive in-service training provided by a physician.RESULTS: In the evaluation phase of both trials, many HHCs were identified, but few started LTBI treatment. After the intervention, the number of HHCs initiating treatment per 100 active TB patients increased by 10 (95%CI - 11 to 30) in the first trial, and by 44 (95%CI 26 to 61) in the second trial.DISCUSSION: A public health approach with standardised evaluation, local decisions for improvements, followed by intensive initial and in-service training appears promising for improved LTBI management.

Early chest X-ray in persons with presumptive tuberculosis increases Xpert® MTB/RIF diagnostic yield and efficiency.

Adult presumptive tuberculosis (TB) patients (n = 1690) were screened for TB using a questionnaire, chest X-ray (CXR) and sputum microscopy for acid-fast bacilli (AFB); Mycobacterium tuberculosis culture was performed for 74% of the patients and Xpert® MTB/RIF was done for 17.2%. Among patients recruited, 943 (55.8%) were diagnosed with TB, of whom 870 (92.3%) were bacteriologically confirmed and 73 (7.7%) were clinically diagnosed on the basis of CXR. Using CXR prior to culture or Xpert testing reduces the number needed to screen from 7.6 to 5.0. Using CXR to triage for culture or Xpert testing reduces the number of missed cases and increases the efficiency of culture and Xpert testing.

Des patients adultes présumés atteints de TB (n = 1690) ont été dépistés à l'aide d'un questionnaire, d'une radiographie pulmonaire (CXR) et d'une microscopie de crachats à la recherche des bacilles acido-alcoolo-résistants; une culture de Mycobacterium tuberculosis a été réalisée chez 74% des patients et un test Xpert® MTB/RIF, chez 17,2%. Parmi les patients recrutés, 943 (55,8%) ont eu un diagnostic de TB, dont 870 (92,3%) ont été confirmés par bactériologie et 73 (7,7%) ont été diagnostiqués sur la CXR. Recourir à la CXR avant la culture ou le test Xpert réduit le nombre requis pour dépister un cas de 7,6 à 5,0. L'utilisation de la CXR pour le triage avant la culture ou le test Xpert réduit les cas manqués et augmente l'efficacité de l'utilisation de la culture et de l'Xpert.

Se investigó de la tuberculosis (TB) en pacientes adultos con presunción clínica de la enfermedad (n = 1690) mediante un cuestionario, la radiografía de tórax (CXR) y la baciloscopia del esputo; se practicó el cultivo para Mycobacterium tuberculosis en 74% de los pacientes y la prueba Xpert® MTB/RIF en 17,2%. De los pacientes que participaron se diagnosticó la TB en 943 (55,8%), de los cuales 870 (92,3%) con confirmación bacteriológica y 73 (7,7%) con diagnóstico clínico a partir de la CXR. El hecho de realizar la CXR o la prueba Xpert antes del cultivo disminuye de 7,6 a 5,0 el número de pacientes que deben someterse a detección. El uso de la CXR para seleccionar los casos en que se debe practicar el cultivo o la prueba Xpert disminuye los casos pasados por alto y aumenta la eficiencia del uso del cultivo y la prueba Xpert.

Prevalence of positive reactions in intradermal and IgE serological allergy tests in dogs from South Australia, and the subsequent outcome of allergen-specific immunotherapy.

OBJECTIVE: To determine the prevalence of positive allergen reactions in intradermal and IgE serological tests in dogs presenting to a dermatology referral centre in South Australia and the clinical efficacy of subsequent allergen-specific immunotherapy. DESIGN: Retrospective study. METHODS: Results from 108 intradermal allergy tests, 25 IgE serological assays and immunotherapy outcomes in 37 dogs were retrospectively analysed. Immunotherapy outcomes were determined as excellent, good, modest or failure using a global assessment of efficacy matrix which incorporated pruritus scores, lesion severity, medication requirements, and owner and clinician opinion. RESULTS: The most common positive reactions in intradermal allergy tests were Red clover (59%), Dermatophagoides farinae (29%), Tyrophagus putrescentiae (28%), Yellow dock (25%) and Malassezia pachydermatis (24%). In the IgE serological tests, Yorkshire fog grass (40%), Yellow dock (36%), Kentucky bluegrass (36%) and T. putrescentiae (36%) were the most commonly reported positive results. The outcome of allergen-specific immunotherapy was judged to be excellent in 20% of dogs, good in 15%, modest in 18% and a failure in 47%. CONCLUSION: As has been reported in other geographical areas, environmental mites and plant pollens frequently gave positive reactions in allergy tests in South Australia. However, the prevalence of individual allergen reactions differed between intradermal and IgE serological tests, with M. pachydermatis being identified as a common cause of hypersensitivity in intradermal tests but not in IgE serological assays. Immunotherapy was judged to be a beneficial treatment in 35% of dogs but was essentially unsuccessful in 65%.

Lesion distribution in cases of canine atopic dermatitis in South Australia.

OBJECTIVE: To determine the lesion distribution patterns in different breeds of dogs affected by atopic dermatitis in South Australia. METHODS: The presence or absence of erythematous skin lesions in 267 cases of canine atopic dermatitis (CAD) was recorded across 36 anatomical sites. Breeds represented by ≥ 9 dogs were included in the analysis. The percentage of dogs showing lesions at each of the body sites was calculated and illustrated on colour-coded diagrams. Variations in affected body sites within and between breeds were compared using Kruskal-Wallis ANOVA and Dunn's multiple comparison tests. RESULTS: The prevalence of skin lesions at different body sites differed significantly both in the population as a whole and within breeds. The sites affected in ≥ 75% dogs were the dorsal and ventral aspects of the front and hind paws. The sites affected in 50-74% were the medial pinnae, axillae, ventral chest, abdomen and perineum. Sites affected in 25-49% of dogs included the face, periocular region and forelimb. Remaining body sites were affected in < 25% of dogs. Analysis at the breed level revealed some differences from this standard distribution pattern. CONCLUSION: The results of this study confirmed the typical lesion distributions seen in CAD and highlighted some subtle differences in breeds commonly seen in South Australia. This will be useful for clinical practitioners in prioritising differential diagnoses for pruritic skin conditions.

Application of Bayesian statistics to estimate nitrous oxide emission factors of three nitrogen fertilisers on UK grasslands.

Trapezoidal integration by linear interpolation of data points is by far the most commonly used method of cumulative flux calculations of nitrous oxide (N2O) in studies that use flux chambers; however, this method is incapable of providing accurate uncertainty estimates. A Bayesian approach was used to calculate N2O emission factors (EFs) and their associated uncertainties from flux chamber measurements made after the application of nitrogen fertilisers, in the form of ammonium nitrate (AN), urea (Ur) and urea treated with Agrotain® urease inhibitor (UI) at four grassland sites in the UK. The comparison between the cumulative fluxes estimated using the Bayesian and linear interpolation methods were broadly similar (R2 = 0.79); however, the Bayesian method was capable of providing realistic uncertainties when a limited number of data points is available. The study reports mean EF values (and 95% confidence intervals) of 0.60 ±â€¯0.63, 0.29 ±â€¯0.22 and 0.26 ±â€¯0.17% of applied N emitted as N2O for the AN, Ur and UI treatments, respectively. There was no significant difference between N2O emissions from the Ur and UI treatments. In the case of the automatic chamber data collected at one site in this study, the data did not fit the log-normal model, implying that more complex models may be needed, particularly for measurement data with high temporal resolution.

Point of care HbA1c level for diabetes mellitus management and its accuracy among tuberculosis patients: a study in four countries.

BACKGROUND: Diabetes mellitus (DM) is common among tuberculosis (TB) patients and often undiagnosed or poorly controlled. We compared point of care (POC) with laboratory glycated haemoglobin (HbA1c) testing among newly diagnosed TB patients to assess POC test accuracy, safety and acceptability in settings in which immediate access to DM services may be difficult. METHODS: We measured POC and accredited laboratory HbA1c (using high-performance liquid chromatography) in 1942 TB patients aged 18 years recruited from Peru, Romania, Indonesia and South Africa. We calculated overall agreement and individual variation (mean ± 2 standard deviations) stratified by country, age, sex, body mass index (BMI), HbA1c level and comorbidities (anaemia, human immunodeficiency virus [HIV]). We used an error grid approach to identify disagreement that could raise significant concerns. RESULTS: Overall mean POC HbA1c values were modestly higher than laboratory HbA1c levels by 0.1% units (95%CI 0.1-0.2); however, there was a substantial discrepancy for those with severe anaemia (1.1% HbA1c, 95%CI 0.7-1.5). For 89.6% of 1942 patients, both values indicated the same DM status (no DM, HbA1c <6.5%) or had acceptable deviation (relative difference <6%). Individual agreement was variable, with POC values up to 1.8% units higher or 1.6% lower. For a minority, use of POC HbA1c alone could result in error leading to potential overtreatment (n = 40, 2.1%) or undertreatment (n = 1, 0.1%). The remainder had moderate disagreement, which was less likely to influence clinical decisions. CONCLUSION: POC HbA1c is pragmatic and sufficiently accurate to screen for hyperglycaemia and DM risk among TB patients.

Trained innate immunity and resistance to Mycobacterium tuberculosis infection.

BACKGROUND: Some individuals, even when heavily exposed to an infectious tuberculosis patient, develop neither active nor latent tuberculosis infection (LTBI). This 'early clearance' of Mycobacterium tuberculosis is associated with a history of bacillus Calmette-Guérin (BCG) vaccination. As BCG vaccination can boost innate immune responses through a process termed 'trained immunity', we hypothesize that BCG-induced trained innate immunity contributes to early clearance of M. tuberculosis. OBJECTIVES: We describe the epidemiological evidence and biological concepts of early clearance and trained immunity, and the possible relation between these two processes through BCG vaccination. SOURCES: Relevant data from published reports up to November 2018 were examined in the conduct of this review. CONTENT: Several observational studies and one recent randomized trial support the concept that boosting innate immunity contributes to protection against M. tuberculosis infection, with BCG vaccination providing approximately 50% protection. The molecular mechanisms mediating early clearance remain largely unknown, but we propose that trained immunity, characterized by epigenetic and metabolic reprogramming of innate immune cells such as monocytes or macrophages, is at least partially responsible for eliminating the mycobacteria and inducing early clearance. IMPLICATIONS: Future studies should examine if BCG revaccination increases early clearance of M. tuberculosis through induction of trained immunity. Epigenetic or metabolic modulation may further boost BCG-induced trained innate immunity to promote tuberculosis prevention. New tuberculosis vaccine candidates should also be examined for their capacity to improve protection against M. tuberculosis infection and induce trained immunity.

The cost of treating diabetic ketoacidosis in an adolescent population in the UK: a national survey of hospital resource use.

AIMS: Adolescents with Type 1 diabetes commonly experience episodes of ketoacidosis. In 2014, we conducted a nationwide survey on the management of diabetic ketoacidosis in young people. The survey reported how individual adolescents with diabetes were managed. However, the costs of treating diabetic ketoacidosis were not reported. METHODS: Using this mixed population sample of adolescents, we took a 'bottom-up' approach to cost analysis aiming to determine the total expense associated with treating diabetic ketoacidosis. The data were derived using the information from the national UK survey of 71 individuals, collected via questionnaires sent to specialist paediatric diabetes services in England and Wales. RESULTS: Several assumptions had to be made when analysing the data because the initial survey collection tool was not designed with a health economic model in mind. The mean time to resolution of diabetic ketoacidosis was 15.0 h [95% confidence interval (CI) 13.2, 16.8] and the mean total length of stay was 2.4 days (95% CI 1.9, 3.0). Based on data for individuals and using the British Society of Paediatric Endocrinology and Diabetes (BSPED) guidelines, the cost analysis shows that for this cohort, the average cost for an episode of diabetic ketoacidosis was £1387 (95% CI 1120, 1653). Regression analysis showed a significant cost saving of £762 (95% CI 140, 1574; P = 0.04) among those treated using BSPED guidelines. CONCLUSION: We have used a bottom-up approach to calculate the costs of an episode of diabetic ketoacidosis in adolescents. These data suggest that following treatment guidelines can significantly lower the costs for managing episodes of diabetic ketoacidosis.

Evidence for supercoughers in an analysis of six tuberculosis cohorts from China, Peru, The Gambia and Uganda.

BACKGROUND: It is very difficult to observe tuberculosis (TB) transmission chains and thus, identify superspreaders. We investigate cough duration as a proxy measure of transmission to assess the presence of potential TB superspreaders.DESIGN: We analyzed six studies from China, Peru, The Gambia and Uganda, and determined the distribution of cough duration and compared it with several theoretical distributions. To determine factors associated with cough duration, we used linear regression and boosted regression trees to examine the predictive power of patient, clinical and environmental characteristics.RESULTS: We found within-study heterogeneity in cough duration and strong similarities across studies. Approximately 20% of patients contributed 50% of total cough days, and around 50% of patients contributed 80% of total cough days. The cough duration distribution suggested an initially increasing, and subsequently, decreasing hazard of diagnosis. While some of the exposure variables showed statistically significant associations with cough duration, none of them had a strong effect. Multivariate analyses of different model types did not produce a model that had good predictive power.CONCLUSION: We found consistent evidence for the presence of supercoughers, but no characteristics predictive of such individuals.

Nonlinear Kinetic Ion Response to Small Scale Magnetic Islands in Tokamak Plasmas: Neoclassical Tearing Mode Threshold Physics.

A new drift-kinetic theory of the ion response to magnetic islands in tokamak plasmas is presented. Small islands are considered, with widths w much smaller than the plasma radius r, but comparable to the trapped ion orbit width ρ_{bi}. An expansion in w/r reduces the system dimensions from five down to four. In the absence of an electrostatic potential, the ions follow stream lines that map out a drift-island structure that is identical to the magnetic island, but shifted by an amount ∼ few ρ_{bi}. The ion distribution function is flattened across these drift islands, not the magnetic island. For small islands, w∼ρ_{bi}, the shifted drift islands result in a pressure gradient being maintained across the magnetic island, explaining previous simulation results [E. Poli et al., Phys. Rev. Lett. 88, 075001 (2002)PRLTAO0031-900710.1103/PhysRevLett.88.075001]. To maintain quasineutrality an electrostatic potential forms, which then supports a pressure gradient in the electrons also. This influence on the electron physics is shown to stabilize small magnetic islands of width a few ion banana widths, providing a new threshold mechanism for neoclassical tearing modes-a key result for the performance of future tokamaks, including ITER.

Computer-assisted chest radiography reading for tuberculosis screening in people living with diabetes mellitus.

BACKGROUND: Diabetes mellitus is a significant risk factor for tuberculosis (TB). We evaluated the performance of computer-aided detection for tuberculosis (CAD4TB) in people living with diabetes mellitus (PLWD) in Indonesia. METHODS: PLWD underwent symptom screening and chest X-ray (CXR); sputum was examined in those with positive symptoms and/or CXR. Digital CXRs were scored using CAD4TB and analysed retrospectively using clinical and microbiological diagnosis as a reference. The area under the receiver operator curve (AUC) of CAD4TB scores was determined, and an optimal threshold score established. Agreement between CAD4TB and the radiologist's reading was determined. RESULTS: Among 346 included PLWD, seven (2.0%) had microbiologically confirmed and two (0.6%) had clinically diagnosed TB. The highest agreement of CAD4TB with radiologist reading was achieved using a threshold score of 70 (κ = 0.41, P < 0.001). The AUC for CAD4TB was 0.89 (95%CI 0.73-1.00). A threshold score of 65 for CAD4TB resulted in a sensitivity, specificity, positive predictive value and negative predictive value of respectively 88.9% (95%CI 51.8-99.7), 88.5% (95%CI 84.6-91.7), 17.0% (95%CI 7.6-30.8) and 99.6% (95%CI 98.2-100). With this threshold, 48 (13.9%) individuals needed microbiological examination and no microbiologically confirmed cases were missed. CONCLUSIONS: CAD4TB has potential as a triage tool for TB screening in PLWD, thereby significantly reducing the need for microbiological examination.

Clinical management of combined tuberculosis and diabetes.

Optimal management of combined tuberculosis (TB) and diabetes (DM) is important but challenging in terms of achieving good disease outcomes and avoiding toxicity, drug interactions and other challenges. DM management during anti-tuberculosis treatment, aimed at improving TB treatment outcomes and reducing DM-related morbidity and mortality, consists of glycaemic control and measures to reduce the risk of cardiovascular disease. Metformin, the glucose-lowering drug of choice for TB patients, has no meaningful interaction with rifampicin (RMP), and may reduce TB mortality. Insulin is effective for severe hyperglycaemia, but has several disadvantages that limit its use in TB patients. Cardiovascular risk assessment should be considered in TB-DM patients to guide management in terms of counselling and prescription of antihypertensive, lipid-lowering and anti-platelet treatment. With regard to anti-tuberculosis treatment, DM is associated with an increased risk of drug resistance, lower exposure to anti-tuberculosis drugs, treatment failure and recurrent TB. Patients therefore need careful assessment before, during and possibly after anti-tuberculosis treatment. Although no studies have been performed, anti-tuberculosis treatment may also have to be prolonged or intensified in terms of regimen or drug dosage if DM is present. With regard to service delivery, combined treatment should probably be administered, supervised and monitored as much as possible in a TB clinic. Local circumstances and severity of DM will guide the need for referral of patients to specialised DM care, and continuation of DM care after completion of anti-tuberculosis treatment. More data are also needed for the management of TB-DM patients with human immunodeficiency virus co-infection.

Nephrogenic Adenoma Complicating Renal Transplantation: A Case Report and Discussion.

Nephrogenic adenoma (NA) is a benign adenomatous lesion of the urinary tract. Long considered to be a rare phenomenon, case series from the renal transplant population suggest that it may be much more common within this group. Although NA is considered to be a lesion with low premalignant potential, hematuria, lower urinary tract symptoms, and recurrent urinary tract infections (UTIs) are frequently observed in the context of NA. Furthermore, after resection of NA, lesion recurrence and persistent symptoms are frequently observed. Here we present the case of a 69-year-old male renal transplant recipient with NA and associated recurrent UTIs despite cystoscopic resection of the primary lesion. This case is illustrative of the clinical impact of NA and the need for ongoing work into the development of strategies to manage this problematic phenomenon.

Feasibility of two active case finding approaches for detection of tuberculosis in Bandung City, Indonesia.

Setting: A community health clinic catchment area in the eastern part of Bandung City, Indonesia. Objective: To evaluate the feasibility of two different screening interventions using community health workers (CHWs) in detecting tuberculosis (TB) cases. Design: This was a feasibility study of 1) house-to-house TB symptom screening of five randomly selected 'neighbourhoods' in the catchment area, and 2) selected screening of household contacts of TB index patients and their neighbouring households. Acceptability was assessed through focus group discussions with key stakeholders. Results: Of 5100 individuals screened in randomly selected neighbourhoods, 48 (0.9%) reported symptoms, of whom 38 provided sputum samples; no positive TB was found. No TB cases were found among the 88 household contacts or the 423 neighbourhood contacts. With training, regular support and supervision from research staff and local community health centre staff, CHWs were able to undertake screening effectively, and almost all householders were willing to participate. Conclusion: The use of CHWs for TB screening could be integrated into routine practice relatively easily in Indonesia. The effectiveness of this would need further exploration, particularly with the use of improved diagnostics such as chest X-ray and sputum culture.

Contexte : Une zone de desserte d'un centre de santé communautaire dans la partie est de la ville de Bandung, Indonésie.Objectif : Evaluer la faisabilité de deux différentes interventions de dépistage recourant à des travailleurs de santé communautaire (CHW) dans la détection des cas de la tuberculose (TB).Schéma : Une étude de faisabilité : 1) du dépistage des symptômes de TB en porte à porte dans cinq quartiers sélectionnés au hasard dans la zone de desserte, et 2) recherche des contacts familiaux des patients TB index et leur voisinage. L'acceptabilité a été évaluée grâce à des groupes focaux avec les partenaires clés.Résultats : Sur 5100 individus dépistés dans des quartiers sélectionnés au hasard, 48 (0,9%) ont rapporté des symptômes, dont 38 ont fourni des crachats : aucune TB n'a été découverte. Aucun cas de TB n'a été trouvé parmi les 88 contacts familiaux ni parmi les 423 personnes du voisinage. Avec une formation, un soutien régulier et une supervision par le personnel de recherche et le personnel du centre de santé communautaire local, les CHW pourraient efficacement entreprendre le dépistage, et presque tous les habitants ont accepté de participer.Conclusion : Le recours aux CHW pour le dépistage de la TB pourrait assez facilement être intégré dans la pratique de routine en Indonésie. L'efficacité de cette stratégie mériterait d'être explorée davantage, en particulier en recourant à des outils diagnostiques améliorés comme une radiographie pulmonaire et une culture de crachats.

Marco de referencia: La zona de influencia de un consultorio comunitario en la parte oriental de la ciudad de Bandung, en Indonesia.Objetivo: Evaluar la factibilidad de dos intervenciones diferentes de detección sistemática practicadas por los agentes de salud comunitarios (CHW) en la búsqueda de casos de tuberculosis (TB).Método: Se llevó a cabo un estudio de factibilidad que examinó: 1) la detección sistemática de los síntomas de TB, de puerta a puerta, en cinco barrios de la zona de influencia escogidos de manera aleatoria y 2) la investigación de contactos de los casos nuevos de TB en sus hogares y en el vecindario. Se organizaron grupos de opinión con interesados directos clave a fin de evaluar la factibilidad de la intervención.Resultados: De las 5100 personas participantes en los vecindarios escogidos, 48 refirieron síntomas (0,9%) y 38 aportaron muestras de esputo, de las cuales ninguna fue positiva para TB. No se detectaron casos de TB en los 88 hogares de los contactos ni en los 423 contactos del vecindario. Con la capacitación, el apoyo periódico y la supervisión por parte del grupo de investigación y del personal de salud del centro comunitario local, los CHW emprendieron de manera eficaz una detección sistemática y casi todos los miembros de los hogares aceptaron participar.Conclusión: La participación de los CHW en la detección sistemática de la TB se puede integrar sin dificultad en la práctica corriente en Indonesia. Se precisa un examen más detenido de la eficacia práctica de esta medida, en especial con la utilización de métodos diagnósticos mejorados como la radiografía de tórax y el cultivo de muestras de esputo.

Epithelial requirement for in vitro proliferation and xenograft growth and metastasis of MDA-MB-468 human breast cancer cells: oncogenic rather than tumor-suppressive role of E-cadherin.

BACKGROUND: Epithelial-to-mesenchymal transition (EMT) is associated with downregulated E-cadherin and frequently with decreased proliferation. Proliferation may be restored in secondary metastases by mesenchymal-to-epithelial transition (MET). We tested whether E-cadherin maintains epithelial proliferation in MDA-MB-468 breast cancer cells, facilitating metastatic colonization in severe combined immunodeficiency (SCID) mice. METHODS: EMT/MET markers were assessed in xenograft tumors by immunohistochemistry. Stable E-cadherin manipulation was effected by transfection and verified by Western blotting, immunocytochemistry, and quantitative polymerase chain reaction (qPCR). Effects of E-cadherin manipulation on proliferation and chemomigration were assessed in vitro by performing sulforhodamine B assays and Transwell assays, respectively. Invasion was assessed by Matrigel outgrowth; growth in vivo was assessed in SCID mice; and EMT status was assessed by qPCR. Hypoxic response of E-cadherin knockdown cell lines was assessed by qPCR after hypoxic culture. Repeated measures analysis of variance (ANOVA), one- and two-way ANOVA with posttests, and paired Student's t tests were performed to determine significance (p < 0.05). RESULTS: EMT occurred at the necrotic interface of MDA-MB-468 xenografts in regions of hypoxia. Extratumoral deposits (vascular and lymphatic inclusions, local and axillary nodes, and lung metastases) strongly expressed E-cadherin. MDA-MB-468 cells overexpressing E-cadherin were more proliferative and less migratory in vitro, whereas E-cadherin knockdown (short hairpin CDH1 [shCDH1]) cells were more migratory and invasive, less proliferative, and took longer to form tumors. shCDH1-MDA-MB-468 xenografts did not contain the hypoxia-induced necrotic areas observed in wild-type (WT) and shSCR-MDA-MB-468 tumors, but they did not exhibit an impaired hypoxic response in vitro. Although vimentin expression was not stimulated by E-cadherin knockdown in 2D or 3D cultures, xenografts of these cells were globally vimentin-positive rather than exhibiting regional EMT, and they expressed higher SNA1 than their in vitro counterparts. E-cadherin suppression caused a trend toward reduced lung metastasis, whereas E-cadherin overexpression resulted in the reverse trend, consistent with the increased proliferation rate and predominantly epithelial phenotype of MDA-MB-468 cells outside the primary xenograft. This was also originally observed in WT xenografts. Furthermore, we found that patients with breast cancer that expressed E-cadherin were more likely to have metastases. CONCLUSIONS: E-cadherin expression promotes growth of primary breast tumors and conceivably the formation of metastases, supporting a role for MET in metastasis. E-cadherin needs to be reevaluated as a tumor suppressor.