Contributions of GeneXpert® to TB diagnosis in Myanmar.

BACKGROUND: Xpert® MTB/RIF, a rapid, molecular TB diagnostic assay, can detect Mycobacterium tuberculosis and rifampin resistance directly from clinical sputum samples in <2 h with high sensitivity and specificity. The added diagnostic value of Xpert over smear microscopy at a national level in Myanmar has not been previously reported.METHODS: We evaluated 339,358 Xpert and demographic records captured from January 2015 to December 2018 as part of the Myanmar National TB Program Data Utilization and Connectivity Project to examine the additional diagnostic yield of Xpert relative to smear for the detection of M. tuberculosis for TB diagnosis in Myanmar, with a focus on people living with HIV (PLHIV) and sample type.RESULTS: Use of Xpert increased TB case detection by 40% compared to smear microscopy results. Among PLHIV, use of Xpert increased TB case detection by almost 100% compared to smear microscopy results.CONCLUSION: Xpert testing identified more patients with TB than smear microscopy alone, particularly in cohorts with significant proportions of PLHIV. The use of Xpert as a screening tool in countries with a high burden of TB could lead to significantly increased diagnosis of TB at a regional and national level.

Promoting evidence-based practices for breast cancer care through web-based collaborative learning.

The Knowledge Summaries for Comprehensive Breast Cancer Control (KSBCs) are a series of 14 publications aligned with World Health Organization guidance on evidence-based breast cancer control and accepted frameworks for action. To study utilization of the KSBCs in the development of locally relevant breast cancer control policies and programs in limited resource settings, the National Cancer Institute Center for Global Health, the University of Washington and the Fred Hutchinson Cancer Research Center developed the Project ECHO® for KSBCs (KSBC ECHO). Project ECHO is an online model which employs case-based learning, while promoting multi-directional learning and network-building. The program was evaluated using a pre-post study design to assess if this online collaborative learning platform can be an effective model for dissemination and utilization of the KSBCs to inform breast cancer control programs and policy advocacy in limited resource settings. A total of 28 KSBC ECHO participants (57%) responded to the baseline and endpoint program evaluation surveys. Across all 28 respondents, analysis of the data indicates that knowledge increase was statistically significant overall: average knowledge gain was 0.77, 95% CI [0.44 - 1.08] and p value < 0.0001. A majority of responding team leads reported that the core ECHO components (case/didactic presentations, discussion) contributed to a great extent to strengthening their project proposal/goals. Program evaluation survey responses indicate that utilization of this online platform provided an opportunity for individual knowledge gain, multi-directional information exchange, network-building, and strengthening of the proposed breast cancer control projects based in limited resource settings.

Fully vs. partially integrated services for TB-HIV in Myanmar: a health services review and a cohort study.

In Myanmar, integrated services for tuberculosis (TB) and human immunodeficiency virus (HIV) are operated either fully (as one single unit) or partially (each vertical programme provides both services). To review the fully and partially integrated services for TB-HIV and to assess their TB treatment outcomes. We analysed the compiled service database and conducted a cohort study on newly registered TB-HIV patients in 12 townships in Myanmar. No significant association between region/state and types of integration was detected. Townships with partially integrated services had a significantly larger population size, higher proportion of urban population as well as higher TB and TB-HIV case notification rates; however, the cartridge-based Xpert® MTB/RIF assay was used less frequently than in townships with fully integrated services. Treatment completion rate and unfavourable outcomes were not significantly different between the two models, although fully integrated services reported a higher cure rate. These mixed results suggest that during expansion of fully integrated services, the progress of treatment outcomes should be monitored carefully. .

IPT in people living with HIV in Myanmar: a five-fold decrease in incidence of TB disease and all-cause mortality.

SETTING: Myanmar, a country with a high human immunodeficiency virus-tuberculosis (HIV-TB) burden, where the tuberculin skin test or interferon-gamma release assays are not routinely available for the diagnosis of latent tuberculous infection. OBJECTIVE: To assess the effect of isoniazid (INH) preventive therapy (IPT) on the risk of TB disease and mortality among people living with HIV (PLHIV). DESIGN: A retrospective cohort study of routinely collected data on PLHIV enrolled into care between 2009 and 2014. RESULTS: Of 7177 patients (median age 36 years, interquartile range 31-42; 53% male) included in the study, 1278 (18%) patients received IPT. Among patients receiving IPT, 855 (67%) completed 6 or 9 months of INH. Patients who completed IPT had a significantly lower risk of incident TB than those who never received IPT (adjusted hazard ratio [aHR] 0.21, 95%CI 0.12-0.34) after controlling for potential confounders. PLHIV who received IPT had a significantly lower risk of death than those who never received IPT (PLHIV who completed IPT, aHR 0.25, 95%CI 0.16-0.37; those who received but did not complete IPT, aHR 0.55, 95%CI 0.37-0.82). CONCLUSION: Among PLHIV in Myanmar, completing a course of IPT significantly reduced the risk of TB disease, and receiving IPT significantly reduced the risk of death.

High prevalence and incidence of tuberculosis in people living with the HIV in Mandalay, Myanmar, 2011-2017.

SETTING: Two human immunodeficiency virus (HIV) clinics providing antiretroviral therapy (ART), Mandalay, Myanmar. OBJECTIVE: To assess prevalent TB at enrolment, incident TB during follow-up and associated risk factors in adult people living with HIV (PLHIV) between 2011 and 2017. DESIGN: Cohort study using secondary data. RESULTS: Of 11 777 PLHIV, 2911 (25%) had prevalent TB at or within 6 weeks of enrolment. Independent risk factors for prevalent TB were being male or single/widowed, daily alcohol consumption, CD4 count 200 cells/µl and anaemia. During 6 years follow-up in 8866 PLHIV with no prevalent TB, the rate of new TB was 2.9 per 100 person-years (95%CI 2.6-3.1). Cumulative TB incidence was 9.6%, with 370 (72%) of 517 new TB cases occurring in the first year. Independent risk factors for incident TB were being male and anaemia. Incident TB was highest in the first year of ART, in PLHIV with CD4 counts 200 cells/µl and those not receiving isoniazid preventive therapy (IPT). Incident TB declined with time on ART and rising CD4 counts. CONCLUSION: Prevalent and incident TB were high in PLHIV in the Mandalay clinics. Consideration should be given to earlier TB diagnosis using more sensitive diagnostic tools, effective ART and scaling up IPT.

Childhood TB in Myanmar: trends in notification, profile and treatment outcomes in the private sector.

SETTING: Myanmar National Tuberculosis (TB) programme (NTP). OBJECTIVE: To describe 1) the trends in childhood TB (aged ⩾ 14 years) notification from 2014 to 2017 and quantify the private sector contribution to this notification; and 2) the profile and treatment outcomes of childhood TB managed in the private sector in 2016. STUDY DESIGN: This was an observational study involving the review of routine records and reports of the NTP public-private mix (PPM) projects managed by the Myanmar Medical Association and Population Service International. RESULTS: The total number of childhood TB notified has declined from 36 314 in 2014 to 28 723 in 2017 (average annual decline = 2607 cases per year). The private sector contribution to the notification remained between 17% and 19%. Of the 5616 childhood TB cases diagnosed and treated under the two PPM projects in 2016, 99% were clinically diagnosed and 5459 (97.7%) had successful treatment outcomes. Children aged ⩾10 years, males, those with bacteriologically confirmed TB, those treated in the regions or states of Mandalay, Chin and Shan had a higher risk of an unfavourable outcome (lost to follow-up, death, move to second-line treatment and not evaluated). CONCLUSION: Childhood TB notification is showing a declining trend. One of five notified childhood TB cases was diagnosed and treated in the private sector, where the successful treatment rate was high.

Current and Emerging Therapeutic Options for Gastroparesis.

Gastroparesis is a complex, debilitating dysmotility disorder with challenging symptom management. A diagnosis of gastroparesis is based on objectively delayed gastric emptying in the absence of mechanical obstruction. Given the limited efficacy of treatment options and serious side effects, significant research continues for therapeutic options for gastroparesis. Promising investigational pharmacologic therapies include relamorelin, prucalopride, and aprepitant. A novel endoscopic therapy is gastric peroral endoscopic pyloromyotomy, which is associated with improved gastric emptying. This article reviews both current and emerging therapeutic options for gastroparesis, including dietary modification and pharmacologic, electrical stimulation, endoscopic, and surgical therapies. Further research and novel treatment options are needed to address the substantial morbidity of gastroparesis.

Treatment outcome of tuberculosis patients detected using accelerated vs. passive case finding in Myanmar.

SETTING: Several projects involving accelerated or active case finding (ACF) of tuberculosis (TB) cases are being implemented in Myanmar. However, there is a concern that patients detected using ACF have poorer TB treatment outcomes than those detected using passive case finding (PCF). OBJECTIVE: To assess differences in the demographics, clinical profile and treatment outcomes of patients detected using ACF and PCF. DESIGN: Retrospective cohort study of TB patients diagnosed and enrolled for treatment during 2014-2016. RESULTS: Of 16 048 patients enrolled, 2226 (16%) were detected using ACF; the treatment success rate (cured and completed) was 88%. A higher proportion of cases detected using ACF were aged 55 years, human immunodeficiency virus (HIV) negative and sputum smear-positive pulmonary TB. After adjusting for differences in demographic and clinical characteristics, we found that treatment outcomes in patients detected using ACF and PCF were not significantly different (adjusted relative risk [aRR] 0.89, 95%CI 0.78-1.00). Male sex, age  55 years, patients with a previous history of TB and HIV positivity were independently associated with unsuccessful outcomes. CONCLUSION: ACF detected a significant proportion of TB cases in study townships; treatment outcomes in cases detected using ACF and those detected using PCF were similar. More tailored interventions are needed to improve treatment outcomes in patients at a higher risk of unsuccessful treatment outcomes.

Rifampicin-resistant tuberculosis patients in Myanmar in 2016: how many are lost on the path to treatment?

SETTING: Regional tuberculosis (TB) centres of the Yangon and Mandalay Regions of Myanmar, which account for 65% of all notified rifampicin-resistant tuberculosis (RR-TB) cases countrywide. OBJECTIVE: To determine 1) initial loss to follow-up (LTFU), 2) treatment delay, and 3) factors associated with initial LTFU and treatment delay among RR-TB patients residing in the Yangon and Mandalay regions diagnosed using Xpert® during January-August 2016. DESIGN: This was a retrospective cohort study. Each diagnosed patient was tracked in the drug-resistant TB treatment registers of the Yangon and Mandalay regional treatment centres for January-December 2016 using patient name, age, sex, township and date of diagnosis. If the diagnosed patient was not found in the treatment register by 31 December 2016, he/she was considered 'initial LTFU'. RESULTS: Of the 1037 RR-TB patients diagnosed, 310 (30%) experienced initial LTFU, which was significantly higher among patients aged 55 years and among those diagnosed in the Mandalay Region. A treatment delay of >1 month was observed in 440 (70%) patients (median delay 41 days). Delay was uniformly high across patient subgroups, and was not associated with any factor. CONCLUSION: Initial LTFU and treatment delays among RR-TB patients were high. Future studies using qualitative research methods are needed to ascertain the reasons for this observation.

Extensively drug-resistant tuberculosis in Myanmar: burden and mutations causing second-line drug resistance.

SETTING: Two tuberculosis (TB) reference laboratories in Myanmar. OBJECTIVES: To determine the proportion of extensively drug-resistant TB (XDR-TB) cases among multidrug-resistant TB (MDR-TB) cases and the mutations that cause resistance to second-line drugs in Myanmar. DESIGN: This was a cross-sectional, retrospective study. Multidrug-resistant Mycobacterium tuberculosis isolates were collected during 2015-2016. Phenotypic drug susceptibility testing (DST) was performed and drug-resistant mutations identified by sequencing. Genotypes were determined to explain relationships between drug resistance patterns and genotypes. RESULTS: Of 89 MDR-TB isolates, 12 were XDR-TB and 24 were pre-XDR-TB, with 21 resistant to fluoroquinolones (FQs) and 3 to second-line injectable agents (SLIDs). High rates of cross-resistance among second-line drugs were observed. Correlations between phenotypic and molecular DST against FQs and SLIDs were 91% in both cases. The most frequent mutation in FQ-resistant isolates was D94G (8/21) in gyrA and A1401G (11/15) in rrs in those resistant to SLIDs. The dominant genotype was the Beijing type (76/89). CONCLUSION: There were high proportions of XDR-TB and pre-XDR-TB among MDR-TB cases; cross-resistance among second-line drugs was high, with various types of genetic mutations. These data suggest that resistance to second-line anti-tuberculosis drugs should be monitored intensively, and molecular DST should be employed.

How many sputum samples should be examined during follow-up of tuberculosis patients in Myanmar: two or one?

Setting: Ten selected microscopy centres in Sagaing Region, Myanmar, functioning under an external quality assurance system with no reported major errors. Objective: To assess the pattern of serial sputum results (NN, both smear-negative; NP, first smear-negative and second smear-positive; PN, first smear-positive and second smear-negative; and PP, both smear-positive) among follow-up sputum microscopy examinations of tuberculosis (TB) patients (end of intensive phase, mid-continuation phase and end of treatment) conducted from 1 November 2017 to 15 April 2018. Design: Cross-sectional study using secondary data (laboratory registers). Results: Of 2001 examinations, 94 (4.7%) were smear-positive: 66 PP (3.3%), 12 PN (0.6%) and 16 NP (0.8%); 75% of NP results were scanty. The proportion of NP results was 0.8% (95%CI 0.5-1.3), i.e., 125 smears (95%CI 77-200) were required to detect one additional smear-positive result in the second sample. Of the 16 NP results (15 patients), 14 were tested using Xpert® MTB/RIF and none had rifampicin resistance. During the continuation phase of treatment, 13 became smear-negative, one remained smear-positive and one had unknown follow-up smear status. Conclusion: The benefit of the second sputum sample for monitoring anti-tuberculosis treatment was negligible. Given the favourable resource implications (reduced laboratory workload and costs), we recommend changing the policy from two sputum smears to one during follow-up sputum examinations of TB patients.

Contexte : Dix centres de microscopie sélectionnés de la région de Sagaing, Myanmar, fonctionnant avec un système d'assurance de qualité externe sans erreurs majeures rapportées.Objectif : Evaluer les profils de séries de résultats de crachats (NN, deux frottis négatifs ; NP, premier frottis négatif et deuxième frottis positif ; PN, premier frottis positif et deuxième frottis négatif ; et PP, deux frottis positifs) parmi les examens de suivi de microscopie de crachats de patients TB (à la fin de la phase intensive, au milieu de la phase de continuation et à la fin du traitement) réalisés du 1e novembre 2017 au 15 avril 2018.Schéma : Etude transversale grâce à des données secondaires (registres de laboratoire).Résultats : Sur 2001 examens, 94 (4,7%) ont eu un frottis positif : 66 (3,3%) PP ; 12 (0,6%) PN ; 16 (0,8%) NP ; 75% des NP avaient de rares bacilles. La proportion de NP a été de 0,8% (IC95% 0,5­1,3), impliquant qu'il a fallu 125 frottis (IC95% 77­200) pour détecter un frottis positif supplémentaire dans un deuxième échantillon. Sur les 16 NP (15 patients), 14 ont été testés par Xpert® MTB/RIF et aucun n'a eu de résistance à la rifampicine. Lors de la continuation du traitement, 13 sont devenus à frottis négatif, un patient est resté à frottis positif et un autre a eu un frottis de suivi « indéterminé ¼.Conclusion : Le bénéfice du deuxième échantillon de crachats pour le suivi du traitement antituberculeux a été négligeable. Devant les implications favorables en termes de ressources (charge de travail et coûts réduits pour le laboratoire), nous recommandons de modifier la politique de deux frottis de crachats à un seul lors du suivi de patients TB par examens des crachats.

Marco de Referencia: Diez centros de microscopia escogidos en la región de Sagaing de Birmania, que funcionan con un sistema externo de garantía de la calidad y no notifican errores importantes.Objetivos: Evaluar el perfil de los resultados seriados del esputo (NN, ambas baciloscopias negativas; NP, primera baciloscopia negativa y segunda positiva; PN, primera baciloscopia positiva y segunda negativa; y PP, ambas baciloscopias positivas) en las baciloscopias de esputo de seguimiento de los pacientes con tuberculosis (TB) (al final de la fase intensiva, en medio de la fase de continuación y al final del tratamiento), realizadas del 1° de noviembre del 2017 al 15 de abril del 2018.Métodom: Fue este un estudio transversal que utilizó datos secundarios (los registros de laboratorio).Resultados: De las 2001 baciloscopias realizadas, 94 (4,7%) fueron positivas, a saber: 66 (3,3%) PP; 12 (0,6%) PN; 16 (0,8%) NP; 75% de los resultados NP se notificaron como 'escasos bacilos'. La proporción de resultados NP fue 0,8% (IC95% 0,5­1,3), lo cual indica que se precisaron 125 baciloscopias a fin de detectar una baciloscopia positiva adicional en la segunda muestra (IC95% 77­200). De los 16 casos NP (15 pacientes), 14 se examinaron mediante la prueba Xpert® MTB/RIF y ninguno exhibió resistencia a rifampicina. Durante la fase de continuación del tratamiento, en 13 casos la baciloscopia se hizo negativa, uno permaneció positivo y en otro caso el resultado de la baciloscopia de seguimiento era 'desconocido'.Conclusión: La utilidad de una segunda muestra de esputo en la supervisión del tratamiento antituberculoso fue insignificante. Teniendo en cuenta sus repercusiones económicas favorables (disminución de la carga de trabajo y los costos de laboratorio), se recomienda cambiar la norma de practicar dos muestras de esputo por una sola muestra, durante las baciloscopias de seguimiento de los pacientes con TB.

Sputum smear-positive, Xpert® MTB/RIF-negative results: magnitude and treatment outcomes of patients in Myanmar.

Setting: Myanmar's National Tuberculosis Programme (NTP) uses the Xpert® MTB/RIF assay to diagnose rifampicin (RMP) resistance in sputum smear-positive (Sm+) pulmonary tuberculosis (TB) patients. The Xpert test may occasionally yield negative results (Xpert-) for Mycobacterium tuberculosis complex, indicating a false-positive sputum smear result, false-negative Xpert result or infection with non-tuberculous mycobacteria (NTM). Patients with NTM may respond poorly to first-line anti-tuberculosis treatment. Objective: To assess the burden of Sm+, Xpert- results at the national level and treatment outcomes of Sm+, Xpert- patients in Yangon Region. Design: A cohort study involving a retrospective record review of routinely collected NTP data. Result: In 2015 and 2016, 4% of the 25 359 Sm+ patients who underwent Xpert testing nationally were Sm+, Xpert-. Similarly, in the Yangon Region, 5% of the 5301 Sm+ patients were also Xpert- and were treated with first-line anti-tuberculosis regimens. Smear grade (scanty/1+) and age ⩾65 years were associated with Sm+, Xpert- results. The 88% treatment success rate for this group was similar to that of Sm+, Xpert+ patients without RMP resistance. Conclusion: Approximately 4-5% of Sm+ TB patients were Xpert-. There is an urgent need to formulate guidelines on how to reassess and manage these patients.

Contexte : Le programme national tuberculose du Myanmar (PNT) recourt au test Xpert® MTB/RIF pour diagnostiquer la résistance à la rifampicine (RMP) chez les patients atteints de tuberculose (TB) pulmonaire à frottis de crachats positif (Sm+). Les résultats du test Xpert peuvent parfois être négatifs (Xpert­) pour le complexe Mycobacterium tuberculosis indiquant soit un résultat de frottis de crachats faussement positif, soit un résultat de test Xpert faussement négatif ou une infection à mycobactéries non-tuberculeuse (NTM). Les patients atteints de NTM peuvent répondre de façon médiocre au traitement anti-tuberculose de première ligne.Objectif : Evaluer la proportion de patients Sm+/Xpert­ au niveau national et les résultats du traitement dans la région de Yangon.Schéma : Etude de cohorte impliquant une revue rétrospective des dossiers de données recueillies en routine par le PNT.Résultats: Au niveau national, en 2015 et 2016, 4% des 25 359 patients Sm+ qui ont eu un test Xpert ont été Xpert­. De même, dans la région de Yangon, 5% des 5301 patients Sm+ ont été Xpert­ et ils ont été traités avec des protocoles anti-tuberculose de première ligne. Le grade du frottis (rare/1+) et l'âge ⩾ 65 ans ont été associés aux résultats Sm+/Xpert­. Le taux de succès du traitement a été de 88% ce qui a été similaire aux résultats des patients Sm+/Xpert+ sans résistance à la RMP.Conclusion : La proportion de patients TB Sm+/Xpert­ a été d'environ 4­5%. Il y a un besoin urgent de formuler des directives sur la manière de réévaluer et de prendre en charge de façon optimale ces patients.

Marco de referencia: En el Programa Nacional contra la Tuberculosis (PNT) de Birmania se utiliza la prueba Xpert® MTB/RIF con el fin de diagnosticar la resistencia a rifampicina (RMP) en los pacientes con diagnóstico de tuberculosis (TB) pulmonar y baciloscopia positiva (Sm+). El resultado de la prueba Xpert en ocasiones puede ser negativa para el complejo Mycobacterium tuberculosis, lo cual puede corresponder ya sea a un resultado positivo falso de la baciloscopia del esputo, un resultado negativo falso de la prueba Xpert o a la infección por una micobacteria atípica. Los pacientes infectados por micobacterias atípicas pueden tener una respuesta deficiente al tratamiento antituberculoso de primera línea.Objetivo: Evaluar la proporción de casos SM+, Xpert­ a escala nacional y los desenlaces terapéuticos de estos pacientes en la región de Yangon.Método: Se realizó un estudio de cohortes retrospectivo a partir del análisis de los datos corrientes recogidos en las historias clínicas en el PNT.Resultados: A escala nacional, en el 2015 y el 2016, el 4% de los 25 359 pacientes Sm+ que realizaron la prueba Xpert obtuvo un resultado negativo. Asimismo, en la región de Yangon, el 5% de los 5301 pacientes con Sm+ tuvo un resultado negativo de la prueba Xpert y recibió tratamiento con esquemas antituberculosos de primera línea. Los factores que se asociaron con Sm+ y una prueba Xpert­ fueron el grado de la baciloscopia (bacilos escasos o 1+) y la edad a ⩾ 65 años. La tasa de éxito terapéutico en estos casos fue 88%, una proporción equivalente a los desenlaces de los pacientes Sm+ y Xpert+, sin resistencia a RMP.Conclusión: La proporción de pacientes con Sm+ y Xpert­ fue del 4% al 5%. Existe una necesidad urgente de formular directrices sobre la forma reevaluar estos pacientes y tratarlos de manera óptima.

Safety and efficacy of sofosbuvir-based direct-acting antiviral regimens for hepatitis C virus genotypes 1-4 and 6 in Myanmar: Real-world experience.

This open-label, clinical experience investigated the safety and efficacy of direct-acting antiviral (DAA) hepatitis C virus (HCV) therapy in Myanmar; 344 patients completed treatment between June 2015 and May 2016. Patients with HCV genotypes 1-4 and 6 received one of four treatments: (i) Peg-interferon (PEG-IFN)+sofosbuvir (SOF)+ribavirin (RBV) for 12 weeks, (ii) SOF+RBV for 24 weeks, (iii) ledipasvir (LDV)+SOF for 12 weeks or (iv) daclatasvir (DCV)+SOF+RBV for 12 or 24 weeks. Genotype 3 was most common (n=133, 38.7%), followed by genotype 6 (n=122, 35.5%) and genotype 1 (n=86, 25%). Overall, 91% of patients achieved sustained virologic response (SVR); 99% in group 1, (n=148/149), 90% in group 2 (n=95/106), 78% in group 3 (n=65/83) and 100% in group 4 (n=6/6). In group 3, SVR rates were 96.8% in genotype 1 (n=30/31) and 64.1% in genotype 6 (n=25/39). Multivariable regression analysis identified advanced fibrosis (F3-4) (OR=.16 CI: 0.05-0.57, P=.005), genotype 6 (OR=.35, CI: 0.16-0.79, P=.012) and diabetes (OR=.29, CI: 0.12-0.71, P=.007) as negative independent predictors of response. Adverse events were mild with all-oral therapy. CONCLUSION: DAA therapy ±PEG-IFN achieved high SVR rates. Genotype 6 patients had a low SVR to 12 weeks of LDV and SOF raising the need for other regimens, RBV or longer treatment duration in this population.

Left atrial strain in heart failure with preserved ejection fraction.

BACKGROUND: Heart failure with preserved ejection fraction (HFpEF) is a syndrome in which patients have symptoms and signs of heart failure but preserved ejection fraction. Left atrial (LA) volume and function are known to be impaired in these patients. Two-dimensional speckle-tracking echocardiography (2D-STE) has recently enabled the quantification of LA deformation dynamics. In this study, we evaluated the use of 2D-STE for the diagnosis of HFpEF. PATIENTS AND METHODS: The study included 83 patients with suspected HFpEF. Patients were divided into two groups after HFpEF had been diagnosed according to current guidelines. Parameters of diastolic dysfunction were evaluated, including left ventricular mass index (LVMI), LA volume index (LAVI), E/A ratio, deceleration time (DT), E/E', and STE parameters such as global longitudinal LA strain during ventricular systole (GLAs-res) and strain during late diastole (GLAs-pump). RESULTS: The values of BNP, LVMI, DT, LAVI, and GLAs-res were significantly different between the two groups. In univariate analysis, a strong negative correlation was seen between GLAs-res and BNP (r = -0.567, p < 0.001) as well as between GLAs-res and DT (r = -0.665, p < 0.001), while a moderate negative correlation was found between GLAs-res and LVMI (r = -0.458, p < 0.001) and GLAs-res and LAVI (r = -0.316, p = 0.004). In logistic regression analysis, GLAs-res (p = 0.049, OR = 0.71, 95 % CI = 0.451-0.99), BNP (p = 0.025, OR = 1.08, 95 % CI = 1.01-1.14), and LAVI (p = 0.042, OR = 1.59, 95 % CI = 1.02-2.48) were found to be independent predictors of HFpEF. CONCLUSION: LA function as assessed by 2D-STE is impaired in patients with HFpEF. A GLAs-res value of < 17.5 % can be useful for the diagnosis of HFpEF.

Timing of antiretroviral therapy and TB treatment outcomes in patients with TB-HIV in Myanmar.

SETTING: Integrated HIV Care programme, Mandalay, Myanmar. OBJECTIVES: To determine time to starting antiretroviral treatment (ART) in relation to anti-tuberculosis treatment (ATT) and its association with TB treatment outcomes in patients co-infected with tuberculosis (TB) and the human immunodeficiency virus (HIV) enrolled from 2011 to 2014. DESIGN: Retrospective cohort study. RESULTS: Of 1708 TB-HIV patients, 1565 (92%) started ATT first and 143 (8%) started ART first. Treatment outcomes were missing for 226 patients and were thus not included. In those starting ATT first, the median time to starting ART was 8.6 weeks. ART was initiated after 8 weeks in 830 (53%) patients. Unsuccessful outcome was found in 7%, with anaemia being an independent predictor. In patients starting ART first, the median time to starting ATT was 21.6 weeks. ATT was initiated within 3 months in 56 (39%) patients. Unsuccessful outcome was found in 12%, and in 20% of those starting ATT within 3 months. Patients with CD4 count <100/mm(3) had a four times higher risk of an unsuccessful outcome. CONCLUSIONS: Timing of ART in relation to ATT was not an independent risk factor for unsuccessful outcome. Extensive screening for TB with rapid and sensitive diagnostic tests in HIV-infected persons and close monitoring of anaemia and immunosuppression are recommended to further improve TB treatment outcomes among patients with TB-HIV.

Contexte : Programme intégré de prise en charge du virus de l'immunodéficience humaine (VIH), Mandalay, Myanmar.Objectifs : Chez les patients atteints de tuberculose (TB) et VIH enrôlés entre 2011 et 2014, déterminer la date du début du traitement antirétroviral (TAR) en relation avec le traitement antituberculeux (ATT) et son association avec le résultat d'ATT.Schéma : Etude rétrospective de cohorte.Résultats : Sur 1708 patients TB-VIH, 1565 (92%) ont débuté l'ATT en premier et 143 (8%) ont commencé le TAR en premier. Le résultat du traitement a été manquant pour 226 patients qui n'ont pas été inclus. Chez les patients ayant débuté l'ATT en premier, le délai médian de mise en route du TAR a été de 8,6 semaines. L'initiation du TAR a été retardée d'un délai médian de 8 semaines chez 830 (53%) patients. Parmi ces patients, 7% ont eu un résultat médiocre, avec une anémie qui a constitué un facteur de risque indépendant. Chez les patients ayant débuté le TAR en premier, le délai médian de mise en route de l'ATT a été de 21,6 semaines. L'ATT a été initié au cours des 3 mois chez 56 (39%) patients. Le traitement a échoué chez 12% des patients et chez 20% de ceux qui ont débuté l'ATT dans les 3 mois. Les patients ayant des CD4 <100/mm3 ont eu un risque quatre fois plus élevé d'échec.Conclusions: La chronologie du TAR en rapport avec l'ATT n'a pas été un facteur de risque indépendant d'échec du traitement. Un dépistage extensif de la TB avec des tests de diagnostic rapides et sensibles chez les personnes infectées par le VIH et un suivi étroit de l'anémie et de l'immunosuppression sont recommandés afin d'améliorer encore le résultat du traitement de TB parmi les patients TB-VIH.

Marco de referencia: El programa integrado de atención de la infección por el virus de la inmunodeficiencia humana (VIH) en Mandalay, en Birmania.Objetivos: Determinar el lapso entre el comienzo del tratamiento antirretrovírico (ART) y el inicio del tratamiento antituberculoso (ATT) en los pacientes coinfectados registrados del 2011 al 2014 y su asociación con el desenlace del ATT.Método: Fue este un estudio retrospectivo de cohortes.Resultados: De los 1708 pacientes coinfectados por el VIH y la tuberculosis (TB), 1565 iniciaron primero el ATT (92%) y 143 comenzaron en primer lugar el ART (8%). Se excluyeron 226 casos que carecían de registro del desenlace terapéutico. En los pacientes que iniciaron en primer lugar el ATT, la mediana del lapso hasta el comienzo del ART fue 8,6 semanas; este tratamiento se inició después de 8 semanas en 830 pacientes (53%). Se observó un desenlace terapéutico desfavorable en 7% de estos pacientes; la principal variable independiente asociada fue la presencia de anemia. Cuando el ART se inició en primer lugar, la mediana hasta el comienzo del ATT fue 21,6 semanas; este tratamiento se inició durante los 3 primeros meses en 56 pacientes (39%). Se observó un desenlace terapéutico desfavorable en 12% de estos pacientes y en 20% de los pacientes que iniciaron el ART en los primeros 3 meses. El riesgo de un desenlace desfavorable fue cuatro veces más alto en los pacientes con un recuento de linfocitos CD4 <100 células/mm3.Conclusión: La coordinación cronológica del ART y el ATT no representó un factor independiente de riesgo de obtener un desenlace desfavorable. Se recomienda la detección sistemática de la TB en los pacientes infectados por el VIH mediante pruebas diagnósticas rápidas y sensibles y una supervisión cuidadosa de la anemia y la inmunodepresión, con el objeto de obtener aun mejores desenlaces del ATT en los pacientes aquejados de coinfección TB-VIH.

Clinical, angiographic and procedural characteristics of longitudinal stent deformation.

Recently, longitudinal stent deformation (LSD) has been reported increasingly. Even though the reported cases included almost all stent designs, most cases were seen in the Element™ stent design (Boston Scientific, Natick, MA, USA). It is considered that stent design, lesion and procedural characteristics play a role in the etiology of LSD. Yet, the effect of LSD on long-term clinical outcomes has not been studied well. Element stents implanted between January 2013 and April 2015 in our hospital were examined retrospectively. Patients were grouped into two according to the presence of LSD, and their clinical, lesion and procedural characteristics were studied. Twenty-four LSD's were detected in 1812 Element stents deployed in 1314 patients (1.83 % of PCI cases and 1.32 % of all Element stents). LMCA lesions (16.7 % vs 1.6 %, p < 0.001), complex lesions (75 % vs 35.1 %, p < 0.001), bifurcation lesions (37.5 % vs 18.3 %, p = 0.017), ostial lesions (33.3 % vs 12.8 %, p = 0.003), using of extra-support guiding catheter (54.2 % vs 22.3 %, p < 0.001) and extra-support guidewire (37.5 % vs 16.2 %, p = 0.005) were found to be more frequent in cases with LSD than in cases without it. In addition, the number of stents, stent inflation pressure and the use of post-dilatation were significantly different between the two groups. Two patients had an adverse event during the follow-up period. LSD is a rarely encountered complication, and is more common in complex lesions such as ostial, bifurcation and LMCA lesions. The use of extra-support guiding catheter, extra-support guidewires and low stent inflation pressure increases the occurrence of LSD. Nevertheless, with increased awareness of LSD and proper treatment, unwanted long-term outcomes can be successfully prevented.

Little Polymorphism at the K13 Propeller Locus in Worldwide Plasmodium falciparum Populations Prior to the Introduction of Artemisinin Combination Therapies.

The emergence and spread of artemisinin-resistant Plasmodium falciparum is of huge concern for the global effort toward malaria control and elimination. Artemisinin resistance, defined as a delayed time to parasite clearance following administration of artemisinin, is associated with mutations in the Pfkelch13 gene of resistant parasites. To date, as many as 60 nonsynonymous mutations have been identified in this gene, but whether these mutations have been selected by artemisinin usage or merely reflect natural polymorphism independent of selection is currently unknown. To clarify this, we sequenced the Pfkelch13 propeller domain in 581 isolates collected before (420 isolates) and after (161 isolates) the implementation of artemisinin combination therapies (ACTs), from various regions of endemicity worldwide. Nonsynonymous mutations were observed in 1% of parasites isolated prior to the introduction of ACTs. Frequencies of mutant isolates, nucleotide diversity, and haplotype diversity were significantly higher in the parasites isolated from populations exposed to artemisinin than in those from populations that had not been exposed to the drug. In the artemisinin-exposed population, a significant excess of dN compared to dS was observed, suggesting the presence of positive selection. In contrast, pairwise comparison of dN and dS and the McDonald and Kreitman test indicate that purifying selection acts on the Pfkelch13 propeller domain in populations not exposed to ACTs. These population genetic analyses reveal a low baseline of Pfkelch13 polymorphism, probably due to purifying selection in the absence of artemisinin selection. In contrast, various Pfkelch13 mutations have been selected under artemisinin pressure.

Are current case-finding methods under-diagnosing tuberculosis among women in Myanmar? An analysis of operational data from Yangon and the nationwide prevalence survey.

BACKGROUND: Although there is a large increase in investment for tuberculosis control in Myanmar, there are few operational analyses to inform policies. Only 34% of nationally reported cases are from women. In this study, we investigate sex differences in tuberculosis diagnoses in Myanmar in order to identify potential health systems barriers that may be driving lower tuberculosis case finding among women. METHODS: From October 2014 to March 2015, we systematically collected data on all new adult smear positive tuberculosis cases in ten township health centres across Yangon, the largest city in Myanmar, to produce an electronic tuberculosis database. We conducted a descriptive cross-sectional analysis of sex differences in tuberculosis diagnoses at the township health centres. We also analysed national prevalence survey data to calculate additional case finding in men and women by using sputum culture when smear microscopy was negative, and estimated the sex-specific impact of using a more sensitive diagnostic tool at township health centres. RESULTS: Overall, only 514 (30%) out of 1371 new smear positive tuberculosis patients diagnosed at the township health centres were female. The proportion of female patients varied by township (from 21% to 37%, p = 0.0172), month of diagnosis (37% in February 2015 and 23% in March 2015 p = 0.0004) and age group (26% in 25-64 years and 49% in 18-25 years, p < 0.0001). Smear microscopy grading of sputum specimens was not substantially different between sexes. The prevalence survey analysis indicated that the use of a more sensitive diagnostic tool could result in the proportion of females diagnosed at township health centres increasing to 36% from 30%. CONCLUSIONS: Our study, which is the first to systematically compile and analyse routine operational data from tuberculosis diagnostic centres in Myanmar, found that substantially fewer women than men were diagnosed in all study townships. The sex ratio of newly diagnosed cases varied by age group, month of diagnosis and township of diagnosis. Low sensitivity of tuberculosis diagnosis may lead to a potential under-diagnosis of tuberculosis among women.

Awareness of rabies and response to dog bites in a Bangladesh community.

Community awareness regarding rabies and treatment seeking behaviours are critical both for the prevention and control of the disease in human and animals. We conducted a study to explore people's awareness about rabies, their attitudes towards dogs and practices associated with treating dog bites in Satkhira Sadar, a south-western sub-district of Bangladesh. Of the total 3200 households (HHs) surveyed, the majority of the respondents have heard about rabies (73%) and there was a high level of awareness that dog bite is the main cause of rabies (86%), and that rabies can be prevented by vaccination (85%). However, 59% of the dog bite victims first seek treatment from traditional healers instead of visiting the hospitals, 29% received the rabies vaccine, 2% practiced proper wound washing with soap and water, while 4.8% have not taken any measures. None of the victims have received rabies immunoglobulin (RIG). Of the respondents, 5.2% reported a history of dog bite in at least one family member, and 11.8% reported a history of dog bite in domestic animals during the previous year. The HHs having a higher number of family members (OR: 1.13, 95% CI: 1.07-1.2), having a pet dog (OR: 2.1, 95% CI: 1.4-3.2) and caring or feeding a community dog (OR: 2.1, 95% CI: 1.4-2.9) showed an increased risk of getting a dog bite. Among the bite victims, 3.6% (n = 6) humans and 15.8% (n = 60) animals died. As a measure for dog population management (DPM), 56% preferred sterilization while the rest preferred killing of dogs. The current treatment seeking behaviours of the respondents should be improved through additional education and awareness programme and better availability for the provision of post-exposure prophylaxis in Bangladesh. We recommend scaling up national mass dog vaccination and DPM to reduce the burden of rabies cases and dog bites in Bangladesh.

Primary care management of early stage chronic lymphocytic leukaemia is safe and effective.

BACKGROUND: Chronic lymphocytic leukaemia (CLL) is the commonest leukaemia in western society. Most patients are detected incidentally at an early stage and require 'watch and wait' follow-up. In the UK, management of Stage A0 CLL varies with some centres advising regular outpatient haematology follow-up, whereas others recommend management within primary care. The safety and effectiveness of these two management options are currently unknown. METHODS: An observational retrospective cohort study in outpatient Haematology clinics at Queen Elizabeth Hospital Birmingham (QEH) and Birmingham Heartlands Hospital (BHH) and primary care practices in West Midlands, UK. All patients diagnosed with stable stage A0 CLL since 2002 at BHH or QEH were identified. At BHH, patients were discharged to primary care follow-up, whilst QEH patients remained under haematology for follow-up. Evidence of disease progression, need for treatment and overall mortality was documented. RESULTS: Two hundred and forty-six Stage A0 CLL patients were identified. One hundred and five (43%) patients were discharged to primary care, whilst 141 (57%) patients were followed up in haematology outpatient clinics. No difference in mortality or need for treatment was found between the two groups. Of those discharged, 93 (66%) remained in primary care. CONCLUSION: The management of stable-stage A0 CLL within primary or secondary care leads to equivalent clinical outcomes. The prevalence of early-stage CLL is expected to increase with the ageing population and management within primary care should be considered as a potentially effective approach.