Fractional Angular Momenta, Gouy and Berry Phases in Relativistic Bateman-Hillion-Gaussian Beams of Electrons.

A new Bateman-Hillion solution to the Dirac equation for a relativistic Gaussian electron beam taking explicit account of the four-position of the beam waist is presented. This solution has a pure Gaussian form in the paraxial limit but beyond it contains higher order Laguerre-Gaussian components attributable to the tighter focusing. One implication of the mixed mode nature of strongly diffracting beams is that the expectation values for spin and orbital angular momenta are fractional and are interrelated to each other by intrinsic spin-orbit coupling. Our results for these properties align with earlier work on Bessel beams [Bliokh et al., Phys. Rev. Lett. 107, 174802 (2011)PRLTAO0031-900710.1103/PhysRevLett.107.174802] and show that fractional angular momenta can be expressed by means of a Berry phase. The most significant difference arises, though, due to the fact that Laguerre-Gaussian beams naturally contain Gouy phase, while Bessel beams do not. We show that Gouy phase is also related to Berry phase and that Gouy phase fronts that are flat in the paraxial limit become curved beyond it.

Outcomes of Bedaquiline Treatment in Patients with Multidrug-Resistant Tuberculosis.

Bedaquiline is recommended by the World Health Organization for the treatment of multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis (TB). We pooled data from 5 cohorts of patients treated with bedaquiline in France, Georgia, Armenia, and South Africa and in a multicountry study. The rate of culture conversion to negative at 6 months (by the end of 6 months of treatment) was 78% (95% CI 73.5%-81.9%), and the treatment success rate was 65.8% (95% CI 59.9%-71.3%). Death rate was 11.7% (95% CI 7.0%-19.1%). Up to 91.1% (95% CI 82.2%-95.8%) of the patients experienced >1 adverse event, and 11.2% (95% CI 5.0%-23.2%) experienced a serious adverse event. Lung cavitations were consistently associated with unfavorable outcomes. The use of bedaquiline in MDR and XDR TB treatment regimens appears to be effective and safe across different settings, although the certainty of evidence was assessed as very low.

Shifting from an inpatient to outpatient centered model through transforming the TB financing in ex-Soviet countries.

INTRODUCTION: In former Soviet Union countries, tuberculosis (TB) financing largely relies on a hospital-centered model. The World Health Organization favors transformation to ambulatory treatment since it is cheaper and patient-centered. We explored policy and decision maker's perspectives on: a) enabling factors for transformation in Armenia and b) challenges and ways forward in doing so in Ukraine and Tajikistan. METHODOLOGY: Qualitative study of key informants from government, donors and the national TB program. RESULTS: 52 informants with a mean service record of 20 years were involved. Key enablers in Armenia included collaborative partnership and political will, carefully selecting an adapted financing scheme that avoided financial penalization of hospitals and health workers, and use of operational research. The operational challenges in Ukraine and Tajikistan hovered around the lack of technical capacity and guidance on "how to implement" alternative financing. Shortcomings in strategic planning, uncertainty/fear that existing hospital funding would be cut and reluctance to change were highlighted. Suggested ways forwards to change the current paradigm included country-level technical assistance, capacity building, regional exchanges and operational research. CONCLUSIONS: the perspectives of "those who decide" on transforming TB financing have been highlighted. Taking these perspectives on-board is vital for achieving the end-TB goals.

Mind the gap: Improving the performance of the reference laboratory to end-tuberculosis in Armenia.

INTRODUCTION: A one of the step towards achieving TB related targets is to ensure early and quality diagnosis of TB in national laboratories. WHO recommends that all national reference laboratories in TB burden countries strive to reach accreditation by 2025, based on ISO15189:2012 quality management system standard. To identify gaps, progress and evaluated the evolution in implementation QMS we performed a formal assessment of the national TB reference laboratory of Armenia, as well as estimates the specific quality indicators of NRL activity. METHODOLOGY: This is retrospective study cross-sectional study using laboratory data from the National TB Reference Laboratory in Armenia. Quality Management System assessments was conducted twice a year, using TB SLMTA assessment checklist. The sputum rejection and culture rates for quality indicators are calculated and assessed monthly. RESULTS: Compared to the baseline in 2016, there was a quality improvement reflecting the progress from zero to a "one star" in 2018. Areas that reached half of the target score included document and records, management review and responsibilities, evaluation and audits. Sections as "client management and customer service" and "evaluation and audits" stagnated in terms of progress. In terms of NRL performace, all indicators improved except for culture positivity in smear negative tuberculosis. CONCLUSION: Although a quality management system was introduced in the NRL there is now an urgent need to develop and implement an adapted roadmap for Armenia. This will be vital to hasten the much-needed pace towards accreditation.

Change in TB diagnostic profile after introduction of GeneXpert MTB/RIF assay in National TB Program of Armenia, 2013-2017.

INTRODUCTION: In 2013, the National Tuberculosis (TB) Program of Armenia introduced GeneXpert MTB/RIF (Xpert) assay to address World Health Organization (WHO) target of 80% (2020) of notified new and relapse TB cases to be tested with WHO recommended rapid diagnostic methods. This study aimed to assess the change in laboratory diagnostic profile of Mycobacterium tuberculosis after introduction of the Xpert assay from 2013 to 2017. METHODOLOGY: Retrospective cohort analysis of all presumptive TB patients' records retrieved from the National Reference Laboratory database was performed. RESULTS: This study showed increased trend of Xpert coverage for suspected TB cases from 25% in 2013 to 86% in 2017 which is in line with WHO TB global strategy's target of 80% in 2020. In 4.7% cases, Xpert tested positive while microscopy showed negative results. There was also an improved detection of Rifampicin resistance with increased concordance from 99.1% to 99.4% and decreased discordance from 6.7% to 1.4% between culture and Xpert results. CONCLUSION: Armenia has achieved the 2020 target; in terms of utilizing the GeneXpert it is on track to achieve the End TB strategy target of 100% by 2025. The next step of this research will be assessment of the impact of GeneXpert and other TB tests utilization on the treatment outcomes in Armenia.

Quality of care provided to tuberculosis patients in Armenia: How satisfied are the patients?

INTRODUCTION: Adherence to tuberculosis (TB) treatment as an important determinant for the successful cure of patients can be increased by focusing on patient satisfaction. The objective of this study was to evaluate patient satisfaction with TB services, different aspects of patient satisfaction, and demographic, health and treatment characteristics associated with satisfaction. METHODOLOGY: Overall 505 randomly selected TB patients that received treatment during 2014-2015 in Armenia underwent a cross-sectional telephone survey. Patient satisfaction items were selected from the Patient Satisfaction Questionnaire (PSQ-18). The Consultation and Relational Empathy (CARE) and Patient Enablement Instrument (PEI) were also used. Treatment adherence was assessed using the Morisky Adherence Scale. RESULTS: The respondents comprised 386 (76.4%) men and 119 (23.6%) women with a mean age of 45.5 ± 0.7 years. Nearly 99% (n = 500) of them were treatment-adherent. However, 45 (8.9%) mentioned the side effects as a reason for not following the treatment, revealing the non-adherence level of approximately 9%. About 93% of the patients were generally satisfied with the TB services, about 46% were satisfied with consultation and relational empathy and about 95% were satisfied with patient enablement. Being unsatisfied with TB services was associated with treatment non-adherence, inpatient treatment, drug-resistant TB, higher education, being unmarried, having a family income of below 50,000AMD (~120 USD) on average, being unsatisfied with consultation and empathy and place of residence. CONCLUSIONS: This study reports that TB patients are highly satisfied with TB care in Armenia. However, addressing specific characteristics associated with satisfaction may improve the TB program.

High prevalence of infection and low incidence of disease in child contacts of patients with drug-resistant tuberculosis: a prospective cohort study.

OBJECTIVE: We aimed to measure the prevalence and incidence of latent tuberculosis infection (LTBI) and tuberculosis (TB) disease in children in close contact with patients with drug-resistant TB (DR-TB) in a country with high DR-TB prevalence. DESIGN AND SETTING: This is a prospective cohort study of paediatric contacts of adult patients with pulmonary DR-TB in Armenia. Children were screened using tuberculin skin test, interferon-gamma release assay and chest X-ray at the initial consultation, and were reassessed every 3-6 months for a period of 24 months. Children did not receive preventive treatment. MAIN OUTCOME MEASURES: Prevalence and incidence of LTBI and TB disease; factors associated with prevalent LTBI. RESULTS: At initial evaluation, 3 of the 150 children included were diagnosed with TB disease (2.0%). The prevalence of LTBI was 58.7%. The incidence of LTBI was 19.9 per 100 children per year, and was especially high during the first 6 months of follow-up (33.3 per 100 children per year). No additional cases with incident disease were diagnosed during follow-up. After adjustment, prevalent LTBI was significantly associated with the child's age, sleeping in the same house, higher household density, the index case's age, positive smear result and presence of lung cavities. CONCLUSIONS: Children in close contact with patients with DR-TB or in contact with very contagious patients had an increased risk of prevalent LTBI. Although none of the children developed TB disease during a 2-year follow-up period, screening for symptoms of TB disease, based on the prevalence of disease at recruitment, together with follow-up and repeated testing of non-infected contacts, is highly recommended in paediatric contacts of patients with DR-TB.

Outcomes of HIV-infected versus HIV-non-infected patients treated for drug-resistance tuberculosis: Multicenter cohort study.

BACKGROUND: The emergence of resistance to anti-tuberculosis (DR-TB) drugs and the HIV epidemic represent a serious threat for reducing the global burden of TB. Although data on HIV-negative DR-TB treatment outcomes are well published, few data on DR-TB outcomes among HIV co-infected people is available despite the great public health importance. METHODS: We retrospectively reported and compared the DR-TB treatment outcomes of HIV-positive and HIV-negative patients treated with an individualized regimen based on WHO guidelines in seven countries: Abkhazia, Armenia, Colombia, Kenya, Kyrgyzstan, Swaziland and Uzbekistan. RESULTS: Of the 1,369 patients started DRTB treatment, 809 (59.1%) were multi-drug resistant (MDR-TB) and 418 (30.5%) were HIV-positive. HIV-positive patients were mainly from African countries (90.1%) while HIV-negative originated from Former Soviet Union (FSU) countries. Despite a higher case fatality rate (19.0% vs 9.4%), HIV-positive MDR-TB patients had a 10% higher success rate than HIV-negative patients (64.0% vs 53.2%, p = 0.007). No difference in treatment success was found among polydrug-resistant (PDR-TB) patients. Overall, lost to follow-up rate was much higher among HIV-negative (22.0% vs. 8.4%). Older age and not receiving ART were the only factors associated with unfavorable treatment outcome among HIV-positive patients. CONCLUSIONS: As already known for HIV-negative patients, success rate of DR-TB HIV-positive patients remains low and requires more effective DR-TB regimen using new drugs also suitable to HIV-infected patients on ART. The study also confirms the need of ART introduction in HIV co-infected patients.

Nonuniform Currents and Spins of Relativistic Electron Vortices in a Magnetic Field.

We present a relativistic description of electron vortex beams in a homogeneous magnetic field. Including spin from the beginning reveals that spin-polarized electron vortex beams have a complicated azimuthal current structure, containing small rings of counterrotating current between rings of stronger corotating current. Contrary to many other problems in relativistic quantum mechanics, there exists a set of vortex beams with exactly zero spin-orbit mixing in the highly relativistic and nonparaxial regime. The well-defined phase structure of these beams is analogous to simpler scalar vortex beams, owing to the protection by the Zeeman effect. For states that do show spin-orbit mixing, the spin polarization across the beam is nonuniform rendering the spin and orbital degrees of freedom inherently inseparable.

Six-Month Response to Delamanid Treatment in MDR TB Patients.

Delamanid, recently available for the treatment of multidrug-resistant tuberculosis (MDR TB), has had limited use outside clinical trials. We present the early treatment results for 53 patients from 7 countries who received a delamanid-containing treatment for MDR TB. Results show good tolerability and treatment response at 6 months.

Tuberculosis treatment and Smoking, Armenia, 2014-2016.

INTRODUCTION: Tuberculosis and tobacco prove to be increasingly apparent world problems. Armenia is a developing country which is facing issues related to the high rates of tobacco consumption. Moreover, it is among the list of high multi-drug resistant (MDR) Tuberculosis TB burden countries. Treatment success rate in Armenia for sputum smear-positive cases never reached World Health Organization's (WHO) target of 85% in last 15 years. Data from different studies completed across the world suggests that there is an association between smoking and negative treatment outcomes. METHODS: This retrospective study was designed to investigate aforementioned associations between TB treatment outcomes and smoking status of TB patients. Data for the study were derived from the national data available in the electronic database of the Armenian National TB Center. RESULTS: Based on inclusion and exclusion criteria 992 TB patients registered in 2014 were enrolled in this study. All of them are were TB patients in which 387 were smokers and 605 were non-smokers. Notably, adjusted analysis showed that individuals who smoked during TB treatment had 1.61 higher odds of having unsuccessful TB treatment outcome. Additionally, consistent with the literature, statistically significant association was identified between TB treatment outcome and other well factors such as sputum smear status (OR = 2.24, p < 0.01), HIV status (OR, = 1.87, p < 0.01) of patients, etc. CONCLUSIONS: The smoking, HIV positive status, positive sputum smear microscopy test were identified as an important factors associated with the unsuccessful TB treatment outcome in Armenia. It highlights the necessity of having specific restrictions and campaign programs to reduce smoking rates among TB patients in order to improve current TB treatment and care services throughout Armenia.

Molecular genetics of Mycobacterium tuberculosis resistant to aminoglycosides and cyclic peptide testing by MTBDRsl in Armenia.

OBJECTIVE/BACKGROUND: The GenoType MTBDRsl test rapidly detects resistance to ethambutol, fluoroquinolones, second-line aminoglycosides (amikacin [AMK] and kanamycin [KAN]), and cyclic peptides (capreomycin [CAP]) in Mycobacterium tuberculosis. According to data from Global Drug Resistance Surveillance Report (2007), Armenia is counted as a high-burden country for multidrug-resistant tuberculosis (MDR-TB). The estimated burden of MDR-TB in 2012 was 9.4 (7-12) and 43 (38-49) among retreatment TB cases. A total of 92 laboratory confirmed cases were reported to the World Health Organization (57 new and 35 previously treated) out of 511 cases tested for MDR-TB. METHODS: A set of 77 drug-resistant TB isolates during 2011 and 2012 period, being either acid-fast bacterium positive or negative but culture-positive resistant to isoniazid, rifampin, or both according to the GenoType MTBDR plus assay, were consecutively tested using GenoType MTBDRsl. rrs gene analysis and the results from GenoType MTBDRsl were compared with phenotypic drug resistance testing. The DNA preparation method was performed as recommended by the manufacturer (Genotype MTBDR plus version 1.0 and Genotype MTBDRsl version 2.0 Hain Lifescience Nehren, Germany). RESULTS: Aminoglycosides are key drugs for the treatment of MDR-TB. A total of 77 drug-resistant TB and four extensively drug-resistant M. tuberculosis isolates from Armenian TB patients were analyzed to characterize mutations within rrs and to compare with phenotypic drug resistance testing. Simultaneously, the following were identified: 65 (84.41%) rrs wild type (WT), 1 (1.3%) rrs WT MUT1 and MUT2 (WT; A1401G and G1484T), 1 (1.3%) rrs WT1, MUT1 (A1401G), 9 (11.7%) rrs WT1, MUT1 (A1401G), and 1 (1.3%) rrs WT1, MUT1. Mutation at position 1401 in rrs leads to resistance to KAN (7/77=9%), AMK (9/77=11.68%), and CAP (5/77=6.49%). Eleven (14.28%) streptomycin-resistant strains had a rrs mutation. CONCLUSION: Isolates with rrs structural gene mutations were cross-resistant to streptomycin, KAN, CAP, and AMK. Detection of the A1401G mutation appeared to be 100% specific for the detection of resistance to KAN and AMK. Being the first assessment, these data establish the presence of phenotypic drug-resistant and extensively drug-resistant strains using molecular profiling and are helpful in understanding aminoglycoside resistance on a molecular level.

Effects of treatment interruption patterns on treatment success among patients with multidrug-resistant tuberculosis in Armenia and Abkhazia.

BACKGROUND: The success of the current treatment regimen for multidrug-resistant (MDR) tuberculosis is poor partly owing to a high default rate. Many studies have explored predictors of poor outcomes, but very few have assessed the effects of treatment interruptions on treatment outcomes for MDR tuberculosis. METHODS: We conducted a retrospective analysis among patients with MDR tuberculosis enrolled in 2 MDR tuberculosis programs using regimens recommended by the World Health Organization under directly observed therapy. Treatment outcomes were defined as successful if the patient was cured or completed treatment and unsuccessful if the patient died or defaulted from treatment or if treatment failed. The effect of patterns of interruptions on treatment outcomes was assessed through multivariate logistic regression. RESULTS: A total of 393 patients with MDR tuberculosis were included in the study; 171 (43.5%) had a successful outcome, and 222 (56.5%) an unsuccessful outcome: 39 (9.9%) died, 56 (14.3%) had failed treatment, and 127 (32.3%) defaulted from treatment. In multivariate analysis, long interruptions (≥3 days) (adjusted odds ratio, 3.87; 95% confidence interval, 1.66-8.98) and short gaps (<10 days) between interruptions (3.94; 1.76-8.81) were independently associated with an unsuccessful treatment outcome. DISCUSSION: This study shows that in a directly observed therapy-based MDR tuberculosis program, treatment interruptions at short intervals of ≥3 days directly affect treatment outcome.