B cells from Patients with Rheumatoid Arthritis Show Conserved CD39-Mediated Regulatory Function and increased CD39 Expression After Positive Response to Therapy.

Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by progressive joint destruction associated with increased pro-inflammatory mediators. In inflammatory microenvironments, exogenous ATP (eATP) is hydrolyzed to adenosine, which exerts immunosuppressive effects, by the consecutive action of the ectonucleotidases CD39 and CD73. Mature B cells constitutively express both ectonucleotidases, converting these cells to potential suppressors. Here, we assessed CD39 and CD73 expression on B cells from treated or untreated patients with RA. Neither the frequency of CD73+CD39+ and CD73-CD39+ B cell subsets nor the levels of CD73 and CD39 expression on B cells from untreated or treated RA patients showed significant changes in comparison to healthy controls (HC). CpG+IL-2-stimulated B cells from HC or untreated RA patients increased their CD39 expression, and suppressed CD4+ and CD8+ T cell proliferation and intracellular TNF-production. A CD39 inhibitor significantly restored proliferation and TNF-producing capacity in CD4+ T cells, but not in CD8+ T cells, from HC and untreated RA patients, indicating that B cells from untreated RA patients conserved CD39-mediated regulatory function. Good responder patients to therapy (R-RA) exhibited an increased CD39 but not CD73 expression on B cells after treatment, while most of the non-responder (NR) patients showed a reduction in ectoenzyme expression. The positive changes of CD39 expression on B cells exhibited a negative correlation with disease activity and rheumatoid factor levels. Our results suggest modulating the ectoenzymes/ADO pathway as a potential therapy target for improving the course of RA.

Maternal near-miss case reviews: the UK approach.

The UK has a well-established programme of Confidential Enquiries into Maternal Deaths and a national system for research into near-miss maternal morbidities, the UK Obstetric Surveillance System. The addition of a programme of near-miss case reviews, the Confidential Enquiries into Maternal Morbidity, permits a complete examination of the incidence, risk factors, care and outcomes of the severest complications in pregnancy, and enables the lessons learnt to improve future care to be identified more quickly. This in turn allows for more rapid inclusion of recommendations into national guidance and hence the potential of better health for both women and babies.

First national survey of anti-tuberculosis drug resistance in Azerbaijan and risk factors analysis.

SETTING: Civilian population of the Republic of Azerbaijan. OBJECTIVES: To determine patterns of anti-tuberculosis drug resistance among new and previously treated pulmonary tuberculosis (TB) cases, and explore their association with socio-demographic and clinical characteristics. DESIGN: National cross-sectional survey conducted in 2012-2013. RESULTS: Of 789 patients (549 new and 240 previously treated) who met the enrolment criteria, 231 (42%) new and 146 (61%) previously treated patients were resistant to any anti-tuberculosis drug; 72 (13%) new and 66 (28%) previously treated patients had multidrug-resistant TB (MDR-TB). Among MDR-TB cases, 38% of new and 46% of previously treated cases had pre-extensively drug-resistant TB (pre-XDR-TB) or XDR-TB. In previously treated cases, 51% of those who had failed treatment had MDR-TB, which was 15 times higher than in relapse cases (OR 15.2, 95%CI 6-39). The only characteristic significantly associated with MDR-TB was a history of previous treatment (OR 3.1, 95%CI 2.1-4.7); for this group, history of incarceration was an additional risk factor for MDR-TB (OR 2.8, 95%CI 1.1-7.4). CONCLUSION: Azerbaijan remains a high MDR-TB burden country. There is a need to implement countrywide control and innovative measures to accelerate early diagnosis of drug resistance in individual patients, improve treatment adherence and strengthen routine surveillance of drug resistance.

Tuberculosis in health care workers in Belarus.

SETTING: Tuberculosis (TB), including drug-resistant TB, is a serious problem in Belarus. OBJECTIVES: To determine the prevalence of TB among health care workers (HCWs) along with patient characteristics, treatment outcomes and drug resistance patterns between 2008 and 2012. DESIGN: A retrospective national record review. RESULTS: There were 116 HCWs with TB. Case notification rates were higher among HCWs than in the general population (349 vs. 40/100 000 in 2012). Most HCWs with TB were nurses (n = 46, 40%) or nurse assistants (n = 37, 32%), female (n = 100, 86%) and aged 25-44 years (n = 84, 72%). Most common places of work for HCWs with TB were multidrug-resistant (MDR-) and extensively drug-resistant (XDR-TB) wards (n = 23, 20%), general medical (n = 26, 22%) and non-medical (n = 34, 29%) departments. All HCWs had pulmonary TB, 107 (92%) had new TB and 103 (89%) had negative sputum smears. Of the 38 (33%) with culture and drug susceptibility testing (DST), 28 (74%) had MDR-/XDR-TB. In 109 HCWs evaluated for final treatment outcomes, 97 (89%) were successfully treated, and their results were not affected by DST status. CONCLUSION: This study highlights the high prevalence of recorded TB in HCWs in TB health facilities in Belarus: there is a need to better understand and rectify this problem.

Drug-resistant tuberculosis in Eastern Europe: challenges and ways forward.

Encouragingly, global rates of new tuberculosis (TB) cases have been falling since 2005, in line with the Millennium Development Goal targets; however, cases of multidrug-resistant (MDR-) and extensively drug-resistant TB (XDR-TB) have been increasing. Fifteen of the world's 27 high MDR- and XDR-TB burden countries are in the World Health Organization (WHO) European Region, of which 10 are in Eastern Europe (including Baltic and Caucasus countries). To address the MDR- and XDR-TB situation in the WHO European Region, a Consolidated Action Plan to Prevent and Combat M/XDR-TB (2011-2015) was developed for all 53 Member States and implemented in 2011. Since the implementation of the Action Plan, the proportion of MDR-TB appears largely to have levelled off among bacteriologically confirmed TB cases in high-burden countries with universal or near universal (>95%) first-line drug susceptibility testing (DST). The treatment success rate, however, continues to decrease. A contributing factor is the substantial proportion of MDR-TB cases that are additionally resistant to either a fluoroquinolone, a second-line injectable agent or both (XDR-TB); high-burden country proportions range from 12.6% to 80.4%. Proportions of XDR-TB range from 5% to 24.8%. Despite much progress in Eastern Europe, critical challenges remain as regards access to appropriate treatment regimens; patient hospitalisation; scale-up of laboratory capacity, including the use of rapid diagnostics and second-line DST; vulnerable populations; human resources; and financing. Solutions to these challenges are aligned with the Post-2015 Global TB strategy. As a first step, the global strategy should be adapted at regional and country levels to serve as a framework for immediate actions as well as longer-term ways forward.

A four-year nationwide molecular epidemiological study in Estonia: risk factors for tuberculosis transmission.

SETTING: Estonia has a high proportion of multidrug-resistant tuberculosis (MDR-TB). It is important to link molecular and epidemiological data to understand TB transmission patterns. OBJECTIVE: To use 24-locus variable numbers of tandem repeat (VNTR) typing and national TB registry data in Estonia from 2009 to 2012 to identify the distribution of drug resistance patterns, Mycobacterium tuberculosis isolate clustering as an index for recent transmission, socio-demographic and clinical characteristics associated with recent transmission, and the distribution of transmission between index and secondary cases. DESIGN: A retrospective nationwide cross-sectional study. RESULTS: Of 912 cases with isolate and patient information, 39.1% of isolates were from the Beijing lineage. Cluster analysis identified 87 clusters encompassing 69.1% of isolates. The largest cluster comprised 178 isolates from the Beijing lineage, of which 92.1% were MDR- or extensively drug-resistant TB (XDR-TB). Factors associated with recent transmission were polyresistant TB, MDR- and XDR-TB, human immunodeficiency virus positivity, Russian ethnicity, non-permanent living situation, alcohol abuse and detention. XDR-TB cases had the highest risk of recent transmission. The majority of transmission cases involved individuals aged 30-39 years. CONCLUSION: Recent TB transmission in Estonia is high and is particularly associated with MDR- and XDR-TB and the Beijing lineage.

Multi- and extensively drug-resistant tuberculosis in Latvia: trends, characteristics and treatment outcomes.

SETTING: Drug-resistant tuberculosis (TB) is an important public health problem in Latvia. OBJECTIVE: To document trends, characteristics and treatment outcomes of registered patients with multi-drug-resistant (MDR-) and extensively drug-resistant (XDR-) TB in Latvia from 2000 to 2010. DESIGN: A retrospective national cohort study. RESULTS: Of 1779 patients, 1646 (92%) had MDR- and 133 (8%) XDR-TB. Over 11 years, the proportion of XDR-TB among MDR-TB patients increased from 2% to 18%. Compared to MDR-TB patients, those with XDR-TB were significantly more likely to have failed MDR-TB treatment (OR 8.4, 95%CI 4.3-16.2), have human immunodeficiency virus infection (OR 3.2, 95%CI 1.8-5.7), be illegal drug users (OR 5.7, 95%CI 2.6-11.6) or have had contact with MDR-TB patients (OR 1.9, 95%CI 1.3-2.8). Cure rates for XDR-TB were 50%. Compared with MDR-TB patients, those with XDR-TB had a higher risk of treatment failure (29% vs. 8%, respectively, P < 0.001). Unfavourable treatment outcomes were significantly associated with being male; having smear-positive disease; pulmonary cavities; failure, default or relapse after previous MDR-TB treatment; and a history of incarceration. CONCLUSION: More MDR-TB in Latvia is now also XDR-TB. This study identified several risk factors for XDR-TB and, for unfavourable treatment outcomes, highlighting the importance of early diagnosis and appropriate management of MDR-/XDR-TB.

Maternal sepsis: a Scottish population-based case-control study.

OBJECTIVE: To describe the risk of maternal sepsis associated with obesity and other understudied risk factors such as operative vaginal delivery. DESIGN: Population-based, case-control study. SETTING: North NHS region of Scotland. POPULATION: All cases of pregnant, intrapartum and postpartum women with International Classification of Disease-9 codes for sepsis or severe sepsis recorded in the Aberdeen Maternal and Neonatal Databank (AMND) from 1986 to 2009. Four controls per case selected from the AMND were frequency matched on year-of-delivery. METHODS: Cases and controls were compared; significant variables from univariable regression were adjusted in a multivariable logistic regression model. MAIN OUTCOME MEASURES: Dependent variables were uncomplicated sepsis or severe ('near-miss') sepsis. Independent variables were demographic, medical and clinical delivery characteristics. Unadjusted and adjusted odds ratios (OR) with 95% confidence intervals (95% CI) are reported. RESULTS: Controlling for mode of delivery and demographic and clinical factors, obese women had twice the odds of uncomplicated sepsis (OR 2.12; 95% CI 1.14-3.89) compared with women of normal weight. Age <25 years (OR 5.15; 95% CI 2.43-10.90) and operative vaginal delivery (OR 2.20; 95% CI 1.02-4.87) were also significant predictors of sepsis. Known risk factors for maternal sepsis were also significant in this study (OR for uncomplicated and severe sepsis respectively): multiparity (OR 6.29, 12.04), anaemia (OR 3.43, 18.49), labour induction (OR 3.92 severe only), caesarean section (OR 3.23, 13.35), and preterm birth (OR 2.46 uncomplicated only). CONCLUSIONS: Obesity, operative vaginal delivery and age <25 years are significant risk factors for sepsis and should be considered in clinical obstetric care.

The Innovative Socio-economic Interventions Against Tuberculosis (ISIAT) project: an operational assessment.

SETTING: Tuberculosis (TB) affected households in impoverished shantytowns, Lima, Peru. OBJECTIVE: To evaluate socio-economic interventions for strengthening TB control by improving uptake of TB care and prevention services. DESIGN: Barriers to TB control were characterised by interviews with TB-affected families. To reduce these barriers, a multidisciplinary team offered integrated community and household socio-economic interventions aiming to: 1) enhance uptake of TB care by education, community mobilisation and psychosocial support; and 2) reduce poverty through food and cash transfers, microcredit, microenterprise and vocational training. An interim analysis was performed after the socio-economic interventions had been provided for 2078 people in 311 households of newly diagnosed TB patients for up to 34 months. RESULTS: Poverty (46% earned