Large studies on bedaquiline used to treat multidrug-resistant (MDR-) and extensively drug-resistant tuberculosis (XDR-TB) are lacking. This study aimed to evaluate the safety and effectiveness of bedaquiline-containing regimens in a large, retrospective, observational study conducted in 25 centres and 15 countries in five continents.428 culture-confirmed MDR-TB cases were analysed (61.5% male; 22.1% HIV-positive, 45.6% XDR-TB). MDR-TB cases were admitted to hospital for a median (interquartile range (IQR)) 179 (92-280) days and exposed to bedaquiline for 168 (86-180) days. Treatment regimens included, among others, linezolid, moxifloxacin, clofazimine and carbapenems (82.0%, 58.4%, 52.6% and 15.3% of cases, respectively).Sputum smear and culture conversion rates in MDR-TB cases were 63.6% and 30.1%, respectively at 30 days, 81.1% and 56.7%, respectively at 60 days; 85.5% and 80.5%, respectively at 90 days and 88.7% and 91.2%, respectively at the end of treatment. The median (IQR) time to smear and culture conversion was 34 (30-60) days and 60 (33-90) days. Out of 247 culture-confirmed MDR-TB cases completing treatment, 71.3% achieved success (62.4% cured; 8.9% completed treatment), 13.4% died, 7.3% defaulted and 7.7% failed. Bedaquiline was interrupted due to adverse events in 5.8% of cases. A single case died, having electrocardiographic abnormalities that were probably non-bedaquiline related.Bedaquiline-containing regimens achieved high conversion and success rates under different nonexperimental conditions.

The continuous flow of new research articles on MDR-TB diagnosis, treatment, prevention and rehabilitation requires frequent update of existing guidelines. This review is aimed at providing clinicians and public health staff with an updated and easy-to-consult document arising from consensus of Global Tuberculosis Network (GTN) experts.The core published documents and guidelines have been reviewed, including the recently published MDR-TB WHO rapid advice and ATS/CDC/ERS/IDSA guidelines.After a rapid review of epidemiology and risk factors, the clinical priorities on MDR-TB diagnosis (including whole genome sequencing and drug-susceptibility testing interpretations) and treatment (treatment design and management, TB in children) are discussed. Furthermore, the review comprehensively describes the latest information on contact tracing and LTBI management in MDR-TB contacts, while providing guidance on post-treatment functional evaluation and rehabilitation of TB sequelae, infection control and other public health priorities.

The World Health Organization (WHO) recommends that countries implement pharmacovigilance and collect information on active drug safety monitoring (aDSM) and management of adverse events.The aim of this prospective study was to evaluate the frequency and severity of adverse events to anti-tuberculosis (TB) drugs in a cohort of consecutive TB patients treated with new (i.e. bedaquiline, delamanid) and repurposed (i.e. clofazimine, linezolid) drugs, based on the WHO aDSM project. Adverse events were collected prospectively after attribution to a specific drug together with demographic, bacteriological, radiological and clinical information at diagnosis and during therapy. This interim analysis included patients who completed or were still on treatment at time of data collection.Globally, 45 centres from 26 countries/regions reported 658 patients (68.7% male, 4.4% HIV co-infected) treated as follows: 87.7% with bedaquiline, 18.4% with delamanid (6.1% with both), 81.5% with linezolid and 32.4% with clofazimine. Overall, 504 adverse event episodes were reported: 447 (88.7%) were classified as minor (grade 1–2) and 57 (11.3%) as serious (grade 3–5). The majority of the 57 serious adverse events reported by 55 patients (51 out of 57, 89.5%) ultimately resolved. Among patients reporting serious adverse events, some drugs held responsible were discontinued: bedaquiline in 0.35% (two out of 577), delamanid in 0.8% (one out of 121), linezolid in 1.9% (10 out of 536) and clofazimine in 1.4% (three out of 213) of patients. Serious adverse events were reported in 6.9% (nine out of 131) of patients treated with amikacin, 0.4% (one out of 221) with ethionamide/prothionamide, 2.8% (15 out of 536) with linezolid and 1.8% (eight out of 498) with cycloserine/terizidone.The aDSM study provided valuable information, but implementation needs scaling-up to support patient-centred care.

6This 8-week, randomized, double-blind, controlled study compared efficacy and tolerability of telmisartan ⁄ amlodipine (T ⁄ A) single-pill combination (SPC) vs the respective monotherapies in 858 patients with severe hypertension (systolic ⁄ diastolic blood pressure [SBP ⁄ DBP] !180 ⁄ 95 mm Hg). At 8 weeks, T ⁄ A provided significantly greater reductions from baseline in seated trough cuff SBP ⁄ DBP ()47.5 mm Hg ⁄ )18.7 mm Hg) vs T (P<.0001) or A (P=.0002) monotherapy; superior reductions were also evident at 1, 2, 4, and 6 weeks. Blood pressure (BP) goal and response rates were consistently higher with T ⁄ A vs T or A. T ⁄ A was well tolerated, with less frequent treatmentrelated adverse events vs A (12.6% vs 16.4%) and a numerically lower incidence of peripheral edema and treatment discontinuation. In conclusion, treatment of patients with substantially elevated BP with T ⁄ A SPCs resulted in high and significantly greater BP reductions and higher BP goal and response rates than the respective monotherapies. T ⁄ A SPCs were well tolerated. J Clin Hypertens (Greenwich). 2012;14:206-215. Ó2012 Wiley Periodicals, Inc.Based on evidence from a number of large antihypertensive trials, 1-9 most guidelines acknowledge that combination therapy is needed to reduce blood pressure (BP) successfully to goal in the majority of patients; only a minority of patients achieve their BP goal with a single agent.10-14 Also, the Avoiding Cardiovascular Events Through Combination Therapy in Patients Living With Systolic Hypertension (ACCOMPLISH) study showed a significant reduction of cardiovascular (CV) events and death in hypertensive patients at high CV risk treated with a combination of an angiotensin-converting enzyme (ACE) inhibitor and a calcium channel blocker (CCB).15 Nevertheless, despite rigorous and comprehensive guidelines, and a trend towards an increase in the use of combination therapy in treatment practice, 16 several studies have demonstrated the persistence of poor BP goal rates in treated patients. [17][18][19] The impact of poor BP control is compounded by the often high prevalence of other CV risk factors in hypertensive patients (eg, hypercholesterolemia, obesity, type 2 diabetes mellitus [T2DM], and smoking).13 Therefore, an urgent need still remains to improve the management of hypertension. One logical approach would be to use 2 drugs from different classes and complementary mechanisms of action in combination. Such combinations may result in additional BP decreases and improved goal rates, compared with either agent used alone. 20-23Furthermore, single-pill combinations (SPCs) are known to increase treatment adherence and reduce health care costs. [24][25][26][27] A combination of a CCB and an angiotensin II receptor blocker (ARB) is a rational approach for managing hypertension and there is increasing evidence that this combination is effective. 11,13,28,29 The aim of the current study was to compare the efficacy and tolerability of the SPC of telmisartan 80 mg ⁄ amlodipine 10 mg (T80 ⁄ A10) with that of...

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