Serupslater0452

Worldwide uptake of new drugs in the treatment of rifampicin-resistant tuberculosis (RR-TB) has been extremely low. In June 2018, ahead of the release of the updated WHO guidelines for the management of RR-TB, South Africa announced that bedaquiline (BDQ) would be provided to virtually all RR-TB patients on shorter or longer regimens. South Africa has been the global leader in accessing BDQ for patients with RR-TB, who now represent 60% of the global BDQ cohort. The use of BDQ within a shorter modified regimen has generated the programmatic data underpinning the most recent change in WHO guidelines endorsing a shorter, injectable-free regimen. Progressive policies on access to new drugs have resulted in improved favourable outcomes and a reduction in mortality among RR-TB patients in South Africa. This supported global policy change. BIBR 1532 research buy The strategies underpinning these bold actions include close collaboration between the South African National TB Programme and partners, introduction of new TB diagnostic tools in closely monitored conditions and the use of locally generated programmatic evidence to inform country policy changes. In this paper, we summarise a decade´s work that led to the bold decision to use a modified, short, injectable-free regimen with BDQ and linezolid under carefully monitored programmatic conditions.BACKGROUND Addressing TB in India is critical to meeting global targets. With the scale-up of diagnostic networks and the availability of new TB drugs, India had the opportunity to improve the detection and treatment outcomes in drug-resistant TB (DR-TB).OBJECTIVE To document how the introduction of new drugs and regimens is helping India improve the care of DR-TB patients.DESIGN In 2016, India´s National TB Programme (NTP) introduced bedaquiline (BDQ) under a Conditional Access Programme (BDQ-CAP) at six sites after providing extensive training and strengthening laboratory testing, pre-treatment evaluation, active drug safety monitoring and management (aDSM) and follow-up systems.RESULTS An interim analysis reflected earlier and better culture conversion rates 83% of the 620 patients converted within a median time of 60 days. However, 248 serious adverse events were reported, including 73 deaths (12%) and 100 cardiotoxicity events (16.3%). Encouraged by the evidence of safety and efficacy of BDQ, the NTP took steps to systematically expand its access to cover the entire population by 2018.CONCLUSION The cautious yet focused approach used to introduce BDQ under BDQ-CAP paved the way for the rapid introduction of delamanid, as well as the shorter treatment regimen and the all-oral regimen for DR-TB.Treatment outcomes in patients with drug-resistant tuberculosis (DR-TB) remains unsatisfactory in the Philippines. To address this, we implemented the use of new anti-TB drugs and novel regimens. The Philippine National Tuberculosis Control Program (NTP) participated in the Bedaquiline (BDQ) Donation Program created by the US Agency for International Development and Janssen. Despite availability of donated medicine, there was a delay in the implementation of BDQ, both under operational research and programme conditions. The main challenges encountered were delayed approval by national and institutional ethics boards; limited experience of the NTP in the conduct of operational research into new drugs; and the lack of confidence of healthcare staff in the use of new and re-purposed anti-TB drugs. Technical assistance from partners and capacity building on clinical management of DR-TB and on pharmacovigilance among health workers were vital in overcoming these challenges. Over a 3-year period (from 2016-2018), 448 patients were initiated on BDQ-based regimens.The number of multidrug-resistant tuberculosis (MDR-TB) cases reported in the Americas has increased by 21.2%, from 3737 in 2016 to 4791 in 2018. The WHO has been recommending changes on the treatment of DR-TB, moving from long-duration treatment with injectables to a short oral regimen with new drugs such as bedaquiline (BDQ) and delamanid (DLM), in selected cases and only under programmatic conditions. Injectables are no longer recommended by the WHO due to lower efficacy and the increasing seriousness of adverse events. The introduction of new oral drugs for DR-TB received a boost with a global donation of BDQ to some eligible countries, which continues with the countries purchasing drugs through the Pan American Health Organization Strategic Fund. The main challenges in the scaling up of new drugs for DR-TB include low DR-TB detection rate, the slow pace in transitioning to molecular testing and delays in the introduction of new oral short regimens for MDR-TB. link2 The Americas need to accelerate the scale up of new oral treatments, improve detection rates, increase molecular diagnosis of resistance, and ensure the registration and introduction of the shorter treatment regimen in national MDR-TB guidelines.To improve the unsatisfactory treatment outcomes of multidrug-resistant TB (MDR-TB), it is essential we use new regimens based on newer drugs. To address challenges in the introduction of BDQ and the shorter treatment regimen (STR), the USAID has committed to support countries receiving BDQ (through the USAID/Janssen Bedaquiline Donation Program), with targeted short-term technical assistance (TA). Six MDR-TB clinical consultants were recruited and provided TA to 17 countries between 2017 and 2019. Building on other in-country support, this short-term TA proved instrumental in overcoming barriers, such as misconceptions about BDQ safety, inadequate clinical skills to manage patients and limited expansion plans to increase access to BDQ and the STR.BACKGROUND Drug-resistant tuberculosis (DR-TB) remains a global public health crisis. In 2013, the World Health Organization recommended the introduction of bedaquiline (BDQ) for eligible DR-TB patients.METHODS We conducted a retrospective review and analyses of project reports from 2016 to mid-2019 on the processes, activities implemented, available results on enrolment and interim treatment outcomes, across the 23 Challenge TB (CTB) supported countries.RESULTS Initial introduction of BDQ-containing regimens in the 23 CTB-supported countries took on average 2 years, with subsequent nation-wide scale-up achieved in Ethiopia and Kyrgyzstan within a short time period. Successful implementation required critical interventions including advocacy, revision of policies and guidelines, capacity building of health care workers, and strengthening of laboratory networks. The number of countries providing BDQ increased from 9 to 23; 9398 patients were enrolled on bedaquiline containing regimens; 71% were culture-negative after 6 months of treatment; and the number of countries reporting serious adverse events increased (from 5 to 18). Major challenges included limited in-country coordination with drug regulatory agencies, unrealistic quantification and drug ordering, weak laboratory networks and reporting systems for drug safety.CONCLUSION BDQ introduction required a systematic and programmatic approach. The initial time investment helped achieve initial introduction and scale-up of coverage, ownership and sustainability by National TB Programmes.The Bedaquiline Donation Program was a global public-private partnership between the US Agency for International Development (USAID) and Janssen Therapeutics. The 4-year program was intended to accelerate access to bedaquiline (BDQ) by committing 30 000 treatment courses to more than eligible 100 countries. The program was designed to remove barriers by making the drug available through the Global Drug Facility (GDF); prepare TB programs to a changing drug-resistant TB (DR-TB) treatment landscape; improve quality of the entire DR-TB care paradigm; gather additional effectiveness and safety data in programmatic settings; and identify programmatic challenges associated with new TB drug introduction. By the end of the program (in April 2019), 80 countries had ordered 104 344 BDQ courses, of which 33 119 had been delivered (the rest were pending delivery). The introduction of new TB drugs offers hope to patients and an opportunity to transform DR-TB treatment with shorter, simpler and more tolerable regimens. The Bedaquiline Donation Program demonstrated that access to new drugs can be accelerated. Technical support to improve the overall quality of care is critical as are investments beyond the cost of the drug.OBJECTIVE To evaluate the clinical features of disease progression among patients with COVID-19 to help early identification of patients at high risk.DESIGN This was a retrospective, multi-centre cohort study. From 10 January to 29 February 2020, all cases diagnosed with COVID-19 at 24 hospitals (with complete medical records) in Jiangsu Province, China were recruited. The primary outcome was deterioration in condition, i.e., the dramatic progression from asymptomatic or mild or moderate status into severe or critically ill status during 14 days´ follow-up.RESULTS Of the 625 patients in Jiangsu, none died; 597 patients were asymptomatic or had mild or moderate disease on admission, of whom 36 (6%) experienced disease deterioration to become severe or critically ill.CONCLUSION Disease deterioration to severe or critically ill status was associated with age, pulmonary opacity score, lymphocyte count on admission and exposure to the pandemic centre in Wuhan.BACKGROUND Bedaquiline (BDQ) has not been extensively studied among patients co-infected with HIV drug-resistant tuberculosis (DR-TB). We compared treatment outcomes in DR-TB patients treated with BDQ- and linezolid (LZD) containing regimens to historic controls treated with second-line injectable-containing regimens.METHODS Retrospective cohort study of consecutive DR-TB patients initiated on BDQ- and LZD-containing regimens at a TB referral hospital in KwaZulu-Natal, South Africa. Participants were prospectively followed through 24 months for treatment outcome and adverse events. Outcomes were compared to a historic control cohort of DR-TB HIV patients enrolled at the same facility prior to BDQ introduction.RESULTS Adult DR-TB patients initiating BDQ between January 2014 and November 2015 were enrolled (n = 151). The majority of patients were female (52%), HIV co-infected (77%) and on antiretroviral therapy (100%). End of treatment outcomes included cure (63%), TB culture conversion (83%), completion (0.7%), loss to follow-up (15%), treatment failure (5%), and death (17%). Compared to historic controls (n = 105), patients treated with BDQ experienced significantly higher TB culture conversion and cure, with significantly lower mortality. Adverse effects were common (92%), and most frequently attributed to LZD (24.1%). QT segment prolongation was common but without clinical sequelae.CONCLUSION Treatment with BDQ- and LZD-containing regimens was associated with improved treatment outcomes and survival in DR-TB HIV patients.BACKGROUND As there had been no reduction in the TB burden in South Korea since 2000, a public-private mix (PPM) strategy was launched in 2011. The purpose of this study was to investigate the reasons for lost to follow-up (LTFU) among TB patients and their clinical characteristics.METHOD A multicentre, cross-sectional study based on in-depth interviews with patients and their families by TB specialist nurses was conducted. Patients who were reported with a final outcome of LTFU in 2015-2017 at all PPM hospitals across the country were enrolled. Enrolled patients were classified into six subgroups by age and three major reasons for LTFU (adverse effects, refusal of treatment, marginalisation) and their clinical features were compared.RESULTS Among 780 patients, those who were lost to follow-up due to adverse effects accounted for the largest proportion (n = 387). link3 LTFU in those aged less then 65 years who refused treatment (n = 189) and those aged less then 65 years who were marginalised (n = 108) were related to having smear-positive TB and a previous history of unfavourable outcomes.