Background Treatment success rates for multidrug-resistant tuberculosis (MDR-TB) remain low globally. Availability of newer drugs has given scope to develop regimens that can be patient-friendly, less toxic, with improved outcomes. We proposed to determine the effectiveness of an entirely oral, short-course regimen with bedaquiline and delamanid in treating MDR-TB with additional resistance to fluoroquinolones (MDR-TBFQ+) or second-line injectable (MDR-TBSLI+). Methods We prospectively determined the effectiveness and safety of combining 2 new drugs with 2 repurposed drugs—bedaquiline, delamanid, linezolid, and clofazimine—for 24–36 weeks in adults with pulmonary MDR-TBFQ+ and/or MDR-TBSLI+. The primary outcome was a favorable response at end of treatment, defined as 2 consecutive negative cultures taken 4 weeks apart. The unfavorable outcomes included bacteriologic or clinical failure during the treatment period. Results Of the 165 participants enrolled, 158 had MDR-TBFQ+. At the end of treatment, after excluding 12 patients due to baseline drug susceptibility and culture negatives, 139 of 153 patients (91%) had a favorable outcome. Fourteen patients (9%) had unfavorable outcomes: 4 deaths, 7 treatment changes, 2 bacteriological failures, and 1 withdrawal. During treatment, 85 patients (52%) developed myelosuppression, 69 (42%) reported peripheral neuropathy, and none had QTc(F) prolongation >500 ms. At 48 weeks of follow-up, 131 patients showed sustained treatment success with the resolution of adverse events in the majority. Conclusions After 24–36 weeks of treatment, this regimen resulted in a satisfactory favorable outcome in pulmonary MDR-TB patients with additional drug resistance. Cardiotoxicity was minimal, and myelosuppression, while common, was detected early and treated successfully. Clinical Trials Registration. ClinicalTrials Registry of India (CTRI/2019/01/017310).

Summary Drug resistant tuberculosis (DR-TB) is challenging to diagnose, treat, and prevent, but that is slowly changing. If the world is to drastically reduce the incidence of DR-TB, we must stop creating new drug-resistant TB as an essential first step. The drug-resistant TB epidemic that is ongoing must also be directly addressed. First-line drug resistance must be rapidly detected through universal molecular testing for resistance to at least rifampin and preferably other key drugs at initial TB diagnosis. DR-TB treatment outcomes must also improve dramatically. Effective use of currently-available, new, and repurposed drugs, combined with patient-centered treatment that aids adherence and reduces catastrophic costs, are essential. Innovations within sight, such as short, highly-effective, broadly-indicated regimens, paired with point-of-care drug susceptibility tests, could accelerate progress in treatment outcomes. Preventing or containing resistance to second-line and novel drugs is also critical and will require high-quality systems for diagnosis, regimen selection, and treatment monitoring. Finally, earlier detection and/or prevention of DR-TB is necessary, with particular attention to airborne infection control, case finding, and preventive therapy for contacts of patients with DR-TB. Implementing these strategies can overcome the barrier that DR-TB represents for global TB elimination efforts, and could ultimately make global elimination of DR-TB (fewer than one annual case per million population worldwide) attainable. There is a strong cost-effectiveness case to support pursuing DR-TB elimination, but achieving this goal will require substantial global investment plus political and societal commitment at the national and local levels.

19Background: Tuberculosis (TB) poses a global health crisis requiring robust international and 20 country-level action. Adopting and implementing TB policies from the World Health Organization 21 (WHO) is essential to meeting global targets for reducing TB burden. However, many high TB burden 22 countries lag in implementing WHO recommendations. Assessing the progress of implementation at 23 national level can identify key gaps that must be addressed to expand and improve TB care. 24 Methods: In 2016/2017, Médecins Sans Frontières and the Stop TB Partnership conducted a survey 25 on adoption and implementation of 47 WHO TB policies in the national TB programs of 29 countries. 26Here we analyze a subset of 23 key policies in diagnosis, models of care, treatment, prevention, and 27 drug regulation to provide a snapshot of national TB policy adoption and implementation. We 28 examine progress since an analogous 2015 survey of 23 of the same countries. 29Results: At the time of the survey, many countries had not yet aligned their national guidelines with 30 all WHO recommendations, although some progress was seen since 2015. For diagnosis, about half 31 of surveyed countries had adopted the WHO-recommended initial rapid test (Xpert MTB/RIF). A 32 majority of countries had adopted decentralized models of care, although one-third of them still 33 required hospitalization for drug-resistant (DR-)TB. Recommended use of the newer drugs 34 bedaquiline (registered in only 6 high-burden TB countries) and delamanid (not registered in any 35 high-burden country) was adopted by 23 and 18 countries, respectively, but short-course (9-month) 36 and newer pediatric regimens by only 13 and 14 countries, respectively. Guidelines in all countries 37 included preventive treatment of latent TB infection for child TB contacts and people living with 38 HIV/AIDS, but only four extended this to adult contacts. 39 Conclusion:To reach global TB targets, greater political will is needed to rapidly adopt and 40 implement internationally recognized care guidelines. 41 102 *At the time of the survey, all countries were WHO-defined as high burden for TB, MDR-TB, or TB/HIV co-103 infection, except for Afghanistan, Armenia, and Georgia. 107Policy Adoption Questionnaire 108 A semi-structured questionnaire was developed between September and November 2016, to assess 109 the national adoption and implementation of 47 WHO TB policies and related practices in five key 110 areas: diagnostics; models of care; treatment regimens for drug-sensitive (DS) and DR-TB; 111 prevention; and drug regulatory environment. The policies included in the survey were selected 112 based on their importance reflecting a relatively recent optimization or improvement over a 113

OBJECTIVES: The objective of this study is to determine the factors that influence satisfaction with non‐sedating antihistamines (NSA) among people who suffer from allergies/hay fever. METHODS: An online survey was conducted in September, 2000 on respondents who had been told by a health care professional that they suffer from allergies/hay fever and were recently (within 12 months) prescribed one of three NSAs to relieve their symptoms. The sample was weighted to ensure the generalizability of the results. Satisfaction was measured according to the medication's ability to relieve side effects and control symptoms from allergies/hay fever. A total of 4,081 respondents were included in the analysis. RESULTS: (1) The mean satisfaction score for the first time users (defined as never having taken any medication for allergies/hay fever) was higher than those who had used some medication in the past (p < .01) (2) Of the respondents who had a specific choice of medication in mind, those who received their first choice medication had a higher satisfaction score than those who did not (p < .01). (3) The respondents who discussed their medication jointly with their physician had a higher satisfaction score than those whose doctor chose their medication for them (p < .01). (4) Respondents who were not taking any over‐the‐counter (OTC) medications reported higher satisfaction scores than those who supplemented their NSA with over‐the‐counter medications (p < .01). (5) Finally, respondents who had never requested a prescription after seeing an advertisement for any medication had a higher satisfaction score than those who did. (p < .01) CONCLUSIONS: The data provides evidence to suggest that past knowledge or experience with NSAs, patient preference, and patient involvement in the treatment decision‐making process all play a role in determining satisfaction with NSAs. Furthermore, both over‐the‐counter medication usage and direct‐to‐consumer advertising are likely to influence how satisfied people are with their NSA.