scholarly journals Strengthened capacity of India´s bedaquiline Conditional Access Programme for introducing new drugs and regimens

2020 ◽  
Vol 24 (10) ◽  
pp. 1067-1072
Author(s):  
K. S. Sachdeva ◽  
N. Arora ◽  
R. Solanki ◽  
R. Singla ◽  
R. Sarin ◽  
...  
Keyword(s):  
Scale Up ◽  
New Drugs ◽  
Serious Adverse Events ◽  
Conditional Access ◽  
Conversion Rates ◽  
Drug Safety Monitoring ◽  
Access Programme ◽  
Pre Treatment ◽  
Culture Conversion

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.

scholarly journals One Step Forward: Successful End-of-Treatment Outcomes of Patients With Drug-Resistant Tuberculosis Who Received Concomitant Bedaquiline and Delamanid in Mumbai, India

2020 ◽  
Author(s):  
Mrinalini Das ◽  
Alpa Dalal ◽  
Chinmay Laxmeshwar ◽  
Shilpa Ravi ◽  
Fatima Mamnoon ◽  
...  
Keyword(s):  
Treatment Outcomes ◽  
Scale Up ◽  
New Drugs ◽  
Drug Resistant ◽  
Serious Adverse Events ◽  
Drug Resistant Tuberculosis ◽  
Resistant Tuberculosis ◽  
End Of Treatment ◽  
Conversion Rates ◽  
Culture Conversion

Abstract Background The Médecins Sans Frontières Clinic in Mumbai, India, has been providing concomitant bedaquiline (BDQ) and delamanid (DLM) in treatment regimen for patients with drug-resistant tuberculosis (DR-TB) and limited therapeutic options, referred from other healthcare institutions, since 2016. The study documents the end-of-treatment outcomes, culture-conversion rates, and serious adverse events (SAEs) during treatment. Methods This was a retrospective cohort study based on routinely collected program data. In clinic, treatment regimens are designed based on culture drug sensitivity test patterns and previous drug exposures, and are provided for 20–22 months. BDQ and DLM are extended beyond 24 weeks as off-label use. Patients who initiated DR-TB treatment including BDQ and DLM (concomitantly for at least 4 weeks) during February 2016–February 2018 were included. Results Of the 70 patients included, the median age was 25 (interquartile range [IQR], 22–32) years and 56% were females. All except 1 were fluoroquinolone resistant. The median duration of exposure to BDQ and DLM was 77 (IQR, 43–96) weeks. Thirty-nine episodes of SAEs were reported among 30 (43%) patients, including 5 instances of QTc prolongation, assessed as possibly related to BDQ and/or DLM. The majority (69%) had culture conversion before 24 weeks of treatment. In 61 (87%), use of BDQ and DLM was extended beyond 24 weeks. Successful end-of-treatment outcomes were reported in 49 (70%) patients. Conclusions The successful treatment outcomes of this cohort show that regimens including concomitant BDQ and DLM for longer than 24 weeks are effective and can be safely administered on an ambulatory basis. National TB programs globally should scale up access to life-saving DR-TB regimens with new drugs.

scholarly journals Setting up pharmacovigilance based on available endTB Project data for bedaquiline

2020 ◽  
Vol 24 (10) ◽  
pp. 1087-1094
Author(s):  
N. Lachenal ◽  
C. Hewison ◽  
C. Mitnick ◽  
N. Lomtadze ◽  
S. Coutisson ◽  
...  
Keyword(s):  
Adverse Events ◽  
Multidrug Resistant ◽  
Routine Care ◽  
New Drugs ◽  
Drug Markets ◽  
Serious Adverse Events ◽  
National Programmes ◽  
Mdr Tb ◽  
Drug Safety Monitoring ◽  
Project Data

SETTING: Active pharmacovigilance (PV) is recommended for TB programmes, notably for multidrug-resistant TB (MDR-TB) patients treated with new drugs. Launched with the support of UNITAID in April 2015, endTB (Expand New Drug markets for TB) facilitated treatment with bedaquiline (BDQ) and/or delamanid of >2600 patients in 17 countries, and contributed to the creation of a central PV unit (PVU).OBJECTIVE: To explain the endTB PVU process by describing the serious adverse events (SAEs) experienced by patients who received BDQ-containing regimens.DESIGN: The overall PV strategy was in line with the ‘advanced´ WHO active TB drug safety monitoring and management (aDSM) system. All adverse events (AEs) of clinical significance were followed up; the PVU focused on signal detection from SAEs.RESULTS and CONCLUSION: Between 1 April 2015 and 31 March 2019, the PVU received and assessed 626 SAEs experienced by 417 BDQ patients. A board of MDR-TB/PV experts reviewed unexpected and possibly drug-related SAEs to detect safety signals. The experts communicated on clusters of risks factors, notably polypharmacy and off-label drug use, encouraging a patient-centred approach of care. Organising advanced PV in routine care is possible but demanding. It is reasonable to expect local/national programmes to focus on clinical management, and to limit reporting to aDSM systems to key data, such as the SAEs.

A Moxifloxacin-based Regimen for the Treatment of Recurrent, Drug-sensitive Pulmonary Tuberculosis: An Open-label, Randomized, Controlled Trial

2019 ◽  
Vol 70 (1) ◽  
pp. 90-98 ◽  
Author(s):  
Rubeshan Perumal ◽  
Nesri Padayatchi ◽  
Nonhlanhla Yende-Zuma ◽  
Anushka Naidoo ◽  
Dhineshree Govender ◽  
...  
Keyword(s):  
Adverse Events ◽  
Absolute Risk ◽  
Controlled Trial ◽  
Treatment Success ◽  
Control Group ◽  
Open Label ◽  
Serious Adverse Events ◽  
Conversion Rates ◽  
Significant Difference ◽  
Culture Conversion

Abstract Background The substitution of moxifloxacin for ethambutol produced promising results for improved tuberculosis treatment outcomes. Methods We conducted an open-label, randomized trial to test whether a moxifloxacin-containing treatment regimen was superior to the standard regimen for the treatment of recurrent tuberculosis. The primary and secondary outcomes were the sputum culture conversion rate at the end of 8 weeks and the proportion of participants with a favorable outcome, respectively. Results We enrolled 196 participants; 69.9% were male and 70.4% were co-infected with human immunodeficiency virus (HIV). There was no significant difference between the study groups in the proportion of patients achieving culture conversion at the end of 8 weeks (83.0% [moxifloxacin] vs 78.5% [control]; P = .463); however, the median time to culture conversion was significantly shorter (6.0 weeks, interquartile range [IQR] 4.0–8.3) in the moxifloxacin group than the control group (7.9 weeks, IQR 4.0– 11.4; P = .018). A favorable end-of-treatment outcome was reported in 86 participants (87.8%) in the moxifloxacin group and 93 participants (94.9%) in the control group, for an adjusted absolute risk difference of −5.5 (95% confidence interval −13.8 to 2.8; P = .193) percentage points. There were significantly higher proportions of participants with Grade 3 or 4 adverse events (43.9% [43/98] vs 25.5% [25/98]; P = .01) and serious adverse events (27.6% [27/98] vs 12.2% [12/98]; P = .012) in the moxifloxacin group. Conclusions The replacement of ethambutol with moxifloxacin did not significantly improve either culture conversion rates at the end of 8 weeks or treatment success, and was associated with a higher incidence of adverse events. Clinical Trials Registration NCT02114684.

scholarly journals Effectiveness and cardiovascular safety of delamanid-containing regimens in adults with multidrug-resistant or extensively drug-resistant tuberculosis: A nationwide cohort study from Belarus, 2016-18

2021 ◽  
Vol 91 (1) ◽  
Author(s):  
Vera Auchynka ◽  
Ajay M.V. Kumar ◽  
Hennadz Hurevich ◽  
Yuliia Sereda ◽  
Varvara Solodovnikova ◽  
...  
Keyword(s):  
Treatment Outcomes ◽  
Multivariable Analysis ◽  
Multidrug Resistant ◽  
New Drugs ◽  
Resistant Tuberculosis ◽  
Unsuccessful Treatment ◽  
Mdr Tb ◽  
Ecg Abnormalities ◽  
Culture Conversion

To address the sub-optimal treatment outcomes among patients with multidrug-resistant (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB), the National TB Programme in Belarus started using new drugs such as bedaquiline and delamanid in 2015-16. In this study, we assessed cardiovascular safety and effectiveness (culture conversion, treatment outcomes and post-treatment recurrence) of delamanid-containing regimens among adults (>18 years) with MDR-TB or XDR-TB from June 2016 to February 2018. This was a nationwide cohort study involving analysis of routinely collected programme data from the national and six regional TB hospitals. Cardiovascular adverse events (AEs) were classified as serious or not, based on international guidelines. We conducted Cox proportional hazards regression and calculated adjusted hazards ratio(aHR) and 95% confidence intervals(CI) to evaluate factors associated with AEs and unsuccessful treatment outcomes (death, failure and lost-to-follow-up). Of 125 patients enrolled (35, 28% females; mean age 43 years), 85(68%) had XDR-TB. All the patients received delamanid and 20 patients received both delamanid and bedaquiline. Cardiovascular AEs (177 episodes in total), were observed in the majority (73%) of patients but were mild and managed easily. The most common cardiovascular AEs were QTcF prolongation (64/177, 36%) and other electrocardiography (ECG) abnormalities (40/177, 23%). There were two instances of serious AEs leading to death, both of which were not related to delamanid. In multivariable analysis, male sex (aHR 0.72; 95% CI 0.51-0.99), and baseline ECG abnormalities (aHR 1.68; 95% CI 1.19-2.36) were associated with cardiovascular AEs. Median time to culture conversion was 1.1 months (interquartile range: 1.0-2.1). Culture conversion was observed in 115 (92%) patients at six months of treatment and 110 (88%) completed the treatment successfully. Loss to follow-up, failure and death were observed in 6%, 4% and 2% patients respectively. Among those assessed at 12 months post-treatment (n=33), recurrence was seen in one patient. The only factor associated with unsuccessful treatment outcomes in multivariable analysis was baseline Hepatitis C co-infection (aHR 3.61; 95% CI 1.09-11.95). In conclusion, treatment using delamanid-containing regimens was effective and had a favourable safety profile. We hope our findings inform the development of national clinical guidelines and scale-up of new drugs in other countries.

scholarly journals Relationship between metamorphopsia and inner retinal microstructure following intravitreal ranibizumab injection for branch retinal vein occlusion

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yoshimi Sugiura ◽  
Fumiki Okamoto ◽  
Tomoya Murakami ◽  
Shohei Morikawa ◽  
Takahiro Hiraoka ◽  
...  
Keyword(s):  
Macular Edema ◽  
Retinal Vein Occlusion ◽  
Branch Retinal Vein Occlusion ◽  
Post Treatment ◽  
Intravitreal Ranibizumab ◽  
Vein Occlusion ◽  
Treatment Naïve ◽  
Pre Treatment ◽  
Number Of Injections

AbstractTo evaluate the effects of intravitreal ranibizumab injection (IVR) on metamorphopsia in patients with branch retinal vein occlusion (BRVO), and to assess the relationship between metamorphopsia and inner retinal microstructure and other factors. Thirty-three treatment-naïve eyes of 33 patients with macular edema caused by BRVO with at least 12 months of follow-up were included. The degree of metamorphopsia was quantified using the M-CHARTS. Retinal microstructure was assessed with spectral-domain optical coherence tomography. Disorganization of the retinal inner layers (DRIL) at the first month after resolution of the macular edema (early DRIL) and at 12 months after treatment (after DRIL) was studied. Central retinal thickness (CRT), and status of the external limiting membrane as well as ellipsoid zone were also evaluated. IVR treatment significantly improved best-corrected visual acuity (BCVA) and CRT, but the mean metamorphopsia score did not improve even after 12 months. Post-treatment metamorphopsia scores showed a significant correlation with pre-treatment metamorphopsia scores (P < 0.005), the extent of early DRIL (P < 0.05) and after DRIL (P < 0.05), and the number of injections (P < 0.05). Multivariate analysis revealed that the post-treatment mean metamorphopsia score was significantly correlated with the pre-treatment mean metamorphopsia score (P < 0.05). IVR treatment significantly improved BCVA and CRT, but not metamorphopsia. Post-treatment metamorphopsia scores were significantly associated with pre-treatment metamorphopsia scores, the extent of DRIL, and the number of injections. Prognostic factor of metamorphopsia was the degree of pre-treatment metamorphopsia.

scholarly journals A 17 year experience of attrition from care among HIV infected children in Nnewi South-East Nigeria

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Chinyere Ukamaka Onubogu ◽  
Ebelechuku Francesca Ugochukwu
Keyword(s):  
Financial Constraints ◽  
Scale Up ◽  
Linkage To Care ◽  
Late Presentation ◽  
Young Age ◽  
Attrition Rate ◽  
Bivariate Analysis ◽  
Female Ratio ◽  
Art Initiation

Abstract Background A large number of HIV-infected children continue to die despite reported scale-up of paediatric HIV services. Aim The trend in attrition among children enrolled in an anti-retroviral therapy (ART) programme was evaluated. Methods This was a retrospective review of children enrolled into NAUTH ART programme between 2003 and 2019. Results 1114 children < 15 years at enrolment were studied. The male: female ratio was 1:1 while median age at enrolment was 4.3 years. About two-thirds had WHO stage 3 or 4 disease at enrolment. The rate of loss to follow-up (LTFU) and death were 41.0 and 8.4%, respectively, with overall attrition incidence of 108/1000PY. Despite the downward trend, spikes occurred among those enrolled in 2008 to 2011 and in 2017. The trend in 6-, 12-, 24- and 36-months attrition varied similarly with overall rates being 20.4, 27.7, 34.3 and 37.3%, respectively. Among those on ART, > 50% of attrition was recorded within 6 months of care. Advanced WHO stage, young age, non-initiation on ART or period of enrolment (P <  0.001), and caregiver (p = 0.026) were associated with attrition in bivariate analysis. Apart from caregiver category, these factors remained significant in multivariate analysis. Most LTFU could not be reached on phone. Among those contacted, common reasons for being lost to follow-up were financial constraints, caregiver loss, claim to divine healing, family disharmony/child custody issues and relocation of family/child. Conclusion/recommendation Attrition rate was high and was mostly due to LTFU. Predictors of attrition were late presentation, young age, delay in ART initiation and financial constraints. Efforts should be intensified at early diagnosis, linkage to care and implementation of “test and treat” strategy. Innovative child centered approaches should be adopted to enable the HIV-infected children remain in care despite challenges which can truncate treatment.

scholarly journals Determinants of therapeutic lag in multiple sclerosis

2021 ◽  
pp. 135245852098130
Author(s):  
Izanne Roos ◽  
Emmanuelle Leray ◽  
Federico Frascoli ◽  
Romain Casey ◽  
J William L Brown ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Expanded Disability Status Scale ◽  
Disability Progression ◽  
Delayed Onset ◽  
Disease Characteristics ◽  
Disability Status ◽  
Male Sex ◽  
Pre Treatment ◽  
Patient Subgroups

Background: A delayed onset of treatment effect, termed therapeutic lag, may influence the assessment of treatment response in some patient subgroups. Objectives: The objective of this study is to explore the associations of patient and disease characteristics with therapeutic lag on relapses and disability accumulation. Methods: Data from MSBase, a multinational multiple sclerosis (MS) registry, and OFSEP, the French MS registry, were used. Patients diagnosed with MS, minimum 1 year of exposure to MS treatment and 3 years of pre-treatment follow-up, were included in the analysis. Studied outcomes were incidence of relapses and disability accumulation. Therapeutic lag was calculated using an objective, validated method in subgroups stratified by patient and disease characteristics. Therapeutic lag under specific circumstances was then estimated in subgroups defined by combinations of clinical and demographic determinants. Results: High baseline disability scores, annualised relapse rate (ARR) ⩾ 1 and male sex were associated with longer therapeutic lag on disability progression in sufficiently populated groups: females with expanded disability status scale (EDSS) < 6 and ARR < 1 had mean lag of 26.6 weeks (95% CI = 18.2–34.9), males with EDSS < 6 and ARR < 1 31.0 weeks (95% CI = 25.3–36.8), females with EDSS < 6 and ARR ⩾ 1 44.8 weeks (95% CI = 24.5–65.1), and females with EDSS ⩾ 6 and ARR < 1 54.3 weeks (95% CI = 47.2–61.5). Conclusions: Pre-treatment EDSS and ARR are the most important determinants of therapeutic lag.

scholarly journals Flow diverter stents in the treatment of recanalized intracranial aneurysms

2021 ◽  
pp. 159101992199050
Author(s):  
Erol Akgul ◽  
Hasan Bilen Onan ◽  
Irem Islek ◽  
Mehmet Tonge ◽  
Yavuz Durmus ◽  
...  
Keyword(s):  
Intracranial Aneurysms ◽  
Demographic Data ◽  
Previous Treatment ◽  
Flow Diverter ◽  
Serious Adverse Events ◽  
Clinical Complications ◽  
Tertiary Hospitals ◽  
The Mean ◽  
Technical Complication

Background We assessed the safety and efficacy of flow diverter stents (FDSs) in the treatment of recanalized or residual intracranial aneurysms treated endovascularly. Materials & Methods Patients whose recanalized or residual aneurysms were treated with FDSs in five tertiary hospitals were reviewed retrospectively. The patients’ demographic data, aneurysm characteristics, types of previous treatment, and clinical complications, or serious adverse events associated with FDSs, as well as the results of neurological and angiographic follow-up assessments, were recorded. Results Eighty-six patients (37 males) with 87 aneurysms were included in this study. Eighty (91.9%) aneurysms were in the anterior and seven (8.1%) in the posterior circulation. The initial treatment methods were the primary coiling or balloon remodeling technique in 69 (79.3%) and stent-assisted coiling in 18 (20.7%) aneurysms. The endovascular procedure was successful in all patients. Complications occurred in four patients, for a total complication rate of 4.6%. A technical complication developed in one patient (1.2%). An in-stent thrombosis treated with tirofiban was seen in two cases. Late in-stent stenosis exceeding 50% was treated with balloon angioplasty in one patient. The mean length of follow-up was 21.0 months. The first angiographic follow-up (3–6 months) revealed the complete occlusion of 74 aneurysms (85.1%). While 76 aneurysms (87.4%) were occluded at the last angiographic follow-up (mean: 26.0 months), 11 aneurysms (12.6%) were still filling. Morbimortality was zero. Conclusion The drawback of endovascular treatment is aneurysmal remnants or recurrences, which is safely and durably amenable to flow diversion.

scholarly journals Bioabsorbable Implant for Treatment of Nasal Valve Collapse with or without Concomitant Procedures

2021 ◽  
Author(s):  
Douglas M. Sidle ◽  
Pablo Stolovitzky ◽  
Ellen M. O'Malley ◽  
Randall A. Ow ◽  
Nathan E. Nachlas ◽  
...  
Keyword(s):  
Adverse Events ◽  
Nasal Obstruction ◽  
Large Population ◽  
Inferior Turbinate ◽  
Nasal Valve ◽  
Serious Adverse Events ◽  
Vas Scores ◽  
Nasal Implant ◽  
Nasal Valve Collapse

AbstractThe aim of the study is to report outcomes after treatment of nasal valve collapse with a bioabsorbable nasal implant. It involves two prospective, multicenter, post-market studies evaluating long-term effectiveness of the LATERA implant for severe to extreme nasal obstruction. Participants underwent implant alone or with concomitant inferior turbinate reduction (ITR) and/or septoplasty. Outcome measures included the change from baseline Nasal Obstruction Symptom Evaluation (NOSE) scores, NOSE responder rates, visual analog scale (VAS) scores, and adverse events. A total cohort of 277 participants (109 implants only, 67 implants + ITR, 101 implants + septoplasty + ITR) enrolled at 19 U.S. centers was available for analysis with 177 participants (69 implants only, 39 implants + ITR, 69 implants + septoplasty + ITR) available at 2 years. The mean changes from baseline in NOSE scores and VAS scores were statistically significant (p < 0.001) at all follow-up periods. The baseline NOSE score of 77.8 ± 13.6 was improved to 24.2 ± 23.6 at 24 months. Greater than 90% of participants were NOSE responders across all follow-up periods, 6.1% withdrew for lack of treatment effect. The baseline VAS score of 66.7 ± 18.8 was improved to 21.1 ± 23.9 at 24 months. There were no serious adverse events related to the device or implant procedure. Implant retrieval rate was 4.0% (22/543 implants). Nonserious adverse events were mild to moderate in severity, typically occurred within 6 months of implant, and resolved or were stable. Significant reductions in NOSE and VAS scores and high responder rates from our large population of patients with nasal obstruction who had nasal valve implants confirm sustained effectiveness at 24 months after treatment. The studies are registered on www.clinicaltrials.gov (NCT02952313 and NCT02964312).

Sign in / Sign up

Export Citation Format

Share Document