scholarly journals Prediction of anti-tuberculosis treatment duration based on a 22-gene transcriptomic model

2021 ◽  
pp. 2003492
Author(s):  
Jan Heyckendorf ◽  
Sebastian Marwitz ◽  
Maja Reimann ◽  
Korkut Avsar ◽  
Andrew DiNardo ◽  
...  
Keyword(s):  
Treatment Outcomes ◽  
Whole Blood ◽  
Learning Algorithm ◽  
Multidrug Resistant ◽  
World Health ◽  
End Of Treatment ◽  
One Year ◽  
Health Organization ◽  
Therapy Treatment

BackgroundThe World Health Organization recommends standardised treatment durations for patients with tuberculosis. We identified and validated a host-RNA signature as a biomarker for individualised therapy durations for patients with drug-susceptible (DS)- and multidrug-resistant (MDR)-tuberculosis.MethodsAdult patients with pulmonary tuberculosis were prospectively enrolled into 5 independent cohorts in Germany and Romania. Clinical and microbiological data, and whole-blood for RNA transcriptomic analysis were collected at pre-defined timepoints throughout therapy. Treatment outcomes were ascertained Treatment outcomes were ascertained by TBNET criteria (6-month culture status/one-year follow-up). A whole-blood RNA therapy end model was developed in a multi-step process involving a machine-learning algorithm to identify hypothetical individual end-of-treatment timepoints.ResultsFifty patients with drug-susceptible (DS)-tuberculosis and 30 patients with MDR-tuberculosis were recruited in the German identification cohorts (DS- and MDR-GIC), 28 patients with DS-tuberculosis and 32 patients with MDR-tuberculosis in the German validation cohorts (DS- and MDR-GVC), and 52 patients with MDR-tuberculosis in the Romanian validation cohort (MDR-RVC). A 22-gene RNA model that defined cure-associated end-of-therapy timepoints was derived from the DS- and MDR-GIC data. The model was superior to other published signatures to accurately predict clinical outcomes for patients in the DS-GVC (AUC=0.94 [95%CI:0.9–0.98]) and suggests that cure may be achieved with shorter treatment durations for tuberculosis patients in the MDR-GIC (mean reduction 218.0 days, 34.2%, p<0.001), the MDR-GVC (mean reduction 211.0 days, 32.9%, p<0.001), and the MDR-RVC (mean reduction of 161.0 days, 23.4%, p=0.001).ConclusionBiomarker-guided management may substantially shorten the duration of therapy for many patients with MDR-tuberculosis.

scholarly journals A 22-gene transcriptomic model indicating individual therapy durations in multidrug-resistant tuberculosis

2020 ◽  
Author(s):  
Jan Heyckendorf ◽  
Sebastian Marwitz ◽  
Maja Reimann ◽  
Korkut Avsar ◽  
Andrew R DiNardo ◽  
...  
Keyword(s):  
Whole Blood ◽  
Learning Algorithm ◽  
Multidrug Resistant ◽  
Individual Therapy ◽  
World Health ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
End Of Treatment ◽  
One Year ◽  
Health Organization

Emerging multidrug-resistant tuberculosis is a major global health challenge. The World Health Organization currently recommends treatment durations of 9-18 months or more for patients with multidrug-resistant tuberculosis. We identified and validated a host-RNA signature to serve as a biomarker for individualized therapy durations for patients with multidrug-resistant tuberculosis. Adult patients with pulmonary tuberculosis were prospectively enrolled into 5 independent cohorts in Germany and Romania. Clinical and microbiological data, and whole-blood for RNA transcriptomic analysis were collected at pre-defined timepoints throughout therapy. Treatment outcomes were ascertained one year after end-of-therapy. A whole-blood RNA therapy end model was developed in a multi-step process involving a machine-learning algorithm to identify hypothetical individual end-of-treatment timepoints. Fifty patients with drug-susceptible tuberculosis and 30 patients with multidrug-resistant tuberculosis were recruited in the German identification cohorts (DS- and MDR-GIC), 28 patients with drug-susceptible tuberculosis and 32 patients with multidrug-resistant tuberculosis in the German validation cohorts (DS- and MDR-GVC), and 52 patients with multidrug-resistant tuberculosis in the Romanian validation cohort (MDR-RVC). A 22-gene RNA model that defined cure-associated end-of-therapy timepoints was derived from the DS- and MDR-GIC data. The model accurately predicted clinical outcomes for patients in the DS-GVC (AUC=0.937 [95%CI:0.899-0.976]) and suggested that cure may be achieved with shorter treatment durations for tuberculosis patients in the MDR-GIC (mean reduction 218.0 days, 34.2%, p<0.001), the MDR-GVC (mean reduction 211.0 days, 32.9%, p<0.001), and the MDR-RVC (mean reduction of 161.0 days, 23.4%, p=0.001). Biomarker-guided management may substantially shorten the duration of therapy for many patients with multidrug-resistant tuberculosis.

scholarly journals Effectiveness and Safety of a Shorter Treatment Regimen in a Setting with a High Burden of Multidrug-Resistant Tuberculosis

2021 ◽  
Vol 18 (8) ◽  
pp. 4121
Author(s):  
Aleksandr Trubnikov ◽  
Arax Hovhannesyan ◽  
Kristina Akopyan ◽  
Ana Ciobanu ◽  
Dilbar Sadirova ◽  
...  
Keyword(s):  
Multidrug Resistant ◽  
World Health ◽  
Hiv Status ◽  
Treatment Regimens ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Grade 3 ◽  
Health Organization ◽  
Lost To Follow Up

Treatment of drug-resistant tuberculosis is lengthy, insufficiently effective, and toxic. Since 2016, the World Health Organization has recommended shorter treatment regimens (STR). We assessed effectiveness and predictors of drug adverse events (DAE) among patients treated with STR. There were 95 consecutive rifampicin-resistant patients enrolled in STR in Tashkent between June 2018 and September 2019. Of these, 66.3% were successfully treated, 17.9% suffered failed treatment, 7.4% died, 5.3% were lost to follow-up and 3.2% were not evaluated. No recurrence was identified in 54 patients after 12 months of successful treatment completion. There were 47 reported DAE: the incidence rate was 6.15 DAE per 100 person-months-of-treatment. Any DAE was reported in 38 (40%) patients and grade 3/4 DAE were recorded in 21 (22.1%) patients. Median time to DAE was 101 (interquartile range 64–139) days. The most frequently encountered DAE were gastro-intestinal disorders, followed by hepatotoxicity and ototoxicity. The most commonly offending drug inducing DAE was protionamide. The dose was temporarily interrupted in 55.3% of DAE, reduced in 8.5% of DAE and permanently withdrawn in another 8.5% of DAE. HIV status was the only predictor associated with increased hazard of DAE. In Uzbekistan STR showed moderate effectiveness and safety, although treatment failure was high.

scholarly journals Emergence of bedaquiline-resistance in a high-burden country of tuberculosis

2021 ◽  
pp. 2100621
Author(s):  
Elena Chesov ◽  
Dumitru Chesov ◽  
Florian P. Maurer ◽  
Sönke Andres ◽  
Christian Utpatel ◽  
...  
Keyword(s):  
Treatment Failure ◽  
Multidrug Resistant ◽  
World Health ◽  
Cross Sectional ◽  
Treatment Regimens ◽  
Cavitary Disease ◽  
Mdr Tb ◽  
The Republic ◽  
Health Organization

RationaleBedaquiline has been classified as a Group A drug for the treatment of multidrug-resistant tuberculosis (MDR-TB) by the World Health Organization, however globally emerging resistance threatens the effectivity of novel MDR-TB treatment regimens.ObjectivesWe analysed pre-existing and emerging bedaquiline resistance in bedaquiline-based MDR-TB therapies, and risk factors associated with treatment failure and death.MethodsIn a cross-sectional cohort study, we employed patient data, whole genome sequencing (WGS) and phenotyping of Mycobacterium tuberculosis complex (MTBC) isolates. We could retrieve baseline isolates from 30.5% (62/203) of all MDR-TB patients who received bedaquiline between 2016 and 2018 in the Republic of Moldova. This includes 26 patients for whom we could also retrieve a follow-up isolate.Measurements and Main ResultsAt baseline, all MTBC isolates were susceptible to bedaquiline. Among 26 patients with available baseline and follow-up isolates, 4/26 (15.3%) patients harbored strains which acquired bedaquiline resistance under therapy, while 1/26 (3.8%) patients was re-infected with a second bedaquiline resistant strain. Treatment failure and death were associated with cavitary disease (p=0.011), and any additional drug prescribed in the bedaquiline containing regimen with WGS-predicted resistance at baseline (p=0.012, OR 1.92 per unit increase, 95%CI 1.15–3.21).ConclusionsMDR-TB treatments based on bedaquiline require a functional background regimen to achieve high cure rates and to prevent the evolution of bedaquiline resistance. Novel MDR-TB therapies with bedaquiline require timely and comprehensive drug resistance monitoring.

scholarly journals Trend of the spread of COVID-19 in Indonesia using the machine learning prophet algorithm

2021 ◽  
Vol 24 (3) ◽  
pp. 1780
Author(s):  
Nur Hayati ◽  
Fauziah Fauziah ◽  
Dendi Rizka Poetra ◽  
Dede Wandi
Keyword(s):  
Machine Learning ◽  
Learning Algorithm ◽  
Research Data ◽  
Government Policies ◽  
World Health ◽  
Positive Rate ◽  
Time Variables ◽  
One Year ◽  
Health Organization ◽  
High Level

Based on information on the <span>BNPB website on 2 September 2020, the positive rate for coronavirus disease (COVID-19) in Indonesia reached 25.25% on 30 August 2020. This is a big challenge for the Indonesian government to reduce the positivity rate to meet the standards safe accepted by World Health Organization (WHO) is 5%. To ensure the accuracy of government policies, accurate data predictions are needed. Therefore, the prophet's machine learning algorithm can be used to see trends in the spread of COVID-19 in the next one year. This algorithm has a fairly high level of accuracy because the data contains time variables which are adjusted to the dataset. In several previous research, the dataset was vast uncertain and small. Meanwhile in this research, data was taken from 2 March 2020 to 12 February 2021 on the KawalCOVID19 website. This data is used to predict from 13 February 2021 to 12 February 2022. There are 3 data used; namely data confirmed, recovered and died. Based on the analysis, the confirmed patient was 22.60-42.11%, died amounted to 21.67%-39.00%, and recovered by 22.53-41.82%. The prediction percentage that the average cases died was 2.43% every day. The accuracy of data confirmed was 43.97%, died was 72.50% and recovered was 84.24%.</span>

Is effective patient support missing in the global response to multidrug-resistant tuberculosis?

2020 ◽  
Vol 24 (6) ◽  
pp. 626-630
Author(s):  
A. M. Cocozza ◽  
N. N. Linh ◽  
E. Jaramillo
Keyword(s):  
Treatment Outcomes ◽  
Multidrug Resistant ◽  
World Health ◽  
Drug Resistant ◽  
Patient Support ◽  
Global Response ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Mdr Tb ◽  
Health Organization

Multidrug-resistant tuberculosis (MDR-TB) is a threat to the achievement of the global targets to the World Health Organization (WHO) End TB by 2030 Strategy. The WHO consolidated guidelines for the treatment of drug-resistant TB emphasise the importance of addressing health systems issues, including supporting patients during treatment, contributing to improved adherence, reduced catastrophic costs and better treatment outcomes. The recently published results of the STREAM (Standardised Treatment Regimen of Anti-TB Drugs for Patients with MDR-TB) clinical trial and the Delamanid 213 Trial suggest that the implementation of a proper patient-centred approach to the clinical and programmatic management of MDR-TB as per the WHO guidelines is key to improving treatment outcomes in MDR-TB patients.

scholarly journals A national survey of prisoners on antiretroviral therapy in Malawi: access to treatment and outcomes on therapy

2007 ◽  
Vol 1 (03) ◽  
pp. 303-307 ◽  
Author(s):  
Simon D. Makombe ◽  
Andreas Jahn ◽  
Hannock Tweya ◽  
Lameck Thambo ◽  
Joseph Kwong-Leung Yu ◽  
...  
Keyword(s):  
Antiretroviral Therapy ◽  
Treatment Outcomes ◽  
Clinical Stage ◽  
National Level ◽  
Scale Up ◽  
World Health ◽  
Access To Treatment ◽  
Art Initiation ◽  
Health Organization

Background: Malawi is making good progress scaling up antiretroviral therapy (ART), but we do not know the levels of access of high-risk, disadvantaged groups such as prisoners. The aim of this study was to measure access and treatment outcomes of prisoners on ART at the national level. Methodology: A retrospective cohort study was conducted examining patient follow-up records from all 103 public sector ART clinics in Malawi, and observations were censored on December 31, 2006. Results: By December 31, 2006, a total of 81,821 patients had been started on ART. Of these, 103 (0.13%) were prisoners. At ART initiation, 93% of prisoners were in World Health Organization (WHO) clinical stage 3 or 4 while 7% started in stage 1 or 2 with a CD4-lymphocyte count of ≤250/mm3. Treatment outcomes by the end of December 2006 were as follows: 66 (64%) alive and on ART at their registration facility; 9 (9%) dead; 8 (8%) lost to follow-up; and 20 (19%) transferred out to another facility. The probability of being alive and on ART at 6 and 12 months was 82.5% and 77.7%. Conclusions: In spite of the rapid scale-up of ART, only a small number of HIV-positive prisoners had accessed ART by the end of 2006. Treatment outcomes were good. Initiatives are now needed to improve access to HIV testing and ART in Malawi’s prisons.

scholarly journals Bacillus Calmette-Guerin Vaccine-Associated Lymphadenitis in Children

2022 ◽  
Vol In Press (In Press) ◽  
Author(s):  
Ahmad Shamsizadeh ◽  
Roya Nikfar ◽  
Sina Nazari
Keyword(s):  
Needle Aspiration ◽  
World Health ◽  
Bacillus Calmette Guerin ◽  
Childhood Immunization ◽  
Live Attenuated Vaccine ◽  
Suppurative Lymphadenitis ◽  
Southwestern Iran ◽  
One Year ◽  
Health Organization

Background: Tuberculosis (TB) is one of the most important infectious diseases worldwide. Bacillus Calmette-Guerin (BCG) is a live attenuated vaccine, entered into the childhood immunization program by the World Health Organization (WHO) in 1974 to prevent TB. One of the relatively common complications of BCG vaccination is regional lymphadenitis. Objectives: This study aimed to determine the lymphadenitis incidence in BCG-vaccinated children in southwest Iran. Methods: In a prospective descriptive study, infants born from March to June 2017 were evaluated for BCG vaccine complications at two, four, six, nine, and 12 months of age in Ahvaz, southwestern Iran. Results: The study enrolled 1,506 infants (794 males and 712 females). Among the vaccinated infants, four (0.26%) had injection site reactions, and 106 (7.03%) presented lymphadenitis (66 males and 40 females). The lymphadenitis rate was significantly higher in males than in females (P = 0.024). The mean age at presentation was 4.28 ± 0.79 months. Suppurative lymphadenitis was seen in 53 (50%) cases and nonsuppurative lymphadenitis in 53 (50%) cases. About 80% of nonsuppurative lymphadenitis resolved entirely or partially after a one-year follow-up. Of 53 cases with suppurative lymphadenitis, 46 (43.4%) developed spontaneous drainage, and seven (6.6%) were drained by needle aspiration. No significant relationship was found between the BCG inoculation site and lymphadenitis rate. No other complications such as osteomyelitis or disseminated BCG infection were observed after one year of follow-up. Conclusions: The relatively high incidence of BCG lymphadenitis in this study may be due to the vaccine strain, young vaccinees, and improper vaccination techniques. In most cases, nonsuppurative lymphadenitis regressed spontaneously, and suppurative lymphadenitis was drained spontaneously or by needle aspiration.

scholarly journals Innovative strategies for a successful SLMTA country programme: The Rwanda story

2014 ◽  
Vol 3 (2) ◽  
Author(s):  
Innocent Nzabahimana ◽  
Sabin Sebasirimu ◽  
John B. Gatabazi ◽  
Emmanuel Ruzindana ◽  
Claver Kayobotsi ◽  
...  
Keyword(s):  
Quality Improvement ◽  
World Health ◽  
Reference Laboratory ◽  
Regional Office ◽  
Innovative Strategies ◽  
Quality Improvement Process ◽  
Performance Based Financing ◽  
One Year ◽  
Health Organization

Background: In 2009, to improve the performance of laboratories and strengthen healthcare systems, the World Health Organization Regional Office for Africa (WHO AFRO) and partners launched two initiatives: a laboratory quality improvement programme called Strengthening Laboratory Management Toward Accreditation (SLMTA), and what is now called the Stepwise Laboratory Quality Improvement Process Towards Accreditation (SLIPTA).Objectives: This study describes the achievements of Rwandan laboratories four years after the introduction of SLMTA in the country, using the SLIPTA scoring system to measure laboratory progress.Methods: Three cohorts of five laboratories each were enrolled in the SLMTA programme in 2010, 2011 and 2013. The cohorts used SLMTA workshops, improvement projects, mentorship and quarterly performance-based financing incentives to accelerate laboratory quality improvement. Baseline, exit and follow-up audits were conducted over a two-year period from the time of enrolment. Audit scores were used to categorise laboratory quality on a scale of zero (< 55%) to five (95% – 100%) stars.Results: At baseline, 14 of the 15 laboratories received zero stars with the remaining laboratory receiving a two-star rating. At exit, five laboratories received one star, six received two stars and four received three stars. At the follow-up audit conducted in the first two cohorts approximately one year after exit, one laboratory scored two stars, five laboratories earned three stars and four laboratories, including the National Reference Laboratory, achieved four stars.Conclusion: Rwandan laboratories enrolled in SLMTA showed improvement in quality management systems. Sustaining the gains and further expansion of the SLMTA programme to meet country targets will require continued programme strengthening.

Preventing Premature Weaning: Management Options for Common Lactation Conditions, Including OMT

2020 ◽  
pp. 20-25
Author(s):  
Denise Sackett ◽  
Tala Dajani ◽  
David Shoup ◽  
Uzoma Ikonne
Keyword(s):  
Postpartum Depression ◽  
Family Physician ◽  
Treatment Options ◽  
World Health ◽  
Management Options ◽  
Pharmacological Management ◽  
Control And Prevention ◽  
Lactational Mastitis ◽  
One Year ◽  
Health Organization

The benefits of breastfeeding are well established. The World Health Organization and the Centers for Disease Control and Prevention recommend that mothers breastfeed infants for at least one year, but most children are not breastfed that long because of many factors. Breastfeeding mothers face many challenges to continued breastfeeding, including medical conditions that arise during this period, such as postpartum depression and lactational mastitis. Because of a perceived lack of consistent guidance on medication safety, it can be difficult for the family physician to treat these conditions while encouraging mothers to continue breastfeeding. The purpose of the current review is to summarize and clarify treatment options for the osteopathic family physician treating lactating mothers. We specifically focus on the pharmacological management of contraception, postpartum depression, and lactational mastitis.

scholarly journals Programme for Harmonization to the International Scale in Latin America for BCR-ABL1 quantification in CML patients: findings and recommendations

2020 ◽  
Vol 58 (12) ◽  
pp. 2025-2035
Author(s):  
María Sol Ruiz ◽  
María Belén Sánchez ◽  
Yuly Masiel Vera Contreras ◽  
Evangelina Agrielo ◽  
Marta Alonso ◽  
...  
Keyword(s):  
Latin America ◽  
Myeloid Leukemia ◽  
World Health ◽  
Molecular Response ◽  
Limit Of Quantification ◽  
International Scale ◽  
Deep Molecular Response ◽  
Health Organization ◽  
First Time

AbstractObjectivesThe quantitation of BCR-ABL1 mRNA is mandatory for chronic myeloid leukemia (CML) patients, and RT-qPCR is the most extensively used method in testing laboratories worldwide. Nevertheless, substantial variation in RT-qPCR results makes inter-laboratory comparability hard. To facilitate inter-laboratory comparative assessment, an international scale (IS) for BCR-ABL1 was proposed.MethodsThe laboratory-specific conversion factor (CF) to the IS can be derived from the World Health Organization (WHO) genetic reference panel; however, this material is limited to the manufacturers to produce and calibrate secondary reference reagents. Therefore, we developed secondary reference calibrators, as lyophilized cellular material, aligned to the IS. Our purpose was both to re-evaluate the CF in 18 previously harmonized laboratories and to propagate the IS to new laboratories.ResultsOur field trial including 30 laboratories across Latin America showed that, after correction of raw BCR-ABL1/ABL1 ratios using CF, the relative mean bias was significantly reduced. We also performed a follow-up of participating laboratories by annually revalidating the process; our results support the need for continuous revalidation of CFs. All participating laboratories also received a calibrator to determine the limit of quantification (LOQ); 90% of them could reproducibly detect BCR-ABL1, indicating that these laboratories can report a consistent deep molecular response. In addition, aiming to investigate the variability of BCR-ABL1 measurements across different RNA inputs, we calculated PCR efficiency for each individual assay by using different amounts of RNA.ConclusionsIn conclusion, for the first time in Latin America, we have successfully organized a harmonization platform for BCR-ABL1 measurement that could be of immediate clinical benefit for monitoring the molecular response of patients in low-resource regions.

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