The Tuberculosis Network European Trials Group (TBNET): new directions in the management of tuberculosis

The Tuberculosis Network European Trials Group (TBNET) is the largest clinical research organisation in Europe. Educational activities include the TBNET Academy and the European Advanced Course in Clinical Tuberculosis. Four of their publications are reviewed to show how the clinical management of tuberculosis is changing.Key pointsMost tuberculosis (TB) in contacts is found at their first visit.In contacts of pulmonary TB patients, the likelihood of later TB is ≤3%.Genetic tests can indicate when another antimycobacterial drug in the same class might be effective (e.g.rifabutin when there is rifampicin resistance or which injectable to choose).The short-course “Bangladesh” regimen can only be rarely used in Europe.Treatment completion in multidrug-resistant TB should not be included as a successful outcome.

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Managing multidrug-resistant tuberculosis in South Africa: a budget impact analysis

The International Journal of Tuberculosis and Lung Disease ◽

10.5588/ijtld.19.0409 ◽

2020 ◽

Vol 24 (4) ◽

pp. 376-382

Author(s):

S. D. Masuku ◽

R. Berhanu ◽

C. Van Rensburg ◽

N. Ndjeka ◽

S. Rosen ◽

...

Keyword(s):

South Africa ◽

Treatment Outcomes ◽

Impact Analysis ◽

Cost Savings ◽

Multidrug Resistant ◽

Successful Outcome ◽

Case Register ◽

Resistant Tuberculosis ◽

Short Course ◽

Long Course

SETTING: In South Africa prior to 2016, the standard treatment regimen for multidrug- and rifampicin-resistant tuberculosis (MDR/RR-TB) was 24 months long and required daily injectable aminoglycoside (IA) treatment during the first 6 months. Recent evidence supports the replacement of IA with well-tolerated oral bedaquiline (BDQ) and a shortened 9–12 month regimen.DESIGN: Using a Markov model, we analyzed the 5-year budgetary impact and cost per successful treatment outcome of four regimens: 1) IA long-course, 2) oral long-course, 3) IA short-course, and 4) oral short-course. We used the South African MDR/RR-TB case register (2013–2015) to assess treatment outcomes for the then-standard IA long-course. Data on the improvement in outcomes for BDQ-based regimens were based on the literature. Costs were estimated from the provider perspective using costs incurred to provide decentralized treatment for MDR-TB at a Johannesburg hospital.RESULTS: Based on our analysis, by 2023, the cost/successful outcome for the four regimens was respectively 1) US$7374, 2) US$7860, 3) US$5149, and 4) US$4922. The annual total cost of each regimen was US$37 million, US$43 million, US$26 million, and US$28 million.CONCLUSION: Despite the high cost of BDQ, a BDQ-based shortened regimen for the treatment of MDR/RR-TB will result in improved treatment outcomes and cost savings for South Africa.

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Successful Treatment of Staphylococcus aureus Prosthetic Joint Infection with Bacteriophage Therapy

Viruses ◽

10.3390/v13061182 ◽

2021 ◽

Vol 13 (6) ◽

pp. 1182

Author(s):

Claudia Ramirez-Sanchez ◽

Francis Gonzales ◽

Maureen Buckley ◽

Biswajit Biswas ◽

Matthew Henry ◽

...

Keyword(s):

Staphylococcus Aureus ◽

Prosthetic Joint Infection ◽

Joint Infection ◽

Multidrug Resistant ◽

Successful Outcome ◽

Prolonged Treatment ◽

Lytic Phage ◽

Bacteriophage Therapy ◽

Prosthetic Joint ◽

Knee Joint Infection

Successful joint replacement is a life-enhancing procedure with significant growth in the past decade. Prosthetic joint infection occurs rarely; it is a biofilm-based infection that is poorly responsive to antibiotic alone. Recent interest in bacteriophage therapy has made it possible to treat some biofilm-based infections, as well as those caused by multidrug-resistant pathogens, successfully when conventional antibiotic therapy has failed. Here, we describe the case of a 61-year-old woman who was successfully treated after a second cycle of bacteriophage therapy administered at the time of a two-stage exchange procedure for a persistent methicillin-sensitive Staphylococcus aureus (MSSA) prosthetic knee-joint infection. We highlight the safety and efficacy of both intravenous and intra-articular infusions of bacteriophage therapy, a successful outcome with a single lytic phage, and the development of serum neutralization with prolonged treatment.

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West German clinical research seeks new directions

Nature ◽

10.1038/333201a0 ◽

1988 ◽

Vol 333 (6170) ◽

pp. 201-201

Author(s):

Steven Dickman

Keyword(s):

Clinical Research ◽

New Directions

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Clostridium subterminale Septicemia in a Patient with Metastatic Gastrointestinal Adenocarcinoma

Case Reports in Infectious Diseases ◽

10.1155/2018/6031510 ◽

2018 ◽

Vol 2018 ◽

pp. 1-3 ◽

Cited By ~ 2

Author(s):

Kevin M. Trapani ◽

Leigh J. Boghossian ◽

Elizabeth Caskey

Keyword(s):

Public Health ◽

Intensive Care Unit ◽

Intensive Care ◽

Clinical Management ◽

Health Planning ◽

Multidrug Resistant ◽

Gi Tract ◽

Public Health Planning ◽

Clostridium Subterminale ◽

Gi Mucosa

Clostridium subterminale is a rare member of the Clostridiaceae family that is rarely cultured. This report examines a case of Clostridium subterminale cultured from the blood of a 72-year-old man who was ultimately diagnosed with metastatic gastrointestinal (GI) adenocarcinoma. The patient was receiving treatment for nosocomial pneumonia prior to culture of the C. subterminale, which led to suspicion for malignancy. Extensive GI and oncologic workup demonstrated multiple comorbidities and a primary GI cancer, which likely caused a breach in the GI mucosa and C. subterminale entrance into the bloodstream. After a prolonged intensive care unit (ICU) stay, the patient died on hospital day 23. Though rarely reported, C. subterminale septicemia has been demonstrated in patients with malignancy, specifically of the GI tract. Therefore, this case represents a typical C. subterminale septicemia patient. Given the prevalence of Clostridia and the contemporary emergence of multidrug resistant (MDR) microorganisms, both typical and atypical cases regarding rare members of the species have a significant role in the clinical management and public health planning.

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The European Multicentre Bronchiectasis Audit and Research Collaboration (EMBARC): experiences from a successful ERS Clinical Research Collaboration

Breathe ◽

10.1183/20734735.005117 ◽

2017 ◽

Vol 13 (3) ◽

pp. 180-192 ◽

Cited By ~ 17

Author(s):

James D. Chalmers ◽

Megan Crichton ◽

Pieter C. Goeminne ◽

Michael R. Loebinger ◽

Charles Haworth ◽

...

Keyword(s):

Clinical Trials ◽

Clinical Research ◽

Research Collaboration ◽

Clinical Care ◽

Research Priorities ◽

Chronic Obstructive ◽

List Type ◽

European Respiratory Society ◽

Obstructive Pulmonary Disease ◽

Research Education

In contrast to airway diseases like chronic obstructive pulmonary disease or asthma, and rare diseases such as cystic fibrosis, there has been little research and few clinical trials in bronchiectasis. Guidelines are primarily based on expert opinion and treatment is challenging because of the heterogeneous nature of the disease.In an effort to address decades of underinvestment in bronchiectasis research, education and clinical care, the European Multicentre Bronchiectasis Audit and Research Collaboration (EMBARC) was established in 2012 as a collaborative pan-European network to bring together bronchiectasis researchers. The European Respiratory Society officially funded EMBARC in 2013 as a Clinical Research Collaboration, providing support and infrastructure to allow the project to grow.EMBARC has now established an international bronchiectasis registry that is active in more than 30 countries both within and outside Europe. Beyond the registry, the network participates in designing and facilitating clinical trials, has set international research priorities, promotes education and has participated in producing the first international bronchiectasis guidelines. This manuscript article the development, structure and achievements of EMBARC from 2012 to 2017.Educational aimsTo understand the role of Clinical Research Collaborations as the major way in which the European Respiratory Society can stimulate clinical research in different disease areasTo understand some of the key features of successful disease registriesTo review key epidemiological, clinical and translational studies of bronchiectasis contributed by the European Multicentre Bronchiectasis Audit and Research Collaboration (EMBARC) project in the past 5 yearsTo understand the key research priorities identified by EMBARC for the next 5 years

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Diabetes mellitus: an important risk factor for reactivation of tuberculosis

Endocrinology Diabetes and Metabolism Case Reports ◽

10.1530/edm-16-0035 ◽

2016 ◽

Vol 2016 ◽

Cited By ~ 3

Author(s):

Ernesto Solá ◽

Carmen Rivera ◽

Michelle Mangual ◽

José Martinez ◽

Kelvin Rivera ◽

...

Keyword(s):

Public Health ◽

Diabetes Mellitus ◽

Risk Factor ◽

Pulmonary Tuberculosis ◽

Important Risk Factor ◽

World Population ◽

Lung Field ◽

List Type ◽

Global Public Health ◽

Pulmonary Tb

Summary Diabetes mellitus was identified as a risk factor for developing tuberculosis (TB) infection, and relapse after therapy. The risk of acquiring TB is described as comparable to that of HIV population. The fact that diabetics are 3× times more prone to develop pulmonary TB than nondiabetics cannot be overlooked. With DM recognized as global epidemic, and TB affecting one-third of the world population, physicians must remain vigilant. We present a 45-year-old woman born in Dominican Republic (DR), with 10-year history of T2DM treated with metformin, arrived to our Urgency Room complaining of dry cough for the past 3months. Interview unveiled unintentional 15lbs weight loss, night sweats, occasional unquantified fever, and general malaise but denied bloody sputum. She traveled to DR 2years before, with no known ill exposure. Physical examination showed a thin body habitus, otherwise well appearing woman with stable vital signs, presenting solely right middle lung field ronchi. LDH, ESR, hsCRP and Hg A1C were elevated. Imaging revealed a right middle lobe cavitation. Sputum for AFB disclosed active pulmonary TB. Our case portrays that the consideration of TB as differential diagnosis in diabetics should be exercised with the same strength, as it is undertaken during the evaluation of HIV patients with lung cavitation. Inability to recognize TB will endanger the patient, hospital dwellers and staff, and perpetuate this global public health menace. Learning points Diabetes mellitus should be considered an important risk factor for the reactivation of pulmonary tuberculosis. High clinical suspicious should be taken into consideration as radiological findings for pulmonary tuberculosis in patients with diabetes mellitus may be atypical, involving middle and lower lobes. Inability to recognize pulmonary tuberculosis will endanger the patient, hospital dwellers and staff, and perpetuate this global public health menace.

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Efficacy of autologous platelet-rich plasma on graft uptake in myringoplasty: a single-blinded randomized control trial

The Egyptian Journal of Otolaryngology ◽

10.1186/s43163-021-00190-x ◽

2022 ◽

Vol 38 (1) ◽

Author(s):

R. Vignesh ◽

V. Nirmal Coumare ◽

S. Gopalakrishnan ◽

P. Karthikeyan

Keyword(s):

Otitis Media ◽

Platelet Rich Plasma ◽

Successful Outcome ◽

Control Group ◽

List Type ◽

Graft Material ◽

Group I ◽

Autologous Platelet Rich Plasma ◽

Conventional Myringoplasty ◽

Autologous Platelet

Abstract Background and aim Chronic otitis media is defined as a chronic inflammation of the middle ear cleft producing irreversible pathological changes. The myringoplasty aims at the reconstruction of the tympanic membrane using a graft material. Autologous platelet-rich plasma can be used along with the graft to have a successful outcome. The aim of the study was to assess the efficacy of autologous platelet-rich plasma on graft uptake in myringoplasty. Methods This was a randomized controlled trial with a sample size of 76 patients. All patients were above 18 and below 55 years of age diagnosed with chronic suppurative otitis media and were planned for myringoplasty. The participants were randomly allotted to two groups by block randomization (block of 4). Intra-operatively, group I (n=38) received platelet-rich plasma–soaked gel foam and group II (n=38) was taken as the control group who received saline-soaked gel foam and examined by a blinded examiner at the end of 1st and 3rd months. Results The mean air-bone gap reduction post-operatively in the platelet-rich plasma group was 8.68 ± 4.8 (P value 0.034) and 6.05 ± 4.05 in the control group. The improvement in pure-tone average in the platelet-rich plasma group (P = 0.009) is more than that in the control group. The graft uptake was higher among the platelet-rich plasma group than the control group both at 1st and 3rd months (P value 0.049) which were statistically significant. Conclusion The present study concludes that the usage of platelet-rich plasma in the conventional myringoplasty technique has improved the success rate of graft uptake and reduced the graft migration. Trial registration Clinical Trials Registry-India (ICMR-NIMS) CTRI/2020/04/024416. Date of registration: 01/04/2020. Date of enrolment of the first participant to the trial: 06/04/2020. URL of the trial registry: http://www.ctri.nic.in. Highlights Usage of autologous platelet-rich plasma (PRP) in conventional myringoplasty in underlay technique. Assessment of graft uptake, percentage of perforation closure, and the audiological outcome. Significant mean reduction of ABG in the PRP group. Significant improvement in PTA average in the PRP group. Graft uptake and percentage of perforation closure were higher in the PRP group and the control group. PRP is also beneficial in revision cases.

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Genetic Diversity of IFγ, IL1β, TLR2, and TLR8 Loci in Pulmonary Tuberculosis in Kazakhstan

Central Asian Journal of Global Health ◽

10.5195/cajgh.2014.181 ◽

2014 ◽

Vol 3 ◽

Cited By ~ 1

Author(s):

Dauren Yerezhepov ◽

Axat Zhabagin ◽

Ayken Askapuli ◽

Saule Rakhimova ◽

Zhannur Nurkina ◽

...

Keyword(s):

Epidemiological Data ◽

Multidrug Resistant ◽

Taqman Assay ◽

World Population ◽

Protection Mechanism ◽

Pulmonary Tb ◽

Increased Risk ◽

Mdr Tb ◽

Latent Tb ◽

Genotype A

Introduction. Tuberculosis (TB) is caused by bacterium Mycobacterium tuberculosis (MTB), and according to the WHO, up to 30% of world population is infected with latent TB. Pathogenesis of TB is multifactorial, and its development depends on environmental, social, microbial, and genetic factors of both the bacterium and the host. The number of TB cases in Kazakhstan has decreased in the past decade, but multidrug-resistant (MDR) TB cases are dramatically increasing. Polymorphisms in genes responsible for immune response have been associated with TB susceptibility. The objective of this study was to investigate the risk of developing pulmonary TB (PTB) associated with polymorphisms in several inflammatory pathway genes among Kazakhstani population.Methods. 703 participants from 3 regions of Kazakhstan were recruited for a case-control study. 251 participants had pulmonary TB (PTB), and 452 were healthy controls (HC). Males and females represented 42.39% and 57.61%, respectively. Of all participants, 67.4% were Kazakhs, 22.8% Russians, 3.4% Ukrainians, and 6.4% were of other origins. Clinical and epidemiological data were collected from medical records, interviews, and questionnaires. DNA samples were genotyped using TaqMan assay on 4 polymorphisms: IFNγ (rs2430561) and IL1β (rs16944), TLR2 (rs5743708) and TLR8 (rs3764880). Statistical data was analyzed using SPSS 19.Results. Genotyping by IFγ, IL1β, TLR2 showed no significant association with PTB susceptibility (p > 0.05). TLR8 genotype A/G was significantly higher in females (F/M – 41.5%/1.3%) and G/G in males (M/F – 49%/20.7%) (χ2=161.43, p < 0.001). A significantly increased risk of PTB development was observed for TLR A/G with an adjusted OR of 1.48 (95%, CI: 0.96 - 2.28), and a protective feature was revealed for TLR8 G/G genotype (OR: 0.81, 95%, CI: 0.56 - 1.16, p = 0.024). Additional grouping by gender revealed that TLR8 G/G contributes as protective genotype (OR: 1.83, 95%, CI: 1.18 - 2.83, p = 0.036) in males of the control group.Conclusion. Results indicate that heterozygous genotype A/G of TLR8 increases the risk of PTB development, while G/G genotype may serve as protection mechanism. A/A genotype is strongly associated with susceptibility to PTB. To clarify the role of other polymorphisms in susceptibility to PTB in Kazakhstani population, further investigations are needed.

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Magnitude, change over time, demographic characteristics and geographic distribution of excess deaths among nursing home residents during the first wave of COVID-19 in France: a nationwide cohort study

10.1101/2021.01.09.20248472 ◽

2021 ◽

Author(s):

Florence Canouï-Poitrine ◽

Antoine Rachas ◽

Martine Thomas ◽

Laure Carcaillon-Bentata ◽

Roméo Fontaine ◽

...

Keyword(s):

Nursing Home ◽

General Population ◽

Excess Mortality ◽

Nursing Home Residents ◽

Primary Objective ◽

List Type ◽

Key Points ◽

Standardized Mortality Ratios ◽

Using Data ◽

Excess Deaths

AbstractImportanceNursing home (NH) residents are particularly vulnerable to SARS-CoV-2 infections and coronavirus disease 2019 (COVID-19) lethality. However, excess deaths in this population have rarely been documented.ObjectivesThe primary objective was to assess the number of excess deaths among NH residents during the first wave of the COVID-19 pandemic in France. The secondary objectives were to determine the number of excess deaths as a proportion of the total excess deaths in the general population and determine whether a harvesting effect was present.DesignWe studied a cohort of 494,753 adults (as of March 1st, 2020) aged 60 and over in 6,515 NHs in mainland France. This cohort was exposed to the first wave of the COVID-19 pandemic (from March 1st to May 31st, 2020) and was compared with the corresponding, reference cohorts from 2014 to 2019 (using data from the French National Health Data System).Main outcome and measuresThe main outcome was all-cause death. Weekly excess deaths and standardized mortality ratios (SMRs) were estimated.ResultThere were 13,505 excess deaths among NH residents. Mortality increased by 43% (SMR: 1.43). The mortality excess was higher among males than among females (SMR: 1.51 and 1.38, respectively) and decreased with age (SMRs in females: 1.61 in the 60-74 age group, 1.58 for 75-84, 1.41 for 85-94, and 1.31 for 95 or over; Males: SMRs: 1.59 for 60-74, 1.69 for 75-84, 1.47 for 85-94, and 1.41 for 95 or over). We did not observe a harvesting effect (up until August 30th, 2020). By extrapolating to all NH residents nationally (N=570,003), the latter accounted for 51% of the total excess deaths in the general population (N=15,114 out of 29,563).ConclusionNH residents accounted for about half of the total excess deaths in France during the first wave of the COVID-19 pandemic. The excess death rate was higher among males than females and among younger residents than among older residents. We did not observe a harvesting effect. A real-time mortality surveillance system and the identification of individual and environmental risk factors might help to design the future model of care for older dependent adults.Key pointsDuring the first wave of the COVID-19 pandemic in France, the mortality among nursing home residents increased by 43%.Nursing home residents accounted for 51% of the total excess deaths in France.The excess mortality was higher among younger residents than among older residents.The excess mortality was higher among males than among females.We did not observe a harvesting effect during the study period (ending on August 30th, 2020, i.e., three months after the end of the first wave).

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Mapping densely distributed membrane receptors in blood platelets with expansion microscopy

10.1101/2021.02.16.431449 ◽

2021 ◽

Author(s):

Hannah S. Heil ◽

Max Aigner ◽

Sophia Maier ◽

Vanessa Göb ◽

Charly Kusch ◽

...

Keyword(s):

Blood Platelets ◽

Super Resolution ◽

Membrane Receptors ◽

List Type ◽

Platelet Receptor ◽

Key Points ◽

Major Vessel ◽

Integrin Clustering ◽

Receptor Interactions ◽

3D Scenarios

AbstractInterrogating small platelets and their densely packed, highly abundant receptor landscape is key to understand platelet clotting. Blot clots can save lives when stopping blood loss after an injury, but also kill when blocking a major vessel. The highly abundant and densely distributed GPIIb/IIIa receptors are one reason why the underlying key distributions and interactions, in particular the relevance of integrin clustering, are not fully understood. Such dense receptor scenarios are difficult to assess even by super-resolution fluorescence microscopy. Here, we quantify various receptor interactions, and demonstrate that expansion microscopy can pinpoint such challenging interactions where conventional methods fail in such dense 3D scenarios with highly abundant receptors. We successfully combine dual-color expansion and confocal microscopy with colocalization analysis and assess platelet receptor organization without the need of a super-resolution microscope. We reveal that GPIIb/IIIa receptors are organized in pre-formed clusters in resting platelets – a pattern that orchestrates platelet clotting. We show that 4x expansion is most straight-forward for platelet imaging, while 10x expansion provides highest precision which turned out to be absolutely necessary for the most difficult of the scenarios described here.Graphical AbstractNonstandard Abbreviations and AcronymsGPIX: glycoprotein IXExM: expansion microscopyKey PointsMapping of the very dense, highly abundant platelet receptor landscape requires 10x Expansion MicroscopyExM reveals that GPIIb/IIIa receptors are organized in pre-formed clusters in resting platelets.

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