Concordance of three approaches for operationalizing outcome definitions for multidrug-resistant TB.

BACKGROUND: The WHO provides standardized outcome definitions for rifampicin-resistant (RR) and multidrug-resistant (MDR) TB. However, operationalizing these definitions can be challenging in some clinical settings, and incorrect classification may generate bias in reporting and research. Outcomes calculated by algorithms can increase standardization and be adapted to suit the research question. We evaluated concordance between clinician-assigned treatment outcomes and outcomes calculated based on one of two standardized algorithms, one which identified failure at its earliest possible recurrence (i.e., failure-dominant algorithm), and one which calculated the outcome based on culture results at the end of treatment, regardless of early occurrence of failure (i.e., success-dominant algorithm).METHODS: Among 2,525 patients enrolled in the multi-country endTB observational study, we calculated the frequencies of concordance using cross-tabulations of clinician-assigned and algorithm-assigned outcomes. We summarized the common discrepancies.RESULTS: Treatment success calculated by algorithms had high concordance with treatment success assigned by clinicians (95.8 and 97.7% for failure-dominant and success-dominant algorithms, respectively). The frequency and pattern of the most common discrepancies varied by country.CONCLUSION: High concordance was found between clinician-assigned and algorithm-assigned outcomes. Heterogeneity in discrepancies across settings suggests that using algorithms to calculate outcomes may minimize bias.

International Validation of a Methicillin-Resistant Staphylococcus aureus Risk Assessment Tool for Skin and Soft Tissue Infections.

INTRODUCTION: To promote judicious prescribing of methicillin-resistant Staphylococcus aureus (MRSA)-active therapy for skin and soft tissue infections (SSTI), we previously developed an MRSA risk assessment tool. The objective of this study was to validate this risk assessment tool internationally. METHODS: A multicenter, prospective cohort study of adults with purulent SSTI was performed at seven international sites from July 2016 to March 2018. Patient MRSA risk scores were computed as follows: MRSA infection/colonization history (2 points); previous hospitalization, previous antibiotics, chronic kidney disease, intravenous drug use, human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS), diabetes with obesity (1 point each). Predictive performance of MRSA surveillance percentage, MRSA risk score, and estimated MRSA probability (surveillance percentage adjusted by risk score) were quantified using the area under the receiver operating characteristic curves (aROC) and compared. Performance characteristics of different risk score thresholds across varying baseline MRSA prevalence were examined. RESULTS: Two hundred three patients were included. Common SSTI were wounds (28.6%), abscess (25.1%), and cellulitis with abscess (20.7%). Patients with higher risk scores were more likely to have MRSA (P < 0.001). The MRSA risk score aROC (95%CI) [0.748 (0.678-0.819)] was significantly greater than MRSA surveillance percentage [0.646 (0.569-0.722)] (P = 0.016). Estimated MRSA probability aROC [0.781 (0.716-0.845)] was significantly greater than surveillance percentage (P < 0.001) but not the risk score (P = 0.192). The estimated negative predictive value (NPV) of an MRSA score ≥ 1 (i.e., a score of 0) was greater than 90% when MRSA prevalence was 30% or less. CONCLUSION: The MRSA risk score and estimated MRSA probability were significantly more predictive of MRSA compared with surveillance percentage. An MRSA risk score of zero had high predictive value and could help avoid unnecessary empiric MRSA coverage in low-acuity patients. Further study, including impact of such risk assessment tools on prescribing patterns and outcomes are required before implementation.

Integrating hepatitis C treatment into multidrug-resistant TB care.

BACKGROUND: Direct-acting antivirals (DAAs) are not widely used for patients with chronic hepatitis C virus (HCV) infection and multidrug- or rifampicin-resistant TB (MDR/RR-TB). We describe the implementation aspects of a new integrated model of care in Armenia and the perceptions of the healthcare staff and patients. METHODS: We used qualitative methods, including a desktop review and semi-structured individual interviews with healthcare staff and with patients receiving HCV and MDR/RR-TB treatment. RESULTS: The new integrated model resulted in simplified management of HCV and MDR/RR-TB at public TB facilities. Training on HCV was provided for TB clinic staff. All MDR/RR-TB patients were systematically offered HCV testing and those diagnosed with HCV, offered treatment with DAAs. Treatment monitoring was performed by TB staff in coordination with a hepatologist. The staff interviewed had a positive opinion of the new model. They suggested that additional training should be provided. Most patients were fully satisfied with the care received. Some were concerned about the increased pill burden. CONCLUSION: Integrating HCV treatment into MDR/ RR-TB care was feasible and appreciated by patients and staff. This new model facilitated HCV diagnosis and treatment among people with MDR/RR-TB. Our results encourage piloting this model in other settings.

CONTEXTE: Les antiviraux à action directe (DAA) sont peu prescrits aux patients atteints d'hépatite C (HCV) chronique et de TB multirésistante ou résistante à la rifampicine (MDR/RR-TB). Nous décrivons la mise en place d'un nouveau modèle de soins intégrés en Arménie, ainsi que l'opinion du personnel soignant et des patients. MÉTHODES: Nous avons utilisé des méthodes qualitatives, comprenant un examen électronique de la documentation et des entretiens individuels semi-structurés avec le personnel soignant et les patients sous traitement pour HCV et MDR/RR-TB. RÉSULTATS: Le nouveau modèle intégré a permis de simplifier la prise en charge du HCV et de la MDR/RR-TB dans les centres de soins publics de la TB. Une formation sur le HCV a été dispensée au personnel des centres antituberculeux. Tous les patients atteints de MDR/RR-TB se sont vu systématiquement proposer un test de dépistage du HCV, et un traitement par DAA a été proposé à ceux dont le résultat était positif. Le suivi du traitement a été réalisé par le personnel des centres antituberculeux, conjointement à un hépatologue. Les membres du personnel interrogés avaient une opinion positive du nouveau modèle et suggéraient de dispenser d'autres formations. La plupart des patients étaient pleinement satisfaits des soins reçus, mais certains étaient inquiets au vu du nombre accru de comprimés à prendre. CONCLUSION: L'intégration du traitement du HCV aux soins de la MDR/RR-TB s'est avérée possible et a été appréciée par les patients et le personnel soignant. Ce nouveau modèle a facilité le diagnostic et le traitement du HCV chez les patients atteints de MDR/RR-TB. Ce modèle devrait être testé dans d'autres contextes.

[Adherence and efficacy of long-term PAP therapy in patients with sleep-related breathing disorders associated with cardiac conduction disorders].

AIM: To study the effectiveness of prolonged use of PAP therapy (positive airway pressure therapy) in eliminating sleep respiratory disorders and associated cardiac conduction disturbances. MATERIALS AND METHODS: We included 21 patients who were examined at the Myasnikov Institute of Clinical Cardiology, National Medical Research Center of Cardiology, regarding cardiac rhythm and conduction disturbances, as well as obstructive sleep apnea and who have been on PAP therapy for more than 12 months. The average age was 66.5 [63.5; 73.2] years, body mass index 33.0 [30.2; 38.5] kg/m2, apnea-hypopnea index 65.0 [59.0; 86.3]/h. At the time of analysis, 15 patients continued to use PAP therapy (mean time of use: 6.0 years [4.7; 9.2]) and 6 patients refused long-term use of PAP therapy, mean time to use PAP therapy until failure amounted to 2.82.1 years. RESULTS: PAP therapy lead to a persistent decrease in apnea-hypopnea index of 63.6/h to 3.7/h was (p=0.0002). 86% of patients met the criteria for adherence to PAP therapy (use 4 hours/night, more than 70% of nights). Initially, before the use of PAP therapy, all cardiac conduction disorders were during sleep and exceeded 3 seconds, with fluctuations from 3.1 to 10.6 seconds. PAP therapy appeared to be effective in all patients: no asystoles, duration of more than 3 seconds, were detected. CONCLUSION: In obstructive sleep apnea patients with concomitant nighttime cardiac conduction disturbances, the long-term use of PAP therapy is effective and with good adherence.

[Results of 300 pancreatic duct stenting in acute pancreatitis]. / Rezul'taty 300 stentirovanii virsungova protoka pri ostrom pankreatite.

OBJECTIVE: To analyze the results of pancreatic duct stenting in moderate and severe forms of pancreatitis. MATERIAL AND METHODS: Pancreatic duct stenting in 300 patients with acute pancreatitis was analyzed. Examination and treatment were carried out in accordance with national clinical guidelines for acute pancreatitis (2015). RESULTS: Pancreatic duct stenting was performed in 300 patients with moderate and severe forms of pancreatitis (according to APACHE II) in the first 8-72 hours after the onset of the disease. Plastic stent sizes range from 4 to 7 cm in length and 5 to 7 Fr in diameter. Infection with pancreonecrosis occurred in 22 (7.3%) of 300 patients in the main group, and 20% of 150 patients in the control group. Mortality was 16 (5.3%) in the main group, and 24 (16%) - in the control group. CONCLUSIONS: Pancreatic stenting reduced infection by 3, 2 times, and mortality by 4 times. The dosage of Octreotide was personalized depending on the severity of the disease according to APACHE II.

Introducing new and repurposed TB drugs: the endTB experience.

In 2015, the initiative Expand New Drug Markets for TB (endTB) began, with the objective of reducing barriers to access to the new and repurposed TB drugs. Here we describe the major implementation challenges encountered in 17 endTB countries. We provide insights on how national TB programmes and other stakeholders can scale-up the programmatic use of new and repurposed TB drugs, while building scientific evidence about their safety and efficacy. For any new drug or diagnostic, multiple market barriers can slow the pace of scale-up. During 2015-2019, endTB was successful in increasing the number of patients receiving new and repurposed TB drugs in 17 countries. The endTB experience has many lessons, which are relevant to country level introduction of new TB drugs, as well as non-TB drugs and diagnostics. For example: the importation of TB drugs is possible even in the absence of registration; emphasis on good clinical monitoring is more important than pharmacovigilance reporting; national guidelines and expert committees can both facilitate and hinder innovative practice; clinicians use new and repurposed TB drugs when they are available; data collection to generate scientific evidence requires financial and human resources; pilot projects can drive national scale-up.

[Clinical profile of patients with obstructive sleep apnea syndrome in a cardiology hospital].

RELEVANCE: Obstructive sleep apnea syndrome (OSAS) is an important medical and social problem due to its high prevalence and impact on quality of life. The relationship between OSAS and cardiovascular pathology has been proven by many studies, which confirms the necessity for early diagnosis of OSAS and its treatment for the prevention of fatal and non-fatal events. AIM: to study epidemiological and clinical profile of the patients referred by a cardiologist to a specialized sleep laboratory to verify the diagnosis of OSAS. MATERIALS AND METHODS: Object of study 527 patients aged 56.912.5 years who were hospitalized to the Myasnikov Clinical Cardiology Research Institute from 20162018 and had OSAS risk factors. Initially, complaints, medical history, anthropometric data were collected. As a screening survey, questionnaires were conducted using questionnaire scales. Verification of the diagnosis of OSAS and determination of the severity was carried out by cardiorespiratory or respiratory monitoring. Subsequently, 4 groups were formed depending on the presence and severity of OSAS. RESULTS: The prevalence of OSAS among patients in a cardiology hospital referred to a verification study was 88.6%. A comparative analysis of the groups revealed a progressive increase in the values of anthropometric indicators with increasing severity of OSAS. No differences were found between the groups by gender and daytime sleepiness on the Karolinska Sleepiness Scale. The average score on the Epworth sleepiness scale was statistically significantly lower only in the group of patients without OSAS when compared with the group with a severe degree of OSAS, and is comparable with the scores in the groups of mild and moderate degrees of OSAS. In a multivariate model of logistic regression, independent predictors of OSAS were identified as: age over 45 years, indications of loud intermittent snoring, frequent nightly urination, overweight or obesity. According to the results of assessing the incidence of various cardiovascular diseases in patients referred to the sleep laboratory, no significant differences were detected. At the same time, a significant difference was found in the frequency of obesity in patients with severe OSAS compared with other groups, as well as the frequency of type 2 diabetes mellitus or impaired glucose tolerance when compared with groups without OSAS, and with mild OSAS. In one-factor logistic regression models, it was found that the likelihood of having a severe degree of OSAS increases with increasing both comorbidity and age. CONCLUSIONS: High prevalence of OSAS in patients of a cardiological hospital, referred to a sleep laboratory for verification study, was confirmed. Considering the data that early diagnosis and treatment of OSAS can affect the course of both nosologies, the quality of life and prognosis of these patients, it is advisable to routinely screen and verify the diagnosis of OSAS in patients with cardiovascular diseases.

[New possibilities in antibacterial treatment of intra-abdominal infections caused by multiresistant microflora]. / Novye vozmozhnosti antibakterial'noi terapii intraabdominal'nykh infektsii, vyzvannykh polirezistentnoi mikrobnoi floroi.

AIM: To determine the place of new drugs with activity against multidrug resistant strains of microorganisms in the treatment of complicated intraabdominal infections. MATERIAL AND METHODS: The incidence and distribution of pathogens isolated from intra-abdominal specimens in patients with intra-abdominal infections are analyzed. RESULTS: The current situation on the growth of resistant strains among pathogens causing intra-abdominal infections is rewied. New combined drugs for the treatment of multidrug resistant infections - ceftolozane/tazobactam and ceftazidim/avibactam plus metronidazole, has been suggested. Their potential role in empiric and targeted antibacterial treatment of complicated intraabdominal infections is defined. CONCLUSION: Taking into consideration local monitoring data and risk factors of multi resistant strains Ceftolozane/tazobactam in combination with metronidazole can be used in empiric regime of treatment. Due to the high activity on carbapenem resistant strains of Klebsiella pneumonia and the lack of alternatives, it is advisable to use Ceftazidim/avibactam for the targeted therapy.

Is 6 months of bedaquiline enough? Results from the compassionate use of bedaquiline in Armenia and Georgia.

BACKGROUND AND SETTING: Bedaquiline (BDQ) was initially only available through compassionate use programmes. OBJECTIVE: To assess the effectiveness and safety of multidrug-resistant tuberculosis (MDR-TB) treatment containing BDQ. METHOD: Retrospective analysis of data from patients receiving BDQ through compassionate use in Armenia and Georgia from April 2013 to April 2015. Logistic regression was used to assess the risk factors associated with unsuccessful treatment outcomes. RESULTS: Of 82 patients included, 84.2% (69/82) had fluoroquinolone-resistant MDR-TB and 43.4% (23/53) were seropositive for the hepatitis C virus (HCV). The culture conversion rate was 84.4% (54/64), and 18.5% (10/54) reverted back to positive. In total, 79.3% (65/82) of the patients reported at least one adverse event. Serious adverse events were reported in 14 patients, with 10/14 patients experiencing fatal outcomes-6/10 related to advanced TB and 2/10 assessed as possibly related to BDQ. Treatment outcomes were as follows: 58.5% treatment success, 12.2% deaths, 7.3% failures and 21.9% lost to follow-up. HCV coinfection was associated with unsuccessful outcomes (adjusted OR 4.45, 95%CI 1.23-16.13). CONCLUSION: BDQ through compassionate use showed relatively good success rates and safety profiles in a cohort with difficult-to-treat MDR-TB. High rates of reversion may indicate that >24 weeks of BDQ is necessary in some cases. HCV coinfection should be diagnosed and treatment considered in MDR-TB patients.