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Objectives: The oxazolidinone linezolid is an effective component of drug-resistant TB treatment, but its use is limited by toxicity and the optimumdose is uncertain. Current strategies are not informed by clinical pharmacokinetic (PK)/pharmacodynamic (PD) data; we aimed to address this gap.Methods: We defined linezolid PK/PD targets for efficacy (fAUC(0-24): MIC > 119 mg/L/h) and safety (fC(min)Results: The efficacy target was attained in all simulated individuals at 300mg q12h and 600mg q12h, but only 20.7% missed the safety target at 300mg q12h versus 98.5% at 600mg q12h. Although suggesting 300mg q12h should be used preferentially, these data were reliant on a single centre. Efficacy and safety targets were missed by 41.0% and 24.2%, respectively, at 300mg q24h and by 44.6% and 27.5%, respectively, at 600mg q24h. However, the confounding effect of between-study heterogeneity on target attainment for q24h regimens was considerable.Conclusions: Linezolid dosing at 300mg q12h may retain the efficacy of the 600mg q12h licensed dosing with improved safety. Data to evaluate commonly used 300mg q24h and 600mg q24h doses are limited. Comprehensive, prospectively obtained PK/PD data for linezolid doses in drug-resistant TB treatment are required.

Objectives: The oxazolidinone linezolid is an effective component of drug-resistant TB treatment, but its use is limited by toxicity and the optimumdose is uncertain. Current strategies are not informed by clinical pharmacokinetic (PK)/pharmacodynamic (PD) data; we aimed to address this gap. Methods: We defined linezolid PK/PD targets for efficacy (fAUC(0-24): MIC > 119 mg/L/h) and safety (fC(min)

Edita Lycholip,1,2 Ina Thon Aamodt,3,4 Irene Lie,3 Toma Šimbelytė,5 Roma Puronaitė,2,6,7 Hans Hillege,8 Arjen de Vries,8 Imke Kraai,9 Anna Stromberg,10 Tiny Jaarsma,11 Jelena Čelutkienė1,2 1Institute of Clinical Medicine, Faculty of Medicine, Vilnius University, Vilnius, Lithuania; 2Center of Cardiology and Angiology, Vilnius University Hospital Santaros Clinics, Vilnius, Lithuania; 3Centre for Patient-Centered Heart and Lung Research, Department of Cardiothoracic Surgery, Division of Cardiovascular and Pulmonary Diseases, Oslo University Hospital, Oslo, Norway; 4Department of Nursing Science, Institute of Health and Society, Faculty of Medicine, University of Oslo, Oslo, Norway; 5Clinic of Internal Medicine, Centre of Family and Internal Medicine, Vilnius University Santaros Clinics, Vilnius University, Vilnius, Lithuania; 6Centre of Informatics and Development, Vilnius University Hospital Santaros Clinics, Vilnius, Lithuania; 7Institute of Mathematics and Informatics, Vilnius University, Vilnius, Lithuania; 8Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands; 9PRA Health Sciences – Early Development Services, Groningen, the Netherlands; 10Department of Medical and Health Sciences, Linkoping University, Linkoping, Sweden; 11Department of Social and Welfare Studies, Linkoping University, Norrkoping, Sweden Introduction: Self-care is an important patient-reported outcome (PRO) for heart failure (HF) patients, which might be affected by disease management and/or telemonitoring (TM). The number of studies reporting the influence of TM on self-care is limited.Aims: This study aimed: to assess whether TM, in addition to information-and-communication-technology (ICT)-guided disease management system (ICT-guided DMS), affects self-care behavior; to evaluate the dynamics of self-care during the study; to investigate factors contributing to self-care changes; and to identify a patient profile that predisposes the patient to improvement in self-care. Methods: In the INnovative ICT-guided-DMS combined with Telemonitoring in OUtpatient clinics for Chronic HF patients (IN TOUCH) study, 177 patients were randomized to either ICT-guided DMS or TM+ICT-guided DMS, with a follow-up of 9months. The current analysis included 118 participants (mean age: 69±11.5years; 70% male) who filled the following PRO instruments: the nine-item European Heart Failure Self-care Behaviour scale (EHFScBs), Hospital Anxiety and Depression scale (HADs), and Minnesota Living with HF Questionnaire (MLHFQ). Results: The baseline level of self-care was better in the TM+ICT-guided-DMS group (n=58) compared to ICT-guided-DMS group (n=60, p=0.023). Self-care behavior improved in the ICT-guided-DMS group (p28, or from 17 to 28 with concomitant HADs depression subscale (HADs_D) score ≤8, demonstrated the greatest potential to improve self-care during the study. Conclusion: TM did not have an advantage on self-care improvement. Poor physical aspect of quality of life, lower LVEF, and lower NYHA class were associated with self-care worsening. The greatest self-care improvement may be achieved in those patients who have low or medium initial self-care level in the absence of depression. Keywords: heart failure, self-care, telemonitoring, disease management, patient-reported outcomes

Introduction: Success rates for treatment of extensively drug resistant tuberculosis (XDR-TB) are low due to limited treatment options, delayed diagnosis and inadequate health care infrastructure.Areas covered: This review analyses existing programmes of prevention, diagnosis and treatment of XDR-TB. Improved diagnostic procedures and rapid molecular tests help to select appropriate drugs and dosages. Drugs dosages can be further tailored to the specific conditions of the patient based on quantitative susceptibility testing of the M. tuberculosis isolate and use of therapeutic drug monitoring. Pharmacovigilance is important for preserving activity of the novel drugs bedaquiline and delamanid. Furthermore, biomarkers of treatment response must be developed and validated to guide therapeutic decisions.Expert commentary: Given the currently poor treatment outcomes and the association of XDR-TB with HIV in endemic regions, a more patient oriented approach regarding diagnostics, drug selection and tailoring and treatment evaluation will improve treatment outcome. The different areas of expertise should be covered by a multidisciplinary team and may involve the transition of patients from hospitalized to home or community-based treatment.

Contains fulltext : 170267.pdf (Publisher’s version ) (Open Access) INTRODUCTION: Success rates for treatment of extensively drug resistant tuberculosis (XDR-TB) are low due to limited treatment options, delayed diagnosis and inadequate health care infrastructure. Areas covered: This review analyses existing programmes of prevention, diagnosis and treatment of XDR-TB. Improved diagnostic procedures and rapid molecular tests help to select appropriate drugs and dosages. Drugs dosages can be further tailored to the specific conditions of the patient based on quantitative susceptibility testing of the M. tuberculosis isolate and use of therapeutic drug monitoring. Pharmacovigilance is important for preserving activity of the novel drugs bedaquiline and delamanid. Furthermore, biomarkers of treatment response must be developed and validated to guide therapeutic decisions. Expert commentary: Given the currently poor treatment outcomes and the association of XDR-TB with HIV in endemic regions, a more patient oriented approach regarding diagnostics, drug selection and tailoring and treatment evaluation will improve treatment outcome. The different areas of expertise should be covered by a multidisciplinary team and may involve the transition of patients from hospitalized to home or community-based treatment.

There is a need for more accurate Chlamydia trachomatis (CT) IgG antibody tests for tubal factor infertility (TFI) diagnostics. We evaluated the predictive value for TFI of Medac ELISA plus (MOMP) and multitarget Mikrogen ELISA (MOMP-CPAF-TARP). Based on Medac ELISA plus results, 183 subfertile women underwent either hysterosalpingography or laparoscopy to diagnose TFI. TFI was defined as extensive adhesions and/or distal occlusion of at least one tube. Women not fulfilling the definition of TFI served as controls. Serum was subsequently tested with Mikrogen ELISA and results were compared. 48 patients had TFI, 135 were controls. Mikrogen ELISA tested 125 patients positive/borderline of which 32% had TFI. Medac ELISA plus tested 77 patients positive/borderline of which 29.9% had TFI. Mikrogen tested 40 out of 48 TFI patients positive/borderline, Medac 23 out of 48. Kappa value was 0.34. PPV of Mikrogen ELISA and Medac ELISA plus were respectively 32% (95% CI 26%-39%) and 30% (95% CI 24%-37%), and NPV 86% (95% CI 81%-91%) and 76% (95% CI 70%-82%). Both tests were comparable in the prediction of TFI. However, Mikrogen ELISA had a higher NPV and might be more reliable in identifying patients without TFI. Kappa-value showed limited concordance between both tests.

Purpose Doublet chemotherapy is more effective than single-agent as first-line treatment of advanced non–small-cell lung cancer (NSCLC). As second-line treatment, several randomized trials have been performed comparing single-agent with doublet chemotherapy, but each trial had an insufficient power to detect potentially relevant differences in survival. Methods We performed meta-analysis of individual patient data from randomized trials, both published and unpublished, comparing single-agent with doublet chemotherapy as second-line treatment of advanced NSCLC. Primary end point was overall survival (OS). All statistical analyses were stratified by trial. Results Eight eligible trials were identified. Data of two trials were not available, and data of six trials (847 patients) were collected. Median age was 61 years. Performance status was 0 or 1 in 90%; 80% of patients had received previous platin-based chemotherapy. OS was not significantly different between arms (P = .32). Median OS was 37.3 and 34.7 weeks in the doublet and single-agent arms, respectively. Hazard ratio (HR) was 0.92 (95% CI, 0.79 to 1.08). Response rate was 15.1% with doublet and 7.3% with single-agent (P = .0004). Median progression-free survival was 14 weeks for doublet and 11.7 weeks for single agent (P = .0009; HR, 0.79; 95% CI, 0.68 to 0.91). There was no significant heterogeneity among trials for the three efficacy outcomes. Patients treated with doublet chemotherapy had significantly more grade 3 to 4 hematologic (41% v 25%; P < .0001) and grade 3 to 4 nonhematologic toxicity (28% v 22%; P = .034). Conclusion Doublet chemotherapy as second-line treatment of advanced NSCLC significantly increases response rate and progression-free survival, but is more toxic and does not improve overall survival compared to single-agent.

Individual variations in susceptibility to an infection as well as in the clinical course of the infection can be explained by pathogen related factors, environmental factors, and host genetic differences. In this paper we review the state-of-the-art basic host genomic and genetic findings’ translational potential of human immunodeficiency virus (HIV),Chlamydia trachomatis(CT), and Human Papilloma Virus (HPV) into applications in public health, especially in diagnosis, treatment, and prevention of complications of these infectious diseases. There is a significant amount of knowledge about genetic variants having a positive or negative influence on the course and outcome of HIV infection. In the field ofChlamydia trachomatis, genomic advances hold the promise of a more accurate subfertility prediction test based on single nucleotide polymorphisms (SNPs). In HPV research, recent developments in early diagnosis of infection-induced cervical cancer are based on methylation tests. Indeed, triage based on methylation markers might be a step forward in a more effective stratification of women at risk for cervical cancer. Our review found an imbalance between the number of host genetic variants with a role in modulating the immune response and the number of practical genomic applications developed thanks to this knowledge.