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Abstract: Objectives. To evaluate the access to comprehensive diagnostics and novel anti-tuberculosis medicines in European countries. Methods. We investigated access to genotypic and phenotypic M. tuberculosis drug susceptibility testing, availability of anti-tuberculosis drugs and calculated cost of drugs and treatment regimens at major tuberculosis treatment centers in countries of the World Health Organization (WHO) European region where rates of drug-resistant tuberculosis are highest among all WHO regions. Results are stratified by middle-income and high-income countries. Results. Overall, 43 treatment centers in 43 countries participated in the study. For WHO Group A drugs, the frequency of countries with availability of phenotypic drug susceptibility testing was as follows: 30/40 (75%) for levofloxacin, 33/40 (82%) for moxifloxacin, 19/40 (48%) for bedaquiline and 29/40 (72%) for linezolid, respectively. Overall, 36/43 (84%) and 24/43 (56%) of countries had access to bedaquiline and delamanid, while only 6/43 (14%) had access to rifapentine. Treatment of patients with extensively drug-resistant tuberculosis with a regimen including a carbapenem was only available in 17/43 (40%) of the countries. Median cost of regimens for drug-susceptible tuberculosis, multidrug-resistant/rifampicin-resistant tuberculosis (shorter regimen, including bedaquiline for six months) and extensively drug-resistant tuberculosis (including bedaquiline, delamanid and a carbapenem) were € 44 (min-max € 15-152), € 764 (min-max € 542-15152) and € 8709 (min-max € 7965-11759) in middle-income countries (n=12), and € 280 (min-max-€78-1084), € 29765 (min-max 11116-40584), € 217591 (min-max € 82827-320146) in high-income countries (n=29). Conclusion. In countries of the WHO Europe Region there is a widespread lack of drug susceptibility testing capacity to new and re-purposed anti-tuberculosis drugs, lack of access to essential medications in several countries and high treatment cost for drug-resistant tuberculosis.
Keywords: tuberculosis - drug therapy, Mycobacterium tuberculosis - drug therapy, health care costs - drug therapy, Europe
Published in DiRROS: 31.08.2022; Views: 788; Downloads: 159
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Abstract: Background: Hydroxychloroquine and chloroquine have been proposed as treatments for coronavirus disease 2019 (Covid-19) on the basis of in vitro activity and data from uncontrolled studies and small, randomized trials. Methods: In this randomized, controlled, open-label platform trial comparing a range of possible treatments with usual care in patients hospitalized with Covid-19, we randomly assigned 1561 patients to receive hydroxychloroquine and 3155 to receive usual care. The primary outcome was 28-day mortality. Results: The enrollment of patients in the hydroxychloroquine group was closed on June 5, 2020, after an interim analysis determined that there was a lack of efficacy. Death within 28 days occurred in 421 patients (27.0%) in the hydroxychloroquine group and in 790 (25.0%) in the usual-care group (rate ratio, 1.09; 95% confidence interval [CI], 0.97 to 1.23; P = 0.15). Consistent results were seen in all prespecified subgroups of patients. The results suggest that patients in the hydroxychloroquine group were less likely to be discharged from the hospital alive within 28 days than those in the usual-care group (59.6% vs. 62.9%; rate ratio, 0.90; 95% CI, 0.83 to 0.98). Among the patients who were not undergoing mechanical ventilation at baseline, those in the hydroxychloroquine group had a higher frequency of invasive mechanical ventilation or death (30.7% vs. 26.9%; risk ratio, 1.14; 95% CI, 1.03 to 1.27). There was a small numerical excess of cardiac deaths (0.4 percentage points) but no difference in the incidence of new major cardiac arrhythmia among the patients who received hydroxychloroquine. Conclusions: Among patients hospitalized with Covid-19, those who received hydroxychloroquine did not have a lower incidence of death at 28 days than those who received usual care. (Funded by UK Research and Innovation and National Institute for Health Research and others; RECOVERY ISRCTN number, ISRCTN50189673; ClinicalTrials.gov number, NCT04381936.).
Keywords: Covid-19 -- drug therapy, hydroxychloroquine, chloroquine
Published in DiRROS: 30.05.2022; Views: 546; Downloads: 308
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Abstract: Objectives: The aim was to quantify the effects of selective digestive tract decontamination (SDD) consisting of a mouth paste and gastro-enteral suspension, selective oropharyngeal decontamination with a mouth paste (SOD) and 1-2% chlorhexidine (CHX) mouthwash on eradication and acquisition of carriage of third-generation cephalosporin-resistant Enterobacterales (3GCR-E) and carbapenem-resistant Gram-negative bacteria (CR-GNB) in Intensive Care Unit (ICU) patients. Methods: This was a nested cohort study within a cluster-randomized cross-over trial in six European countries and 13 ICUs with 8665 patients. Eradication and acquisition during ICU stay of 3GCR-E and CRGNB were investigated separately in the rectum and respiratory tract for the three interventions and compared with standard care (SC) using Cox-regression competing events analyses. Results: Adjusted cause specific hazard ratios (CSHR) for eradication of rectal carriage for SDD were 1.76 (95% CI 1.31-2.36) for 3GCR-E and 3.17 (95% CI 1.60-6.29) for CR-GNB compared with SC. For the respiratory tract, adjusted CSHR for eradication of 3GCR-E were 1.47 (0.98-2.20) for SDD and 1.38 (0.92-2.06) for SOD compared with SC, and for eradication of CR-GNB these were 0.77 (0.41-1.45) for SDD and 0.81 (0.44-1.51) for SOD, compared with SC. Adjusted CSHRs for acquisition of rectal carriage during SDD (compared with SC) were 0.51 (0.40-0.64) for 3GCR-E and of 0.56 (0.40-0.78) for CR-GNB. Adjusted CSHRs for acquiring respiratory tract carriage with 3GCR-E compared with SC were 0.38 (0.28-0.50) for SDD and 0.55 (0.42-0.71) for SOD, and for CR-GNB 0.46 (0.33-0.64) during SDD and 0.60 (0.44-0.81) during SOD, respectively. SOD was not associated with eradication or acquisition of 3GCR-E and CR-GNB in the rectum. Conclusions: Among mechanically ventilated ICU patients, SDD was associated with more eradication and less acquisition of 3GCR-E and CR-GNB in the rectum than SC. SDD and SOD were associated with less acquisition of both 3GCR-E and CR-GNB than SC in the respiratory tract.
Keywords: intensive care units -- analysis -- epidemiology, bacterial drug resistance, anti-infective agents -- therapeutic use decontamination, beta-lactamases, Gram-negative bacteria, gastrointestinal tract -- microbiology -- drug therapy, cohort studies, colonization, ESBL, digestive tract
Published in DiRROS: 27.05.2022; Views: 578; Downloads: 216
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Abstract: Introduction: Rearranged during transfection (RET) gene fusions are rare genetic drivers in non-small cell lung cancer (NSCLC). Selective RET-inhibitors such as selpercatinib have shown therapeutic activity in early clinical trials; however, their efficacy in the real-world setting is unknown. Methods: A retrospective efficacy and safety analysis was performed on data from RET fusio-%positive NSCLC patients who participated in a selpercatinib access program (named patient protocol) between August 2019 and January 2021. Results: Data from 50 patients with RET fusion-positive advanced NSCLC treated with selpercatinib at 27 centers in 12 countries was analyzed. Most patients were Non-Asian (90%), female (60%), never-smokers (74%), with a median age of 65 years (range, 38-89). 32% of the patients had known brain metastasis at the time of selpercatinib treatment. Overall, 13 patients were treatment-naïve, while 37 were pretreated with a median of three lines of therapy (range, 1-8). The objective response rate (ORR) was 68% [95% confidence interval (CI), 53-81] in the overall population. The disease control rate was 92%. The median progression-free survival was 15.6 months (95% CI, 8.8-22.4) after a median follow-up of 9 months. In patients with measurable brain metastases (n=8) intracranial ORR reached 100%. In total, 88% of patients experienced treatment-related adverse events (TRAEs), a large majority of them being grade 1 or 2. The most common grade >/=3 TRAEs were increased liver enzyme levels (in 10% of patients), prolonged QTc time (4%), abdominal pain (4%), hypertension (4%), and fatigue/asthenia (4%). None of patients discontinued selpercatinib treatment for safety reasons. No new safety concerns were observed, nor where there any treatment-related death. Conclusions: In this real-world setting, the selective RET-inhibitor selpercatinib demonstrated durable systemic and intracranial antitumor activity in RET fusion-positive NSCLC and was well tolerated.
Keywords: non-small cell lung carcinoma -- drug therapy -- genetics, molecular targeted therapy, real-world data, selpercatinib, targeted therapy, tyrosine kinase inhibitor
Published in DiRROS: 16.06.2021; Views: 1344; Downloads: 739
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Abstract: This clinical case series describes our experience with the use of Janus kinase 1/2 inhibitor baricitinib in two patients suffering from refractory adult-onset Still's disease (AOSD) as well as in one case suffering from AOSD-like autoinflammatory disease in the context of myelodysplastic syndrome. All patients suffered from disease nonresponsive to conventional Disease-modifying antirheumatic drugs (DMARDs) as well as biological therapies including interleukin (IL)-1 and IL-6 blockade, relying instead on high daily doses of prednisolone. We also report the first case of Pneumocystis jirovecii infection following baricitinib use.
Keywords: adult onset Still's disease -- drug therapy, ankylosing spondylitis, arthritis, antirheumatic agents, undifferentiated systemic autoinflammatory disease, disease-modifying antirheumatic drugs
Published in DiRROS: 08.04.2021; Views: 1359; Downloads: 860
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