Randomized non-inferiority trial to compare trimethoprim/sulfamethoxazole plus rifampicin versus linezolid for the treatment of MRSA infection

Objectives The therapeutic arsenal for MRSA infections is limited. The aim of this study was to assess the non-inferiority of a combination of trimethoprim/sulfamethoxazole plus rifampicin versus linezolid alone for the treatment of MRSA infection. Methods We conducted a randomized, open-label, single-centre, non-inferiority trial comparing trimethoprim/sulfamethoxazole (160 mg/800 mg three times daily) plus rifampicin (600 mg once a day) versus linezolid (600 mg twice a day) alone in adult patients with various types of MRSA infection. Patients were allocated 1: 1 to either regimen. The primary outcome was clinical cure at 6 weeks after the end of treatment (non-inferiority margin 20%) assessed by both ITT and PP analyses. Secondary outcomes included the microbiologically documented persistence of MRSA in clinical cultures, mortality and adverse events. The study protocol has been registered with ClinicalTrials.gov (NCT00711854). Results Overall, 150 patients were randomized to one of the two treatment arms between January 2009 and December 2013 and were included in the ITT analysis. Of these 56/75 (74.7%) in the linezolid group and 59/75 (78.7%) in the trimethoprim/sulfamethoxazole and rifampicin group experienced clinical success (risk difference 4%, 95% CI −9.7% to 17.6%). The results were confirmed by the PP analysis, with 54/66 (81.8%) cured patients in the linezolid group versus 52/59 (88.1%) in the trimethoprim/sulfamethoxazole and rifampicin group (risk difference 6.3%, 95% CI −6.8% to 19.2%). There were no statistically significant differences between the two groups in any of the secondary outcomes, including microbiologically documented failure. Four adverse drug reactions attributed to the study medication occurred in the linezolid group versus nine in the trimethoprim/sulfamethoxazole and rifampicin group. Conclusions Compared with linezolid, trimethoprim/sulfamethoxazole and rifampicin seems to be non-inferior in the treatment of MRSA infectio

Comparing the cost-effectiveness of linezolid to trimethoprim/sulfamethoxazole plus rifampicin for the treatment of MRSA infection: a health-care system perspective

To date few industry-independent studies were conducted to compare the relative costs and benefits of drugs to treat MRSA infection. We performed a stochastic cost-effectiveness analysis comparing two treatment strategies -- linezolid versus trimethoprim-sulfamethoxazole plus rifampicin -- for the treatment of MRSA infection

Methodological approach to the 3D ultrasound reconstruction of human fetal thymus: a preliminary study.

The aim of this preliminary study is to propose a new methodological approach to the study of thymic morphology and volume in human fetus by ultrasound, using mathematical three-dimensional (3D) models and comparing them to the volumes obtained by Virtual Organ Computer-aided (VOCAL). Thymic volume and morphology of two fetuses at 21 and at 28 weeks of gestational age were reconstructed using VOCAL system and two different 3D models of fetal thymus were created with a CAD 3D software by an addition of geometrical solids: a conical model for the 21 weeks thymus; an elliptical model for the 28 weeks thymus. We believe that dysmorphism, volume and involution of fetal thymus should be investigated by this method during pregnancy. The relationship between the volumes obtained by VOCAL and those obtained with 3D models should be confirmed by further studies

Should phenotype of previous preterm birth influence management of women with short cervix in subsequent pregnancy? Comparison of vaginal progesterone and Arabin pessary

Pessari Arabin; Coll uterí curt; Progesterona vaginalPesario de Arabin; Cuello uterino corto; Progesterona vaginalArabin pessary; Short cervix; Vaginal progesteroneObjective To investigate whether the classification of a previous spontaneous preterm birth (sPTB) as preterm labor (PTL) with intact membranes (IM) or as preterm prelabor rupture of membranes (PPROM) impacts the efficacy of cervical pessary or vaginal progesterone for prevention of sPTB in pregnant women with short cervix on transvaginal ultrasound. Methods This was a retrospective cohort study of asymptomatic high‐risk singleton pregnancies with a short cervix and history of sPTB, treated using Arabin pessary or vaginal progesterone for primary PTB prevention, conducted at four European hospitals. A log‐rank test on Kaplan–Meier curves was used to assess the difference in performance of pessary and progesterone, according to history of PTL‐IM or PPROM. Linear regression analysis was used to evaluate significant predictors of gestational age at delivery. Results Between 2008 and 2015, 170 women were treated with a pessary and 88 with vaginal progesterone. In women treated with a pessary, rate of sPTB < 34 weeks was 16% in those with a history of PTL‐IM and 55% in those with a history of PPROM. In women treated with progesterone, rate of sPTB < 34 weeks was 13% in those with a history of PTL‐IM and 21% in those with a history of PPROM. Treatment with a pessary resulted in earlier delivery in women with previous PPROM than in any other subgroup (P < 0.0001). Linear regression analysis showed a clear effect of PPROM history (P < 0.0001), combination of PPROM history and treatment (P = 0.0003) and cervical length (P = 0.0004) on gestational age at birth. Conclusions Cervical pessary may be a less efficacious treatment option for women with previous PPROM; however, these results require prospective validation before change in practice is recommended. Phenotype of previous preterm birth may be an important risk predictor and treatment effect modifier; this information should be reported in future clinical trials

Should phenotype of previous preterm birth influence management of women with short cervix in subsequent pregnancy? Comparison of vaginal progesterone and Arabin pessary

Objective: To investigate whether the classification of a previous spontaneous preterm birth (sPTB) as preterm labor (PTL) with intact membranes (IM) or as preterm prelabor rupture of membranes (PPROM) impacts the efficacy of cervical pessary or vaginal progesterone for prevention of sPTB in pregnant women with short cervix on transvaginal ultrasound. Methods: This was a retrospective cohort study of asymptomatic high-risk singleton pregnancies with a short cervix and history of sPTB, treated using Arabin pessary or vaginal progesterone for primary PTB prevention, conducted at four European hospitals. A log-rank test on Kaplan-Meier curves was used to assess the difference in performance of pessary and progesterone, according to history of PTL-IM or PPROM. Linear regression analysis was used to evaluate significant predictors of gestational age at delivery. Results: Between 2008 and 2015, 170 women were treated with a pessary and 88 with vaginal progesterone. In women treated with a pessary, rate of sPTB < 34 weeks was 16% in those with a history of PTL-IM and 55% in those with a history of PPROM. In women treated with progesterone, rate of sPTB < 34 weeks was 13% in those with a history of PTL-IM and 21% in those with a history of PPROM. Treatment with a pessary resulted in earlier delivery in women with previous PPROM than in any other subgroup (P < 0.0001). Linear regression analysis showed a clear effect of PPROM history (P < 0.0001), combination of PPROM history and treatment (P = 0.0003) and cervical length (P = 0.0004) on gestational age at birth. Conclusions: Cervical pessary may be a less efficacious treatment option for women with previous PPROM; however, these results require prospective validation before change in practice is recommended. Phenotype of previous preterm birth may be an important risk predictor and treatment effect modifier; this information should be reported in future clinical trials. © 2018 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology

Association between multimorbidity and postoperative mortality in patients undergoing major surgery: a prospective study in 29 countries across Europe

BackgroundMultimorbidity poses a global challenge to healthcare delivery. This study aimed to describe the prevalence of multimorbidity, common disease combinations and outcomes in a contemporary cohort of patients undergoing major abdominal surgery.MethodsThis was a pre-planned analysis of a prospective, multicentre, international study investigating cardiovascular complications after major abdominal surgery conducted in 446 hospitals in 29 countries across Europe. The primary outcome was 30-day postoperative mortality. The secondary outcome measure was the incidence of complications within 30 days of surgery.ResultsOf 24,227 patients, 7006 (28.9%) had one long-term condition and 10,486 (43.9%) had multimorbidity (two or more long-term health conditions). The most common conditions were primary cancer (39.6%); hypertension (37.9%); chronic kidney disease (17.4%); and diabetes (15.4%). Patients with multimorbidity had a higher incidence of frailty compared with patients &lt;= 1 long-term health condition. Mortality was higher in patients with one long-term health condition (adjusted odds ratio 1.93 (95%CI 1.16-3.23)) and multimorbidity (adjusted odds ratio 2.22 (95%CI 1.35-3.64)). Frailty and ASA physical status 3-5 mediated an estimated 31.7% of the 30-day mortality in patients with one long-term health condition (adjusted odds ratio 1.30 (95%CI 1.12-1.51)) and an estimated 36.9% of the 30-day mortality in patients with multimorbidity (adjusted odds ratio 1.61 (95%CI 1.36-1.91)). There was no improvement in 30-day mortality in patients with multimorbidity who received pre-operative medical assessment.ConclusionsMultimorbidity is common and outcomes are poor among surgical patients across Europe. Addressing multimorbidity in elective and emergency patients requires innovative strategies to account for frailty and disease control. The development of such strategies, that integrate care targeting whole surgical pathways to strengthen current systems, is urgently needed for multimorbid patients. Interventional trials are warranted to determine the effectiveness of targeted management for surgical patients with multimorbidity