Chest computed tomography outcomes in a randomized clinical trial in cystic fibrosis: Lessons learned from the first ataluren phase 3 study

A phase 3 randomized double blind controlled, trial in 238 people with cystic fibrosis (CF) and at least one nonsense mutation (nmCF) investigated the effect of ataluren on FEV1. The study was of 48 weeks duration and failed to meet its primary endpoint. Unexpectedly

Infective Endocarditis After Melody Valve Implantation in the Pulmonary Position: A Systematic Review

Developmen

Predniso(lo)ne Dosage and Chance of Remission in Patients With Autoimmune Hepatitis

Background & Aims Patients with autoimmune hepatitis (AIH) commonly receive induction therapy with predniso(lo)ne followed by maintenance therapy with azathioprine. European Association for Study of the Liver clinical practice guidelines advise a predniso(lo)ne dose range of 0.50–1 mg/kg/day, which leaves room for practice variation. We performed a multicenter study to determine the efficacy of different dose ranges of predniso(lo)ne induction therapy in a large European cohort of patients with AIH. Methods We performed a retrospective cohort study using a comparative effectiveness design. We collected data from 451 adults with AIH who began treatment from 1978 through 2017 at 9 centers in 5 European countries. We assigned patients to a high-dose group (initial predniso(lo)ne dose ≥0.50 mg/kg/day; n=281) or a low-dose group (<0.50 mg/kg/day; n=170). Logistic regression was performed to determine difference in outcomes between the groups. The primary outcome was normal serum levels of transaminases at 6 months after initiation of therapy. Results There was no significant difference in rates of normalization of transaminases between the high-dose predniso(lo)ne group and the low-dose group (70.5% vs 64.7%; P =.20). After multivariable logistic regression with correction for confounders, there was no difference in the likelihood of normalization of transaminases between the groups (odds ratio, 1.21; 95% CI, 0.78 – 1.87; P =.38). Patients given an initial high dose of predniso(lo)ne received more predniso(lo)ne over time than patients started on a lower dose (median doses over 6 months: 3780 mg vs 2573 mg) ( P <.01). Conclusions In a retrospective study of patients with AIH in Europe, we found that the dose of predniso(lo)ne to induce remission in patients with AIH is less relevant than assumed. An initial predniso(lo)ne dose below 0.50 mg/kg/day substantially decreases unnecessary exposure to predniso(lo)ne in patients with AIH

From marine bands to hybrid flows: sedimentology of a Mississippian black shale

Organic‐rich mudstones have long been of interest as conventional and unconventional source rocks and are an important organic carbon sink. Yet the processes that deposited organic‐rich muds in epicontinental seaways are poorly understood, partly because few modern analogues exist. This study investigates the processes that transported and deposited sediment and organic matter through part of the Bowland Shale Formation, from the Mississippian Rheic–Tethys seaway. Field to micron‐scale sedimentological analysis reveals a heterogeneous succession of carbonate‐rich, siliceous, and siliciclastic, argillaceous muds. Deposition of these facies at basinal and slope locations was moderated by progradation of the nearby Pendle delta system, fourth‐order eustatic sea‐level fluctuation and localized block and basin tectonism. Marine transgressions deposited bioclastic ‘marine band’ (hemi)pelagic packages. These include abundant euhaline macrofaunal tests, and phosphatic concretions of organic matter and radiolarian tests interpreted as faecal pellets sourced from a productive water column. Lens‐rich (lenticular) mudstones, hybrid, debrite and turbidite beds successively overlie marine band packages and suggest reducing basin accommodation promoted sediment deposition via laminar and hybrid flows sourced from the basin margins. Mud lenses in lenticular mudstones lack organic linings and bioclasts and are equant in early‐cemented lenses and in plan‐view, and are largest and most abundant in mudstones overlying marine band packages. Thus, lenses likely represent partially consolidated mud clasts that were scoured and transported in bedload from the shelf or proximal slope, as a ‘shelf to basin’ conveyor, during periods of reduced basin accommodation. Candidate in situ microbial mats in strongly lenticular mudstones, and as rip‐up fragments in the down‐dip hybrid beds, suggest that these were potentially key biostabilizers of mud. Deltaic mud export was fast, despite the intrabasinal complexity, likely an order of magnitude higher than similar successions deposited in North America. Epicontinental basins remotely linked to delta systems were therefore capable of rapidly accumulating both sediment and organic matter

Patients with squamous cell versus adeno(squamous) carcinoma of the cervix, what factors determine the prognosis?

Patients with squamous cell carcinoma of the cervix FIGO stages IB to IV (n = 306) were compared to patients with adeno(squamous) carcinoma (n = 70). There was no difference between the mean ages of the groups. In the patients who underwent radical surgical treatment, whether or not in combination with radiotherapy (n = 209), stepwise regression analysis showed that a positive lymph node status was the most unfavorable prognostic factor, followed by the histologic type (adeno(squamous) carcinoma) and the tumor diameter (> 3 cm). Vascular-space invasion had no additional prognostic value. Patient's age did not affect the prognosis. Distant metastases were not found to be more prevalent in the patients with adeno(squamous) carcinoma. In patients with adeno(squamous) carcinoma and positive lymph nodes, it is worth considering more intensive locoregional treatment than is usually prescribed for these patients and/or adjunctive chemotherapy, because there is a high risk of tumor recurrence

Voluntary turnover in the Omani public sector: an Islamic values perspective

Following four decades of economic growth the public sector in Oman is experiencing an emerging problem of labour turnover to the private sector. We examine this phenomenon through semi-structured interviews with 26 current and former public employees. The rate of turnover is low but this masks the impact of losses to key technical and management roles. The main reasons for turnover are dissatisfaction with management style, reward practices and promotion opportunities. Findings are interpreted in the context of Islamic work values and implications for public management reform in Oman are given

Release of lipopolysaccharide toxicity-modulating proteins in patients undergoing cardiopulmonary bypass using noncoated and heparin-coated extracorporeal circuits. A clinical pilot study.

Department of Surgery, University of Limburg, Maastricht, The Netherlands. STUDY OBJECTIVE: Cardiopulmonary bypass (CPB) induces a generalized inflammatory response, including activation of leukocytes, contributing to postoperative morbidity. The inflammatory pathways leading to this systemic inflammatory response syndrome are considered identical to those involved in septic shock. Therefore, we studied the release of bactericidal/permeability-increasing protein (BPI), lipopolysaccharide binding protein (LBP), and soluble CD14 (sCD14)-all proteins that modulate the effects of lipopolysaccharide (LPS)-in patients undergoing CPB. In addition, the effect of heparin coating of the extracorporeal bypass circuit on the release of these parameters was assessed. DESIGN: Prospective, randomized clinical pilot study. SETTING: Cardiothoracic Surgery Department in a university hospital. PATIENTS: Fourteen patients undergoing elective coronary artery bypass grafting were included. Seven patients underwent CPB using a standard, noncoated extracorporeal circuit, and seven patients had CPB using a heparin-coated extracorporeal circuit (Duraflo II). INTERVENTIONS: Blood samples were taken after induction of anesthesia, just before aortic crossclamping, and 0, 0.5, 1.5, 3, 6, 12, and 24 h after declamping. MEASUREMENTS AND RESULTS: CPB with a noncoated extracorporeal circuit induced a sharp increase in neutrophil-derived BPI, manifest directly after release of the aortic crossclamp, which was significantly attenuated using a heparin-coated system. Also, CPB induced a gradual increase of the acute-phase reactant LBP, which was identical in the noncoated and heparin-coated groups. Systemic release of sCD14 after crossclamp release was significantly higher in the noncoated group compared with the heparin-coated group, but did not rise above baseline levels. CONCLUSIONS: These data confirm that CPB-induced leukocyte activation is attenuated using a heparin-treated extracorporeal circuit and point to the possible role of LPS toxicity-modulating proteins in the systemic inflammatory response after bypass surgery. Publication Types: Clinical Trial Randomized Controlled Tria