Posaconazole is a novel lipophilic antifungal triazole that inhibits cytochrome P450-dependent 14-α demethylase in the biosynthetic pathway of ergosterol. Inhibition of this enzyme leads to an ...accumulation of toxic 14-α methylsterols and a depletion of ergosterol, resulting in a perturbation of the function of the fungal cell membrane and blockage of cell growth and division. In vitro, posaconazole has potent and broad-spectrum activity against opportunistic, endemic and dermatophytic fungi. This activity extends to organisms that are often refractory to existing triazoles, amphotericin B or echinocandins, such as Candida glabrata, Candida krusei, Aspergillus terreus, Fusarium spp. and the Zygomycetes. A large variety of animal models of invasive fungal infections have provided consistent evidence of efficacy against these organisms in vivo, both in normal and immunocompromised animals. Posaconazole is available as an oral suspension and optimal exposure is achieved when the drug is administered in two to four divided doses along with food or a nutritional supplement. The compound has a large volume of distribution, in the order of 5 l/kg, and a half-life of approximately 20 h. Posaconazole is not metabolized to a significant extent through the cytochrome P450 enzyme system and is primarily excreted in an unchanged form in the feces. Although it is inhibitory, cytochrome P3A4 has no effect on 1A2, 2C8, 2C9, 2D6 and 2E1 isoenzymes, and therefore, a limited spectrum of drug-drug interactions can be expected. Pharmacokinetic studies in special populations revealed no necessity for dosage adjustment based on differences in age, gender, race, renal or hepatic function. Posaconazole has demonstrated strong antifungal efficacy in Phase II and III clinical trials in immunocompromised patients with oropharyngeal and esophageal candidiasis. Posaconazole also showed promising efficacy as salvage therapy in a large Phase II study including 330 patients with invasive fungal infections intolerant to or refractory to standard therapies. Posaconazole appears to be well tolerated in a manner comparable with that of fluconazole and it is currently under regulatory review in the USA and Europe for the treatment of refractory invasive fungal infections. This drug profile reviews the preclinical and clinical pharmacology of posaconazole and its potential role for prevention and treatment of invasive fungal infections.
Providers may use several treatment options for patients with Peyronie's disease; however, it is unclear whether practice patterns have evolved over recent years and if this has impacted cost.
To ...investigate trends in the treatment of Peyronie's disease over time and the associated costs using a national, commercial insurance claims database.
A retrospective cohort study was conducted using claims from the Truven MarketScan database from 2007 to 2018 for men with Peyronie's disease. Cost was estimated as either the sum of prescription oral or injectable treatment costs or as the single net cost associated with the operative procedure.
Frequency of use of various treatments for Peyronie's disease and associated costs were assessed as trends over the timeline by year.
The estimated annual incidence of Peyronie's disease in this population rose from 61 to 77 per 100,000 patients over the included years, and the percent annual treatment rate rose from 17.8% to 26.2%. Colchicine was the most commonly prescribed oral agent in 2007 used in 22% of treated individuals; by 2018, pentoxifylline was the most common prescribed oral agent used in 33%. In 2007, 11% of treated patients received intralesional verapamil; however, by 2018, 24% received injectable collagenase, whereas <1% received intralesional verapamil. The mean annual, per-individual cost of Peyronie's disease treatment increased from $1,531 in 2007 to $10,339 in 2018. The cost increase was greatest for injectable therapies, which rose from $811 per individual in 2007 to $16,184 in 2018, a 19-fold increase.
Diagnosis and treatment of Peyronie's disease is increasing over time. Pentoxifylline has become the most common oral prescription, whereas injectable collagenase has become most common injection. The mean cost associated with Peyronie's disease treatment increased more than 5 times from 2007 to 2018 corresponding with Federal Drug Administration's approval of injectable collagenase.
Loftus CJ, Rajanahally S, Holt SK, et al. Treatment Trends and Cost Associated With Peyronie's Disease. Sex Med 2020;8:673–678.
The mitochondrial genome (mitogenome) of the bollworm, Helicoverpa zea (Boddie), was assembled using paired-end nucleotide sequence reads generated with a next-generation sequencing platform. ...Assembly resulted in a mitogenome of 15,348 bp with greater than 17,000-fold average coverage. Organization of the H. zea mitogenome (gene order and orientation) was identical to other known lepidopteran mitogenome sequences. Compared with Helicoverpa armigera (Hübner) mitogenome, there were a few differences in the lengths of gaps between genes, but the lengths of nucleotide overlaps were essentially conserved between the two species. Nucleotide composition of the H. zea mitochondrial genome was very similar to those of the related species H. armigera and Helicoverpa punctigera Wallengren. Mapping of RNA-Seq reads obtained from 2-h eggs and 48-h embryos to protein coding genes (PCG) revealed that all H. zea PCGs were processed as single mature gene transcripts except for the bicistronic atp8 + atp6 transcript. A tRNA-like sequence predicted to form a hammer-head-like secondary structure that may play a role in transcription start and mitogenome replication was identified within the control region of the H. zea mitogenome. Similar structures were also found within the control regions of several other lepidopteran species. Expression analysis revealed significant differences in levels of expression of PCGs within each developmental stage, but the pattern of variation was similar in both developmental stages analyzed in this study. Mapping of RNA-Seq reads to PCG transcripts also identified transcription termination and polyadenylation sites that differed from the sites described in other lepidopteran species.
Abstract
Candidemia and invasive candidiasis (CIC) is associated with considerable morbidity and mortality, with a paucity of controlled data in neutropenic patients. A systematic review was ...conducted of available data for the treatment of CIC during neutropenia. A structured OVID search of multiple databases was performed. Data from randomized controlled trials of CIC and of empirical antifungal therapy in febrile neutropenic patients was included. A total of 17 trials randomizing 342 neutropenic patients were included. Eight of the studies compared amphotericin B (AmB) to other non-polyene antifungal agents. Pooling of results favored use of comparator compounds (odds ratio OR 0.73; 95% confidence interval CI 0.42-1.29). To strengthen our analysis, a pre-planned sensitivity analysis was also conducted. Overall, there was a non-significant benefit in favor of non-polyene compounds. Across studies, echinocandins provided the benefit of favorable outcomes with fewest side effects and toxicity.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Introduction
The introduction of minimally invasive surgery and the use of laparoscopic techniques have significantly improved patient outcomes and have offered a new range of options for the ...restoration of intestinal continuity. Various reconstruction techniques have been described and various devices employed but none has been established as superior. This study evaluates our experience with, and modifications of, the orally inserted anvil (OrVil™).
Methods
We conducted a prospective observational study on 72 consecutive patients who underwent OrVil™-assisted oesophago-gastric or oesophago-jejunal anastomosis between September 2010 and September 2013. We collected data including patient demographics, disease site, type of procedure, location of the anastomosis, involvement of resection margins and peri-operative complications.
Results
Seventy-two patients were included in the study. Patient ages ranged from 45 to 92 years (median ± SD = 69 ± 10 years). Total gastrectomy with Roux-en-Y anastomosis was the most-commonly performed procedure (
n
= 41; 57 %).
R
0
resection was achieved in 67 patients (93 %). There were no Orvil™-related clinical leaks during the study period, and just two patients (2.8 %) demonstrated radiological evidence of leak, both of whom were managed conservatively. There were three in-hospital mortalities during the study period; these were unrelated to the anastomotic technique.
Conclusion
Despite a steep learning curve, the OrVil™ device is safe and reliable. It also permits the creation of higher trans-hiatal anastomoses without resorting to thoracotomy in high-risk patients with cardia tumours. Certain shortcomings of the device, that had implications for patient safety, were identified and addressed by intra-operative modification during the study period. We commend the use of a prepared OrVil™ device, as a game changer, for upper gastrointestinal reconstruction.
Objective To compare the clinical characteristics of primarily and secondarily infertile men with varicocele. Design Cross-sectional analysis. Setting Male infertility clinic, tertiary health care ...center. Patient(s) Two hundred ninety-five infertile men with palpable varicoceles. Intervention(s) Clinical evaluation including patient reproductive history (including assessment of primary or secondary infertility), physical examination, hormonal assessment and at least two semen analyses. Main Outcome Measure(s) Differences in the characteristics of men with primary vs. secondary infertility. Result(s) Two hundred five subjects were identified with primary infertility and 90 with secondary infertility. Secondarily infertile men were older (39.6 years vs. 35.0 years), with older partners (35.4 years vs. 33.2 years), but had higher sperm densities (51.3 vs. 36.0 million/mL) and a greater percentage of morphologically normal sperm (30.6% vs. 24.1%). A lower proportion of secondarily infertile men had total motile sperm count (TMC) <20 million compared with primarily infertile men (31.1% vs. 46.5%). Groups did not differ regarding infertility duration, tobacco or alcohol use, varicocele grade or laterality, testis volumes, or hormonal parameters. In multivariate modeling, secondary infertility (vs. primary) was an independent predictor of TMC >20 million (odds ratio 1.9). Conclusion(s) Men with secondary infertility are older and have older partners than primarily infertile men, yet they have significantly better sperm concentrations. Infertility in this group may be influenced by maternal reproductive potential.
It is important to realize that guidelines cannot always account for individual variation among patients. They are not intended to supplant physician judgment with respect to particular patients or ...special clinical situations. IDSA considers adherence to these guidelines to be voluntary, with the ultimate determination regarding their application to be made by the physician in the light of each patient's individual circumstances.
AbstractGlobal challenges increasingly require interdisciplinary approaches to problem solving. This need should be facilitated by institutions of higher education. With increasing climatic and ...anthropogenic changes, graduate students must gain collaborative experience communicating and working across disciplines. The evolution of multidisciplinary problem-solving and global, sustainability-minded education provides the impetus for universities to reframe researchers’ understanding of the environment and reimagine the spheres of curriculum, research, teaching, outreach, culture, and management. This paper describes a successful multidisciplinary approach at the University of Utah, centered on the project-based Global Changes and Society course. This method has brought about changes within the university and improved linkages to the greater community. Of particular importance is the development and implementation of the course framework, which transitions over time to address region-specific sustainability objectives. The results, pitfalls, and recommendations from this evolving venture are highlighted through a series of universal examples, with the potential to be applied at any institution of higher education focused on adapting the culture, environment, and structure to facilitate multilevel sustainability.
► Priming of PMNs by IFN-gamma and G-CSF augmented fungal damage of planktonic cells. ► Priming of PMNs did not have the same effect against
Candida biofilms. ► Biofilm phenotype appears to play an ...important role in protecting
C. albicans from the innate immune system.
Candida albicans is a leading cause of biofilm-related infections. As
Candida biofilms are recalcitrant to host defenses, we sought to determine the effects of interferon-γ and granulocyte colony-stimulating factor, two pro-inflammatory cytokines, on the antifungal activities of human polymorphonuclear neutrophils (PMNs) against
C. albicans biofilms, using an
in vitro biofilm model. Priming of PMNs by these cytokines augmented fungal damage of planktonic cells; however, priming of PMNs did not have the same effect against
Candida biofilms. Biofilm phenotype appears to play an important role in protecting
C. albicans from the innate immune system.
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