Variation in use and outcomes related to midline catheters: results from a multicentre pilot study.

BACKGROUND: While midline vascular catheters are gaining popularity in clinical practice, patterns of use and outcomes related to these devices are not well known. METHODS: Trained abstractors collected data from medical records of hospitalised patients who received midline catheters in 12 hospitals. Device characteristics, patterns of use and outcomes were assessed at device removal or at 30 days. Rates of major (upper-extremity deep vein thrombosis [DVT], bloodstream infection [BSI] and catheter occlusion) and minor complications were assessed. χ2 tests were used to examine differences in rates of complication by number of lumens, reasons for catheter removal l, and hospital-level differences in rates of midline use. RESULTS: Complete data on 1161 midlines representing 5%-72% of all midlines placed in participating hospitals between 1 January 2017 and 1 March 2018 were available. Most (70.8%) midlines were placed in general ward settings for difficult intravenous access (61.4%). The median dwell time of midlines across hospitals was 6 days; almost half (49%) were removed within 5 days of insertion. A major or minor complication occurred in 10.3% of midlines, with minor complications such as dislodgement, leaking and infiltration accounting for 71% of all adverse events. While rates of major complications including occlusion, upper-extremity DVT and BSI were low (2.2%, 1.4% and 0.3%, respectively), they were just as likely to lead to midline removal as minor complications (53.8% vs 52.5%, p=0.90). Across hospitals, absolute volume of midlines placed varied from 100 to 1837 devices, with corresponding utilisation rates of 0.97%-12.92% (p<0.001). CONCLUSION: Midline use and outcomes vary widely across hospitals. Although rates of major complications are low, device removal as a result of adverse events is common.

Preimplantation factor (PIF) analog prevents type I diabetes mellitus (TIDM) development by preserving pancreatic function in NOD mice.

Preimplantation factor (PIF) is a novel embryo-secreted immunomodulatory peptide. Its synthetic analog (sPIF) modulates maternal immunity without suppression. There is an urgent need to develop agents that could prevent the development of type 1 diabetes mellitus (TIDM). Herein, we examine sPIF's preventive effect on TIDM development by using acute adoptive-transfer (ATDM) and spontaneously developing (SDM) in non-obese diabetic (NOD) murine models. Diabetes was evaluated by urinary and plasma glucose, intraperitoneal glucose tolerance test (IPGTT), pancreatic islets insulin staining by immunohistochemistry and by pancreatic proteome evaluation using mass spectrometry, followed by signal pathway analysis. Continuous administration of sPIF for 4-weeks prevents diabetes development in ATDM model in >90% of recipients demonstrated by normal IPGTT, preserved islets architecture, number, and insulin staining. (P < 0.01). sPIF effect was specific; its protective effects are not replicated by scrambled PIF (χ(2) = 0.009) control. sPIF led also to increased circulating Th2 and Th1 cytokines. In SDM model, 4-week continuous sPIF administration prevented onset of diabetes for 21 weeks post-therapy (P < 0.01). Low-dose sPIF administration for 16 weeks prevented diabetes development up to 14 weeks post-therapy, evidenced by preserved islets architecture and insulin staining. In SDM model, pancreatic proteome pathway analysis demonstrated that sPIF regulates protein traffic, prevents protein misfolding and aggregation, and reduces oxidative stress and islets apoptosis, leading to preserved insulin staining. sPIF further increased insulin receptor expression and reduced actin and tubulin proteins, thereby blocking neutrophil invasion and inflammation. Exocrine pancreatic function was also preserved. sPIF administration results in marked prevention of spontaneous and induced adoptive-transfer diabetes suggesting its potential effectiveness in treating early-stage TIDM.

Vasoactive intestinal peptide induction by ciliary neurotrophic factor in donor human corneal endothelium in situ.

After peripheral nerve axotomy, vasoactive intestinal peptide (VIP) gene expression is upregulated in neurons, whereas ciliary neurotrophic factor (CNTF) accumulates extracellularly at the lesion site. Although CNTF-induced VIP gene expression has been reported in cultured sympathetic neurons and neuroblastoma cells, it still remains to be determined if CNTF and VIP play interrelated roles in nerve injury. The corneal endothelium, like sympathetic neurons, derives from the neural crest. Previously, we demonstrated that a sublethal-level of oxidative stress induces CNTF release from corneal endothelial (CE) cells in situ. Here, we show that human CE cells express the 53 kDa ligand-binding alpha subunit of the CNTF receptor (CNTFRalpha). We further demonstrate that CNTF induces VIP immunoreactivity in human donor corneas. To determine if the increase in VIP immunoreactivity was reflected by an increase in gene expression, donor human corneas were bisected and treated with CNTF or vehicle, and analyzed by real-time RT-qPCR. Two experiments using different sets of bisected corneas indicated that CNTF induced increases in VIP mRNA levels of 6.5+/-2.2-fold (N=7 corneas) and 2.3+/-0.6-fold (N=10 corneas) (mean+/-S.E.M.), respectively. Whereas VIP is produced as a CE autocrine factor against oxidative stress, the present study suggested that oxidative stress-released CNTF plays a role in protecting CE cells against oxidative stress injury by upregulating VIP expression.

Treatment of mild to moderate psoriasis with Reliéva, a Mahonia aquifolium extract--a double-blind, placebo-controlled study.

Psoriasis is usually treated with local and systemic medications that have varying degrees of efficacy and safety profiles. We investigated the efficacy and safety of an alternative treatment from natural sources, Mahonia aquifolium, for the management of mild to moderate psoriasis. Two hundred subjects participated in a randomized, double-blind, placebo-controlled study using either the topical cream Reliéva (a homeopathic product containing a proprietary M. aquifolium extract) or control (placebo) twice a day for 12 weeks. Efficacy and safety were assessed using the Psoriasis Area Severity Index (PASI) and the Quality of Life Index (QLI) questionnaires at different times throughout the 12-week study. The PASI was evaluated by the physician at the beginning (week 0) and end (week 12) of the study. The QLI was assessed by patients at weeks 0, 4, 8, and 12. The results indicate statistically significant (P < 0.05) improvements in PASI and QLI in the Mahonia-treated group, compared with the control group. The side effects reported were infrequent, < 1% and minor; the most frequent side effects were rash, a burning sensation when applying the cream, and clothing stain. These data indicate that Reliéva, a proprietary form of M. aquifolium, is effective and well tolerated in patients with mild to moderate psoriasis.

PCDH15 is expressed in the neurosensory epithelium of the eye and ear and mutant alleles are responsible for both USH1F and DFNB23.

Recessive splice site and nonsense mutations of PCDH15, encoding protocadherin 15, are known to cause deafness and retinitis pigmentosa in Usher syndrome type 1F (USH1F). Here we report that non-syndromic recessive hearing loss (DFNB23) is caused by missense mutations of PCDH15. This suggests a genotype-phenotype correlation in which hypomorphic alleles cause non-syndromic hearing loss, while more severe mutations of this gene result in USH1F. We localized protocadherin 15 to inner ear hair cell stereocilia, and to retinal photoreceptors by immunocytochemistry. Our results further strengthen the importance of protocadherin 15 in the morphogenesis and cohesion of stereocilia bundles and retinal photoreceptor cell maintenance or function.