Zirconia-Based Compositions for Use in Passive NO\u3csub\u3ex\u3c/sub\u3e Adsorber Devices

A passive NOx adsorbent includes: palladium, platinum or a mixture thereof and a mixed or composite oxide including the following elements in percentage by weight, expressed in terms of oxide: 10-90% by weight zirconium and 0.1-50% by weight of least one of the following: a transition metal or a lanthanide series element other than Ce. Although the passive NOx adsorbent can include Ce in an amount ranging from 0.1 to 20% by weight expressed in terms of oxide, advantages are obtained particularly in the case of low-Ce or a substantially Ce-free passive NOx adsorbent

Stapled hemorrhoidopexy, an innovative surgical procedure for hemorrhoidal prolapse: cost-utility analysis

Aim To undertake full economic evaluation of stapled hemorrhoidopexy (PPH) to establish its cost-effectiveness and investigate whether PPH can become cost-saving compared to conventional excisional hemorrhoidectomy (CH). Methods A cost–utility analysis in hospital and health care system (UK) was undertaken using a probabilistic, cohortbased decision tree to compare the use of PPH with CH. Sensitivity analyses allowed showing outcomes in regard to the variations in clinical practice of PPH procedure. The participants were patients undergoing initial surgical treatment of third and fourth degree hemorrhoids within a 1-year time-horizon. Data on clinical effectiveness were obtained from a systematic review of the literature. Main outcome measures were the cost per procedure at the hospital level, total direct costs from the health care system perspective, quality adjusted life years (QALY) gained and incremental cost per QALY gained. Results A decrease in operating theater time and hospital stay associated with PPH led to a cost saving compared to CH of GBP 27 (US $43.11, €30.50) per procedure at the hospital level and to an incremental cost of GBP 33 (US$52.68, €37.29) after one year from the societal perspective. Calculation of QALYs induced an incremental QALY of 0.0076 and showed an incremental cost-effective ratio (ICER) of GBP 4316 (US $6890.47, €4878.37). Taking into consideration recent literature on clinical outcomes, PPH becomes cost saving compared to CH for the health care system. Conclusions PPH is a cost-effective procedure with an ICER of GBP 4136 and it seems that an innovative surgical procedure could be cost saving in routine clinical practice

Modified medication use in dysphagia: the effect of thickener on drug bioavailability—a systematic review

Introduction Dysphagia is associated with long-term conditions including strokes, dementia, Parkinson’s disease and frailty. Dysphagia affects 30–40% of the population aged over 65 years-old. Adults with dysphagia often experience long-term conditions requiring multiple medications (often > 5) to manage these. The thickening of liquids is a common compensatory strategy in dysphagia management. Studies suggest that immersion in thickened liquids affects medicines’ solubility in vitro. Clinicians and pharmacists are unaware of the pharmacokinetic/therapeutic effects of thickened liquids on oral medicines. We conducted a systematic review of existing literature on thickeners’ effects on drug bioavailability. Methodology We performed a literature search of MEDLINE & EMBASE. Search terms included: dysphagia/thickened diet (EMBASE only)/ bioavailability or absorption of medicines or pharmacokinetics; excluded: NG feeds/animal studies. Studies included: all genders, countries, > 18 years, community and hospital settings. PRISMA guidance was followed. Results Five hundred seventy results were found, and 23 articles identified following the reference list review. Following an abstract and full-text review, 18 were included. Most articles evaluated thickeners on dissolution profiles in-vitro, with a few investigating in-vivo. Most studies were single-centre prospective studies identifying that thickeners generally affect dissolution rates of medications. Few studies assessed bioavailability or used clinical outcomes. Conclusion Dysphagia and polypharmacy are common in older adults, but little is known about the effects of altering liquid viscosity on the therapeutic effect of most medications. Further larger-scale studies are required to evaluate the therapeutic impact of thickener, on a bigger range of medications, factoring in other variables such as type of thickener, viscosity of thickener and duration of immersion

Does single application of topical chloramphenicol to high risk sutured wounds reduce incidence of wound infection after minor surgery? Prospective randomised placebo controlled double blind trial

Objective To determine the effectiveness of a single application of topical chloramphenicol ointment in preventing wound infection after minor dermatological surgery

Faecal haemoglobin concentration in adenoma, before and after polypectomy, approaches the ideal tumour marker

BACKGROUND: Polypectomy may be performed at colonoscopy and then subsequent surveillance undertaken. It is thought that faecal haemoglobin concentration (f-Hb), estimated by quantitative faecal immunochemical tests (FIT), might be a useful tumour marker. METHODS: Consecutive patients enrolled in colonoscopy surveillance were approached at two hospitals. A specimen for FIT was provided before colonoscopy and, ideally after 3 weeks, a second FIT sample from those who had polypectomy. A single FIT system (OC-Sensor io, Eiken Chemical Co., Ltd) was used to generate f-Hb. RESULTS: 1103 Patients were invited; 643 returned a FIT device (uptake: 58.3%). Four patients had known inflammatory bowel disease (IBD) and were excluded, leaving 639 (57.9%) with an age range of 25–90 years (median 64 years), 54.6% male. Of 593 patients who had a f-Hb result and completed colonoscopy, advanced neoplasia was found in 41 (6.9%); four colorectal cancer (CRC): 0.7% and 37 advanced adenoma (AA): 6.3%, and a further 127 (21.4%) had non-advanced adenoma (NAA). The median f-Hb was significantly greater in AA as compared to NAA; 6.0 versus 1.0 μg Hb/g faeces, p < 0.0001.134/164 (81.7%) of invited patients returned a second FIT device: 28 were patients with AA in whom median pre-polypectomy f-Hb was 19.2, falling to 3.5 μg Hb/g faeces post-polypectomy, p = 0.01, and 106 with NAA had median pre-polypectomy f-Hb 0.8 compared to 1.0 μg Hb/g faeces post-polypectomy, p = 0.96. CONCLUSIONS: Quantitative FIT could provide a good tumour marker in post-polypectomy surveillance, reduce colonoscopy requirements and minimise potential risk to patients

Loss of Integrin-linked kinase sensitizes breast cancer to SRC inhibitors

SRC is a nonreceptor tyrosine kinase with key roles in breast cancer development and progression. Despite this, SRC tyrosine kinase inhibitors have so far failed to live up to their promise in clinical trials, with poor overall response rates. We aimed to identify possible synergistic gene–drug interactions to discover new rational combination therapies for SRC inhibitors. An unbiased genome-wide CRISPR-Cas9 knockout screen in a model of triple-negative breast cancer revealed that loss of integrin-linked kinase (ILK) and its binding partners α-Parvin and PINCH-1 sensitizes cells to bosutinib, a clinically approved SRC/ABL kinase inhibitor. Sensitivity to bosutinib did not correlate with ABL dependency; instead, bosutinib likely induces these effects by acting as a SRC tyrosine kinase inhibitor. Furthermore, in vitro and in vivo models showed that loss of ILK enhanced sensitivity to eCF506, a novel and highly selective inhibitor of SRC with a unique mode of action. Whole-genome RNA sequencing following bosutinib treatment in ILK knockout cells identified broad changes in the expression of genes regulating cell adhesion and cell–extracellular matrix. Increased sensitivity to SRC inhibition in ILK knockout cells was associated with defective adhesion, resulting in reduced cell number as well as increased G(1) arrest and apoptosis. These findings support the potential of ILK loss as an exploitable therapeutic vulnerability in breast cancer, enhancing the effectiveness of clinical SRC inhibitors. SIGNIFICANCE: A CRISPR-Cas9 screen reveals that loss of integrin-linked kinase synergizes with SRC inhibition, providing a new opportunity for enhancing the clinical effectiveness of SRC inhibitors in breast cancer