Palliative care patient emergency department visits at tertiary university-based emergency department in Ireland.

INTRODUCTION: Palliative care patients often present to the emergency department (ED) for various reasons e.g., acute illness, pain, altered mental status, and complications of therapy. Many visits involve less severe etiologies e.g., dyspnea, constipation, fear as patients approach the end of life, which may be more effectively and efficiently managed outside of the ED. The objective of this study is to identify and assess the frequency of presenting complaints, primary diagnosis, triage acuity, need for admission, in an Irish setting. METHODS: A single-center retrospective, observational study of palliative care patients presenting to a tertiary-care university hospital emergency department in Dublin, Ireland. Study subjects were identified using the palliative care database and cross-referencing with the ED electronic patient record system database. The primary objective to identify potential areas to minimize ED visits and improve patient care and quality of life by elucidating reasons for visits. Outcome measures include presenting complaint, primary diagnosis, triage severity score, admission, discharge, death in hospital. Statistical analysis presented as descriptive statistics. RESULTS: Four-hundred-ninety-nine ED visits, 245 (49%) were male, and 254 (51%) were female with a mean age of 69.3 years-of-age. Most patients, 285 (57.1%) self-referred to the emergency department, with general practitioners and skilled nursing facility referrals 72 (14.4%) and 39 (7.8%), respectively. Primary diagnoses were various cancers, chronic obstructive pulmonary disease, congestive heart failure, and dementia. Major reasons for visits were dyspnea, pain, falls, trauma, fever, and altered mental status. Two-hundred-eighty-nine patients (58%) had an emergency severity index (ESI) score of 1 or 2 demonstrating a higher level of acuity. Three-hundred-fifty-eight (71.7%) were admitted, 141 (28.3%) discharged to home, 64 (12.8%) admitted patients died during their hospital admission. CONCLUSIONS: Palliative care patients utilize ED services not uncommonly. Though many of these patients presented with higher acuity triage scores, 42% had lower ESI scores and may be effectively managed outside of the ED. These data suggest developing mechanisms for these patients to be urgently evaluated in their homes or facilities obviating the need for an ED evaluation.

Voluntary and non-voluntary blood donations among doctors.

BACKGROUND: Physicians may be an important source of blood donations as they are more likely to be familiar with the importance of donating and the donation process. The aim of this study is to report physicians' knowledge, attitudes, and practices towards voluntary and non-voluntary blood donations. STUDY DESIGN AND METHODS: This was a cross-sectional study conducted at King Faisal Specialist Hospital and Research Centre (KFSH&RC), Saudi Arabia. One-hundred-and-sixteen physicians and dentists responded to an online structured questionnaire sent to their institutional emails. RESULTS: Sixty-eight percent of participants (79% of males and 43% of females) reported previously having donated blood. Eighty-six percent of donors had previously donated on a voluntary basis, whereas 31% of donors had previously donated for a specific person. A recent donation within 5 years was associated with the younger age group and knowledge of the minimum interval between donations. Fifty-six percent of participants agreed with using replacement donations. Compared to participants in the youngest age group (25-35 years), older participants in the age groups (46-55 years) and (>55 years) were less likely to express intention to donate in the next 6 months (OR 0.289, P = .022 and OR 0.083, P = .004, respectively). Participants reporting poor nutritional status or other medical reasons as a barrier to donating blood were less likely to intend to donate (OR 0.146, P < .001). Among previous donors, intention to donate was associated with a recent donation within 1 year (OR 27.13, P = .002) and having had a pleasant donation experience (OR 14.98, P < .001). CONCLUSION: Blood donation practices are strongly tied to physicians' gender and age and their knowledge of the donation process. The most significant barrier to blood donation was found to be nutritional and medical status.

BBG enhances OLT1177-induced NLRP3 inflammasome inactivation by targeting P2X7R/NLRP3 and MyD88/NF-κB signaling in DSS-induced colitis in rats.

Chronic ulceration of the colon is associated with the activation of TLR4/NF-κB and P2X7R/NLRP3 signaling pathways. We investigated the effect of individual or combined administration of BBG, a P2X7R blocker, and OLT1177, a selective NLRP3 inhibitor, in the dextran sodium sulfate-induced ulcerative colitis (UC) rat model. The ulcerative rats were treated orally with brilliant blue G (BBG) (50 mg/kg/day) or OLT1177 (200 mg/kg/day) or a combination of both. Myd88 and NF-κB levels were measured by ELISA, qRT-PCR, and immunohistochemical staining. Cytokines known to be associated with TLR4/NF-κB or P2X7R/NLRP3 signaling were measured by ELISA. P2X7R and NLRP3 expression were measured by ELISA and qRT-PCR. The administration of BBG or OLT1177 ameliorated the toxic effects of DSS on the colon as they restored normal colonic macroscopic and microscopic morphology. BBG administration, but not OLT1177, reduced the expression of Myd88, NF-κB, IL-6, and TNF-α in addition to lowering P2X7R and oxidative stress levels. Individual BBG or OLT1177 administration decreased NLRP3 inflammasome recruitment and subsequent activation of caspase-1, IL-1ß, and IL-18. However, the combined administration of OLT1177 with BBG potentiated its inhibitory effect on the NLRP3, which was reflected by the additional suppressive effect on caspase-1, IL-1ß, IL-18 levels. In conclusion, BBG/OLT1177 exhibited complementary effects and effectively ameliorated UC. This novel approach provides a basis for the clinical application of this combination for the treatment of IBDs and might also be promising for the pharmacological intervention of other NLRP3 inflammasome-dependent inflammatory conditions.

The Supportive Role of NSC328382, a P2X7R Antagonist, in Enhancing the Inhibitory Effect of CRID3 on NLRP3 Inflammasome Activation in Rats with Dextran Sodium Sulfate-Induced Colitis.

PURPOSE: The NLRP3 inflammasome is a substantial component of the inflammation process. The complex pathogenesis of and the implication of a vast number of components in the inflammasome-activation pathway prompted us to search for compounds that have a wide therapeutic index and act at the level of multiple cellular targets. Although CRID3 blocks NLRP3 with high specificity in the laboratory, clinical trials of the compound reported weaker potency. METHODS: We used NSC328382, a P2X7R antagonist, as an adjunctive therapy and generated a strategy to potentiate the effects of CRID3 in rats with DSS-induced colitis. RESULTS: NSC328382/CRID3 combined therapy exhibited a significantly increased efficacy compared with either of the monotherapies. NSC328382/CRID3 was more efficient in 1) attenuating colon shortening and disease activity; 2) improving goblet cell density and both the macroscopic and microscopic scenario of the injured colon; 3) improving the antioxidant defense mechanisms of the inflamed colon against oxidative stress; and 4) mitigating the inflammation state by downregulating the proinflammatory cytokines. Pyroptotic cell death was also conspicuously restrained. Additionally, NSC328382 interrupted the MyD88/NF-κB axis. Moreover, NSC328382/CRID3 exhibited the ability to alter Th1/Th2 dominance. CONCLUSION: The clinical application of NSC328382/CRID3 may result in the generation of a novel approach for the treatment of IBDs.