A Meta-Ethnographic Review of Paid Staff and Volunteers Working together in Palliative Care.

CONTEXT: Volunteers in palliative care settings are an essential part of care provision for patients and those important to them. Effective collaboration between volunteers and paid staff has been regarded as an important element of successful working, however, at times failures in coordination, information sharing and tensions within teams have been highlighted. OBJECTIVES: To explore the views expressed by volunteers and paid staff about their experiences of working together in palliative care settings. METHODS: A systematic exploration of qualitative research using a meta-ethnographic approach. PsycINFO, CINAHL, Medline Complete, and AMED databases were searched from inception to December 2021 for the concepts "volunteers" and "palliative care." Repeated in-depth reading and appraisal of papers identified metaphors and concepts, providing new interpretations. RESULTS: Included papers (n = 14) enabled the construction of five storylines: 1) "we are the cake, and they are the cream": understanding the volunteer role-separate, but part of a whole. 2) "…we don't know what's wrong with people but sometimes we need to know": access to information and importance of trust. 3) "everybody looks out for each other": access to paid staff and their support. 4) "...we don't meddle in the medical": boundaries. 5) "it's the small things that the staff does for me that makes me feel good about my work": sense of value and significance. CONCLUSIONS: For effective working relationships between paid staff and volunteers, proactive engagement, recognition of each other's role and contribution, mutual sharing of information, and intentional interaction between both groups is needed.

Narrow Spectrum Kinase Inhibitors Demonstrate Promise for the Treatment of Dry Eye Disease and Other Ocular Inflammatory Disorders.

Purpose: The purpose of this study is to determine the potential of narrow spectrum kinase inhibitors (NSKIs) to treat inflammatory eye disorders. Methods: Human conjunctival epithelial (HCE) cells were retrieved from subjects via impression cytology. Real-time quantitative PCR (qPCR) was performed on HCE cells to determine gene expression of NSKI kinase targets and proinflammatory cytokines in dry eye disease (DED) patients versus healthy controls. qPCR also assessed p38α expression in hyperosmolar-treated Chang conjunctival epithelial cells. Interaction of NSKI TOP1362 with the kinases was evaluated in ATP-dependent Z-LYTE and competition binding assays. Anti-inflammatory activity was assessed in human peripheral blood mononuclear cells and primary macrophages. In an endotoxin-induced uveitis (EIU) study, lipopolysaccharide (LPS) was administered intravitreally to Lewis rats. TOP1362, dexamethasone, or vehicle was administered topically, and inflammatory cytokine levels were measured 6 hours after LPS injection. Results: HCE cells from DED patients showed significantly increased expression of p38α, spleen tyrosine kinase (Syk), Src, lymphocyte-specific protein tyrosine kinase (Lck), interleukin one beta (IL-1ß), interleukin eight (IL-8), monocyte chemotactic protein-1 (MCP-1), and matrix metalloproteinase-9 (MMP-9). TOP1362 strongly inhibited the kinase targets p38α, Syk, Src, and Lck, blocked the rise in p38α expression in hyperosmolar Chang cells, and potently reduced inflammatory cytokine release in cellular models of innate and adaptive immunities. In the EIU model, TOP1362 dose-dependently attenuated the LPS-induced rise in inflammatory cell infiltration and ocular cytokine levels with efficacy comparable to that of dexamethasone. Conclusions: TOP1362 is a potent inhibitor of kinases upregulated in DED and markedly attenuates proinflammatory cytokine release in vitro and in vivo, highlighting the therapeutic potential of NSKIs for treating ocular inflammation, such as that observed in DED.

Infrared vibrational spectroscopy: a rapid and novel diagnostic and monitoring tool for cystinuria.

Cystinuria is the commonest inherited cause of nephrolithiasis (~1% in adults; ~6% in children) and is the result of impaired cystine reabsorption in the renal proximal tubule. Cystine is poorly soluble in urine with a solubility of ~1 mM and can readily form microcrystals that lead to cystine stone formation, especially at low urine pH. Diagnosis of cystinuria is made typically by ion-exchange chromatography (IEC) detection and quantitation, which is slow, laboursome and costly. More rapid and frequent monitoring of urinary cystine concentration would significantly improve the diagnosis and clinical management of cystinuria. We used attenuated total reflection - Fourier transform infrared spectroscopy (ATR-FTIR) to detect and quantitate insoluble cystine in 22 cystinuric and 5 healthy control urine samples. Creatinine concentration was also determined by ATR-FTIR to adjust for urinary concentration/dilution. Urine was centrifuged, the insoluble fraction re-suspended in 5 µL water and dried on the ATR prism. Cystine was quantitated using its 1296 cm-1 absorption band and levels matched with parallel measurements made using IEC. ATR-FTIR afforded a rapid and inexpensive method of detecting and quantitating insoluble urinary cystine. This proof-of-concept study provides a basis for developing a high-throughput, cost-effective diagnostic method for cystinuria, and for point-of-care clinical monitoring.

A Phase 1, Multi-Center, Open-Label, Dose-Escalation Study of 131I-CLR1404 in Subjects with Relapsed or Refractory Advanced Solid Malignancies.

This study explores the imaging and therapeutic properties of a novel radiopharmaceutical, (131)I-CLR1404. Phase 1a data demonstrated safety and tumor localization by SPECT-CT. This 1b study assessed safety, imaging characteristics, and possible antineoplastic properties and provided further proof-of-concept of phospholipid ether analogues' retention within tumors. A total of 10 patients received (131)I-CLR1404 in an adaptive dose-escalation design. Imaging characteristics were consistent with prior studies, showing tumor uptake in primary tumors and metastases. At doses of 31.25 mCi/m(2) and greater, DLTs were thrombocytopenia and neutropenia. Disease-specific studies are underway to identify cancers most likely to benefit from (131)I-CLR1404 monotherapy.

A phase I study of capecitabine, oxaliplatin, and lapatinib in metastatic or advanced solid tumors.

BACKGROUND: Metastatic colorectal cancer (mCRC) is a leading cause of cancer-related mortality in the United States, and new treatment options are needed. This phase I study investigated a novel regimen combining 2 chemotherapy drugs with proven efficacy in mCRC (capecitabine and oxaliplatin) with a tyrosine kinase inhibitor (lapatinib). Lapatinib has already been approved by the US Food and Drug Administration for treatment of selected cases of breast cancer. PATIENTS AND METHODS: Patients with solid tumors responsive to fluoropyrimidines or oxaliplatin were eligible for enrollment. Treatment was given over a 21-day cycle with a fixed dosing of intravenous oxaliplatin of 130 mg/m(2) on day 1. Capecitabine and lapatinib were given orally at escalating doses, starting at capecitabine 1500 mg/m(2)/day on days 1-14 and lapatinib 1000 mg daily on days 1-21. RESULTS: Ten patients received treatment per study protocol. All had received previous systemic treatment. Diarrhea was one of the most common side effects and accounted for nearly all grade 3/4 toxicity. The starting dose level was determined to be the maximum tolerated dose. One patient with pancreatic cancer had evidence of a partial response. Three other patients demonstrated stable disease. There were no complete responses. CONCLUSION: Results of this study suggest the regimen of capecitabine, oxaliplatin, and lapatinib has some efficacy in types of advanced or metastatic solid malignancies with known responsiveness to fluoropyrimidines or oxaliplatin. Further research may help determine whether this regimen can improve on the response rates seen with current standard regimens for mCRC.

Dendritic cells and HNSCC: a potential treatment option? (Review).

Patient survival in head and neck squamous cell cancer (HNSCC) has not changed significantly in many years, despite progress in surgical, radiotherapy and chemotherapy techniques. Immunotherapy, a rapidly progressing alternative cancer treatment, aims to prompt or assist the body's immune system to combat the disease itself. A number of strategies exist including the use of dendritic cells, natural antigen presenting cells capable of stimulating an anti-tumor immune response. Encouraging work has been performed using these cells as vaccines against a number of tumors especially melanoma. Work with head and neck cancer is also encouraging, but less advanced. Dendritic cell presence in head and neck squamous cell cancers is associated with an improved prognosis, however due to immunosuppression, the exact mechanism of which remains poorly understood, these cells do not function efficiently. This prevents the stimulation of an effective anti-tumor immune response by the patient and allows tumor growth to continue. This review summarises the current level of understanding of dendritic cells and their relationship with HNSCC. It briefly summarises work with dendritic cells and other cancers where relevant to HNSCC; dendritic cells and head and neck cancer; the possible causes of dendritic cell impairment; the techniques used to restore their function and the methods used to prime the dendritic cells prior to their use as vaccines for the stimulation of an anti-tumor response.

Effect of hyperopic photorefractive keratectomy on corneal sensitivity: a longitudinal study.

PURPOSE: To investigate corneal sensitivity after photorefractive keratectomy (PRK) for low hyperopia, as measured with a non-invasive stimulus. METHODS: Two experimental groups were recruited: a control group of 17 patients (mean age 61.65 years) who underwent no treatment, and a PRK group of 11 patients (mean age 58.64 years) who underwent one of three attempted hyperopic corrections: +2.00 D (two patients), +3.00 D (four patients), +4.00 D (five patients). Corneal sensitivity was assessed centrally and peripherally, at temporal, medial, and inferior locations, approximately 1 mm from the limbus, using the Non-Contact Corneal Aesthesiometer (NCCA). Measurements were taken at each location for the control group and at preoperative, and postoperative weeks 1 and 2, 1, 3, and 6 months for the PRK group. RESULTS: Comparison of control and PRK groups (preoperative sensation threshold) (t-test): central P=.715, temporal P=.719, medial P=.943, inferior P= .920. Comparison of longitudinal changes in PRK group (one-way ANOVA): central P=.612, temporal P=.997, medial P=.981, inferior P=.993. CONCLUSIONS: Using the Non-Contact Corneal Aesthesiometer, no significant difference was found between the control and PRK groups for preoperative sensation thresholds, and no significant change in corneal sensitivity was found between any of the test time periods at any of the four corneal test locations for the PRK group.