Ribonucleicacid interference or small molecule inhibition of Runx1 in the border zone prevents cardiac contractile dysfunction following myocardial infarction.

AIMS: Myocardial infarction (MI) is a major cause of death worldwide. Effective treatments are required to improve recovery of cardiac function following MI, with the aim of improving patient outcomes and preventing progression to heart failure. The perfused but hypocontractile region bordering an infarct is functionally distinct from the remote surviving myocardium and is a determinant of adverse remodelling and cardiac contractility. Expression of the transcription factor RUNX1 is increased in the border zone 1-day after MI, suggesting potential for targeted therapeutic intervention. OBJECTIVE: This study sought to investigate whether an increase in RUNX1 in the border zone can be therapeutically targeted to preserve contractility following MI. METHODS AND RESULTS: In this work we demonstrate that Runx1 drives reductions in cardiomyocyte contractility, calcium handling, mitochondrial density, and expression of genes important for oxidative phosphorylation. Both tamoxifen-inducible Runx1-deficient and essential co-factor common ß subunit (Cbfß)-deficient cardiomyocyte-specific mouse models demonstrated that antagonizing RUNX1 function preserves the expression of genes important for oxidative phosphorylation following MI. Antagonizing RUNX1 expression via short-hairpin RNA interference preserved contractile function following MI. Equivalent effects were obtained with a small molecule inhibitor (Ro5-3335) that reduces RUNX1 function by blocking its interaction with CBFß. CONCLUSIONS: Our results confirm the translational potential of RUNX1 as a novel therapeutic target in MI, with wider opportunities for use across a range of cardiac diseases where RUNX1 drives adverse cardiac remodelling.

Systematic review: what interventions improve dignity for older patients in hospital?

AIMS AND OBJECTIVES: To review the evidence for interventions to improve dignity for older patients in acute care. BACKGROUND: High profile cases have highlighted failure to provide dignified care for older people in hospitals. There is good evidence on what older people consider is important for dignified care and abundant recommendations on improving dignity, but it is unclear which interventions are effective. DESIGN: Narrative systematic review. METHODS: The Cochrane library, MEDLINE, EMBASE, CINAHL, BNI and HMIC electronic databases were searched for intervention studies of any design aiming to improve inpatients' dignity. The main population of interest was older patients, but the search included all patients. Studies that focused on 'dignity therapy' were excluded. RESULTS: There were no intervention studies found in any country which aimed to improve patient dignity in hospitals which included evaluation of the effect. A narrative overview of papers that described implementing dignity interventions in practice but included no formal evaluation was, therefore, undertaken. Five papers were identified. Three themes were identified: knowing the person; partnership between older people and health care professionals; and, effective communication and clinical leadership. The effect on dignity of improving these is untested. CONCLUSIONS: There are currently no studies that have tested interventions to improve the dignity of older people (nor anyone else) in hospitals. Further research using well designed trials of interventions is needed. There is also a need to develop and validate outcome measures for interventions to improve dignity. RELEVANCE TO CLINICAL PRACTICE: At present nurses lack robust evidence on how to improve dignity. There is ample evidence on what undermines patients' dignity and there is a need to develop and test interventions designed to improve patient dignity.

Biosimilars in the United States: Considerations for Oncology Advanced Practitioners.

Biosimilars will enter the US market soon, potentially lowering costs and increasing patient access to important oncology biologics. Biosimilars are highly similar, but not identical, to their reference product. Subtle variations arise due to their inherent complexity and differences in manufacturing. Biosimilars are not generic drugs. They will be approved through a separate US regulatory pathway-distinct from conventional biologics license applications-based on analytic and clinical studies demonstrating no clinically meaningful differences from the reference product. As policies on US biosimilars evolve, it is important that advanced practitioners receive comprehensive, ongoing education on them, particularly regarding differences from small-molecule drugs; their approval pathways vs. conventional regulatory pathways; evaluation of quality, safety, and efficacy; safety monitoring; and product identification to facilitate accurate safety reporting. Advanced practitioners will play a key role in educating nurses and patients on biosimilars. Nurse education should highlight any differences from the reference product (e.g., approved indications and delivery devices) and should emphasize assessment of substitutions, monitoring for adverse events (e.g., immune reactions), and the need for precise documentation for safety reports. Patient education should address differences between the biosimilar and reference product in administration, handling and storage, and self-monitoring for adverse events.

A review of relative dose intensity and survival in patients with metastatic solid tumors.

Studies have shown that in the curative setting patients with cancer receiving chemotherapy at higher relative dose intensity (RDI) had better clinical outcomes than those receiving treatment at lower RDI. However, the impact of RDI in advanced/metastatic disease remains unclear. A review of the literature was performed to evaluate the relationship between RDI and survival in patients with metastatic lung, breast, or ovarian cancer receiving chemotherapy. Few studies attempted to specifically associate RDI with survival in a systematic way. Findings from studies that analyzed overall survival with a prespecified RDI threshold support the emerging perception that maintaining an RDI≥85% has a favorable impact on survival. Nonetheless, these studies were limited by their retrospective nature. More studies are needed to further evaluate the impact of maintaining planned chemotherapy dose intensity on outcomes in metastatic solid tumors.

Student life - Your place on the ward.

The first day of your first placement can be a daunting experience, especially for students who may not have worked in a hospital before. The pace can seem very fast and it may be difficult to know where you fit in.

Allevyn Life app.

This app is a training and educational tool for healthcare professionals and users of the Allevyn Life dressings.

Student life - African learning experience.

Archbishop Desmond Tutu once claimed that TB was the child of poverty, as well as its parent and provider. My first insight into the truth of this came while I was on a placement with Find & Treat, a pan-London tuberculosis (TB) service for vulnerable communities.

Discrete choice experiment to estimate breast cancer patients' preferences and willingness to pay for prophylactic granulocyte colony-stimulating factors.

OBJECTIVES: Rising out-of-pocket costs for cancer patients have increased shared decision making. Clinical guidelines recommend prophylactic granulocyte colony-stimulating factor (G-CSF) for patients receiving chemotherapy with a 20% or greater risk of febrile neutropenia. A discrete choice experiment was conducted to explore breast cancer patients' preferences and willingness to pay (WTP) for prophylactic G-CSF to decrease the risk of chemotherapy-induced febrile neutropenia. METHODS: An online discrete choice experiment questionnaire survey of a national US convenience sample of self-reported breast cancer patients with prior chemotherapy treatment was conducted. Sixteen paired G-CSF treatment scenarios, each with four attributes (risk of disruption to chemotherapy schedule due to low white blood cell counts, risk of developing an infection requiring hospitalization, frequency of administration, and total out-of-pocket cost) were presented with a follow-up "no treatment" option. Participant preferences and WTP out of pocket were estimated by logistic regression. RESULTS: Participants (n = 296) preferred G-CSF regimens with lower out-of-pocket costs, lower risk of chemotherapy disruption, lower risk of infection, and greater convenience (one G-CSF injection per chemotherapy cycle). Participants' WTP was $1076 out of pocket per cycle to reduce the risk (high to low) of disrupting their chemotherapy schedule, $884 per cycle to reduce the risk (24% [high] to 7% [low]) of infection, and $851 per cycle to decrease the number of G-CSF injections (11 to 1) per cycle. CONCLUSIONS: Participants highly valued specific features of prophylactic G-CSF treatment including maintaining their chemotherapy schedule, lowering their risk of infection, and reducing the number of injections. Physicians should consider patient preferences to inform the best treatment choices for individual patients.

Visual compatibility of common nebulizer medications with 7% sodium chloride solution.

PURPOSE: The visual compatibility of hypertonic saline solution with various other drugs used for nebulizer therapy in cystic fibrosis (CF) was assessed. METHODS: Nebulized hypertonic saline solution has proved to be an effective adjunctive therapy for management of CF-related respiratory symptoms. Admixing of hypertonic saline solution and standard medications for nebulizer delivery has been suggested as a way to reduce the time-treatment burden on patients with CF, but that practice has been discouraged due to concerns about potential incompatibilities that could lead to precipitate formation (in the nebulizer or airway) and impeded drug delivery. For the study described here, visual and turbidimetric testing was conducted to assess the compatibility of admixtures of hypertonic saline solution and 11 medications widely used in CF (acetylcysteine, albuterol, atropine, cromolyn sodium, dexamethasone, glycopyrrolate, ipratropium, metaproterenol, sodium bicarbonate, terbutaline, and tobramycin). Three samples each of admixtures of the 11 drugs and 7% sodium chloride (experimental samples) or sterile water for injection (control samples) were prepared. The testing procedure entailed four turbidimetry measurements obtained at 15-minute intervals, as well as visual checks for signs of incompatibility (e.g., haze, particle or gas formation, alteration of color); analysis of variance was used to evaluate differences in test results between the experimental and control samples. RESULTS: Ten of the 11 medications assessed were visually compatible with 7% sodium chloride solution, as determined by serial turbidimetric testing and visual inspection; only cromolyn sodium was found to be visually incompatible with hypertonic saline. CONCLUSION: Eleven medications used in nebulizers for the treatment of CF were visually compatible with 7% sodium chloride solution.

Prophylactic ketoconazole shampoo for tinea capitis in a high-risk pediatric population.

OBJECTIVES: Although topical agents for the treatment of tinea capitis decrease viable fungal elements and reduce shedding, their use as a prophylactic agent has not been investigated. This study evaluated the effectiveness of a prophylactic ketoconazole shampoo (Nizoral 2%) protocol to reduce the number of clinically evident tinea capitis infections in a high-risk African American, urban population. METHODS: We conducted a retrospective analysis of a ketoconazole prophylaxis protocol that was implemented at an urban pediatric clinic for medically fragile children. Patients at high risk for tinea capitis received twice-weekly ketoconazole shampoo. The primary outcome of the study was a reduction in the number of documented tinea capitis infections between the 12-month preprotocol and 12-month postprotocol periods. A secondary outcome included the evaluation of predisposing risk factors for acquiring tinea infections. RESULTS: Ninety-seven patients, with a mean age of 8.06 years, were included. Most patients (78%) were African American. There were a total of 13 tinea capitis infections during the 12-month preprotocol period. During the 12-month postprotocol period, 41 infections were documented: 37 (90.2%) in the prophylaxis group and 4 (9.8%) in the nonprophylaxis group. The average numbers of per-patient infections in the postprotocol period were 0.79 and 0.08 in the prophylaxis and nonprophylaxis groups, respectively. Initiation of prophylaxis did not reduce tinea capitis infections (p=NS). Previous history of infection and a high level of care were significant predictors of infections (p<0.05). CONCLUSIONS: Improved hygiene, adherence to prescribed treatment regimens, and prevention of recurrent environmental exposure to surviving fomites should be stressed in high-risk patients and supersede the need for an antifungal (ketoconazole shampoo) prophylaxis protocol.

Phase II study of weekly docetaxel and capecitabine in patients with metastatic breast cancer.

PURPOSE: This phase II study evaluated the safety and efficacy of weekly docetaxel and capecitabine in patients with metastatic breast cancer. PATIENTS AND METHODS: Thirty-nine patients with metastatic breast cancer received 30 mg/m2 of docetaxel on days 1, 8, and 15 in combination with capecitabine 800 mg/m2 twice daily on days 1-21, repeated every 28 days. RESULTS: The median number of treatment cycles was 4 (range, 1-20 cycles). Grade 3 toxicities per patient were asthenia (n = 7; 18%), diarrhea (n = 7; 18%), nausea/vomiting (n = 5; 13%), stomatitis (n = 5; 13%), neutropenia (n = 5; 13%), and hand-foot syndrome (n = 4; 10%). There were only 2 grade 4 toxicities, febrile neutropenia and pulmonary embolism. The overall response rate was 44% (95% confidence interval (CI), 28%-60%), median duration of response was 9.1 months (95% CI, 6.2-12 months), and median time to progression was 5.5 months (95% CI, 3.7-7.3 months). CONCLUSION: Weekly docetaxel with capecitabine was active with acceptable toxicities. Additional trials to define the optimal schedule of docetaxel and capecitabine are justified.