Rapid Adaptation of Breast Radiation Therapy Use During the Coronavirus Disease 2019 Pandemic at a Large Academic Cancer Center in Canada.

PURPOSE: Mitigation strategies to balance the risk of coronavirus disease 2019 (COVID-19) infection against oncologic risk in patients with breast cancer undergoing radiation therapy have been deployed. To this end, shorter hypofractionated regimens have been recommended where appropriate, with prioritization of radiation therapy by oncologic risk and omission or deferral of radiation therapy for lower risk cases. Timely adoption of these measures reduces COVID-19 risk to both patients and health care workers and preserves resources. Herein, we present our early response and adaptation of breast radiation therapy utilization during the COVID-19 pandemic at a large academic cancer center in Canada. METHODS AND MATERIALS: A state of emergency was announced in Ontario on March 17, 2020, owing to the COVID-19 pandemic. Emergency guidelines were instituted. To examine our response, the number of weekly breast radiation therapy starts, type of breast radiation therapy, and patient age were compared from March 1 to April 30, 2020 to the same period in 2019. RESULTS: After the declaration of emergency in Ontario, there was a decrease of 39% in radiation therapy starts in 2020 compared with 2019 (79 vs 129, P < .001). There was a relative increase in the proportion of patients receiving regional nodal irradiation (RNI) in 2020 compared with 2019 (46% vs 29%, respectively), with the introduction of hypofractionated RNI in 2020 (27 of 54 cases, 50%). A smaller proportion of patients starting radiation therapy were aged >50 years in 2020, 66% (78 of 118) versus 83% (132 of 160) in 2019, P = .0027. CONCLUSIONS: A significant reduction in breast radiation therapy starts was noted during the early response to the COVID-19 pandemic, with prioritization of radiation therapy to patients associated with higher oncologic risk requiring RNI. A quick response to a health care crisis is critical and is of particular importance for higher volume cancer sites where the potential effect on resources is greater.

Interprofessional education in a student-led emergency department: A realist evaluation.

This article reports a realist evaluation undertaken to identify factors that facilitated or hindered the successful implementation of interprofessional clinical training for undergraduate students in an emergency department. A realist evaluation provides a framework for understanding how the context and underlying mechanisms affect the outcome patterns of an intervention. The researchers gathered both qualitative and quantitative data from internal documents, semi-structured interviews, observations, and questionnaires to study what worked, for whom, and under what circumstances in this specific interprofessional setting. The study participants were medical, nursing, and physiotherapy students, their supervisors, and two members of the emergency department's management staff. The data analysis indicated that the emergency ward provided an excellent environment for interprofessional education (IPE), as attested by the students, supervisors, and the clinical managers. An essential prerequisite is that the students have obtained adequate skills to work independently. Exemplary conditions for IPE to work well in an emergency department demand the continuity of effective and encouraging supervision throughout the training period and supervisors who are knowledgeable about developing a team.

Changing caring behaviours in rehabilitation after a hip fracture - A tool for empowerment?

Different rehabilitation programs after surgery have been presented to improve the outcome for patients with a hip fracture. Empowerment has been suggested as useful, but requires a change in the caring behaviours of health professionals. The aim with this study was to evaluate if training and supervision of the nursing staff could alter caring behaviours. A case-control study of nursing staff treating hip fracture patients was performed at a hospital with two sites. Training and supervision was given to the nursing staff at the intervention site. The intervention focused on creating positive care interaction by using eight guidelines. The evaluation was performed with recordings of a constructed caring situation before training, and observations of care situations at the ward before and after intervention. The results showed no differences at baseline between the two sites in the caring behaviours. After intervention, significant effects of caring behaviours were seen in seven out of eight guidelines, the effect sizes ranged from medium to large. The findings indicate that the nursing staff can change caring behaviours and facilitate the empowerment of patients with a hip fracture.

Coordination pays off: a comparison of two models for organizing hip fracture care, outcomes and costs.

BACKGROUND AND PURPOSE: With the "graying" of the population, hip fractures place an increasing burden on health systems and call for efficient forms of care. The aim was to compare two models of organizing hip fracture care at one university hospital working at two sites. The differences in organization were coordinated care provided in one of the sites and traditional care, divided between different institutions, in the other. MATERIAL AND METHODS: The study was conducted at a Swedish university hospital and included all 503 hip fracture patients, admitted during the 1-year period of February 2009 through January 2010. Patient gender, age, type of fracture, admission and discharge dates were documented. The patients were surveyed of their health-related quality of life at the time of admission and at 4 and 12 months after discharge. The costs for the inpatient care episode were estimated using three costing methods. RESULTS: The coordinated care model resulted in a shorter hospital stay and consistently lower costs. There was no difference between patient-reported quality of life. INTERPRETATION: The care of hip fracture patients coordinated by a geriatric ward throughout the whole care episode is more cost-efficient than uncoordinated where patients are transferred to other institutions for rehabilitation.

Power to the patient: care tracks and empowerment a recipe for improving rehabilitation for hip fracture patients.

BACKGROUND/AIM: New surgical procedures, early operation and medical optimisation in patients with hip fracture have shown positive results on length of hospital stay. Our aims were to investigate whether patient empowerment along with an individually designed, postoperative rehabilitation programme could reduce length of hospital stay and whether the patients would have better chances to return to their previous living. DESIGN/METHOD: Patients were recruited during a 12-month period 2009-2010, with an intervention group treated with an individually designed, postoperative rehabilitation programme and a control group treated in a traditional way according to the hospitals routines. Final assessment was performed 4 month after surgery. The postoperative programme for the intervention group consisted of four standardised care tracks adapted individually for the patients. Assessments of Activity of Daily Living, American Society of Anesthesiologists classification of medical disease status and Short Portable Mental Status Questionnaire and living conditions were used to determine which care track was most appropriate. The patients were cared for with focus of empowerment in their rehabilitation. RESULTS: The study involved 503 hip fracture patients, 285 patients in the intervention group and 218 patients in the control group. The mean length of stay was 4 days shorter in the intervention group than in the control group (p = 0.04). Varied only to a small extent between the age groups in the intervention group and was greater between the age groups in the control. Patients in the intervention group returned to their previous living in 90% compared with 80% in the control group (p < 0.05). There were no significant differences between the age groups. CONCLUSION: Patient empowerment administrated by specially trained nursing staff and with specialised, tailor-made rehabilitation programme may be of benefit in helping patients to a shorter hospital stay and to return to their previous living.

Context challenges the champion: improving hip fracture care in a Swedish university hospital.

PURPOSE: The purpose of this paper is to describe and explain a clinician-led improvement of a hip fracture care process in a university hospital, and to assess the results and factors helping and hindering change implementation. DESIGN/METHODOLOGY/APPROACH: The paper has a mixed methods case study design. Data collection was guided by a framework directing attention to the content and process of the change, its context and outcomes. FINDINGS: Using a multiprofessional project team, beneficial changes in the early parts of the care process were achieved, but inability to change surgical staff work practices meant that the original goal of operating patients within 24 hours was not reached. After three years, top management introduced a hospital-wide process improvement programme, which "took over" the responsibility for improving hip fracture care. RESEARCH IMPLICATIONS/LIMITATIONS: A clear vision why change is needed and what needs to be done, which is well communicated by a respected clinical leader, can motivate personnel, but other influences are also needed to bring about change. Without a plan agreed and supported by top management, changes are likely to be limited to parts of the process and improvements to patient care may be minimal. These and other findings may be applicable to similar situations in other services. ORIGINALITY/VALUE: This case study is an illustration of both the strengths and the weaknesses of a "bottom-up, clinician-champion-led improvement initiative" in a complex university hospital.

Regulation of human CYP2C18 and CYP2C19 in transgenic mice: influence of castration, testosterone, and growth hormone.

The hormonal regulation of human CYP2C18 and CYP2C19, which are expressed in a male-specific manner in liver and kidney in a mouse transgenic model, was examined. The influence of prepubertal castration in male mice and testosterone treatment of female mice was investigated, as was the effect of continuous administration of growth hormone (GH) to transgenic males. Prepubertal castration of transgenic male mice suppressed the expression of CYP2C18 and CYP2C19 in liver and kidney to female levels, whereas expression was increased for the endogenous female-specific mouse hepatic genes Cyp2c37, Cyp2c38, Cyp2c39, and Cyp2c40. Testosterone treatment of female mice increased CYP2C18 and CYP2C19 expression in kidney, and to a lesser extent in liver, but was without effect in brain or small intestine, where gene expression was not gender-dependent. Continuous GH treatment of transgenic males for 7 days suppressed hepatic expression of CYP2C19 (>90% decrease) and CYP2C18 ( approximately 50% decrease) but had minimal effect on the expression of these genes in kidney, brain, or small intestine. Under these conditions, continuous GH induced all four female-specific mouse liver Cyp2c genes in males to normal female levels. These studies indicate that the human CYP2C18 and CYP2C19 genes contain regulatory elements that respond to the endogenous mouse hormonal profiles, with androgen being the primary regulator of male-specific expression in kidney, whereas the androgen-dependent pituitary GH secretory pattern is the primary regulator of male-specific expression in liver in a manner that is similar to the regulation of the endogenous gender-specific hepatic genes.

Few alterations in clinical pathology and histopathology observed in a CYP2C18&19 humanized mice model.

BACKGROUND: This study was performed to characterize a gene-addition transgenic mouse containing a BAC (bacterial artificial chromosome) clone spanning the human CYP2C18&19 genes (tg-CYP2C18&19). METHODS: Hemizygous tg-CYP2C18&19, 11 week old mice were compared with wild-type littermates to obtain information regarding clinical status, clinical pathology and anatomical pathology. After one week of clinical observations, blood samples were collected, organs weighed, and tissues collected for histopathology. RESULTS: In males, the tissue weights were lower in tg-CYP2C18&19 than in wild-type mice for brain (p < or = 0.05), adrenal glands (p < or = 0.05) and brown fat deposits (p < or = 0.001) while the heart weight was higher (p < or = 0.001). In female tg-CYP2C18&19, the tissue weights were lower for brain (p < or = 0.001) and spleen (p < or = 0.001) compared to wild-type females. Male tg-CYP2C18&19 had increased blood glucose levels (p < or = 0.01) while females had decreased blood triglyceride levels (p < or = 0.01). CONCLUSION: Despite the observed alterations, tg-CYP2C18&19 did not show any macroscopic or microscopic pathology at the examined age. Hence, these hemizygous transgenic mice were considered to be viable and healthy animals.

Generation of mice transgenic for human CYP2C18 and CYP2C19: characterization of the sexually dimorphic gene and enzyme expression.

CYP2C19 is an important enzyme for human drug metabolism, and it also participates in the metabolism of endogenous substrates, whereas the CYP2C18 enzyme is not expressed in human liver despite high mRNA expression. Mice transgenic for the human CYP2C18 and CYP2C19 genes were generated. Quantitative mRNA analysis showed CYP2C18 and CYP2C19 transcripts in liver, kidneys, and heart to be expressed in a sexually dimorphic manner, with male mice having 2- to 100-fold higher levels. Transcript levels in the small intestine were somewhat higher than liver but were similar in both sexes. Transgene mRNA expression was much lower in lung and brain and least in the heart. Immunoblotting using an antipeptide antiserum, reactive with human CYP2Cs and mouse CYP2C70, revealed increased immunoreactive protein in liver microsomes from heterozygous transgenic male mice and a concomitant increase in 5'-hydroxylation of R-omeprazole and S-mephenytoin intrinsic clearance, consistent with CYP2C19 overexpression. A CYP2C18-specific antiserum showed that this enzyme was not expressed in livers or kidneys from heterozygous transgenic mice, but the antiserum had high affinity for recombinant CYP2C18 expressed in COS-7 cells. It is concluded that 1) both the CYP2C18 and CYP2C19 genes are subject to sexually dimorphic regulation in murine liver, kidney, and heart; 2) the CYP2C18 protein is not expressed in murine liver or kidney despite high levels of the corresponding mRNA; and 3) this transgenic model may be suitable for studying sex-dependent regulation of the human CYP2C genes and possibly serve as an in vivo model for CYP2C19-dependent drug metabolism.