Management of endocrine resistant breast cancer

Metastatic breast cancer (MBC) may present de novo but more commonly develops in women initially presenting with early breast cancer despite the widespread use of adjuvant hormonal and cytotoxic chemotherapy. MBC is incurable. Hormone sensitive MBC eventually becomes resistant to endocrine therapy in most women. Anthracyclines are the agents of choice in the treatment of endocrine resistant MBC. With the widespread use of anthracyclines in the adjuvant setting, taxanes have become the agents of choice for many patients. Recently capecitabine has become established as a standard of care for patients pretreated with anthracyclines and taxanes. However, a range of agents have activity as third line treatment. These include gemcitabine, vinorelbine and platinum analogues. The sequential use of non-cross resistant single agents rather than combination therapy is preferable in most women with MBC. Even though combination therapy can improve response rates and increase progression free interval, there is no robust evidence to indicate an advantage in terms of overall survival. Moreover, combination therapy is associated with a higher toxicity rate and poor quality of life. There is no role for dose-intense therapy, high dose therapy or maintenance chemotherapy outside the context of a clinical trial. The introduction of trastuzumab, monoclonal antibody targeting growth factor receptors, has improved the therapeutic options for women with tumours overexpressing HER2/neu. DNA micro-array profiles of tumours can potentially help to individualise therapy in future. Molecular targeted therapy has the potential to revolutionise the management of MBC.

Incidence of unilateral arm lymphoedema after breast cancer : a systematic review and meta-analysis

Background The body of evidence related to breast-cancer-related lymphoedema incidence and risk factors has substantially grown and improved in quality over the past decade. We assessed the incidence of unilateral arm lymphoedema after breast cancer and explored the evidence available for lymphoedema risk factors. Methods We searched Academic Search Elite, Cumulative Index to Nursing and Allied Health, Cochrane Central Register of Controlled Trials (clinical trials), and Medline for research articles that assessed the incidence or prevalence of, or risk factors for, arm lymphoedema after breast cancer, published between January 1, 2000, and June 30, 2012. We extracted incidence data and calculated corresponding exact binomial 95% CIs. We used random effects models to calculate a pooled overall estimate of lymphoedema incidence, with subgroup analyses to assess the effect of different study designs, countries of study origin, diagnostic methods, time since diagnosis, and extent of axillary surgery. We assessed risk factors and collated them into four levels of evidence, depending on consistency of findings and quality and quantity of studies contributing to findings. Findings 72 studies met the inclusion criteria for the assessment of lymphoedema incidence, giving a pooled estimate of 16·6% (95% CI 13·6–20·2). Our estimate was 21·4% (14·9–29·8) when restricted to data from prospective cohort studies (30 studies). The incidence of arm lymphoedema seemed to increase up to 2 years after diagnosis or surgery of breast cancer (24 studies with time since diagnosis or surgery of 12 to <24 months; 18·9%, 14·2–24·7), was highest when assessed by more than one diagnostic method (nine studies; 28·2%, 11·8–53·5), and was about four times higher in women who had an axillary-lymph-node dissection (18 studies; 19·9%, 13·5–28·2) than it was in those who had sentinel-node biopsy (18 studies; 5·6%, 6·1–7·9). 29 studies met the inclusion criteria for the assessment of risk factors. Risk factors that had a strong level of evidence were extensive surgery (ie, axillary-lymph-node dissection, greater number of lymph nodes dissected, mastectomy) and being overweight or obese. Interpretation Our findings suggest that more than one in five women who survive breast cancer will develop arm lymphoedema. A clear need exists for improved understanding of contributing risk factors, as well as of prevention and management strategies to reduce the individual and public health burden of this disabling and distressing disorder.

Polymorphisms in inflammation pathway genes and endometrial cancer risk

BACKGROUND Experimental and epidemiologic evidence have suggested that chronic inflammation may play a critical role in endometrial carcinogenesis. METHODS To investigate this hypothesis, a two-stage study was carried out to evaluate single-nucleotide polymorphisms (SNP) in inflammatory pathway genes in association with endometrial cancer risk. In stage I, 64 candidate pathway genes were identified and 4,542 directly genotyped or imputed SNPs were analyzed among 832 endometrial cancer cases and 2,049 controls, using data from the Shanghai Endometrial Cancer Genetics Study. Linkage disequilibrium of stage I SNPs significantly associated with endometrial cancer (P < 0.05) indicated that the majority of associations could be linked to one of 24 distinct loci. One SNP from each of the 24 loci was then selected for follow-up genotyping. Of these, 21 SNPs were successfully designed and genotyped in stage II, which consisted of 10 additional studies including 6,604 endometrial cancer cases and 8,511 controls. RESULTS Five of the 21 SNPs had significant allelic odds ratios (ORs) and 95% confidence intervals (CI) as follows: FABP1, 0.92 (0.85-0.99); CXCL3, 1.16 (1.05-1.29); IL6, 1.08 (1.00-1.17); MSR1, 0.90 (0.82-0.98); and MMP9, 0.91 (0.87-0.97). Two of these polymorphisms were independently significant in the replication sample (rs352038 in CXCL3 and rs3918249 in MMP9). The association for the MMP9 polymorphism remained significant after Bonferroni correction and showed a significant association with endometrial cancer in both Asian- and European-ancestry samples. CONCLUSIONS These findings lend support to the hypothesis that genetic polymorphisms in genes involved in the inflammatory pathway may contribute to genetic susceptibility to endometrial cancer. Impact statement: This study adds to the growing evidence that inflammation plays an important role in endometrial carcinogenesis.

Prevention of surgical site infection in total joint arthroplasty : an international tertiary care center survery

Background Prevention strategies are critical to reduce infection rates in total joint arthroplasty (TJA), but evidence-based consensus guidelines on prevention of surgical site infection (SSI) remain heterogeneous and do not necessarily represent this particular patient population. Questions/Purposes What infection prevention measures are recommended by consensus evidence-based guidelines for prevention of periprosthetic joint infection? How do these recommendations compare to expert consensus on infection prevention strategies from orthopedic surgeons from the largest international tertiary referral centers for TJA? Patients and Methods A review of consensus guidelines was undertaken as described by Merollini et al. Four clinical guidelines met inclusion criteria: Centers for Disease Control and Prevention's, British Orthopedic Association, National Institute of Clinical Excellence's, and National Health and Medical Research Council's (NHMRC). Twenty-eight recommendations from these guidelines were used to create an evidence-based survey of infection prevention strategies that was administered to 28 orthopedic surgeons from members of the International Society of Orthopedic Centers. The results between existing consensus guidelines and expert opinion were then compared. Results Recommended strategies in the guidelines such as prophylactic antibiotics, preoperative skin preparation of patients and staff, and sterile surgical attire were considered critically or significantly important by the surveyed surgeons. Additional strategies such as ultraclean air/laminar flow, antibiotic cement, wound irrigation, and preoperative blood glucose control were also considered highly important by surveyed surgeons, but were not recommended or not uniformly addressed in existing guidelines on SSI prevention. Conclusion Current evidence-based guidelines are incomplete and evidence should be updated specifically to address patient needs undergoing TJA.

Classification of cancer-related death certificates using machine learning

Background Cancer monitoring and prevention relies on the critical aspect of timely notification of cancer cases. However, the abstraction and classification of cancer from the free-text of pathology reports and other relevant documents, such as death certificates, exist as complex and time-consuming activities. Aims In this paper, approaches for the automatic detection of notifiable cancer cases as the cause of death from free-text death certificates supplied to Cancer Registries are investigated. Method A number of machine learning classifiers were studied. Features were extracted using natural language techniques and the Medtex toolkit. The numerous features encompassed stemmed words, bi-grams, and concepts from the SNOMED CT medical terminology. The baseline consisted of a keyword spotter using keywords extracted from the long description of ICD-10 cancer related codes. Results Death certificates with notifiable cancer listed as the cause of death can be effectively identified with the methods studied in this paper. A Support Vector Machine (SVM) classifier achieved best performance with an overall F-measure of 0.9866 when evaluated on a set of 5,000 free-text death certificates using the token stem feature set. The SNOMED CT concept plus token stem feature set reached the lowest variance (0.0032) and false negative rate (0.0297) while achieving an F-measure of 0.9864. The SVM classifier accounts for the first 18 of the top 40 evaluated runs, and entails the most robust classifier with a variance of 0.001141, half the variance of the other classifiers. Conclusion The selection of features significantly produced the most influences on the performance of the classifiers, although the type of classifier employed also affects performance. In contrast, the feature weighting schema created a negligible effect on performance. Specifically, it is found that stemmed tokens with or without SNOMED CT concepts create the most effective feature when combined with an SVM classifier.

An MMP13-selective inhibitor delays primary tumor growth and the onset of tumor-associated osteolytic lesions in experimental models of breast cancer

We investigated the effects of the matrix metalloproteinase 13 (MMP13)-selective inhibitor, 5-(4-{4-[4-(4-fluorophenyl)-1,3-oxazol-2-yl]phenoxy}phenoxy)-5-(2-methoxyethyl) pyrimidine-2,4,6(1H,3H,5H)-trione (Cmpd-1), on the primary tumor growth and breast cancer-associated bone remodeling using xenograft and syngeneic mouse models. We used human breast cancer MDA-MB-231 cells inoculated into the mammary fat pad and left ventricle of BALB/c Nu/Nu mice, respectively, and spontaneously metastasizing 4T1.2-Luc mouse mammary cells inoculated into mammary fat pad of BALB/c mice. In a prevention setting, treatment with Cmpd-1 markedly delayed the growth of primary tumors in both models, and reduced the onset and severity of osteolytic lesions in the MDA-MB-231 intracardiac model. Intervention treatment with Cmpd-1 on established MDA-MB-231 primary tumors also significantly inhibited subsequent growth. In contrast, no effects of Cmpd-1 were observed on soft organ metastatic burden following intracardiac or mammary fat pad inoculations of MDA-MB-231 and 4T1.2-Luc cells respectively. MMP13 immunostaining of clinical primary breast tumors and experimental mice tumors revealed intra-tumoral and stromal expression in most tumors, and vasculature expression in all. MMP13 was also detected in osteoblasts in clinical samples of breast-to-bone metastases. The data suggest that MMP13-selective inhibitors, which lack musculoskeletal side effects, may have therapeutic potential both in primary breast cancer and cancer-induced bone osteolysis.

Molecular profiling of human mammary gland links breast cancer risk to a p27(+) cell population with progenitor characteristics

Early full-term pregnancy is one of the most effective natural protections against breast cancer. To investigate this effect, we have characterized the global gene expression and epigenetic profiles of multiple cell types from normal breast tissue of nulliparous and parous women and carriers of BRCA1 or BRCA2 mutations. We found significant differences in CD44+ progenitor cells, where the levels of many stem cell-related genes and pathways, including the cell-cycle regulator p27, are lower in parous women without BRCA1/BRCA2 mutations. We also noted a significant reduction in the frequency of CD44+p27+ cells in parous women and showed, using explant cultures, that parity-related signaling pathways play a role in regulating the number of p27+ cells and their proliferation. Our results suggest that pathways controlling p27+ mammary epithelial cells and the numbers of these cells relate to breast cancer risk and can be explored for cancer risk assessment and prevention.

Clinicopathological relevance of BRAF mutations in human cancer

BRAF represents one of the most frequently mutated protein kinase genes in human tumours. The mutation is commonly tested in pathology practice. BRAF mutation is seen in melanoma, papillary thyroid carcinoma (including papillary thyroid carcinoma arising from ovarian teratoma), ovarian serous tumours, colorectal carcinoma, gliomas, hepatobiliary carcinomas and hairy cell leukaemia. In these cancers, various genetic aberrations of the BRAF proto-oncogene, such as different point mutations and chromosomal rearrangements, have been reported. The most common mutation, BRAF V600E, can be detected by DNA sequencing and immunohistochemistry on formalin fixed, paraffin embedded tumour tissue. Detection of BRAF V600E mutation has the potential for clinical use as a diagnostic and prognostic marker. In addition, a great deal of research effort has been spent in strategies inhibiting its activity. Indeed, recent clinical trials involving BRAF selective inhibitors exhibited promising response rates in metastatic melanoma patients. Clinical trials are underway for other cancers. However, cutaneous side effects of treatment have been reported and therapeutic response to cancer is short-lived due to the emergence of several resistance mechanisms. In this review, we give an update on the clinical pathological relevance of BRAF mutation in cancer. It is hoped that the review will enhance the direction of future research and assist in more effective use of the knowledge of BRAF mutation in clinical practice.

2nd ESMO consensus conference on lung cancer : early-stage non-small-cell lung cancer consensus on diagnosis, treatment and follow-up

To complement the existing treatment guidelines for all tumour types, ESMO organises consensus conferences to focus on specific issues in each type of tumour. The 2nd ESMO Consensus Conference on Lung Cancer was held on 11-12 May 2013 in Lugano. A total of 35 experts met to address several questions on non-small-cell lung cancer (NSCLC) in each of four areas: pathology and molecular biomarkers, first-line/second and further lines in advanced disease, earlystage disease and locally advanced disease. For each question, recommendations were made including reference to the grade of recommendation and level of evidence. This consensus paper focuses on early-stage disease. © The Author 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.

Demographics and survivial of a cohort of blood and breast cancer patients who developed heart failure following cancer treatment

Background/Aim: Cardiotoxicity resulting in heart failure is a devastating complication of cancer therapy. It is possible that a patient may survive cancer only to develop heart failure (HF), which is more deadly than cancer. The aim of this project was to profile the characteristics of patients at risk of cancer treatment induced heart failure. Methods: Linked Health Data Analysis of Queensland Cancer Registry (QCR) from 1996-2009, Death Registry and Hospital Administration records for HF and chemotherapy admissions were reviewed. Index heart failure admission must have occurred after the date of cancer registry entry. Results: A total of 15,987 patients were included in this analysis; 1,062 (6.6%) had chemotherapy+HF admission (51.4% Female) and 14,925 (93.4%) chemotherapy_no HF admission. Median age of chemotherapy+HF patients was 67 years (IQR 58 to 75) vs. 54 years (IQR 44 to 64) for chemotherapy_no HF admission. Chemotherapy+HF patients had increased risk of all cause mortality (HR 2.79 [95% CI 2.58-3.02] and 1.67 [95% CI, 1.54 to 1.81] after adjusting for age, sex, marital status, country of birth, cancer site and chemotherapy dose). Index HF admission occurred within one year of cancer diagnosis in 47% of HF patients with 80% of patinets having there index admission with 3 years. The number of chemotherapy cycles was not associated with significant reduction in survival time in chemotherapy+HF patients. Mean survival for heart failure patients was 5.3 years (95% CI, 4.99 - 5.62) vs.9.57 years (95% CI, 9.47-9.68) for chemotherapy_no HF admission patients. Conclusion: All-cause mortality was 67% higher in patients diagnosed with HF following chemotherapy in adjusted analysis for covariates. Methods to improve and better coordinate of the interdisciplinary care for cancer patients with HF involving cardiologists and oncologists are required, including evidence-based guidelines for the comprehensive assessment, monitoring and management of this cohort.

Adverse breast cancer treatment effects: The economic case for making rehabilitative programs standard of care

Purpose: The purpose of this work was to evaluate the patient-borne financial cost of common, adverse breast cancer treatment-associated effects, comparing cost across women with or without these side-effects. Methods: 287 Australian women diagnosed with early-stage breast cancer were prospectively followed starting at six months post-surgery for 12 months, with three-monthly assessment of detailed treatment-related side effects and their direct and indirect patient costs attributable to breast cancer. Bootstrapping statistics were used to analyze cost data and adjusted logistic regression was used to evaluate the association between costs and adverse events from breast cancer. Costs were inflated and converted from 2002 Australian to 2014 US dollars. Results: More than 90% of women experienced at least one adverse effect (i.e. post-surgical issue, reaction to radiotherapy, upper-body symptoms or reduced function, lymphedema, fatigue or weight gain). On average, women paid $5,636 (95%CI: $4,694, $6,577) in total costs. Women with any one of the following symptoms (fatigue, reduced upper-body function, upper-body symptoms) or women who report ≥4 adverse treatment-related effects, have 1.5 to nearly 4 times the odds of having higher healthcare costs than women who do not report these complaints (p<0.05). Conclusions: Women face substantial economic burden due to a range of treatment-related health problems, which may persist beyond the treatment period. Improving breast cancer care by incorporating prospective surveillance of treatment-related side effects, and strategies for prevention and treatment of concerns (e.g., exercise) has real potential for reducing patient-borne costs.

A systematic review of patient-reported outcome instruments of dermatologic adverse events associated with targeted cancer therapies

Purpose Dermatologic adverse events (dAEs) in cancer treatment are frequent with the use of targeted therapies. These dAEs have been shown to have significant impact on health-related quality of life (HRQoL). While standardized assessment tools have been developed for physicians to assess severity of dAEs, there is a discord between objective and subjective measures. The identification of patient-reported outcome (PRO) instruments useful in the context of targeted cancer therapies is therefore important in both the clinical and research settings for the overall evaluation of dAEs and their impact on HRQoL. Methods A comprehensive, systematic literature search of published articles was conducted by two independent reviewers in order to identify PRO instruments previously utilized in patient populations with dAEs from targeted cancer therapies. The identified PRO instruments were studied to determine which HRQoL issues relevant to dAEs were addressed, as well as the process of development and validation of these instruments. Results Thirteen articles identifying six PRO instruments met the inclusion criteria. Four instruments were general dermatology (Skindex-16©, Skindex-29©, Dermatology Life Quality Index (DLQI), and DIELH-24) and two were symptom-specific (functional assessment of cancer therapy-epidermal growth factor receptor inhibitor-18 (FACT-EGFRI-18) and hand-foot syndrome-14 (HFS-14)). Conclusions While there are several PRO instruments that have been tested in the context of targeted cancer therapy, additional work is needed to develop new instruments and to further validate the instruments identified in this study in patients receiving targeted therapies.

Improving wound management for residents in Residential Aged Care Facilities: National dissemination and implementation of the evidence based Champions for Skin Integrity Program

Overview The incidence of skin tears, pressure injuries and chronic wounds increases with age [1-4] and therefore is a serious issue for staff and residents in Residential Aged Care Facilities (RACFs). A pilot project funded in Round 2 of the Encouraging Best Practice in Residential Aged Care (EBPRAC) program by the then Australian Government Department of Health and Ageing found that a substantial proportion of residents in aged care facilities experienced pressure injuries, skin tears or chronic wounds. It also found the implementation of the evidence based Champions for Skin Integrity (CSI) model of wound care was successful in significantly decreasing the prevalence and severity of wounds in residents, improving staff skills and knowledge of evidence based wound management, increasing staff confidence with wound management, increasing implementation of evidence based wound management and prevention strategies, and increasing staff awareness of their roles in evidence based wound care at all levels [5]. Importantly, during the project, the project team developed a resource kit on evidence based wound management. Two critical recommendations resulting from the project were that: - The CSI model or a similar strategic approach should be implemented in RACFs to facilitate the uptake of evidence based wound management and prevention - The resource kit on evidence based wound management should be made available to all Residential Aged Care Facilities and interested parties A proposal to disseminate or rollout the CSI model of wound care to all RACFs across Australia was submitted to the department in 2012. The department approved funding from the Aged Care Services Improvement Healthy Ageing Grant (ACSIHAG) at the same time as the Round 3 of the Encouraging Better Practice in Aged Care (EBPAC) program. The dissemination involved two crucial elements: 1. The updating, refining and distribution of a Champions for Skin Integrity Resource Kit, more commonly known as a CSI Resource Kit and 2. The presentation of intensive one day Promoting Healthy Skin “Train the Trainer” workshops in all capital cities and major regional towns across Australia Due to demand, the department agreed to fund a second round of workshops focussing on regional centres and the completion date was extended to accommodate the workshops. Later, the department also decided to host a departmental website for a number of clinical domains, including wound management, so that staff from the residential aged care sector had easy access to a central repository of helpful clinical resource material that could be used for improving the health and wellbeing of their older adults, consumers and carers. CSI Resource Kit Upgrade and Distribution: At the start of the project, a full evidence review was carried out on the material produced during the EBPRAC-CSI Stage 1 project and the relevant evidence based changes were made to the documentation. At the same time participants in the EBPRAC-CSI Stage 1 project were interviewed for advice on how to improve the resource material. Following this the documentation, included in the kit, was sent to independent experts for peer review. When this process was finalised, a learning designer and QUT’s Visual Communications Services were engaged to completely refine and update the design of the resources, and combined resource kit with the goal of keeping the overall size of the kit suitable for bookshelf mounting and the cost at reasonable levels. Both goals were achieved in that the kit is about the same size as a 25 mm A4 binder and costs between $19.00 and $28.00 per kit depending on the size of the print run. The dissemination of the updated CSI resource kit was an outstanding success. Demand for the kits was so great that a second print run of 2,000 kits was arranged on top of the initial print run of 4,000 kits. All RACFs across Australia were issued with a kit, some 2,740 in total. Since the initial distribution another 1,100 requests for kits has been fulfilled as well as 1,619 kits being distributed to participants at the Promoting Healthy Skin workshops. As the project was winding up a final request email was sent to all workshop participants asking if they required additional kits or resources to distribute the remaining kits and resources. This has resulted in requests for 200 additional kits and resources. Feedback from the residential aged care sector and other clinical providers who have interest in wound care has been very positive regarding the utility of the kit, (see Appendix 4). Promoting Healthy Skin Workshops The workshops also exceeded the project team’s initial objective. Our goal of providing workshop training for staff from one in four facilities and 450 participants was exceeded, with overwhelming demand for workshop places resulting in the need to provide a second round of workshops across Australia. At the completion of the second round, 37 workshops had been given, with 1286 participants, representing 835 facilities. A number of strategies were used to promote the workshops ranging from invitations included in the kit, to postcard mail-outs, broadcast emailing to all facilities and aged care networks and to articles and paid advertising in aged care journals. The most effective method, by far, was directly phoning the facilities. This enabled the caller to contact the relevant staff member and enlist their support for the workshop. As this is a labour intensive exercise, it was only used where numbers needed bolstering, with one venue rising from 3 registrants before the calls to 53 registrants after. The workshops were aimed at staff who had the interest and the capability of implementing evidence-based wound management within their facility or organisation. This targeting was successful in that a large proportion (68%) of participants were Registered Nurses, Nurse Managers, Educators or Consultants. Twenty percent were Endorsed Enrolled Nurses with the remaining 12% being made up of Personal Care Workers or Allied Health Professionals. To facilitate long term sustainability, the workshop employed train-the-trainer strategies. Feedback from the EBPRAC-CSI Stage 1 interviews was used in the development of workshop content. In addition, feedback from the workshop conducted at the end of the EBPRAC-CSI Stage 1 project suggested that change management and leadership training should be included in the workshops. The program was trialled in the first workshop conducted in Brisbane and then rolled out across Australia. Participants were asked to complete pre and post workshop surveys at the beginning and end of the workshop to determine how knowledge and confidence improved over the day. Results from the pre and post surveys showed significant improvements in the level of confidence in attendees’ ability to implement evidence based wound management. The results also indicated a significant increase in the level of confidence in ability to implement change within their facility or organisation. This is an important indication that the inclusion of change management/leadership training with clinical instruction can increase staff capacity and confidence in translating evidence into practice. To encourage the transfer of the evidence based content of the workshop into practice, participants were asked to prepare an Action Plan to be followed by a simple one page progress report three months after the workshop. These reports ranged from simple (e.g. skin moisturising to prevent skin tears), to complex implementation plans for introducing the CSI model across the whole organisation. Outcomes described in the project reports included decreased prevalence of skin tears, pressure injuries and chronic wounds, along with increased staff and resident knowledge and resident comfort. As stated above, some organisations prepared large, complex plans to roll out the CSI model across their organisation. These plans included a review of the organisation’s wound care system, policies and procedures, the creation of new processes, the education of staff and clients, uploading education and resource material onto internal electronic platforms and setting up formal review and evaluation processes. The CSI Resources have been enthusiastically sought and incorporated into multiple health care settings, including aged care, acute care, Medicare Local intranets (e.g. Map of Medicine e-pathways), primary health care, community and home care organisations, education providers and New Zealand aged and community health providers. Recommendations: Recommendations for RACFs, aged care and health service providers and government  Skin integrity and the evidence-practice gap in this area should be recognised as a major health issue for health service providers for older adults, with wounds experienced by up to 50% of residents in aged care settings (Edwards et al. 2010). Implementation of evidence based wound care through the Champions for Skin Integrity model in this and the pilot project has demonstrated the prevalence of wounds, wound healing times and wound infections can be halved.  A national program and Centre for Evidence Based Wound Management should be established to: - expand the reach of the model to other aged care facilities and health service providers for older adults - sustain the uptake of models such as the Champions for Skin Integrity (CSI) model - ensure current resources, expertise and training are available for consumers and health care professionals to promote skin integrity for all older adults  Evidence based resources for the CSI program and similar projects should be reviewed and updated every 3 – 4 years as per NH&MRC recommendations  Leadership and change management training is fundamental to increasing staff capacity, at all levels, to promote within-organisation dissemination of skills and knowledge gained from projects providing evidence based training Recommendations for future national dissemination projects  A formal program of opportunities for small groups of like projects to share information and resources, coordinate activities and synergise education programs interactively would benefit future national dissemination projects - Future workshop programs could explore an incentive program to optimise attendance and reduce ‘no shows’ - Future projects should build in the capacity and funding for increased follow-up with workshop attendees, to explore the reasons behind those who are unable to translate workshop learnings into the workplace and identify factors to address these barriers.

A two-arm cluster randomized control trial to determine the effectiveness of a pressure ulcer prevention bundle for critically ill patients

Purpose This study tested the effectiveness of a pressure ulcer (PU) prevention bundle in reducing the incidence of PUs in critically ill patients in two Saudi intensive care units (ICUs). Design A two-arm cluster randomized experimental control trial. Methods Participants in the intervention group received the PU prevention bundle, while the control group received standard skin care as per the local ICU policies. Data collected included demographic variables (age, diagnosis, comorbidities, admission trajectory, length of stay) and clinical variables (Braden Scale score, severity of organ function score, mechanical ventilation, PU presence, and staging). All patients were followed every two days from admission through to discharge, death, or up to a maximum of 28 days. Data were analyzed with descriptive correlation statistics, Kaplan-Meier survival analysis, and Poisson regression. Findings The total number of participants recruited was 140: 70 control participants (with a total of 728 days of observation) and 70 intervention participants (784 days of observation). PU cumulative incidence was significantly lower in the intervention group (7.14%) compared to the control group (32.86%). Poisson regression revealed the likelihood of PU development was 70% lower in the intervention group. The intervention group had significantly less Stage I (p = 002) and Stage II PU development (p = 026). Conclusions Significant improvements were observed in PU-related outcomes with the implementation of the PU prevention bundle in the ICU; PU incidence, severity, and total number of PUs per patient were reduced. Clinical Relevance Utilizing a bundle approach and standardized nursing language through skin assessment and translation of the knowledge to practice has the potential to impact positively on the quality of care and patient outcome.