Frequent high-level expression of the immunotherapeutic target Ep-CAM in colon, stomach, prostate and lung cancers

Epithelial cell adhesion molecule (Ep-CAM; CD326) is used as a target by many immunotherapeutic approaches, but little data are available about Ep-CAM expression in major human malignancies with respect to level, frequency, tumour stage, grade, histologic tumour type and impact on survival. We analysed by immunohistochemical staining tissue microarrays with 4046 primary human carcinoma samples from colon, stomach, prostate and lung cancers for both frequency and intensity of Ep-CAM expression under highly standardised conditions. A total of 3360 samples were analysable. High-level Ep-CAM expression was observed in 97.7% (n=1186) of colon, 90.7% of gastric (n=473), and 87.2% of prostate cancers (n=414), and in 63.9% of lung cancers (n=1287). No detectable Ep-CAM staining was found with only 0.4% of colon, 2.5% of gastric, 1.9% of prostate cancers, and 13.5% of lung cancers. The only significant correlation of Ep-CAM expression with tumour grading was observed in colon cancer where high-level Ep-CAM expression on grade 3 tumours was down to 92.1% (P<0.0001). Adenosquamous and squamous carcinomas of the lung had a lower percentage of high-level Ep-CAM expression compared to adenocarcinomas with 35.4 and 53.6%, respectively, and with 45.5 and 17.3% of tumours being Ep-CAM negative. With the exception of moderately differentiated colon carcinoma, where patients not expressing Ep-CAM on their tumours showed an inferior survival (P=0.0014), correlation of Ep-CAM expression with survival did not reach statistical significance for any of the other cancer indications and subgroups. In conclusion, the data strongly support the notion that Ep-CAM is a prime target for immunotherapies in major human malignancies. This is because the most common human cancers show (i) a low frequency of Ep-CAM-negative tumours, (ii) a high frequency of Ep-CAM expression on cells of a given tumour, and (iii) for most cancers, an insignificant influence of tumour staging, grading and histology on Ep-CAM expression

An overview of tissue engineering approaches for management of spinal cord injuries

Severe spinal cord injury (SCI) leads to devastating neurological deficits and disabilities, which necessitates spending a great deal of health budget for psychological and healthcare problems of these patients and their relatives. This justifies the cost of research into the new modalities for treatment of spinal cord injuries, even in developing countries. Apart from surgical management and nerve grafting, several other approaches have been adopted for management of this condition including pharmacologic and gene therapy, cell therapy, and use of different cell-free or cell-seeded bioscaffolds. In current paper, the recent developments for therapeutic delivery of stem and non-stem cells to the site of injury, and application of cell-free and cell-seeded natural and synthetic scaffolds have been reviewed

Recovery from musculoskeletal injury: the role of social support following a transport accident

BACKGROUND: Social support can be an important coping resource for persons recovering from injury. In this study, we examined the effects of family structure and sources of social support on physical health, persistent pain and return to work (RTW) outcomes following musculoskeletal injury (MSI) sustained in a transport accident. METHODS: Secondary analysis of Transport Accident Commission (TAC) cross-sectional surveys held in 2010 and 2011 was conducted. In total 1649 persons with MSI were identified and included. Family structure was determined by marital status and number of children. Sources of social support were measured as perceived help from family, friends, neighbours and employers. Physical health was measured with the Physical Component Summary (PCS) score of the Short-Form-12 Health Survey Version 2. Persistent pain was defined as self-reported persistent pain experienced in the last 3 months, and RTW was defined as being back at work for ≥3 months at time of interview. Multiple linear and logistic regressions were used for the analyses. RESULTS: Family and friends' support was associated with better physical health among persons with >1 day hospital stay. Being married or in a de facto relationship was associated with greater PCS score among non-hospitalised persons. Being widowed/separated/divorced was associated with more self-reported persistent pain (odds ratio 1.62 [95 % confidence intervals 1.11-2.37]). Support from family (0.40 [0.24-0.68]), friends (0.29 [0.17-0.47]) and neighbours (0.59 [0.41-0.84]) was associated with less persistent pain. Among women, support from family (0.09 [0.01-0.78]) was negatively associated with RTW, whereas support from friends (3.03 [1.15-8.02]) was positively associated with RTW. These associations were not observed among men. For both men (5.62 [2.77-11.38]) and women (7.22 [2.58-20.20]), support from employers was positively associated with RTW. CONCLUSION: Family structure and sources of social support had a positive impact on physical health, persistent pain and RTW following MSI. This study highlights the importance of identifying people who have limited access to a social support network. Those with limited access to social support after a transport accident could potentially benefit from the provision of formal sources of practical and psychological support

Mechanisms and impact of public reporting on physicians and hospitals' performance: A systematic review (2000-2020)

BACKGROUND: Public performance reporting (PPR) of physician and hospital data aims to improve health outcomes by promoting quality improvement and informing consumer choice. However, previous studies have demonstrated inconsistent effects of PPR, potentially due to the various PPR characteristics examined. The aim of this study was to undertake a systematic review of the impact and mechanisms (selection and change), by which PPR exerts its influence. METHODS: Studies published between 2000 and 2020 were retrieved from five databases and eight reviews. Data extraction, quality assessment and synthesis were conducted. Studies were categorised into: user and provider responses to PPR and impact of PPR on quality of care. RESULTS: Forty-five studies were identified: 24 on user and provider responses to PPR, 14 on impact of PPR on quality of care, and seven on both. Most of the studies reported positive effects of PPR on the selection of providers by patients, purchasers and providers, quality improvement activities in primary care clinics and hospitals, clinical outcomes and patient experiences. CONCLUSIONS: The findings provide moderate level of evidence to support the role of PPR in stimulating quality improvement activities, informing consumer choice and improving clinical outcomes. There was some evidence to demonstrate a relationship between PPR and patient experience. The effects of PPR varied across clinical areas which may be related to the type of indicators, level of data reported and the mode of dissemination. It is important to ensure that the design and implementation of PPR considered the perspectives of different users and the health system in which PPR operates in. There is a need to account for factors such as the structural characteristics and culture of the hospitals that could influence the uptake of PPR

The impact of price transparency on consumers and providers: A scoping review

Escalating levels of healthcare spending and price variation in the healthcare market have driven government and insurer interest in price transparency tools that are intended to help consumers shop for services and reduce overall healthcare spending. However, it is unclear whether the objectives of price transparency are being achieved. We conducted a scoping review to synthesize the impact of price transparency on consumer, provider, and purchaser behaviours and outcomes. Price transparency tools had weak impact overall on consumers due to low uptake, and mixed effects on providers. Price-aware patients chose less costly services that led to out-of-pocket cost savings and savings for health insurers; however, these savings did not translate into reductions in aggregate healthcare spending. Disclosure of list prices had no effect, however disclosure of negotiated prices prompted supply-side competition which led to decreases in prices for shoppable services

The impact of Australian healthcare reforms on emergency department time-based process outcomes: An interrupted time series study

BACKGROUND: In 2011, the Australian government introduced national healthcare reforms aimed at increasing the timeliness and quality of hospital care. The healthcare reforms included, but were not limited to, emergency department (ED) time-based targets, financial incentives, and public performance reporting of hospital data. We sought to evaluate the impact of the national healthcare reforms on ED time-based process outcomes. METHODS: A quasi-experimental study of ED presentations from 2006 to 2016 in the state of Victoria, Australia. Uncontrolled, interrupted time-series analyses were used to evaluate, by hospital peer groups, the effect of national healthcare reforms on: patient wait times for treatment; treatment within recommended time; and patient departure within four hours of arrival in ED. RESULTS: There were small improvements in ED time-based process outcomes following the introduction of the national healthcare reforms. These occurred in most hospital peer groups immediately and over the longer term, across the various triage categories. The largest improvements occurred in small hospitals and smallest improvements in medium sized hospitals. ED time-based targets, now abolished by the Australian government, were not achieved in any hospital peer groups. CONCLUSIONS: Our findings suggest that national healthcare reforms had the potential to prompt fundamental changes in ED processes leading to significant improvements in ED performances across most hospital peer groups but were generally unable to reach the ED targets imposed nationally. ED performances also varied by hospital peer groups. Attention to ED time-based process outcomes within hospital peer groups may provide insights into hospital practices that could improve the quality and efficiency of ED care

Public disclosure of hospital clinicians' performance data: insights from medical directors

Objective This study gathered information from public hospital chief medical officers to better understand underlying mechanisms through which public reporting affects institutional behavioural change and decision making towards quality improvement. Methods This qualitative study used thematic analysis of 17 semistructured, in-depth interviews among a peak group of medical directors representing 26 health services in Victoria, Australia. Results The medical directors indicated a high level of in-principle support for public reporting of identifiable, individual clinician-level data. However, they also described varying conceptual understanding of what public reporting of performance data is. Overall, they considered public reporting of individual clinicians' performance data a means to improve health care quality, increase transparency and inform consumer healthcare decision making. Most identified caveats that would need to be met before such data should be publicly released, in particular the need to resolve issues around data quality and timeliness, context and interpretation and ethics. Acknowledgement of the public's right to access individual clinician-level data was at odds with some medical directors' belief that such reporting may diminish trust between clinicians and their employers, thus eroding rather than motivating quality improvement. Conclusions Public reporting of identifiable individual healthcare clinicians' performance data is an issue that merits robust research and debate given the effects such reporting may have on doctors and on hospital quality and safety. What is known about the topic? The public reporting of individual clinician-level data is a mechanism used in some countries, but not in Australia, for increasing health care transparency and quality. Clinician-level public reporting of doctors' performance attracts contention and debate in Australia. What does this paper add? This paper informs debate around the public reporting of individual clinician-level performance data. Among a discrete cohort of senior hospital administrators in Victoria, Australia, there was strong in-principle support for such public reporting as a means to improve hospital quality and safety. What are the implications for practitioners? Before public reporting of individual clinician performance data could occur in Australia, resolution of issues would be required relating to legality and ethics, data context and interpretation, data quality and timeliness

The use of public performance reporting by general practitioners: a study of perceptions and referral behaviours

BACKGROUND: Public performance reporting (PPR) of hospital data aims to improve quality of care in hospitals and to inform consumer choice. In Australia, general practitioners (GPs) are gatekeepers to secondary care with patients requiring their referral for non-emergency access. Despite their intermediary role, GPs have been generally overlooked as potential users of PPR of hospital data, with the majority of the PPR research focussing on consumers, surgeons and hospitals. METHODS: We examined the use of PPR of hospital data by GPs when referring patients to hospitals. Semi-structured interviews were conducted with 40 GPs, recruited via the Victorian Primary Care Practice-Based Research Network and GP teaching practices in Victoria, Australia. The interviews were recorded, transcribed and analysed thematically. RESULTS: We found that the majority of GPs did not use PPR when referring patients to hospitals. Instead, they relied mostly on informal sources of information such as their own or patients' previous experiences. Barriers that prevented GPs' use of PPR in their decision making included: lack of awareness and accessibility; perceived lack of data credibility; restrictive geographical catchments for certain hospitals; limited choices of public hospitals in regional and rural areas; and no mandatory PPR for private hospitals. CONCLUSIONS: Our findings suggest that lack of PPR awareness prevented GPs from using it in their referral practice. As gatekeepers to secondary care, GPs are in a position to guide patients in their treatment decisions and referrals using available PPR data. We suggest that there needs to be greater involvement by GPs in the development of hospital performance and quality indicators in Australia if GPs are to make greater use of them. The indicators require further development before GPs perceive them as valid, credible, and of use for informing their referral practices

The impact of public performance reporting on cancer elective surgery waiting times: a data linkage study

BACKGROUND: Excessive waiting times for cancer elective surgery are a concern in publicly funded healthcare systems. Several countries including Australia have introduced healthcare reforms involving time-based targets and public performance reporting (PPR) of hospital data. However, there is mixed evidence of their benefits. We sought to examine the impact of targets and PPR of cancer elective surgery waiting times on access to breast, bowel and lung cancer elective surgery. METHODS: We analysed routinely-collected linked data on admissions and waiting times for patients aged 15 years or over (n = 199,885) who underwent cancer surgery in a public hospital in Victoria, Australia over a 10-year period. We conducted difference-in-differences analyses to compare waiting times before (2006-07 to 2011-12) and after (2012-13 to 2015-16) the introduction of PPR in meeting these targets. RESULTS: Across all cancer types, urgent patients were all treated within 30 days before and after PPR. Following PPR, there was a slight increase in the mean waiting times across all cancer types and urgency categories. Patients with lung cancer waited on average two and half days longer for treatment and patients with breast cancer waited on average half-a-day less. There was no effect of PPR on waiting times for patients with bowel cancer across urgency categories. CONCLUSIONS: Our findings suggest that time-based targets and PPR had minimal impact on surgical waiting times. This may be due to reasonable waiting times prior to PPR, improved efficiency being masked by 20% growth in the population, lack of public knowledge that waiting times are publicly reported, or lack of real-time reporting to drive behavioural change. The use of generic elective surgery recommended waiting time measures for cancer is discussed