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The study aims to summarise the literature on cancer care pathways at the diagnostic and treatment phases. The objectives are to find factors influencing the delivery of cancer care pathways; to highlight any interrelating factors; to find gaps in the literature concerning areas of research; to summarise the strategies and recommendations implemented in the studies.

The study used a qualitative approach and developed a causal loop diagram to summarise the current literature on cancer care pathways, from screening and diagnosis to treatment. A total of 46 papers was finally included in the analysis, which highlights the recurring themes in the literature.

The study highlights the myriad areas of research applied to cancer care pathways. Factors influencing the delivery of cancer care pathways were classified into different albeit interrelated themes. These include access barriers to care, hospital emergency admissions, fast track diagnostics, delay in diagnosis, waiting time to treatment and strategies to increase system efficiency.

As far as the authors know, this is the first study to present a visual representation of the complex relationship between factors influencing the delivery of cancer care pathways.

Delay in histologically confirming rectal cancer may lead to late treatment as histological confirmation is required prior to chemo-radiotherapy or surgical intervention. Multidisciplinary colorectal meetings indicate that there are patients who require multiple tissue biopsy episodes prior to histologically confirming rectal cancer. The purpose of this paper is to examine a quality improvement (QI) measure’s impact on tissue biopsy process diagnostic yield.

The authors performed the study in two phases (pre- and post-QI), between February 2012 and April 2014 in a district general hospital. The QI measures were derived from process mapping a rectal cancer diagnostic pathway. The primary outcome was to assess the tissue biopsy process diagnostic yield. The secondary outcome included total breaches for a 62-day target in the pre- and post-QI study phases.

There was no significant difference in demographics or referral mode in both study phases. There were 81 patients in the pre-QI phase compared to 38 in the post-QI phase, 68 per cent and 74 per cent were referred via the two-week wait urgent pathway, respectively. Diagnostic tissue biopsy process yield improved from 58.1 to 77.6 per cent after implementing the QI measure (p=0.02). The 62-day target breach was reduced from 14.8 to 3.5 per cent (p=0.42).

Simple QI measures can achieve significant improvements in rectal cancer diagnostic tissue biopsy process yields. A multidisciplinary approach, involving process mapping and cause and effect modelling, proved useful tools.

A process mapping exercise and QI measures resulted in significant improvements in diagnostic yield, reducing the episodes per patient before histological diagnosis was confirmed.

Ovarian cancer (OC) is the most common type of gynecologic cancer in the world with a high rate of mortality. Due to manifestation of generic symptoms and absence of specific biomarkers, OC is usually diagnosed at a late stage. Machine learning models can be employed to predict driver genes implicated in causative mutations.

In the present study, a comprehensive next generation sequencing (NGS) analysis of whole exome sequences of 47 OC patients was carried out to identify clinically significant mutations. Nine functional features of 708 mutations identified were input into a machine learning classification model by employing the eXtreme Gradient Boosting (XGBoost) classifier method for prediction of OC driver genes.

The XGBoost classifier model yielded a classification accuracy of 0.946, which was superior to that obtained by other classifiers such as decision tree, Naive Bayes, random forest and support vector machine. Further, an interaction network was generated to identify and establish correlations with cancer-associated pathways and gene ontology data.

The final results revealed 12 putative candidate cancer driver genes, namely LAMA3, LAMC3, COL6A1, COL5A1, COL2A1, UGT1A1, BDNF, ANK1, WNT10A, FZD4, PLEKHG5 and CYP2C9, that may have implications in clinical diagnosis.

Higher caseloads are associated with better outcomes for many conditions treated in secondary and tertiary care settings, including colorectal cancer (CRC). There is little known whether such volume-outcome relationship exist in primary care settings. The purpose of this paper is to examine general practitioner (GP) CRC-specific caseload for possible associations with referral pathways, disease stage and CRC patients’ overall survival.

The paper retrospectively analyses a prospectively maintained CRC database for 2009-2014 in a single district hospital providing bowel cancer screening and tertiary rectal cancer services.

Of 1,145 CRC patients, 937 (81.8 per cent) were diagnosed as symptomatic cancers. In total, 210 GPs from 44 practices were stratified according to their CRC caseload over the study period into low volume (LV, 1-4); medium volume (MV, 5-7); and high volume (HV, 8-21 cases). Emergency presentation (LV: 49/287 (17.1 per cent); MV: 75/264 (28.4 per cent); HV: 105/386 (27.2 per cent); p=0.007) and advanced disease at presentation (LV: 84/287 (29.3 per cent); MV: 94/264 (35.6 per cent); HV: 144/386 (37.3 per cent); p=0.034) was more common amongst HV GPs. Three-year mortality risk was significantly higher for HV GPs (MV: (hazard ratio) HR 1.185 (confidence interval=0.897-1.566), p=0.231, and HV: HR 1.366 (CI=1.061-1.759), p=0.016), but adjustment for emergency presentation and advanced disease largely accounted for this difference. There was some evidence that HV GPs used elective cancer pathways less frequently (LV: 166/287 (57.8 per cent); MV: 130/264 (49.2 per cent); HV: 182/386 (47.2 per cent); p=0.007) and more selectively (CRC/referrals: LV: 166/2,743 (6.1 per cent); MV: 130/2,321 (5.6 per cent); HV: 182/2,508 (7.3 per cent); p=0.048).

Higher GP CRC caseload in primary care may be associated with advanced disease and poorer survival; more work is required to determine the reasons and to develop targeted intervention at local level to improve elective referral rates.

Traditional Malaysian vegetables, also known as ulam, are believed to have healing properties among the local community. Ulam is commonly reported to have high antioxidant content which makes it a popular food. The purpose of this paper is to determine the teratogenic potential of eight ulam, using zebrafish model. The tested ulam were Cosmos caudatus, Gynura procumbens, Labisia pumila var. alata, Phaleria macrocarpa, Polygonum minus, Piper sarmentosum, Premna foetida and Sauropus androgynous.

Methanol extract of ulam was prepared using the maceration method. Various concentrations of extracts were tested against fish embryo short-term toxicity test. The lethal concentration (LC₅₀) and teratogenic effect of the ulam were determined.

Among all tested species, L. pumila, P. foetida and S. androgynous showed 100% lethal effect towards zebrafish embryos at concentrations of 10 µg/mL, 1,000 µg/mL and 100 µg/mL, respectively. The three ulam have exhibited teratogenic effect on zebrafish embryos after 72 h post-fertilization. L. pumila had induced yolk sac edema at 1.0 µg/mL for normalized measurement of 108.3 ± 2.0% (which is higher than negative control, p < 0.05, median = 110.7%), while P. foetida had induced pericardial edema at 100 µg/mL for normalized measurement of 124.0 ± 4.6% (which is higher than negative control, p < 0.05, median = 124.3%). On the other hand, S. androgynus induced curve trunk at 30 µg/mL for the presence of 70.9 ± 4.2%.

The teratogenic effect of L. pumila, P. foetida and S. androgynous suggests the possible disruption in the embryogenesis in zebrafish, namely Notch, vascular endothelial growth factor (VEGF) and retinoic acid pathways. The results of ulam gave possible implications and insights on the cancer pathways involved, which could be a useful target for cancer research. This is the first report on teratogenicity evaluation of Malaysian ulam showing relationship to cancer pathways by using zebrafish embryo model.

Genetic risk for depressive disorders is poorly understood despite consistent suggestions of a high heritable component. Most genetic studies have focused on risk associated with single variants, a strategy which has so far only yielded small (often non-replicable) risks for depressive disorders. In this paper we argue that more substantial risks are likely to emerge from genetic variants acting in synergy within and across larger neurobiological systems (polygenic risk factors). We show how knowledge of major integrated neurobiological systems provides a robust basis for defining and testing theoretically defensible polygenic risk factors. We do this by describing the architecture of the overall stress response. Maladaptation via impaired stress responsiveness is central to the aetiology of depression and anxiety and provides a framework for a systems biology approach to candidate gene selection. We propose principles for identifying genes and gene networks within the neurosystems involved in the stress response and for defining polygenic risk factors based on the neurobiology of stress-related behaviour. We conclude that knowledge of the neurobiology of the stress response system is likely to play a central role in future efforts to improve genetic prediction of depression and related disorders.

The purpose of this paper is to propose a unified definition of integrated palliative care (IPC), and to identify the elements that facilitate or hinder implementation of an integrated palliative care system (IPCS).

A scoping review of the conceptualization and essential elements of IPC was undertaken, based on a search of the PubMed, Scopus and ISI Web of Science databases. The search identified 79 unduplicated articles; 43 articles were selected for content analysis.

IPC is coordinated and collaborative across different health organizations, levels of care and types of providers. Eight key elements facilitate implementation of an IPCS: coordination, early patient identification, patient-centered services, care continuity, provider education and training, a standard implementation model and screening tool, shared information technology system, and supportive policies and funding. These elements were plotted as a “Circle of Integrated Palliative Care System Elements.”

This paper offers researchers an inclusive definition of IPC and describes the essential elements of its successful implementation.

This study provides evidence from researchers on five continents, offering insights from multiple countries and cultures on the topic of IPC. The findings of this thematic analysis could assist international researchers aiming to develop a standard evaluative model or assess the level of integration in a health care system’s delivery of palliative care.

This chapter presents a framework for an action research based intervention to develop and transform sustainable healthcare in a regional context. The framework is illustrated by the case of the Regional Cancer Centre (RCC) West in western Sweden.

The framework draws upon and develops Pettigrew’s context–content–process model of strategic change and applies it to the unfolding narrative of the change effort. The empirical focus is the activities of a learning platform consisting of the RCC leadership, senior cancer physicians designated as process owners and an action research team. Data were collected from documents, observations of the learning platform, notes from meetings and interviews. Outcome data were obtained via the self-reporting of the physicians.

The learning platform established the capability for wide ranging development and quality improvement on the 23 cancer pathways as well as some support activities around principles of patient-centred care. A clear result is greater inter-organisational collaboration between care professionals as well as the introduction of new medicines, clinical methods, joint learning activities and new forms of measurement and monitoring of care practices. All of the improved measures are sustained.

Whilst there is no shortage of rhetoric on patient-centred care, the reality is that in complex healthcare systems solutions such as process-oriented approaches often fail. This case presents a model and an approach that eschews clear visions for change and instead places an emphasis on dialogue, participation, professional autonomy and collaborative communities as means for achieving the patient-centred ideal. The case also shows the value of seeing sustainable health systems as being grounded on practitioner–scholar collaboration that combines practical knowing with scientific knowledge.

Much work about health reform and systems improvement in healthcare looks at shortcomings and universal problems facing health systems, but rarely are accomplishments dissected and analyzed internationally. The purpose of this paper is to address this knowledge gap by examining the lessons learned from health system reform and improvement efforts in 60 countries.

In total, 60 low-, middle- and high-income countries provided a case study of successful health reform, which was gathered into a compendium as a recently published book. Here, the extensive source material was re-examined through inductive content analysis to derive broad themes of systems change internationally.

Nine themes were identified: improving policy, coverage and governance; enhancing the quality of care; keeping patients safe; regulating standards and accreditation; organizing care at the macro-level; organizing care at the meso- and micro-level; developing workforces and resources; harnessing technology and IT; and making collaboratives and partnerships work.

These themes provide a model of what constitutes successful systems change across a wide sample of health systems, offering a store of knowledge about how reformers and improvement initiators achieve their goals.

Few comparative international studies of health systems include a sufficiently wide selection of low-, middle- and high-income countries in their analysis. This paper provides a more balanced approach to consider where achievements are being made across healthcare, and what we can do to replicate and spread successful examples of systems change internationally.

The purpose of this paper is to identify actual (as-is) patient pathway variation among breast cancer patients and to investigate the relationship between pathways and the cost incurred by patients.

Both quantitative and qualitative methods were employed to analyze data from four Swedish hospital groups. Quantitative methods include event-log data mining and statistical analyses on the related patient cost from the Swedish breast cancer quality registry and case-costing system. Qualitative methods included collaboration with and interviewing domain experts.

Unique pathways, followed by only one patient, were generally costlier than the most and less frequent pathways. Earlier study findings are confirmed for mastectomy patients, with more frequent pathways having a lower cost, whereas contradicting and inconclusive results emerged for the partial mastectomy patient groups. Highest variation in pathways was identified for patients receiving chemotherapy.

The common belief – if one follows a standardized patient pathway, then the cost will be lower – should be re-examined based on the actual pathways that occur in reality.

The relationships between patient pathways and patient cost allow more complex insights, beyond the general causal relationship between successfully implementing a “to-be” care pathway and lower cost. This highlights data-driven research’s importance, where actual pathways (as-is) provide more useful information than to-be care pathways.