Applications of liquid biopsy in the Pharmacological Audit Trail for anticancer drug development.

Anticancer drug development is a costly and protracted activity, and failure at late phases of clinical testing is common. We have previously proposed the Pharmacological Audit Trail (PhAT) intended to improve the efficiency of drug development, with a focus on the use of tumour tissue-based biomarkers. Blood-based 'liquid biopsy' approaches, such as targeted or whole-genome sequencing studies of plasma circulating cell-free tumour DNA (ctDNA) and circulating tumour cells (CTCs), are of increasing relevance to this drug development paradigm. Liquid biopsy assays can provide quantitative and qualitative data on prognostic, predictive, pharmacodynamic and clinical response biomarkers, and can also enable the characterization of disease evolution and resistance mechanisms. In this Perspective, we examine the promise of integrating liquid biopsy analyses into the PhAT, focusing on the current evidence, advances, limitations and challenges. We emphasize the continued importance of analytical validation and clinical qualification of circulating tumour biomarkers through prospective clinical trials.

A importância dos registros de enfermagem no contexto avaliativo da auditoria / The importance of nursing records within the audit assessment context

Objetivo: Analisar a importância dos registros de enfermagem no contexto avaliativo da auditoria. Método: Trata-se de uma revisão integrativa da literatura realizada nas bases de dados LILACS, MEDLINE e BDENF, por meio dos descritores Auditoria de Enfermagem; Auditoria Clínica; Registros de Enfermagem; Anotações de Enfermagem e Enfermagem. A busca foi realizada de 12 de janeiro a 26 de fevereiro de 2018 e selecionados 17 artigos que compõem o estudo. Resultados: a importância dos registros de enfermagem no contexto avaliativo da auditoria se dá pela investigação da qualidade do cuidado prestado por meio das evidências proporcionadas nos registro/anotações de enfermagem no portuário do paciente, evitar prejuízos na continuação do cuidado, intensificar sugestões de implantações de valores educacionais por meio da educação continuada e permanente, resgatar os valores econômicos perdidos por glosas em contas hospitalares e promover a melhoria da qualidade da assistência. Conclusão: foi possível verificar que, mesmo sendo uma prática que deva ser realizada com qualidade, o processo de auditora ainda encontra muita fragilidade nas informações encontradas nos diversos registros do profissional de enfermagem, o que acarreta grandes prejuízos.

Objective: To analyze the importance of nursing records in the evaluative context of the audit. Method: This is an integrative literature review performed in the LILACS, MEDLINE and BDENF databases using the descriptors Nursing Audit; Clinical audit; Nursing records; Nursing and Nursing Notes. The search was performed from January 12 to February 26, 2018, selecting a total of 17 articles. Results: the importance of nursing records in the evaluative context of the audit is due to the investigation of the quality of care provided through the evidence provided in the nursing records/annotations in the patient's chart, avoiding losses in the continuation of care, intensifying suggestions for implantation of nursing care, educational values through continuing and continuing education, recovering the economic values lost by disallowances in hospital bills and promoting the improvement of the quality of care. Conclusion: it was possible to verify that, even though it is a practice that should be performed with quality, the audit process still finds a lot of fragility in the information found in the various records of the nursing professional, which causes great losses.

Outcomes following colorectal cancer surgery: Results from a population-based study in Queensland, Australia, using quality indicators.

RATIONALE, AIMS AND OBJECTIVES: Colorectal cancer (CRC) is one of the most common cancers diagnosed worldwide, and rates are continuing to rise. Surgery is the primary treatment for CRC, and our aim was to examine clinical outcomes following major resection using a series of established quality indicators and to identify factors associated with poor clinical outcomes. METHOD: This population-based retrospective study included 4321 patients with diagnosed with CRC in 2012 and 2014 in Queensland, Australia, who underwent a major resection. Primary outcomes included in-hospital mortality, 30-day unplanned readmission, extended hospital stay (>21 days), and 30- and 90-day mortality. Multivariable logistic regression modelling was conducted to establish factors independently associated with each outcome of interest. RESULTS: Overall, in-hospital mortality was 1.5%, 3.0% had an unplanned readmission, 8% had an extended hospital stay, and 30- and 90-day postoperative mortality was 1.6% and 3.1%, respectively. After adjustment, we found that factors such as older age, presence of comorbidities, emergency admission, and stoma formation were significantly associated with poorer outcomes with these findings being consistent across each of the outcomes of interest. In addition to these factors, the risk of 90-day mortality was significantly elevated for patients with advanced stage disease (OR = 1.95, CI 1.35-2.82). Sex, primary site, hospital volume, residential location, nor socioeconomic status was found to be associated with any of the outcomes of interest. CONCLUSION: Overall, the risk of poorer clinical outcomes for CRC patients in Queensland, Australia, is low. There is however a subgroup of patients at particularly elevated risk of poorer outcomes following CRC. Strategies to reduce the poorer clinical outcomes this group of patients experience should be explored.

Team Training in the Perioperative Arena: A Methodology for Implementation and Auditing Behavior.

Preventable medical errors in the operating room are most often caused by ineffective communication and suboptimal team dynamics. TeamSTEPPS is a government-funded, evidence-based program that provides tools and education to improve teamwork in medicine. The study hospital implemented TeamSTEPPS in the operating room and merged the program with a surgical safety checklist. Audits were performed to collect both quantitative and qualitative information on time out (brief) and debrief conversations, using a standardized audit tool. A total of 1610 audits over 6 months were performed by live auditors. Performance was sustained at desired levels or improved for all qualitative metrics using χ2 and linear regression analyses. Additionally, the absolute number of wrong site/side/person surgery and unintentionally retained foreign body counts decreased after TeamSTEPPS implementation.

How is feedback from national clinical audits used? Views from English National Health Service trust audit leads.

OBJECTIVE: To explore how the output of national clinical audits in England is used by professionals and whether and how their impact could be enhanced. METHODS: A mixed-methods study with the primary recipients of four national clinical audits of cancer care of 607 local audit leads, 274 (45%) completed a questionnaire and 32 participated in an interview. Our questions focused on how the audits were used and whether barriers existed to using the audits for local service improvement. We described variation in questionnaire responses between the audits using chi-squared tests. Results are reported as percentages with their 95% confidence intervals. Qualitative data were analysed using Framework analysis. RESULTS: More than 90% of survey respondents believed that the audit findings were relevant to their clinical work, and interviewees described how they used the audits for a range of purposes. Forty-two percent of survey respondents said they had changed their clinical practice, and 56% had implemented service improvements in response to the audits. The degree of change differed between the four audits, evident in both the questionnaire and the interview data. In the interviews, two recurring barriers emerged: (1) the importance of data quality, which, in turn, influenced the perceived relevance and validity of the audit data and therefore the ability to make changes based on it and (2) the need for clear presentation of benchmarked local performance data. The perceived authority and credibility of the professional bodies supporting the audits was a key factor underpinning the use of the audit findings. CONCLUSION: National cancer audit and feedback is used to improve services, but their impact could be enhanced by improving the data quality and relevance of feedback.

Head and neck cancer in the south west of England, Hampshire, and the Isle of Wight: trends in survival 1996-2008.

There are reasons why survival may have improved in people with head and neck cancer, but few studies have reported on trends in the UK, and results are not consistent. We examined recent trends in survival for people diagnosed with head and neck cancer in the south west of England. Patients were identified over four one-year audits in a population (roughly 6.5 million) served by five cancer networks, and the work was collated by the South West Public Health Observatory (SWPHO) tumour panel. The SWPHO cancer registry provided data on death. Prognostic data, including stage, time to treatment, and deprivation index were extracted or derived from clinical records. A total of 2164 cases of oral, laryngeal, and pharyngeal squamous cell carcinomas (SCC) were diagnosed. Crude total 5-year mortality decreased from 55% (95% CI 50.3-59.4) in people diagnosed in 1996 to 44% (95% CI 37.9-46.4) in those diagnosed in 2003 (p<0.001). Adjusted hazard ratios (HRs) for death within five years of diagnosis for surveys 2, 3, and 4 (compared with survey 1), respectively, were reduced in subsequent groups: HR 0.79 (95% CI 0.64-0.98), HR 0.70 (95% CI 0.56-0.87), and HR 0.72 (95% CI 0.58-0.90) (chi square for trend, p<0.001). Improvements over time were most pronounced among those with late-stage disease and with pharyngeal tumours. We have shown that survival has improved for people with head and neck cancer. Further large prospective studies are required to understand how quality of care, treatment, aetiology of tumour, individual risk, and behaviour contribute to survival.

A story of scrutiny and fear: Australian midwives' experiences of an external review of obstetric services, being involved with litigation and the impact on clinical practice.

OBJECTIVES: to describe Australian midwives' experiences of an external review of obstetric services, involvement in legal proceedings and the impact on midwives' clinical practice and personal wellbeing. BACKGROUND: the external review process (commonly referred to as the 'Douglas Inquiry') was initiated by a state government and was in response to hospital staff and consumer complaints that focused on anomalies in client care and a significantly high rate of adverse outcomes and clinical errors. It took place within the context of a number of legal proceedings against medical practitioners. As a result, some midwives employed by the hospital were called to give evidence at a variety of legal forums. DESIGN: a qualitative study using an explorative descriptive design. Snowball sampling was used to invite 16 Australian midwives to participate in a tape-recorded interview. Thematic analysis and the techniques associated with constant comparison were used to analyse the data. SETTING: Australian maternity tertiary referral centre. FINDINGS: the analysis identified two overarching themes, 'A story of scrutiny' and 'A story of fear', each with a number of subthemes. 'A story of scrutiny' consists of three subthemes. 'A cloak and dagger affair' reflects the midwives' sense of being and feeling 'exposed' and 'vulnerable' whilst simultaneously being 'kept in the dark' and uninformed during the review process. The subtheme 'Being thrown to the wolves' describes the midwives' experiences of being involved, as witnesses, in medico-legal proceedings. The third subtheme, 'The Inquiry followed them home' outlines the effect on midwives' emotional wellbeing and personal relationships. The second major theme, 'A story of fear' again consists of a number of subthemes. 'Feeling unsafe at work: a culture of fear' describes the midwives' experiences of working within an environment they perceive as driven by the fear of litigation. In order to protect themselves and maintain a sense of control, the midwives adopted a number of strategies to 'feel safe' including defensive decision making and moving towards a medical philosophy of care. These concepts are captured within the subtheme 'Covering your back: setting boundaries'. The impact on relationships between midwives, women and medical practitioners is described within the subtheme 'Professional relationship: coloured by fear'. The effect on midwives' confidence and the resultant negative emotions elicited make up the subtheme 'Between a rock and a hard place: the midwives' distressing dilemma'. Finally the subtheme, 'Opting out: the changing nature of professional work practices' describes the specific professional decisions and work strategies that midwives made about their ability to continue working in an environment that they perceived as threatening. CONCLUSION: the findings suggest that the midwife participants in this small study were totally unprepared and ill equipped, both personally and professionally, to deal with the consequences of working within an environment that was the centre of a number of high profile legal proceedings and an extensive external review of obstetric services. The midwives were naïve about legal processes and unprepared for the legal 'game playing' and media attention that often accompanies court proceedings. Despite the fact that no midwife faced litigation, the participants described their work environment as becoming increasingly stressful and permeated by a culture of fear. In turn, this situation has reinforced the need for some midwives to adopt an 'institution' ideology which reinforces birth as an abnormal event that needs to be medically managed. This has led to changes in professional and personal work practices. The findings also have implications for the midwifery workforce and retention. Although the findings are context specific, this study provides valuable insight into the phenomena of fear of litigation and its impact on midwifery practice. Given the similarities concerning obstetric litigation in some other Western nations, the findings have relevance in the international midwifery arena.

A robust clinical review process: the catalyst for clinical governance in an Australian tertiary hospital.

OBJECTIVE: To determine if a robust clinical review process can influence an organisation's response to adverse patient outcomes. DESIGN AND SETTING: Retrospective analysis of the activity and outputs of the Clinical Review Committee (CRC) of a university-affiliated tertiary hospital from 1 September 2002 to 30 June 2006. MAIN OUTCOME MEASURES: Engagement of clinicians (number on CRC, number interviewed for the clinical review process, number of specific referrals from clinicians); and numbers of cases reviewed, system issues identified, recommendations made to the hospital board, and ensuing actions. RESULTS: A multidisciplinary CRC with 34 members established a robust clinical review process and identified 5925 cases for initial case review. Of these, 2776 (46.8%) fulfilled one or more of the specified criteria for adverse events and progressed to detailed review; 342 of these (12.3%) were classed as serious or major. A total of 317 staff (11%) were interviewed, and 881 system issues were identified, resulting in 98 specific recommendations being made to the Clinical Board and implementation of 81 practice changes (including seven hospital-wide projects) to improve patient care. CONCLUSION: A robust, multidisciplinary clinical review process with strong links to managers and policymakers can influence an organisation's response to adverse patient outcomes and underpin a clinical governance framework.

The creation of an international audit and database of equine colic surgery: survey of attitudes of surgeons.

REASONS FOR PERFORMING STUDY: Currently, there is a lack of available evidence-based data concerning the optimum treatments for horses affected by different types of colic and this precludes the application of clinical audit in this area. In order to accumulate such data, a large-scale, multicentre database of the outcomes of colic surgery is proposed. The attitudes of surgeons is an important consideration in determining the feasibility of developing this database. OBJECTIVES: To assess attitudes and opinions of equine surgeons concerning clinical audit and to assess the perceived advantages and problems of setting up a large-scale international audit/database of colic surgery. METHODS: Interviews were conducted with 30 equine surgeons (large animal/equine surgeons who are diplomates of either the American College of Veterinary Surgeons or the European College of Veterinary Surgeons). Questionnaires were sent by e-mail to 98 equine surgeons. RESULTS: Face to face interviews were conducted (n = 30) and 43/98 completed questionnaires received (44%). The results of the 2 techniques were very similar. There was generally a high level of interest in the development of a large scale database of colic surgery, but perceived problems included time to collect and submit data, and confidentiality issues. A minority of surgeons reported that they were undertaking any form of specific monitoring of the results of colic surgery within their hospitals. CONCLUSIONS: There is a good level of interest among equine surgeons to develop a large scale database of colic surgery and most would be willing to contribute data from their own hospitals provided that data collection is quick and easy, and that confidentiality is maintained.

Audit, quality control, and performance in thoracic surgery: a North American perspective.

Although difficult to precisely define, health care quality is often measured by components of structure, outcomes, and process. One way for thoracic surgeons to evaluate their practices is to compare themselves with evidence-based national guidelines. Outcomes data are often generated from entries into large patient databases. The largest examples of these databases include the STS National Databases and the VA/ACS NSQIP programs. Each of these has unique features, but there is the common goal of enabling participants to examine their surgical outcomes and results relative to others. The data integrity of these databases is high. The new STS composite quality score for CABG combines providers' outcome and practice data into a calculated index for comparison with national averages. In addition to providing meaningful information regarding surgical outcomes and quality, these databases are used as the basis for risk-adjusted models to accurately predict surgical morbidity and mortality. These models can be used as auditing tools against which surgeon- and site-specific morbidity and mortality can be compared with predicted values. As practices and methods continue to evolve, measures of quality--and therefore quality itself--will continue to improve, resulting in better patient care.

Audit, quality control, and performance in thoracic surgery--a European perspective.

The internal audit process is preparatory to independent, external quality control assessment. The current status of quality control implementation in European thoracic surgery comprises existing and functioning but uncoordinated resources. There is a need to coordinate these resources to achieve a consistent external audit process.

Statewide identification of adverse events using retrospective nurse review: methods and outcomes.

This study was conducted as part of a two-state study of the validity of hospital discharge data for adverse event (AE) surveillance. Reliability of nurse identification of AEs was assessed through comparison with physician review. Nurses reviewed 6,296 medical records selected from two sampling frames. All were patients in 41 Utah acute care hospitals and surgery patients in 36 Missouri hospitals. A total of 1,035 records were independently reviewed by physicians using the same methods. Overall agreement between nurse and physician findings in Utah and Missouri, at the case level, was 78.5% (238/303) and 68.2% (499/732), respectively. Nurse review of medical records to identify AEs represents a cost-effective alternative to physician review for large-scale and ongoing patient safety improvements and surveillance purposes.