Protocol for a national, multicentre study of post-endoscopy colorectal and upper gastrointestinal cancers: The POET study.

AIM: The primary aim of the study is to define the post-colonoscopy colorectal cancer (PCCRC) three-year rate and the post-endoscopy upper gastrointestinal cancer (PEUGIC) three-year rate across public hospitals in Aotearoa New Zealand. METHOD: This retrospective cohort study will be conducted via the trainee-led STRATA Collaborative network. All public hospitals in Aotearoa New Zealand will be eligible to participate. Data will be collected on all adult patients who are diagnosed with colorectal adenocarcinoma within 6 to 48 months of a colonoscopy and all adult patients diagnosed with gastroesophageal cancer within 6 to 48 months of an upper gastrointestinal endoscopy. The study period will be from 2010 to 2022. The primary outcome is the PCCRC 3-year rate and the PEUGIC 3-year rate. Secondary aims are to define and characterize survival after PCCRC or PEUGIC, the cause of PCCRC as based on the World Endoscopy Organization System of Analysis definitions, trends over time, and centre level variation. CONCLUSION: This protocol describes the methodology for a nationwide retrospective cohort study on PCCRC and PEUGIC in Aotearoa New Zealand. These data will lay the foundation for future studies and quality improvement initiatives.

Combining TP53 mutation and isoform has the potential to improve clinical practice.

The clinical importance of assessing and combining data on TP53 mutations and isoforms is discussed in this article. It gives a succinct overview of the structural makeup and key biological roles of the isoforms. It then provides a comprehensive summary of the roles that p53 isoforms play in cancer development, therapy response and resistance. The review provides a summary of studies demonstrating the role of p53 isoforms as potential prognostic indicators. It further provides evidence on how the presence of TP53 mutations may affect one or more of these activities and the association of p53 isoforms with clinicopathological data in various tumour types. The review gives insight into the present diagnostic hurdles for identifying TP53 isoforms and makes recommendations to improve their evaluation. In conclusion, this review offers suggestions for enhancing the identification and integration of TP53 isoforms in conjunction with mutation data within the clinical context.

Impact of implementing the aseptic compounding management system, Medcura, on internal error rates within an oncology pharmacy aseptic unit: a mixed methods evaluation.

BACKGROUND: As cancer survivorship improves, pressure on oncology services to provide safe, timely treatments increases. Traditional manual compounding processes are error prone, putting patients at risk. Additionally, errors have a detrimental impact on service delivery and staff morale. Information technology is increasingly utilised to improve safety and service delivery of systemic anti-cancer therapy (SACT). The compounding process control system, Medcura, was developed to manage the end-to-end process and reduce transcription and calculation errors. OBJECTIVES: To evaluate the impact of implementing Medcura on internal errors and staff perceptions of errors. METHOD: An aseptic process control system, Medcura, was implemented in a busy pharmacy chemotherapy production unit. Internal error and severity data were collected and analysed for 14 months before and during implementation, and 24 months after implementation. In addition, one-to-one semi-structured interviews were carried out with pharmacy staff, pre- and post-implementation. Interviews were transcribed and thematically analysed. RESULTS: Error rates decreased after implementation from 2.9% to 2.1%. The types of error detected also changed with a decrease in worksheet and labelling errors, and an increase in assembly errors. The severity of the errors, as a percentage of total errors made, also decreased after implementation. Staff were predominantly positive about Medcura; it reduced the number of errors, eased the preparation of worksheets and labels, reduced pressure and work-related stress, and improved job satisfaction. CONCLUSIONS: Implementing Medcura has resulted in a reduction in both error rate and severity. Specifically, errors related to label and worksheet generation have seen the largest reduction. Staff have viewed these changes positively and report reduced levels of work-related stress. Further development and roll-out will improve patient safety and staff morale.

Impact of Clinical Data Veracity on Cancer Genomic Research.

Genomic analysis of tumors is transforming our understanding of cancer. However, although a great deal of attention is paid to the accuracy of the cancer genomic data itself, less attention has been paid to the accuracy of the associated clinical information that renders the genomic data useful for research. In this brief communication, we suggest that omissions and errors in clinical annotations have a major impact on the interpretation of cancer genomic data. We describe our discovery of annotation omissions and errors when reviewing an already carefully annotated colorectal cancer gene expression dataset from our laboratory. The potential importance of clinical annotation omissions and errors was then explored using simulation analyses with an independent genomic dataset. We suggest that the completeness and veracity of clinical annotations accompanying cancer genomic data require renewed focus by the oncology research community, when planning new collections and when interpreting existing cancer genomic data.

Barriers and solutions to trainee-led research collaboratives in New Zealand.

This article seeks to describe our experience enabling large-scale collaborative studies within trainee-led surgical research networks, to highlight systemic barriers to the use of this methodology and to propose solutions that will facilitate trainee-led collaborative research in New Zealand.

Initiation of a formalized precision medicine program in gynecologic oncology.

OBJECTIVE: In an effort to better incorporate precision medicine into clinical practice, we initiated a pilot project to screen, discuss, and genetically characterize patients with metastatic or recurrent gynecologic malignancies for whom no curative standard of care exists. METHODS: In 7/2014, we initiated a multi-disciplinary Precision Medicine Board (PMB) whose purpose was to apply molecular profiling to select and prioritize early phase clinical trial enrollment for high-risk gynecologic malignancies. Additional objectives were to record outcomes and enable scientific discussions of mutations which may foster local translational research. FoundationOne was the preferred genomic platform; results were reviewed by a team comprised of disease site specialists, phase I trialists, and basic and translational scientists affiliated with the Gynecologic Cancer Program. A detailed database for each patient was created and is followed prospectively for treatment use and resultant outcomes. RESULTS: To date, we have presented 62 cases with interpretable FoundationOne testing on 60 tumor samples (31 ovarian, 18 uterine, 9 cervical, and 4 other female genital tract). Significant genomic alterations were commonly found in all tumor types (median: 3); TP53 (45%) and PIK3CA (27%) were the most frequently noted mutations; however, molecular profiling resulted in identification of few actionable mutations (6%). To date, we have matched 4 patients on therapies based on actionable mutations. CONCLUSIONS: The predominant function of our PMB is establishment of a forum to enhance research while providing clinical care for refractory malignancies. We have matched patients with specific mutations to ongoing trials and are developing investigator-initiated studies based on trends within genomic profiling results. Longer-term follow up will be required to determine the success of this strategy.

Predictors of posttraumatic stress in parents of children diagnosed with a disorder of sex development.

The aims of the current study were twofold: (1) to assess the prevalence/severity of posttraumatic stress symptoms (PTSS) as well as cognitive and emotional responses in parents whose children were diagnosed with a disorder of sex development (DSD); and (2) to assess factors which contributed to PTSS. We hypothesized that parents would show elevated levels of PTSS and that negative cognitive and/or emotional responses would be predictive. Participants were parents of children diagnosed with a DSD. Thirty-six mothers and 11 fathers completed a measure of posttraumatic stress and reported difficulties in the domains of cognition (e.g., confusion) and emotion (e.g., grief). Using multiple regression, we determined factors contributing to parental PTSS. Reported PTSS was high: 31 % of mothers and 18 % of fathers met the threshold for caseness for Posttraumatic Stress Disorder. Regression included: child sex, parent sex, child age at diagnosis, years since diagnosis, genital ambiguity, father occupation, cognitive confusion, and emotional distress. Only cognitive confusion contributed significantly to variance in PTSS. Parents of children with DSD may experience the diagnosis as traumatic, evidenced by high rates of PTSS in the current report. Assessment of reactions to their children's diagnoses revealed that cognitive confusion, and not emotional distress, predicted PTSS. In this case, direct cognitive interventions may be applicable. Though psychological support is widely recommended, no detailed intervention has been offered. Our findings suggest that we may directly apply models successful in other areas of pediatrics, such as pediatric oncology. Future studies may assess the usefulness of such an intervention.

Great expectations: use of molecular tests and computerised prognostic tools in New Zealand cancer care.

BACKGROUND: Use of molecular tests and computerised prognostic tools designed to individualise cancer care appears to be rapidly increasing in New Zealand. These tests have important clinical and health economic implications, but their impact on cancer care has not been fully assessed. AIM: To determine cancer clinicians' use of and expectations for molecular tests and computerised prognostic tools. METHOD: Online survey of clinicians managing cancer in New Zealand. RESULTS: 137 clinicians participated, 31% used molecular tests and 57% used computerised prognostic tools. These technologies affected clinical decisions made by a quarter of participants. Over 85% of participants believed that the impact of molecular tests and computerised prognostic tools would increase over the next decade and that a stronger evidence base would support their use. CONCLUSIONS: Molecular tests and computerised prognostic tools already influence treatment provided to many New Zealand cancer patients. Clinicians who participated in this survey overwhelmingly expect the use of these tests to increase, which has important clinical implications since there is little high quality prospective data assessing the ability of these tests to improve patient outcomes. Expanded use of these often-expensive tests also has economic implications. The role of these technologies needs to be considered in the context of a wide-ranging cancer control strategy.

Complications of Foley catheters--is infection the greatest risk?

PURPOSE: Foley catheters cause a variety of harms, including infection, pain and trauma. Although symptomatic urinary tract infection and asymptomatic bacteriuria are frequently discussed, genitourinary trauma receives comparatively little attention. MATERIALS AND METHODS: A dedicated Foley catheter nurse prospectively reviewed the medical records of inpatients with a Foley catheter at the Minneapolis Veterans Affairs Medical Center from August 21, 2008 to December 31, 2009. Daily surveillance included Foley catheter related bacteriuria and trauma. Data were analyzed as the number of event days per 100 Foley catheter days. RESULTS: During 6,513 surveyed Foley catheter days, urinalysis/urine culture was done on 407 (6.3%) days. This testing identified 116 possible urinary tract infection episodes (1.8% of Foley catheter days), of which only 21 (18%) involved clinical manifestations. However, the remaining 95 asymptomatic bacteriuria episodes accounted for 39 (70%) of 56 antimicrobial treated possible urinary tract infection episodes (for proportion of treated episodes with vs without symptomatic urinary tract infection manifestations, p = 0.005). Concurrently 100 instances of catheter associated genitourinary trauma (1.5% of Foley catheter days) were recorded, of which 32 (32%) led to interventions such as prolonged catheterization or cystoscopy. Trauma prompting an intervention accounted for as great a proportion of Foley catheter days (0.5%) as did symptomatic urinary tract infection (0.3%) (p = 0.17). CONCLUSIONS: In this prospective surveillance project, intervention triggering Foley catheter related genitourinary trauma was as common as symptomatic urinary tract infection. Moreover, despite recent increased attention to the distinction between asymptomatic bacteriuria and symptomatic urinary tract infection in catheterized patients, asymptomatic bacteriuria accounted for significantly more antimicrobial treatment than did symptomatic urinary tract infection. Elimination of unnecessary Foley catheter use could prevent symptomatic urinary tract infection, unnecessary antimicrobial therapy for asymptomatic bacteriuria and Foley catheter related trauma.

Immunohistochemistry to detect hereditary nonpolyposis colorectal cancer in young patients: the 7-year Auckland experience.

BACKGROUND: In accordance with the Bethesda Guidelines, Auckland's metropolitan hospitals routinely perform immunohistochemistry for mismatch repair proteins on the tumor specimens of all patients with colorectal cancer aged 50 years and younger. When loss of expression is evident, patients are offered genetic counseling and gene mutation analysis. OBJECTIVES: This study aimed to determine the completeness of young patient capture over the first 7 years of routine testing, to find whether patients were referred for genetic testing, and to determine the proportion of patients found to have a mismatch repair gene mutation. DESIGN: This study retrospectively reviewed clinical, pathological, and genetic data. SETTINGS: The study was conducted at 3 public hospitals in Auckland, New Zealand. PATIENTS: All patients aged 50 years and younger treated for colorectal cancer at Auckland's metropolitan hospitals between January 2001 and December 2007 (n = 243) were included. MAIN OUTCOME MEASURES: The loss of expression of mismatch repair proteins by immunohistochemistry, referral for genetic testing, and proportion with mismatch repair gene mutation were the main outcome measures. RESULTS: Two hundred fourteen (88%) eligible patients had immunohistochemical analysis of their tumor and 33 (14%) had loss of expression of one or more mismatch repair proteins. Twenty-six patients were referred for genetic counseling, of whom 22 underwent genetic testing. A mismatch repair gene mutation was identified in 10 patients. LIMITATIONS: Seven patients with loss of expression of mismatch repair proteins by immunohistochemistry were not referred for genetic assessment. CONCLUSIONS: We have identified a mismatch repair gene mutation diagnostic of hereditary nonpolyposis colorectal cancer in 5% of all patients with colorectal cancer who were aged 50 years and younger. Routine immunohistochemical prescreening has important clinical benefit for these patients and their relatives.

Speculum 'self-insertion': a pilot study.

AIM: This paper reports phase II of a pilot study that aimed to determine whether self-insertion of a speculum by women undergoing a pap smear would be more comfortable and lead to an improvement in satisfaction and a decrease in anxiety associated with this procedure. BACKGROUND: Research demonstrates that pelvic examinations are considered by most women to be unpleasant and are routinely associated with embarrassment, apprehension, fear and often some level of discomfort and/or pain. DESIGN: The study used quantitative and qualitative data collection techniques. Phase I (described elsewhere) tested the newly developed Speculum Self-Insertion Satisfaction Questionnaire for content validity, internal consistency and clarity. Phase II pilot study tested the technique of speculum self-insertion. Women's general level of anxiety was measured using the State Trait Anxiety Inventory, both before and after they performed the self-insertion procedure. Women's satisfaction and acceptance of the procedure was measured using the Speculum Self-Insertion Satisfaction Questionnaire and explored through the use of qualitative research techniques. PARTICIPANTS: A total of 198 women attending family planning clinics in Perth, Western Australia, between September and December 2003 were invited to participate in the study. One hundred and thirty-three women agreed to self-insert their own speculum. RESULTS: The study demonstrated that speculum self-insertion was acceptable to most women, especially younger women. Nearly 91% of women either agreed or strongly agreed that they were satisfied with the experience of self-insertion and would choose to self-insert the speculum again. This included the women who had not previously had a speculum examination. The quality of specimen collected was not detrimentally affected by speculum self-insertion. CONCLUSIONS: The results of this pilot research, while needing to be replicated in a larger study, demonstrate that offering women the opportunity to self-insert a speculum during a routine pelvic examination is an acceptable, innovative, simple and cost-neutral change in clinical practice that increases women's comfort and satisfaction and potentially makes sexual health screening less threatening to women of all ages. RELEVANCE TO CLINICAL PRACTICE: Speculum self-insertion may encourage women's attendance at clinics for regular screening. Early diagnosis and treatment will result in better health outcomes for women, families and the community at large.

UV irradiation and desiccation modulate the three-dimensional extracellular matrix of Nostoc commune (Cyanobacteria).

Cyanobacterium Nostoc commune can tolerate the simultaneous stresses of desiccation, UV irradiation, and oxidation. Acidic WspA, of approximately 33.6 kDa, is secreted to the three-dimensional extracellular matrix and accounts for greater than 70% of the total soluble protein. The wspA gene of N. commune strain DRH1 was cloned and found in a single genomic copy, in a monocistronic operon. Transcription of wspA and sodF (superoxide dismutase), and synthesis and secretion of WspA, were induced upon desiccation or UV-A/B irradiation of cells. Recombinant WspA binds the UV-A/B absorbing pigment scytonemin through non-covalent interactions. WspA peptide polymorphism, and heterogeneity of multiple wspA sequences within cells of a single colony, account for distinct WspA isoforms. WspA has no similarity to entries in the sequence databases and wspA, a possible xenolog, is restricted to a subset of strains in the "form species" N. commune characterized through group I intron phylogeny. We hypothesize that WspA plays a central role in the global stress response of N. commune through modulation of the structure and function of the three-dimensional extracellular matrix, particularly the transport, distribution, and/or macromolecular architecture of mycosporine and scytonemin UV-A/B absorbing pigment complexes.