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.

Monkeypox virus-infected individuals mount comparable humoral immune responses as Smallpox-vaccinated individuals.

In early 2022, a cluster of monkeypox virus (MPXV) infection (mpox) cases were identified within the UK with no prior travel history to MPXV-endemic regions. Subsequently, case numbers exceeding 80,000 were reported worldwide, primarily affecting gay, bisexual, and other men who have sex with men (GBMSM). Public health agencies worldwide have offered the IMVANEX Smallpox vaccination to these individuals at high-risk to provide protection and limit the spread of MPXV. We have developed a comprehensive array of ELISAs to study poxvirus-induced antibodies, utilising 24 MPXV and 3 Vaccinia virus (VACV) recombinant antigens. Panels of serum samples from individuals with differing Smallpox-vaccine doses and those with prior MPXV infection were tested on these assays, where we observed that one dose of Smallpox vaccination induces a low number of antibodies to a limited number of MPXV antigens but increasing with further vaccination doses. MPXV infection induced similar antibody responses to diverse poxvirus antigens observed in Smallpox-vaccinated individuals. We identify MPXV A27 as a serological marker of MPXV-infection, whilst MPXV M1 (VACV L1) is likely IMVANEX-specific. Here, we demonstrate analogous humoral antigen recognition between both MPXV-infected or Smallpox-vaccinated individuals, with binding to diverse yet core set of poxvirus antigens, providing opportunities for future vaccine (e.g., mRNA) and therapeutic (e.g., mAbs) design.

Fostering Authenticity in Surgical Education: Creating a Safe Space for Medical Students to Practice as Doctors.

Over the past 10 years we have witnessed major changes to the medical education landscape in response to advances in digital technologies. Couple this with the disruptions imposed by the COVID-19 pandemic and we have what could be described as a 'perfect storm.' Rather than hunker down and wait for it to pass, we took it as an opportunity to re-evaluate how we practice surgical education in the fourth year of our 6 year medical programme. In this article, we describe the formation of 6 core principles that function as pivot points in developing a new perspective centered on the importance of engaging and empowering our students as emerging clinicians. From these 6 principles, we designed and developed 3 interventions. Each intervention is discussed in regard to its purpose, operation and overall integration into the program.

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.

Late Outcomes of the RAPID-TnT Randomized Controlled Trial: 0/1-Hour High-Sensitivity Troponin T Protocol in Suspected ACS.

BACKGROUND: High-sensitivity troponin assays are increasingly being adopted to expedite evaluation of patients with suspected acute coronary syndromes. Few direct comparisons have examined whether the enhanced performance of these assays at low concentrations leads to changes in care that improves longer-term outcomes. This study evaluated late outcomes of participants managed under an unmasked 0/1-hour high-sensitivity cardiac troponin T (hs-cTnT) protocol compared with a 0/3-hour masked hs-cTnT protocol. METHODS: We conducted a multicenter prospective patient-level randomized comparison of care informed by unmasked 0/1-hour hs-cTnT protocol (reported to <5 ng/L) versus standard practice masked hs-cTnT testing (reported to ≤29 ng/L) assessed at 0/3 hours and followed participants for 12 months. Participants included were those presenting to metropolitan emergency departments with suspected acute coronary syndromes, without ECG evidence of coronary ischemia. The primary end point was time to all-cause death or myocardial infarction using Cox proportional hazards models adjusted for clustering within hospitals. RESULTS: Between August 2015 and April 2019, we randomized 3378 participants, of whom 108 withdrew, resulting in 12-month follow-up for 3270 participants (masked: 1632; unmasked: 1638). Among these, 2993 (91.5%) had an initial troponin concentration of ≤29 ng/L. Deployment of the 0/1-hour hs-cTnT protocol was associated with reductions in functional testing. Over 12-month follow-up, there was no difference in invasive coronary angiography (0/1-hour unmasked: 232/1638 [14.2%]; 0/3-hour masked: 202/1632 [12.4%]; P=0.13), although an increase was seen among patients with hs-cTnT levels within the masked range (0/1-hour unmasked arm: 168/1507 [11.2%]; 0/3-hour masked arm: 124/1486 [8.3%]; P=0.010). By 12 months, all-cause death and myocardial infarction did not differ between study arms overall (0/1-hour: 82/1638 [5.0%] versus 0/3-hour: 62/1632 [3.8%]; hazard ratio, 1.32 [95% CI, 0.95-1.83]; P=0.10). Among participants with initial troponin T concentrations ≤29 ng/L, unmasked hs-cTnT reporting was associated with an increase in death or myocardial infarction (0/1-hour: 55/1507 [3.7%] versus 0/3-hour: 34/1486 [2.3%]; hazard ratio, 1.60 [95% CI, 1.05-2.46]; P=0.030). CONCLUSIONS: Unmasked hs-cTnT reporting deployed within a 0/1-hour protocol did not reduce ischemic events over 12-month follow-up. Changes in practice associated with the implementation of this protocol may be associated with an increase in death and myocardial infarction among those with newly identified troponin elevations. Registration: URL: https://www.anzctr.org.au; Unique identifier: ACTRN12615001379505.

A Randomized Trial of a 1-Hour Troponin T Protocol in Suspected Acute Coronary Syndromes: The Rapid Assessment of Possible Acute Coronary Syndrome in the Emergency Department With High-Sensitivity Troponin T Study (RAPID-TnT).

BACKGROUND: High-sensitivity troponin assays promise earlier discrimination of myocardial infarction. Yet, the benefits and harms of this improved discriminatory performance when incorporated within rapid testing protocols, with respect to subsequent testing and clinical events, has not been evaluated in an in-practice patient-level randomized study. This multicenter study evaluated the noninferiority of a 0/1-hour high-sensitivity cardiac troponin T (hs-cTnT) protocol in comparison with a 0/3-hour masked hs-cTnT protocol in patients with suspected acute coronary syndrome presenting to the emergency department (ED). METHODS: Patients were randomly assigned to either a 0/1-hour hs-cTnT protocol (reported to the limit of detection [<5 ng/L]) or masked hs-cTnT reported to ≤29 ng/L evaluated at 0/3-hours (standard arm). The 30-day primary end point was all-cause death and myocardial infarction. Noninferiority was defined as an absolute margin of 0.5% determined by Poisson regression. RESULTS: In total, 3378 participants with an emergency presentation were randomly assigned between August 2015 and April 2019. Ninety participants were deemed ineligible or withdrew consent. The remaining participants received care guided either by the 0/1-hour hs-cTnT protocol (n=1646) or the 0/3-hour standard masked hs-cTnT protocol (n=1642) and were followed for 30 days. Median age was 59 (49-70) years, and 47% were female. Participants in the 0/1-hour arm were more likely to be discharged from the ED (0/1-hour arm: 45.1% versus standard arm: 32.3%, P<0.001) and median ED length of stay was shorter (0/1-hour arm: 4.6 [interquartile range, 3.4-6.4] hours versus standard arm: 5.6 (interquartile range, 4.0-7.1) hours, P<0.001). Those randomly assigned to the 0/1-hour protocol were less likely to undergo functional cardiac testing (0/1-hour arm: 7.5% versus standard arm: 11.0%, P<0.001). The 0/1-hour hs-cTnT protocol was not inferior to standard care (0/1-hour arm: 17/1646 [1.0%] versus 16/1642 [1.0%]; incidence rate ratio, 1.06 [ 0.53-2.11], noninferiority P value=0.006, superiority P value=0.867), although an increase in myocardial injury was observed. Among patients discharged from ED, the 0/1-hour protocol had a negative predictive value of 99.6% (95% CI, 99.0-99.9%) for 30-day death or myocardial infarction. CONCLUSIONS: This in-practice evaluation of a 0/1-hour hs-cTnT protocol embedded in ED care enabled more rapid discharge of patients with suspected acute coronary syndrome. Improving short-term outcomes among patients with newly recognized troponin T elevation will require an evolution in management strategies for these patients. CLINICAL TRIAL REGISTRATION: URL: https://www.anzctr.org.au. Unique identifier: ACTRN12615001379505.

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.

Alcohol and remembering a hypothetical sexual assault: Can people who were under the influence of alcohol during the event provide accurate testimony?

We examined the influence of alcohol on remembering an interactive hypothetical sexual assault scenario in the laboratory using a balanced placebo design. Female participants completed a memory test 24 hours and 4 months later. Participants reported less information (i.e., responded "don't know" more often to questions) if they were under the influence of alcohol during scenario encoding. The accuracy of the information intoxicated participants reported did not differ compared to sober participants, however, suggesting intoxicated participants were effectively monitoring the accuracy of their memory at test. Additionally, peripheral details were remembered less accurately than central details, regardless of the intoxication level; and memory accuracy for peripheral details decreased by a larger amount compared to central details across the retention interval. Finally, participants were more accurate if they were told they were drinking alcohol rather than a placebo. We discuss theoretical implications for alcohol myopia and memory regulation, together with applied implications for interviewing intoxicated witnesses.

Seroconversion for infectious pathogens among UK military personnel deployed to Afghanistan, 2008-2011.

Military personnel are at high risk of contracting vector-borne and zoonotic infections, particularly during overseas deployments, when they may be exposed to endemic or emerging infections not prevalent in their native countries. We conducted seroprevalence testing of 467 UK military personnel deployed to Helmand Province, Afghanistan, during 2008-2011 and found that up to 3.1% showed seroconversion for infection with Rickettsia spp., Coxiella burnetii, sandfly fever virus, or hantavirus; none showed seroconversion for infection with Crimean-Congo hemorrhagic fever virus. Most seroconversions occurred in personnel who did not report illness, except for those with hantavirus (70% symptomatic). These results indicate that many exposures to infectious pathogens, and potentially infections resulting from those exposures, may go unreported. Our findings reinforce the need for continued surveillance of military personnel and for education of health care providers to help recognize and prevent illnesses and transmission of pathogens during and after overseas deployments.

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.

Supply and demand mismatch for flexible (part-time) surgical training in Australasia.

OBJECTIVES: To define current patterns of flexible (part-time) surgical training in Australasia, determine supply and demand for part-time positions, and identify work-related factors motivating interest in flexible training. DESIGN, SETTING AND PARTICIPANTS: All Royal Australasian College of Surgeons trainees (n = 1191) were surveyed in 2010. Questions assessed demographic characteristics and working patterns, interest in flexible training, work-related fatigue and work-life balance preferences. MAIN OUTCOME MEASURES: Interest in part-time training, and work-related factors motivating this interest. RESULTS: Of the 1191 trainees, 659 responded (response rate, 55.3%). Respondents were representative of all trainees in terms of specialty and sex. The median age of respondents was 32 2013s, and 187 (28.4%) were female. Most of the 659 respondents (627, 95.1%) were in full-time clinical training; only two (0.3%) were in part-time clinical training, and 30 (4.6%) were not in active clinical training. An interest in part-time training was reported by 208 respondents (31.6%; 54.3% of women v 25.9% of men; P < 0.001). Trainees expressing an interest in part-time training were more likely to report that fatigue impaired their performance at work and limited their social or family life, and that they had insufficient time in life for things outside surgical training, including study or research (P < 0.05). CONCLUSIONS: There is a striking mismatch between demand for flexible surgical training and the number of trainees currently in part-time training positions in Australia and New Zealand. Efforts are needed to facilitate part-time surgical training.

Delay and déjà vu: timing and repetition increase the power of false evidence.

False images and videos can induce people to believe in and remember events that never happened. Using a novel method, we examined whether the timing of false evidence would influence its effect (Experiment 1) and determined the relationship between timing and repetition (Experiment 2). Subjects completed a hazard perception driving test and were falsely accused of cheating. Some subjects were shown a fake video or photograph of the cheating either after a 9-min delay (Experiment 1) or more than once with or without a delay (Experiment 2). Subjects were more likely to falsely believe that they had cheated and to provide details about how the cheating happened when the false evidence was delayed or repeated-especially when repeated over time-relative to controls. The results show that even a strikingly short delay between an event and when false evidence is disclosed can distort people's beliefs and that repeating false evidence over a brief delay fosters false beliefs more so than without a delay. These findings have theoretical implications for metacognitive models of autobiographical memory and practical implications for police interrogations.

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.

Reduction of inappropriate urinary catheter use at a Veterans Affairs hospital through a multifaceted quality improvement project.

BACKGROUND: Foley catheter (FC) use is a modifiable risk factor for hospital-acquired urinary tract infection, the most common type of nosocomial infection. It is unknown whether sustained, hospital-wide reductions in FC use are achievable by combining interventions with demonstrated short-term effectiveness in selected units. METHODS: A multifaceted quality improvement project to decrease unnecessary FC use and increase order documentation was instituted throughout the Minneapolis Veterans Affairs Medical Center in March 2005, after a >2-year baseline period. Bundled interventions included multiple types of education, system redesign, rewards, and feedback (phases I and II), plus, in phase III, involvement of a dedicated FC nurse. RESULTS: The daily prevalence of FC use dropped steeply during intervention phase I (5.5 months), from a 15.2% baseline mean to a 9.3% nadir, but rebounded quickly during the subsequent hiatus phase (1.2 months). It dropped again (mean, 13.6%) during intervention phase II (27.3 months) and even further (mean, 12.0%) during intervention phase III (22.8 months) (P ≤ .001, phase II or III vs baseline). Compared with baseline, during phase III (with the dedicated FC nurse) the mean daily percentages of nonordered and nonindicated FCs dropped from 17% to 5.1% and from 15% to 1.2%, respectively. During phases II and III combined, an estimated total of 6691 FC days were avoided. CONCLUSIONS: Significant hospital-wide reductions in total and inappropriate FC use and improved FC order documentation were achieved through a multicomponent campaign. The greatest and most sustained improvements accompanied the involvement of a dedicated FC nurse.