Critical Analysis of the Causes of In-Hospital Mortality following Colorectal Resection: A Queensland Audit of Surgical Mortality (QASM) Registry Study.

BACKGROUND: Colorectal resection is a major gastrointestinal operation. Improvements in peri-operative care has led to improved outcomes; however, mortalities still occur. Using data from the Queensland Audit of Surgical Mortality (QASM), this study examines the demographic and clinical characteristics of patients who died in hospital following colorectal resection, and also reports the primary cause of death in this population. METHODS: Patients who died in hospital following colorectal resection in Queensland between January 2010 and December 2020 were identified from the QASM database. RESULTS: There were 755 patients who died in the 10 year study period. Pre-operatively, the risk of death as subjectively determined by operating surgeons was 'considerable' in 397 cases (53.0%) and 'expected' in 90 cases (12.0%). The patients had a mean of 2.7 (±1.5) co-morbidities, and a mean American Society of Anaesthesiologists (ASA) score of 3.6 (±0.8). Operations were categorised as emergency in 579 patients (77.2%), with 637 patients (85.0%) requiring post-operative Intensive Care Unit (ICU) support. The primary cause of death was related to a surgical cause in 395 patients (52.7%) and to a medical cause in 355 patients (47.3%). The primary causes of death were advanced surgical pathology (n=292, 38.9%), complications from surgery (n=103, 13.7%), complications arising from pre-existing medical co-morbidity (n=282, 37.6%) or new medical complications unrelated to pre-existing conditions (n=73, 9.7%). CONCLUSIONS: Patients who died had significant co-morbidities and often presented emergently with an advanced surgical pathology. Surgical and medical causes of death both contributed equally to the mortality burden.

Surgeons' Responses to a Surgical Mortality Audit: Accepting and Improving: A Cross Sectional Survey.

BACKGROUND: Surgeons strive to provide the best care possible to their patients. The Australian and New Zealand Audit of Surgical Mortality is a process for improving surgical care and outcomes via peer-review assessment of mortality cases. This article examines the acceptability of the assessments to Queensland surgeons, in addition to examining their impact on surgical care. METHODS: This study was a cross-sectional survey. Evaluation forms were sent to all Queensland surgeons who had received a first-line assessment with clinical incidents identified or a second-line assessment (with or without clinical incidents), between April 2018 and January 2020 (n = 484). A total of 102 evaluation forms were returned, giving a response rate of 21%. RESULTS: Most respondents agreed that their assessments were fair (78%) and informative (69%). Almost half (43%) agreed that their assessment improved the subsequent surgical care they provided. Comments supported this, with surgeons describing reflections, meetings and changes that had occurred following their assessments. Despite the strong proportion of positive comments, some surgeons disagreed with the opinions or recommendations of their assessors. A large percentage (41%) was neutral towards the ability of the assessments they had received to improve surgical care at the hospital level. CONCLUSIONS: There was a high degree of acceptance of the QASM peer-review assessment process. The assessments facilitated discussion, reflection and implementation of surgical care improvements in Queensland surgeons. Further research into this topic should involve refinement of the study tool with a larger, and therefore more representative, proportion of the surgical population.

Variability in clinicians' understanding and reported methods of identifying high-risk surgical patients: a qualitative study.

BACKGROUND: High-risk patients presenting for surgery require complex decision-making and perioperative management. However, given there is no gold standard for identifying high-risk patients, doing so may be challenging for clinicians in practice. Before a gold standard can be established, the state of current practice must be determined. This study aimed to understand how working clinicians define and identify high-risk surgical patients. METHODS: Clinicians involved in the care of high-risk surgical patients at a public hospital in regional Australia were interviewed as part of an ongoing study evaluating a new shared decision-making process for high-risk patients. The new process, Patient-Centred Advanced Care Planning (PC-ACP) engages patients, families, and clinicians from all relevant specialties in shared decision-making in line with the patient's goals and values. The semi-structured interviews were conducted before the implementation of the new process and were coded using a modified form of the 'constant comparative method' to reveal key themes. Themes concerning patient risk, clinician's understanding of high risk, and methods for identifying high-risk surgical patients were extricated for close examination. RESULTS: Thirteen staff involved in high-risk surgery at the hospital at which PC-ACP was to be implemented were interviewed. Analysis revealed six sub-themes within the major theme of factors related to patient risk: (1) increase in high-risk patients, (2) recognising frailty, (3) risk-benefit balance, (4) suitability and readiness for surgery, (5) avoiding negative outcomes, and (6) methods in use for identifying high-risk patients. There was considerable variability in clinicians' methods of identifying high-risk patients and regarding their definition of high risk. This variability occurred even among clinicians within the same disciplines and specialties. CONCLUSIONS: Although clinicians were confident in their own ability to identify high-risk patients, they acknowledged limitations in recognising frail, high-risk patients and predicting and articulating possible outcomes when consenting these patients. Importantly, little consistency in clinicians' reported methods for identifying high-risk patients was found. Consensus regarding the definition of high-risk surgical patients is necessary to ensure rigorous decision-making.

How participation in surgical mortality audit impacts surgical practice.

BACKGROUND: Surgical mortality audit is an important tool for quality assurance and professional development but little is known about the impact of such activity on professional practice at the individual surgeon level. This paper reports the findings of a survey conducted with a self-selected cohort of surgeons in Queensland, Australia, on their experience of participating in the audit and its impact on their professional practice, as well as implications for hospital systems. METHODS: The study used a descriptive cross-sectional survey design. All surgeons registered in Queensland in 2015 (n = 919) were invited to complete an anonymous online questionnaire between September and October 2015. 184 surgeons completed and returned the questionnaire at a response rate of 20%. RESULTS: Thirty-nine percent of the participants reported that involvement in the audit process affected their clinical practice. This was particularly the case for surgeons whose participation included being an assessor. Thirteen percent of the participants had perceived improvement to hospital practices or advancement in patient care and safety as a result of audit recommendations. Analysis of the open-ended responses suggested the audit experience had led surgeons to become more cautious, reflective in action and with increased confidence in best practice, and recognise the importance of effective communication and clear documentation. CONCLUSIONS: This is the first study to examine the impact of participation in a mortality audit process on the professional practice of surgeons. The findings offer evidence for surgical mortality audit as an effective strategy for continuous professional development and for improving patient safety initiatives.

Efficacy of a Gluten-Free Diet in Subjects With Irritable Bowel Syndrome-Diarrhea Unaware of Their HLA-DQ2/8 Genotype.

BACKGROUND & AIMS: A gluten-containing diet alters bowel barrier function in patients with irritable bowel syndrome with diarrhea (IBS-D), particularly those who are positive for HLA allele DQ2/8. We studied the effects of a gluten-free diet (GFD) in patients with IBS-D who have not previously considered the effects of gluten in their diet and were unaware of their HLA-DQ2/8 genotype. METHODS: We performed a prospective study of 41 patients with IBS-D (20 HLA-DQ2/8-positive and 21 HLA-DQ2/8-negative) at the Royal Hallamshire Hospital in Sheffield, United Kingdom, from September 2012 through July 2015. All subjects were placed on a 6-week GFD following evaluation by a dietician. Subjects completed validated questionnaires at baseline and Week 6 of the GFD. The primary endpoint was mean change in IBS Symptom Severity Score; a 50-point reduction was considered to indicate a clinical response. Secondary endpoints were changes in hospital anxiety and depression score, fatigue impact score, and Short Form-36 results. Clinical responders who chose to continue a GFD after the study period were evaluated on average 18 months later to assess diet durability, symptom scores, and anthropometric and biochemical status. RESULTS: A 6-week GFD reduced IBS Symptom Severity Score by ≥50 points in 29 patients overall (71%). The mean total IBS Symptom Severity Score decreased from 286 before the diet to 131 points after 6 weeks on the diet (P < .001); the reduction was similar in each HLA-DQ group. However, HLA-DQ2/8-negative subjects had a greater reduction in abdominal distention (P = .04). Both groups had marked mean improvements in hospital anxiety and depression scores, fatigue impact score, and Short Form-36 results, although HLA-DQ2/8-positive subjects had a greater reduction in depression score and increase in vitality score than HLA-DQ2/8-negative subjects (P = .02 and P = .03, respectively). Twenty-one of the 29 subjects with a clinical response (72%) planned to continue the GFD long term; 18 months after the study they were still on a GFD, with maintained symptom reductions, and demonstrated similar anthropometric and biochemical features compared with baseline. CONCLUSIONS: A dietitian-led GFD provided sustained benefit to patients with IBS-D. The symptoms that improved differed in magnitude according to HLA-DQ status. Clinical trials.gov no: NCT02528929.

Medical versus surgical causes of death following colorectal resection: a Queensland Audit of Surgical Mortality (QASM) study.

BACKGROUND: The causes of death following colorectal resection remain poorly explored. Few studies have addressed whether early post-operative mortality is predominantly caused by a patient's medical co-morbidities, or from factors pertaining to the presenting surgical disease process itself. This study analyses data from the Queensland audit of surgical mortality (QASM) to report the causes of in-hospital death following colorectal resection, identifies whether these were due to either medical or surgical factors, and determines the patient characteristics associated with a medical cause of death. METHODS: Through analysis of QASM Surgical Case Forms, the causes of in-hospital death were determined in 750 patients who died in Queensland following colorectal resection between January 2010 and December 2020. Deaths were attributed to a specific medical or surgical cause, with multivariate analysis used to identify independent risk factors associated with a medical cause of death. RESULTS: In total, 395 patients (52.7%) died due to surgical causes and 355 (47.3%) died due to medical causes. Respiratory co-morbidities (OR 1.832, 95% CI: 1.267-2.650), advanced malignancy (OR 1.814, 95% CI: 1.262-2.607), neurological co-morbidities (OR 1.794, 95% CI: 1.168-2.757) and advanced age (OR 1.430, 95% CI: 1.013-2.017) were independent risk factors associated with increased risk of a medical cause of death. CONCLUSION: Even in the absence of complicating surgical factors, a significant number of patients died in hospital following colorectal resection due to their underlying co-morbidities. Multi-disciplinary models of care which allow for the early recognition and treatment of medical complications may reduce post-operative mortality in these patients.

Short-term neoadjuvant androgen deprivation and radiotherapy for locally advanced prostate cancer: 10-year data from the TROG 96.01 randomised trial.

BACKGROUND: The TROG 96.01 trial assessed whether 3-month and 6-month short-term neoadjuvant androgen deprivation therapy (NADT) decreases clinical progression and mortality after radiotherapy for locally advanced prostate cancer. Here we report the 10-year results. METHODS: Between June, 1996, and February, 2000, 818 men with T2b, T2c, T3, and T4 N0 M0 prostate cancers were randomly assigned to receive radiotherapy alone, 3 months of NADT plus radiotherapy, or 6 months of NADT plus radiotherapy. The radiotherapy dose for all groups was 66 Gy, delivered to the prostate and seminal vesicles (excluding pelvic nodes) in 33 fractions of 2 Gy per day (excluding weekends) over 6·5-7·0 weeks. NADT consisted of 3·6 mg goserelin given subcutaneously every month and 250 mg flutamide given orally three times a day. NADT began 2 months before radiotherapy for the 3-month NADT group and 5 months before radiotherapy for the 6-month NADT group. Primary endpoints were prostate-cancer-specific mortality and all-cause mortality. Treatment allocation was open label and randomisation was done with a minimisation technique according to age, clinical stage, tumour grade, and initial prostate-specific antigen concentration (PSA). Analysis was by intention-to-treat. The trial has been closed to follow-up and all main endpoint analyses are completed. The trial is registered with the Australian New Zealand Clinical Trials Registry, number ACTRN12607000237482. FINDINGS: 802 men were eligible for analysis (270 in the radiotherapy alone group, 265 in the 3-month NADT group, and 267 in the 6-month NADT group) after a median follow-up of 10·6 years (IQR 6·9-11·6). Compared with radiotherapy alone, 3 months of NADT decreased the cumulative incidence of PSA progression (adjusted hazard ratio 0·72, 95% CI 0·57-0·90; p=0·003) and local progression (0·49, 0·33-0·73; p=0·0005), and improved event-free survival (0·63, 0·52-0·77; p<0·0001). 6 months of NADT further reduced PSA progression (0·57, 0·46-0·72; p<0·0001) and local progression (0·45, 0·30-0·66; p=0·0001), and led to a greater improvement in event-free survival (0·51, 0·42-0·61, p<0·0001), compared with radiotherapy alone. 3-month NADT had no effect on distant progression (0·89, 0·60-1·31; p=0·550), prostate cancer-specific mortality (0·86, 0·60-1·23; p=0·398), or all-cause mortality (0·84, 0·65-1·08; p=0·180), compared with radiotherapy alone. By contrast, 6-month NADT decreased distant progression (0·49, 0·31-0·76; p=0·001), prostate cancer-specific mortality (0·49, 0·32-0·74; p=0·0008), and all-cause mortality (0·63, 0·48-0·83; p=0·0008), compared with radiotherapy alone. Treatment-related morbidity was not increased with NADT within the first 5 years after randomisation. INTERPRETATION: 6 months of neoadjuvant androgen deprivation combined radiotherapy is an effective treatment option for locally advanced prostate cancer, particularly in men without nodal metastases or pre-existing metabolic comorbidities that could be exacerbated by prolonged androgen deprivation. FUNDING: Australian Government National Health and Medical Research Council, Hunter Medical Research Institute, AstraZeneca, and Schering-Plough.

The associations of factors with previous alcohol use in the Northern Territory compared to other states - an observational study.

BACKGROUND: Data on previous alcohol use in surgical patients who died in the Northern Territory (NT) are lacking and have important public health implications. METHODS: The prevalence of previous alcohol (ab)use among surgical patients who died (n=560) was assessed in patients within the Northern Territory and the remainder of Australia (n=28,245) over nine years. RESULTS: The likelihood of previous alcohol use (21.4%; 120 of 560), was the outcome measured and was higher in the Northern Territory than outside it (5.9%; 1,660 of 28,245). Factors associated with the outcome of previous alcohol use were: male gender (aOR 1.6); Aboriginal and Torres Strait Islander status (aOR 2.0); liver disease (aOR 7.8); comorbidities (aOR 2.5); and trauma (aOR 1.1), in both the Northern Territory (aOR 11.5) and all Australia (aOR 7.8). In the Northern Territory, alcohol use was high in both Aboriginal and Torres Strait Islander people (31%) and non-Aboriginal and Torres Strait Islander (16%) people (p=0.316). CONCLUSION: Of surgical patients who died, the likelihood of being a previous alcohol user was double in the Northern Territory as opposed to other states. Alcohol misuse is widespread across all groups in the Northern Territory. Implications for public health: Previous alcohol (ab)use is a negative factor for survival in any racial group.

Telehealth in surgery: an umbrella review.

BACKGROUND: Telehealth use has increased worldwide during the COVID-19 pandemic. However, hands-on requirements of surgical care may have resulted in slower implementation. This umbrella review (review of systematic reviews) evaluated the perceptions, safety and implementation of telehealth services in surgery, and telehealth usage in Australia between 2020 and 2021. METHODS: PubMed was searched from 2015 to 2021 for systematic reviews evaluating real-time telehealth modalities in surgery. Outcomes of interest were patient and provider satisfaction, safety, and barriers and facilitators associated with its use. Study quality was appraised using the AMSTAR 2 tool. A working group of surgeons provided insights into the clinical relevance to telehealth in surgical practice of the evidence collated. RESULTS: From 2025 identified studies, 17 were included, which were of low to moderate risk of bias. Patient and provider satisfaction with telehealth was high. Time savings, decreased healthcare resource use and lower costs were reported as key advantages of the service. Inability to perform comprehensive examinations was noted as the primary barrier. In Australia, peak telehealth usage coincided with the introduction of temporary telehealth services and increased lockdown measures. CONCLUSIONS: Patients and providers are broadly satisfied with telehealth and its benefits. Barriers may be overcome via multidisciplinary collaboration. Telehealth may benefit surgical care long-term if implemented correctly both during and after the COVID-19 pandemic.

Sequestosome-1/p62 is the key intracellular target of innate defense regulator peptide.

Innate defense regulator-1 (IDR-1) is a synthetic peptide with no antimicrobial activity that enhances microbial infection control while suppressing inflammation. Previously, the effects of IDR-1 were postulated to impact several regulatory pathways including mitogen-activated protein kinase (MAPK) p38 and CCAAT-enhancer-binding protein, but how this was mediated was unknown. Using a combined stable isotope labeling by amino acids in cell culture-proteomics methodology, we identified the cytoplasmic scaffold protein p62 as the molecular target of IDR-1. Direct IDR-1 binding to p62 was confirmed by several biochemical binding experiments, and the p62 ZZ-type zinc finger domain was identified as the IDR-1 binding site. Co-immunoprecipitation analysis of p62 molecular complexes demonstrated that IDR-1 enhanced the tumor necrosis factor alpha-induced p62 receptor-interacting protein 1 (RIP1) complex formation but did not affect tumor necrosis factor alpha-induced p62-protein kinase zeta complex formation. In addition, IDR-1 induced p38 MAPK activity in a p62-dependent manner and increased CCAAT-enhancer-binding protein beta activity, whereas NF-kappaB activity was unaffected. Collectively, these results demonstrate that IDR-1 binding to p62 specifically affects protein-protein interactions and subsequent downstream events. Our results implicate p62 in the molecular mechanisms governing innate immunity and identify p62 as a potential therapeutic target in both infectious and inflammatory diseases.

An anti-infective peptide that selectively modulates the innate immune response.

We show that an innate defense-regulator peptide (IDR-1) was protective in mouse models of infection with important Gram-positive and Gram-negative pathogens, including methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus and Salmonella enterica serovar Typhimurium. When given from 48 h before to 6 h after infection, the peptide was effective by both local and systemic administration. Because protection by IDR-1 was prevented by in vivo depletion of monocytes and macrophages, but not neutrophils or B- and T-lymphocytes, we conclude that monocytes and macrophages are key effector cells. IDR-1 was not directly antimicrobial: gene and protein expression analysis in human and mouse monocytes and macrophages indicated that IDR-1, acting through mitogen-activated protein kinase and other signaling pathways, enhanced the levels of monocyte chemokines while reducing pro-inflammatory cytokine responses. To our knowledge, an innate defense regulator that counters infection by selective modulation of innate immunity without obvious toxicities has not been reported previously.

Economic Advantages of Telehealth and Virtual Health Practitioners: Return on Investment Analysis.

BACKGROUND: Telehealth is a disruptive modality that challenges the traditional model of having a clinician or patient physically present for an appointment. The benefit is that it offers the opportunity to redesign the way services are offered. For instance, a virtual health practitioner can provide videoconference consultations while being located anywhere in the world that has internet. A virtual health practitioner also obviates the issues of attracting a specialist medical workforce to rural areas, and allows the rural health service to control the specialist services that they offer. OBJECTIVE: The aim of this research was to evaluate the economic effects of 3 different models of care on rural and metropolitan hospital sites. The models of care examined were patient travel, telehealth using videoconferencing, and employment of a virtual health practitioner by a rural site. METHODS: Using retrospective activity data for 3 years, a return on investment (ROI) analysis was undertaken from the perspective of a rural site and metropolitan partner site using a telehealth orthopedic fracture clinic as an example. Further analysis was conducted to calculate the number of patients that would be required to attend the clinic in each model of care for the sites to break even. RESULTS: The only service model that resulted in a positive ROI for the rural site over the 3-year period was the virtual health practitioner model. The breakeven analysis demonstrated that the rural site required the lowest number of patients to recoup costs in the virtual health practitioner model of care. The rural site was unable to recoup its costs within the travel model due to the lack of opportunity for reimbursement for services and the requirement to cover the cost of travel for patients. CONCLUSIONS: Our model demonstrated that rural health care providers can increase their ROI by employing a virtual health practitioner.

Is there more than one proctitis syndrome? A revisitation using data from the TROG 96.01 trial.

PURPOSE: We sought to categorize longitudinal radiation-induced rectal toxicity data obtained from men participating in a randomised controlled trial for locally advanced prostate cancer. MATERIALS AND METHODS: Data from self-assessed questionnaires of rectal symptoms and clinician recorded remedial interventions were collected during the TROG 96.01 trial. In this trial, volunteers were randomised to radiation with or without neoadjuvant androgen deprivation. Characterization of longitudinal variations in symptom intensity was achieved using prevalence data. An integrated visualization and clustering approach based on memetic algorithms was used to define the compositions of symptom clusters occurring before, during and after radiation. The utility of the CTC grading system as a means of identifying specific injury profiles was evaluated using concordance analyses. RESULTS: Seven well-defined clusters of rectal symptoms were present prior to treatment, 25 were seen immediately following radiation and 7 at years 1, 2 and 3 following radiation. CTC grading did not concord with the degree of rectal 'distress' and 'problems' at all time points. Concordance was not improved by adding urgency to the CTC scale. CONCLUSIONS: The CTC scale has serious shortcomings. A powerful new technique for non-hierarchical clustering may contribute to the categorization of rectal toxicity data for genomic profiling studies and detailed patho-physiological studies.

Quantifying the Impact of Excluding Insecticide Classes From Cotton Integrated Pest Management Programs in the U.S. Mid-South.

Current assessments from the U.S. Environmental Protection Agency suggest that some current insecticides may be lost or severely restricted in the near future. An experiment was conducted from 2014 to 2015 at two locations in Mississippi to determine the impact of losses of insecticide classes on integrated pest management of insect pests in cotton. The treatments included cotton treated with all available classes of insecticides, cotton treated with all classes except neonicotinoids, cotton treated with all classes except pyrethroids, cotton treated with all classes except carbamates and organophosphates, and an untreated control. Plots were scouted weekly and insecticide applications were made with the most efficacious and economical insecticides for each treatment when that treatment reached threshold for a particular insect pest(s). The primary insects at both locations were tobacco thrips and tarnished plant bugs. Thrips pressure was similar at both locations and generally showed that all insecticide treatments provided a similar level of protection compared with the untreated control. At the Stoneville location where tarnished plant bug pressure was greatest, cotton yields and economic returns differed between plots where all classes of insecticides were applied compared with the untreated control and where neonicotinoids were excluded. However, in Starkville where tarnished plant bug pressure was less, there were no differences among treatments. Although yield and economic returns were similar in high tarnished plant bug pressure areas when using all classes compared with managing without pyrethroids or organophosphates, a rotation among all insecticide classes should be beneficial for resistance management in Mid-South cotton production.