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Earlier studies have suggested an association between breast cancer aggressiveness and the presence of viral sequences resembling mouse mammary tumor virus (MMTV). This study was to determine if inflammatory breast cancer (IBC) in the United States had a higher proportion of cases with these viral sequences than non-IBC patients and if specific risk factors for the sequences could be identified. Biospecimens from 67 patients in the North American IBC Registry were selected for sequencing of MMTV envlike sequences. The presence or absence of the viral sequences was compared to progression free survival (PFS), risk factors including exogenous hormones, and tumor markers. Of the 67 cases, 44 were positive for viral sequences (VSP), 17 were negative (VSN) and six were excluded from analysis because of insufficient DNA to perform replicates. The 72% of VSP cases was significantly more than the 40% in non-IBC U.S. breast cancer patients (p < 0.0001). Non-significant trends suggested that VSP patients were more likely to be HER-2 neu positive and ER negative, have a stronger exposure to exogenous hormones, and have a shorter PFS than VSN patients. MMTV-related sequences appear to be related to the aggressiveness of breast cancer with a higher incidence in North American IBC than in non-IBC breast cancer. [ABSTRACT FROM AUTHOR]

Background: The possible link between psychological factors and length of cancer survival has generated a literature of contradictory findings. Associations usually have not been found when general psychological symptoms are assessed. Associations usually have been found for predictors related to expressive versus repressive emotional coping (e.g., depression, "fighting spirit," hostility, and type C personality); however, even these associations have been relatively small, when compared with those for medical factors. Yet few studies have adequately controlled for medical and treatment-related factors.Purpose: Within a Cancer and Leukemia Group B (CALGB) national clinical trial of four adjuvant therapy regimens for stage II breast cancer (CALGB 8082), this study prospectively examined the contribution of potential psychological predictors to length of disease-free and overall survival over a 15-year period.Methods: Subjects were 280 women with stage II breast cancer, out of a total of 899, who were randomly assigned to receive CMFVP (cyclophosphamide-methotrexate-fluorouracil-vincristine-prednisone) for two 6-week cycles or six 4-week cycles, then subsequently randomly assigned to receive or not to receive VATH (vinblastine-doxorubicin-thiotepa-fluoxymesterone). Subjects were recruited during the period between October 1980 and August 1984, inclusive, and followed until January 1996. Prior to chemotherapy, psychological symptoms were assessed using the Symptom Check List-90-Revised (SCL-90-R). SCL-90-R scores were trichotomized into categories representing high, medium, and low distress. Basic base-line sociodemographic data (including age, ethnicity, education, and marital status) and medical data (including lymph node status, estrogen receptor status, menopausal status, and performance status) were collected. Subjects with psychosocial data differed from those without psychosocial data solely in their higher percentage of classification in the mild limitation category of the Zubrod (Eastern Cooperative Oncology Group) performance status rating (subjects with psychosocial data: 14%; subjects without psychosocial data: 8%).Results: In stepwise Cox regression analyses that controlled for sociodemographic and medical variables, there was no significant predictive effect of the level of distress (as measured by the SCL-90-R trichotomized scores) on length of disease-free and overall survival of the study subjects. Risk ratios for low versus high distress were 1.01 (95% confidence interval [CI] = 0.62-1.66) for disease-free survival and 1.03 (95% CI = 0.58-1.82) for overall survival.Conclusions: This study failed to provide evidence that psychological factors contributed to length of disease-free or overall survival of women who received adjuvant chemotherapy (either CMFVP alone or CMFVP followed by VATH) for treatment of stage II breast cancer.Implications: In the context of far more potent medical factors, the contribution of psychological factors to disease-free and overall survival is likely to be relatively small. Future research should focus on specific theory-driven predictors rather than on general psychological symptoms. Moreover, it should be based on clinical studies using a controlled, prospective design, in which the effects of medical factors may be distinguished and psychological predictors are clear antecedents of survival outcomes. [ABSTRACT FROM AUTHOR]

The lack of standardization in patient-reported outcome measures (PROMs) has made measurement and comparison of quality of life (QoL) outcomes in research focused on obesity treatment challenging. This study reports on the results of the second and third global multidisciplinary Standardizing Quality of life measures in Obesity Treatment (S.Q.O.T.) consensus meetings, where a core set of PROMs to measure nine previously selected patient-reported outcomes (PROs) in obesity treatment research was established. The S.Q.O.T. II online and S.Q.O.T. III face-to-face hybrid consensus meetings were held in October 2021 and May 2022. The meetings were led by an independent moderator specializing in PRO measurement. Nominal group techniques, Delphi exercises, and anonymous voting were used to select the most suitable PROMs by consensus. The meetings were attended by 28 and 27 participants, respectively, including a geographically diverse selection of people living with obesity (PLWO) and experts from various disciplines. Out of 24 PROs and 16 PROMs identified in the first S.Q.O.T. consensus meeting, the following nine PROs and three PROMs were selected via consensus: BODY-Q (physical function, physical symptoms, psychological function, social function, eating behavior, and body image), IWQOL-Lite (self-esteem), and QOLOS (excess skin). No PROM was selected to measure stigma as existing PROMs deemed to be inadequate. A core set of PROMs to measure QoL in research focused on obesity treatment has been selected incorporating patients' and experts' opinions. This core set should serve as a minimum to use in obesity research studies and can be combined with clinical parameters., (© 2024 World Obesity Federation.)

Purpose: The focus of measuring success in obesity treatment is shifting from weight loss to patients' health and quality of life. The objective of this study was to select a core set of patient-reported outcomes and patient-reported outcome measures to be used in clinical obesity care., Materials and Methods: The Standardizing Quality of Life in Obesity Treatment III, face-to-face hybrid consensus meeting, including people living with obesity as well as healthcare providers, was held in Maastricht, the Netherlands, in 2022. It was preceded by two prior multinational consensus meetings and a systematic review., Results: The meeting was attended by 27 participants, representing twelve countries from five continents. The participants included healthcare providers, such as surgeons, endocrinologists, dietitians, psychologists, researchers, and people living with obesity, most of whom were involved in patient representative networks. Three patient-reported outcome measures (patient-reported outcomes) were selected: the Impact of Weight on Quality of Life-Lite (self-esteem) measure, the BODY-Q (physical function, physical symptoms, psychological function, social function, eating behavior, and body image), and the Quality of Life for Obesity Surgery questionnaire (excess skin). No patient-reported outcome measure was selected for stigma., Conclusion: A core set of patient-reported outcomes and patient-reported outcome measures for measuring quality of life in clinical obesity care is established incorporating patients' and experts' opinions. This set should be used as a minimum for measuring quality of life in routine clinical practice. It is essential that individual patient-reported outcome measure scores are shared with people living with obesity in order to enhance patient engagement and shared decision-making., (© 2024. The Author(s).)

Background: The length of a patient's stay (LOS) in a hospital is one metric used to compare the quality of care, as a longer LOS may flag higher complication rates or less efficient processes. A meaningful comparison of LOS can only occur if the expected average length of stay (ALOS) is defined first. This study aimed to define the expected ALOS of primary and conversion bariatric surgery in Australia and to quantify the effect of patient, procedure, system, and surgeon factors on ALOS., Methods: This was a retrospective observational study of prospectively maintained data from the Bariatric Surgery Registry of 63 604 bariatric procedures performed in Australia. The primary outcome measure was the expected ALOS for primary and conversion bariatric procedures. The secondary outcome measures quantified the change in ALOS for bariatric surgery resulting from patient, procedure, hospital, and surgeon factors., Results: Uncomplicated primary bariatric surgery had an ALOS (SD) of 2.30 (1.31) days, whereas conversion procedures had an ALOS (SD) of 2.71 (2.75) days yielding a mean difference (SEM) in ALOS of 0.41 (0.05) days, P < 0.001. The occurrence of any defined adverse event extended the ALOS of primary and conversion procedures by 1.14 days (CI 95% 1.04-1.25), P < 0.001 and 2.33 days (CI 95% 1.54-3.11), P < 0.001, respectively. Older age, diabetes, rural home address, surgeon operating volume and hospital case volume increased the ALOS following bariatric surgery., Conclusions: Our findings have defined Australia's expected ALOS following bariatric surgery. Increased patient age, diabetes, rural living, procedural complications and surgeon and hospital case volume exerted a small but significant increase in ALOS., Study Type: Retrospective observational study of prospectively collected data., (© 2023 The Authors. ANZ Journal of Surgery published by John Wiley & Sons Australia, Ltd on behalf of Royal Australasian College of Surgeons.)

Purpose: This study aims to determine if the hospital efficiency, safety and health outcomes are equal in patients who receive bariatric surgery in government-funded hospitals (GFH) versus privately funded hospitals (PFH)., Materials and Methods: This is a retrospective observational study of prospectively maintained data from the Australia and New Zealand Bariatric Surgery Registry of 14,862 procedures (2134 GFH and 12,728 PFH) from 33 hospitals (8 GFH and 25 PFH) performed in Victoria, Australia, between January 1st, 2015, and December 31st, 2020. Outcome measures included the difference in efficacy (weight loss, diabetes remission), safety (defined adverse event and complications) and efficiency (hospital length of stay) between the two health systems., Results: GFH treated a higher risk patient group who were older by a mean (SD) 2.4 years (0.27), P < 0.001; had a mean 9.0 kg (0.6) greater weight at time of surgery, P < 0.001; and a higher prevalence of diabetes at day of surgery OR = 2.57 (CI 95% 2.29-2.89), P < 0.001. Despite these baseline differences, both GFH and PFH yielded near identical remission of diabetes which was stable up to 4 years post-operatively (57%). There was no statistically significant difference in defined adverse events between the GFH and PFH (OR = 1.24 (CI 95% 0.93-1.67), P = 0.14). Both healthcare settings demonstrated that similar covariates affect length of stay (LOS) (diabetes, conversion bariatric procedures and defined adverse event); however, these covariates had a greater effect on LOS in GFH compared to PFH., Conclusions: Bariatric surgery performed in GFH and PFH yields comparable health outcomes (metabolic and weight loss) and safety. There was a small but statistically significant increased LOS following bariatric surgery in GFH., (© 2023. The Author(s).)

Objective: There is limited evidence on the development of pancreatic and oesophagogastric cancer, how patients decide to seek help and the factors impacting help-seeking. Our study, the first in Australia, aimed to explore symptom appraisal and diagnostic pathways in these patients. A secondary aim was to examine the potential to recruit cancer patients through a cancer quality registry., Methods: Patients diagnosed with pancreatic or oesophagogastric cancer were recruited through Monash University's Upper-Gastrointestinal Cancer Registry. Data collected through general practitioners (GP) and patient questionnaires included symptoms and their onset, whereas patient interviews focused on the patient's decision-making in seeking help from healthcare pracitioners. Data collection and analysis was informed by the Aarhus statement. Coding was inductive, and themes were mapped onto the Model of Pathways to Treatment., Results: Between November 2018 and March 2020, 27 patient questionnaires and 13 phone interviews were completed. Prior to diagnosis, patients lacked awareness of pancreatic and oesophagogastric cancer symptoms, leading to the normalisation, dismissal and misattribution of the symptoms. Patients initially self-managed symptoms, but worsening of symptoms and jaundice triggered help-seeking. Competing priorities, beliefs about illnesses and difficulties accessing healthcare delayed help-seeking., Conclusion: Increased awareness of insidious pancreatic and oesophagogastric cancer symptoms in patients and general practitioners may prompt more urgent investigations and lead to earlier diagnosis., (© 2022 The Authors. European Journal of Cancer Care published by John Wiley & Sons Ltd.)

Background: This study: (i) assessed compliance with a consensus set of quality indicators (QIs) in pancreatic cancer (PC); and (ii) evaluated the association between compliance with these QIs and survival., Methods: Four years of data were collected for patients diagnosed with PC. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). A multivariable analysis tested the relationship between significant patient and hospital characteristics, patient cluster effects within hospitals and survival., Results: 1061 patients were eligible for this study. Significant association with improved survival were: (i) in the potentially resectable group having adjuvant chemotherapy administered following surgery or a reason documented (HR, 0.29; 95 CI, 0.19-0.46); (ii) in the locally advanced group included having chemotherapy ± chemoradiation, or a reason documented for not undergoing treatment (HR, 0.38; 95 CI, 0.25-0.58); and (iii) in the metastatic disease group included having documented performance status at presentation (HR, 0.65; 95 CI, 0.47-0.89), being seen by an oncologist in the absence of treatment (HR, 0.48; 95 CI, 0.31-0.77), and disease management discussed at a multidisciplinary team meeting (HR, 0.79; 95 CI, 0.64-0.96)., Conclusion: Capture of a concise data set has enabled quality of care to be assessed., (Copyright © 2021 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Multiple genome-wide association studies of schizophrenia have reported associations between genetic variants within the MHC region and disease risk, an association that has been partially accounted for by alleles of the complement component 4 (C4) gene. Following on previous findings of association between both C4 and other complement-related variants and memory function, we tested the hypothesis that polygenic scores calculated based on identified schizophrenia risk alleles within the "complement" system would be broadly associated with memory function and associated brain structure. We tested this using a polygenic risk score (PRS) calculated for complement genes, but excluding C4 variants. Higher complement-based PRS scores were observed to be associated with lower memory scores for the sample as a whole (N = 620, F change = 8.25; p = .004). A significant association between higher PRS and lower hippocampal volume was also observed (N = 216, R 2 change = 0.016, p = .015). However, after correcting for further testing of association with the more general indices of cortical thickness, surface area or total brain volume, none of which were associated with complement, the association with hippocampal volume became non-significant. A post-hoc analysis of hippocampal subfields suggested an association between complement PRS and several hippocampal subfields, findings that appeared to be particularly driven by the patient sample. In conclusion, our study yielded suggestive evidence of association between complement-based schizophrenia PRS and variation in memory function and hippocampal volume., (© 2020 Wiley Periodicals LLC.)

Background: Early life adversity (ELA) is a significant risk factor for mental health disorders. One hypothesised mechanism by which this occurs is via an effect on immune response. In this analysis of epidemiological data, we tested whether ELA was associated with cognitive performance, and if so, whether these effects were influenced by immune function., Methods: We investigated the longitudinal relationship between ELA, inflammatory markers, and cognition in data from Avon Longitudinal Study of Parents And Children (ALSPAC; n ~ 5000). ELA was defined in terms of physical/emotional abuse, harsh parenting, or domestic violence before 5 years. Social cognition was measured in terms of theory of mind, and general cognitive ability was measured using IQ. Inflammatory markers included serum C-reactive protein and interleukin-6 levels., Results: A significant association was observed between IQ and harsh parenting, whereby children who were physically disciplined had lower IQ scores (accounting for relevant social factors). Both immune markers were associated with variation in cognition, however, neither accounted for the effects of ELA on cognition., Discussion: This study highlights the impact of ELA on cognition. In the absence of evidence that these effects are explained by inflammation, other mechanisms by which the effects of ELA are mediated are discussed.

Variation in cognitive performance, which strongly predicts functional outcome in schizophrenia (SZ), has been associated with multiple immune-relevant genetic loci. These loci include complement component 4 (C4A), structural variation at which was recently associated with SZ risk and synaptic pruning during neurodevelopment and cognitive function. Here, we test whether this genetic association with cognition and SZ risk is specific to C4A, or extends more broadly to genes related to the complement system. Using a gene-set with an identified role in "complement" function (excluding C4A), we used MAGMA to test if this gene-set was enriched for genes associated with human intelligence and SZ risk, using genome-wide association summary statistics (IQ; N = 269 867, SZ; N = 105 318). We followed up this gene-set analysis with a complement gene-set polygenic score (PGS) regression analysis in an independent data set of patients with psychotic disorders and healthy participants with cognitive and genomic data (N = 1000). Enrichment analysis suggested that genes within the complement pathway were significantly enriched for genes associated with IQ, but not SZ. In a gene-based analysis of 90 genes, SERPING1 was the most enriched gene for the phenotype of IQ. In a PGS regression analysis, we found that a complement pathway PGS associated with IQ genome-wide association studies statistics also predicted variation in IQ in our independent sample. This association (observed across both patients and controls) remained significant after controlling for the relationship between C4A and cognition. These results suggest a robust association between the complement system and cognitive function, extending beyond structural variation at C4A., (© 2019 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.)

Purpose: The Upper Gastrointestinal Cancer Registry (UGICR) was developed to monitor and improve the quality of care provided to patients with upper gastrointestinal cancers in Australia., Participants: It supports four cancer modules: pancreatic, oesophagogastric, biliary and primary liver cancer. The pancreatic cancer (PC) module was the first module to be implemented, with others being established in a staged approach. Individuals are recruited to the registry if they are aged 18 years or older, have received care for their cancer at a participating public/private hospital or private clinic in Australia and do not opt out of participation., Findings to Date: The UGICR is governed by a multidisciplinary steering committee that provides clinical governance and oversees clinical working parties. The role of the working parties is to develop quality indicators based on best practice for each registry module, develop the minimum datasets and provide guidance in analysing and reporting of results. Data are captured from existing data sources (population-based cancer incidence registries, pathology databases and hospital-coded data) and manually from clinical records. Data collectors directly enter information into a secure web-based Research Electronic Data Capture (REDCap) data collection platform. The PC module began with a pilot phase, and subsequently, we used a formal modified Delphi consensus process to establish a core set of quality indicators for PC. The second module developed was the oesophagogastric cancer (OGC) module. Results of the 1 year pilot phases for PC and OGC modules are included in this cohort profile., Future Plans: The UGICR will provide regular reports of risk-adjusted, benchmarked performance on a range of quality indicators that will highlight variations in care and clinical outcomes at a health service level. The registry has also been developed with the view to collect patient-reported outcomes (PROs), which will further add to our understanding of the care of patients with these cancers., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

This Phase 1/2, dose-escalating study of rigosertib enrolled 22 patients with higher-risk myelodysplastic syndromes (MDS) (n=9) and acute myeloid leukemia (AML; n=13) who had relapsed or were refractory to standard therapy and for whom no second-line therapies were approved. Patients received 3- to 7-day continuous intravenous infusions of rigosertib, an inhibitor of Ras-effector pathways that interacts with the Ras-binding domains, common to several signaling proteins including Raf and PI3 kinase. Rigosertib was administered at doses of 650-1700mg/m 2 /day in 14-day cycles. Initial dose escalation followed a Fibonacci scheme, followed by recommended phase 2 dose confirmation in an expanded cohort. Rigosertib was well tolerated for up to 23 cycles, with no treatment-related deaths and 18% of patients with related serious adverse events (AEs). Common AEs were fatigue, diarrhea, pyrexia, dyspnea, insomnia, and anemia. Rigosertib exhibited biologic activity, with reduction or stabilization of bone marrow blasts and improved peripheral blood counts in a subset of patients. Ten of 19 evaluable patients (53%) demonstrated bone marrow/peripheral blood responses (n=4 MDS, n=1 AML) or stable disease (n=3 MDS, n=2 AML). Median survival was 15.7 and 2.0 months for responders and non-responders, respectively. Additional studies of rigosertib are ongoing in higher-risk MDS (NCT00854646)., (Copyright © 2017 Elsevier Ltd. All rights reserved.)