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Competing Interests: EP has received funding from the NHMRC and NSW Health. She is a clinical geneticist at Sydney Children’s Hospitals Network-Randwick and a member of the medical and scientific advisory committee for Rare Voices Australia, the national peak body for Australians living with a rare condition. IS has received funding from the NHMRC and the NSW Department of Health. She is also a Board member of Self Advocacy Sydney, an organisation run by and for people with intellectual disability. JS is Director of the Disability Innovation Institute, which has received funding from the NHMRC and the NSW Department of Health. JL, OAM has received funding from the NHMRC and the NSW Department of Health. She is also a Board member of Self Advocacy Sydney, an organisation run by and for people with intellectual disability. SS has received funding from the NHMRC and the NSW Department of Health. She is also an employee at Self-Advocacy Sydney, an organisation run by and for people with intellectual disability. JB and BT have received funding from the NHMRC. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Objectives: To document how many pregnant women with COVID-19 reported in the literature had participated in randomised trials, what treatments they received outside such trials and compare the latter with evidence-based treatment recommendations., Study Design: A systematic review of observational studies., Methods: Two clinical trial registries were searched to identify COVID-19 trials open to pregnant women. Studies were then extracted from a regularly updated list of scientific case reports and case series of confirmed or suspected maternal COVID-19 in pregnancy to identify the number of women enrolled into a trial and the pharmaceutical treatments they received outside such trials., Results: 156 studies (case reports, case series and registries) reporting 43,185 pregnant women with COVID-19, after de-duplication. Of these 2,671 (6.2%) were potentially eligible for a randomised trial but only seven women (0.26%) were reported to have enrolled. For 2,839 women the papers included information on treatment received, 1515/2829 (54%) women had received ≥ 1 treatment and in total a COVID-19 pharmaceutical treatment was administered 1,296 times outside of a trial. In 566 (44%) cases the treatments administered to the pregnant women were not recommended by the National Institutes of Health (NIH) at the time of administration. Of 179 case reports of women with COVID 19 in pregnancy, 109/179 women received ≥ 1 COVID-19 pharmaceutical treatment and in total COVID-19 experimental pharmaceutical treatments were administered 274 times., Conclusion: During the early phase of the COVID-19 pandemic, pregnant women excluded from randomised trials did not avoid unproven or ineffective treatments., (Copyright © 2022. Published by Elsevier B.V.)

Adenomatous polyposis coli (APC) truncations occur in many colorectal cancers and are often associated with immune infiltration. The aim of this study was to determine whether a combination of Wnt inhibition with anti-inflammatory (sulindac) and/or proapototic (ABT263) drugs can reduce colon adenomas. Apc min/+ and doublecortin-like kinase 1 ( Dclk1 ) Cre/+ ;Apc fl/fl mice were exposed to dextran sulphate sodium (DSS) in their drinking water to promote the formation of colon adenomas. Mice were then treated with either a Wnt-signaling antagonist pyrvinium pamoate (PP), an anti-inflammatory agent sulindac or proapoptotic compound ABT263 or a combination of PP+ABT263, or PP+sulindac. Colon adenoma frequency, size, and T-cell abundance were measured. DSS treatment resulted in significant increases in colon adenoma number ( P < 0.001, n > 5) and burden in Apc min/+ ( P < 0.01, n > 5) and Dclk1 Cre/+ ;Apc fl/fl ( P < 0.02, n > 5) mice. There was no effect on adenomas following treatment with PP in combination with ABT263. Adenoma number and burden were reduced with PP+sulindac treatment in Dclk1 Cre/+ ; Apc fl/fl mice ( P < 0.01, n > 17) and in Apc min/+ mice ( P < 0.001, n > 7) treated with sulindac or PP+sulindac with no detectable toxicity. PP treatment of Apc min/+ mice increased the frequency of CD3 + cells in the adenomas. The combination of Wnt pathway inhibition with sulindac was more effective in Dclk1 Cre/+ ; Apc fl/fl mice and provides an opportunity for killing Apc -mutant colon adenoma cells, indicating a strategy for both colorectal cancer prevention and potential new treatments for patients with advanced colorectal cancer. Outcomes from the results of this study may be translatable to the clinic for management of FAP and other patients with a high risk of developing colorectal cancer., Significance: Colorectal cancer is one of the most common cancers worldwide with limited therapeutic options. APC and other Wnt signaling mutations occur in the majority of colorectal cancers but there are currently no Wnt inhibitors in the clinic. The combination of Wnt pathway inhibition with sulindac provides an opportunity for killing Apc -mutant colon adenoma cells and suggests a strategy for colorectal cancer prevention and new treatments for patients with advanced colorectal cancer., Competing Interests: M.C. Faux reports grants from National Health and Medical Research Council of Australia during the conduct of the study. No other disclosures were reported., (© 2022 The Authors; Published by the American Association for Cancer Research.)

Background: Selection, outcome and publication biases are well described in case reports and case series but may be less of a problem early in the appearance of a new disease when all cases might appear to be worth publishing., Objective: To use a prospectively collected database of primary sources to compare the reporting of COVID-19 in pregnancy in case reports, case series and in registries over the first 8 months of the pandemic., Study Design: MEDLINE, Embase and Maternity and Infant Care databases were searched from 22 March to 5 November 2020, to create a curated list of primary sources. Duplicate reports were excluded. Case reports, case series and registry studies of pregnant women with confirmed COVID-19, where neonatal outcomes were reported, were selected and data extracted on neonatal infection status, neonatal death, neonatal intensive care unit admission, preterm birth, stillbirth, maternal critical care unit admission and maternal death., Results: 149 studies comprising 41,658 mothers and 8,854 neonates were included. All complications were more common in case reports, and in retrospective series compared with presumably prospective registry studies. Extensive overlap is likely in registry studies, with cases from seven countries reported by multiple registries. The UK Obstetric Surveillance System was the only registry to explicitly report identification and removal of duplicate cases, although five other registries reported collection of patient identifiable data which would facilitate identification of duplicates., Conclusions: Since it is likely that registries provide the least biased estimates, the higher rates seen in the other two study designs are probably due to selection or publication bias. However even some registry studies include self- or doctor-reported cases, so might be biased, and we could not completely exclude overlap of cases in some registries., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)