Extracting the truth through chemical analyses: Early life histories of Victorian-era dental patients in Aotearoa New Zealand.

OBJECTIVES: There are few bioarcheological analyses of life experiences in colonial period Aotearoa New Zealand, despite this being a time of major adaptation and social change. In our study, early life histories are constructed from multi-isotope and enamel peptide analysis of permanent first molars associated with Victorian era dental practices operating between AD 1881 and 1905 in Invercargill. Chemical analyses of the teeth provide insight into the childhood feeding practices, diet, and mobility of the people who had their teeth extracted. MATERIALS AND METHODS: Four permanent left mandibular first molars were analyzed from a cache of teeth discovered at the Leviathan Gift Depot site during excavations in 2019. The methods used were: (1) enamel peptide analysis to assess chromosomal sex; (2) bulk (δ13 Ccarbonate ) and incremental (δ13 Ccollagen and δ15 N) isotope analysis of dentin to assess childhood diet; and (3) strontium (87 Sr/86 Sr) and oxygen (δ18 O) isotope analysis of enamel to assess childhood residency. Two modern permanent first molars from known individuals were analyzed as controls. RESULTS: The archaeological teeth were from three chromosomal males and one female. The protein and whole diets were predominately based on C3 -plants and domestic animal products (meat and milk). A breastfeeding signal was only identified in one historic male. All individuals likely had childhood residences in Aotearoa. DISCUSSION: Unlike most bioarcheological studies that rely on the remains of the dead, the teeth analysed in this study were extracted from living people. We suggest that the dental patients were likely second or third generation colonists to Aotearoa, with fairly similar childhood diets. They were potentially lower-class individuals either living in, or passing through, the growing colonial center of Invercargill.

Evaluating atezolizumab in patients with urinary tract squamous cell carcinoma (AURORA): study protocol for a single arm, open-label, multicentre, phase II clinical trial.

BACKGROUND: Bladder and urinary tract cancers account for approximately 21,000 new diagnoses and 5,000 deaths annually in the UK. Approximately 90% are transitional cell carcinomas where advanced disease is treated with platinum based chemotherapy and PD-1/PD-L1 directed immunotherapy. Urinary tract squamous cell carcinoma (UTSCC) accounts for about 5% of urinary tract cancers overall making this a rare disease. We have yet to establish definitive systemic treatment options for advanced UTSCC. Preliminary translational data, from UTSCC patient tumour samples, indicate high PD-L1 expression and tumour infiltrating lymphocytes in a proportion of cases. Both of these features are associated with differential gene expression consistent with a tumour/immune microenvironment predicted to be susceptible to immune checkpoint directed immunotherapy which we will evaluate in the AURORA trial. METHODS: AURORA is a single arm, open-label, multicentre,UK phase II clinical trial. 33 patients will be recruited from UK secondary care sites. Patients with UTSCC, suitable for treatment with palliative intent, will receive atezolizumab PD-L1 directed immunotherapy (IV infusion, 1680 mg, every 28 days) for one year if tolerated. Response assessment, by cross sectional imaging will occur every 12 weeks. AURORA uses a Simon's 2-stage optimal design with best overall objective response rate (ORR, by RECIST v1.1) at a minimum of 12 weeks from commencing treatment as the primary endpoint. Secondary endpoints will include overall survival, progression-free survival, duration of response, magnitude of response using waterfall plots of target lesion measurements, quality of life using the EORTC QLQ-C30 tool, safety and tolerability (CTCAE v5) and evaluation of potential biomarkers of treatment response including PD-L1 expression. Archival tumour samples and blood samples will be collected for translational analyses. DISCUSSION: If this trial shows atezolizumab to be safe and effective it may lead to a future late phase randomised controlled trial in UTSCC. Ultimately, we hope to provide a new option for treatment for such patients. TRIAL REGISTRATIONS: EudraCT Number: 2021-001995-32 (issued 8th September 2021); ISRCTN83474167 (registered 11 May 2022); NCT05038657 (issued 9th September 2021).

A randomised controlled trial of a digital intervention (Renewed) to support symptom management, wellbeing and quality of life in cancer survivors.

BACKGROUND: Many cancer survivors following primary treatment have prolonged poor quality of life. AIM: To determine the effectiveness of a bespoke digital intervention to support cancer survivors. DESIGN: Pragmatic parallel open randomised trial. SETTING: UK general practices. METHODS: People having finished primary treatment (<= 10 years previously) for colo-rectal, breast or prostate cancers, with European-Organization-for-Research-and-Treatment-of-Cancer QLQ-C30 score <85, were randomised by online software to: 1)detailed 'generic' digital NHS support ('LiveWell';n=906), 2) a bespoke complex digital intervention ('Renewed';n=903) addressing symptom management, physical activity, diet, weight loss, distress, or 3) 'Renewed-with-support' (n=903): 'Renewed' with additional brief email and telephone support. RESULTS: Mixed linear regression provided estimates of the differences between each intervention group and generic advice: at 6 months (primary time point: n's respectively 806;749;705) all groups improved, with no significant between-group differences for EORTC QLQ-C30, but global health improved more in both intervention groups. By 12 months there were: small improvements in EORTC QLQ-C30 for Renewed-with-support (versus generic advice: 1.42, 95% CIs 0.33-2.51); both groups improved global health (12 months: renewed: 3.06, 1.39-4.74; renewed-with-support: 2.78, 1.08-4.48), dyspnoea, constipation, and enablement, and lower NHS costs (generic advice £265: in comparison respectively £141 (153-128) and £77 (90-65) lower); and for Renewed-with-support improvement in several other symptom subscales. No harms were identified. CONCLUSION: Cancer survivors quality of life improved with detailed generic online support. Robustly developed bespoke digital support provides limited additional short term benefit, but additional longer term improvement in global health enablement and symptom management, with substantially lower NHS costs.