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The definition of cure in colon cancer: a pooled analysis of 15 randomized clinical trials
No full textImportance: The definition of cure in stage II to III colon cancer (CC) remains unclear due to limitations in conventional end points, which include deaths and second primary tumors as events. These can complicate communication with patients regarding long-term outcomes. Objective: To distinguish relapses from competing health-related events to classify long-term outcomes years after surgery and explore when the incidence of true relapses of the initial CC approaches 0% to define cure in this disease. Design, Setting, and Participants: This pooled analysis of individual patient–level data from 15 phase 3 randomized clinical trials assessed time to CC-related relapse using Kaplan-Meier and Aalen-Johansen methods, with death and second primary tumors treated as competing risks. Cox regression models evaluated prognostic associations, stratified by sex, stage, and tumor. Patients with stage II to III CC who underwent adjuvant chemotherapy were included. All patients had undergone radical surgery for CC and received adjuvant chemotherapy with a median follow-up of at least 6 years. The Adjuvant Colon Cancer Endpoints (ACCENT) and the International Duration Evaluation of Adjuvant Chemotherapy (IDEA) databases included adjuvant studies conducted between 1996 and 2015. Data were analyzed from February 2022 to June 2025. Exposures Adjuvant chemotherapy regimens varied across trials, including fluoropyrimidines alone or in combination with oxaliplatin or biologic agents. Main Outcomes and Measures: The primary outcome was time to CC-related recurrence. The predefined threshold for cure was a recurrence risk below 0.5%. Results: Of 35 213 included patients, 19 346 (54.9%) were male, and the mean (SD) age was 60.2 (10.8) years. The incidence rate of recurrence peaked at 6.4% (1993 of 31 373) between month 6 and month 12 and decreased continuously until year 10 of follow-up never exceeding 0.5%. Recurrence rate appeared to increase again after year 10 and peaked at 2.0% during year 12.5 to year 13, a pattern observed exclusively in the MOSAIC trial. Competing-event analysis revealed that death and second primary tumors inflated the apparent recurrence rate, especially for older patients. The overall cumulative incidence of relapse with death as competing risk was lower among female patients (hazard ratio, 0.58; 95% CI, 0.45-0.76; P < .001). Conclusions and Relevance: In this pooled analysis of phase 3 randomized clinical trials, a recurrence rate less than 0.5% occurred after 6 years from surgery, supporting a practical definition of cure. Recognizing this milestone may improve patient communication, guide follow-up duration, and reduce unnecessary long-term surveillance
Introduction: Tracing women's activism through crises
Get PDFIntroduction to the Nottingham French Studies special issue Women and Activism in the Francophone World
Access to services for mental ill-health and substance use among people released from prison in Scotland (RELEASE): Retrospective observational cohort study protocol.
Get PDFINTRODUCTION:
Mental health and substance use (MH/SU) problems are highly prevalent among the prison population. However, early and preventative post-imprisonment care appears to be insufficient to meet the MH/SU needs of people released. This is demonstrated by elevated rates of MH/SU-related emergency care and deaths attributable to alcohol, drugs and suicide. Studies examining post-imprisonment healthcare contacts across community, outpatient, inpatient and emergency services for MH/SU are required to address this issue. This protocol paper describes the outcome of data linkage and details our plans for data cleaning and analysis.
METHODS:
The RELEASE study will follow a retrospective observational cohort design. This is the first study using national individual-level linked administrative health and prison data from Scotland. We report the results of creating the cohort, and outline proposed methods for data preparation and analysis. Within the cohort, the exposed group comprises everyone released from prison in 2015, and the unexposed group consists of a random sample of the general population matched (1:5 ratio) on age, sex, postcode and postcode-derived index of multiple deprivation, and with no prison exposure in the preceding 5 years. Health data (community prescribing, outpatient visits, specialist substance use, psychiatric inpatient, general inpatient, out-of-hours general practice, 24-hour National Health Service [NHS] helpline, ambulance, and emergency services), deaths data, and prison data (admissions, releases, demographic data) were linked to the cohort using unique identifiers. Service contacts associated with MH/SU will be quantified and compared across the two groups using regression modelling, controlling for potential confounding variables, reimprisonment and deaths.
CONCLUSION:
RELEASE is a comprehensive study with potential to inform post-imprisonment MH/SU service delivery, whilst the dataset holds significant potential for exploring other health conditions and outcomes. This research will allow for an unprecedented understanding of post-imprisonment service use patterns in Scotland, and RELEASE will make a significant public health contribution given the overrepresentation of people released in costly emergency care contact and death rates
A phenomenological exploration of women's experiences of matrescence: implications for identity development
No full textMatrescence is the term used to refer to the developmental process of becoming a mother, encompassing conception through to the postpartum period. This vulnerable period involves profound neurological restructuring driven by hormonal and environmental changes. Despite the high rates of maternal mental illness, the socioemotional developments that accompany this neurological restructuring remain under researched. To better understand the social experience of matrescence, this study investigated how women experience the transition into motherhood, exploring the topics of body autonomy, social expectations, mental health, and identity development. Interviews with six postpartum women revealed how the experience reduced personal autonomy in motherhood, alongside the necessary cognitive adjustment, functioned as a key mechanism driving maternal identity transformation. The findings of this study provide critical context for understanding how neuroplasticity observed in matrescence can be expressed in real-time. The analysis also illuminated how social support functions as a crucial buffer against emotional distress for new mothers, providing insight into potential strategies to support new mothers. This study underscores the importance of further research into maternal identity transformation and the role of social support in facilitating this transition
Against conferencing-as-usual in times of genocide: criminology, complicity, and sexual violence in Palestine
Get PDFNo abstract available
India is not a teaching shop: Rethinking foreign university campuses
No full textAs foreign university campuses consolidate their position in India, will there be a void in its teaching culture and a lack of an Indian ethos? Read this article by Prof Sreevas Sahasranamam to know more... [blog post
Joint neutrino oscillation analysis from the T2K and NOvA experiments
Get PDFThe landmark discovery that neutrinos have mass and can change type (or flavour) as they propagate—a process called neutrino oscillation1–6—has opened up a rich array of theoretical and experimental questions being actively pursued today. Neutrino oscillation remains the most powerful experimental tool for addressing many of these questions, including whether neutrinos violate charge-parity (CP) symmetry, which has possible connections to the unexplained preponderance of matter over antimatter in the Universe7–11. Oscillation measurements also probe the mass-squared differences between the different neutrino mass states (Δm2), whether there are two light states and a heavier one (normal ordering) or vice versa (inverted ordering), and the structure of neutrino mass and flavour mixing12. Here we carry out the first joint analysis of datasets from NOvA13 and T2K14, the two currently operating long-baseline neutrino oscillation experiments (hundreds of kilometres of neutrino travel distance), taking advantage of our complementary experimental designs and setting new constraints on several neutrino sector parameters. This analysis provides new precision on the m Δ 32 2 mass difference, finding 2.43 × +0.04 − −0.03 +0.03 − −2.48 × −0.04 10 eV 10 eV 3 2 in the normal ordering and 3 2 in the inverted ordering, as well as a 3σ interval on δCP of [−1.38π, 0.30π] in the normal ordering and [−0.92π, −0.04π] in the inverted ordering. The data show no strong preference for either mass ordering, but notably, if inverted ordering were assumed true within the three-flavour mixing model, then our results would provide evidence of CP symmetry violation in the lepton sector
Edges of Care: Systemic Inequalities and Experiences of Care for Children Affected by Parental Drug Use in School
No full textNo abstract available
Molnupiravir or nirmatrelvir–ritonavir plus usual care versus usual care alone in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial
Get PDFBackground:
Molnupiravir and nirmatrelvir–ritonavir are oral antivirals that have shown efficacy in preventing disease progression in outpatients with COVID-19. We aimed to evaluate these treatments for patients hospitalised with COVID-19 pneumonia, for whom data on these antivirals are scarce.
Methods:
The RECOVERY trial is a randomised, controlled, open-label, adaptive platform trial testing treatments for COVID-19. In this study we report the molnupiravir and nirmatrelvir–ritonavir comparisons from the RECOVERY trial. In each comparison, participants aged 18 years and older were randomly allocated (1:1) to the relevant antiviral (5 days of molnupiravir 800 mg twice daily or 300 mg nirmatrelvir and 100 mg ritonavir twice daily) in addition to usual care, or to usual care alone. The molnupiravir comparison was conducted at 75 hospitals in the UK, two in Nepal, and two in Indonesia; the nirmatrelvir–ritonavir comparison was conducted at 32 hospitals in the UK. Participants could take part in both comparisons. The primary outcome was 28-day mortality, and secondary outcomes were time to discharge alive from hospital and progression to invasive ventilation or death. Analysis was by intention to treat. Both comparisons were stopped because of low recruitment. This study is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936.
Findings:
From Jan 24, 2022, to May 24, 2023, 923 participants were recruited to the molnupiravir comparison (445 allocated to molnupiravir and 478 to usual care), and from March 31, 2022, to May 24, 2023, 137 participants were recruited to the nirmatrelvir–ritonavir comparison (68 allocated to nirmatrelvir–ritonavir and 69 to usual care). More than three-quarters of participants were vaccinated and had antispike antibodies at randomisation, and more than two-thirds were receiving other SARS-CoV-2 antivirals. In the molnupiravir comparison, 74 (17%) participants allocated to molnupiravir and 79 (17%) allocated to usual care died within 28 days (hazard ratio [HR] 0·93 [95% CI 0·68–1·28], p=0·66). In the nirmatrelvir–ritonavir comparison, 13 (19%) participants allocated to nirmatrelvir–ritonavir and 13 (19%) allocated to usual care died within 28 days (HR 1·02 [0·47–2·23], p=0·96). In neither comparison was there evidence of any difference in the duration of hospitalisation or the proportion of participants progressing to invasive ventilation or death.
Interpretation:
Adding molnupiravir or nirmatrelvir–ritonavir to usual care was not associated with improvements in clinical outcomes. However, low recruitment meant a clinically meaningful benefit of treatment could not be ruled out, particularly for nirmatrelvir–ritonavir
Data sources:
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