Geographic and sociodemographic access to systemic anticancer therapies for secondary breast cancer: a systematic review.

BACKGROUND: The review aimed to investigate geographic and sociodemographic factors associated with receipt of systemic anticancer therapies (SACT) for women with secondary (metastatic) breast cancer (SBC). METHODS: Included studies reported geographic and sociodemographic factors associated with receipt of treatment with SACT for women > 18 years with an SBC diagnosis. Information sources searched were Ovid CINAHL, Ovid MEDLINE, Ovid Embase and Ovid PsychINFO. Assessment of methodological quality was undertaken using the Joanna Briggs Institute method. Findings were synthesised using a narrative synthesis approach. RESULTS: Nineteen studies published between 2009 and 2023 were included in the review. Overall methodological quality was assessed as low to moderate. Outcomes were reported for treatment receipt and time to treatment. Overall treatment receipt ranged from 4% for immunotherapy treatment in one study to 83% for systemic anticancer therapies (unspecified). Time to treatment ranged from median 54 days to 95 days with 81% of patients who received treatment < 60 days. Younger women, women of White origin, and those women with a higher socioeconomic status had an increased likelihood of timely treatment receipt. Treatment receipt varied by geographical region, and place of care was associated with variation in timely receipt of treatment with women treated at teaching, research and private institutions being more likely to receive treatment in a timely manner. CONCLUSIONS: Treatment receipt varied depending upon type of SACT. A number of factors were associated with treatment receipt. Barriers included older age, non-White race, lower socioeconomic status, significant comorbidities, hospital setting and geographical location. Findings should however be interpreted with caution given the limitations in overall methodological quality of included studies and significant heterogeneity in measures of exposure and outcome. Generalisability was limited due to included study populations. Findings have practical implications for the development and piloting of targeted interventions to address specific barriers in a socioculturally sensitive manner. Addressing geographical variation and place of care may require intervention at a commissioning policy level. Further qualitative research is required to understand the experience and of women and clinicians. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020196490.

Murine models of advanced maternal age: a systematic review and meta-analysis.

In brief: Animal models have been developed to aid understanding of the increased incidence of adverse pregnancy complications observed in women of advanced maternal age (AMA). This systematic review of murine models of AMA demonstrates consistent effects of decreased litter size and fetal weight; this supports the future use of these models to determine pathophysiological mechanisms and test therapeutic strategies to improve poor pregnancy outcomes in AMA. Abstract: Advanced maternal age (AMA; ≥35 years of age) is associated with an increased risk of adverse pregnancy outcomes. To explore causes of adverse pregnancy outcomes in AMA, and to test candidate therapies, an increasing number of murine AMA models have been developed. The aim of this study was to systematically review the literature to assess whether murine AMA models demonstrate a reproducible effect on pregnancy outcomes. PubMed, Ovid, Web of Science and Google Scholar were searched. Studies that reported on pregnancy outcomes in AMA mice and rats were included; the SYstematic Review Centre for Laboratory animal Experimentation (SYRCLE) tool evaluated the risk of bias. Eleven mouse and six rat studies were included. AMA mice and rats had reduced litter size (standardised mean difference (SMD): -1.59, 95% confidence interval (CI): -1.84, -1.34 for mice; SMD: -1.66, 95% (CI): -2.09, -1.23 for rats) and reduced fetal weight (SMD: -0.87, 95% CI: -1.24, -0.49 for mice; SMD: -1.05, 95% CI: -1.40, -0.69 for rats). Placental weight was increased in AMA mice (SMD: 0.62, 95% CI: 0.16, 1.08). Subgroup analysis indicated that C57Bl/6 mice had less heterogeneity than other, mostly outbred, mouse strains with regards to litter size (C57 strain I2 = 68.2% vs other strain types I2 = 85.7%). The risk of bias was high, mostly due to the lack of methodological detail and unclear reporting of findings. Murine models of AMA demonstrate similar adverse pregnancy outcomes to those observed in large human epidemiological studies. The reproducible phenotypes in AMA murine models allow the exploration of mechanisms underpinning poor pregnancy outcomes and the pursuit of therapeutic interventions.

The impact of common genetic variants in the mitochondrial glycine cleavage system on relevant metabolites.

The glycine cleavage system (GCS) is a complex of four enzymes enabling glycine to serve as a source of one-carbon units to the cell. We asked whether concentrations of glycine, dimethylglycine, formate, and serine in blood are influenced by variation within GCS genes in a sample of young, healthy individuals. Fifty-two variants tagging (r2 < 0.9) the four GCS genes were tested; one variant, GLDC rs2297442-G, was significantly associated (p = .0007) with decreased glycine concentrations in serum.

The rapid disintegration of projections: the West Antarctic Ice Sheet and the intergovernmental panel on climate change.

How and why did the scientific consensus about sea level rise due to the disintegration of the West Antarctic Ice Sheet (WAIS), expressed in the third Intergovernmental Panel on Climate Change (IPCC) assessment, disintegrate on the road to the fourth? Using ethnographic interviews and analysis of IPCC documents, we trace the abrupt disintegration of the WAIS consensus. First, we provide a brief historical overview of scientific assessments of the WAIS. Second, we provide a detailed case study of the decision not to provide a WAIS prediction in the Fourth Assessment Report. Third, we discuss the implications of this outcome for the general issue of scientists and policymakers working in assessment organizations to make projections. IPCC authors were less certain about potential WAIS futures than in previous assessment reports in part because of new information, but also because of the outcome of cultural processes within the IPCC, including how people were selected for and worked together within their writing groups. It became too difficult for IPCC assessors to project the range of possible futures for WAIS due to shifts in scientific knowledge as well as in the institutions that facilitated the interpretations of this knowledge.