Recurrence of severe maternal morbidity: A population-based cohort analysis of California women.
Paediatric and perinatal epidemiology
BACKGROUND: Severe maternal morbidity (SMM) has increased in the United States by 45% in the last decade. While the recurrence of several adverse pregnancy outcomes from one pregnancy to the next has been established, the recurrence risk of SMM is unknown.OBJECTIVE: To determine whether women who have SMM in a first pregnancy are at increased risk of SMM in their second pregnancy, compared to women who did not have SMM in their first pregnancy.METHODS: This is a population-based study using linked vital statistics and hospital discharge records from the Office of Statewide Health Planning and Development in California from 1997 to 2012. The study population had their first two singleton births (live births or stillbirths) in California between 1997 and 2012 (n=1180357). The primary exposure was SMM during the hospitalisation at first birth, and the primary outcome was SMM during the hospitalisation at second birth. Prevalence and risk ratios of SMM at second birth were computed for women who did and did not have SMM at first birth, as well as for certain specific indicators of SMM.RESULTS: Of the 1180357 women included in this analysis, 9088 (77 per 10000 births) experienced SMM at first birth. Among these women, the prevalence of SMM at second birth was 470 per 10000 births, compared to 68 per 10000 births among women without SMM at first birth. This corresponded to an unadjusted risk ratio of 6.87 (95%CI 6.23, 7.57), which did not differ substantially when adjusted for factors known to be associated with SMM (6.42, 95% CI 5.86, 7.13).CONCLUSION: Women experiencing SMM in their first pregnancy were at an approximately sixfold increased risk of experiencing SMM in their second pregnancy.
View details for DOI 10.1111/ppe.12714
View details for PubMedID 33155710
Severe Maternal Morbidity among US- and Foreign-born Asian and Pacific Islander women in California.
Annals of epidemiology
To examine risk of severe maternal morbidity (SMM) - a composite of serious, potentially life-threatening conditions related to childbirth - among subgroups of nulliparous women with Asian and Pacific Islander race/ethnicity.This study used linked hospital discharge and vital record data California to identify nulliparous Asian and Pacific Islander women from 1997 to 2012 (n = 453,525). We examined risk of SMM for 15 Asian and Pacific Islander subgroups and compared risk between US- and foreign-born women.Risk of SMM was higher among Pacific Islander women than Asian women (148 and 127 cases per 10,000 births, respectively). Among Asian women, risk of SMM ranged from 94 (Korean) to 165 (Filipina) cases per 10,000 births, and among Pacific Islander women, risk ranged from 125 (Hawaiian) to 162 (Other). With the exception of Korean and Filipina women, relative risks of SMM for US- versus foreign-born Asian and Pacific Islander women were similar.Differences in risk of SMM exist between subgroups of the Asian and Pacific Islander community. These differences should be considered when conducting research on racial and ethnic differences of SMM and when counselling Asian and Pacific Islander women regarding their risk of SMM.
View details for DOI 10.1016/j.annepidem.2020.07.016
View details for PubMedID 32795600
Tumor Mutational Burden as a Predictive Biomarker for Response to Immune Checkpoint Inhibitors: A Review of Current Evidence
2020; 25 (1): E147–E159
Treatment with immune checkpoint inhibitors (ICPIs) extends survival in a proportion of patients across multiple cancers. Tumor mutational burden (TMB)-the number of somatic mutations per DNA megabase (Mb)-has emerged as a proxy for neoantigen burden that is an independent biomarker associated with ICPI outcomes. Based on findings from recent studies, TMB can be reliably estimated using validated algorithms from next-generation sequencing assays that interrogate a sufficiently large subset of the exome as an alternative to whole-exome sequencing. Biological processes contributing to elevated TMB can result from exposure to cigarette smoke and ultraviolet radiation, from deleterious mutations in mismatch repair leading to microsatellite instability, or from mutations in the DNA repair machinery. A variety of clinical studies have shown that patients with higher TMB experience longer survival and greater response rates following treatment with ICPIs compared with those who have lower TMB levels; this includes a prospective randomized clinical trial that found a TMB threshold of ≥10 mutations per Mb to be predictive of longer progression-free survival in patients with non-small cell lung cancer. Multiple trials are underway to validate the predictive values of TMB across cancer types and in patients treated with other immunotherapies. Here we review the rationale, algorithm development methodology, and existing clinical data supporting the use of TMB as a predictive biomarker for treatment with ICPIs. We discuss emerging roles for TMB and its potential future value for stratifying patients according to their likelihood of ICPI treatment response. IMPLICATIONS FOR PRACTICE: Tumor mutational burden (TMB) is a newly established independent predictor of immune checkpoint inhibitor (ICPI) treatment outcome across multiple tumor types. Certain next-generation sequencing-based techniques allow TMB to be reliably estimated from a subset of the exome without the use of whole-exome sequencing, thus facilitating the adoption of TMB assessment in community oncology settings. Analyses of multiple clinical trials across several cancer types have demonstrated that TMB stratifies patients who are receiving ICPIs by response rate and survival. TMB, alongside other genomic biomarkers, may provide complementary information in selecting patients for ICPI-based therapies.
View details for DOI 10.1634/theoncologist.2019-0244
View details for Web of Science ID 000491932900001
View details for PubMedID 31578273
View details for PubMedCentralID PMC6964127
Reentrainment Impairs Spatial Working Memory until Both Activity Onset and Offset Reentrain.
Journal of biological rhythms
2015; 30 (5): 408-416
Compression of the active phase (α) during reentrainment to phase-shifted light-dark (LD) cycles is a common feature of circadian systems, but its functional consequences have not been investigated. This study tested whether α compression in Siberian hamsters (Phodopus sungorus) impaired their spatial working memory as assessed by spontaneous alternation (SA) behavior in a T-maze. Animals were exposed to a 1- or 3-h phase delay of the LD cycle (16 h light/8 h dark). SA behavior was tested at 4 multiday intervals after the phase shift, and α was quantified for those days. All animals failed at the SA task while α was decompressing but recovered spatial memory ability once α returned to baseline levels. A second experiment exposed hamsters to a 2-h light pulse either early or late at night to compress α without phase-shifting the LD cycle. SA behavior was impaired until α decompressed to baseline levels. In a third experiment, α was compressed by changing photoperiod (LD 16:8, 18:6, 20:4) to see if absolute differences in α were related to spatial memory ability. Animals performed the SA task successfully in all 3 photoperiods. These data show that the dynamic process of α compression and decompression impairs spatial working memory and suggests that α modulation is a potential biomarker for assessing the impact of transmeridian flight or shift work on memory.
View details for DOI 10.1177/0748730415596254
View details for PubMedID 26224657