Category: Statistics

J Gynecol Oncol. 2021 Aug 5. doi: 10.3802/jgo.2021.32.e90. Online ahead of print.

ABSTRACT

OBJECTIVE: To compare survival outcomes between bevacizumab (BEV) and olaparib (OLA) maintenance therapy in BRCA-mutated, platinum-sensitive relapsed (PSR) high-grade serous ovarian carcinoma (HGSOC).

METHODS: From 10 institutions, we identified HGSOC patients with germline and/or somatic BRCA1/2 mutations, who experienced platinum-sensitive recurrence between 2013 and 2019, and received second-line platinum-based chemotherapy. Patients were divided into BEV (n=29), OLA (n=83), and non-BEV/non-OLA users (n=36). The OLA and non-BEV/non-OLA users were grouped as the OLA intent group. We conducted 1:2 nearest neighbor-matching between the BEV and OLA intent groups, setting the proportion of OLA users in the OLA intent group from 65% to 100% at 5% intervals, and compared survival outcomes among the matched groups.

RESULTS: Overall, OLA users showed significantly better progression-free survival (PFS) than BEV users (median, 23.8 vs. 17.4 months; p=0.004). Before matching, PFS improved in the OLA intent group but marginal statistical significance (p=0.057). After matching, multivariate analyses adjusting confounders identified intention-to-treat OLA as an independent favorable prognostic factor for PFS in the OLA 65P (adjusted hazard ratio [aHR]=0.505; 95% confidence interval [CI]=0.280-0.911; p=0.023) to OLA 100P (aHR=0.348; 95% CI=0.184-0.658; p=0.001) datasets. The aHR of intention-to-treat OLA for recurrence decreased with increasing proportions of OLA users. No differences in overall survival were observed between the BEV and OLA intent groups, and between the BEV and OLA users.

CONCLUSION: Compared to BEV, intention-to-treat OLA and actual use of OLA maintenance therapy were significantly associated with decreased disease recurrence risk in patients with BRCA-mutated, PSR HGSOC.

PMID:34431258 | DOI:10.3802/jgo.2021.32.e90

J Gynecol Oncol. 2021 Jul 16. doi: 10.3802/jgo.2021.32.e85. Online ahead of print.

ABSTRACT

OBJECTIVE: External beam radiation therapy (EBRT) with concurrent chemotherapy followed by intracavitary brachytherapy is the standard treatment in locally advanced cervical cancer. This study examined the brachytherapy utilization rate and evaluated the effect of brachytherapy on survival in cervical cancer patients in Korea.

METHODS: In this study, data from the Korea Central Cancer Registry and Korean National Health Insurance Service and data on mortality from Statistics Korea were linked and used. Patients with other cancers, distant metastasis at diagnosis, or unknown stage or who underwent hysterectomy were excluded. A total of 12,721 cervical cancer patients were analyzed in this study.

RESULTS: The brachytherapy utilization rate (%) was calculated as the proportion of patients who received brachytherapy among those who received curative EBRT. The brachytherapy utilization rate decreased from 84% in 2005 to 78% in 2013 (p<0.001). Brachytherapy utilization rates varied by region, ranging from 72% to 100% except for in Jeju Island, where the rate was 56%. The brachytherapy utilization rate was lower in patients older than 80 years; patients with localized disease, non-squamous cell carcinoma, or Charlson comorbidity index 3 or more; patients diagnosed after 2010; patients from certain regions; patients receiving medical aid; and patients who underwent gynecologic procedures. Multivariable Cox regression analysis showed that brachytherapy when added to curative EBRT was independently associated with better cancer-specific survival (CSS) and overall survival (OS) than curative EBRT only.

CONCLUSION: The brachytherapy utilization rate decreased from 2005 to 2013 and varied by region in Korea. Brachytherapy use is independently associated with significantly higher CSS and OS in cervical cancer.

PMID:34431256 | DOI:10.3802/jgo.2021.32.e85

J Gynecol Oncol. 2021 Jul 23. doi: 10.3802/jgo.2021.32.e87. Online ahead of print.

ABSTRACT

OBJECTIVE: To evaluate financial toxicity and assess its risk factors among patients with gynecologic cancers.

METHODS: This is a cross sectional study that included 2 survey tools, as well as patient demographics, disease characteristics, and treatment regimen. Financial toxicity is measured by validated Comprehensive Score for Financial Toxicity (COST) tool. Participants were also asked to complete a 55-question-survey on attitudes and perspectives surrounding cost of care. Descriptive statistics was used to report patient demographics. Spearman’s rank correlation was calculated to assess the relation between financial toxicity and patient/disease related variables. Graphpad Prism Software Version 8.0 was used for analyses.

RESULTS: A total of 50 patients with various gynecologic malignancies were enrolled. Median COST score was 20.5 (range, 1-33). Sixty-five percent of the patients reported being in debt due to their cancer care and 4% filed bankruptcy. Correlation analysis showed that COST score was correlated with age (r=-0.3, p=0.028), malignancy type (r=0.3, p=0.039) and income (r=0.3, p=0.047). Ovarian cancer patients had significantly less financial toxicity (median COST score=23) when compared to patients with other gynecologic malignancies (median COST score=17, p=0.043). When scores were dichotomized into low (score ≥22) and high toxicity (score <22), 58% (29/50) of the patients were noted to have high financial toxicity. Enrollment to a clinical trial did not significantly alleviate financial burden.

CONCLUSION: Financial toxicity is a significant burden even among highly insured gynecologic oncology patients. Age, malignancy type and income were correlated with high financial burden.

PMID:34431257 | DOI:10.3802/jgo.2021.32.e87

Nat Commun. 2021 Aug 24;12(1):5095. doi: 10.1038/s41467-021-24558-y.

ABSTRACT

Maternal smoking during pregnancy (MSDP) contributes to poor birth outcomes, in part through disrupted placental functions, which may be reflected in the placental epigenome. Here we present a meta-analysis of the associations between MSDP and placental DNA methylation (DNAm) and between DNAm and birth outcomes within the Pregnancy And Childhood Epigenetics (PACE) consortium (N = 1700, 344 with MSDP). We identify 443 CpGs that are associated with MSDP, of which 142 associated with birth outcomes, 40 associated with gene expression, and 13 CpGs are associated with all three. Only two CpGs have consistent associations from a prior meta-analysis of cord blood DNAm, demonstrating substantial tissue-specific responses to MSDP. The placental MSDP-associated CpGs are enriched for environmental response genes, growth-factor signaling, and inflammation, which play important roles in placental function. We demonstrate links between placental DNAm, MSDP and poor birth outcomes, which may better inform the mechanisms through which MSDP impacts placental function and fetal growth.

PMID:34429407 | DOI:10.1038/s41467-021-24558-y

Nat Commun. 2021 Aug 24;12(1):5099. doi: 10.1038/s41467-021-25266-3.

ABSTRACT

Rotational dynamics often challenge physical intuition while enabling unique realizations, from the rotor of a gyroscope that maintains its orientation regardless of the outer gimbals, to a tennis racket that rotates around its handle when tossed face-up in the air. In the context of inertial sensing, which can measure mass with atomic precision, rotational dynamics are normally considered a complication hindering measurement interpretation. Here, we exploit the rotational dynamics of a microfluidic device to develop a modality in inertial sensing. Combining theory with experiments, we show that this modality measures the volume of a rigid particle while normally being insensitive to its density. Paradoxically, particle density only emerges when fluid viscosity becomes dominant over inertia. We explain this paradox via a viscosity-driven, hydrodynamic coupling between the fluid and the particle that activates the rotational inertia of the particle, converting it into a ‘viscous flywheel’. This modality now enables the simultaneous measurement of particle volume and mass in fluid, using a single, high-throughput measurement.

PMID:34429420 | DOI:10.1038/s41467-021-25266-3

Nat Commun. 2021 Aug 24;12(1):5084. doi: 10.1038/s41467-021-25053-0.

ABSTRACT

The investigation of thermalization in isolated quantum many-body systems has a long history, dating back to the time of developing statistical mechanics. Most quantum many-body systems in nature are considered to thermalize, while some never achieve thermal equilibrium. The central problem is to clarify whether a given system thermalizes, which has been addressed previously, but not resolved. Here, we show that this problem is undecidable. The resulting undecidability even applies when the system is restricted to one-dimensional shift-invariant systems with nearest-neighbour interaction, and the initial state is a fixed product state. We construct a family of Hamiltonians encoding dynamics of a reversible universal Turing machine, where the fate of a relaxation process changes considerably depending on whether the Turing machine halts. Our result indicates that there is no general theorem, algorithm, or systematic procedure determining the presence or absence of thermalization in any given Hamiltonian.

PMID:34429406 | DOI:10.1038/s41467-021-25053-0

Pediatrics. 2021 Aug 24:e2020024091. doi: 10.1542/peds.2020-024091. Online ahead of print.

ABSTRACT

OBJECTIVES: To investigate racial and ethnic differences in unexpected, term newborn morbidity and the influence of hospital quality on disparities.

METHODS: We used 2010-2014 birth certificate and discharge abstract data from 40 New York City hospitals in a retrospective cohort study of 483 834 low-risk (term, singleton, birth weight ≥2500 g, without preexisting fetal conditions) neonates. We classified morbidity according to The Joint Commission’s unexpected newborn complications metric and used multivariable logistic regression to compare morbidity risk among racial and ethnic groups. We generated risk-standardized complication rates for each hospital using mixed-effects logistic regression to evaluate quality, ranked hospitals on this measure, and assessed differences in the racial and ethnic distribution of births across facilities.

RESULTS: The unexpected complications rate was 48.0 per 1000 births. Adjusted for patient characteristics, morbidity risk was higher among Black and Hispanic infants compared with white infants (odds ratio: 1.5 [95% confidence interval 1.3-1.9]; odds ratio: 1.2 [95% confidence interval 1.1-1.4], respectively). Among the 40 hospitals, risk-standardized complications ranged from 25.3 to 162.8 per 1000 births. One-third of Black and Hispanic women gave birth in hospitals ranking in the highest-morbidity tertile, compared with 10% of white and Asian American women (P < .001).

CONCLUSIONS: Black and Hispanic women were more likely to deliver in hospitals with high complication rates than were white or Asian American women. Findings implicate hospital quality in contributing to preventable newborn health disparities among low-risk, term births. Quality improvement targeting routine obstetric and neonatal care is critical for equity in perinatal outcomes.

PMID:34429339 | DOI:10.1542/peds.2020-024091

Sci Transl Med. 2021 Aug 24:eabh2624. doi: 10.1126/scitranslmed.abh2624. Online ahead of print.

ABSTRACT

Neutralizing autoantibodies against type I interferons (IFNs) have been found in some patients with critical coronavirus disease 2019 (COVID-19), the disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, the prevalence of these antibodies, their longitudinal dynamics across the disease severity scale, and their functional effects on circulating leukocytes remain unknown. Here, in 284 patients with COVID-19, we found type I IFN-specific autoantibodies in peripheral blood samples from 19% of patients with critical disease and 6% of patients with severe disease. We found no type I IFN autoantibodies in individuals with moderate disease. Longitudinal profiling of over 600,000 peripheral blood mononuclear cells using multiplexed single-cell epitope and transcriptome sequencing from 54 patients with COVID-19 and 26 non-COVID-19 controls revealed a lack of type I IFN-stimulated gene (ISG-I) responses in myeloid cells from patients with critical disease. This was especially evident in dendritic cell populations isolated from patients with critical disease producing type I IFN-specific autoantibodies. Moreover, we found elevated expression of the inhibitory receptor leukocyte-associated immunoglobulin-like receptor 1 (LAIR1) on the surface of monocytes isolated from patients with critical disease early in the disease course. LAIR1 expression is inversely correlated with ISG-I expression response in patients with COVID-19 but is not expressed in healthy controls. The deficient ISG-I response observed in patients with critical COVID-19 with and without type I IFN-specific autoantibodies supports a unifying model for disease pathogenesis involving ISG-I suppression through convergent mechanisms.

PMID:34429372 | DOI:10.1126/scitranslmed.abh2624

BMJ Open. 2021 Aug 24;11(8):e051099. doi: 10.1136/bmjopen-2021-051099.

ABSTRACT

INTRODUCTION: Although several authors have been interested in the well-being and social participation of teleworkers in the context of the COVID-19 pandemic, it appears that most of the recommendations issued are based on literature reviews or expert opinions; yet few authors have documented the perspectives of the workers. The aim of this study is to explore workers’ perspectives of teleworking in the context of the COVID-19 pandemic regarding the effects on their well-being and social participation.

METHODS AND ANALYSIS: Using a participatory study protocol involving the collaboration of a community organisation defending workers’ rights, the first step will be to conduct focus groups to qualitatively describe workers’ perspectives of their teleworking conditions. Then, an online questionnaire will be administered to a large pool or workers to quantitatively explore the influence of individual, organisational and environmental variables on the well-being and social participation of workers. The thematic and statistical analyses of the data collected will indicate successful practices to be adopted by workers and organisations. These successful practices will be validated by workers through a Technique for Research of Information by Animation of a Group of Experts group and will serve as concrete tools to better support workers’ participation in teleworking.

ETHICS AND DISSEMINATION: The approval of the research ethics board of the Centre intégré universitaire de santé et de services sociaux de la Capitale Nationale has been obtained. Findings will be shared with various stakeholders including workers, employers, insurers and unions. Findings will be disseminated in webinars, peer-reviewed journals and lectures.

PMID:34429318 | DOI:10.1136/bmjopen-2021-051099

Arch Dis Child. 2021 Aug 24:archdischild-2021-322012. doi: 10.1136/archdischild-2021-322012. Online ahead of print.

ABSTRACT

BACKGROUND: Lead damages most body organs and its effects are most profound in children. In a study in Beirut in 2003, before banning the leaded gasoline, 79% of the participants showed blood lead levels (BLLs) higher than 5 µg/dL. The prevalence of lead exposure in Lebanon after the ban on leaded gasoline has not been studied. This study assessed the BLL in Lebanese children aged 1-6 years.

METHODS: This cross-sectional study was conducted in three hospitals in Beirut. The children’s BLLs were tested, and their caregiver completed a questionnaire to identify subgroups at risk of exposure. Participants were provided with a WHO brochure highlighting the risks of lead.

RESULTS: Ninety children with a mean age of 3.5±1.5 years were enrolled in the study and had a mean BLL of 1.1±0.7 µg/dL, with all values being below 5.0 µg/dL, showing a marked decrease in BLL compared with the mean BLL before the ban on leaded gasoline in 2002. Having a father or a mother with a college degree (p=0.01 and p=0.035, respectively) and having a monthly household income greater than $1000 (p=0.021) were associated with significantly lower BLL. Having more rooms at home and residing close to construction sites were associated with a significantly lower BLL (p=0.001 and p=0.026, respectively). Residing in a house aged >40 years and receiving traditional remedies were associated with a significantly higher BLL (p=0.009 and p<0.0001, respectively).

CONCLUSION: BLLs have declined among Lebanese children and this could be attributed to multiple factors including the ban of leaded gasoline. It would be beneficial to conduct a larger study with a nationally representative sample to better characterise the BLL.

PMID:34429329 | DOI:10.1136/archdischild-2021-322012