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Cervical cancer outcomes remain poor among disadvantaged populations, including ethnic minorities, low-income, and underinsured women. The aim of this study was to evaluate the mechanisms that underlie the observed association between race/ethnicity and cervical cancer survival. We identified 13,698 women, ages 21 to 64 years, diagnosed with stages I-III primary cervical cancer between 2007-2013 in Surveillance, Epidemiology, and End Results (SEER). Multivariable Cox proportional hazards regression models evaluated associations between race/ethnicity (Non-Hispanic White, Non-Hispanic Black, Hispanic, Other) and cervical cancer-specific mortality. We conducted mediation analysis to calculate the mediation proportion and its 95% confidence interval. Non-Hispanic black women had an increased risk of cervical cancer-specific mortality (HR: 1.23, 95% CI: 1.08-1.39), and Hispanic women a decreased risk of dying from their disease (HR: 0.82, 95% CI: 0.72-0.93), compared with non-Hispanic white. The estimated proportion of excess cervical cancer mortality for non-Hispanic black women relative to non-Hispanic white women that was mediated by insurance was 18.6% and by treatment was 47.2%. Furthermore, non-Hispanic black women were more likely to receive radiation and less likely to receive surgery for early-stage disease. In this population-based study we found that some of the excess cervical cancer-specific mortality for non-Hispanic black women is mediated by factors such as insurance status and treatment. These findings suggest that enhancing existing insurance coverage and ensuring equal and adequate treatment in all women may be a key strategy for improving cervical cancer outcomes.

Based on preclinical studies showing synergism with simultaneous inhibition of the estrogen receptor (ER), CDK4/6 and PI3K pathways and based on window of opportunity studies showing that metformin suppresses PI3K/mTOR signaling in endometrial cancer (EC), we conduct a non-randomized phase 2 study of letrozole/abemaciclib/metformin in ER positive endometrioid EC (NCT03675893). Primary objectives include objective response rate (ORR) and rate of progression-free survival (PFS) at 6 months (PFS6) while secondary objectives include PFS, overall survival, duration of response and toxicity. Twenty-five patients initiate protocol therapy [letrozole 2.5 mg orally (PO) once a day (qd), abemaciclib 150 mg PO twice a day (bid) and metformin 500 mg PO qd]. ORR is 32% (3 complete and 5 partial responses, 95% CI 14.9%-53.5%), Kaplan Meier estimate of PFS6 is 69.8% (95% CI 46.9%-84.3%) and median PFS is 19.4 months (95% CI 5.7 months–not estimable). No patients discontinue therapy because of toxicity. There are no objective responses among TP53 mutated ECs and among NSMP (no specific molecular profile) tumors with RB1 or CCNE1 alterations; CTNNB1 mutations correlate with clinical benefit. Pharmacokinetic analyses demonstrate that administration of letrozole and abemaciclib with metformin result in a more than 3-fold increase in metformin exposure. Combined hormonal therapy and CDK4/6 inhibition face resistance challenges in endometrial cancer. Here, the authors present a phase 2, one-arm clinical trial, where metformin is combined with letrozole (hormonal therapy) and abemaciclib (a CDK4/6 inhibitor) reporting safety and efficacy in patients with endometrial cancer.

AbstractObjectiveTo estimate the causal effect of increased use of neoadjuvant chemotherapy (NACT) on all cause mortality in advanced epithelial ovarian cancer.DesignQuasi-experimental fuzzy regression discontinuity design and cross sectional analysis. SettingCancer programs throughout the United States accredited by the Commission on Cancer.Participants6034 women with a diagnosis of stage 3C or 4 epithelial ovarian cancer from regions that rapidly adopted use of NACT from 2011 to 2012 (27% increase in the New England and east south central regions) or remained unchanged (control regions, south Atlantic, west north central, and east north central regions).Main outcome measureAll cause mortality within three years of diagnosis. Kaplan-Meier curves and proportional hazard models were estimated to compare mortality differences between rapidly adopting regions and controls. Results1156 women were treated for advanced epithelial ovarian cancer during 2011 and 2012 in the two rapidly adopting regions and 4878 women in the three control regions. In the rapidly adopting regions, patients treated in 2012 compared with 2011 had a mortality hazard ratio of 0.81 (95% confidence interval 0.71 to 0.94) after adjusting for mortality time trends, whereas no difference was observed in control regions (1.02, 0.93 to 1.12). Compared with control regions, larger declines in 90 day surgical mortality (7.0% to 4.0% v 5.0% to 4.3%, P=0.01) and in the proportion of women not receiving surgery and chemotherapy (20.0% to 17.4% v 19.0 to 19.5%, P=0.04) were observed in rapidly adopting regions. Cross sectional analysis confirmed that treatment in regions with greater use of NACT was associated was lower mortality (P=0.001).ConclusionsAdoption of NACT for advanced epithelial ovarian cancer in New England and east south central regions led to a sizable reduction in mortality within three years after diagnosis.

Background Managing advanced cancer can be psychologically distressing and burdensome for family caregivers and their care recipients. Innovations in the collection and modelling of passive data from personally-owned smartphones (e.g., GPS), called digital phenotyping, may afford the possibility of remotely monitoring and detecting distress and burden. We explored the potential of using passively-collected GPS data from smartphones to assess and predict caregiver and patient distress and burden. Methods This exploratory longitudinal cohort study enrolled smartphone-owning family caregiver and patient participants with advanced cancer (August 2021-July 2023) recruited via an oncology clinic or self-referral through Facebook. Participants downloaded a digital phenotyping research app, called Beiwe, that passively collected GPS data for 24 weeks. Participants completed self-report measures (PROs) of anxiety and depressive symptoms (Hospital Anxiety and Depression Scale [HADS]), mental health (PROMIS Mental Health), and caregiver burden (Montgomery-Borgatta Caregiver Burden scale) at baseline and every 6 weeks for 24 weeks. After pre-processing raw GPS data into daily GPS features (e.g., time spent at home, distance traveled/day), computing biweekly moving averages and standard deviations, and conducting a principal components analysis (PCA) of the resulting variables, within-person regression models were used to assess associations between changes in PRO measures and changes in PCA scores, with adjusted-R 2 as the measure of effect size (small = 0.02, medium = 0.13, large = 0.26). Results Evaluable data were collected from 48 participants (family caregivers = 32; patients = 16). Caregiver smartphone data explained small-to-medium variance in caregiver anxiety (0.06), depression (0.15), and mental health (0.07). Patient smartphone data predicted small to medium variance in caregiver depressive symptoms (0.12) and burden (0.05). Combined caregiver and patient smartphone data explained small variance in caregiver depressive (0.02) and anxiety symptoms (0.10) and large variance for PROMIS-mental health (0.36) and burden (0.50). For patient outcomes, caregiver smartphone data accounted for small variance in anxiety symptoms (0.07); patient smartphone data predicted large variance in anxiety symptoms (0.24). Combined data explained medium variance in patient depressive symptoms (0.18). Conclusions The exploratory study demonstrates the potential predictive utility of using passive smartphone data to detect changes in caregiver and patient psychological distress and burden. A larger study is needed to validate these findings and further explore the clinical application of digital phenotyping in cancer.

High burnout rates among physicians are taking a high financial and human toll. Burnout can undermine a physician’s sense of purpose and altruism and lead to substance use, depression, and suicidality. Some medical organizations are starting to tackle the challenge.

Ovarian cancer is often diagnosed in advanced stages, when survival is poor. Treatment advances have been made, but are inconsistently implemented. Our purpose was to project the maximum life expectancy gains that could be achieved in women with stage IIIC epithelial ovarian cancer if the implementation of available chemotherapy regimens could be optimized. We used a microsimulation model to estimate life expectancy benefits associated with \"optimized\" implementation of four post-operative chemotherapy options: standard intravenous chemotherapy; intraperitoneal + intravenous chemotherapy; bevacizumab + intravenous chemotherapy; and hyperthermic intraperitoneal chemotherapy + intravenous chemotherapy. Optimized implementation was defined as follows. Patients triaged to primary cytoreductive surgery received intraperitoneal + intravenous chemotherapy if optimally or completely cytoreduced, and bevacizumab + intravenous chemotherapy if suboptimally cytoreduced. Patients triaged to neoadjuvant chemotherapy received hyperthermic intraperitoneal chemotherapy at interval cytoreductive surgery if optimally or completely cytoreduced, and standard IV chemotherapy if suboptimally cytoreduced. Life expectancy associated with optimized implementation was compared with that of current utilization practices, estimated using published literature and the National Cancer Database. Effects of model uncertainty were evaluated in sensitivity analyses. Life expectancy associated with optimized implementation vs. current practice was 76.7 vs. 64.5 months (life expectancy gain = 12.2 months). Providing intraperitoneal + intravenous chemotherapy to all eligible patients was the largest driver of life expectancy gains, due to both the potential benefit conferred by intraperitoneal + intravenous chemotherapy and the proportion of eligible women who do not receive intraperitoneal + intravenous chemotherapy in current practice. Population-level life expectancy in stage IIIC epithelial ovarian cancer could be substantially improved through greater uptake of available chemotherapy regimens.

Recruitment of health research participants through social media is becoming more common. In the United States, 80% of adults use at least one social media platform. Social media platforms may allow researchers to reach potential participants efficiently. However, online research methods may be associated with unique threats to sample validity and data integrity. Limited research has described issues of data quality and authenticity associated with the recruitment of health research participants through social media, and sources of low-quality and fraudulent data in this context are poorly understood. The goal of the research was to describe and explain threats to sample validity and data integrity following recruitment of health research participants through social media and summarize recommended strategies to mitigate these threats. Our experience designing and implementing a research study using social media recruitment and online data collection serves as a case study. Using published strategies to preserve data integrity, we recruited participants to complete an online survey through the social media platforms Twitter and Facebook. Participants were to receive $15 upon survey completion. Prior to manually issuing remuneration, we reviewed completed surveys for indicators of fraudulent or low-quality data. Indicators attributable to respondent error were labeled suspicious, while those suggesting misrepresentation were labeled fraudulent. We planned to remove cases with 1 fraudulent indicator or at least 3 suspicious indicators. Within 7 hours of survey activation, we received 271 completed surveys. We classified 94.5% (256/271) of cases as fraudulent and 5.5% (15/271) as suspicious. In total, 86.7% (235/271) provided inconsistent responses to verifiable items and 16.2% (44/271) exhibited evidence of bot automation. Of the fraudulent cases, 53.9% (138/256) provided a duplicate or unusual response to one or more open-ended items and 52.0% (133/256) exhibited evidence of inattention. Research findings from several disciplines suggest studies in which research participants are recruited through social media are susceptible to data quality issues. Opportunistic individuals who use virtual private servers to fraudulently complete research surveys for profit may contribute to low-quality data. Strategies to preserve data integrity following research participant recruitment through social media are limited. Development and testing of novel strategies to prevent and detect fraud is a research priority.

Step counts are increasingly used in public health and clinical research to assess well-being, lifestyle, and health status. However, estimating step counts using commercial activity trackers has several limitations, including a lack of reproducibility, generalizability, and scalability. Smartphones are a potentially promising alternative, but their step-counting algorithms require robust validation that accounts for temporal sensor body location, individual gait characteristics, and heterogeneous health states. Our goal was to evaluate an open-source, step-counting method for smartphones under various measurement conditions against step counts estimated from data collected simultaneously from different body locations (\"cross-body\" validation), manually ascertained ground truth (\"visually assessed\" validation), and step counts from a commercial activity tracker (Fitbit Charge 2) in patients with advanced cancer (\"commercial wearable\" validation). We used 8 independent data sets collected in controlled, semicontrolled, and free-living environments with different devices (primarily Android smartphones and wearable accelerometers) carried at typical body locations. A total of 5 data sets (n=103) were used for cross-body validation, 2 data sets (n=107) for visually assessed validation, and 1 data set (n=45) was used for commercial wearable validation. In each scenario, step counts were estimated using a previously published step-counting method for smartphones that uses raw subsecond-level accelerometer data. We calculated the mean bias and limits of agreement (LoA) between step count estimates and validation criteria using Bland-Altman analysis. In the cross-body validation data sets, participants performed 751.7 (SD 581.2) steps, and the mean bias was -7.2 (LoA -47.6, 33.3) steps, or -0.5%. In the visually assessed validation data sets, the ground truth step count was 367.4 (SD 359.4) steps, while the mean bias was -0.4 (LoA -75.2, 74.3) steps, or 0.1%. In the commercial wearable validation data set, Fitbit devices indicated mean step counts of 1931.2 (SD 2338.4), while the calculated bias was equal to -67.1 (LoA -603.8, 469.7) steps, or a difference of 3.4%. This study demonstrates that our open-source, step-counting method for smartphone data provides reliable step counts across sensor locations, measurement scenarios, and populations, including healthy adults and patients with cancer.

Background Currently, little is known about the effect of the Patient Protection and Affordable Care Act's Medicaid expansion on care delivery and outcomes in cervical cancer. Aim We evaluated whether Medicaid expansion was associated with changes in insurance status, stage at diagnosis, timely treatment, and survival outcomes in cervical cancer. Methods and results Using the National Cancer Database, we performed a difference‐in‐differences (DID) cross‐sectional analysis to compare insurance status, stage at diagnosis, timely treatment, and survival outcomes among cervical cancer patients residing in Medicaid expansion and nonexpansion states before (2011–2013) and after (2014–2015) Medicaid expansion. January 1, 2014 was used as the timepoint for Medicaid expansion. The primary outcomes of interest were insurance status, stage at diagnosis, treatment within 30 and 90 days of diagnosis, and overall survival. Fifteen thousand two hundred sixty‐five patients (median age 50) were included: 42% from Medicaid expansion and 58% from nonexpansion states. Medicaid expansion was significantly associated with increased Medicaid coverage (adjusted DID = 11.0%, 95%CI = 8.2, 13.8, p < .01) and decreased rates of uninsured (adjusted DID = −3.0%, 95%CI = −5.2, −0.8, p < .01) among patients in expansion states compared with non‐expansion states. However, Medicaid expansion was not associated with any significant changes in cancer stage at diagnosis or timely treatment. There was no significant change in survival from the pre‐ to post‐expansion period in either expansion or nonexpansion states, and no significant differences between the two (DID‐HR = 0.95, 95%CI = 0.83, 1.09, p = .48). Conclusion Although Medicaid expansion was associated with an increase in Medicaid coverage and decrease in uninsured among patients with cervical cancer, the effects of increased coverage on diagnosis and treatment outcomes may have yet to unfold. Future studies, including longer follow‐up are necessary to understand the effects of Medicaid expansion.

In South Africa, the prevalence of oncogenic Human Papillomavirus (HPV) may be as high as 64%, and cervical cancer is the leading cause of cancer-related death among women. The development of efficacious prophylactic vaccines has provided an opportunity for primary prevention. Given the importance of psycho-social forces in vaccine uptake, we sought to elucidate factors influencing HPV vaccination among a sample of low-income South African adolescents receiving the vaccine for the first time in Soweto. The HPV vaccine was introduced to adolescents in low-income townships throughout South Africa as part of a nationwide trial to understand adolescent involvement in future vaccine research targeting human immunodeficiency virus (HIV). We performed in-depth semi-structured interviews with purposively-sampled adolescents and their care providers to understand what forces shaped HPV vaccine uptake. Interviews were recorded, transcribed, translated, and examined using thematic analysis. Of 224 adolescents recruited, 201 initiated the vaccine; 192 (95.5%) received a second immunization; and 164 (81.6%) completed three doses. In our qualitative study of 39 adolescent-caregiver dyads, we found that factors driving vaccine uptake reflected a socio-cultural backdrop of high HIV endemnicity, sexual violence, poverty, and an abundance of female-headed households. Adolescents exercised a high level of autonomy and often initiated decision-making. Healthcare providers and peers provided support and guidance that was absent at home. The impact of the HIV epidemic on decision-making was substantial, leading participants to mistakenly conflate HPV and HIV. In a setting of perceived rampant sexual violence and epidemic levels of HIV, adolescents and caregivers sought to decrease harm by seeking a vaccine targeting a sexually transmitted infection (STI). Despite careful consenting, there was confusion regarding the vaccine's target. Future interventions promoting STI vaccines will need to provide substantial information for participants, particularly adolescents who may exercise a significant level of autonomy in decision-making.