One dose versus two doses of COVID-19 vaccine for the prevention of breakthrough infections among people previously infected with SARS-Cov-2.

Studies have suggested the effectiveness of COVID-19 vaccines in preventing SARS-CoV-2 reinfection among those previously infected. However, it is not yet clear if one dose of the vaccine is enough to prevent breakthrough infections compared to two doses. Using data from Optum deidentified COVID-19 Electronic Health Record (EHR) data set, we assessed breakthrough infection risks in individuals previously infected, comparing those with one vaccine dose to those with two doses. Propensity scores were applied to mitigate confounding factors. Follow-up spanned 6 months, beginning 2 weeks postvaccination. Among 213 845 individuals, those receiving one vaccine dose had a significantly higher breakthrough infection risk than the two-dose group (HR 1.69, 95% CI 1.54-1.85). This pattern was observed across genders, racial/ethnic groups, age categories, and vaccine types. This study reveals a substantial disparity in the risk of breakthrough infections between individuals receiving one versus two doses of the COVID-19 vaccine, suggesting that a single dose may not provide adequate protection against reinfection.

Cost Effectiveness of Additional Preoperative Telephone Call to Increase Surgical Preparedness: Analysis of a Randomized Clinical Trial.

INTRODUCTION AND HYPOTHESIS: There is a need for cost effective interventions that increase surgical preparedness in urogynecology. METHODS: We performed an ancillary prospective economic evaluation of the Telehealth Intervention to Increase Patient Preparedness for Surgery (TIPPS) Trial, a randomized multicenter trial that evaluated the impact of a preoperative telehealth call on surgical preparedness in women undergoing urogynecologic surgery. A within-trial analysis from the health care sector and societal perspective was performed. Cost-effectiveness was computed from health care sector and societal perspectives, with an 8-week time horizon. RESULTS: A total of 126 women were included in our analysis. QALYs gained were similar between groups (telehealth 0.1414 + 0.0249; usual care 0.1409 + 0.0179). The cumulative mean per-person costs at 8 weeks from the healthcare sector perspective were telehealth call: $8696 +/- 3341; usual care: $8473 +/- 3118 (p = 0.693) and from the societal perspective were telehealth call: $11,195 + 5191; usual care: $11,213 +/- 4869 (p = 0.944). The preoperative telehealth call intervention was not cost effective from the health care sector perspective with an ICER of $460,091/QALY (95%CI -$7,382,608/QALY, $7,673,961) using the generally accepted maximum willingness to pay threshold of $150,000/QALY (Neumann et al. N Engl J Med. 371(9):796-7, 2014). From the societal perspective, because incremental costs per QALY gained were negative $-35,925/QALY (95%CI, -$382,978/QALY, $317,226), results suggest that preoperative telehealth call dominated usual care. CONCLUSIONS: A preoperative telehealth call is cost effective from the society perspective. CLINICAL TRIAL REGISTRATION: Registered with http://ClinicalTrials.gov . Date of registration: March 26, 2019 Date of initial participant enrollment: June 5, 2019 URL: https://clinicaltrials.gov/ct2/show/record/NCT03890471 Clinical trial identification number: NCT03890471.

Knowledge, Attitudes, Willingness to Pay, and Patient Preferences About Genetic Testing and Subsequent Risk Management for Cancer Prevention.

Knowledge, attitudes, and patient preferences about genetic testing and subsequent risk management for cancer prevention among average risk populations are understudied, especially among Hispanics. This study was to assess these items by conducting an in-person survey in this understudied population. We conducted in-person surveys using a self-administered, structured questionnaire among young women in 2017. Survey questions were adapted from other validated surveys. This study had 677 participants in the final analyses. Data were collected in 2017 and analyzed in 2018 and 2019. Participants had little knowledge about genes or breast cancer risk, but most felt that genetic testing for cancer prevention is "a good idea" (87.0%), "a reassuring idea" (84.0%), and that "everyone should get the test" (87.7%). Most (64.0%) of these women would pay up to $25 for the test, 29.3% would pay $25-$500, and < 10% would pay more than $500 for the test. When asked about a hypothetical scenario of high breast cancer risk, 34.2% Hispanics and 24.5% non-Hispanics would choose chemoprevention. Women would be less likely to choose risk reduction procedures, such as mastectomy (19.6% among Hispanics and 15.1% among non-Hispanics) and salpingo-oophorectomy (11.8% among Hispanics and 10.7% among non-Hispanics). In this low-income, mostly Hispanic population, knowledge about genetic testing and cancer risk is poor, but most have positive opinions about genetic testing for cancer prevention. However, their strong preference for chemoprevention and lesser preference for prophylactic surgeries in a hypothetical scenario underscore the importance of genetic counseling and education.

How cognitive and reactive fear circuits optimize escape decisions in humans.

Flight initiation distance (FID), the distance at which an organism flees from an approaching threat, is an ecological metric of cost-benefit functions of escape decisions. We adapted the FID paradigm to investigate how fast- or slow-attacking "virtual predators" constrain escape decisions. We show that rapid escape decisions rely on "reactive fear" circuits in the periaqueductal gray and midcingulate cortex (MCC), while protracted escape decisions, defined by larger buffer zones, were associated with "cognitive fear" circuits, which include posterior cingulate cortex, hippocampus, and the ventromedial prefrontal cortex, circuits implicated in more complex information processing, cognitive avoidance strategies, and behavioral flexibility. Using a Bayesian decision-making model, we further show that optimization of escape decisions under rapid flight were localized to the MCC, a region involved in adaptive motor control, while the hippocampus is implicated in optimizing decisions that update and control slower escape initiation. These results demonstrate an unexplored link between defensive survival circuits and their role in adaptive escape decisions.

BRCA testing in unaffected young women in the United States, 2006-2017.

BACKGROUND: The discovery of the BRCA gene in the 1990s created an opportunity for individualized cancer prevention. BRCA testing in young women before cancer onset enables early detection of those with an increased cancer risk and creates an opportunity to offer lifesaving prophylactic procedures and medications. This study assessed trends in BRCA testing in women younger than 40 years without diagnosed breast or ovarian cancer (unaffected young women [UYW]) for cancer prevention between 2006 and 2017 in the United States. METHODS: This study included 93,278 adult women 18 to 65 years old with insurance claims for BRCA testing between 2006 and 2017 from the de-identified Optum Clinformatics Data Mart database. The data contained medical claims and administrative information from privately insured individuals in the United States. The proportion of BRCA testing in UYW younger than 40 years among adult women aged 18 to 65 years who received BRCA testing was assessed. RESULTS: In 2006, only 10.5% of the tests were performed in UYW. The proportion of BRCA tests performed in UYW increased significantly to 25.5% in 2017 (annual percentage change for the 2006-2017 period, 6.9; 95% confidence interval, 6.4-7.3; P < .001). The increased trend in the proportion of BRCA tests in UYW significantly differed by region of residence and family history of breast or ovarian cancer. CONCLUSIONS: Over the past decade, there was increased use of BRCA testing for cancer prevention. Additional efforts are needed to maximize the early detection of women with BRCA pathogenic variants so that these cancers may be prevented.

Trends in breast cancer mortality by stage at diagnosis among young women in the United States.

BACKGROUND: Assessing trends in breast cancer survival among young women who are largely unaffected by breast cancer screening will provide important information regarding improvements in the effectiveness of cancer care for breast cancer in the last few decades. METHODS: The cohort for this study consisted of women who were diagnosed with breast cancer between ages 20 and 39 years from the Surveillance, Epidemiology, and End Results program's 9-registry areas from 1975 to 2015. Trends in the breast cancer incidence rate and survival were assessed among young women. RESULTS: Among women aged 20 to 39 years, breast cancer incidence increased from 24.6 per 100,000 in 1975 to 31.7 per 100,000 in 2015 (annual percent change, 0.5; 95% confidence interval [CI], 0.4-0.6). Among women with breast cancer, 5-year breast-cancer-specific survival increased significantly from 74.0% during 1975 to 1979 to 88.5% during 2010 to 2015 (hazard ratio for dying from breast cancer for 2010-2015 vs 1975-1979, 0.37; 95% CI, 0.32-0.41). The increase in cancer-specific survival reached a plateau in 2005; however, among young women with metastatic breast cancer, it continued to increase after 2005, from 45.6% during 2005 to 2009 to 56.5% during 2010 to 2015 (hazard ratio for dying from breast cancer for 2010-2015 vs 2005-2009, 0.74; 95% CI, 0.60-0.92). Similar patterns also were observed for 5-year overall survival and among women aged 20 to 29 years and those aged 30 to 39 years. CONCLUSIONS: There were substantial improvements in the effectiveness of breast cancer treatment on overall and cancer-specific survival from 1975 to 2015. However, improvements appeared to have reached a plateau after 2005, except among young women with metastatic breast cancer, in whom survival continued to improve throughout the period.

Roles of Health Care Providers and Patients in Initiation of Unnecessary Papanicolaou Testing After Total Hysterectomy.

OBJECTIVES: To assess Papanicolaou (Pap) testing use among US adult women with a history of a total hysterectomy for a benign condition and the roles of health care providers and patients in the initiation of screening Pap tests. METHODS: We used 2000 to 2013 data from the National Health Interview Survey on women aged 20 years or older who had undergone a hysterectomy (n = 11 616) to estimate unnecessary Pap test use. RESULTS: The percentage of self-reported Pap testing in the preceding 3 years among women who had undergone a hysterectomy decreased from 72.2% in 2000 to 53.3% in 2013. In 2013, 42.4% of women who had undergone a hysterectomy reported receiving recommendations for screening from a health care provider in the past year (32% of which were unnecessary), and 32.1% reported undergoing Pap tests in the preceding year (22.1% of which were unnecessary). Although the majority of Pap tests were performed at a clinician's recommendation, approximately one fourth were initiated by patients without clinician recommendations. CONCLUSIONS: Health care providers should advise women who have had a total hysterectomy for a benign condition on appropriate use of screening services.

Cervical cancer screening among women ≥70 years of age in the United States-A referral problem or patient choice.

OBJECTIVE: Clinical guidelines recommend that women with a history of adequate screening and not otherwise at high risk may discontinue cervical cancer screening after 65 years of age. However, screening remains common among US women over 65 years old. This study was conducted to examine whether overutilization was attributable to provider's recommendation or patient choice. METHOD: This cross-sectional study used data from 1752 female participants (70+ years) from the 2013 National Health Interview Survey (NHIS). We quantitatively assessed the proportions of provider-recommended and patient self-initiated Pap smears. RESULTS: Among female respondents, 40.8% had a Pap smear within the past 3 years, 19.4% had a Pap smear in the last year, and 39.7% reported receiving a recommendation for a Pap smear from their provider in the past year. Among women who received a recommendation to obtain a Pap smear, 39.8% did so within the past 12 months compared to 5.9% of women who did not receive a recommendation (adjusted odds ratio 10.5, 95% confidence interval 7.39-15.0). About 70% of women who visited an obstetrician/gynecologist and reported receiving a recommendation to have a Pap smear did so in the past year, while 32.3% of women who visited an obstetrician/gynecologist but did not receive a recommendation obtained one. CONCLUSION: Pap smears were common among women ≥70 years of age. Health care providers may need additional education on current guidelines regarding indications for Pap smears in this age group to help reduce screening of patients who may not benefit.

Liver retinol transporter and receptor for serum retinol-binding protein (RBP4).

Vitamin A (retinol) is absorbed in the small intestine, stored in liver, and secreted into circulation bound to serum retinol-binding protein (RBP4). Circulating retinol may be taken up by extrahepatic tissues or recycled back to liver multiple times before it is finally metabolized or degraded. Liver exhibits high affinity binding sites for RBP4, but specific receptors have not been identified. The only known high affinity receptor for RBP4, Stra6, is not expressed in the liver. Here we report discovery of RBP4 receptor-2 (RBPR2), a novel retinol transporter expressed primarily in liver and intestine and induced in adipose tissue of obese mice. RBPR2 is structurally related to Stra6 and highly conserved in vertebrates, including humans. Expression of RBPR2 in cultured cells confers high affinity RBP4 binding and retinol transport, and RBPR2 knockdown reduces RBP4 binding/retinol transport. RBPR2 expression is suppressed by retinol and retinoic acid and correlates inversely with liver retinol stores in vivo. We conclude that RBPR2 is a novel retinol transporter that potentially regulates retinol homeostasis in liver and other tissues. In addition, expression of RBPR2 in liver and fat suggests a possible role in mediating established metabolic actions of RBP4 in those tissues.

Cost-Effectiveness of Population-Based Multigene Testing for Breast and Ovarian Cancer Prevention.

Importance: The current method of BRCA testing for breast and ovarian cancer prevention, which is based on family history, often fails to identify many carriers of pathogenic variants. Population-based genetic testing offers a transformative approach in cancer prevention by allowing for proactive identification of any high-risk individuals and enabling early interventions. Objective: To assess the lifetime incremental effectiveness, costs, and cost-effectiveness of population-based multigene testing vs family history-based testing. Design, Setting, and Participants: This economic evaluation used a microsimulation model to assess the cost-effectiveness of multigene testing (BRCA1, BRCA2, and PALB2) for all women aged 30 to 35 years compared with the current standard of care that is family history based. Carriers of pathogenic variants were offered interventions, such as magnetic resonance imaging with or without mammography, chemoprevention, or risk-reducing mastectomy and salpingo-oophorectomy, to reduce cancer risk. A total of 2000 simulations were run on 1 000 000 women, using a lifetime time horizon and payer perspective, and costs were adjusted to 2022 US dollars. This study was conducted from September 1, 2020, to December 15, 2023. Main Outcomes and Measures: The main outcome measure was the incremental cost-effectiveness ratio (ICER), quantified as cost per quality-adjusted life-year (QALY) gained. Secondary outcomes included incremental cost, additional breast and ovarian cancer cases prevented, and excess deaths due to coronary heart disease (CHD). Results: The study assessed 1 000 000 simulated women aged 30 to 35 years in the US. In the base case, population-based multigene testing was more cost-effective compared with family history-based testing, with an ICER of $55 548 per QALY (95% CI, $47 288-$65 850 per QALY). Population-based multigene testing would be able to prevent an additional 1338 cases of breast cancer and 663 cases of ovarian cancer, but it would also result in 69 cases of excess CHD and 10 excess CHD deaths per million women. The probabilistic sensitivity analyses show that the probability that population-based multigene testing is cost-effective was 100%. When the cost of the multigene test exceeded $825, population-based testing was no longer cost-effective (ICER, $100 005 per QALY; 95% CI, $87 601-$11 6323). Conclusions and Relevance: In this economic analysis of population-based multigene testing, population-based testing was a more cost-effective strategy for the prevention of breast cancer and ovarian cancer when compared with the current family history-based testing strategy at the $100 000 per QALY willingness-to-pay threshold. These findings support the need for more comprehensive genetic testing strategies to identify pathogenic variant carriers and enable informed decision-making for personalized risk management.

Temporal Trends in Treatment and Outcomes of Endometrial Carcinoma in the United States, 2005-2020.

Endometrial cancer has continued to see a rising incidence in the US over the years. The main aim of this study was to assess current trends in patients' characteristics and outcomes of treatment for endometrial carcinoma over 16 years. A dataset from the National Cancer Database (NCDB) for patients diagnosed with endometrial carcinoma from 2005 to 2020 was used in this retrospective, case series study. The main outcomes and measures of interest included tumor characteristics, hospitalization, treatments, mortality, and overall survival. Then, 569,817 patients who were diagnosed with endometrial carcinoma were included in this study. The mean (SD) age at diagnosis was 62.7 (11.6) years, but 66,184 patients (11.6%) were younger than 50 years, indicating that more patients are getting diagnosed at younger ages. Of the patients studied, 37,079 (6.3%) were Hispanic, 52,801 (9.3%) were non-Hispanic Black, 432,058 (75.8%) were non-Hispanic White, and 48,879 (8.6%) were other non-Hispanic. Patients in the 4th period from 2017 to 2020 were diagnosed more with stage IV (7.1% vs. 5.2% vs. 5.4% vs. 5.9%; p < 0.001) disease compared with those in the other three periods. More patients with severe comorbidities (Charlson Comorbidity Index score of three) were seen in period 4 compared to the first three periods (3.9% vs. ≤1.9%). Systemic chemotherapy use (14.1% vs. 17.7% vs. 20.4% vs. 21.1%; p < 0.001) and immunotherapy (0.01% vs. 0.01% vs. 0.2% vs. 1.1%; p < 0.001) significantly increased from period 1 to 4. The use of laparotomy decreased significantly from 42.1% in period 2 to 16.7% in period 4, while robotic surgery usage significantly increased from 41.5% in period 2 to 64.3% in period 4. The 30-day and 90-day mortality decreased from 0.6% in period 1 to 0.2% in period 4 and 1.4% in period 1 to 0.6% in period 4, respectively. Over the period studied, we found increased use of immunotherapy, chemotherapy, and minimally invasive surgery for the management of endometrial cancer. Overall, the time interval from cancer diagnosis to final surgery increased by about 6 days. The improvements observed in the outcomes examined can probably be associated with the treatment trends observed.

Incidence of human papillomavirus-related cancers among males and females aged 15-34 years in the United States.

Postmarket surveillance of the incidence of human papillomavirus (HPV)-related cancers is essential to monitor the effectiveness of HPV vaccines. We directly compared HPV-related cancer incidences during the pre- and postvaccine era to assess the effects of HPV vaccination among vaccine-eligible age groups in the United States using data from the US Cancer Statistics database. The 5-year average annual incidence rates for HPV-related cancers decreased in 2015-2019 compared with 2002-2006 among females aged 15-24 years and 25-34 years. Overall, a decrease in young males was not observed, whereas males aged 25-34 years experienced a slight decline in oropharyngeal squamous cell carcinoma between 2005-2009 and 2015-2019. Incidence rates for HPV-related cancers statistically significantly decreased in the vaccine era compared with the prevaccine era among females aged 15-34 years, suggesting the potential early effects of the introduction of HPV vaccination in the United States.

Incomplete HPV Vaccination among Individuals Aged 27-45 Years in the United States: A Mixed-Effect Analysis of Individual and Contextual Factors.

Background: In the United States, the human papillomavirus (HPV) vaccine is approved for use in individuals up to age 45. Individuals 15 years and older require three doses of the vaccine to complete the recommended dosing series. Incomplete HPV vaccination rates (i.e., one or two doses) among those over age 26, however, remain high. This study examined the independent effects of individual- and neighborhood-level factors on incomplete HPV vaccination rates in the United States (U.S.) among those aged 27-45 years. Methods: This retrospective cohort study used administrative data from Optum's de-identified Clinformatics® Data Mart Database to identify individuals aged 27-45 years who received one or more doses of HPV vaccine between July 2019 and June 2022. Multilevel multivariable logistic regression models were applied to the data on 7662 individuals identified as being fully or partially vaccinated against HPV, nested within 3839 neighborhoods across the U.S. Results: Approximately half of the patients in this study (52.93%) were not completely vaccinated against HPV. After adjusting for all other covariates in the final model, being older than 30 years old decreased the odds of not completing the HPV vaccine series. Participants living in South-region neighborhoods of the U.S. had enhanced odds of not completing the vaccine series compared with those residing in Northeast-region neighborhoods (aOR 1.21; 95% CrI 1.03-1.42). There was significant clustering of incomplete HPV vaccination rates at the neighborhood level. Conclusions: This study revealed that individual- and neighborhood-level factors were associated with the risk of not completing the HPV vaccine series among individuals aged 27-45 years in the U.S. Interventions to improve HPV vaccination series completion rates for this age group should take into consideration both individual and contextual factors.

Trends in Oropharyngeal Cancer Incidence Among Adult Men and Women in the United States From 2001 to 2018.

Background: The human papillomavirus (HPV) vaccine was approved in 2006 and has been shown to decrease vaccine-related HPV types in the oropharynx. Its impact on the incidence of HPV-related oropharyngeal squamous cell carcinoma (OPSCC) has not been examined. We investigated the impact of HPV vaccination on the incidence of HPV-related OPSCC in the US among male and female adults from different age groups. Methods: The US Cancer Statistics 2001-2018 database and the National Cancer Institute (NCI)'s Surveillance Epidemiology and End Results (SEER) program were used in this study. OPSCC incidence was age-adjusted to the US standard population in 2000. Cause-specific 5-year survival probability was calculated using 60 monthly intervals in SEER*Stat software. Results: Incidence of HPV-related OPSCC was much higher in males than in females. Age-adjusted annual incidence of OPSCC was significantly lower in 2014-2018 than in 2002-2006 among males 20-44 years old (11.4 vs 12.8 per 1,000,000, rate ratio 0.89, 95% confidence interval 0.84-0.93) and among females 20-44 years old (3.0 vs 3.6 per 1,000,000, rate ratio 0.86, 95% confidence interval 0.78-0.95), but increased in both 45-64 year old and 65+ year old males and females. Joinpoint regression revealed a significant joint in the HPV-OPSCC incidence trend for 20-44-year-old males in 2008 at which time the incidence began to decrease. Except for 20-44 year old females (74.8% in 2002-2006 vs. 75.7% in 2009-2013, p=0.84), cancer-specific 5-year survivals significantly improved for males and females of all age groups. Conclusions: HPV-related OPSCC was much more common in males. Incidence of HPV-related OPSCC declined among young adults during the vaccination era compared with pre-vaccination era. Cancer-specific 5-year survival was significantly improved in young males but not in young females.

BRCA testing and testing results among women 18-65 years old.

Since the 1990 s discovery of BRCA1 and BRCA2 pathogenic variants in breast or ovarian cancer patients, genetic testing has been recommended as part of a targeted, individualized approach for cancer prevention and treatment in eligible individuals. The aim of this study was to assess trends in BRCA test rates and results among adult women aged 18 to 65 in the US between 2007 and 2017. Using Clinformatics© Data Mart (CDM) Electronic Health Records, we included 223,211 women 18-65 years old with documented BRCA testing results from 1/1/2007-9/30/2017. Positive results indicated the presence of pathogenic variantss. BRCA test rates increased significantly from 34 per 100,000 women in 2007 to 488 per 100,000 women in 2016 (APC 30.8, 95% confidence interval 26.6-35.1). Documented positive results decreased from 86.1% in 2007 to 78.0% in 2017(APC -0.6, 95% confidence interval -1.4-0.2). From 2007 to 2017, decreasing trends in the rates of documented positive results were observed among all three age groups (18-39, 40-54, and 55-65 years; largest in 40-54 group). In 2015-2017, women with positive test results were less likely to be non-Hispanic Whites, cancer patients, or living in the Northeast or an area with average household income ≥$50,000. Between 2007 and 2017, increasing use of BRCA testing for cancer prevention and treatment occurred, correlating to the observed decreasing documented positive test rate. The utilization of testing and corresponding test results differed significantly across races/ethnicities, suggestive of a divergent application of the same testing criteria.

Infant vaccination education preferences among low-income pregnant women.

Childhood vaccination is an important public health intervention, yet many children remain under-vaccinated. The objective of this study was to examine infant vaccination education preferences in a population of low-income pregnant women by ethnicity, nativity, and language. Pregnant women 14-44 y old (n = 335) attending a participating low-income reproductive health clinic in southeast Texas from May 26-July 21, 2017, and who completed a paper survey offered in English and Spanish were included. Participants were asked to complete questions about their demographic characteristics and preferences about infant vaccination education. To examine differences in vaccine education preferences by participant demographic characteristics, chi-squared tests, or Fisher's exact tests and one-way analysis of variance (ANOVA) were conducted using Stata SE Version 15.1 with α = 0.05. Nearly half (47.5%) of participants considered pregnancy the best time to get information about infant vaccination and were most likely (40.6%) to indicate the nurse who gives vaccines during pregnancy as the health-care worker with whom they would like to discuss infant vaccination. There were no demographic differences in preferred timing of vaccine education delivery or provider who delivers vaccine education. Prenatal, nurse-delivered vaccine educational programs would be well accepted in this low-income population.