Innovations in research and clinical care using patient-generated health data.

Patient-generated health data (PGHD), or health-related data gathered from patients to help address a health concern, are used increasingly in oncology to make regulatory decisions and evaluate quality of care. PGHD include self-reported health and treatment histories, patient-reported outcomes (PROs), and biometric sensor data. Advances in wireless technology, smartphones, and the Internet of Things have facilitated new ways to collect PGHD during clinic visits and in daily life. The goal of the current review was to provide an overview of the current clinical, regulatory, technological, and analytic landscape as it relates to PGHD in oncology research and care. The review begins with a rationale for PGHD as described by the US Food and Drug Administration, the Institute of Medicine, and other regulatory and scientific organizations. The evidence base for clinic-based and remote symptom monitoring using PGHD is described, with an emphasis on PROs. An overview is presented of current approaches to digital phenotyping or device-based, real-time assessment of biometric, behavioral, self-report, and performance data. Analytic opportunities regarding PGHD are envisioned in the context of big data and artificial intelligence in medicine. Finally, challenges and solutions for the integration of PGHD into clinical care are presented. The challenges include electronic medical record integration of PROs and biometric data, analysis of large and complex biometric data sets, and potential clinic workflow redesign. In addition, there is currently more limited evidence for the use of biometric data relative to PROs. Despite these challenges, the potential benefits of PGHD make them increasingly likely to be integrated into oncology research and clinical care.

Attitudes toward the American Cancer Society's 2020 cervical cancer screening guidelines: A qualitative study of a national sample of US clinicians.

BACKGROUND: The 2020 American Cancer Society (ACS) guidelines are the most recent national guidelines for cervical cancer screening. These guidelines propose two major changes from current practice: initiating screening at age 25 years and using primary human papillomavirus (HPV) testing. Adoption of guidelines often occurs slowly, and therefore understanding clinician attitudes is important to facilitate practice change. METHODS: Interviews with a national sample of clinicians who perform cervical cancer screening in a variety of settings explored attitudes toward the two major changes from the 2020 ACS cervical cancer screening guidelines. Clinicians participated in 30- to 60-min interviews exploring their attitudes toward various aspects of cervical cancer screening. Qualitative analysis was performed. RESULTS: Seventy clinicians participated from across the United States. Few respondents were initiating screening at age 25 years, and none were using primary HPV testing. However, over half would be willing to adopt these practices if supported by scientific evidence and recommended by professional medical organizations. Barriers to adoption included the lack of endorsement by professional societies, lack of laboratory availability and insurance coverage, limited autonomy within large health care systems, and concerns related to missed disease. CONCLUSIONS: Few clinicians have adopted screening initiation or primary HPV testing, as recommended by the 2020 ACS guidelines, but over half were open to adopting these changes. Implementation may be facilitated via professional organization endorsement, clinician education, and laboratory, health care system, and insurance support. PLAIN LANGUAGE SUMMARY: In 2020, the American Cancer Society (ACS) released updated guidelines for cervical cancer screening. The main changes to current practices were to initiate screening at age 25 years instead of age 21 years and to screen using primary human papillomavirus (HPV) testing rather than cytology alone or in combination with HPV testing. We performed in-depth interviews with 70 obstetrics and gynecology, family medicine, and internal medicine physicians and advanced practice providers about their attitudes toward these guidelines. Few clinicians are following the 2020 ACS guidelines, but over half were open to changing practice if the changes were supported by evidence and recommended by professional medical organizations. Barriers to adoption included the lack of endorsement by professional medical organizations, logistical issues, and concerns about missed disease.

Implementation of an "opt-out" tobacco treatment program in six hospitals in South Carolina.

OBJECTIVE: Describe the screening, referral, and treatment delivery associated with an opt-out tobacco treatment program (TTP) implemented in six hospitals varying in size, rurality and patient populations. METHODS: Between March 6, 2021 and December 17, 2021, adult patients (≥ 18 years) admitted to six hospitals affiliated with the Medical University of South Carolina were screened for smoking status. The hospitals ranged in size from 82 to 715 beds. Those currently smoking were automatically referred to one of two tobacco treatment options: 1) Enhanced care (EC) where patients could receive a bedside consult by a trained tobacco treatment specialist plus an automated post-discharge follow-up call designed to connect those smoking to the South Carolina Quitline (SCQL); or 2) Basic care (BC) consisting of the post-discharge follow-up call only. An attempt was made to survey patients at 6-weeks after hospitalization to assess smoking status. RESULTS: Smoking prevalence ranged from 14 to 49% across the six hospitals; 6,000 patients were referred to the TTP.The delivery of the bedside consult varied across the hospitals with the lowest in the Charleston hospitals which had the highest caseload of referred patients per specialist. Among patients who received a consult visit during their hospitalization, 50% accepted the consult, 8% opted out, 3% claimed not to be current smokers, and 38% were unavailable at the time of the consult visit. Most of those enrolled in the TTP were long-term daily smokers.Forty-three percent of patients eligible for the automated post-discharge follow-up call answered the call, of those, 61% reported smoking in the past seven days, and of those, 34% accepted the referral to theSCQL. Among the 986 of patients surveyed at 6-weeks after hospitalization quit rates ranged from 20%-30% based on duration of reported cessation and were similar between hospitals and for patients assigned to EC versus BC intervention groups. CONCLUSION: Findings demonstrate the broad reach of an opt-out TTP. Elements of treatment delivery can be improved by addressing patient-to-staffing ratios, improving systems to prescribe stop smoking medications for patients at discharge and linking patients to stop smoking services after hospital discharge.

Consumption of Health-Related Videos and Human Papillomavirus Awareness: Cross-Sectional Analyses of a US National Survey and YouTube From the Urban-Rural Context.

BACKGROUND: Nearly 70% of Americans use the internet as their first source of information for health-related questions. Contemporary data on the consumption of web-based videos containing health information among American adults by urbanity or rurality is currently unavailable, and its link with health topic awareness, particularly for human papillomavirus (HPV), is not known. OBJECTIVE: We aim to describe trends and patterns in the consumption of health-related videos on social media from an urban-rural context, examine the association between exposure to health-related videos on social media and awareness of health topics (ie, HPV and HPV vaccine), and understand public interest in HPV-related video content through search terms and engagement analytics. METHODS: We conducted a cross-sectional analysis of the US Health Information National Trends Survey 6, a nationally representative survey that collects data from civilian, noninstitutionalized adults aged 18 years or older residing in the United States. Bivariable analyses were used to estimate the prevalence of consumption of health-related videos on social media among US adults overall and by urbanity or rurality. Multivariable logistic regression models were used to examine the association between the consumption of health-related videos and HPV awareness among urban and rural adults. To provide additional context on the public's interest in HPV-specific video content, we examined search volumes (quantitative) and related query searches (qualitative) for the terms "HPV" and "HPV vaccine" on YouTube. RESULTS: In 2022, 59.6% of US adults (152.3 million) consumed health-related videos on social media, an increase of nearly 100% from 2017 to 2022. Prevalence increased among adults living in both urban (from 31.4% in 2017 to 59.8% in 2022; P<.001) and rural (from 22.4% in 2017 to 58% in 2022; P<.001) regions. Within the urban and rural groups, consumption of health-related videos on social media was most prevalent among adults aged between 18 and 40 years and college graduates or higher-educated adults. Among both urban and rural groups, adults who consumed health-related videos had a significantly higher probability of being aware of HPV and the HPV vaccine compared with those who did not watch health videos on the internet. The term "HPV" was more frequently searched on YouTube compared with "HPV vaccine." Individuals were most commonly searching for videos that covered content about the HPV vaccine, HPV in males, and side effects of the HPV vaccine. CONCLUSIONS: The consumption of health-related videos on social media in the United States increased dramatically between 2017 and 2022. The rise was prominent among both urban and rural adults. Watching a health-related video on social media was associated with a greater probability of being aware of HPV and the HPV vaccine. Additional research on designing and developing social media strategies is needed to increase public awareness of health topics.

Sparse clusterability: testing for cluster structure in high dimensions.

BACKGROUND: Cluster analysis is utilized frequently in scientific theory and applications to separate data into groups. A key assumption in many clustering algorithms is that the data was generated from a population consisting of multiple distinct clusters. Clusterability testing allows users to question the inherent assumption of latent cluster structure, a theoretical requirement for meaningful results in cluster analysis. RESULTS: This paper proposes methods for clusterability testing designed for high-dimensional data by utilizing sparse principal component analysis. Type I error and power of the clusterability tests are evaluated using simulated data with different types of cluster structure in high dimensions. Empirical performance of the new methods is evaluated and compared with prior methods on gene expression, microarray, and shotgun proteomics data. Our methods had reasonably low Type I error and maintained power for many datasets with a variety of structures and dimensions. Cluster structure was not detectable in other datasets with spatially close clusters. CONCLUSION: This is the first analysis of clusterability testing on both simulated and real-world high-dimensional data.

A cross-sectional survey examining clinician characteristics, practices, and attitudes associated with adoption of the 2019 American Society for Colposcopy and Cervical Pathology risk-based management consensus guidelines.

BACKGROUND: The 2019 American Society for Colposcopy and Cervical Pathology (ASCCP) risk-based management consensus guidelines are the most recent national guidelines for the management of abnormal cervical cancer screening tests. These guidelines benefit patients by concentrating testing and treatment in those at highest cervical cancer risk. Adoption of guidelines often occurs slowly, with few studies examining the factors associated with guideline-adherent management of abnormal results. METHODS: To elucidate the factors associated with the use of the 2019 ASCCP guidelines among clinicians who perform cervical cancer screening, physicians and advanced practice professionals who perform cervical cancer screening were cross-sectionally surveyed. Clinicians responded to screening vignettes with differing recommendations for management between the 2019 and prior management guidelines. Screening vignette 1 involved reduction of invasive testing on a low-risk patient; screening vignette 2 involved increased surveillance testing on a high-risk patient. Binomial logistic regression models determined the factors associated with the use of the 2019 guidelines. RESULTS: A total of 1251 clinicians participated from across the United States. For screening vignettes 1 and 2, guideline-adherent responses were given by 28% and 36% of participants, respectively. Management recommendations differed by specialty and were incorrect in different situations: there was inappropriate invasive testing by obstetrics and gynecology physicians (vignette 1) and inappropriate discontinuation of screening by family and internal medicine physicians (vignette 2). Regardless of their chosen response, over half erroneously believed they were guideline adherent. CONCLUSIONS: Many clinicians who believe they are following appropriate guidelines may not realize their management strategy is inconsistent with the 2019 guidelines. Education initiatives tailored to clinician specialty could address the understanding of current guidelines, encourage the use of updated guidelines, maximize patient benefits, and minimize harms. PLAIN LANGUAGE SUMMARY: The 2019 American Society for Colposcopy and Cervical Pathology risk-based management consensus guidelines are the most recent national guidelines for abnormal cervical cancer screening test management. We surveyed over 1200 obstetrics and gynecology (OB/GYN), family medicine, and internal medicine physicians and advanced practice providers about their screening and abnormal results follow-up practices in relation to guidelines. Few clinicians are following the 2019 guidelines. Management recommendations differed by clinician specialty and were incorrect in different situations: there was inappropriate invasive testing by OB/GYN physicians and inappropriate screening discontinuation by family and internal medicine physicians. Education tailored by clinician specialty could address the understanding of current guidelines, encourage the use of updated guidelines, maximize patient benefits, and minimize harms.

Factors related to human papillomavirus vaccine uptake and intentions among adults aged 18-26 and 27-45 years in the United States: A cross-sectional study.

BACKGROUND: The current study examined self-reported human papillomavirus (HPV) vaccination uptake and intentions, and associations with psychosocial constructs among United States adults aged 18 to 26 and 27 to 45 years. METHODS: Data were collected via an online survey from participants recruited from a research panel. Outcomes were HPV vaccination uptake and intentions. Multivariable binary and ordered logistic regression models were used to examine associations between HPV vaccination outcomes and psychosocial constructs, sociodemographics, and previous health behaviors. RESULTS: HPV vaccination uptake in both age cohorts (N =  2722) was associated with multiple variables, including but not limited to: provider recommendation (adjusted odds ratio [aOR], 11.63 [95% CI, 7.70-17.56] and aOR, 14.26 [95% CI, 9.52-21.38], for those aged 18 to 26 and 27 to 45 years, respectively) and positive HPV vaccine attitudes (aOR, 2.40 [95% CI, 1.70-3.40] and aOR, 1.46 [95% CI,1.06-2.02]). Among those who did not report or were unsure of prior HPV vaccination (N =1894), only 4.6% and 8.1% (aged 18-26 and 27-45 years, respectively) reported being very likely to receive the HPV vaccine in the next year. Increased intentions were associated with more positive vaccine attitudes (aOR, 2.45 [95% CI, 1.91-3.15] and aOR, 2.19 [95% CI, 1.72-2.78]) and provider recommendation (yes vs no; aOR, 1.97 [95% CI, 1.38-2.83] and aOR, 1.82 [95% CI, 1.31-2.52]; don't know/can't remember vs no; aOR, 1.38 [95% CI, 1.03-1.84] and aOR, 1.60 [95% CI, 1.17-2.18]). Sociodemographics and health behaviors associated with increased intentions differed for each age cohort. CONCLUSIONS: Individual and interpersonal factors were associated with HPV vaccination uptake and intentions. Findings reveal the need for targeted interventions to improve HPV vaccination rates among these age groups.

Self-reported barriers to screening breast MRI among women at high risk for breast cancer.

BACKGROUND: Annual screening breast MRI is recommended for women at high (≥ 20% lifetime) breast cancer risk, but is underutilized. Guided by the Health Services Utilization Model (HSUM), we assessed factors associated with screening breast MRI among high-risk women. METHODS: From August 2020-January 2021, we recruited an online convenience sample of high-risk women ages 25-85 (N = 232). High-risk was defined as: pathogenic genetic mutation in self or first-degree relative; history of lobular carcinoma in situ; history of thoracic radiation; or estimated lifetime risk ≥ 20%. Participants self-reported predisposing factors (breast cancer knowledge, health locus of control), enabling factors (health insurance type, social support), need factors (perceived risk, screening-supportive social norms, provider recommendation), and prior receipt of screening breast MRI. Multivariable logistic regression analysis with backward selection identified HSUM factors associated with receipt of screening breast MRI. RESULTS: About half (51%) of participants had received a provider recommendation for screening breast MRI; only 32% had ever received a breast MRI. Breast cancer knowledge (OR = 1.15, 95% CI = 1.04-1.27) and screening-supportive social norms (OR = 2.21, 95% CI = 1.64-2.97) were positively related to breast MRI receipt. No other HSUM variables were associated with breast MRI receipt (all p's > 0.1). CONCLUSIONS: High-risk women reported low uptake of screening breast MRI, indicating a gap in guideline-concordant care. Breast cancer knowledge and screening-supportive social norms are two key areas to target in future interventions. Data were collected during the COVID-19 pandemic and generalizability of results is unclear. Future studies with larger, more heterogeneous samples are needed to replicate these findings.

Factors associated with parental COVID-19 vaccine attitudes and intentions among a national sample of United States adults ages 18-45.

PURPOSE: This study explored factors associated with parents' attitudes and intentions to seek information about the COVID-19 vaccine for their children (ages 0-18) and intentions to vaccinate their age-eligible children. DESIGN AND METHODS: As part of an anonymous online cross-sectional survey, parents' vaccine attitudes, COVID-19 vaccine intentions for their children, health literacy, health numeracy, and sociodemographic variables were assessed. Multivariable ordered logistic regression models identified factors associated with parents' COVID-19 vaccine intentions for their children. RESULTS: Parents/guardians (n = 963) were mostly White (82.3%), insured (88.0%), and college graduates (57.3%). Men reported higher intentions than women to seek information about the COVID-19 vaccine for their children (p = 0.003) and higher intentions to vaccinate their children (p = 0.049). Parental characteristics associated with increased intentions to have their children vaccinated included higher educational attainment (p < 0.001), more positive general vaccine attitudes (p < 0.001), preference for health information in a language other than English (p = 0.006), higher income (p = 0.048), having health insurance (p = 0.05), health literacy (p = 0.024), and health numeracy (p = 0.049). CONCLUSIONS: Multiple sociodemographic characteristics including male gender, higher health literacy and numeracy, and language preference are noteworthy factors associated with parental COVID-19 vaccine intentions that could inform the planning and implementation of educational interventions. PRACTICE IMPLICATIONS: Nurses are important sources of trusted information and play an important role in parent/family health education and in understanding myriad factors that may improve attitudes and enhance readiness toward vaccine uptake. Our findings emphasize the potential value of examining tailored/targeted COVID-19 vaccine education according to key influencing factors.

Smoking Is Related to Worse Cancer-related Symptom Burden.

BACKGROUND: Cigarette smoking is related to greater cancer incidence, worse cancer-related clinical outcomes, and worse patient quality of life. Few studies have evaluated the role of smoking in patients' experiences of cancer-related symptom burden. This study examined relationships between smoking and total symptom burden as well as the incidence of severe symptoms among adult cancer patients. PATIENTS AND METHODS: Patients at Moffitt Cancer Center completed self-report surveys as part of routine cancer care. Symptom burden was evaluated as the sum of individual symptom ratings (total symptom burden) and the number of symptoms rated severe (incidence of severe symptoms). Zero-inflated negative binomial modeling was used to evaluate the relationships between smoking status (ever vs never smoker) and symptom burden outcomes controlling for relevant sociodemographic and clinical covariates and accounting for the proportion of participants reporting no symptom burden. RESULTS: This study included 12 571 cancer patients. More than half reported a history of cigarette smoking (n = 6771, 55%). Relative to never smokers, participants with a smoking history had 15% worse expected total symptom burden (ratio = 1.15, 95% confidence interval [CI] 1.11-1.20, P < .001) and 13% more expected severe symptoms (ratio = 1.13, 95% CI 1.05-1.21, P = .001) above and beyond the effects of relevant sociodemographic and clinical characteristics. CONCLUSION: Results provide support that smoking is associated with worse cancer symptom burden. More research is needed to evaluate how smoking history (ie, current vs former smoker) and smoking cessation influence cancer symptom burden.

Developing the Florida Academic Cancer Center Alliance Health Disparities Common Measure: The Florida Health and Ancestry Survey.

PURPOSE: Our specific aim was to develop and assess the consensus-based validity of common measures for understanding health behaviors and ancestry in Florida's population subgroups and establish the feasibility of wide-scale implementation of the measures and biospecimen collection within three cancer centers' catchment areas. METHODS: Using the National Cancer Institute's Grid-Enabled Measures web-based platform and an iterative process, we developed the Florida Health and Ancestry Survey (FHAS). We then used three sampling approaches to implement the FHAS: community-engaged, panel respondent, and random digit dialing (RDD). We asked a subset of participants to provide a saliva sample for future validation of subjective ancestry report with DNA-derived ancestry markers. RESULTS: This process supported the FHAS content validity. As an indicator of feasibility, the goals for completed surveys by sampling approach were met for two of the three cancer centers, yielding a total of 1438 completed surveys. The RDD approach produced the most representative sample. The panel sampling approach produced inadequate representation of older individuals and males. The community-engaged approach along with social media recruitment produced extreme underrepresentation only for males. Two of the cancer centers mailed biospecimen kits, whereas one did not due to resource constraints. On average, the community engaged approach was more productive in obtaining returned biospecimen samples (80%) than the panel approach (48%). CONCLUSIONS: We successfully developed and implemented the FHAS as a common measure to show its feasibility for understanding cancer health disparities in Florida. We identified sampling approach successes and challenges to obtaining biospecimens for ancestry research.

COVID-19 vaccine behaviors and intentions among a national sample of United States adults ages 18-45.

BACKGROUND: Vaccination for SARS-CoV-2, the virus that causes COVID-19 illness, is an important public health tool to reduce hospitalizations and deaths. PURPOSE: This report focuses on intentions and behaviors related to COVID-19 vaccination among United States (U.S.) adults ages 18-45. METHODS: From February 25-March 24, 2021, we conducted an online survey assessing COVID-19 vaccine intentions and behaviors, health beliefs, vaccine attitudes, and sociodemographic characteristics. Participants were adults aged 18-45, living throughout the U.S. with oversampling in Florida, panelists of a research panel company directly or via verified partners, and able to read, write, and understand English. Associations between COVID-19 vaccination uptake, intentions, and other study variables were examined through multivariable logistic and proportional odds regression analyses. RESULTS: Among participants in the final analytic sample (n = 2722), 18% reported having received at least one dose of a COVID-19 vaccine. Approximately 31% of unvaccinated participants reported strong intentions to receive a COVID-19 vaccine in the next year, whereas 35% reported strong intentions to receive a COVID-19 vaccine if it were strongly recommended by a healthcare provider. All COVID-19 vaccination outcomes were associated with male gender, sexual minority status, higher levels of education, and previous influenza vaccination. All vaccination intention outcomes were associated with vaccine attitudes and geographic region. Vaccination status and intentions were differentially associated with multiple additional sociodemographic, attitudinal, and/or healthcare experience variables. CONCLUSIONS: Several demographic variables, vaccine attitudes, and healthcare experiences were found to contribute to COVID-19 vaccine receipt and intentions. Targeted efforts are necessary to increase uptake of the vaccine in the U.S.

Diet quality indices and changes in cognition during chemotherapy.

PURPOSE: No evidence-based prevention strategies currently exist for cancer-related cognitive decline (CRCD). Although patients are often advised to engage in healthy lifestyle activities (e.g., nutritious diet), little is known about the impact of diet on preventing CRCD. This secondary analysis evaluated the association of pre-treatment diet quality indices on change in self-reported cognition during chemotherapy. METHODS: Study participants (n = 96) completed the Block Brief Food Frequency Questionnaire (FFQ) before receiving their first infusion and the PROMIS cognitive function and cognitive abilities questionnaires before infusion and again 5 days later (i.e., when symptoms were expected to be their worst). Diet quality indices included the Dietary Approaches to Stop Hypertension (DASH), Alternate Mediterranean Diet (aMED), and a low carbohydrate diet index and their components. Descriptive statistics were generated for demographic and clinical variables and diet indices. Residualized change models were computed to examine whether diet was associated with change in cognitive function and cognitive abilities, controlling for age, sex, cancer type, treatment type, depression, and fatigue. RESULTS: Study participants had a mean age of 59 ± 10.8 years and 69% were female. Although total diet index scores did not predict change in cognitive function or cognitive abilities, higher pre-treatment ratio of aMED monounsaturated/saturated fat was associated with less decline in cognitive function and cognitive abilities at 5-day post-infusion (P ≤ .001). CONCLUSIONS: Higher pre-treatment ratio of monounsaturated/saturated fat intake was associated with less CRCD early in chemotherapy. Results suggest greater monounsaturated fat and less saturated fat intake could be protective against CRCD during chemotherapy.

Bayesian analysis of survival data with missing censoring indicators.

In some large clinical studies, it may be impractical to perform the physical examination to every subject at his/her last monitoring time in order to diagnose the occurrence of the event of interest. This gives rise to survival data with missing censoring indicators where the probability of missing may depend on time of last monitoring and some covariates. We present a fully Bayesian semi-parametric method for such survival data to estimate regression parameters of the proportional hazards model of Cox. Theoretical investigation and simulation studies show that our method performs better than competing methods. We apply the proposed method to analyze the survival data with missing censoring indicators from the Orofacial Pain: Prospective Evaluation and Risk Assessment study.

Tests of trend between disease outcomes and ordinal covariates discretized from underlying continuous variables: simulation studies and applications to NHANES 2007-2008.

BACKGROUND: Many epidemiological studies test trends when investigating the association between a risk factor and a disease outcome. Continuous exposures are commonly discretized when the outcome is nonlinearly related to exposure as well as to facilitate interpretation and reduce measurement error. Guidance is needed regarding statistically valid trend tests for epidemiological data of this nature. METHODS: The association between a discretized variable and a disease is modeled through logistic regression or survival analysis. Linear regression is then conducted by regressing the odds ratio or relative risk on the midpoint of the exposure interval. The trend test is based on the slope of the regression line. In order to investigate the performance of this approach, we conducted simulation studies, considering ten different approaches for the linear regression based on the inclusion or exclusion of an intercept in the model and the form of the weights. The proposed methods are applied to the National Health and Nutrition Examination Survey (NHANES) 2007-2008 for illustration. RESULTS: The simulation studies show that eight of these methods are valid, and the relative efficiency depends on the underlying relationship between the covariate and the outcome. CONCLUSIONS: The significance of the study is its potential to help practitioners select an appropriate method to test for trend in their future studies that utilize ordinal covariates.

Improving Underrepresented Minority in Medicine Representation in Medical School.

OBJECTIVES: Despite the efforts of various leading organizations in medical education, representation of black students in US medical schools has declined since the mid-1990s. The Florida State University College of Medicine (FSUCOM) has undertaken efforts to increase black and other underrepresented minority in medicine (URMM) representation in medical school through the Bridge to Clinical Medicine Program. This program is described and analyzed by the authors. METHODS: Demographic information, Medical College Admission Test scores, undergraduate grade point average, US Medical Licensing Examination (USMLE) scores (Steps 1 and 2), residency match information, and current practice location from 2006 to 2015 were collected from the FSUCOM. Data were analyzed using SAS and linear regression analyses were performed, comparing Bridge students with the College of Medicine and national averages. RESULTS: Sixty percent of Bridge students were black, 21% were other URMM, and the remainder were non-URMM. Black Bridge students scored 7.4 points lower on their Medical College Admission Test, and other-URMM Bridge students scored 6.0 points lower (P < 0.0001) than their non-URMM non-Bridge classmates. Black Bridge students also started with a grade point average that was 0.28 points lower than their non-URMM non-Bridge counterparts, but there was no statistical difference for other-URMM Bridge students. Black students, regardless of Bridge participation, were less likely to pass USMLE Step 1 when compared with non-URMM classmates (P < 0.0001). For USMLE Step 2, however, there were no significant differences in passing rates for Bridge students compared with non-Bridge students. CONCLUSIONS: The FSUCOM Bridge program has not only increased its URMM enrollment but it also has effectively doubled the number of black students in its medical college. Other universities could produce similar results using the program outlined in this article.

Ultrahigh-resolution Fourier transform ion cyclotron resonance mass spectrometry and tandem mass spectrometry for peptide de novo amino acid sequencing for a seven-protein mixture by paired single-residue transposed Lys-N and Lys-C digestion.

RATIONALE: Bottom-up tandem mass spectrometry (MS/MS) is regularly used in proteomics to identify proteins from a sequence database. De novo sequencing is also available for sequencing peptides with relatively short sequence lengths. We recently showed that paired Lys-C and Lys-N proteases produce peptides of identical mass and similar retention time, but different tandem mass spectra. Such parallel experiments provide complementary information, and allow for up to 100% MS/MS sequence coverage. METHODS: Here, we report digestion by paired Lys-C and Lys-N proteases of a seven-protein mixture: human hemoglobin alpha, bovine carbonic anhydrase 2, horse skeletal muscle myoglobin, hen egg white lysozyme, bovine pancreatic ribonuclease, bovine rhodanese, and bovine serum albumin, followed by reversed-phase nanoflow liquid chromatography, collision-induced dissociation, and 14.5 T Fourier transform ion cyclotron resonance mass spectrometry. RESULTS: Matched pairs of product peptide ions of equal precursor mass and similar retention times from each digestion are compared, leveraging single-residue transposed information with independent interferences to confidently identify fragment ion types, residues, and peptides. Selected pairs of product ion mass spectra for de novo sequenced protein segments from each member of the mixture are presented. CONCLUSIONS: Pairs of the transposed product ions as well as complementary information from the parallel experiments allow for both high MS/MS coverage for long peptide sequences and high confidence in the amino acid identification. Moreover, the parallel experiments in the de novo sequencing reduce false-positive matches of product ions from the single-residue transposed peptides from the same segment, and thereby further improve the confidence in protein identification. Copyright © 2016 John Wiley & Sons, Ltd.

Maternal residential exposure to agricultural pesticides and birth defects in a 2003 to 2005 North Carolina birth cohort.

BACKGROUND: Birth defects are responsible for a large proportion of disability and infant mortality. Exposure to a variety of pesticides have been linked to increased risk of birth defects. METHODS: We conducted a case-control study to estimate the associations between a residence-based metric of agricultural pesticide exposure and birth defects. We linked singleton live birth records for 2003 to 2005 from the North Carolina (NC) State Center for Health Statistics to data from the NC Birth Defects Monitoring Program. Included women had residence at delivery inside NC and infants with gestational ages from 20 to 44 weeks (n = 304,906). Pesticide exposure was assigned using a previously constructed metric, estimating total chemical exposure (pounds of active ingredient) based on crops within 500 meters of maternal residence, specific dates of pregnancy, and chemical application dates based on the planting/harvesting dates of each crop. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals for four categories of exposure (<10(th) , 10-50(th) , 50-90(th) , and >90(th) percentiles) compared with unexposed. Models were adjusted for maternal race, age at delivery, education, marital status, and smoking status. RESULTS: We observed elevated ORs for congenital heart defects and certain structural defects affecting the gastrointestinal, genitourinary and musculoskeletal systems (e.g., OR [95% confidence interval] [highest exposure vs. unexposed] for tracheal esophageal fistula/esophageal atresia = 1.98 [0.69, 5.66], and OR for atrial septal defects: 1.70 [1.34, 2.14]). CONCLUSION: Our results provide some evidence of associations between residential exposure to agricultural pesticides and several birth defects phenotypes. Birth Defects Research (Part A) 106:240-249, 2016. © 2016 Wiley Periodicals, Inc.

Parameter estimation in Cox models with missing failure indicators and the OPPERA study.

In a prospective cohort study, examining all participants for incidence of the condition of interest may be prohibitively expensive. For example, the "gold standard" for diagnosing temporomandibular disorder (TMD) is a physical examination by a trained clinician. In large studies, examining all participants in this manner is infeasible. Instead, it is common to use questionnaires to screen for incidence of TMD and perform the "gold standard" examination only on participants who screen positively. Unfortunately, some participants may leave the study before receiving the "gold standard" examination. Within the framework of survival analysis, this results in missing failure indicators. Motivated by the Orofacial Pain: Prospective Evaluation and Risk Assessment (OPPERA) study, a large cohort study of TMD, we propose a method for parameter estimation in survival models with missing failure indicators. We estimate the probability of being an incident case for those lacking a "gold standard" examination using logistic regression. These estimated probabilities are used to generate multiple imputations of case status for each missing examination that are combined with observed data in appropriate regression models. The variance introduced by the procedure is estimated using multiple imputation. The method can be used to estimate both regression coefficients in Cox proportional hazard models as well as incidence rates using Poisson regression. We simulate data with missing failure indicators and show that our method performs as well as or better than competing methods. Finally, we apply the proposed method to data from the OPPERA study.

Paired single residue-transposed Lys-N and Lys-C digestions for label-free identification of N-terminal and C-terminal MS/MS peptide product ions: ultrahigh resolution Fourier transform ion cyclotron resonance mass spectrometry and tandem mass spectrometry for peptide de novo sequencing.

RATIONALE: Paired Lys-N and Lys-C proteases produce peptides of identical mass and similar retention time, but different tandem mass spectra. Data from these parallel experiments provide constraints that are applied before data analysis. With this approach, we can find matched spectra before analysis, distinguish ion type, and determine residue level confidence. METHODS: Aliquots are digested separately by Lys-N and Lys-C peptidases, and analyzed by reversed-phase nano-flow liquid chromatography, collision-induced dissociation, and 14.5 T Fourier transform ion cyclotron resonance mass spectrometry. Matched pairs of fragmentation spectra with equal precursor mass and similar retention times from each digestion are compared, leveraging single-residue transposed information with independent interferences to confidently identify fragment ion type, residues, and peptides. The paired spectra are solved together as a single de novo sequencing problem. RESULTS: Two pairs of spectra of a de novo sequenced 18-mer are presented. In one example, the 18-mer has coverage of all residues except the N- and C- terminal lysines and their adjacent residues. The confidence level is high due to six pairs of transposed ions. In the other example, the coverage is incomplete. Nonetheless, nine pairs of transposed ions facilitate identification of two trimer sequence tags with high confidence, one with medium confidence, and additional sequence information with residue-by-residue confidence, thus demonstrating the value of residue-by-residue confidence. CONCLUSIONS: Sequence identity and variability, such as post-translational modifications (PTMs), are essential to understanding biological function and disease. The present method facilitates discovery of new peptides with multiple levels of confidence, promises potential characterization of PTMs, and validates peptides from databases. Independent validation may be of interest for a number of applications.