Causes of death in individuals with trisomy 18 after the first year of life.

Mortality in individuals with trisomy 18 has significantly decreased over the past 20 years, but there is scant literature addressing the prognosis and cause of death in individuals with trisomy 18 and survival past the first year of life (YOL). This study analyzed factors associated with mortality and cause of death in a retrospective cohort of 174 individuals with trisomy 18 and survival past the first YOL, the largest such series to date. Data were collected via retrospective survey of parents of affected individuals. Prenatal diagnosis of trisomy 18; postnatal respiratory distress; maternal age > 35 years; birthweight <2000 g; brain and spinal cord defect(s); atrial and/or ventricular septal defect(s); inability to feed orally without medical assistance; and failure to meet sitting and rolling milestones were associated with mortality in this sample. Cause of death was compared between our cohort of individuals with trisomy 18 and existing literature on those with mortality before the first YOL. Individuals with trisomy 18 with mortality after the first YOL demonstrated a predominance of infectious (n = 10/22) and postoperative (n = 6/22) contributing causes of death, in contrast to the existing literature, which shows a predominance of cardiopulmonary causes of death (e.g., cardiopulmonary arrest, pulmonary hypertension). These findings demonstrate that individuals with trisomy 18 and survival past the first YOL have unique medical needs, but further research is needed to develop clinical guidelines for this growing population.

Increasing and sustaining discharges by noon - a multi-year process improvement project.

High hospital occupancy degrades emergency department performance by increasing wait times, decreasing patient satisfaction, and increasing patient morbidity and mortality. Late discharges contribute to high hospital occupancy by increasing emergency department (ED) patient length of stay (LOS). We share our experience with increasing and sustaining early discharges at a 650-bed academic medical center in the United States. Our process improvement project followed the Institute of Medicine Model for Improvement of successive Plan‒Do‒Study‒Act cycles. We implemented multiple iterative interventions over 41 months. As a result, the proportion of discharge orders before 10 am increased from 8.7% at baseline to 22.2% (p < 0.001), and the proportion of discharges by noon (DBN) increased from 9.5% to 26.8% (p < 0.001). There was no increase in balancing metrics because of our interventions. RA-LOS (Risk Adjusted Length Of Stay) decreased from 1.16 to 1.09 (p = 0.01), RA-Mortality decreased from 0.65 to 0.61 (p = 0.62) and RA-Readmissions decreased from 0.92 to 0.74 (p < 0.001). Our study provides a roadmap to large academic facilities to increase and sustain the proportion of patients discharged by noon without negatively impacting LOS, 30-day readmissions, and mortality. Continuous performance evaluation, adaptability to changing resources, multidisciplinary engagement, and institutional buy-in were crucial drivers of our success.

New C-indices for assessing importance of longitudinal biomarkers in fitting competing risks survival data in the presence of partially masked causes.

Competing risks survival data in the presence of partially masked causes are frequently encountered in medical research or clinical trials. When longitudinal biomarkers are also available, it is of great clinical importance to examine associations between the longitudinal biomarkers and the cause-specific survival outcomes. In this article, we propose a cause-specific C-index for joint models of longitudinal and competing risks survival data accounting for masked causes. We also develop a posterior predictive algorithm for computing the out-of-sample cause-specific C-index using Markov chain Monte Carlo samples from the joint posterior of the in-sample longitudinal and competing risks survival data. We further construct the Δ $$ \Delta $$ C-index to quantify the strength of association between the longitudinal and cause-specific survival data, or between the out-of-sample longitudinal and survival data. Empirical performance of the proposed assessment criteria is examined through an extensive simulation study. An in-depth analysis of the real data from large cancer prevention trials is carried out to demonstrate the usefulness of the proposed methodology.

Prediction of future risk of any and higher-grade prostate cancer based on the PLCO and SELECT trials.

BACKGROUND: A model was built that characterized effects of individual factors on five-year prostate cancer (PCa) risk in the Prostate, Lung, Colon, and Ovarian Cancer Screening Trial (PLCO) and the Selenium and Vitamin E Cancer Prevention Trial (SELECT). This model was validated in a third San Antonio Biomarkers of Risk (SABOR) screening cohort. METHODS: A prediction model for 1- to 5-year risk of developing PCa and Gleason > 7 PCa (HG PCa) was built on PLCO and SELECT using the Cox proportional hazards model adjusting for patient baseline characteristics. Random forests and neural networks were compared to Cox proportional hazard survival models, using the trial datasets for model building and the SABOR cohort for model evaluation. The most accurate prediction model is included in an online calculator. RESULTS: The respective rates of PCa were 8.9%, 7.2%, and 11.1% in PLCO (n = 31,495), SELECT (n = 35,507), and SABOR (n = 1790) over median follow-up of 11.7, 8.1 and 9.0 years. The Cox model showed higher prostate-specific antigen (PSA), BMI and age, and African American race to be associated with PCa and HGPCa. Five-year risk predictions from the combined SELECT and PLCO model effectively discriminated risk in the SABOR cohort with C-index 0.76 (95% CI [0.72, 0.79]) for PCa, and 0.74 (95% CI [0.65,0.83]) for HGPCa. CONCLUSIONS: A 1- to 5-year PCa risk prediction model developed from PLCO and SELECT was validated with SABOR and implemented online. This model can individualize and inform shared screening decisions.

Survival after minimally invasive vs. open radical nephrectomy for stage I and II renal cell carcinoma.

BACKGROUND: A recently reported phase III randomized trial comparing open and minimally invasive hysterectomy showed significantly higher rates of local recurrence after minimally invasive surgery (MIS) for cervical cancer. This raised concerns regarding patterns of recurrences and survival after MIS in general. This study aims to determine the effect of MIS on all-cause mortality among patients undergoing radical nephrectomy for Stage I and II renal cell carcinoma (RCC). METHODS: We utilized the National Cancer Database to identify patients diagnosed with clinical stage I-II RCCs between 2010 and 2013. Patients for whom a laparoscopic or robotic radical nephrectomy was attempted were compared to patients who underwent open radical nephrectomy (ORN). Adjusted regression models with inverse probability propensity score weighting (IPW) were utilized to identify independent predictors of receiving MIS. All-cause mortality rates were compared using IPW survival functions and log-rank tests. Adjusted Cox proportional hazard models were fitted to determine independent predictors of OS. RESULTS: 27,642 patients were identified; 11,524 (41.7%) had MIS, while 16,118 (58.3%) had ORN. Kaplan-Meier survival curves in the IPW cohort showed significant OS advantage for patients who underwent MIS (p < 0.001). Furthermore, length of hospital stays (3 vs. 4 days), 30 day readmission rates (2.4 vs. 2.87%), 30 day (0.53 vs. 0.96%) and 90 day mortality rates (1.04 vs. 1.77%) were significantly higher in the ORN group (p < 0.001). CONCLUSIONS: MIS was associated with better OS outcomes compared to ORN for stage I and II RCC. In addition, MIS had lower post-operative readmission, 30- and 90 day mortality rates.

A Meta-Analysis of Breastfeeding Effects for Infants With Neonatal Abstinence Syndrome.

BACKGROUND: Neonatal abstinence syndrome (NAS) rates have dramatically increased. Breastfeeding is a nonpharmacological intervention that may be beneficial, reducing NAS symptom severity and thus the need for and duration of pharmacological treatment and length of hospital stay. OBJECTIVES: Conduct meta-analysis to determine whether breastfeeding results in better outcomes for NAS infants. Variables included symptom severity, need for and duration of pharmacological treatment, and length of hospital stay. METHODS: PubMed, Scopus, Embase, and Cochrane Library were searched from 2000 to 2020, and comparative studies examining breastfeeding for NAS infants were extracted. Randomized trials and cohort studies were included. Data were extracted and evaluated with Review Manager Version 5.3. A random-effects model was used to pool discontinuous outcomes using risk ratio and 95% confidence intervals. Continuous outcomes were evaluated by mean differences and 95% confidence intervals. RESULTS: Across 11 studies, 6,375 neonates were included in the meta-analysis. Using a random-effects analysis, breastfeeding reduced initiation of pharmacological treatment, reduced duration of pharmacological treatment, and reduced length of stay. No differences were detected for severity of NAS symptoms. Most studies only reported one to two variables of interest. For most studies, these variables were not the primary study outcomes. All studies were found to be of low risk and good quality based on the Cochrane Risk Assessment Tools. Varying breastfeeding definitions limit generalizability. DISCUSSION: Breastfeeding is associated with decreased initiation and duration of pharmacological treatment and length of stay.

Stress-Busting Program for Family Caregivers: Validation of the Spanish version using biomarkers and quality-of-life measures.

Hispanic family caregivers of people with dementia experience higher levels of stress compared to non-Hispanic white caregivers. Long-term stress causes depression, caregiver burden, cellular aging, and dysregulation of the immune, nervous, and endocrine systems. The purpose of this study was to determine the validity of the Spanish version of the English Stress-Busting Program (SBP) for Family Caregivers by determining changes in quality-of-life measures and biomarkers. Thirty-six caregivers completed the SBP in the language of their choice (14 Spanish-speaking Hispanics [HS], 8 English-speaking Hispanics [HE], and 14 non-Hispanic English [NHE] speakers). Quality-of-life measures included the Perceived Stress Scale, the Screen for Caregiver Burden, and the Center for Epidemiologic Studies Depression Scale. Assessment of oral health and immunity included salivary flow rate, pH, buffer capacity, total protein, and secretory immunoglobulin A (sIgA). Indicators of stress (salivary cortisol), inflammation (C-reactive protein), and cellular aging (leukocyte telomere length) were assessed. Following completion of the SBP, the Spanish-speaking group had less depression and caregiver burden along with improved oral health and reduced cellular aging. When comparing baseline values to post-intervention, all three groups showed significant improvement in subjective caregiver burden. When the data from all three groups were combined, biomarkers that showed improvement after nine weeks of SBP included the stress hormone cortisol, salivary pH, and leukocyte telomere length. The results indicate that the Spanish SBP reduces caregiver stress as assessed by quality-of-life indicators and biomarkers. The Spanish SBP can help to mitigate health disparities in Hispanic Spanish-speaking caregivers.

The Use of FRAX in Identifying Women Less Than 65 Years Needing Bone Mineral Density Testing.

The purpose of this study is to determine if the United States Preventive Services Task Force (USPSTF) screening guideline for osteoporosis identifies women under the age of 65 with osteoporosis needing bone mineral density (BMD) testing. If the Fracture Risk Assessment Tool (FRAX) tool fails to identify women under the age of 65 with undiagnosed osteoporosis, then diagnosis and treatment are delayed, potentially leading to increased fractures and morbidity. Another aim of this study is to characterize women under the age of 65 with osteoporosis that FRAX fails to identify and provide descriptive data on our study population. A retrospective chart review was completed between 2012 and 2018. We extracted data for 113 women ≤ 65-years with osteoporosis confirmed by BMD or fractures. Major osteoporotic fracture (MOF) risk calculation without BMD by FRAX of 9.3% or greater (high risk group) was found in 51 (45.1%) of patients. Osteoporosis by T-score < 2.5 was evident in 102 (90%) of patients. Previous osteoporotic fractures were noted in 29 (25.7%) of patients. The average age of women in the high-risk group was 58 years and 55 years in the low-risk group. The sensitivity of FRAX for identifying women with a T-score <-2.5 was 40%. The sensitivity of FRAX for identifying women with a history of fracture was 32%. The sensitivity of FRAX for identifying women with a T-score <-2.5 or identifying women with a history of fracture was 32%. These results demonstrate that the FRAX tool alone (USPSTF recommendation) fails to identify many women under the age of 65 with osteoporosis in need of BMD testing. Over half of women would not have had a BMD performed based on guidelines for screening BMD in women <65. Further study is needed to characterize women under the age of 65 with osteoporosis with a FRAX MOF risk less than 9.3%.

Joint modelling of longitudinal and survival data in the presence of competing risks with applications to prostate cancer data.

This research is motivated from the data from a large Selenium and Vitamin E Cancer Prevention Trial (SELECT). The prostate specific antigens (PSAs) were collected longitudinally, and the survival endpoint was the time to low-grade cancer or the time to high-grade cancer (competing risks). In this article, the goal is to model the longitudinal PSA data and the time-to-prostate cancer (PC) due to low- or high-grade. We consider the low-grade and high-grade as two competing causes of developing PC. A joint model for simultaneously analysing longitudinal and time-to-event data in the presence of multiple causes of failure (or competing risk) is proposed within the Bayesian framework. The proposed model allows for handling the missing causes of failure in the SELECT data and implementing an efficient Markov chain Monte Carlo sampling algorithm to sample from the posterior distribution via a novel reparameterization technique. Bayesian criteria, ΔDICSurv, and ΔWAICSurv, are introduced to quantify the gain in fit in the survival sub-model due to the inclusion of longitudinal data. A simulation study is conducted to examine the empirical performance of the posterior estimates as well as ΔDICSurv and ΔWAICSurv and a detailed analysis of the SELECT data is also carried out to further demonstrate the proposed methodology.

Joint analysis of single-cell and bulk tissue sequencing data to infer intratumor heterogeneity.

Many computational methods have been developed to discern intratumor heterogeneity (ITH) using DNA sequence data from bulk tumor samples. These methods share an assumption that two mutations arise from the same subclone if they have similar mutant allele-frequencies (MAFs), and thus it is difficult or impossible to distinguish two subclones with similar MAFs. Single-cell DNA sequencing (scDNA-seq) data can be very informative for ITH inference. However, due to the difficulty of DNA amplification, scDNA-seq data are often very noisy. A promising new study design is to collect both bulk and single-cell DNA-seq data and jointly analyze them to mitigate the limitations of each data type. To address the analytic challenges of this new study design, we propose a computational method named BaSiC (Bulk tumor and Single Cell), to discern ITH by jointly analyzing DNA-seq data from bulk tumor and single cells. We demonstrate that BaSiC has comparable or better performance than the methods using either data type. We further evaluate BaSiC using bulk tumor and single-cell DNA-seq data from a breast cancer patient and several leukemia patients.

Machine learning outcome regression improves doubly robust estimation of average causal effects.

BACKGROUND: Doubly robust estimation produces an unbiased estimator for the average treatment effect unless both propensity score (PS) and outcome models are incorrectly specified. Studies have shown that the doubly robust estimator is subject to more bias than the standard weighting estimator when both PS and outcome models are incorrectly specified. METHOD: We evaluated whether various machine learning methods can be used for estimating conditional means of the potential outcomes to enhance the robustness of the doubly robust estimator to various degrees of model misspecification in terms of reducing bias and standard error. We considered four types of methods to predict the outcomes: least squares, tree-based methods, generalized additive models and shrinkage methods. We also considered an ensemble method called the Super Learner (SL), which is a linear combination of multiple learners. We conducted simulations considering different scenarios by the complexity of PS and outcome-generating models and some ranges of treatment prevalence. RESULTS: The shrinkage methods performed well with robust doubly robust estimates in term of bias and mean squared error across the scenarios when the models became rich by including all 2-way interactions of the covariates. The SL performed similarly to the best method in each scenario. CONCLUSIONS: Our findings indicate that machine learning methods such as the SL or the shrinkage methods using interaction models should be used for more accurate doubly robust estimators.

Growth recovery lines: a specific indicator of child abuse and neglect?

BACKGROUND: Growth recovery lines are radiodense lines in long bones reported to be indicators of stress. OBJECTIVE: The purpose of this study was to understand the distribution, quantity and associations of growth recovery lines in children ages 0-24 months with high and low risk for child maltreatment. MATERIALS AND METHODS: We conducted a retrospective cohort study of children ages 0-24 months who had skeletal surveys and an assessment for maltreatment. Growth recovery lines, fractures and osteopenia were assessed independently by two pediatric radiologists blinded to the abuse likelihood. RESULTS: Of the 135 children in this study, 58 were in the low-risk group, 26 were in the neglect group, and 51 were in the physical abuse group. Children in the neglected and physically abused groups had 1.73 times (95% confidence interval [CI] of 1.16, 2.59), P=0.007) and 1.84 times (95% CI 1.28, 2.63, P<0.001) more growth recovery lines than the low-risk group, respectively. Growth recovery lines occurred at an earlier age in the neglect group (age interaction P=0.03) and abuse group (age interaction P=0.01) compared to the low-risk group. The specificity for maltreatment in children with at least 10 growth recovery lines in the long bones was greater than 84%, while sensitivity was less than 35%. The most common locations for growth recovery lines were distal radius, proximal tibia and distal tibia. CONCLUSION: In the absence of a known major stressor, physical abuse and neglect should be considered in children younger than 24 months with at least 10 growth recovery lines.

A retrospective analysis of dental implant survival in HIV patients.

AIM: This 5 years retrospective cohort survival study compared failure rates of dental implants placed in HIV (+) and HIV (-) patients relative to several risk factors. MATERIALS AND METHODS: Between 2006 and 2015, 484 implants placed in HIV (+) patients and 805 implants placed in HIV (-) patients were assessed for survival. The effects of HIV were estimated using propensity weighting. The effects of age, smoking status, diabetes, restoration status, gender, implant type, placement site, hepatitis C status, baseline CD4 count and CD4%, post-placement average CD4%, nadir CD4%, nadir CD4 count and antiviral therapy were analysed. RESULTS: Implants placed in HIV (+) patients and HIV (-) patients had similar failure rates (HR = 1.4, p = 0.34). Increased failure rates were observed in HIV (+) patients with baseline CD4% ≤20 (HR = 2.72, p = 0.04), post-placement CD4% average ≤20% (HR = 2.71, p = 0.04), protease inhibitor administration (HR = 2.74, p = 0.04), smoking (HR = 2.61, p = 0.05) and anterior maxillary placement (HR = 5.82, p < 0.01). Hepatitis C coinfection, viral titre, baseline CD4 count, gender, implant type and restoration type were non-contributory. CONCLUSION: Implants placed in HIV (+) patients had similar survival rates as HIV (-) patients. Failure rates increase significantly when confounding risk factors are present in HIV (+) patients.

Does assisted hatching affect live birth in fresh, first cycle in vitro fertilization in good and poor prognosis patients?

PURPOSE: To assess the effect of assisted hatching (AH) on live birth rate (LBR) in first cycle, fresh in vitro fertilization (IVF) in good and poor prognosis patients. METHODS: Retrospective cohort using cycles reported to the Society for Assisted Reproductive Technology Clinic Outcomes Reporting System. Live birth rate was compared in women who underwent first cycle, autologous, fresh IVF cycles with (n = 48,858) and without (n = 103,413) AH from 2007 to 2015. RESULTS: The propensity-weighted LBR was 39.2% with AH versus 43.9% without AH in all patients. The rate difference (RD) with AH was - 4.7% ([CI - 0.053, - 0.040], P < 0.001) with the calculated number needed to harm being 22. AH affected live birth in both good prognosis and poor prognosis patients. The propensity-weighted monozygotic twinning (MZT) rate was 2.3% in patients treated with AH as compared to 1.2% patients that did not receive AH. The RD with AH on MZT in fresh, first IVF cycles was 1.1% ([0.008, 0.014], P < 0.001). CONCLUSION: AH may affect LBR across all patients and in poor prognosis patients in fresh IVF cycles. Caution should be exercised when applying this technology. More prospective research is needed.

Long-Term Surveillance of Complex Cystic Renal Masses and Heterogeneity of Bosniak 3 Lesions.

PURPOSE: We sought to better characterize the frequency of Bosniak cyst class changes, identify predictors of change and progression, determine the average growth rate of cysts and validate the safety of active surveillance. MATERIALS AND METHODS: Consecutive patients referred for the management of complex cysts (Bosniak 2F or greater) were included in analysis. All imaging studies were reevaluated and any stage change was reviewed with a blinded genitourinary radiologist. Bosniak 3 cysts were subclassified as 3s-septated enhancing Bosniak cysts and 3n-cysts with wall or septation-only nodularity. A multivariate Cox proportional hazards model was used to identify predictors of the Bosniak classification change. Kaplan-Meier curves were applied to analyze Bosniak cyst progression and regression. RESULTS: A total 140 lesions were included in study, necessitating review of a total of 1,011 abdominal scans in 111 patients. Median followup was 46 months (IQR 23-65.5) and patients underwent a mean of 6.8 diagnostic scans. On multivariate analysis nodular cysts progressed (HR 6.16, 95% CI 2.58-14.72, p <0.00004) and entirely endophytic cysts were less likely to progress (HR 0.21, 95% CI 0.05-0.85, p = 0.028). On Kaplan-Meier analysis Bosniak 3s cysts were more likely to regress while Bosniak 3n cysts were more likely to progress than 3s cysts (p = 0.0178 and 0.0002, respectively). The growth rate of 3n and 2F cysts was 0.19 and 0.11 cm per year (p = 0.0493 and 0.0327, respectively). Locally advanced or metastatic disease did not develop in any patient. CONCLUSIONS: A diagnostic change in Bosniak 3s and 2F cysts is common and Bosniak 3n cysts behave more like Bosniak 4 cysts. Most complex kidney cysts can be safely monitored without intervention and the interval between serial imaging procedures should be increased.

The Latino Eyelid: Anthropometric Analysis of a Spectrum of Findings.

PURPOSE: Published anthropometric measurements of the Latino eyelid are limited. This study describes features spanning the morphologic range from non-Latino whites to East Asians in the spectrum of the Latino eyelid. METHODS: A cross-sectional study of 68 people (32 Latinos, 18 non-Latino whites, and 18 East Asians, ages 18-39), approved by the Institutional Review Board and HIPAA-compliant, was performed. Saliva samples determined genetic components. Indirect anthropometric measurements were performed with ImageJ software. Eyelid measurements included margin reflex distance, palpebral fissure height, eyelid crease height, orbital height, horizontal fissure length, inner and outer canthal distances, medial and lateral canthal angles, and lateral canthal angle of inclination. Additionally, exophthalmometry and epicanthal folds were recorded. RESULTS: Analysis of 184 markers from HumanExome Chip data revealed distinct clustering patterns. Genetically, the Asian participants were in 1 group, the whites in another group, and the Latinos spanned the spectrum between these 2 groups. In Latinos, the inner canthal distance and lateral canthal angle of inclination were similar to Asians, whereas the eyelid crease spanned the range from Asians to whites. Half of the Latinos had epicanthal folds. CONCLUSIONS: Latinos possess a spectrum of eyelid features spanning the morphologic characteristics from those of non-Latino whites to those of East Asians. These normative data on Latinos from Texas and Mexico aid in the diagnoses of Latino eyelid disorders and are a reference for optimizing oculofacial surgery outcomes.

Dynamic macrophage polarization-specific miRNA patterns reveal increased soluble VEGF receptor 1 by miR-125a-5p inhibition.

Dynamic, epigenetic mechanisms can regulate macrophage phenotypes following exposure to different stimulating conditions and environments. However, temporal patterns of microRNAs (miRNAs or miRs) across multiple macrophage polarization phenotypes have not been defined. We determined miRNA expression in bone marrow-derived murine macrophages over multiple time points (0.5, 1, 3, 24 h) following exposure to cytokines and/or LPS. We hypothesized that dynamic changes in miRNAs regulate macrophage phenotypes. Changes in macrophage polarization markers were detected as early as 0.5 and as late as 24 h; however, robust responses for most markers occurred within 3 h. In parallel, many polarization-specific miRNAs were also changed by 3 h and expressed divergent patterns between M1 and M2a conditions, with increased expression in M1 (miR-155, 199a-3p, 214-3p, 455-3p, and 125a) or M2a (miR-511 and 449a). Specifically, miR-125a-5p exhibited divergent patterns: increased at 12-24 h in M1 macrophages and decreasing trend in M2a. VEGF in the culture media of macrophages was dependent upon the polarization state, with greatly diminished VEGF in M2a compared with M1 macrophage culture media despite similar VEGF in cell lysates. Inhibition of miR-125a-5p in media-only controls (MO) and M1 macrophages greatly increased expression and secretion of soluble VEGF receptor-1 (sVEGFR1) leading to diminished VEGF in the culture media, partially converting MO and M1 into an M2a phenotype. Thus, the divergent expression patterns of polarization-specific miRNAs led to the identification and demonstrated the regulation of a specific macrophage polarization phenotype, sVEGFR1 by inhibition of miR-125a-5p.

Serial Percent Free Prostate Specific Antigen in Combination with Prostate Specific Antigen for Population Based Early Detection of Prostate Cancer.

PURPOSE: We characterized the diagnostic properties of serial percent free prostate specific antigen in relation to prostate specific antigen in a multiethnic, multiracial cohort of healthy men. MATERIALS AND METHODS: A total of 6,982 percent free prostate specific antigen and prostate specific antigen measurements were obtained from participants in a greater than 12-year Texas screening study comprising 1,625 men who never underwent biopsy, 497 who underwent 1 or more biopsies negative for prostate cancer and 61 diagnosed with prostate cancer. We evaluated the ROC AUC of percent free prostate specific antigen and the proportion of patients with fluctuating values across multiple visits determined according to 2 thresholds (less than 15% vs 25%). The proportion of cancer cases in which percent free prostate specific antigen indicated a positive test before prostate specific antigen greater than 4 ng/ml did and the number of negative biopsies that would have been spared by negative percent free prostate specific antigen test results were calculated. RESULTS: Percent free prostate specific antigen fluctuated around its threshold of less than 25% (less than 15%) in 38.3% (78.1%), 42.2% (20.9%), and 11.4% (25.7%) of patients never biopsied, and with negative and positive biopsies, respectively. At the same thresholds, percent free prostate specific antigen tested positive earlier than prostate specific antigen in 71.4% and 34.2% of cancer cases, respectively. Among men with multiple negative biopsies and PSA greater than 4 ng/ml, percent free PSA would have tested negative in 31.6% and 65.8%, respectively. CONCLUSIONS: Percent free prostate specific antigen should accompany prostate specific antigen testing to potentially spare unnecessary biopsies or detect cancer earlier. When near the threshold, both tests should be repeated due to commonly observed fluctuation.

Preventing Pregnancy in High School Students: Observations From a 3-Year Longitudinal, Quasi-Experimental Study.

OBJECTIVES: To assess whether a sexual health education intervention reduces pregnancy rates in high school students. METHODS: We performed a secondary analysis of a 3-year quasi-experimental study performed in South Texas from 2011 to 2015 in which 1437 students without a history of pregnancy at baseline were surveyed each fall and spring. Potentially confounding risk factors considered included sexual behaviors, intentions, and demographics. The outcome measure was self-reported pregnancy status for male and female students. We performed analyses for male and female students using separate discrete time-to-event models. RESULTS: We found no difference in pregnancy rates between intervention and comparison students within the first 3 years of high school. Female and male students in the intervention groups had pregnancy hazard ratios of, respectively, 1.62 (95% CI = 0.9, 2.61; P = .1) and 0.78 (95% CI = 0.44, 1.48; P = .4) relative to the comparison groups. CONCLUSIONS: The educational intervention had no impact on the pregnancy rate. Social media tools in pregnancy prevention programs should be adaptive to new technologies and rapidly changing adolescent preferences for these services.

Homology cluster differential expression analysis for interspecies mRNA-Seq experiments.

There is an increasing demand for exploration of the transcriptomes of multiple species with extraordinary traits such as the naked-mole rat (NMR). The NMR is remarkable because of its longevity and resistance to developing cancer. It is of scientific interest to understand the molecular mechanisms that impart these traits, and RNA-sequencing experiments with comparator species can correlate transcriptome dynamics with these phenotypes. Comparing transcriptome differences requires a homology mapping of each transcript in one species to transcript(s) within the other. Such mappings are necessary, especially if one species does not have well-annotated genome available. Current approaches for this type of analysis typically identify the best match for each transcript, but the best match analysis ignores the inherent risks of mismatch when there are multiple candidate transcripts with similar homology scores. We present a method that treats the set of homologs from a novel species as a cluster corresponding to a single gene in the reference species, and we compare the cluster-based approach to a conventional best-match analysis in both simulated data and a case study with NMR and mouse tissues. We demonstrate that the cluster-based approach has superior power to detect differential expression.