Test Performance of Cervical Cytology Among Adults With vs Without Human Papillomavirus Vaccination.

Importance: Current US cervical cancer screening guidelines do not differ by human papillomavirus (HPV) vaccination status. However, as the positive predictive value (PPV) of a screening test decreases, the risk of a false-positive result increases. Objective: To evaluate whether HPV vaccination is associated with decreased PPV for abnormal cervical cytology. Design, Setting, and Participants: This retrospective cohort study conducted via electronic medical record review included eligible patients aged 21 to 35 years who had at least 1 cervical cytology result within a single health system between January 2015 and December 2018. The health system comprises a partnership between an academic health center and a private not-for-profit health center. Patients with abnormal screening cytology and no diagnostic test results were omitted from analysis. Data were analyzed from December 2019 to November 2021. Exposures: HPV vaccination, defined as receiving at least 1 dose of HPV vaccine. Subgroup analyses were performed for those completing all vaccination doses per Advisory Committee on Immunization Practices guidelines and by age at vaccination initiation, dichotomized as younger than 21 years vs 21 years or older. Main Outcomes and Measures: PPV of abnormal cervical cytology for risk of cervical intraepithelial neoplasia (CIN) 2 or more severe diagnosis. Results: A total of 46 988 patients (mean [SD] age, 28.7 [4.5] years; 3058 [6.5%] Asian; 4159 [8.9%] Black or African American; 35 446 [75.4%] White) were included; 15 494 (33.0%) were at least partially vaccinated, and 4289 (9.1%) had abnormal cytology results during the study period. Among the individuals with abnormal cytology, the PPV for CIN 2 or more severe diagnosis was lower among vaccinated individuals (17.4%; 95% CI, 16.4%-18.4%) than unvaccinated individuals (21.3%; 95% CI, 20.4%-22.3%). Among vaccinated individuals, PPV was significantly lower among those completing vaccination (15.9%; 95% CI, 14.9%-17.0%) than those with incomplete vaccination (22.4%; 95% CI, 20.0%-25.0%), especially among those initiating vaccination when younger than 21 years (11.9%; 95% CI, 10.9%-12.9%) vs those initiating at age 21 years or older (30.7%; 95% CI, 27.3%-34.4%). Conclusions and Relevance: Among a population with relatively low HPV vaccine coverage, the PPV of cervical cytology for CIN 2 or more severe diagnosis was significantly lower among vaccinated individuals. PPV will likely further decrease in the future as a population with higher HPV vaccination coverage ages into screening. Confirmation of these results will call for changes in screening strategies, particularly for completely vaccinated individuals who initiated vaccination when younger than 21 years.

Impact of Policy Interventions on Postoperative Opioid Prescribing.

OBJECTIVE: To assess postoperative opioid prescribing in response to state and organizational policy changes. METHODS: We used an observational study design at an academic medical center in the Northeast United States over a time during which there were two important influences: 1) implementation of state rules regarding opioid prescribing and 2) changes in organization policies reflecting evolving standards of care. Results were summarized at the surgical specialty and procedure level and compared between baseline (July-December 2016) and postrule (July-December 2017) periods. RESULTS: We analyzed data from 17,937 procedures from July 2016 to December 2017, two-thirds of which were outpatient. Schedule II opioids were prescribed in 61% of cases and no opioids at all in 28%. The median morphine milligram equivalent (MME) prescribed at discharge decreased 40%, from 113 MME in the baseline period to 68 MME in the postrule period. Decreases were seen across all the surgical specialties. CONCLUSIONS: Postoperative opioid prescribing at the time of hospital discharge decreased between 2016 and 2017 in the setting of targeted and replicable state and health care organizational policies. POLICY IMPLICATIONS: Policies governing the use of opioids are an effective and adoptable approach to reducing opioid prescribing following surgery.

Post-Discharge Opioid Prescribing and Use after Common Surgical Procedure.

BACKGROUND: The number of deaths from prescription opioids in the US continues to increase and remains a major public health concern. Opioid-related deaths parallel prescribing trends, and postoperative opioids are a significant source of opioids in the community. Our objective was to identify opioid prescribing and use patterns after surgery to inform evidence-based practices. STUDY DESIGN: Data from a 340-bed academic medical institution and its affiliated outpatient surgical facility included retrospective medical record data and prospective telephone questionnaire and medical record data. Retrospective data included patients discharged after 1 of 19 procedure types, from July 2015 to June 2016 (n = 10,112). Prospective data included a consecutive sample of general and orthopaedic surgery and urology patients undergoing 1 of 13 procedures, from July 2016 to February 2017 (n = 539). Primary outcomes were the quantity of opioid prescribed and used in morphine milligram equivalents (MME), and the proportion of patients receiving instructions on disposal and nonopioid strategies. RESULTS: In the retrospective dataset, 76% of patients received an opioid after surgery, and 87% of prescriptions were prescribed by residents or advanced practice providers. Median prescription size ranged from 0 to 503 MME, with wide interquartile ranges (IQR) for most procedures. In the prospective dataset, there were 359 participants (67% participation rate). Of these, 92% of patients received an opioid and the median proportion used was 27%, or 24 MME (IQR 0 to 96). Only 18% of patients received disposal instructions, while 84% of all patients received instructions on nonopioid strategies. CONCLUSIONS: Median opioid use after surgery was 27% of the total prescribed, and only 18% of patients reported receiving disposal instructions. Significant variability in opioid prescribing and use after surgery warrants investigation into contributing factors.

Utility of quantitative micro-computed tomographic analysis in zebrafish to define gene function during skeletogenesis.

The zebrafish is a powerful experimental model to investigate the genetic and morphologic basis of vertebrate development. Analysis of skeletogenesis in this fish is challenging as a result of the small size of the developing and adult zebrafish. Many of the bones of small fishes such as the zebrafish and medaka are quite thin, precluding many standard assays of bone quality and morphometrics commonly used on bones of larger animals. Microcomputed tomography (microCT) is a common imaging technique used for detailed analysis of the skeleton of the zebrafish and determination of mutant phenotypes. However, the utility of this modality for analysis of the zebrafish skeleton, and the effect of inherent variation among individual zebrafish, including variables such as sex, age and strain, is not well understood. Given the increased use and accessibility of microCT, we set out to define the sensitivity of microCT methods in developing and adult zebrafish. We assessed skeletal shape and density measures in the developing vertebrae and parasphenoid of the skull base. We found most skeletal variables are tightly correlated to standard length, but that at later growth stages (>3months) there are age dependent effects on some skeletal measures. Further we find modest strain but not sex differences in skeletal measures. These data suggest that the appropriate control for assessing mutant phenotypes should be age and strain matched, ideally a wild-type sibling. By analyzing two mutants exhibiting skeletal dysplasia, we show that microCT imaging can be a sensitive method to quantify distinct skeletal parameters of adults. Finally, as developing zebrafish skeletons remain difficult to resolve by radiographic means, we define a contrast agent specific for bone that enhances resolution at early stages, permitting detailed morphometric analysis of the forming skeleton. This increased capability for detection extends the use of this imaging modality to leverage the zebrafish model to understand the development causes of skeletal dysplasias.

Brief Report: Development and Validation of a Semiautomated Method to Measure Erosion Volume in Inflammatory Arthritis by Computed Tomography Scanning.

OBJECTIVE: Valid measurement of erosion volume in rheumatoid arthritis (RA) will facilitate the testing of treatments that may help to heal erosion. This study was undertaken to develop and validate a software method to measure erosion volume on computed tomography (CT) scans of the hand and wrist. METHODS: Duplicate CT acquisitions of both hands of 5 patients with RA were evaluated using a semiautomated software tool to measure erosion volume in the entire hand and wrist and in each of 6 subregions. Reproducibility was quantified using the intraclass correlation coefficient (ICC), root mean square standard deviation (RMSSD), and coefficient of variation (CV), and the analysis was performed at the level of the hand (n = 10) and the subject (n = 5). RESULTS: The ICCs between 2 repositioned acquisitions were excellent, ranging from 0.97 to 1.00. At the hand level, the RMSSD was 15.6 mm(3) with a CV of 7.3%, and the CVs at the 6 regions ranged from 7.6% to 21.0%. At the subject level, the RMSSD was 31.2 mm(3) with a CV of 3.7%, and the CVs at the 6 regions ranged from 0.5% to 15.8%. CONCLUSION: We have developed a novel semiautomated software method to measure erosion volume on hand and wrist CT scans. The method is reproducible and can be used to detect changes in erosion volume. This will facilitate the testing of treatments intended to reduce erosion volume.

Computational gene expression modeling identifies salivary biomarker analysis that predict oral feeding readiness in the newborn.

OBJECTIVE: To combine mathematical modeling of salivary gene expression microarray data and systems biology annotation with reverse-transcription quantitative polymerase chain reaction amplification to identify (phase I) and validate (phase II) salivary biomarker analysis for the prediction of oral feeding readiness in preterm infants. STUDY DESIGN: Comparative whole-transcriptome microarray analysis from 12 preterm newborns pre- and postoral feeding success was used for computational modeling and systems biology analysis to identify potential salivary transcripts associated with oral feeding success (phase I). Selected gene expression biomarkers (15 from computational modeling; 6 evidence-based; and 3 reference) were evaluated by reverse-transcription quantitative polymerase chain reaction amplification on 400 salivary samples from successful (n = 200) and unsuccessful (n = 200) oral feeders (phase II). Genes, alone and in combination, were evaluated by a multivariate analysis controlling for sex and postconceptional age (PCA) to determine the probability that newborns achieved successful oral feeding. RESULTS: Advancing PCA (P < .001) and female sex (P = .05) positively predicted an infant's ability to feed orally. A combination of 5 genes, neuropeptide Y2 receptor (hunger signaling), adneosine-monophosphate-activated protein kinase (energy homeostasis), plexin A1 (olfactory neurogenesis), nephronophthisis 4 (visual behavior), and wingless-type MMTV integration site family, member 3 (facial development), in addition to PCA and sex, demonstrated good accuracy for determining feeding success (area under the receiver operator characteristic curve = 0.78). CONCLUSIONS: We have identified objective and biologically relevant salivary biomarkers that noninvasively assess a newborn's developing brain, sensory, and facial development as they relate to oral feeding success. Understanding the mechanisms that underlie the development of oral feeding readiness through translational and computational methods may improve clinical decision making while decreasing morbidities and health care costs.

Local area cartilage segmentation: a semiautomated novel method of measuring cartilage loss in knee osteoarthritis.

OBJECTIVE: To assess the responsiveness and reader time of a novel semiautomated tool to detect knee cartilage loss over 2 years in subjects with knee osteoarthritis. METHODS: A total of 122 subjects from the Osteoarthritis Initiative progression cohort were selected. A reader used the software method to segment cartilage on double-echo steady-state sequence scans in the medial compartment of the femur from the baseline and 24-month visits. Change in cartilage volume (ΔV) was measured at a fixed weight-bearing (WB) location with respect to the 3-dimensional coordinate system based on cylindrical coordinates. Change was measured for 5 regions of varying WB surface area centered on the fixed point. The average change (ΔV), the SD of ΔV, and the standardized response mean (SRM) are reported. RESULTS: The SRM was −0.52 for the largest region and decreased in magnitude as smaller regions of cartilage were probed. The average evaluation time was <20 minutes per knee compartment, split approximately evenly between a technician and a trained reader. CONCLUSION: The results establish that measurement of cartilage loss in a local region can be done efficiently and that the resultant measures are responsive to loss of cartilage over time. The coordinate system can potentially be used to objectively examine and establish a consistent location for all knees that is most responsive to change in cartilage volume. This technique can provide rapidly an objective quantitative measure of cartilage loss and could substantially reduce study costs for large trials and data sets.