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.