Clinical Data: Sources and Types, Regulatory Constraints, Applications.

Access to clinical data is critical for the advancement of translational research. However, the numerous regulations and policies that surround the use of clinical data, although critical to ensure patient privacy and protect against misuse, often present challenges to data access and sharing. In this article, we provide an overview of clinical data types and associated regulatory constraints and inferential limitations. We highlight several novel approaches that our team has developed for openly exposing clinical data

Imputing Missing Observations with Time Sliced Synthetic Minority Oversampling Technique

We present a simple yet novel time series imputation technique with the goal of constructing an irregular time series that is uniform across every sample in a data set. Specifically, we fix a grid defined by the midpoints of non-overlapping bins (dubbed slices ) of observation times and ensure that each sample has values for all of the features at that given time. This allows one to both impute fully missing observations to allow uniform time series classification across the entire data and, in special cases, to impute individually missing features. To do so, we slightly generalize the well-known class imbalance algorithm SMOTE \cite{smote} to allow component wise nearest neighbor interpolation that preserves correlations when there are no missing features. We visualize the method in the simplified setting of 2-dimensional uncoupled harmonic oscillators. Next, we use tSMOTE to train an Encoder/Decoder long-short term memory (LSTM) model with Logistic Regression for predicting and classifying distinct trajectories of different 2D oscillators. After illustrating the the utility of tSMOTE in this context, we use the same architecture to train a clinical model for COVID-19 disease severity on an imputed data set. Our experiments show an improvement over standard mean and median imputation techniques by allowing a wider class of patient trajectories to be recognized by the model, as well as improvement over aggregated classification models

The impact of maternal SARS-CoV-2 infection and COVID-19 vaccination on maternal-fetal outcomes.

The rapidly evolving COVID-19 pandemic has resulted in an upsurge of scientific productivity to help address the global health crisis. One area of active research is the impact of COVID-19 on pregnancy. Here, we provide an epidemiological overview about what is known about the effects of maternal SARS-CoV-2 infection and COVID-19 vaccination on maternal-fetal outcomes, and identify gaps in knowledge. Pregnant people are at increased risk for severe COVID-19, and maternal SARS-CoV-2 infection increases the risk of negative maternal-fetal outcomes. Despite this elevated risk, there have been high rates of vaccine hesitancy, heightened by the initial lack of safety and efficacy data for COVID-19 vaccination in pregnancy. In response, retrospective cohort studies were performed to examine the impact of COVID-19 vaccination during pregnancy. Here, we report the vaccine\u27s efficacy during pregnancy and its impact on maternal-fetal outcomes, as well as an overview of initial studies on booster shots in pregnancy. We found that pregnant people are at risk for more severe COVID-19 outcomes, maternal SARS-CoV-2 infection is associated with worse birth outcomes, COVID-19 vaccine hesitancy remains prevalent in the pregnant population, and COVID-19 vaccination and boosters promote better maternal-fetal outcomes. The results should help reduce vaccine hesitancy by alleviating concerns about the safety and efficacy of administering the COVID-19 vaccine during pregnancy. Overall, this review provides an introduction to COVID-19 during pregnancy. It is expected to help consolidate current knowledge, accelerate research of COVID-19 during pregnancy and inform clinical, policy, and research decisions regarding COVID-19 vaccination in pregnant people

Adoption of a National Prophylactic Anticoagulation Guideline for Hospitalized Pregnant Women with COVID-19: Retrospective Cohort Study.

BACKGROUND: Both COVID-19 and pregnancy are associated with hypercoagulability. Due to increased risk for thrombosis, the United States National Institute of Health\u27s recommendation for prophylactic anticoagulant use for pregnant patients has expanded from patients hospitalized for severe COVID-19 manifestation to all patients hospitalized for the manifestation of COVID-19 (no guideline: ~12-26-2020, first update: 12-27-2020~02-23-2022, second update: 02-24-2022~present). However, no study has evaluated this recommendation. OBJECTIVE: The objective of this study was to characterize prophylactic anticoagulant use among hospitalized pregnant people with COVID-19 from 03-20-2020~10-19-2022. METHODS: This was a retrospective cohort study in large US healthcare systems across seven states. The cohort of interest was pregnant patients who were hospitalized with COVID-19, without prior coagulopathy or contraindication to anticoagulants (n=2,767). The treatment group consisted of patients prescribed prophylactic dose anticoagulation during -2~+14 days from COVID-19 treatment onset (n=191). The control group was patients with no anticoagulant exposure during -14~+60 days of the SARS-CoV-2 infection date (n=2,534). We ascertained the use of prophylactic anticoagulants with attention to the updates in guidelines and emerging SARS-CoV-2 variants. We propensity score matched the treatment and control group 1:1 on the most important features contributing to the prophylactic anticoagulant administration status classification. Outcome measures included coagulopathy, bleeding, COVID-19-related complications, and maternal-fetal health outcomes. Additionally, the inpatient anticoagulant administration rate was validated in a nationwide population from Truveta, a collective of 700 hospitals across the United States. RESULTS: The overall administration rate of prophylactic anticoagulants was 7.0% (191/2,725). It was lowest after the second guideline update (no guideline: 10.4%, first update: 9.0%, second update: 2.5%; P CONCLUSIONS: Most hospitalized pregnant COVID-19 patients did not receive prophylactic anticoagulants across healthcare systems as recommended by guidelines. Guideline recommended treatment was administered more frequently to patients with greater COVID-19 illness severity. Given the low rate of administration and differences between treated and untreated cohorts, efficacy could not be assessed

Patient experience in nerve-to-masseter-driven smile reanimation

Introduction: The nerve-to-masseter is one of the most frequently used neural sources in smile reanimation surgery. Very little information has been reported on patient experience with regard to reanimated smile usage and sequelae following transfer. The aim of this study was to quantify patient perception of nerve-to-masseter use in smile reanimation surgery. Methods: An online questionnaire was developed based on the clinical expertise of our team, patient interviews, and existing questionnaires of facial palsy-related quality of life and temporomandibular joint dysfunction. All patients treated with nerve-to-masseter-driven smile reanimation surgery, both nerve transfers and muscle transplantations, between 2007 and 2016 with a valid email address were invited to participate. Results: Of 171 operated patients, 122 with a valid email address were invited to participate. Seventy-one patients responded (63.4% female, mean age 51.1 years) after a median follow-up of 3.8 years. A voluntary smile while biting down at least "most of the time" was reported by 83.1% of patients; 46.5% reported ability to smile on the affected side without bite. A "normal" or "almost normal" spontaneous smile was reported in 23.9% of patients. A total of 18.3% of patients self-reported masseter muscle atrophy, and 1.4-14.1% reported temporomandibular joint dysfunction. Forty-one patients (57.7%) reported prandial movement of the face at least "most of the time," with 9 patients (12.7%) considering this bothersome. Conclusion: Patients report good voluntary smiling ability following nerve-to-masseter-driven smile reanimation surgery, with low rates of sequelae. (C) 2019 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved

The effect of maternal SARS-CoV-2 infection timing on birth outcomes: a retrospective multicentre cohort study.

BACKGROUND: The impact of maternal SARS-CoV-2 infection remains unclear. In this study, we evaluated the risk of maternal SARS-CoV-2 infection on birth outcomes and how this is modulated by the pregnancy trimester in which the infection occurs. We also developed models to predict gestational age at delivery for people following a SARS-CoV-2 infection during pregnancy. METHODS: We did a retrospective cohort study of the impact of maternal SARS-CoV-2 infection on birth outcomes. We used clinical data from Providence St Joseph Health electronic health records for pregnant people who delivered in the USA at the Providence, Swedish, or Kadlec sites in Alaska, California, Montana, Oregon, or Washington. The SARS-CoV-2 positive cohort included people who had a positive SARS-CoV-2 PCR-based test during pregnancy, subdivided by trimester of infection. No one in this cohort had been vaccinated for COVID-19 at time of infection. The SARS-CoV-2 negative cohort were people with at least one negative SARS-CoV-2 PCR-based test and no positive tests during pregnancy. Cohorts were matched on common covariates impacting birth outcomes, and univariate and multivariate analysis were done to investigate risk factors and predict outcomes. The primary outcome was gestational age at delivery with annotation of preterm birth classification. We trained multiple supervised learning models on 24 features of the SARS-CoV-2 positive cohort to evaluate performance and feature importance for each model and discuss the impact of SARS-CoV-2 infection on gestational age at delivery. FINDINGS: Between March 5, 2020, and July 4, 2021, 73 666 pregnant people delivered, 18 335 of whom had at least one SARS-CoV-2 test during pregnancy before Feb 14, 2021. We observed 882 people infected with SARS-CoV-2 during their pregnancy (first trimester n=85; second trimester n=226; and third trimester n=571) and 19 769 people who have never tested positive for SARS-CoV-2 and received at least one negative SARS-CoV-2 test during their pregnancy. SARS-CoV-2 infection indicated an increased risk of preterm delivery (p INTERPRETATION: These results suggest that pregnant people would benefit from increased monitoring and enhanced prenatal care after first or second trimester SARS-CoV-2 infection, regardless of acute COVID-19 severity. FUNDING: US National Institutes of Health

The effect of COVID-19 vaccination and booster on maternal-fetal outcomes: a retrospective multicenter cohort study.

Background: COVID-19 infection in pregnant people has previously been shown to increase the risk for poor maternal-fetal outcomes. Despite this, there has been a lag in COVID-19 vaccination in pregnant people due to concerns over the potential effects of the vaccine on maternal-fetal outcomes. Here we examine the impact of COVID-19 vaccination and booster on maternal COVID-19 breakthrough infections and birth outcomes. Methods: This was a retrospective multicenter cohort study on the impact of COVID-19 vaccination on maternal-fetal outcomes for people that delivered (n=86,833) at Providence St. Joseph Health across Alaska, California, Montana, Oregon, New Mexico, Texas, and Washington from January 26, 2021 through July 11, 2022. Cohorts were defined by vaccination status at time of delivery: unvaccinated (n=48,492), unvaccinated propensity score matched (n=26,790), vaccinated (n=26,792; two doses of mRNA-1273 Moderna or BNT162b2 Pfizer-BioNTech), and/or boosted (n=7,616). The primary outcome was maternal COVID-19 infection. COVID-19 vaccination status at delivery, COVID-19 infection-related health care, preterm birth (PTB), stillbirth, very low birth weight (VLBW), and small for gestational age (SGA) were evaluated as secondary outcomes. Findings: Vaccinated pregnant people were significantly less likely to have a maternal COVID-19 infection than unvaccinated matched (p1,500 g; 0.31). Vaccinated people who were boosted had significantly lower rates of maternal COVID-19 infections (p Interpretation: COVID-19 vaccination protects against adverse maternal-fetal outcomes with booster doses conferring additional protection against COVID-19 infection. It is therefore important for pregnant people to have high priority status for vaccination, and for them to stay current with their COVID-19 vaccination schedule. Funding: This study was funded by the National Institute for Child Health & Human Development and the William O. and K. Carole Ellison Foundation

Effect of COVID-19 vaccination and booster on maternal-fetal outcomes: a retrospective cohort study.

BACKGROUND: COVID-19 in pregnant people increases the risk for poor maternal-fetal outcomes. However, COVID-19 vaccination hesitancy remains due to concerns over the vaccine\u27s potential effects on maternal-fetal outcomes. Here we examine the impact of COVID-19 vaccination and boosters on maternal SARS-CoV-2 infections and birth outcomes. METHODS: This was a retrospective multicentre cohort study on the impact of COVID-19 vaccination on maternal-fetal outcomes for people who delivered (n=106 428) at Providence St Joseph Health across seven western US states from Jan 26, 2021 to Oct 26, 2022. Cohorts were defined by vaccination status at delivery: vaccinated (n=35 926; two or more doses of mRNA-1273 Moderna or BNT162b2 Pfizer-BioNTech), unvaccinated (n=55 878), unvaccinated propensity score matched (n=16 771), boosted (n=10 927; three or more doses), vaccinated unboosted (n=13 243; two doses only), and vaccinated unboosted with propensity score matching (n=4414). We built supervised machine learning classification models, which we used to determine which people were more likely to be vaccinated or boosted at delivery. The primary outcome was maternal SARS-CoV-2 infection. COVID-19 vaccination status at delivery, COVID-19-related health care, preterm birth, stillbirth, and very low birthweight were evaluated as secondary outcomes. FINDINGS: Vaccinated people were more likely to conceive later in the pandemic, have commercial insurance, be older, live in areas with lower household composition vulnerability, and have a higher BMI than unvaccinated people. Boosted people were more likely to have more days since receiving the second COVID-19 vaccine dose, conceive earlier in the pandemic, have commercial insurance, be older, and live in areas with lower household composition vulnerability than vaccinated unboosted people. Vaccinated pregnant people had lower rates of COVID-19 during pregnancy (4·0%) compared with unvaccinated matched people (5·3%; p INTERPRETATION: COVID-19 vaccination protects against adverse maternal-fetal outcomes, with booster doses conferring additional protection. Pregnant people should be high priority for vaccination and stay up to date with their COVID-19 vaccination schedule. FUNDING: National Institute for Child Health & Human Development and the William O and K Carole Ellison Foundation