Prescription medication use during pregnancy in the United States from 2011 to 2020: trends and safety evidence.

BACKGROUND: Medication use during pregnancy has increased in the United States despite the lack of safety data for many medications. OBJECTIVE: This study aimed to inform research priorities by examining trends in medication use during pregnancy and identifying gaps in safety information on the most commonly prescribed medications. STUDY DESIGN: We identified population-based cohorts of commercially (MarketScan 2011-2020) and publicly (Medicaid Analytic eXtract/Transformed Medicaid Statistical Information System Analytic Files 2011-2018) insured pregnancies ending in live birth from 2 health care utilization databases. Medication use was based on filled prescriptions between the date of last menstrual period through delivery, as well as the period before the last menstrual period and during specific trimesters. We also included a cross-sectional representative sample of pregnancies ascertained by the National Health and Nutrition Examination Survey (2011-2020), with information on prescription medication use during the preceding month obtained through maternal interviews. Teratogen Information System was used to classify the available evidence on teratogenic risk. RESULTS: Among over 3 million pregnancies, the medications most commonly dispensed at any time during pregnancy were analgesics, antibiotics, and antiemetics. The top medications were ondansetron (16.8%), amoxicillin (13.5%), and azithromycin (12.4%) in MarketScan, nitrofurantoin (22.2%), acetaminophen (21.3%; mostly as part of acetaminophen-hydrocodone products), and ondansetron (19.5%) in Medicaid Analytic eXtract/Transformed Medicaid Statistical Information System Analytic Files, and levothyroxine (5.0%), sertraline (2.9%), and insulin (2.9%) in the National Health and Nutrition Examination Survey group. The most commonly dispensed suspected teratogens during the first trimester were antithyroid medications. The use of antidiabetic and psychotropic medications has continued to increase in the United States during the last decade, opioid dispensation has decreased by half, and antibiotics and antiemetics continue to be common. For one-quarter of medications, there is insufficient evidence available to characterize their safety profile in pregnancy. CONCLUSION: There is a need for more drug research in pregnant patients. Future research should focus on anti-infectives with high utilization and limited level of evidence on safety for use during pregnancy. Although lack of evidence is not evidence of safety concerns, it does not indicate risk either. In many instances, the benefits outweigh the risks when these medications are used clinically, and some of the medications with no proven safety may be necessary to treat patients.

Characteristics and Management of Pediatric Benign Intraosseous Mandibular Tumors: A 10-Years Prospective Study.

Background: The management of intraosseous mandibular tumors in children is challenging. This study investigated clinical and pathological characteristics, surgical treatment, and outcome of pediatric benign intraosseous mandibular tumors. Materials and Methods: A prospective study included patients under 18 years presenting with benign intraosseous mandibular tumors that were surgically managed. Clinical and surgical data were collected and statistically analyzed. Results: The study included 84 patients (38 males and 46 females): 66.7% had non-odontogenic tumors and 33.3% had odontogenic tumors. The most common non-odontogenic tumors were central giant cell granulomas (31%). The most common odontogenic tumors were odontomas (9.5%). Conservative surgery and radical resection were performed equally. Curettage was the commonest treatment modality (27.4%). Fifty percentage of cases required reconstruction, which was done by costochondral rib graft (42.9%) and free fibula flap (7.1%). One patient had recurrence. All cases got good functional and aesthetic results. Conclusion: Non-odontogenic tumors were more common than odontogenic tumors. Central giant cell granulomas were the most common non-odontogenic tumors, while odontomas were the most common odontogenic tumors. Treatment depended on type, size, and aggressiveness. Pediatric mandibular reconstruction with costochondral rib grafts was simple and satisfactory. Microsurgical reconstruction had high success rates. Appropriate management achieved good aesthetic and functional outcomes.

Bone marrow embolism: should it result from traumatic bone lesions? A histopathological human autopsy study.

Bone marrow embolism (BME) is likely a consequence of fractures in which pulmonary vessels are the most affected. However, some cases of BME were reported in the absence of trauma. Thus, a traumatic injury might not be necessary for developing BME. This study discusses BME cases in patients without signs of fractures or blunt trauma. The discussion addresses various possible mechanisms for the appearance of BME. Options include cancer in which bone marrow metastasis is a suggestive cause. Another proposal is the chemical theory where bone marrow fats are released via lipoprotein lipase in a pro-inflammatory state, resulting in vascular/pulmonary obstruction. Other cases discussed in this study are hypovolemic shock and drug-abuse related BME. All autopsy cases with BME were included regardless of the cause of death for a period of 2 years. Autopsies involved complete dissection with the macroscopic evaluation of the affected organs, including the heart, lungs, and brain. Tissues were also prepared for microscopic examination. Of the 11 cases, eight showed non-traumatic BME (72%). These findings conflict with theories in the literature that BME most commonly occurs after fractures or trauma. One of the eight cases exhibited mucinous carcinoma; one is presented with hepatocellular carcinoma; and two cases showed severe congestion. Lastly, one case was found to be associated with each of the following conditions: liposuction, drug abuse, pulmonary hypertension, and heart failure. Each case suggests a different pathophysiology for developing BME, yet the exact mechanisms are not fully understood. Further study of non-traumatic associated BME is recommended.

The characterization of Pluronic P123 micelles in the presence of sunscreen agents.

OBJECTIVES: The triblock copolymer Pluronic® is widely used in the personal care industry, including sun protection, for its film-forming and solubilization capabilities. In this study, the effect of three commonly used organic UV filters (ethylhexyl methoxycinnamate [EMC], ethylhexyl triazone [EHT], and avobenzone [AVB]) on the structure of Pluronic P123 micelles was investigated. METHODS: The Pluronic P123 micelle structure has been investigated using dynamic surface tension, nuclear magnetic resonance (NMR) and small-angle neutron scattering (SANS). RESULTS: Dynamic surface tension results show strong interactions between the UV filters and Pluronic® evident by sharp changes in the surface activity of the latter. The NMR results have revealed the creation of a hydrophobic microenvironment special to the Pluronic PPO core group in the presence of UV filters. Some interaction with the hydrophilic EO was also recorded, albeit weaker. This is further confirmed by SANS, where the Pluronic P123 micelles interacted with varying strengths with the UV filters, resulting in sharp changes in their size and shape. CONCLUSIONS: We have demonstrated the sensitivity of the Pluronic P123 micelles to the presence of various UVA/B filters. The micelles shape varied from spherical to cylindrical as the concentration and type of the UV filters were varied. These variations in the shape are expected to have a significant effect on the sun protection factor (SPF), as it affects the solubilization of the UV filters within a formulation in addition to the formulations' rheological profile and film-forming behaviour.

OBJECTIFS: le copolymère tribloc Pluronic® est largement utilisé dans le domaine des soins personnels, notamment la protection solaire, pour ses capacités de formation de film et de solubilisation. Cette étude a permis d'étudier l'effet de trois filtres UV organiques couramment utilisés (éthylhexyl méthoxycinnamate [EMC], éthylhexyl triazone [EHT] et avobenzone [AVB]) sur la structure des micelles P123 Pluronic. MÉTHODES: la structure de la micelle P123 Pluronic a été étudiée à l'aide d'une tension superficielle dynamique, d'une résonance magnétique nucléaire (RMN) et d'une diffusion de neutrons aux petits angles (DNPA). RÉSULTATS: les résultats de la tension superficielle dynamique montrent de fortes interactions entre les filtres UV et Pluronic®, ce qui se traduit par de fortes variations de l'activité superficielle de ce dernier. Les résultats de la RMN ont montré la création d'un micro-environnement hydrophobe spécifique au groupe principal de l'OPP pluronique en présence de filtres UV. Une certaine interaction avec l'OE hydrophile a également été enregistrée, quoique plus faible. Ceci est confirmé par la DNPA, où les micelles P123 Pluronic ont interagi avec des forces variables avec les filtres UV, entraînant des changements importants dans leur taille et leur forme. CONCLUSIONS: nous avons démontré la sensibilité des micelles P123 Pluronic à la présence de différents filtres UVA/B. La forme des micelles variait de sphérique à cylindrique en fonction de la concentration et du type de filtres UV. Ces variations de forme devraient avoir un effet significatif sur le facteur de protection solaire (SPF), car elles affectent la solubilisation des filtres UV dans une formulation, en plus du profil rhéologique et du comportement de formation de film des formulations.

A Novel Chronic Kidney Disease Phenotyping Algorithm Using Combined Electronic Health Record and Claims Data.

Purpose: Because chronic kidney disease (CKD) is often under-coded as a diagnosis in claims data, we aimed to develop claims-based prediction models for CKD phenotypes determined by laboratory results in electronic health records (EHRs). Patients and Methods: We linked EHR from two networks (used as training and validation cohorts, respectively) with Medicare claims data. The study cohort included individuals ≥65 years with a valid serum creatinine result in the EHR from 2007 to 2017, excluding those with end-stage kidney disease or on dialysis. We used LASSO regression to select among 134 predictors for predicting continuous estimated glomerular filtration rate (eGFR). We assessed the model performance when predicting eGFR categories of <60, <45, <30 mL/min/1.73m2 in terms of area under the receiver operating curves (AUC). Results: The model training cohort included 117,476 patients (mean age 74.8 years, female 58.2%) and the validation cohort included 56,744 patients (mean age 73.8 years, female 59.6%). In the validation cohort, the AUC of the primary model (with 113 predictors and an adjusted R2 of 0.35) for predicting eGFR <60, eGFR<45, and eGFR <30 mL/min/1.73m2 categories was 0.81, 0.88, and 0.92, respectively, and the corresponding positive predictive values for these 3 phenotypes were 0.80 (95% confidence interval: 0.79, 0.81), 0.79 (0.75, 0.84), and 0.38 (0.30, 0.45), respectively. Conclusion: We developed a claims-based model to determine clinical phenotypes of CKD stages defined by eGFR values. Researchers without access to laboratory results can use the model-predicted phenotypes as a proxy clinical endpoint or confounder and to enhance subgroup effect assessment.

mRNA COVID-19 vaccination early in pregnancy and the risk of spontaneous abortion in an international pregnancy registry.

PURPOSE: mRNA COVID-19 vaccines are used in pregnant populations whether advertently or inadvertently. However, evidence on the safety of these vaccines during pregnancy is limited. The objective of this study is to evaluate the effect of BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna) vaccination during the first 20 weeks of gestation on the risk of spontaneous abortion (SAB). METHODS: All pregnant women who received at least one dose of BNT162b2 or mRNA-1273 and enrolled in the COVID-19 Vaccines International Pregnancy Exposure Registry (C-VIPER) were prospectively followed from enrollment until 20 weeks of gestation, SAB, or loss to follow-up. Baseline demographics, vaccination information, and pregnancy outcomes were collected via monthly online self-administered questionnaires, vaccination certificates, and medical records. Life tables were used to calculate the cumulative risk of SAB. Cox regression was used to estimate the hazard ratio (HR) comparing the two vaccines groups stratified by country of residence and gestational age at enrollment. RESULTS: Among 6840 participants who received at least one dose of BNT162b2 or mRNA-1273 at any time in pregnancy between Jan-Sep, 2021, 2129 met the inclusion criteria (1576 received BNT162b2 and 553 mRNA-1273). The two groups were balanced in terms of baseline characteristics. There were 37 SABs, with an overall 13.4% estimated cumulative risk by 20 weeks of gestation, which is similar to the expected risk in the population. The HR of SAB comparing mRNA-1273 to BNT162b2 was 1.46 (95% CI: 0.66, 3.22). CONCLUSION: The C-VIPER data show no evidence that mRNA COVID-19 vaccines increase the risk of SAB.

Distribution of Abatement Funds Arising From US Opioid Litigation.

This Viewpoint discusses the settlement agreements reached against several major pharmaceutical distributors resulting from the US opioid epidemic and how those funds will be distributed amongst the states.

Clinico-Pathological Characteristics, Management, and Outcome of Benign Intraosseous Maxillary Tumors in Adolescents: A Prospective Study.

INTRODUCTION: Benign intraosseous maxillary tumors, although uncommon among the adolescents, represent a major challenge to the maxillofacial surgeons. Treatment ranges from conservative surgery to radical resection and reconstruction. Maxillary defect reconstruction in adolescents is uncommon. it can be achieved by prosthetic obturators, local and regional flaps, and free-tissue transfer. AIM OF THE WORK: To investigate the clinical and pathological patterns, treatment, and outcome of benign intraosseous maxillary tumors in adolescents. PATIENTS AND METHODS: A 10-years prospective study included patients between 12-18 years who presented with benign intraosseous maxillary tumors and surgically treated (conservative surgery or radical resection) with immediate reconstruction. Cases were followed up to assess functional and aesthetic outcomes and detect complications. RESULTS: Study included 38 patients; 63.2% had non-odontogenic tumors and 36.8% had odontogenic tumors. The most common non-odontogenic tumor was central giant cell granuloma (31.6%). The most common odontogenic tumors were adenomatoid odontogenic tumor and ameloblastoma (10.5% each). Treatment included Conservative surgery (55.3%) and radical resection (44.7%). Reconstruction was performed in 17 cases by temporalis muscle flap (9.83%), obturator (2.46%), and free fibula flap (1.64%). All cases gained accepted functional and esthetic results. CONCLUSIONS: Non-odontogenic tumors were more common than odontogenic tumors. Central giant cell granulomas and ossifying fibromas were the most common non-odontogenic tumors. Ade-nomatoid odontogenic tumor and ameloblastoma were the most common odontogenic tumors. Maxillary reconstructions with tem-poralis muscle flap and obturator were simple and satisfactory. Microsurgical reconstruction had high success rates. Aesthetic, and functional results were satisfactory when appropriate reconstruction was performed.

Effect of reductions in opioid prescribing on opioid use disorder and fatal overdose in the United States: a dynamic Markov model.

BACKGROUND AND AIMS: Despite prescribing declines between 2011 and 2019, opioid morbidity and mortality in the United States continued to rise during this period. We estimated the relationship between opioid prescribing, opioid use disorder (OUD) and fatal opioid overdose in the United States. DESIGN: Dynamic Markov model. SETTING: United States, using data from the National Survey on Drug Use and Health, Centers for Disease Control and Prevention, National Health and Nutrition Examination Survey and National Epidemiologic Survey on Alcohol and Related Conditions III. PARTICIPANTS: Simulated US individuals 12+ years of age from the general population or with prescription opioid medical use, prescription opioid non-medical use, illicit opioid (e.g. heroin, illicit fentanyl) use, prescription OUD, illicit OUD with a history of prior prescription opioid non-medical use or non-fatal or fatal opioid overdose. MEASUREMENTS: Active OUD cases and fatal prescription opioid overdoses. FINDINGS: Between 2010 and 2019, opioid prescribing declined 42.5%. Although fatal opioid overdoses increased by 103.2%, these reductions in opioid prescribing averted an estimated 9600 [95% uncertainty interval (UI) = 7205, 15 478] deaths starting in 2011 relative to continued prescribing at 2010 levels-and are projected to avert another 50 918 (95% UI = 38 829, 79 795) overdose deaths between 2020 and 2029. The median time from initial opioid prescription to fatal opioid overdose was 5.2 years. Of the 2.4 million (95% UI = 2.2 million, 2.7 million) individuals in the United States with estimated active OUD in 2019, 65% (95% UI = 59%, 71%) were attributable to initial opioid use occurring prior to 2011, whereas 14% (95% UI = 12%, 17%) were attributable to initial opioid use occurring between 2017 and 2019. The impact, by 2029, of additional reductions in prescribing initiated in 2020 would be more than three times greater than that of similar reductions initiated in 2025. CONCLUSIONS: Observed reductions in opioid prescribing volume in the United States from 2010 to 2019 appear to have saved approximately 9600 lives by 2019 and are anticipated to avert more than 50 000 fatal overdoses by 2029.

Use of Hydroxychloroquine, Remdesivir, and Dexamethasone Among Adults Hospitalized With COVID-19 in the United States : A Retrospective Cohort Study.

BACKGROUND: Relatively little is known about the use patterns of potential pharmacologic treatments of COVID-19 in the United States. OBJECTIVE: To use the National COVID Cohort Collaborative (N3C), a large, multicenter, longitudinal cohort, to characterize the use of hydroxychloroquine, remdesivir, and dexamethasone, overall as well as across individuals, health systems, and time. DESIGN: Retrospective cohort study. SETTING: 43 health systems in the United States. PARTICIPANTS: 137 870 adults hospitalized with COVID-19 between 1 February 2020 and 28 February 2021. MEASUREMENTS: Inpatient use of hydroxychloroquine, remdesivir, or dexamethasone. RESULTS: Among 137 870 persons hospitalized with confirmed or suspected COVID-19, 8754 (6.3%) received hydroxychloroquine, 29 272 (21.2%) remdesivir, and 53 909 (39.1%) dexamethasone during the study period. Since the release of results from the RECOVERY (Randomised Evaluation of COVID-19 Therapy) trial in mid-June, approximately 78% to 84% of people who have had invasive mechanical ventilation have received dexamethasone or other glucocorticoids. The use of hydroxychloroquine increased during March 2020, peaking at 42%, and started declining by April 2020. By contrast, remdesivir and dexamethasone use gradually increased over the study period. Dexamethasone and remdesivir use varied substantially across health centers (intraclass correlation coefficient, 14.2% for dexamethasone and 84.6% for remdesivir). LIMITATION: Because most N3C data contributors are academic medical centers, findings may not reflect the experience of community hospitals. CONCLUSION: Dexamethasone, an evidence-based treatment of COVID-19, may be underused among persons who are mechanically ventilated. The use of remdesivir and dexamethasone varied across health systems, suggesting variation in patient case mix, drug access, treatment protocols, and quality of care. PRIMARY FUNDING SOURCE: National Center for Advancing Translational Sciences; National Heart, Lung, and Blood Institute; and National Institute on Aging.

Dipeptidyl peptidase-4 inhibitor cardiovascular safety in patients with type 2 diabetes, with cardiovascular and renal disease: a retrospective cohort study.

Clinical trials investigating cardiovascular safety of dipeptidyl peptidase-IV inhibitors (DPP-4i) among patients with cardiovascular and renal disease rarely recruit patients with renal impairment, despite associations with increased risk for major adverse cardiovascular events (MACE). We investigated the risk of MACE associated with the use of DPP-4i among these high-risk patients. Using a new-user, retrospective, cohort design, we analyzed 2010-2015 IBM MarketScan Commercial Claims and Encounters for patients with diabetes, comorbid with cardiovascular disease and/or renal impairment. We compared time to first MACE for DPP-4i versus sulfonylurea and versus metformin. Of 113,296 individuals, 9146 (8.07%) were new DPP-4i users, 17,481 (15.43%) were new sulfonylurea users, and 88,596 (78.20%) were new metformin users. Exposure groups were not mutually exclusive. DPP-4i was associated with lower risk for MACE than sulfonylurea (aHR 0.84; 95% CI 0.74, 0.93) and similar risk for MACE to metformin (aHR 1.07; 95% CI [1.04, 1.16]). DPP-4i use was associated with lower risk for MACE compared to sulfonylureas and similar risk for MACE compared to metformin. This association was most evident in the first year of therapy, suggesting that DPP-4i is a safer choice than sulfonylurea for diabetes treatment initiation in high-risk patients.

Changes in Short-term, Long-term, and Preventive Care Delivery in US Office-Based and Telemedicine Visits During the COVID-19 Pandemic.

Importance: While the COVID-19 pandemic has been associated with some substitution of telemedicine for office-based care in the US, to our knowledge, little is known regarding the pandemic's association with the clinical content of ambulatory care. Objective: To characterize changes in the clinical content of ambulatory care among office-based vs telemedicine encounters in the US before vs during the COVID-19 pandemic. Design Settings and Participants: This analysis of serial cross-sectional data from the IQVIA National Disease and Therapeutic Index was a 2-stage, stratified nationally representative audit of outpatient care in the US from January 1, 2018, through December 31, 2020. The National Disease and Therapeutic Index generates approximately 33 617 quarterly visits that are projected to 306.7 million national visits based on the survey design. Main Outcomes and Measures: (1) Prevalence of common diagnoses and (2) mix of long-term, short-term, and preventive care. Results: The mean (SD) number of projected quarterly, in-person, office-based visits was 282.1 (1.4) million in 2018 and 284.7 (10.3) in 2019 before declining to 250.8 million in quarter 1 of 2020 and 147.8 million in quarter 2 of 2020 and then increasing moderately to 181.5 million in quarter 3 of 2020 and 180.2 million in quarter 4 of 2020. The mean (SD) number of telemedicine visits was 2.8 (0.4) million in 2018 and 3.0 (0.1) million in 2019 before increasing to 8.6 million in quarter 1 of 2020 and 72.2 million in quarter 2 of 2020 and then declining notably to 43.8 million in quarter 3 of 2020 and 44.2 million in quarter 4 of 2020. Office-based care during the second through fourth quarters of 2020 involved 58.0% long-term, 23.0% short-term, and 25.6% preventive care. In contrast to office-based care, 4 of the top 10 diagnoses that were treated by telemedicine during 2020 were for psychiatric or behavioral conditions: depression, attention deficit/hyperactivity, anxiety, and bipolar disorders. Throughout this period, approximately half of office-based visits and nearly two-thirds of telemedicine visits were for established rather than new patients. Conclusions and Relevance: This cross-sectional study's findings suggest that while telemedicine rapidly increased early during course of the COVID-19 pandemic, its use declined modestly since then. In contrast to office-based care, telemedicine was more commonly used for established patients and substantially greater delivery of psychiatric or behavioral treatments rather than preventive care.

Insights into the structure of sunscreen lotions: a small-angle neutron scattering study.

Sunscreen lotions and creams are arguably the most popular products used to protect the skin against harmful UV radiation. Several studies have been conducted to untangle the internal microstructure of creams and lotions. However, the effect of UV filters and other materials such as preservatives, on the internal microstructure and the aesthetics of these products is not yet fully understood. Using small-angle neutron scattering (SANS), we were able to investigate the effect of adding the commonly used organic UV filters (avobenzone (AVB), ethylhexyl methoxycinnamate (EMC), ethylhexyl triazone (EHT) and bemotrizinol (BMT)) and the water soluble preservatives (1,5-pentanediol (1,5-PD) and 1,2-hexanediol (1,2-HD)), on the internal architecture and microstructure of an oil-in-water (o/w) based sunscreen lotion. Our findings highlight the complexities of these formulations, and how the introduction of different additives could influence their structure and possibly their performance.

Modeling Mitigation Strategies to Reduce Opioid-Related Morbidity and Mortality in the US.

Importance: The US opioid epidemic is complex and dynamic, yet relatively little is known regarding its likely future impact and the potential mitigating impact of interventions to address it. Objective: To estimate the future burden of the opioid epidemic and the potential of interventions to address the burden. Design, Setting, and Participants: A decision analytic dynamic Markov model was calibrated using 2010-2018 data from the National Survey on Drug Use and Health, Centers for Disease Control and Prevention, National Health and Nutrition Examination Survey, the US Census, and National Epidemiologic Survey on Alcohol and Related Conditions-III. Data on individuals 12 years or older from the US general population or with prescription opioid medical use; prescription opioid nonmedical use; heroin use; prescription, heroin, or combined prescription and heroin opioid use disorder (OUD); 1 of 7 treatment categories; or nonfatal or fatal overdose were examined. The model was designed to project fatal opioid overdoses between 2020 and 2029. Exposures: The model projected prescribing reductions (5% annually), naloxone distribution (assumed 5% reduction in case-fatality), and treatment expansion (assumed 35% increase in uptake annually for 4 years and 50% relapse reduction), with each compared vs status quo. Main Outcomes and Measures: Projected 10-year overdose deaths and prevalence of OUD. Results: Under status quo, 484 429 (95% confidence band, 390 543-576 631) individuals were projected to experience fatal opioid overdose between 2020 and 2029. Projected decreases in deaths were 0.3% with prescribing reductions, 15.4% with naloxone distribution, and 25.3% with treatment expansion; when combined, these interventions were associated with 179 151 fewer overdose deaths (37.0%) over 10 years. Interventions had a smaller association with the prevalence of OUD; for example, the combined intervention was estimated to reduce OUD prevalence by 27.5%, from 2.47 million in 2019 to 1.79 million in 2029. Model projections were most sensitive to assumptions regarding future rates of fatal and nonfatal overdose. Conclusions and Relevance: The findings of this study suggest that the opioid epidemic is likely to continue to cause tens of thousands of deaths annually over the next decade. Aggressive deployment of evidence-based interventions may reduce deaths by at least a third but will likely have less impact for the number of people with OUD.

Use and Content of Primary Care Office-Based vs Telemedicine Care Visits During the COVID-19 Pandemic in the US.

Importance: Little is known about the association between the coronavirus disease 2019 (COVID-19) pandemic and the level and content of primary care delivery in the US. Objective: To quantify national changes in the volume, type, and content of primary care delivered during the COVID-19 pandemic, especially with regard to office-based vs telemedicine encounters. Design, Setting, and Participants: Analysis of serial cross-sectional data from the IQVIA National Disease and Therapeutic Index, a 2-stage, stratified nationally representative audit of outpatient care in the US from the first calendar quarter (Q1) of 2018 to the second calendar quarter (Q2) of 2020. Main Outcomes and Measures: Visit type (office-based or telemedicine), overall and stratified by patient population and geographic region; assessment of blood pressure or cholesterol measurement; and initiation or continuation of prescription medications. Results: In the 8 calendar quarters between January 1, 2018, and December 31, 2019, between 122.4 million (95% CI, 117.3-127.5 million) and 130.3 million (95% CI, 124.7-135.9 million) quarterly primary care visits occurred in the US (mean, 125.8 million; 95% CI, 121.7-129.9 million), most of which were office-based (92.9%). In 2020, the total number of encounters decreased to 117.9 million (95% CI, 112.6-123.2 million) in Q1 and 99.3 million (95% CI, 94.9-103.8 million) in Q2, a decrease of 21.4% (27.0 million visits) from the average of Q2 levels during 2018 and 2019. Office-based visits decreased 50.2% (59.1 million visits) in Q2 of 2020 compared with Q2 2018-2019, while telemedicine visits increased from 1.1% of total Q2 2018-2019 visits (1.4 million quarterly visits) to 4.1% in Q1 of 2020 (4.8 million visits) and 35.3% in Q2 of 2020 (35.0 million visits). Decreases occurred in blood pressure level assessment (50.1% decrease, 44.4 million visits) and cholesterol level assessment (36.9% decrease, 10.2 million visits) in Q2 of 2020 compared with Q2 2018-2019 levels, and assessment was less common during telemedicine than during office-based visits (9.6% vs 69.7% for blood pressure; P < .001; 13.5% vs 21.6% for cholesterol; P < .001). New medication visits in Q2 of 2020 decreased by 26.0% (14.1 million visits) from Q2 2018-2019 levels. Telemedicine adoption occurred at similar rates among White individuals and Black individuals (19.3% vs 20.5% of patient visits, respectively, in Q1/Q2 of 2020), varied by region (low of 15.1% of visits [East North Central region], high of 26.8% of visits [Pacific region]), and was not correlated with regional COVID-19 burden. Conclusions and Relevance: The COVID-19 pandemic has been associated with changes in the structure of primary care delivery, with the content of telemedicine visits differing from that of office-based encounters.

Retinal Inputs to the Thalamus Are Selectively Gated by Arousal.

The brain can flexibly filter out sensory information in a manner that depends on behavioral state. In the visual thalamus and cortex, arousal and locomotion are associated with changes in the magnitude of responses to visual stimuli. Here, we asked whether such modulation of visual responses might already occur at an earlier stage in this visual pathway. We measured neural activity of retinal axons using wide-field and two-photon calcium imaging in awake mouse thalamus across arousal states associated with different pupil sizes. Surprisingly, visual responses to drifting gratings in retinal axonal boutons were robustly modulated by arousal level in a manner that varied across stimulus dimensions and across functionally distinct subsets of boutons. At low and intermediate spatial frequencies, the majority of boutons were suppressed by arousal. In contrast, at high spatial frequencies, boutons tuned to regions of visual space ahead of the mouse showed enhancement of responses. Arousal-related modulation also varied with a bouton's preference for luminance changes and direction or axis of motion, with greater response suppression in boutons tuned to luminance decrements versus increments, and in boutons preferring motion along directions or axes of optic flow. Together, our results suggest that differential modulation of distinct visual information channels by arousal state occurs at very early stages of visual processing, before the information is transmitted to neurons in visual thalamus. Such early filtering may provide an efficient means of optimizing central visual processing and perception across behavioral contexts.

Outpatient Parenteral Antimicrobial Therapy in the Time of COVID-19: The Urgent Need for Better Insurance Coverage.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the disease it causes, coronavirus disease 2019 (COVID-19), are placing unprecedented pressure on every health care system. Patients who require weeks of intravenous antibiotic therapy after hospital discharge due to severe bacterial infections, generally referred to as outpatient parenteral antibiotic therapy (OPAT), are at increased risk for contracting and/or transmitting COVID-19 due to extensive contact with the health care system. To reduce the risk of COVID-19 among this vulnerable patient population, providers overseeing OPAT care need to consider the relative safety of the different OPAT sites of care. Home-based OPAT should be emphasized to minimize hospital stays and prevent skilled nursing facility admissions. Medicare reimbursement policies need to urgently change to provide comprehensive coverage of home infusion services.

Interaction of Low Molecular Weight Poly(diallyldimethylammonium chloride) and Sodium Dodecyl Sulfate in Low Surfactant-Polyelectrolyte Ratio, Salt-Free Solutions.

Coacervation is widely used in formulations to induce a beneficial character to the formulation, but nonequilibrium effects are often manifest. Electrophoretic NMR (eNMR), pulsed-gradient spin-echo NMR (PGSE-NMR), and small-angle neutron scattering (SANS) have been used to quantify the interaction between low molecular cationic poly(diallyldimethylammonium chloride) (PDADMAC) and the anionic surfactant sodium dodecyl sulfate (SDS) in aqueous solution as a model for the precursor state to such nonequilibrium processes. The NMR data show that, within the low surfactant concentration one-phase region, an increasing surfactant concentration leads to a reduction in the charge on the polymer and a collapse of its solution conformation, attaining minimum values coincident with the macroscopic phase separation boundary. Interpretation of the scattering data reveals how the rodlike polymer changes over the same surfactant concentration window, with no discernible fingerprint of micellar type aggregates, but rather with the emergence of disklike and lamellar structures. At the highest surfactant concentration, the emergence of a weak Bragg peak in both the polymer and surfactant scattering suggests these precursor disk and lamellar structures evolve into paracrystalline stacks which ultimately phase separate. Addition of the nonionic surfactant hexa(ethylene glycol) monododecyl ether (C12E6) to the system seems to have little effect on the PDADMAC/SDS interaction as determined by NMR, merely displacing the observed behavior to lower SDS concentrations, commensurate with the total SDS present in the system. In other words, PDADMAC causes the disruption of the mixed SDS/C12E6 micelle, leading to SDS-rich PDADAMC/surfactant complexes coexisting with C12E6-rich micelles in solution.