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.

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.

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.

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.

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.

Altered interplay between endoplasmic reticulum and mitochondria in Charcot-Marie-Tooth type 2A neuropathy.

Mutations in the MFN2 gene encoding Mitofusin 2 lead to the development of Charcot-Marie-Tooth type 2A (CMT2A), a dominant axonal form of peripheral neuropathy. Mitofusin 2 is localized at both the outer membrane of mitochondria and the endoplasmic reticulum and is particularly enriched at specialized contact regions known as mitochondria-associated membranes (MAM). We observed that expression of MFN2R94Q induces distal axonal degeneration in the absence of overt neuronal death. The presence of mutant protein leads to reduction in endoplasmic reticulum and mitochondria contacts in CMT2A patient-derived fibroblasts, in primary neurons and in vivo, in motoneurons of a mouse model of CMT2A. These changes are concomitant with endoplasmic reticulum stress, calcium handling defects, and changes in the geometry and axonal transport of mitochondria. Importantly, pharmacological treatments reinforcing endoplasmic reticulum-mitochondria cross-talk, or reducing endoplasmic reticulum stress, restore the mitochondria morphology and prevent axonal degeneration. These results highlight defects in MAM as a cellular mechanism contributing to CMT2A pathology mediated by mutated MFN2.

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.

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.

Electrophoretic NMR Characterization of Charged Side Chain Cationic Polyelectrolytes and Their Interaction with the Anionic Surfactant, Sodium Dodecyl Sulfate.

Oppositely charged polymers and surfactants show a complex phase behavior with large regions of solubility and insolubility dependent on the concentrations of the species present. Here, a series of quaternized hydroxyethyl cellulose (cationic) polymers have been characterized by pulsed-gradient spin-echo NMR (PGSE-NMR) and electrophoretic NMR (eNMR) in simple aqueous (D2O) solutions and in combination with the oppositely charged (anionic) surfactant, sodium dodecyl sulfate (SDS). Analysis of the effective charge on the polymer derived from both the eNMR and PGSE-NMR results yields a readily interpretable insight into the polymer behavior; the effective charge on the polymer at infinite dilution shows a linear relationship with the degree of modification. On addition of low concentrations of SDS, typically Csurf < 5 mM, the surfactant interacts with the charged polymers, leading to substantial changes in the dynamics of the system (polymer diffusion, viscosity). At these levels of surfactant addition, there is no macroscopic phase separation. Further, with the absence of an interaction with the parent, the uncharged polymer strongly suggests that the SDS only interacts with the charged moieties present on the functionalized side groups and not the polymer backbone. Ultimately, the charge on the soluble polymer/surfactant complex was found to depend linearly on the level of surfactant binding across a series of polymers with differing levels of modification with the charge becoming effectively zero at the macroscopic phase separation boundary.

Short-term Effects of Mitomycin C Infiltration for Caustic Oesophageal Strictures in Children.

OBJECTIVES: The aim of this study was to investigate the efficacy and safety of endoscopic local infiltration of mitomycin C (MMC) after oesophageal dilation for children suffering from refractory postcorrosive oesophageal stricture (OS). METHODS: Children referred to Cairo University Specialized Paediatric Hospital with refractory postcorrosive OS during the period from March 2016 to August 2017 were included in this study. MMC was infiltrated endoscopically at the stricture site by the end of the dilation session. The measured outcomes were dysphagia score (DS) and periodic dilation index (PDI). RESULTS: During the inclusion period of the presented study, 17 children met the inclusion criteria. There were 7 boys and 10 girls. During the follow-up period, an average of 3.8 dilation sessions with MMC infiltration per case were performed, using a total dose of 1 mg each session. The median follow-up period was 9.5 months. The median DS improved from DS 3 before application of MMC to DS 0 at the last follow-up (P < 0.001). Additionally, the median PDI declined from 1 to 0.75 after MMC application (P = 0.052). Sixteen cases (94%) became dysphagia free after 6 months. Seven patients experienced postdilation minor bleeding that was spontaneously resolved, not triggering blood transfusion. There were no infiltration-related complications in the included series. CONCLUSION: Stricture-site MMC endoscopic infiltration by the end of a dilation session proved to be safe and effective in improving the DS and PDI.

Impact of the implementation of a nurse-managed outpatient parenteral antibiotic therapy (OPAT) system in Baltimore: a case study demonstrating cost savings and reduction in re-admission rates.

Objectives: Evidence supports the safety and effectiveness of outpatient parenteral antibiotic therapy (OPAT). A registered nurse (RN)-managed multidisciplinary team OPAT model was implemented at our hospital. We evaluated the impact of the new OPAT model on readmissions during OPAT and other core OPAT processes. Methods: All potential OPAT cases from 1 November 2013 to 31 June 2017 discharged from the Johns Hopkins Bayview Medical Center were followed up in a retrospective cohort study. Relevant clinical and patient characteristics were collected for the first OPAT course per patient. The primary outcome was all-cause readmission to any facility part of the Johns Hopkins Health System within 30 days of OPAT discharge. Proportions of OPAT patients readmitted before and after the implementation of the new OPAT model were compared. A log-binomial regression was used to compare the risk of readmission, adjusted for age, sex, race/ethnicity, site of OPAT care, opioid dependence and OPAT treatment duration. Results: Five hundred and seventeen OPAT patients were included in the analysis; 51.1% were discharged after the implementation of the new OPAT model. Readmission rates decreased from 20.2% to 13.3% following the RN-managed OPAT programme (P = 0.04). The results of the adjusted model indicated that nurse management was associated with a 39% reduction in the risk of readmission (adjusted relative risk 0.61; 95% CI 0.41-0.91; P = 0.01). Our financial evaluation estimated that the reduction in readmissions achieved by the RN-managed model saved the hospital $649 416 over 15 months. Conclusions: The RN-managed OPAT programme was associated with a significant reduction in readmissions.

Assembly of small molecule surfactants at highly dynamic air-water interfaces.

Small-angle neutron scattering has been used to probe the interfacial structure of foams stabilised by small molecule surfactants at concentrations well below their critical micelle concentration. The data for wet foams showed a pronounced Q-4 dependence at low Q and noticeable inflexions over the mid Q range. These features were found to be dependent on the surfactant structure (mainly the alkyl chain length) with various inflexions across the measured Q range as a function of the chain length but independent of factors such as concentration and foam age/height. By contrast, foam stability (for C < CMC) was significantly different at this experimental range. Drained foams showed different yet equally characteristic features, including additional peaks attributed to the formation of classical micellar structures. Together, these features suggest the dynamic air-water interface is not as simple as often depicted, indeed the data have been successfully described by a model consisting paracrystalline stacks (multilayer) of adsorbed surfactant layers; a structure that we believe is induced by the dynamic nature of the air-water interface in a foam.

Endocytic Uptake, Transport and Macromolecular Interactions of Anionic PAMAM Dendrimers within Lung Tissue.

PURPOSE: Polyamidoamine (PAMAM) dendrimers are a promising class of nanocarrier with applications in both small and large molecule drug delivery. Here we report a comprehensive evaluation of the uptake and transport pathways that contribute to the lung disposition of dendrimers. METHODS: Anionic PAMAM dendrimers and control dextran probes were applied to an isolated perfused rat lung (IPRL) model and lung epithelial monolayers. Endocytosis pathways were examined in primary alveolar epithelial cultures by confocal microscopy. Molecular interactions of dendrimers with protein and lipid lung fluid components were studied using small angle neutron scattering (SANS). RESULTS: Dendrimers were absorbed across the intact lung via a passive, size-dependent transport pathway at rates slower than dextrans of similar molecular sizes. SANS investigations of concentration-dependent PAMAM transport in the IPRL confirmed no aggregation of PAMAMs with either albumin or dipalmitoylphosphatidylcholine lung lining fluid components. Distinct endocytic compartments were identified within primary alveolar epithelial cells and their functionality in the rapid uptake of fluorescent dendrimers and model macromolecular probes was confirmed by co-localisation studies. CONCLUSIONS: PAMAM dendrimers display favourable lung biocompatibility but modest lung to blood absorption kinetics. These data support the investigation of dendrimer-based carriers for controlled-release drug delivery to the deep lung.

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.

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.

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.

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.

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.