Belantamab Mafodotin, Bortezomib, and Dexamethasone for Multiple Myeloma.

BACKGROUND: Belantamab mafodotin had single-agent activity in patients with relapsed or refractory multiple myeloma, a finding that supports further evaluation of the agent in combination with standard-care therapies. METHODS: In this phase 3, open-label, randomized trial, we evaluated belantamab mafodotin, bortezomib, and dexamethasone (BVd), as compared with daratumumab, bortezomib, and dexamethasone (DVd), in patients who had progression of multiple myeloma after at least one line of therapy. The primary end point was progression-free survival. Key secondary end points were overall survival, response duration, and minimal residual disease (MRD)-negative status. RESULTS: In total, 494 patients were randomly assigned to receive BVd (243 patients) or DVd (251 patients). At a median follow-up of 28.2 months (range, 0.1 to 40.0), median progression-free survival was 36.6 months (95% confidence interval [CI], 28.4 to not reached) in the BVd group and 13.4 months (95% CI, 11.1 to 17.5) in the DVd group (hazard ratio for disease progression or death, 0.41; 95% CI, 0.31 to 0.53; P<0.001). Overall survival at 18 months was 84% in the BVd group and 73% in the DVd group. An analysis of the restricted mean response duration favored BVd over DVd (P<0.001). A complete response or better plus MRD-negative status occurred in 25% of the patients in the BVd group and 10% of those in the DVd group. Grade 3 or higher adverse events occurred in 95% of the patients in the BVd group and 78% of those in the DVd group. Ocular events were more common in the BVd group than in the DVd group (79% vs. 29%); such events were managed with dose modifications, and events of worsening visual acuity mostly resolved. CONCLUSIONS: As compared with DVd therapy, BVd therapy conferred a significant benefit with respect to progression-free survival among patients who had relapsed or refractory multiple myeloma after at least one line of therapy. Most patients had grade 3 or higher adverse events. (Funded by GSK; DREAMM-7 ClinicalTrials.gov number, NCT04246047; EudraCT number, 2018-003993-29.).

Gut-educated IgA plasma cells defend the meningeal venous sinuses.

The central nervous system has historically been viewed as an immune-privileged site, but recent data have shown that the meninges-the membranes that surround the brain and spinal cord-contain a diverse population of immune cells1. So far, studies have focused on macrophages and T cells, but have not included a detailed analysis of meningeal humoral immunity. Here we show that, during homeostasis, the mouse and human meninges contain IgA-secreting plasma cells. These cells are positioned adjacent to dural venous sinuses: regions of slow blood flow with fenestrations that can potentially permit blood-borne pathogens to access the brain2. Peri-sinus IgA plasma cells increased with age and following a breach of the intestinal barrier. Conversely, they were scarce in germ-free mice, but their presence was restored by gut re-colonization. B cell receptor sequencing confirmed that meningeal IgA+ cells originated in the intestine. Specific depletion of meningeal plasma cells or IgA deficiency resulted in reduced fungal entrapment in the peri-sinus region and increased spread into the brain following intravenous challenge, showing that meningeal IgA is essential for defending the central nervous system at this vulnerable venous barrier surface.

Understanding Public Perceptions of Per- and Polyfluoroalkyl Substances: Infodemiology Study of Social Media.

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) are environmental contaminants that have received significant public attention. PFAS are a large group of human-made chemicals that have been used in industry and consumer products worldwide since the 1950s. Human exposure to PFAS is a growing public health concern. Studies suggest that exposure to PFAS may increase the risk of some cancers and have negative health impacts on the endocrine, metabolic, and immune systems. Federal and state health partners are investigating the exposure to and possible health effects associated with PFAS. Government agencies can observe social media discourse on PFAS to better understand public concerns and develop targeted communication and outreach efforts. OBJECTIVE: The primary objective of this study is to understand how social media is used to share, disseminate, and engage in public discussions of PFAS-related information in the United States. METHODS: We investigated PFAS-related content across 2 social media platforms between May 1, 2017, and April 30, 2019, to identify how social media is used in the United States to seek and disseminate PFAS-related information. Our key variable of interest was posts that mentioned "PFAS," "PFOA," "PFOS," and their hashtag variations across social media platforms. Additional variables included post type, time, PFAS event, and geographic location. We examined term use and post type differences across platforms. We used descriptive statistics and regression analysis to assess the incidence of PFAS discussions and to identify the date, event, and geographic patterns. We qualitatively analyzed social media content to determine the most prevalent themes discussed on social media platforms. RESULTS: Our analysis revealed that Twitter had a significantly greater volume of PFAS-related posts compared with Reddit (98,264 vs 3126 posts). PFAS-related social media posts increased by 670% over 2 years, indicating a marked increase in social media users' interest in and awareness of PFAS. Active engagement varied across platforms, with Reddit posts demonstrating more in-depth discussions compared with passive likes and reposts among Twitter users. Spikes in PFAS discussions were evident and connected to the discovery of contamination events, media coverage, and scientific publications. Thematic analysis revealed that social media users see PFAS as a significant public health concern and seek a trusted source of information about PFAS-related public health efforts. CONCLUSIONS: The analysis identified a prevalent theme-on social media, PFAS are perceived as an immediate public health concern, which demonstrates a growing sense of urgency to understand this emerging contaminant and its potential health impacts. Government agencies can continue using social media research to better understand the changing community sentiment on PFAS and disseminate targeted information and then use social media as a forum for dispelling misinformation, communicating scientific findings, and providing resources for relevant public health services.

Patient education interventions for prescription opioids: A systematic review.

OBJECTIVE: The objective of this systematic review is to evaluate the impact of prescription opioid-related education provided to a patient by a health care provider on patient outcomes. DATA SOURCES: The databases searched were PubMed, Cumulative Index of Nursing and Allied Health Literature (EBSCO), Academic Search Premier (EBSCO), Health Source: Nursing/Academic Edition (EBSCO), and International Pharmaceutical Abstracts (OVID). STUDY SELECTION: Studies were included if they were in English, peer-reviewed, and published between 1996 and October 22, 2018. Patient educational approaches initiated by health care providers for opioid medications in adults older than 18 years of age were evaluated. Studies were excluded if the full articles were unavailable or duplicates, or if they involved studies that did not explore provider-initiated patient educational interventions targeting opioid medications. Studies taking place outside the United States were excluded, as well. DATA EXTRACTION: Titles and abstracts of 4863 manuscripts were screened for inclusion in this review. Of these, 4794 were removed because they did not meet the inclusion criteria. The full texts of the remaining 69 documents were evaluated for inclusion. RESULTS: Ten articles were identified for inclusion in this review. Studies explored the impact of prescription opioid-related education on mortality, adherence, self-efficacy, self-care, quality of life, or knowledge. A variety of educational methods were used, including face-to-face follow-up, multimedia tools, predischarge counseling, and written information complementing verbal information. The interventions yielded inconsistent results, with improvements in patient outcomes seen in some studies, but not all. CONCLUSION: There are several well-documented interventions identifying methods to manage opioid-use disorder, but less about providing education to patients before they receive opioid prescriptions. Future research should explore the type of education and information being shared with patients, as this could inform pharmacists on how they should educate their patients.

Severity of disease and quality of life in parents of children with alopecia areata, totalis, and universalis: A prospective, cross-sectional study.

BACKGROUND: Caregiver-oriented quality of life (QoL) research in alopecia areata is limited. No study has used a parent-tailored survey to examine the relationship between QoL and severity of alopecia as measured by Severity of Alopecia Tool (SALT) scores. OBJECTIVES: This is a prospective study that describes QoL in parents of pediatric patients with all subtypes of alopecia areata and investigates the relationship between QoL and severity of disease, duration of disease, and age of patients. METHODS: Pediatric patients and their parents were invited to participate during clinic visits. Participating parents completed the Quality of Life in a Child's Chronic Disease Questionnaire (QLCCDQ) and the Family Dermatology Life Quality Index (FDLQI). A subset of children completed the Children's Dermatologic Life Quality Index (CDLQI). SALT scores at time of survey completion were recorded. RESULTS: In total, 153 patients were included. Significant mild-to-moderate negative correlations were found between SALT scores and FDLQI scores, QLCCDQ scores, and QLCCDQ emotional domain scores. Age of child correlated negatively with QLCCDQ scores but not FDLQI scores. No significant correlation was found between duration of disease and FDLQI scores, QLCCDQ scores, or QLCCDQ emotional domain scores. LIMITATIONS: This study is limited by its small sample size and cross-sectional design. CONCLUSIONS: Impaired parent QoL might be associated with increasing severity of disease and age of affected child but not duration of disease. Providers should tailor counseling accordingly and help parents set realistic expectations for long-term experience with the disease.

The role of resilience in healthcare transitions among adolescent kidney transplant recipients.

PURPOSE: AYAs with KTs experience high rates of premature allograft loss during the HCT. There is a critical need to identify protective factors associated with stable HCT. Resilience-the ability to adapt and thrive in the setting of adversity-has known positive impact on health outcomes. This study explored the novel role of resilience constructs as protective factors in securing stable HCT among AYA with KT. METHODS: We conducted semi-structured interviews of adolescents and young adults who transitioned from a single pediatric transplant center to multiple adult nephrology centers between 2010 and 2017. Interviews explored the role of key resilience constructs in participants' lives around the time of HCT. Participants were stratified into stable or unstable HCT groups based on biological markers of allograft function and clinical data from chart review. Content analyses of interview transcripts were reviewed and compared among HCT groups. RESULTS: Thirty-two participants enrolled (17 stable; 15 unstable). Key resilience constructs more salient in the stable versus unstable HCT group were confidence in and connection to one's healthcare team. Reports of healthcare self-management competencies were similar across both HCT groups. CONCLUSIONS: Confidence in and connection to one's healthcare team appear to be linked with a stable HCT among AYA with KT. This suggests that interdependence, the ability to foster connections with and elicit support from healthcare providers, as opposed to complete independence or autonomy, which is often advised in the HCT process, is a critical component of resilience linked to stable HCT.

Understanding alopecia areata characteristics in children under the age of 4 years.

BACKGROUND/OBJECTIVES: Epidemiologic studies of children with alopecia areata (AA) are sparse, and there are no studies that focus on the youngest children with AA. Evaluation of the clinical presentations of AA in children <4 years of age was performed in order to identify the prognostic factors for disease progression. METHODS: We performed a retrospective chart review of 125 pediatric patients seen at the Children's Hospital of Philadelphia with an initial presentation of AA under the age of 4. Disease severity was measured using the Severity of Alopecia Tool (SALT) score at initial presentation, 3-6 months later, 1 year later, and then at 2 years. RESULTS: Initial presentation was most common between ages 2 and 4 years. Most children had mild disease severity and continued mild disease over the next 2 years. Children with more than 50% of hair loss at presentation were much more likely to have worsening SALT scores over time and remain more severe. Approximately 41% had concomitant atopic dermatitis, 28% had a family member with AA, and 27% had a first-degree family member with one or more autoimmune diseases. CONCLUSIONS: In a diverse patient population, most children with AA even when presenting under age 4 have mild disease (<50% hair loss on scalp). Those who present with more severe disease are more likely to worsen or remain severe over time. These findings can aid family counseling and education.

Treatment of severe pediatric atopic dermatitis with methotrexate: A retrospective review.

BACKGROUND/OBJECTIVES: Severe atopic dermatitis (AD) may require systemic immunomodulatory agents to control symptoms. A lack of evidence and guidelines for systemic AD therapy in children has led to variability in agents selected and uncertainty in their comparative efficacy and safety. Evaluation of the efficacy of methotrexate in children with severe AD was performed. METHODS: We performed a retrospective chart review of 55 pediatric patients seen at Children's Hospital of Philadelphia that measured improvement using the Investigator's Global Assessment (IGA), a scale that rates AD symptoms from 0 to 5. RESULTS: About 76% of patients showed improvement with methotrexate. Mean baseline IGA of all patients was 4.18. After 6-9 months of treatment, this improved to 2.94. There was additional improvement to a mean IGA score of 2.39 after 12-15 months of treatment. At the final visit before each patient stopped methotrexate, the mean IGA score was 2.71. Approximately 50% of patients experienced minor side effects with gastrointestinal side effects the most common. CONCLUSIONS: In a diverse patient population, safety and efficacy of methotrexate was demonstrated. Significant improvement in IGA was noted for the majority after 6-9 months of therapy with further improvement when continuing treatment to 12-15 months. Methotrexate remains an important option for long-term symptom control with a favorable side effect profile and low cost.

A Randomized Trial of a Multicomponent Intervention to Promote Medication Adherence: The Teen Adherence in Kidney Transplant Effectiveness of Intervention Trial (TAKE-IT).

BACKGROUND: Poor adherence to immunosuppressive medications is a major cause of premature graft loss among children and young adults. Multicomponent interventions have shown promise but have not been fully evaluated. STUDY DESIGN: Unblinded parallel-arm randomized trial to assess the efficacy of a clinic-based adherence-promoting intervention. SETTING & PARTICIPANTS: Prevalent kidney transplant recipients 11 to 24 years of age and 3 or more months posttransplantation at 8 kidney transplantation centers in Canada and the United States (February 2012 to May 2016) were included. INTERVENTION: Adherence was electronically monitored in all participants during a 3-month run-in, followed by a 12-month intervention. Participants assigned to the TAKE-IT intervention could choose to receive text message, e-mail, and/or visual cue dose reminders and met with a coach at 3-month intervals when adherence data from the prior 3 months were reviewed with the participant. "Action-Focused Problem Solving" was used to address adherence barriers selected as important by the participant. Participants assigned to the control group met with coaches at 3-month intervals but received no feedback about adherence data. OUTCOMES: The primary outcomes were electronically measured "taking" adherence (the proportion of prescribed doses of immunosuppressive medications taken) and "timing" adherence (the proportion of doses of immunosuppressive medications taken between 1 hour before and 2 hours after the prescribed time of administration) on each day of observation. Secondary outcomes included the standard deviation of tacrolimus trough concentrations, self-reported adherence, acute rejection, and graft failure. RESULTS: 81 patients were assigned to intervention (median age, 15.5 years; 57% male) and 88 to the control group (median age, 15.8 years; 61% male). Electronic adherence data were available for 64 intervention and 74 control participants. Participants in the intervention group had significantly greater odds of taking prescribed medications (OR, 1.66; 95% CI, 1.15-2.39) and taking medications at or near the prescribed time (OR, 1.74; 95% CI, 1.21-2.50) than controls. LIMITATIONS: Lack of electronic adherence data for some participants may have introduced bias. There was low statistical power for clinical outcomes. CONCLUSIONS: The multicomponent TAKE-IT intervention resulted in significantly better medication adherence than the control condition. Better medication adherence may result in improved graft outcomes, but this will need to be demonstrated in larger studies. TRIAL REGISTRATION: Registered at ClinicalTrials.gov with study number NCT01356277.

Extracorporeal Cardiopulmonary Resuscitation (E-CPR) During Pediatric In-Hospital Cardiopulmonary Arrest Is Associated With Improved Survival to Discharge: A Report from the American Heart Association's Get With The Guidelines-Resuscitation (GWTG-R) Registry.

BACKGROUND: Although extracorporeal cardiopulmonary resuscitation (E-CPR) can result in survival after failed conventional CPR (C-CPR), no large, systematic comparison of pediatric E-CPR and continued C-CPR has been reported. METHODS AND RESULTS: Consecutive patients <18 years old with CPR events ≥10 minutes in duration reported to the Get With the Guidelines-Resuscitation registry between January 2000 and December 2011 were identified. Hospitals were grouped by teaching status and location. Primary outcome was survival to discharge. Regression modeling was performed, conditioning on hospital groups. A secondary analysis was performed with the use of propensity score matching. Of 3756 evaluable patients, 591 (16%) received E-CPR and 3165 (84%) received C-CPR only. Survival to hospital discharge and survival with favorable neurological outcome (Pediatric Cerebral Performance Category score of 1-3 or unchanged from admission) were greater for E-CPR (40% [237 of 591] and 27% [133 of 496]) versus C-CPR patients (27% [862 of 3165] and 18% [512 of 2840]). Odds ratios (ORs) for survival to hospital discharge and survival with favorable neurological outcome were greater for E-CPR versus C-CPR. After adjustment for covariates, patients receiving E-CPR had higher odds of survival to discharge (OR, 2.80; 95% confidence interval, 2.13-3.69; P<0.001) and survival with favorable neurological outcome (OR, 2.64; 95% confidence interval, 1.91-3.64; P<0.001) than patients who received C-CPR. This association persisted when analyzed by propensity score-matched cohorts (OR, 1.70; 95% confidence interval, 1.33-2.18; P<0.001; and OR, 1.78; 95% confidence interval, 1.31-2.41; P<0.001, respectively]. CONCLUSION: For children with in-hospital CPR of ≥10 minutes duration, E-CPR was associated with improved survival to hospital discharge and survival with favorable neurological outcome compared with C-CPR.

Integrating Behavioral Health into Pediatric Primary Care: Implications for Provider Time and Cost.

OBJECTIVES: Integrating a behavioral health consultant (BHC) into primary care is associated with improved patient outcomes, fewer medical visits, and increased provider satisfaction; however, few studies have evaluated the feasibility of this model from an operations perspective. Specifically, time and cost have been identified as barriers to implementation. Our study aimed to examine time spent, patient volume, and revenue generated during days when the on-site BHC was available compared with days when the consultant was not. METHODS: Data were collected across a 10-day period when a BHC provided services and 10 days when she was not available. Data included time stamps of patient direct care; providers' direct reports of problems raised; and a review of medical and administrative records, including billing codes and reimbursement. This study took place in a rural, stand-alone private pediatric primary care practice. The participants were five pediatric primary care providers (PCPs; two doctors of medicine, 1 doctor of osteopathy, 2 nurse practitioners) and two supervised doctoral students in psychology (BHCs). Pediatric patients (N = 668) and their parents also participated. RESULTS: On days when a BHC was present, medical providers spent 2 fewer minutes on average for every patient seen, saw 42% more patients, and collected $1142 more revenue than on days when no consultant was present. CONCLUSIONS: The time savings demonstrated on days when the consultant was available point to the efficiency and potential financial viability of this model. These results have important implications for the feasibility of hiring behavioral health professionals in a fee-for-service system. They have equally useful implications for the utility of moving to a bundled system of care in which collaborative practice is valued.

Tree canopy cover affects basal resources and nutrient profiles of Aedes and Culex larvae in cemetery vases in New Orleans, Louisiana, United States.

Cemetery vases are important habitat for vector mosquito production, yet there is limited understanding on their food web dynamics and how they vary across environmental gradients. Tree cover is one factor that varies widely across cemeteries, and influence food webs by means of detrital inputs, temperature mediation, and light availability. Such information can be important for determining mosquito adult body size, fecundity, and competition outcomes, all of which may influence mosquito population and disease risk. This study evaluates the relationship between tree canopy cover and indicators of basal resources for Aede aegypti (L.), Aedes albopictuss (Skuse), and Culex quinquefasciatus (Say) larvae, such as stable isotopes (δ13C and δ15N) and nutrient stoichiometry in cemeteries of New Orleans, Louisiana (USA). Stable isotope values suggest that larvae feed directly on the Particulate Organic Matter (POM) suspended in the vase's water, and that POM composition influence the nutrient profiles of mosquito larvae. The POM of open canopy vases had higher δ13C values, than that of closed canopy vases indicating differences in relative proportion of basal carbon sources, with open canopy POM having a lower proportion of allochthonous carbon, and a higher proportion of authoctonous carbon. Accordingly, mosquito larvae collected from open canopy vases had higher δ13C values, and higher C:N than larvae from closed canopy vases. The results of this study show a shift in food web dynamics driven by canopy cover in cemetery vases that directly influence the nutrient profiles of mosquito larvae. The implications for mosquito ecology, and vector management are discussed.

Utility of the Counseling Center Assessment of Psychological Symptoms Screen in a Collegiate Athlete Population.

CONTEXT: Mental health screening as a part of collegiate athletic preparticipation evaluations is becoming increasingly common, but effective and efficient screening depends on a screening tool that can accurately identify mental health symptoms and the need for mental health intervention. DESIGN: Case-control study. SETTING: Archival clinical records review. PATIENTS OR OTHER PARTICIPANTS: Two cohorts of incoming National Collegiate Athletics Association Division I collegiate athletes (N = 353). MAIN OUTCOME MEASURE(S): Athletes completed the Counseling Center Assessment of Psychological Symptoms (CCAPS) Screen as a part of their preparticipation evaluation. These data were then matched with basic demographic data and mental health treatment history from clinical records, and the utility of the CCAPS Screen in determining a future or ongoing need for mental health services was analyzed. RESULTS: Score differences for each of the 8 CCAPS Screen scales (Depression, Generalized Anxiety, Social Anxiety, Academic Distress, Eating Concerns, Frustration, Family Distress, and Alcohol Use) were found based on several demographic variables. Logistic regression analysis demonstrated that female sex, team sport participation, and the Generalized Anxiety scale score predicted future participation in mental health treatment. Decision tree testing of the CCAPS scales showed low utility in classifying those who received mental health treatment versus those who did not. CONCLUSIONS: The CCAPS Screen did not appear to differentiate well between those who eventually received mental health services and those who did not. This should not be taken to mean that mental health screening is not useful but rather that a 1-time, state-based screening is not sufficient for athletes who experience intermittent but recurring stressors in a dynamic environment. A proposed model for improving the current standard of practice for mental health screening is provided as a focus of future research.

The Burden of Neuropsychiatric Disorders in Medicaid Patients Living With HIV-1 Treated With Integrase Inhibitor or Protease Inhibitor Antiretroviral Therapies.

Objective: Data are scarce regarding the incidence of neuropsychiatric events (NPEs) in people living with human immunodeficiency virus (HIV)-1 taking integrase inhibitor (INI)- or protease inhibitor (PI)-based regimens. This study evaluated the prevalence, incidence, and economic burden of NPEs among people living with HIV-1 who were newly treated with INI- or PI-based regimens in a Medicaid population.Methods: A retrospective cohort study was conducted using administrative claims from the IBM MarketScan Multi-State Medicaid Database (January 1, 2014-December 31, 2018). Treatment-naive and treatment-experienced adults with HIV-1 newly treated with an INI- or PI-based regimen were included. Outcomes included NPE prevalence during the 12-month baseline period, prevalence of existing and incidence of new-onset NPEs during the 6-month post-index period, and total all-cause and NPE-related costs between treatment cohorts. Baseline characteristics between the 2 cohorts were balanced using inverse probability treatment weighting.Results: In the INI (n = 3,929) and PI (n = 3,916) cohorts, mean (SD) ages were 44.87 (12.81) and 44.36 (11.85) years, and 41.7% and 41.3% were female, respectively. High proportions of patients in both cohorts had NPEs during the 12-month baseline period. Among patients with no baseline NPEs, adjusted NPE incident rate ratios (95% CIs) during the post-index period were as follows: any, 1.15 (1.00-1.33); chronic, 1.18 (0.98-1.42); and acute, 1.16 (0.96-1.39). Mean all-cause and NPE-related costs were similar between cohorts.Conclusions: In this study of the Medicaid population, the prevalence and incidence of NPEs, as well as health care costs, were similar among people living with HIV-1 newly treated with an INI- or PI-based regimen.

Public health evaluation of PFAS exposures and breastfeeding: a systematic literature review.

Per- and polyfluoroalkyl substances (PFAS) are a class of man-made chemicals that are persistent in the environment. They can be transferred across the placenta to fetuses and through human milk to infants. The American Academy of Pediatrics advises that the benefits of breastfeeding infants almost always outweigh the potential risks of harm from environmental chemicals. However, there are few chemical-specific summaries of the potential harms of exposure to PFAS during the neonatal period through breastfeeding. This systematic review explores whether exposure to PFAS through breastfeeding is associated with adverse health outcomes among infants and children using evidence from human and animal studies. Systematic searches identified 4297 unique records from 7 databases. The review included 37 total articles, including 9 animal studies and 1 human study measuring the direct contribution of exposure of the infant or pup through milk for any health outcome. Animal studies provided evidence of associations between exposure to PFOA through breastfeeding and reduced early life body weight gain, mammary gland development, and thyroid hormone levels. They also provided limited evidence of associations between PFOS exposure through breastfeeding with reduced early life body weight gain and cellular changes in the hippocampus. The direct relevance of any of these outcomes to human health is uncertain, and it is possible that many adverse health effects of exposure through breastfeeding have not yet been studied. This review documents the current state of science and highlights the need for future research to guide clinicians making recommendations on infant feeding.

Community-facing toxicokineticmodels to estimate PFAS serum levels based on life history and drinking water exposures.

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) are drinking water contaminants. Tools to assess the potential body burden associated with drinking PFAS-contaminated water may be helpful for public health assessment of exposed communities. METHODS: We implemented a suite of one-compartment toxicokinetic models using extensively calibrated toxicokinetic parameters (half-life and volume of distribution). We implemented the models both in the R programming language for research purposes, and as a web estimator for the general public (built in typescript.js). These models simulate exposure to PFAS water concentrations for individuals with varying characteristics such as age, sex, weight, and breastfeeding history. The models account for variability and uncertainty in parameter inputs to produce Monte Carlo-based estimates of serum concentration. For children, the models additionally account for gestational exposure, lactational exposure, and potential exposure through formula feeding. For adults who have borne children, the models account for clearance through birth and breastfeeding. We ran simulations of individuals with known PFAS water and serum concentrations to evaluate the model. We then compared the predicted serum PFAS concentrations to measured data. RESULTS: The models accurately estimate individual-level serum levels for each PFAS for most adults within ½ order of magnitude. We found that the models somewhat overestimated serum concentrations for children in the tested locations, and that these overestimates are generally within an order of magnitude. DISCUSSION: This paper presents scientifically robust models that allow users to estimate serum PFAS concentrations based on known PFAS water concentrations and physiologic information. However, accuracy in historical water concentration inputs, exposure from non-drinking water sources, and life-history characteristics of individuals present a complex problem for individual estimation. Additional refinements to the model suite to improve the prediction of individual results may consist of including duration of exposure and additional life-history characteristics.

Practical implementation of remote continuous glucose monitoring in hospitalized patients with diabetes.

PURPOSE: Inpatient diabetes management involves frequent assessment of glucose levels for treatment decisions. Here we describe a program for inpatient real-time continuous glucose monitoring (rtCGM) at a community hospital and the accuracy of rtCGM-based glucose estimates. METHODS: Adult inpatients with preexisting diabetes managed with intensive insulin therapy and a diagnosis of coronavirus disease 2019 (COVID-19) were monitored via rtCGM for safety. An rtCGM system transmitted glucose concentration and trending information at 5-minute intervals to nearby smartphones, which relayed the data to a centralized monitoring station. Hypoglycemia alerts were triggered by rtCGM values of ≤85 mg/dL, but rtCGM data were otherwise not used in management decisions; insulin dosing adjustments were based on blood glucose values measured via fingerstick blood sampling. Accuracy was evaluated retrospectively by comparing rtCGM values to contemporaneous point-of-care (POC) blood glucose values. RESULTS: A total of 238 pairs of rtCGM and POC data points from 10 patients showed an overall mean absolute relative difference (MARD) of 10.3%. Clarke error grid analysis showed 99.2% of points in the clinically acceptable range, and surveillance error grid analysis showed 89.1% of points in the lowest risk category. It was determined that for 25% of the rtCGM values, discordances in rtCGM and POC values would likely have resulted in different insulin doses. Insulin dose recommendations based on rtCGM values differed by 1 to 3 units from POC-based recommendations. CONCLUSION: rtCGM for inpatient diabetes monitoring is feasible. Evaluation of individual rtCGM-POC paired values suggested that using rtCGM data for management decisions poses minimal risks to patients. Further studies to establish the safety and cost implications of using rtCGM data for inpatient diabetes management decisions are warranted.

Real-World Analysis of Weight Gain and Body Mass Index Increase Among Patients with HIV-1 Using Antiretroviral Regimen Containing Tenofovir Alafenamide, Tenofovir Disoproxil Fumarate, or Neither in the United States.

Background: While some studies among patients with HIV-1 suggest that antiretroviral therapy (ART) regimens containing tenofovir alafenamide (TAF) may be associated with greater weight gain than those not containing TAF, no studies have assessed the relationship between TAF doses and weight change. Objectives: To evaluate weight-related outcomes among patients with HIV-1 in the United States initiating ART containing different nucleoside reverse transcriptase inhibitors and doses. Methods: A retrospective longitudinal study was conducted using Decision Resources Group's electronic medical records (July 17, 2017-March 1, 2020). Adult patients with HIV-1 initiating ART (index date) containing TAF 25 mg, TAF 10 mg, tenofovir disoproxil fumarate (TDF), or neither TAF nor TDF on or after July 17, 2018, were included. Changes in weight and body mass index (BMI) from pre-index to 3, 6, 9, and 12 months post-index were compared between cohorts using mean differences obtained from ordinary least squares models adjusted for baseline characteristics. Time-to-weight and BMI increase ≥5% were compared using Cox models adjusted for baseline characteristics. Results: Among 1652 eligible patients (TAF 25 mg, n=710; TAF 10 mg, n=303; TDF, n=219; non-TAF/TDF, n=420), the majority (83.2%-99.5%) initiated an integrase strand transfer inhibitor, except for the TDF cohort (45.2%). Patients initiating TAF 25 mg had greater weight or BMI increase across all time points compared with patients initiating TAF 10 mg, TDF, or non-TAF/TDF regimens (mean differences in weight or BMI changes between cohorts at 12 months post-index ranged from 0.78 kg [1.72 lb] to 1.34 kg [2.95 lb] and from 0.77 kg/m2 to 1.95 kg/m2, respectively), although findings were not statistically significant for all comparisons. Compared with TAF 25 mg, time-to-weight and BMI increase ≥5% in the other treatment cohorts were longer (hazard ratios ranged from 0.77 to 0.94), although findings were generally not statistically significant. Conclusions: Among a population of patients predominantly initiating integrase strand transfer inhibitors, increases in weight and BMI post-ART initiation were common and appeared to be higher and occur more rapidly among patients receiving TAF 25 mg compared with lower TAF doses or other nucleosides. When considering long-term health consequences, weight gain is an important factor to consider when selecting an ART regimen.