School closures and prescription medication use among children and adolescents before and during the COVID-19 pandemic in the USA, 2019-2022.

The impact of schools closing for in-person instruction in the USA during the COVID-19 pandemic on the use of prescription medications is not known. In this study, we examined changes in the total prescriptions filled, specifically for attention deficit hyperactivity disorder (ADHD) medications, among school-aged children and adolescents aged 10-19 years during periods before and after complete school closures between October 2019 and September 2022. Our findings indicate that complete school closures were associated with declines in the use of ADHD medications among younger populations in the USA. These findings suggest that the underuse of ADHD medications may be an overlooked contributor to declines in academic performance observed during periods of school closures during the COVID-19 pandemic.

Shingles Vaccination in Medicare Part D After Inflation Reduction Act Elimination of Cost Sharing.

This cross-sectional study uses data from retail pharmacies to examine shingles vaccine uptake among Medicare Part D beneficiaries following an IRA policy to eliminate cost sharing.

Diagnoses and Treatment of Behavioral and Psychological Symptoms of Dementia Among Racially and Ethnically Diverse Persons Living with Dementia.

Background: Behavioral and psychological symptoms of dementia (BPSD) and prescribed central nervous system (CNS) active drugs to treat them are prevalent among persons living with Alzheimer's disease and related dementias (PLWD) and lead to negative outcomes for PLWD and their caregivers. Yet, little is known about racial/ethnic disparities in diagnosis and use of drugs to treat BPSD. Objective: Quantify racial/ethnic disparities in BPSD diagnoses and CNS-active drug use among community-dwelling PLWD. Methods: We used a retrospective cohort of community-dwelling Medicare Fee-for-Service beneficiaries with dementia, continuously enrolled in Parts A, B and D, 2017-2019. Multivariate logistic models estimated rates of BPSD diagnosis and, conditional on diagnosis, CNS-active drug use. Results: Among PLWD, 67.1% had diagnoses of an affective, psychosis or hyperactivity symptom. White (68.3%) and Hispanic (63.9%) PLWD were most likely, Blacks (56.6%) and Asians (52.7%) least likely, to have diagnoses. Among PLWD with BPSD diagnoses, 78.6% took a CNS-active drug. Use was highest among whites (79.3%) and Hispanics (76.2%) and lowest among Blacks (70.8%) and Asians (69.3%). Racial/ethnic differences in affective disorders were pronounced, 56.8% of white PLWD diagnosed; Asians had the lowest rates (37.8%). Similar differences were found in use of antidepressants. Conclusions: BPSD diagnoses and CNS-active drug use were common in our study. Lower rates of BPSD diagnoses in non-white compared to white populations may indicate underdiagnosis in clinical settings of treatable conditions. Clinicians' review of prescriptions in this population to reduce poor outcomes is important as is informing care partners on the risks/benefits of using CNS-active drugs.

Evaluation of the External Soft Tissue Changes Following the Correction of Class II Skeletal Malocclusion in the Adolescence Period Using Removable and Fixed Functional Appliances: A Systematic Review and Meta-Analysis.

In this systematic review, we aimed to assess the current evidence regarding the effectiveness of functional treatment with both removable and fixed appliances to normalize the external soft tissue for skeletal class II adolescent individuals. We performed a broad electronic search to retrieve relevant studies from nine databases to identify randomized controlled trials (RCTs) and controlled clinical trials (CCTs) that investigated soft tissue changes following functional treatment and evaluated the changes using 2D lateral cephalometric radiographs and 3D-optical surface laser scanning. A total of three RCTs and eight CCTs were included. Ages ranged from 11 to 16 years with the fixed functional appliances, and from eight to 12 years with the removable ones, including 689 skeletal class II patients. Version 2 of Cochran's risk-of-bias (RoB2), and the risk of bias in non-randomized studies of interventions (ROBIN-I) were used to assess the risk of bias for the included papers. Of the 11 eligible studies, three studies were included in the meta-analysis to assess the upper and lower lip position in relation to the E-line (Ricketts's aesthetic line) in addition to the nasolabial angle. The meta-analysis showed that the upper lip retracted after functional treatment with Twin-block in relation to E-line (mean difference (MD) = -1.93; 95% CI: -2.37, -1.50; p < 0.00001; χ² = 5.43; p = 0.07; I2 = 63%), while the lower lip position did not change after functional treatment with Twin-block in relation to E-line (MD = 0.03; 95% CI: -0.56, 0.61; p = 0.92; χ² = 1.74; p = 0.42; I2 = 0%). The nasolabial angle increased after Twin-block treatment (MD = 5.75; 95% CI: 4.57, 6.93; p < 0.00001; χ² = 6.77; p = 0.03; I2 = 70%). The mentolabial angle and Z-angle also increased after functional therapy, where the facial convexity angle decreased, regardless of the functional devices used. On the other hand, using the 3D-optical surface laser scanning showed that the upper lip length and the commissural width did not change following therapy, but the lower lip increased in length, as well as the total face height. More high-quality RCTs are required to obtain accurate evidence in this field.

Assessment of the U.S. Food and Drug Administration's risk evaluation and mitigation strategy (REMS) for prasugrel (EFFIENT): A narrative review.

Background: Prasugrel, first approved in 2009, was subject to a US Food and Drug Administration (FDA) Risk Evaluation and Mitigation Strategy (REMS) to mitigate the risk of bleeding associated with its use. Methods: We performed a narrative review of FDA documents obtained through a Freedom of Information Act request. Document classification and primary evidence extraction was performed by three authors (TM, JC, and SL). Results: The prasugrel REMS consists of a medication guide and a communication plan. Assessment of the REMS was via patient and clinician surveys. 1560 patients were invited to participate and 212 individuals (13.6 %) completed the survey. Rates of awareness among respondents varied across key messages and were highest for those examining the risks of premature discontinuation (96 % and 88 % of respondents), while lower for those regarding the importance of perioperative discontinuation (66 %) and contraindications posed by a history of stroke (16 %) or transient ischemic attack (17 %). Of the 6000 clinicians invited to participate in the survey, 201 (3.4 %) agreed to take part. Four of 11 key risk messages did not meet prespecified acceptable levels of comprehension. No prespecified levels of patient or provider knowledge were required for the retirement of the REMS, which took place on March 23, 2012 based on the sponsor's request. Conclusions: The prasugrel REMS consisted of passive educational materials whose adequacy was evaluated using highly limited, one-time, cross-sectional surveys. Our assessment adds to evidence suggesting the importance of improving the quality and impact of the FDA's post-approval activities to maximize drug safety.

Association Between Pharmacy Proximity With Cardiovascular Medication Use and Risk Factor Control in the United States.

BACKGROUND: Poor neighborhood-level access to health care, including community pharmacies, contributes to cardiovascular disparities in the United States. The authors quantified the association between pharmacy proximity, antihypertensive and statin use, and blood pressure (BP) and low-density lipoprotein cholesterol (LDL-C) among a large, diverse US cohort. METHODS AND RESULTS: A cross-sectional analysis of Black and White participants in the REGARDS (Reasons for Geographic and Racial Differences in Stroke) study during 2013 to 2016 was conducted. The authors designated pharmacy proximity by census tract using road network analysis with population-weighted centroids within a 10-minute drive time, with 5- and 20-minute sensitivity analyses. Pill bottle review measured medication use, and BP and LDL-C were assessed using standard methods. Poisson regression was used to quantify the association between pharmacy proximity with medication use and BP control, and linear regression for LDL-C. Among 16 150 REGARDS participants between 2013 and 2016, 8319 (51.5%) and 8569 (53.1%) had an indication for antihypertensive and statin medication, respectively, and pharmacy proximity data. The authors did not find a consistent association between living in a census tract with higher pharmacy proximity and antihypertensive medication use, BP control, or statin medication use and LDL-C levels, regardless of whether the area was rural, suburban, or urban. Results were similar among the 5- and 20-minute drive-time analyses. CONCLUSIONS: Living in a low pharmacy proximity census tract may be associated with antihypertensive and statin medication use, or with BP control and LDL-C levels. Although, in this US cohort, outcomes were similar for adults living in high or low pharmacy proximity census tracts.

Access to community pharmacies based on drive time and by rurality across the contiguous United States.

BACKGROUND: Considering that mail-order pharmacy use remains low in the United States, geographic accessibility of community pharmacies (pharmacy access) can have an outsized impact on a community's access to services and care, especially among rural residents. However, previous measurements of pharmacy access rely on methods that do not capture all aspects of geographic access. OBJECTIVES: This study aimed to measure pharmacy access across the contiguous United States and by rural, suburban, and urban areas using drive-time analysis and an improved methodological approach. METHODS: The 2-step floating catchment area method was used to measure pharmacy access by considering the supply capacity of pharmacies, population demand for pharmacies, and the interaction between them within a reasonable travel time range. This method is a methodologically improved approach compared with previous methods for measuring geographic access. Network analysis was used to measure drive time from the population-weighted centroids of census tracts to the geocoded location of community pharmacies. Census tract-level pharmacy access was measured using a 10- and 20-minute drive time. Census tracts were also categorized based on population per square mile as rural (< 1000), suburban (1000-3000), and urban (> 3000). RESULTS: Across the contiguous United States, 79.9% and 91.1% of census tracts had access to at least 1 pharmacy per 10,000 people within a 10- and 20-minute drive time, respectively. Rural census tracts had the lowest share of access to at least 1 pharmacy per 10,000 people compared with suburban and urban tracts and for both drive times. CONCLUSION: Community pharmacies are highly accessible health care access points, specifically in urban and suburban areas. Pharmacies should be considered to expand access to services with limited geographic accessibility such as treatment programs for opioid use disorders, primary care, and healthy foods.

Adherence and persistence of HIV pre-exposure prophylaxis use in the United States.

PURPOSE: To describe medication adherence and persistence of HIV PrEP overall and compare between sex and age groups of commercially insured individuals in the United States. METHODS: We conducted a national retrospective cohort study of the Merative MarketScan Claims Database from 2011 to 2019 to describe adherence and persistence of PrEP overall and compared between sex and age groups. High adherence was defined as ≥80% of proportion of days covered and persistence was measured in days from initiation to the first day of a 60-day treatment gap. RESULTS: A total of 29 689 new PrEP users identified. Overall adherence was high (81.9%; 95% confidence interval [CI]: 81.5%-82.3%). Females were more adherent than males (adjusted odds ratio [aOR] 1.87; 95% CI: 1.50-2.34), while those ≥45-years were less adherent than individuals <45-years (aOR 0.87: 95% CI: 0.81-0.93). More than half of individuals discontinued therapy within the first year (median 238.0 days; interquartile range 99.0-507.0 days). Females were less persistent than males (hazard ratio [HR] 1.49; 95% CI: 1.34-1.65), and people ≥45-years old were more persistent (i.e., lower risk of discontinuation) than those <45-years (HR 0.43; 95% CI: 0.33-0.55). CONCLUSIONS: These findings show adherence to daily PrEP is high among commercially insured individuals but the majority still discontinue in the first year. Future research should investigate what factors influence PrEP discontinuation among this population and ways to reduce barriers to therapy maintenance to ensure the population-level benefits of PrEP treatment.

Changes in HIV Pre-exposure Prophylaxis (PrEP) Coverage at State and County Level During the COVID-19 Pandemic in the United States.

This study quantifies the prevalence and trends in weekly PrEP coverage at the national, state and county-level, before and during the COVID-19 pandemic in the United States.We estimated weekly PrEP coverage using longitudinal individual-level pharmacy claims from IQVIA LRx for a cohort of PrEP users (N = 287,493) ages 16 to 85 years between December 29th, 2019 and November 8th, 2020. Weekly PrEP coverage was defined as PrEP use among individuals at high risk for HIV. We conducted an interrupted time series analysis to quantify changes in weekly PrEP coverage before (December 29th, 2019 - March 8th, 2020) and during (March 29th - November 8th, 2020) the COVID-19 pandemic at the national, state and county-level by county characteristics, specifically by EHE priority jurisdiction, racial/ethnic composition, and urbanity. Nationally, weekly PrEP coverage among individuals ages 16 to 85 at high risk for HIV declined by 11.5% (from 11.0% before to 9.5% during the pandemic; t = 8.02,p < 0.01). Weekly PrEP coverage declined in all states and most counties yet varied substantially across states and counties. Geographic disparities in weekly PrEP coverage were also observed between urban EHE priority counties with significantly lower rates in counties with ≥ 50% Black/Latinx population when compared to their counterparts (7.9% vs. 11.2%; t = 18.91,p < 0.01);these disparities were most pronounced in California and New York. Weekly PrEP coverage was much lower than the 25% annual coverage reported by the Centers for Disease Control and geographic disparities observed within states likely contribute to the persistent racial/ethnic disparities in new HIV diagnoses observed within those states.

Patterns of protection, infection, and detection: Country-level effectiveness of COVID-19 vaccination in reducing mortality worldwide.

Background: The relationship between COVID-19 vaccination and mortality has been established through clinical trials and other investigations at the individual level. In this study, we aimed to investigate the negative relationship between mortality and COVID-19 vaccination at country level. Study design: We conducted an exploratory, correlational, country-level analysis of open data centralized by Our World in Data concerning the cumulative COVID-19 mortality for the winter wave (October 2021-March 2022) of the pandemic as function of the vaccination rate in October 2021. Methods: We controlled variables that capture country-level social development and level of testing. We also deployed three segmentation tactics, distinguishing among countries based on their level of COVID-19 testing, age structure, and types of vaccines used. Results: Controlling for confounding factors did not highlight a statistically significant relationship between vaccination and cumulative mortality in the total country sample. Still, a strong, significant, negative relationship between cumulative mortality (log scale) and vaccination was highlighted through segmentation analysis for countries positioned at the higher end of the social development spectrum. The strongest estimate for vaccine effectiveness at ecological level was obtained for the set of countries that used Western-only vaccines. Conclusions: COVID-19 testing (log scale) has a significant and positive relationship with cumulative mortality for all subsamples, consistent with patterns of under- and overreporting of COVID-19 deaths at country level, partly driven by testing. This indicates that testing intensity should be controlled as a potential confounder in future ecological analyses of COVID-19 mortality.

Trends of nonoccupational postexposure prophylaxis in the United States.

OBJECTIVE: To describe national annual rates of nonoccupational postexposure prophylaxis (nPEP) in the United States. DESIGN: Retrospective cohort study of commercially insured individuals in the Merative MarketScan Database from January 1, 2010 to December 31, 2019. METHODS: Patients at least 13 years old prescribed nPEP per recommended Centers for Disease Control and Prevention guidelines were identified using pharmacy claims. Rates of use were described overall and stratified by sex, age group, and region. These rates were qualitatively compared to the diagnosis rates of human immunodeficiency virus (HIV) observed in the data. Joinpoint analysis identified inflection points of nPEP use. RESULTS: Eleven thousand, three hundred and ninety-seven nPEP users were identified, with a mean age of 33.7 years. Most were males (64.6%) and lived in the south (33.2%) and northeast (32.4%). The rate of nPEP use increased 515%, from 1.42 nPEP users per 100 000 enrollees in 2010 to 8.71 nPEP users per 10 000 enrollees in 2019. The comparative nPEP use rates among subgroups largely mirrored their HIV diagnosis rates, that is, subgroups with a higher HIV rate had higher nPEP use. In the Joinpoint analysis significant growth was observed from 2012 to 2015 [estimated annual percentage change (EAPC): 45.8%; 95% confidence interval (CI): 29.4 - 64.3] followed by a more moderate increase from 2015 to 2019 (EAPC 16.0%; 95% CI: 12.6-19.6). CONCLUSIONS: nPEP use increased from 2010 to 2019, but not equally across all risk groups. Further policy interventions should be developed to reduce barriers and ensure adequate access to this important HIV prevention tool.

Insulin Fills by Medicare Enrollees and Out-of-Pocket Caps Under the Inflation Reduction Act.

This study uses data from IQVIA's National Prescription Audit to assess the association of the Inflation Reduction Act's cap on cost sharing with insulin fills by Medicare beneficiaries.

Citizenship status and cost-related nonadherence in the United States, 2017-2021.

OBJECTIVE: To assess inequities in prescription medication use and subsequent cost-related nonadherence (CRN) and cost-saving strategies by citizenship status in the United States. DATA SOURCES/STUDY SETTING: National Health Interview Survey (2017-2021). STUDY DESIGN: This cross-sectional study examined noncitizen (n = 8596), naturalized citizen (n = 12,800), and US-born citizen (n = 120,195) adults. We also examined older adults (≥65 years) separately, including noncitizens without Medicare (a group of importance given their immigration-related barriers to health care access). Multiple mediation analysis was used to examine differences in CRN and determine whether economic, health care, and immigration factors explain observed inequities. PRINCIPAL FINDINGS: Noncitizens (41.9%) were less likely to use prescription medications than naturalized (60.5%) and US-born citizens (68.2%). Among prescription medication users, noncitizens (13.8%) were more likely to report CRN than naturalized (9.5%) and US-born citizens (11.0%). CRN differences between noncitizens and naturalized citizens (OR 1.38, 95% CI 1.21-1.44) and between noncitizens and US-born citizens (OR 1.23, 95% CI 1.07-1.35) were explained by insurance status and food insecurity. Only 4.9% of medication users turned to alternative therapies to lower their drug costs, but there were no substantial differences across citizenship status. More medication users requested lower-cost prescriptions (19.0%); however, noncitizens were less likely to make these requests. Older noncitizens without Medicare, of whom 23.9% requested lower-cost drugs, were an exception. Noncitizens (5.8%), particularly older noncitizens without Medicare (21.8%), were more likely to import their drugs than naturalized (3.5%) and US-born citizens (1.2%). CONCLUSIONS: Noncitizens experience a high burden of cost-related barriers to prescription medications. Efforts to reduce these inequities should focus on dismantling health care and food access barriers, regardless of citizenship status.

Pharmacy Availability of Buprenorphine for Opioid Use Disorder Treatment in the US.

This cross-sectional study assesses the availability of buprenorphine for opioid use disorder treatment at local pharmacies in the US by state and retail pharmacy chain.

Adherence to HIV Pre-Exposure Prophylaxis Testing Guidelines in the United States.

Testing guidelines for initiation of pre-exposure prophylaxis (PrEP) for human immunodeficiency virus (HIV) have been developed to ensure appropriate use of PrEP, such as among those with renal dysfunction or at high risk of seroconversion. While many studies have looked at the trends of use of PrEP in the United States, little is known about compliance with these guidelines, the quality of care of PrEP at a national level, or what provider-level factors are associated with high-quality care. We conducted a retrospective claims analysis of providers of commercially insured new users of PrEP between January 1, 2011, and December 31, 2019. Of the 4200 providers, quality of care was low, with only 6.4% having claims for ≥60% of guideline-recommended testing for their patients in the testing window for all visits. More than half of the providers did not have claims for HIV testing at initiation of PrEP and ≥40% did not for sexually transmitted infections at both initiation and follow-up visits. Even when extending the testing window, quality of care remained low. Logistic regression models found no association between provider type and high quality of care, but did find that providers with one PrEP patient were more likely to have higher quality of care than those with multiple patients for all tests [adjusted odds ratio 0.47 (95% confidence interval: 0.33-0.67)]. The study findings suggest further training and interventions, such as integrated test ordering through electronic health records, are needed to increase quality of care for PrEP and ensure appropriate monitoring of patients.

Changes in anticoagulant and antiplatelet drug supply at US hospitals before and during the COVID-19 pandemic (2018-2021).

PURPOSE: Antithrombotic agents have a role in coronavirus disease 2019 (COVID-19) treatment, but the pandemic disrupted medication supply. This study examined changes in the volume of oral and parenteral anticoagulant and antiplatelet medications at US hospitals during the pandemic. METHODS: IQVIA National Sales Perspective (NSP) data was used to determine the monthly volume of anticoagulants and antiplatelets purchased at US hospitals between January 2018 and February 2021. Mean monthly medication volumes, reported as extended units (EUs), and year-over-year changes in medication volume were determined. A single-group interrupted time series analysis was used to evaluate changes in the rate of growth of monthly medication volumes before (January 2019-February 2020) and during (March 2020-February 2021) the COVID-19 pandemic. RESULTS: Overall, there was a 43.4% decline in the total volume of anticoagulants and antiplatelets at US hospitals in March 2020, driven by a decrease in heparin volume. Mean monthly volumes decreased significantly (P < 0.05) for parenteral anticoagulants (-106,691,340 EU [95% CI, -200,033,910 to -13,348,780]), oral anticoagulants (-354,800 EU [95% CI, -612,180 to -97,420]), and parenteral antiplatelets (-391,880 EU [95% CI, -535,420 to -248,330]). During the pandemic, the monthly volume of oral anticoagulants, parenteral anticoagulants, and parenteral antiplatelets grew significantly more than in the prepandemic period. This growth was primarily seen in volumes of apixaban, argatroban, enoxaparin, heparin, eptifibatide, and tirofiban. Apixaban and heparin volumes continued a prepandemic uptrend, while argatroban and eptifibatide volumes reversed trend. CONCLUSION: Rapid changes in anticoagulant and antiplatelet volume at US hospitals during the COVID-19 pandemic highlight the need for institutional protocols to manage fluctuating medication volume demands.

Federal and State Pharmacy Regulations and Dispensing Barriers to Buprenorphine Access at Retail Pharmacies in the US.

This Viewpoint describes federal and state pharmacy regulations that may create barriers to buprenorphine access at pharmacies and suggests policy changes to address those barriers.

Tunable force sensor based on carbon nanotube fiber for fine mechanical and acoustic technologies.

Design of new smart prosthetics or robotic grippers gives a major impetus to low-cost manufacturing and rapid prototyping of force sensing devices. In this paper, we examine piezoresistive force sensors based on carbon nanotube fibers fabricated by a novel wet pulling technique. The developed sensor is characterized by an adjustable force range coupled with high sensitivity to enable the detection of a wide range of forces and displacements limited by the experimental setup only. We have demonstrated the applicability of the developed unit in tactile sensing, displacement sensing, and nanophone vibration monitoring system and evaluated its force sensing characteristics, i.e. displacement/force input and resistance/mechanical response. In the experiments it measures 0-115 N force range within 2.5 mm displacement. Moreover, the sensor demonstrates good linearity, low hysteresis, and stability when tested over 10 000 cycles. The developed sensor suits multiple applications in the field of soft and transparent sensors, nanophones, actuators, and other robotics devices for both regular and extreme environments, e.g. deep underwater and radioactive environment.

Trends in Medically Integrated Dispensing Among Oncology Practices.

PURPOSE: The integration of pharmacies with oncology practices-known as medically integrated dispensing or in-office dispensing-could improve care coordination but may incentivize overprescribing or inappropriate prescribing. Because little is known about this emerging phenomenon, we analyzed historical trends in medically integrated dispensing. METHODS: Annual IQVIA data on oncologists were linked to 2010-2019 National Council for Prescription Drug Programs pharmacy data; data on commercially insured patients diagnosed with any of six common cancer types; and summary data on providers' Medicare billing. We calculated the national prevalence of medically integrated dispensing among community and hospital-based oncologists. We also analyzed the characteristics of the oncologists and patients affected by this care model. RESULTS: Between 2010 and 2019, the percentage of oncologists in practices with medically integrated dispensing increased from 12.8% to 32.1%. The share of community oncologists in dispensing practices increased from 7.6% to 28.3%, whereas the share of hospital-based oncologists in dispensing practices increased from 18.3% to 33.4%. Rates of medically integrated dispensing varied considerably across states. Oncologists who dispensed had higher patient volumes (P < .001) and a smaller share of Medicare beneficiaries (P < .001) than physicians who did not dispense. Patients treated by dispensing oncologists had higher risk and comorbidity scores (P < .001) and lived in areas with a higher % Black population (P < .001) than patients treated by nondispensing oncologists. CONCLUSION: Medically integrated dispensing has increased significantly among oncology practices over the past 10 years. The reach, clinical impact, and economic implications of medically integrated dispensing should be evaluated on an ongoing basis.