COVID-19 unemployment and access to statin medications in the United States.

Objective: To quantify the effect of the unemployment created by COVID-19 on access to (sales of) statin drugs in the United States population. Methods: Approximately half a billion transactions for statin drugs in the United States between January 2018 and September 2020 are analyzed. We studied the potential causal relation between abnormal levels of unemployment during the first wave of COVID-19 in the U.S. and abnormal levels of sales of statin products (both variables defined at the state/week level). Variables are analyzed using the Two-Stage Least Squares (2SLS) method, which exploits comparisons of statin sales between states where, given the occupational distribution of their workforce, unemployment was more structurally vulnerable to mobility restrictions derived from COVID-19 against states where it was less structurally vulnerable. Results: While we do not find unemployment effects on statin sales on most of the population, our estimates link COVID-fueled unemployment with a sharp sales reduction among Medicaid-insured populations, particularly those in working age. For the period between March and August of 2020, these estimates imply a 31% drop of statin sales among this population. Discussion: COVID-fueled unemployment may have had a negative and significant effect on access to statin populations among Medicaid-insured populations.

Diabetes medications and associations with Covid-19 outcomes in the N3C database: A national retrospective cohort study.

BACKGROUND: While vaccination is the most important way to combat the SARS-CoV-2 pandemic, there may still be a need for early outpatient treatment that is safe, inexpensive, and currently widely available in parts of the world that do not have access to the vaccine. There are in-silico, in-vitro, and in-tissue data suggesting that metformin inhibits the viral life cycle, as well as observational data suggesting that metformin use before infection with SARS-CoV2 is associated with less severe COVID-19. Previous observational analyses from single-center cohorts have been limited by size. METHODS: Conducted a retrospective cohort analysis in adults with type 2 diabetes (T2DM) for associations between metformin use and COVID-19 outcomes with an active comparator design of prevalent users of therapeutically equivalent diabetes monotherapy: metformin versus dipeptidyl-peptidase-4-inhibitors (DPP4i) and sulfonylureas (SU). This took place in the National COVID Cohort Collaborative (N3C) longitudinal U.S. cohort of adults with +SARS-CoV-2 result between January 1 2020 to June 1 2021. Findings included hospitalization or ventilation or mortality from COVID-19. Back pain was assessed as a negative control outcome. RESULTS: 6,626 adults with T2DM and +SARS-CoV-2 from 36 sites. Mean age was 60.7 +/- 12.0 years; 48.7% male; 56.7% White, 21.9% Black, 3.5% Asian, and 16.7% Latinx. Mean BMI was 34.1 +/- 7.8kg/m2. Overall 14.5% of the sample was hospitalized; 1.5% received mechanical ventilation; and 1.8% died. In adjusted outcomes, compared to DPP4i, metformin had non-significant associations with reduced need for ventilation (RR 0.68, 0.32-1.44), and mortality (RR 0.82, 0.41-1.64). Compared to SU, metformin was associated with a lower risk of ventilation (RR 0.5, 95% CI 0.28-0.98, p = 0.044) and mortality (RR 0.56, 95%CI 0.33-0.97, p = 0.037). There was no difference in unadjusted or adjusted results of the negative control. CONCLUSIONS: There were clinically significant associations between metformin use and less severe COVID-19 compared to SU, but not compared to DPP4i. New-user studies and randomized trials are needed to assess early outpatient treatment and post-exposure prophylaxis with therapeutics that are safe in adults, children, pregnancy and available worldwide.

COVID-19 vaccine hesitancy among rural Oklahomans.

INTRODUCTION: COVID-19 vaccination is widely recommended as a prevention strategy; however, vaccine uptake is disproportionately lower among rural Americans compared to their urban counterparts. Development of public health activities to address the rural-urban vaccine gap requires an understanding of determinants of vaccine hesitation. The present study explores perceptions of and barriers to COVID-19 vaccination among rural Oklahomans. METHODS: Between March and May 2021, 222 residents, unvaccinated for COVID-19, within rural Oklahoma counties completed a cross-sectional, online questionnaire to qualitatively assess perceptions, benefits, and concerns regarding getting vaccinated for COVID-19. RESULTS: Approximately two-fifths of rural respondents in the present study were hesitant to get vaccinated, even when a vaccine was made available to them. Major factors included limited knowledge and understanding about the vaccine, including potential side-effects and long-term complications, as well as skepticism surrounding COVID-19 vaccine development and efficacy. Among the potential perceived benefits of vaccination were protecting the health of vulnerable individuals and the ability to return to normal day-to-day activities. CONCLUSION: Increases in COVID-19 cases and deaths in rural areas are expected to continue as new variants are introduced within communities. The present findings highlight the need for the development of culturally tailored vaccine information, to be disseminated by local leaders within rural communities.

Ambulatory Fluoroquinolone Use in the United States, 2015-2019.

BACKGROUND: Frequently used fluoroquinolones have been subject to increasing safety concerns and regulatory alerts. This study characterized ambulatory fluoroquinolone utilization in the United States and evaluated the impact of 2016 Food and Drug Administration (FDA) safety advisories on its use. METHODS: We used IQVIA's National Disease and Therapeutic Index to quantify adult outpatient fluoroquinolone use ("treatment visits"). Descriptive statistics and segmented regression were used to report trends and quantify the varied use before and after FDA's 2016 alerts. RESULTS: Between 2015 to 2019, fluoroquinolone use decreased by 26.7% (18.7 million treatment visits in 2015 to 13.7 million treatment visits in 2019). Annual use declined by 44%, 24%, and 24% for respiratory, urogenital, and gastrointestinal conditions, respectively; and by 66% among providers ≤44 years old vs negligible decline among those ≥65 years old. Before 2016 FDA advisories, there were approximately 4.8 million fluoroquinolone treatment visits/quarter, which had a statistically significant immediate drop by 641035 visits (95% confidence interval [CI], -937368 to -344702; P=.000) after FDA's 2016 advisories. A statistically significant difference of approximately 45000 visits/quarter (95% CI, -85956 to -3122; P=.036) was observed after the advisories. CONCLUSIONS: Large reductions in ambulatory fluoroquinolone use in the United States have coincided with increasing evidence of safety concerns and FDA advisories. However, fluoroquinolone use varies significantly based on patient and provider characteristics, suggesting heterogeneous effects of emerging risks on clinical practice.

Active learning-based framework for optimal reaction mechanism selection from microkinetic modeling: a case study of electrocatalytic oxygen reduction reaction on carbon nanotubes.

The elucidation of complex electrochemical reaction mechanisms requires advanced models with many intermediate reaction steps, which are governed by a large number of parameters like reaction rate constants and charge transfer coefficients. Overcomplicated models introduce high uncertainty in the choice of the parameters and cannot be used to obtain meaningful insights on the reaction pathway. We describe a new framework of optimal reaction mechanism selection based on the mean-field microkinetic modeling approach (MF-MKM) and adaptive sampling of model parameters. The optimal model is selected to provide both the accurate fitting of experimental data within the experimental error and low uncertainty of model parameters choice. Generally, this approach can be applied for any complex heterogeneous electrochemical reaction. We use the "2e-" electrocatalytic oxygen reduction reaction (ORR) on carbon nanotubes (CNTs) as a representative example of a sufficiently complex reaction. Rotating disk electrode (RDE) experimental data for both ORR in O2-saturated 0.1 M KOH solution and hydrogen peroxide oxidation/reduction reaction (HPRR/HPOR) in Ar-purged 0.1 M KOH solution with different HO2- concentrations were used to show the dependence of the model parameters uniqueness on the completeness of the experimental dataset. It is demonstrated that the optimal reaction mechanism for ORR on CNT and available experimental data consists of O2 adsorption step on the electrode surface and effective step of two-electron reduction to HO2- combined with its desorption from the electrode. The low uncertainty of estimated model parameters is provided only within the 2-step model being applied to the full available experimental dataset. The assessment of elementary step mechanisms on electro-catalytic materials including carbon-based electrodes requires more diverse experimental data and/or higher precision of experimental measurements to facilitate more precise microkinetic modeling of more complex reaction mechanisms.

Fairness in drug prices: do economists think differently from the public?

Using dual-entitlement theory as the guide, we conducted a survey of economists from the National Bureau of Economic Research asking them a series of questions about the fairness of drug prices in the United States. Public opinion surveys have repeatedly shown that the public perceives drug prices to be unfair, but economists trained in laws of supply and demand may have different perceptions. Three hundred and ten senior economists responded to our survey. Forty-five percent agreed that drug prices were unfair when people, specifically low-income individuals, could not afford their prescription medications. Sixty-five percent oppose a dollar threshold, or upper limit, on drug prices. The economists recommend the most promising policy change would be to provide the government additional negotiating power and price controls would moderately impact investment in pharmaceutical research and development.

Anion-Based Pseudocapacitance of the Perovskite Library La1- xSr xBO3-δ (B = Fe, Mn, Co).

We have synthesized a library of perovskite oxides with the composition La1- xSr xBO3-δ ( x = 0-1; B = Fe, Mn, Co) to systematically study anion-based pseudocapacitance. The electrochemical capacitance of these materials was evaluated by cyclic voltammetry and galvanostatic charging/discharging in 1 M KOH. We find that greater oxygen vacancy content (δ) upon systematic incorporation of Sr2+ linearly increases the surface-normalized capacity with a slope controlled by the B-site element. La0.2Sr0.8MnO2.7 exhibited the highest specific capacitance of 492 F g-1 at 5 mV s-1 relative to the Fe and Co oxides. In addition, the first all-perovskite asymmetric pseudocapacitor has been successfully constructed and characterized in neutral and alkaline aqueous electrolytes. We demonstrate that the asymmetric pseudocapacitor cell voltage can be increased by widening the difference between the B-site transition metal redox potentials in each electrode resulting in a maximum voltage window of 2.0 V in 1 M KOH. Among the three pairs of asymmetric pseudocapacitors constructed from SrCoO2.7, La0.2Sr0.8MnO2.7, and brownmillerite (BM)-Sr2Fe2O5, the BM-Sr2Fe2O5//SrCoO2.7 combination performed the best with a high energy density of 31 Wh kg-1 at 450 W kg-1 and power density of 10 000 W kg-1 at 28 Wh kg-1.

Exceptional electrocatalytic oxygen evolution via tunable charge transfer interactions in La0.5Sr1.5Ni1-xFexO4±Î´ Ruddlesden-Popper oxides.

The electrolysis of water is of global importance to store renewable energy and the methodical design of next-generation oxygen evolution catalysts requires a greater understanding of the structural and electronic contributions that give rise to increased activities. Herein, we report a series of Ruddlesden-Popper La0.5Sr1.5Ni1-xFexO4±Î´ oxides that promote charge transfer via cross-gap hybridization to enhance electrocatalytic water splitting. Using selective substitution of lanthanum with strontium and nickel with iron to tune the extent to which transition metal and oxygen valence bands hybridize, we demonstrate remarkable catalytic activity of 10 mA cm-2 at a 360 mV overpotential and mass activity of 1930 mA mg-1ox at 1.63 V via a mechanism that utilizes lattice oxygen. This work demonstrates that Ruddlesden-Popper materials can be utilized as active catalysts for oxygen evolution through rational design of structural and electronic configurations that are unattainable in many other crystalline metal oxide phases.

Methadone Prescribing and Overdose and the Association with Medicaid Preferred Drug List Policies - United States, 2007-2014.

Drug overdose is a leading cause of injury death in the United States; 47,055 fatal drug overdoses were reported in 2014, a 6.5% increase from the previous year (1), driven by opioid use disorder (2,3). Methadone is an opioid prescribed for pain management and is also provided through opioid treatment programs to treat opioid use disorders. Because methadone might remain in a person's system long after the pain-relieving benefits have been exhausted, it can cause slow or shallow breathing and dangerous changes in heartbeat that might not be perceived by the patient (4,5). In December 2006, the Food and Drug Administration issued a Public Health Advisory that alerted health care professionals to reports of death and life-threatening adverse events, such as respiratory depression and cardiac arrhythmias, in patients receiving methadone (4); in January 2008, a voluntary manufacturer restriction limited distribution of the 40 mg formulation of methadone.* CDC analyzed state mortality and health care data and preferred drug list (PDL) policies to 1) compare the percentage of deaths involving methadone with the rate of prescribing methadone for pain, 2) characterize variation in methadone prescribing among payers and states, and 3) assess whether an association existed between state Medicaid reimbursement PDL policies and methadone overdose rates. The analyses found that, from 2007 to 2014, large declines in methadone-related overdose deaths occurred. Prescriptions for methadone accounted for 0.85% of all opioid prescriptions for pain in the commercially insured population and 1.1% in the Medicaid population. In addition, an association was observed between Medicaid PDLs requiring prior authorization for methadone and lower rates of methadone overdose among Medicaid enrollees. PDL policies requiring prior authorization might help to reduce the number of methadone overdoses.

Use of advance directives for high-risk operations: a national survey of surgeons.

OBJECTIVE: To characterize surgeons' beliefs and approach to the use of an advance directive in the decision to perform high-risk operations. BACKGROUND: Prior work suggests many surgeons regard advance directives as antithetical to the goals of surgical therapy, yet little is known about surgeons' approach to high-risk operations for patients with directives limiting postoperative care. METHODS: We sent a self-administered survey by US mail to 2100 randomly selected vascular, neurologic, and cardiothoracic surgeons. We used stepwise logistic regression to determine the relationship between explanatory variables and: (1) how often surgeons discuss advance directives preoperatively, and (2) how advance directives limiting postoperative life-supporting therapy influence the decision to operate. RESULTS: The adjusted response rate was 55%. All surgeons reported discussing the potential for unanticipated outcomes and nearly all (95%) discussed the need for postoperative life-supporting therapy. More than four-fifths (81%) reported discussing patient preferences to limit postoperative life-supporting therapy during informed consent. Approximately one half of respondents (52%) either sometimes or always discuss advance directives before surgery, with younger physicians less likely to do so than more experienced surgeons (odds ratio [OR] = 0.46, 95% confidence intervals [CI] = 0.06-0.85). More than one half (54%) of surgeons reported they would decline to operate on patients who have an advance directive limiting postoperative life-supporting therapy. CONCLUSIONS: Many surgeons do not routinely discuss advanced directives preoperatively and more than one half reported they would decline to operate on patients whose directives limit postoperative care. This practice may limit the expression of patient preferences during decision making for high-risk operations.