The impact of a statewide insulin copay cap policy for insured patients with diabetes in Utah.

BACKGROUND: Insulin affordability is a huge concern for patients with diabetes in the United States. On March 30, 2020, Utah signed House Bill 207 into law, aimed at capping copayments for insulin at $30 for a 30-day supply. The bill was enacted on January 1, 2021. OBJECTIVE: To assess patient basal insulin adherence, out-of-pocket costs, health plan costs, total costs on insulin, and hemoglobin A1c (A1c) in prepolicy vs postpolicy periods. METHODS: This study is a retrospective analysis using data from a regional health plan in Utah from October 1, 2019, to September 30, 2021. Inclusion criteria were fully enrolled members of all ages, under commercial insurance, with at least 1 fill for any type of insulin in both the preperiod and the postperiod. Adherence was measured by proportion of days covered (PDC). Paired t-tests and Wilcoxon sign rank tests were conducted to compare the health and economic outcomes. RESULTS: Out of 24,150 commercially insured individuals, a total of 244 patients were included. Across all 244 patients, there was a significant decline in monthly median out-of-pocket costs of insulin by 58.5% (P < 0.001), whereas the monthly median health plan costs of insulin increased by 22.0% (P < 0.001). The total monthly costs of insulin (the sum of out-of-pocket and health plan costs) were unchanged (P = 0.115). Only 74 patients with enough basal insulin fills in both periods were included in the analysis for PDC changes. PDC change was not statistically significant (P = 0.43). Among the 74 patients with PDC calculations, 29 patients had A1c recorded in both periods. The change in A1c was not statistically significant (P = 0.23). CONCLUSIONS: An insulin copayment max of $30 in Utah demonstrated lower patient out-of-pocket costs, subsidized by the health plan. PDC did not change, and HbA1c did not improve. An assessment of a longer period and on a larger population is needed.

Bicarbonate as a predictor of successful insulin transition in critically ill patients with diabetic ketoacidosis: A retrospective cohort study.

BACKGROUND: Treatment of diabetic ketoacidosis with intravenous insulin is effective but resource intensive. Treatment guidelines recommend transitioning to subcutaneous insulin when the anion gap closes, but transition failures due to recrudescent ketoacidosis are common despite adherence to treatment protocols following such guidance. STUDY OBJECTIVE: The primary objective of our study was to evaluate the ability of serum bicarbonate levels of ≤16 mEq/L to predict intravenous to subcutaneous transition failures among those with a normal anion gap at the time of transition. DESIGN AND SETTING: This retrospective cohort study evaluated critically ill adult patients with a primary diagnosis of diabetic ketoacidosis. Historical patient data were obtained by manual chart review. The primary outcome was transition failure, defined as the re-initiation of intravenous insulin within 24 h of transitioning to subcutaneous insulin. Odds ratios were calculated using generalized estimating equations with a logit link and weighted by standardized inverse probability weights to assess the predictive value of serum bicarbonate levels. MAIN RESULTS: The primary analysis included 93 patients with a total of 118 distinct transitions. In the adjusted analysis, patients whose anion gap had normalized but had a serum bicarbonate of ≤16 mEq/L were significantly more likely to experience a transition failure (odds ratio = 4.74, 95% confidence interval: 1.24-18.1, p = 0.02). The results of the unadjusted analysis were similar. CONCLUSIONS: In patients with a normal anion gap at the time of insulin transition, serum bicarbonate levels of ≤16 mEq/L were associated with significantly increased odds of transition failure.

Understanding patient cost-sharing thresholds for diabetes treatment attributes via a discrete choice experiment.

BACKGROUND: The process used to prefer certain products across drug classes for diabetes is generally focused on comparative effectiveness and cost. However, payers rarely tie patient preference for treatment attributes to formulary management resulting in a misalignment of value defined by providers, payers, and patients. OBJECTIVES: To explore patients' willingness to pay (WTP) for the predetermined high-value and low-value type 2 diabetes mellitus (T2DM) treatments within a health plan. METHODS: A cross-sectional discrete choice experiment (DCE) survey was used to determine patient preference for the benefit, risk, and cost attributes of T2DM treatments. A comprehensive literature review of patient preference studies in diabetes and a review of guidelines and medical literature identified study attributes. Patients and diabetes experts were interviewed and instructed to identify, prioritize, and comment on which attributes of diabetes treatments were most important to T2DM patients. The patients enrolled in a health plan were asked to respond to the survey. A multinomial logit model was developed to determine the relative importance and the patient's WTP of each attribute. The patients' relative values based on WTPs for T2DM treatments were calculated and compared with the treatments by a health plan. RESULTS: A total of 7 attributes were selected to develop a web-based DCE questionnaire survey. The responses from a total of 58 patients were analyzed. Almost half (48.3%) of the respondents took oral medications and injections for T2DM. The most prevalent side effects due to diabetes medications were gastrointestinal (43.1%), followed by weight gain (39.7%) and nausea (32.8%). Patients were willing to pay more for treatments with proven cardiovascular benefit and for the risk reduction of hospitalization from heart failure. On the other hand, they would pay less for treatments with higher gastrointestinal side effects. Patients were willing to pay the most for sodium-glucose cotransporter 2 inhibitor and glucagon-like peptide 1 receptor agonist agents and the least for dipeptidyl peptidase-4 inhibitors and thiazolidinediones. CONCLUSIONS: This study provides information to better align patient, provider, and payer preferences in both benefit design and value-based formulary strategy for diabetes treatments. A preferred placement of treatments with cardiovascular benefits and lower adverse gastrointestinal side effects may lead to increased adherence to medications and improved clinical outcomes at a lower overall cost to both patients and their health plan. DISCLOSURES: This study was supported by a grant from the PhRMA Foundation.

Exploration of Race and Ethnicity, Sex, Sport-Related Concussion, Depression History, and Suicide Attempts in US Youth.

Importance: Racial, ethnic, and sex disparities for concussion incidence and suicide attempts in youth have been reported, but data on the interaction of these variables in a large national data set are lacking. Understanding how race and ethnicity interact with sex and concussion to influence suicide attempts could yield critical information on the sociocultural impact of brain injury and mental health in US youth. Objective: To examine the associations of concussion history, race and ethnicity, and sex with reported suicide attempts among adolescents. Design, Setting, and Participants: This population-based cross-sectional cohort study used data from US Youth Risk Behavior Surveillance System (YRBSS) survey respondents between 2017 and 2019. Data were analyzed from May 2021 to January 2022. Exposures: Respondents reported sport- or recreation-related concussion (yes or no), depression (yes or no), and suicide attempt (yes or no) over the previous 12 months, along with race and ethnicity (categorized as American Indian or Alaska Native, Asian, Black, Hispanic/Latino, multiracial, Native Hawaiian or other Pacific Islander, and White), and sex (male or female). Main Outcomes and Measures: Two Chi-Square Automatic Interaction Detection (CHAID) decision tree models were built. The first was suicide attempt with depression history (SA-DEP), the second was suicide attempt without depression history (SA-NO DEP). CHAID uses risk factors (eg, number of concussions, race and ethnicity, sex) to divide the study sample into a series of subgroups that are nested within each other. Risk ratios (RRs) and 95% CIs were calculated for each subgroup to provide effect estimates. Results: A total of 28 442 youths aged up to 18 years (mean [SD] age, 14.6 [3.0] years; 14 411 [50.7%] female) responded to the survey. The CHAID decision trees revealed a complex interaction between race, sex, and concussion history for attempting suicide, which differed by depression history (overall accuracy, 84.4%-97.9%). Overall, depression history was the variable most strongly associated with SA (adjusted odds ratio, 11.24; 95% CI, 10.27-12.29). Concussion was the variable most strongly associated with SA-DEP (RR, 1.31; 95% CI, 1.20-1.51; P < .001). Black, Hispanic/Latino, or multiracial race and ethnicity were associated with increased risk for SA-DEP compared with others (RR, 1.59; 95% CI, 1.38-1.84; P < .001). American Indian or Alaska Native, Black, and Hispanic/Latino race and ethnicity were associated with increased risk for SA-NO DEP (RR, 1.89; 95% CI, 1.54-2.32; P < .001) compared with the remaining population. Conclusions and Relevance: These findings suggest that clinicians should consider race, ethnicity, and sex when evaluating the role of sport- or recreation-related concussion on suicide risk among US youth.

Microglial knockdown does not affect acute withdrawal but delays analgesic tolerance from oxycodone in male and female C57BL/6J mice.

Opioid Use Disorder (OUD) affects approximately 8%-12% of the population. In dependent individuals, abrupt cessation of opioid taking results in adverse withdrawal symptoms that reinforce drug taking behavior. Considerable unmet clinical need exists for new pharmacotherapies to treat opioid withdrawal as well as improve long-term abstinence. The neuroimmune system has received much scientific attention in recent years as a potential therapeutic target to combat various neurodegenerative and psychiatric disorders including addiction. However, the specific contribution of microglia has not been investigated in oxycodone dependence. Chronic daily treatment with the CSF1R inhibitor Pexidartinib (PLX3397) was administered to knockdown microglia expression and evaluate consequences on analgesia and on naloxone induced withdrawal from oxycodone. In vivo results indicated that an approximately 40% reduction in brain IBA1 staining was achieved in the PLX treatment group, which was associated with a delay in the development of analgesic tolerance to oxycodone and maintained antinociceptive efficacy. Acute withdrawal behavioral symptoms, brain astrocyte expression, and levels of many neuroinflammatory markers were not affected by PLX treatment. KC/GRO (also known as CXCL1) was significantly enhanced in the somatosensory cortex in oxycodone-treated mice receiving PLX. Microglial knock-down did not affect the expression of naloxoneinduced opioid withdrawal but affected antinociceptive responsivity. The consequences of increased KC/GRO expression within the somatosensory cortex due to microglial reduction during opioid dependence are unclear but may be important for neural pathways mediating opioid-induced analgesia.

A commentary on ethical decision-making in the pharmacy profession and the APhA Code of Ethics.

The American Pharmacists Association Code of Ethics ("Code") was established in 1852 and has undergone 5 modifications, most recently in 1994. As point of care shifts from product to cognitive clinical service, pharmacists are expected to encounter an increasing quantity and complexity of ethical and moral dilemmas. In view of this professional transformation and current worldwide challenges, this seems an appropriate time for dialogue on a modification of the Code. The 3 important questions before the profession are as follows: (1) Is the scope of available ethical guidance adequate? (2) Are pharmacists competent in ethical decision-making? (3) Is current pharmacy education and training adequately preparing students for ethical decision-making? The first question is included as part of the Pharmacy Law, Ethics, and Risk course at the University of Utah College of Pharmacy. The following commentary is based on a student's persuasive paper that the Code should remain unmodified owing to the following factors: greater detail does not ensure improved guidance, and modification may lead to confusion in professional role and responsibilities and may not consider patients' values and preferences in decision-making. To improve ethical decision-making in the pharmacy profession, this commentary further suggests that questions 2 and 3 are key to facilitating improved readiness and competency in pharmacists' ethical decision-making. Pharmacy students should be given a more thorough education in ethics, and practicing pharmacists should continually expand their knowledge and continued professional development in ethics.

Concussion Symptom Cutoffs for Identification and Prognosis of Sports-Related Concussion: Role of Time Since Injury.

BACKGROUND: Symptom reporting with scales such as the Post-Concussion Symptom Scale (PCSS) is one of the most sensitive markers of concussed status and/or recovery time, It is known that time from injury until initial clinic visit affects symptom presentation and recovery outcomes, but no study to date has evaluated changes in clinical cutoff scores for the PCSS based on earlier versus later clinical presentation postconcussion. PURPOSE: To evaluate if time since injury after sports-related concussion (SRC) affects clinical cutoff scores for total PCSS and PCSS factors in differentiating athletes with SRC from healthy controls and predicting prolonged recovery (>30 days) after SRC. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: A chart review was conducted of clinical data from patients with SRC (age, 13-25 years; n = 588; female, n = 299) who presented to concussion specialty clinics. Participants were categorized on the basis of time from injury: early (≤7 days; n = 348) and late (8-21 days; n = 240). Outcomes were total symptom severity (ie, total PCSS score) and total score for each of 4 symptom factors (cognitive/migraine/fatigue [CMF], affective, sleep, and somatic). Area under the curve (AUC) analyses were conducted using the Youden index to optimize sensitivity and specificity cutoffs. RESULTS: In the early group, the CMF factor (cutoff, ≥7; AUC = 0.944), affective factor (cutoff, ≥1; AUC = 0.614), and total PCSS (cutoff, ≥7; AUC = 0.889) differentiated athletes with SRC from controls. In the late group, the CMF factor cutoff was reduced (cutoff, ≥4; AUC = 0.945), while the total PCSS score (cutoff, ≥7; AUC = 0.892), affective factor (cutoff, ≥1; AUC = 0.603), and sleep factor (cutoff, ≥1; AUC = 0.609) remained the same. In the early cohort, the CMF factor was the strongest predictor of protracted recovery (cutoff, ≥23; AUC = 0.717), followed by the total PCSS (cutoff, ≥39; AUC = 0.695) and affective factor (cutoff, ≥2; AUC = 0.614). The affective factor (cutoff, ≥1; AUC = 0.642) and total PCSS (cutoff, ≥35; AUC = 0.592) were significant predictors in the late cohort, but the cutoff threshold was reduced. CONCLUSION: The findings indicate that PCSS symptom clinical cutoffs for identifying injury and recovery prognosis change on the basis of time since injury. Specifically, the combination of CMF, affective, and sleep factors is the best differentiator of athletes with SRC from controls regardless of time since injury. Furthermore, the CMF factor is the most robust predictor of prolonged recovery if the patient is within 1 week of SRC, whereas the affective factor is the most robust predictor of prolonged recovery if the patient is within 2 to 3 weeks of SRC.

Bupropion for attention deficit hyperactivity and comorbid disorders.

Bupropion is a unique antidepressant with noradrenergic and to a lesser extent dopaminergic effects. These have led investigators to explore bupropion's efficacy in attention deficit hyperactivity disorders, which are believed to be related to aberrations in catecholamines. An expanding body of research has demonstrated bupropion's efficacy in attention deficit hyperactivity disorders over the lifespan. Despite early reports of seizures in select samples, bupropion is generally well-tolerated. While stimulants remain the first-line pharmacological treatments for attention deficit hyperactivity disorders, bupropion offers promise as a medication that treats not only attention deficit hyperactivity disorders, but also common comorbid disorders, including unipolar and bipolar depression, anxiety and substance abuse.