"Positive Kidney Health": Implementation and design of a pharmacist-led intervention for patients at risk for development or progression of chronic kidney disease.

BACKGROUND: Patients with early chronic kidney disease (CKD) or underlying risk factors are often unaware of their kidney test results, common causes of CKD, and ways to lower risk of disease onset/progression. OBJECTIVE: To test feasibility of a pharmacist-led intervention targeting patient education and risk factors in patients with early CKD and those at risk for CKD. PRACTICE DESCRIPTION: Ambulatory care pharmacists in community-based primary care clinics delivered kidney health education, ordered labs, and recommended medication adjustments. PRACTICE INNOVATION: We identified patients with a moderate rate of decline (≥2 mL/min/1.73 m2 per year) in estimated glomerular filtration (eGFR) at-risk for CKD or early stage CKD. An interactive workbook was designed to teach patients about kidney test results and self-management of risk factors including hypertension, type 2 diabetes, cigarette smoking, and chronic oral nonsteroidal anti-inflammatory drug use. EVALUATION METHODS: Outcomes included visit uptake, completion of annual albuminuria screening, and initiation of guideline-directed medications for CKD. Patients were surveyed pre- and post-intervention for kidney health knowledge and perceptions regarding pharmacist-provided information. RESULTS: Our sample of 20 participants had a mean eGFR of 59 mL/min/1.73 m2 and the mean eGFR decline was -4.6 mL/min/1.73 m2 per year. There were 47 visits during the pilot period from February 2021 to October 2021. Thirteen patients were missing albuminuria screening within 12 months; 2 of 9 patients with resulting labs had new microalbuminuria and were started on renoprotective medications. Patients had improved understanding of their kidney function test results and most did not consider the information scary or confusing. CONCLUSION: Barriers to enrollment included fewer participants with multiple risk factors for CKD. The pharmacists were able to engage patients in learning the importance of monitoring and self-management of kidney health. A collaborative practice agreement may enhance a similar intervention that includes initiation of renoprotective medications.

A randomized controlled trial of a shared decision making intervention for diabetes prevention for women with a history of gestational diabetes mellitus: The Gestational diabetes Risk Attenuation for New Diabetes (GRAND study).

BACKGROUND: Gestational diabetes mellitus (GDM) is a risk factor for the development of type 2 diabetes. Metformin and lifestyle change through a Diabetes Prevention Program (DPP) are equally effective in preventing diabetes in patients with a GDM history, so women can choose a strategy based on their preferences. This study aims to test whether shared decision making (SDM) can help women with a history of GDM increase adoption of evidence-based strategies and lose weight to lower their risk of incident diabetes in real-world settings. METHODS: This pragmatic randomized controlled trial (RCT) will test the effectiveness of SDM for diabetes prevention among 310 overweight/obese women with a history of GDM and prediabetes from two large health care systems (n = 155 from UCLA Health and n = 155 from Intermountain Healthcare). The primary outcome is the proportion of participants who lose ≥5% body weight at 12 months. Secondary outcomes include uptake of DPP and/or metformin and other patient-reported outcomes such as patient activation and health-related quality of life. Rates of GDM in a subsequent pregnancy will be an exploratory outcome. A descriptive analysis of costs related to SDM implementation will also be conducted. CONCLUSION: This is the first RCT to examine the effectiveness of SDM on weight loss, lifestyle change and/or metformin use, and other patient-reported outcomes in participants with a GDM history at risk of developing diabetes. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03766256. Registered on 6 December 2018.

Association of Type 2 Diabetes Risk Perception With Interest in Diabetes Prevention Strategies Among Women With a History of Gestational Diabetes.

Objectives: The aims of this study were to identify predictors of perception of type 2 diabetes risk in women with a history of gestational diabetes mellitus (GDM) and to determine factors associated with interest in evidence-based strategies for type 2 diabetes prevention. Research Design and Methods: We surveyed women with a history of GDM who had not progressed to type 2 diabetes from a large academic medical center. We used multivariate logistic regression to assess predictors of high levels of perception of type 2 diabetes risk. We also tested associations between risk perception and interest in a lifestyle change program and/or metformin therapy. Results: In our diverse sample of 264 women, 28% were unaware that GDM is a risk factor for incident type 2 diabetes after pregnancy, and 48% believed their personal risk of type 2 diabetes was low. In multivariate analyses, family history of diabetes (odds ratio [OR] 2.2, 95% CI 1.2-4.4) and knowledge of GDM as a risk factor for incident type 2 diabetes (OR 4.5, 95% CI 2.1-9.8) were significant predictors of greater perception of type 2 diabetes risk. Women with higher risk perception were more likely to express interest in a lifestyle change program compared with women with lower risk perception (OR 2.4, 95% CI 1.3-4.5). Conclusion: Although some women are aware that GDM is a risk factor for incident type 2 diabetes, many still perceive their own risk of developing type 2 diabetes as low. Higher risk perception predicted interest in an evidence-based diabetes prevention program, highlighting the importance of personalized risk assessment and communication about risk for women who have had GDM.

Differences in Weight Loss by Race and Ethnicity in the PRIDE Trial: a Qualitative Analysis of Participant Perspectives.

BACKGROUND: Many Diabetes Prevention Program (DPP) translation efforts have been less effective for underresourced populations. In the cluster-randomized Prediabetes Informed Decision and Education (PRIDE) trial, which evaluated a shared decision-making (SDM) intervention for diabetes prevention, Hispanic and non-Hispanic Black participants lost less weight than non-Hispanic White participants at 12-month follow-up. OBJECTIVE: To explore perspectives about weight loss from PRIDE participants of different racial and ethnic groups. PARTICIPANTS: Sample of participants with prediabetes who were randomized to the PRIDE intervention arm (n=24). APPROACH: We conducted semi-structured interviews within three groups stratified by DPP participation and % weight loss at 12 months: (DPP+/WL+, enrolled in DPP and lost >5% weight; DPP+/WL-, enrolled in DPP and lost <3% weight; DPP-/WL-, did not enroll in DPP and lost <3% weight). Each group was further subdivided on race and ethnicity (non-Hispanic Black (NHB), non-Hispanic White (NHW), Hispanic). Interviews were conducted on Zoom and transcripts were coded and analyzed with Dedoose. KEY RESULTS: Compared to NHW participants, Hispanic and NHB participants more often endorsed weight loss barriers of limited time to make lifestyle changes due to long work and commute hours, inconvenient DPP class locations and offerings, and limited disposable income for extra weight loss activities. Conversely, facilitators of weight loss regardless of race and ethnicity included retirement or having flexible work schedules; being able to identify convenient DPP classes; having a strong, positive support system; and purchasing supplementary resources to support lifestyle change (e.g., gym memberships, one-on-one activity classes). CONCLUSIONS: We found that NHB and Hispanic SDM participants report certain barriers to weight loss more commonly than NHW participants, particularly barriers related to limited disposable income and/or time constraints. Our findings suggest that increased lifestyle change support and flexible program delivery options may be needed to ensure equity in DPP reach, participant engagement, and outcomes.

Educational Attainment, Decision-Making Preferences, and Interest in Evidence-Based Diabetes Prevention among Women with a History of Gestational Diabetes Mellitus.

Background: The Diabetes Prevention Program (DPP) showed that lifestyle change or metformin is equally efficacious in preventing diabetes in women who have had gestational diabetes mellitus (GDM). Few studies have investigated the relationship between education and willingness to engage in either intervention and between education and preferred decision-making style. Methods: Within a large health system, we surveyed insured women 18-64 years old with a history of GDM, identified through the electronic health record. We estimated preference for decision-making style and interest in DPP lifestyle change and/or metformin by educational level, using multivariate logistic regression models controlling for age, race, and ethnicity. Results: Our sample (n = 264) was 36% Latino, 29% Asian, 28% non-Latino white, and 5% African American, with a mean age of 37 years. In terms of education, 31% had a postgraduate degree, 41% were college graduates, and 29% did not graduate from college. In multivariate analyses, willingness to engage in either intervention did not vary by education. Women who did not graduate from college were more likely to leave medical decisions to their provider (p = 0.004) compared to women with a college or postgraduate degree. However, regardless of education, over 80% of women preferred to make medical decisions themselves or jointly with their provider. Conclusions: Most women prefer to play an active role in their own medical decisions and have an interest in both evidence-based diabetes prevention strategies. This suggests that shared decision-making is appropriate for many women with a history of GDM and different levels of educational attainment.

Safety, Tolerability, and Pharmacokinetics of Remdesivir, An Antiviral for Treatment of COVID-19, in Healthy Subjects.

Remdesivir (RDV), a single diastereomeric monophosphoramidate prodrug that inhibits viral RNA polymerases, has potent in vitro antiviral activity against severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2). RDV received the US Food and Drug Administration (FDA)'s emergency use authorization in the United States and approval in Japan for treatment of patients with severe coronavirus disease 2019 (COVID-19). This report describes two phase I studies that evaluated the safety and pharmacokinetics (PKs) of single escalating and multiple i.v. doses of RDV (solution or lyophilized formulation) in healthy subjects. Lyophilized formulation was evaluated for potential future use in clinical trials due to its storage stability in resource-limited settings. All adverse events were grade 1 or 2 in severity. Overall, RDV exhibited a linear profile following single-dose i.v. administration over 2 hours of RDV solution formulation across the dose range of 3-225 mg. Both lyophilized and solution formulations provided comparable PK parameters. High intracellular concentrations of the active triphosphate (~ 220-fold to 370-fold higher than the in vitro half-maximal effective concentration against SARS-CoV-2 clinical isolate) were achieved following infusion of 75 mg or 150 mg lyophilized formulation over 30 minutes or 2 hours. Following multiple-doses of RDV 150 mg once daily for 7 or 14 days, RDV exhibited a PK profile similar to single-dose administration. Metabolite GS-441524 accumulated ~ 1.9-fold after daily dosing. Overall, RDV exhibited favorable safety and PK profiles that supported once-daily dosing.

A randomized, double-blind, placebo-controlled, dose-response study to assess the pharmacokinetics, efficacy, and safety of gabapentin enacarbil in subjects with restless legs syndrome.

OBJECTIVE: The objective of this study was to determine steady-state gabapentin exposures and corresponding relief of symptoms and safety profile produced by 4 dose levels of gabapentin enacarbil (GEn) in subjects with restless legs syndrome (RLS). METHODS: Subjects with RLS (n = 217) were randomized to receive once-daily, orally administered GEn 600 (n = 48), 1200 (n = 45), 1800 (n = 38), or 2400 mg (n = 45) or placebo (n = 41) in this 12-week, double-blind, multicenter study (NCT01332305). Clinic visits were at screening, baseline, and weeks 1, 2, 3, 4, 6, 8, 10, and 12; plasma gabapentin concentrations were measured by a validated liquid chromatography-mass spectrometry/mass spectrometry method at weeks 4 and 12. RESULTS: Exposure to gabapentin was proportional to GEn dose. Time to maximum plasma concentration was 7 to 9 hours, and elimination half-life was ~6 hours. The mean reduction from baseline to week 12 in International Restless Legs Syndrome Rating Scale total score and proportions of subjects with "much improved"/"very much improved" Clinical Global Impression-Improvement scores (investigator and patient ratings) ranged from -12.9 to -13.9 for GEn treatment groups versus -9.3 for placebo. The 2 most commonly reported adverse events were somnolence and dizziness. CONCLUSIONS: Gabapentin exposure was approximately proportional to GEn dose. Efficacy data showed that a once-daily dose of GEn 600 to 2400 mg provides greater relief of RLS symptoms than placebo; GEn was generally well tolerated with an adverse event profile consistent with gabapentin.

Pharmacokinetics and tolerability of single escalating doses of gabapentin enacarbil: a randomized-sequence, double-blind, placebo-controlled crossover study in healthy volunteers.

BACKGROUND: Gabapentin enacarbil is an actively transported prodrug of gabapentin that provides predictable dose-proportional gabapentin exposure with high (> or =68%) oral bioavailability. OBJECTIVES: The aims of this study were to investigate the pharmacokinetics and tolerability of gabapentin enacarbil up to supratherapeutic doses and the effects of gabapentin enacarbil on cardiac repolarization in healthy volunteers, and to provide a dose reference for a future definitive QT/corrected QT (QTc) study. METHODS: This was a randomized-sequence, double-blind, placebo-controlled, single escalating-dose, crossover study of gabapentin enacarbil 600-mg extended-release tablets administered as a single oral dose of 2400, 3600, 4800, or 6000 mg or placebo, with a 1-week washout between administrations. Blood samples were collected over a period of 36 hours after administration and were analyzed using a validated method of liquid chromatography/tandem mass spec-trometry. Blood gabapentin enacarbil and gabapentin concentrations were analyzed using noncompartmental methods. Tolerability was assessed by monitoring adverse events (AEs) (using subject interview/reporting), laboratory parameters, vital sign measurements, and 12-lead electrocardiography (ECG). Holter ECG was also performed. RESULTS: Thirty-two healthy volunteers were included in the study (18 women, 14 men; mean [SD] age, 31.2 [11.4] years; body mass index, 24.9 [3.04] kg/m(2)). Gabapentin enacarbil was converted rapidly to gaba-pentin after absorption. Gabapentin exposure in blood was proportional to gabapentin enacarbil dose over the range of 2400 to 6000 mg (1250-3125 mg-equivalent gabapentin). Blood concentrations of intact gabapen-tin enacarbil were low and transient (< or =0.5% of the released gabapentin concentration at all doses). The most commonly reported AEs were dizziness and nausea (50% and 25% of subjects, respectively). All but 4 AEs were mild to moderate in intensity. Two subjects experienced treatment-emergent AEs rated as severe: psychomotor retardation, vertigo, and sedation (4800-mg dose) and somnolence (6000 mg). All treatment-emergent AEs resolved without medical intervention. No serious AEs were reported, and none of the AEs led to study withdrawal. There were no clinically significant changes in laboratory parameters, vital sign measurements, or ECG values; QTc intervals did not exceed 480 msec or change from baseline >30 msec at any gabapentin enacarbil dose. CONCLUSIONS: Gabapentin enacarbil was associated with dose-proportional gabapentin exposure at doses up to 6000 mg and was generally well tolerated in these healthy subjects. These findings support the use of 6000-mg gabapentin enacarbil in a definitive QT/QTc study.