Disparities in SGLT2 Inhibitor or Glucagon-Like Peptide 1 Receptor Agonist Initiation Among Medicare-Insured Adults With CKD in the United States.

Rationale & Objective: Information regarding disparities in initiating sodium/glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide 1 receptor agonists (GLP-1RA) in patients with chronic kidney disease (CKD) is limited. We examined sociodemographic and clinical factors associated with the initiation of SGLT2i, GLP-1RA, or second-generation sulfonylureas in a Medicare Fee-For-Service patient population with CKD and type 2 diabetes. Study Design: Retrospective cohort study. Setting & Participants: The 20% random sample of Medicare Fee-For-Service claims, 2012-2018. Exposures: Patients' sociodemographic and clinical factors. Outcomes: Use of SGLT2i, GLP-1RA, or sulfonylureas. Analytical Approach: Patients with a newly initiated prescription of SGLT2i, GLP-1RA, or second-generation sulfonylureas from January 1, 2013, to December 31, 2018, were identified. Multinomial logistic regression model was used to evaluate demographic and clinical factors associated with the initiation of SGLT2i, GLP-1RA, or second-generation sulfonylureas. Results: The study cohort comprised 53,029 adults (aged greater than or equal to 18 years) with CKD and type 2 diabetes, of whom 10.0%, 17.4%, and 72.6% had a first prescription for SGLT2i, GLP-1RA, and sulfonylurea, respectively. Patients aged greater than or equal to 75 years versus those aged 65-74 years had lower odds to start SGLT2i or GLP-1RA compared with sulfonylureas. Black patients were associated with lower odds of initiation of SGLT2i (OR, 0.67; 95% CI, 0.61-0.74) and GLP-1RA (OR, 0.73; 95% CI, 0.68-0.79), compared with White patients. Hispanic and Asian patients had lower odds of initiation of GLP-1RA. Patients with cardiovascular disease or hyperlipidemia had higher odds to start SGLT2i or GLP-1RA. Limitations: CKD and type 2 diabetes diagnosis; CKD stage; and patient clinical status were identified with diagnosis or procedure codes. There is potential for residual confounding with the use of retrospective data. Conclusions: The results of this study identified disparities in the use of SGLT2i and GLP-1RA in patients with CKD. Black and older patients were significantly less likely to be initiated on SGLT2i or GLP-1RA than on second-generation sulfonylureas.

Patient Support Program and Healthcare Resource Utilization in Patients Using Clean Intermittent Catheterization for Bladder Management.

PURPOSE: The primary purpose of this study was to evaluate the impact of a patient-centered, chronic care self-management support program of clean intermittent catheterization (CIC) on emergency department (ED) visits and hospitalizations within the first 30 days of starting CIC. Secondary research objectives were to compare reuse of catheters, adherence to healthcare provider-instructed frequency of CIC, and reasons for nonadherence. DESIGN: A correlational survey design with 2 respondent groups. SUBJECTS AND SETTING: Four hundred forty-five respondents met inclusion criteria for this study; 321 respondents enrolled in an intermittent catheter manufacturer-supported CIC support program, and 124 respondents were not enrolled in a support program (comparison group). METHODS: Participants completed a 37-item online questionnaire designed for purposes of this study. Chi-square test was used to assess differences in the proportions of patients with ED visits and overnight hospital admissions comparing respondents enrolled in the patient support program to those not enrolled. Regression analyses were performed to estimate the effect of the CIC support program on ED visit events and on hospital overnight stays. RESULTS: Within the first month of CIC initiation, 16.1% and 10.2% of the respondents in the comparison group reported at least 1 ED visit and at least 1 overnight hospital stay, respectively. Respondents participating in the CIC support program experienced a 47% decrease in ED visits (adjusted rate ratio: 0.53; 95% confidence interval: 0.30-0.94, P = .036) and a 77% decrease (adjusted rate ratio: 0.24; 95% confidence interval: 0.10-0.62, P = .002) in hospital overnight stays within the first month of CIC initiation, while controlling for age, sex, education, duration of CIC use, region, health insurance status, and medical conditions necessitating CIC. Respondents in the CIC support program group reported an 8% higher adherence rate with the healthcare provider-instructed frequency of CIC usage compared to the comparison group (88% vs 80%, P = .039). CONCLUSIONS: The burden of CIC-related complications within the first month of CIC initiation is significant. A patient-centered, chronic care self-management program for CIC was associated with fewer ED visits and overnight hospital stays during the first month of CIC and improved adherence to prescribed frequency of CIC use.

Hypoglycemia Risk With SGLT2 Inhibitors or Glucagon-Like Peptide 1 Receptor Agonists Versus Sulfonylureas Among Medicare Insured Adults With CKD in the United States.

Rationale & Objective: Information on safety issues of newer glucose-lowering medications from a large population perspective in chronic kidney disease (CKD) patients with type 2 diabetes is limited. Our study aimed to examine hypoglycemia risk associated with sodium-glucose cotransporter 2 inhibitors (SGLT2is) and glucagon-like peptide 1 receptor agonists (GLP-1RAs) versus second-generation sulfonylureas in a general population of older patients with CKD and type 2 diabetes, across race, age, sex, and socioeconomic subgroups. Study Design: Retrospective cohort. Setting & Participants: The 20% random sample of Medicare fee-for-service claims, 2012-2018. Exposures: Use of SGLT2is, GLP-1RAs, or sulfonylureas. Outcomes: Hypoglycemic events resulting in health care utilization. Analytical Approach: Cox proportional hazard model evaluated the 90-day risk of hypoglycemia associated with SGLT2is or GLP-1RAs versus sulfonylureas. Results: A total of 18,567 adults (mean age: 73 years) with CKD and type 2 diabetes was included; 14.0% (n = 2,528) had a prescription for a SGLT2i or GLP-1RA, and 86.0% (n = 16,039) with a sulfonylurea. Compared with sulfonylureas, use of SGLT2is or GLP-1RAs was associated with a significantly lower risk of hypoglycemia (adjusted HR, 0.30; 95% CI, 0.14-0.65). Black individuals had higher risk of developing hypoglycemia than White individuals (adjusted HR, 1.55; 95% CI, 1.07-2.26). Low-income subsidy compared to no low-income subsidy status was associated with higher risk of hypoglycemic events. The risk of hypoglycemia also increased with higher comorbid condition score. Limitations: CKD and type 2 diabetes diagnosis, CKD stage, and patient clinical status were identified with diagnosis or procedure codes. There is potential for residual confounding with use of retrospective data. Conclusions: Use of SGLT2is or GLP-1RAs compared with sulfonylureas was associated with a lower risk of hypoglycemia among patients with CKD and type 2 diabetes. Black race was not only associated with lower use of newer agents with demonstrated cardiovascular and kidney benefits and lower hypoglycemia risk, but also with a higher rate of hypoglycemic events as compared with White individuals.

Hippocampus-Anterior Hypothalamic Circuit Modulates Stress-Induced Endocrine and Behavioral Response.

Hippocampal input to the hypothalamus is known to be critically involved in mediating the negative feedback inhibition of stress response. However, the underlying neural circuitry has not been fully elucidated. Using a combination of rabies tracing, pathway-specific optogenetic inhibition, and cell-type specific synaptic silencing, the present study examined the role of hippocampal input to the hypothalamus in modulating neuroendocrine and behavioral responses to stress in mice. Transsynaptic rabies tracing revealed that the ventral hippocampus (vHPC) is monosynaptically connected to inhibitory cells in the anterior hypothalamic nucleus (AHN-GABA cells). Optogenetic inhibition of the vHPC→AHN pathway during a restraint stress resulted in a prolonged and exaggerated release of corticosterone, accompanied by an increase in stress-induced anxiety behaviors. Consistently, tetanus toxin-mediated synaptic inhibition in AHN-GABA cells produced a remarkably similar effect on the corticosterone release profile, corroborating the role of HPC→AHN pathway in mediating the hippocampal control of stress responses. Lastly, we found that chronic inhibition of AHN-GABA cells leads to cognitive impairments in both object and social recognition memory. Together, our data present a novel hypothalamic circuit for the modulation of adaptive stress responses, the dysfunction of which has been implicated in various affective disorders.

Pan-Piscine Orthoreovirus (PRV) Detection Using Reverse Transcription Quantitative PCR.

Piscine orthoreovirus (PRV) infects farmed and wild salmon and trout species in North America, South America, Europe, and East Asia. PRV groups into three distinct genotypes (PRV-1, PRV-2, and PRV-3) that can vary in distribution, host specificity, and/or disease potential. Detection of the virus is currently restricted to genotype specific assays such that surveillance programs require the use of three assays to ensure universal detection of PRV. Consequently, herein, we developed, optimized, and validated a real-time reverse transcription quantitative PCR assay (RT-qPCR) that can detect all known PRV genotypes with high sensitivity and specificity. Targeting a conserved region at the 5' terminus of the M2 segment, the pan-PRV assay reliably detected all PRV genotypes with as few as five copies of RNA. The assay exclusively amplifies PRV and does not cross-react with other salmonid viruses or salmonid host genomes and can be performed as either a one- or two-step RT-qPCR. The assay is highly reproducible and robust, showing 100% agreement in test results from an inter-laboratory comparison between two laboratories in two countries. Overall, as the assay provides a single test to achieve highly sensitive pan-specific PRV detection, it is suitable for research, diagnostic, and surveillance purposes.

Glucose-Lowering Medication Use in CKD: Analysis of US Medicare Beneficiaries Between 2007 and 2016.

BACKGROUND: Information regarding the use of glucose-lowering medications in patients with chronic kidney disease (CKD) is limited. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: Medicare 5% random sample of patients with CKD with type 2 diabetes, 2007 to 2016. PREDICTORS: Study year, CKD stage, low-income subsidy status, and demographic characteristics (age, sex, and race/ethnicity). OUTCOMES: Trends in use of glucose-lowering medications. ANALYTICAL APPROACH: Yearly cohorts of patients with CKD and type 2 diabetes were created. Descriptive statistics were used to report proportions of patients using glucose-lowering medications. To test overall trends in glucose-lowering medication classes, linear probability models with adjustment for age, sex, race/ethnicity, CKD stage, and low-income subsidy status were used. RESULTS: Metformin use increased significantly from 32.7% in 2007 to 48.7% in 2016. Use of newer classes of glucose-lowering medications increased significantly, including dipeptidyl peptidase 4 inhibitors (5.6%, 2007; 21.7%, 2016), glucagon-like peptide 1 receptor agonists (2.3%, 2007; 6.1%, 2016), and sodium-glucose cotransporter 2 inhibitors (0.2%, 2013; 3.3%, 2016). Newer insulin analogue use increased from 37.2% in 2007 to 46.3% in 2013 and then remained steady. Use of sulfonylureas, thiazolidinediones, older insulins (human regular and neutral protamine Hagedorn), α-glucosidase inhibitors, amylin mimetics, and meglitinides decreased significantly. Insulin was the most highly used single medication class. Insulin use was higher among low-income subsidy than among non-low-income subsidy patients. Combination therapy was less common as CKD stage increased. LIMITATIONS: Patients with CKD and type 2 diabetes and the CKD stages were identified with diagnosis codes and could not be verified through medical record review. Our results may not be generalizable to younger patients with CKD with type 2 diabetes. CONCLUSIONS: Use of metformin and newer glucose-lowering medication classes is increasing in patients with CKD with type 2 diabetes. We anticipate that percentages of patients with CKD using these newer agents will increase.

Focal Inflammation Causes Carbenoxolone-Sensitive Tactile Hypersensitivity in Mice.

A focal and transitory inflammation induced by injection of complete Freund's adjuvant (CFA) in the submandibular skin of mice elicits pain behavior that persists for several weeks after the initial inflammation has resolved. Chronic pain, assessed as tactile hypersensitivity to stimulation with von Frey filaments, was evident from 1-7 weeks following CFA injection, although inflammation at the injection site was resolved by 3-4 weeks. In contrast, there were no changes in tactile sensitivity in the paw (un-injected site for comparison), no alterations in open field behavior and no differences in a functional observation battery evident in CFA-treated mice compared to controls (saline-injected) or to baseline (before CFA injection). Neither strain (Balb/c vs. C57BL/6) nor sex differences in baseline tactile threshold were significant in the submandibular skin. CFA-induced tactile hypersensitivity was also not a function of strain or sex. A single intraperitoneal injection of the gap junction blocker carbenoxolone (CBX) restored normal tactile thresholds in CFA-treated mice when administered at the peak of inflammation (1 week), after significant resolution of inflammation (3 weeks) or after total resolution of inflammation (4 and 5 weeks) without altering the tactile threshold of control subjects, tactile threshold in the paw or open field behavior. Thus, in this novel model of post-inflammatory pain, transitory inflammation induced persistent sex- and strain-independent behavioral hypersensitivity that was reversed by the gap junction blocker CBX, suggesting neuronal and/or glial plasticity as a major component of the chronic pain.

Effectiveness of different methods for delivering tailored nutrition education to low income, ethnically diverse adults.

BACKGROUND: Computer-tailored written nutrition interventions have been shown to be more effective than non-tailored materials in changing diet, but continued research is needed. Your Healthy Life/Su Vida Saludable (YHL-SVS) was an intervention study with low income, ethnically diverse, English and Spanish-speaking participants to determine which methods of delivering tailored written nutrition materials were most effective in lowering fat and increasing fruit and vegetable (F&V) intake. METHODS: YHL-SVS was a randomized controlled trial with four experimental conditions: 1) Nontailored (NT) comparison group; 2) Single Tailored (ST) packet; 3) Multiple Tailored (MT) packet mailed in four installments; 4) Multiple Re-Tailored (MRT) MT packets re-tailored between mailings via brief phone surveys. A baseline telephone survey collected information for tailoring as well as evaluation. Follow-up evaluation surveys were collected 4- and 7-months later. Primary outcomes included F&V intake and fat related behaviors. Descriptive statistics, paired t-test and ANOVA were used to examine the effectiveness of different methods of delivering tailored nutrition information. RESULTS: Both the ST and MT groups reported significantly higher F&V intake at 4-months than the NT and MRT groups. At 7 months, only the MT group still had significantly higher F&V intake compared to the NT group. For changes in fat-related behaviors, both the MT and MRT groups showed more change than NT at 4 months, but at 7 months, while these differences persisted, they were no longer statistically significant. There was a significant interaction of experimental group by education for change in F&V intake (P = .0085) with the lowest educational group demonstrating the most change. CONCLUSION: In this study, tailored interventions were more effective than non-tailored interventions in improving the short-term dietary behaviors of low income, ethnically diverse participants. Delivery of information in multiple smaller doses over time appeared to improve effectiveness. Future studies should determine which variables are mediators of dietary change and whether these differ by participant demographics. Moreover, future research should differentiate the effects of tailoring vs. cultural adaptation in ethnically diverse populations and study the dissemination of tailored interventions into community-based settings. TRIAL REGISTRATION: Current Controlled Trials # NCT00301691.