Antihyperglycemic treatment patterns for chronic kidney disease and type 2 diabetes.

OBJECTIVE: Patients with type 2 diabetes (T2D) are at high risk for developing chronic kidney disease (CKD). The onset of incident CKD may complicate glycemic control among these patients. This study aimed to characterize antihyperglycemic medication use after incident CKD onset among patients with T2D to inform disease management. STUDY DESIGN: Retrospective cohort study. METHODS: Patients with incident CKD and prior T2D were identified from the Optum electronic health records database between March 2013 and September 2021. Patterns of antihyperglycemic use were assessed during the 1-year baseline period and after incident CKD diagnosis and described by baseline hemoglobin A1C (HbA1C) level (controlled [< 7%] vs elevated [≥ 7%]) and CKD severity. RESULTS: The study consisted of 262,395 patients, of whom 51% had elevated HbA1C. After CKD onset, 23.9% of patients initiated new antihyperglycemics within 1 year. Patients with elevated HbA1C had shorter time to new treatment initiation compared with those with controlled HbA1C (median, 28.7 vs 83.7 months). Patients with elevated urine albumin-to-creatinine ratio (uACR) had shorter median time to new treatment initiation (39.9-42.4 months) than those with normal uACR (59.8 months). Less than 7% of patients with stage 3 CKD and even smaller percentages of patients with higher stages of CKD utilized glucagon-like peptide 1 receptor agonists and sodium-glucose cotransporter 2 inhibitors. CONCLUSIONS: Treatment of T2D was considerably heterogenous by HbA1C level and CKD severity in patients with incident CKD. Current agents may not sufficiently fulfill the unmet need of T2D management in patients with CKD.

Long-Term Temporal Trends of Real-World Healthcare Costs Associated with Nivolumab Plus Ipilimumab and Pembrolizumab Plus Axitinib as First-Line Treatment for Advanced or Metastatic Renal Cell Carcinoma.

INTRODUCTION: Nivolumab plus ipilimumab (NIVO + IPI) and pembrolizumab plus axitinib (PEM + AXI) are first-line (1L) treatments for advanced or metastatic renal cell carcinoma (aRCC), although the long-term trends in their associated real-world healthcare costs are not well defined. We compared the real-world healthcare costs of patients with aRCC who received 1L NIVO + IPI or PEM + AXI over 24 months. METHODS: Adults with RCC and secondary malignancy who initiated 1L NIVO + IPI or PEM + AXI were identified in the Merative MarketScan Commercial and Medicare Supplemental Databases (01/01/2004 to 09/30/2021). All-cause and RCC-related healthcare costs (unadjusted and adjusted) were assessed per patient per month (PPPM) at 6-month intervals post-treatment initiation (index date) up to 24 months, and differences between the NIVO + IPI and PEM + AXI cohorts were compared. RESULTS: Of 325 patients with aRCC, 219 received NIVO + IPI and 106 received PEM + AXI as the 1L treatment. According to patients' follow-up length, the analyses for months 7-12 included 210 patients in the NIVO + IPI cohort and 103 in the PEM + AXI cohort; months 13-18 included 119 and 48 patients, respectively; and months 19-24 included 81 and 25 patients. PPPM unadjusted all-cause total costs were $46,348 for NIVO + IPI and $38,097 for PEM + AXI in months 1-6; $26,840 versus $27,983, respectively, in months 7-12; $22,899 versus $25,137 in months 13-18; and $22,279 versus $27,947 in months 19-24. PPPM unadjusted RCC-related costs were $44,059 for NIVO + IPI and $36,456 for PEM + AXI in months 1-6; $25,144 versus $26,692, respectively, in months 7-12; $21,645 versus $23,709 in months 13-18; and $20,486 versus $25,515 in months 19-24. PPPM costs declined more rapidly for patients receiving NIVO + IPI compared to those receiving PEM + AXI, resulting in significantly lower all-cause costs associated with NIVO + IPI during months 19-24 (difference - $10,914 [95% confidence interval - $21,436, - $1091]) and RCC-related costs during months 7-12 (- $4747 [(- $8929, - $512]) and 19-24 (- $10,261 [- $20,842, - $421]) after adjustment. Cost savings for NIVO + IPI versus PEM + AXI were driven by differences in drug costs which, after adjustment, were significantly lower in months 7-12 (difference - $5555 [all-cause], - $5689 [RCC-related]); 13-18 (- $7217 and - $6870, respectively); and 19-24 (- $16,682 and - $16,125). CONCLUSION: Although the real-world PPPM healthcare costs of 1L NIVO + IPI were higher compared with PEM + AXI in the first 6 months of treatment, the costs associated with NIVO + IPI rapidly declined thereafter, resulting in significantly lower costs vs. PEM + AXI from months 7 to 24.

Economic burden of early-stage non-small-cell lung cancer: an assessment of healthcare resource utilization and medical costs.

Aim: To quantify the economic burden of early-stage non-small-cell lung cancer (NSCLC) among patients with and without adjuvant therapy. Methods: All-cause and NSCLC-related healthcare resource utilization and medical costs were assessed among patients with resected stage IB-IIIA NSCLC in the SEER-Medicare database (1 January 2011-31 December 2019), from NSCLC diagnosis to death, end of continuous enrollment, or end of data availability (whichever occurred first). Results: Patients receiving adjuvant therapy had the lowest mean NSCLC-related medical costs (adjuvant [n = 1776]: $3738; neoadjuvant [n = 56]: $5793; both [n = 47]: $4818; surgery alone [n = 3478]: $4892, per-person-per-month), driven by lower NSCLC-related hospitalization rates. Conclusion: Post-surgical management of early-stage NSCLC was associated with high economic burden. Adjuvant therapy was associated with numerically lower medical costs over surgical resection alone.

Attenuation of Aeromonas hydrophila Infection in Carassius auratus by YtnP, a N-acyl Homoserine Lactonase from Bacillus licheniformis T-1.

In this experiment, the quorum quenching gene ytnP of Bacillus licheniformis T-1 was cloned and expressed, and the effect against infection of Aeromonas hydrophila ATCC 7966 was evaluated in vitro and vivo. The BLAST results revealed a 99% sequence identity between the ytnP gene of T-1 and its homolog in B.subtilis sub sp. BSP1, and the dendroGram showed that the similarity in the YtnP protein in T-1 was 100% in comparison with B.subtilis 3610, which was categorized as the Aidc cluster of the MBL family. The AHL lactonase activity of the purified YtnP was detected as 1.097 ± 0.7 U/mL with C6-HSL as the substrate. Otherwise, purified YtnP protein could significantly inhibit the biofilm formation of A.hydrophila ATCC 7966 with an inhibition rate of 68%. The MIC of thiamphenicol and doxycycline hydrochloride against A. hydrophila reduced from 4 µg/mL and 0.5 µg/mL to 1 µg/mL and 0.125 µg/mL, respectively, in the presence of YtnP. In addition, YtnP significantly inhibited the expression of five virulence factors hem, ahyB, ast, ep, aerA of A. hydrophila ATCC 7966 as well (p < 0.05). The results of inhibition on virulence showed a time-dependence tendency, while the strongest anti-virulence effects were within 4-24 h. In vivo, when the YtnP protein was co-injected intraperitoneally with A. hydrophila ATCC 7966, it attenuated the pathogenicity of A. hydrophila and the accumulated mortality was 27 ± 4.14% at 96 h, which was significantly lower than the average mortality of 78 ± 2.57% of the Carassius auratus injected with 108 CFU/mL of A. hydrophila ATCC 7966 only (p < 0.001). In conclusion, the AHL lactonase in B. licheniformis T-1 was proven to be YtnP protein and could be developed into an agent against infection of A. hydrophila in aquaculture.

Subscriber continuity in health insurance plans: factors associated with re-enrollment and coverage changes.

Aims: This study examined the extent to which Marketplace health insurance subscribers re-enroll a second year. Among re-enrollees, we sought to examine movement to more and less generous insurance plans (based on actuarial value), and the extent to which adverse selection, adverse retention, and aging in place are evident from re-enrollment choices made.Methods: Re-enrollment from 2015 to 2016 and 2016 to 2017 and movement to more and less generous insurance plans was examined using enrollment and insurance claims data from two US Federally-facilitated Marketplace insurance carriers operating in the state of New Mexico for 2015-2017. Insurance plans are assigned to metal levels based on estimated plan actuarial value: Bronze (60%), Silver (70%), and Gold (80%). Odds ratios (ORs) and 95% confidence intervals (OR CI) were estimated using logistic regressions for subscribers with base-year healthcare utilization. ORs were estimated for (1) re-enrollment in the year following the base year, and (2) movement to a higher or lower actuarial value plan.Results: Approximately 50% of subscribers re-enrolled with the same carrier for 2016 and 60% for 2017. Being enrolled 12 months was the strongest predictor for second year re-enrollment. Older individuals were more likely to re-enroll. Re-enrollment was lower for the insurance carrier with higher second year premium changes. Chronic condition utilization characteristics were positively associated with re-enrollment. Approximately 12% of Bronze subscribers moved to Silver or Gold, and had higher utilization after re-enrollment. Among Silver subscribers, 6% moved to Gold and 6% to Bronze. Approximately 37% of Gold subscribers moved to Silver or Bronze.Discussion: Re-enrollment was similar to published non-group insurance rates. Adverse selection and aging in place were observed. Evidence was weak for adverse retention. Some coverage change choices were rational, while others suggest subscribers may have difficulty making insurance choice decisions.