Association between opioid therapy trajectories and potential opioid-related adverse health events.

PURPOSE: We identified associations between membership in seven group-based trajectories based on supply of filled opioid prescriptions and potential opioid-related adverse health events over a 720-day window. METHODS: We identified two veteran cohorts with chronic non-cancer pain who initiated treatment with long-term opioid therapy between 2008 and 2015, excluding those with prior substance use disorder (n = 373 941) or non-SUD, opioid-related adverse outcome (n = 405 631) diagnoses. Outcomes of interest included opioid use disorder, non-opioid drug use disorder, and alcohol use disorder for the first cohort; or accidents resulting in wounds or injuries, self-inflicted injuries, opioid-related accidents and overdoses, alcohol and non-opioid drug-related accidents and overdoses, and violence-related injuries for the second cohort. Using a cross-sectional design, Veterans were followed until the specific outcome of interest was diagnosed, they died, the study ended, or they were lost to follow up. Accelerated failure time models were estimated for each outcome. RESULTS: Membership in persistent moderate days covered and persistent modest days covered trajectories was associated with decreased risk of opioid use disorder (Moderate: θ = 0.59, 95%CI:0.54, 0.64; Modest: θ = 0.54, 95%CI:0.50, 0.59) and opioid overdose (Moderate: θ = 0.67,95%CI: 0.57, 0.79; Modest: θ = 0.72, 95%CI:0.61, 0.85) versus higher-utilizing persistent users. Rapid discontinuation was associated with decreased risk of opioid use disorder (θ = 0.86, 95% CI:0.77, 0.95) and opioid overdose (θ = 0.54, 95%CI:0.41, 0.71), but increased risk of alcohol use disorder (θ = 1.07, 95%CI:1.00, 1.15) and other substance use disorders. Delayed discontinuation or delayed reduction was associated with increased risk for most opioid related adverse health events. CONCLUSION: Persistent use trajectories with low levels of opioid utilization were associated with lower risks of potential opioid-related adverse health events.

Discrepancy in Insulin Regulation between Gestational Diabetes Mellitus (GDM) Platelets and Placenta.

Earlier findings have identified the requirement of insulin signaling on maturation and the translocation of serotonin (5-HT) transporter, SERT to the plasma membrane of the trophoblast in placenta. Because of the defect on insulin receptor (IR) in the trophoblast of the gestational diabetes mellitus (GDM)-associated placenta, SERT is found entrapped in the cytoplasm of the GDM-trophoblast. SERT is encoded by the same gene expressed in trophoblast and platelets. Additionally, alteration in plasma 5-HT levels and the 5-HT uptake rates are associated with the aggregation rates of platelets. Therefore, here, we investigated a novel hypothesis that GDM-associated defects in platelet IR should change their 5-HT uptake rates, and this should be a leading factor for thrombosis in GDM maternal blood. The maternal blood and the placentas were obtained at the time of cesarean section from the GDM and non-diabetic subjects (n = 6 for each group), and the platelets and trophoblasts were isolated to determine the IR activity, surface level of SERT, and their 5-HT uptake rates.Interestingly, no significant differences were evident in IR tyrosine phosphorylation or the downstream elements, AKT and S6K in platelets and their aggregation rates in both groups. Furthermore, insulin stimulation up-regulated 5-HT uptake rates of GDM-platelets as it does in the control group. However, the phosphorylation of IR and the downstream elements were significantly lower in GDM-trophoblast and showed no response to the insulin stimulation while they showed 4-fold increase to insulin stimulation in control group. Similarly, the 5-HT uptake rates of GDM-trophoblast and the SERT expression on their surface were severalfold lower compared with control subjects. IR is expressed in all tissues, but it is not known if diabetes affects IR in all tissues equally. Here, for the first time, our findings with clinical samples show that in GDM-associated defect on IR is tissue type-dependent. While IR is impaired in GDM-placenta, it is unaffected in GDM-platelet.

The association between suspected long-COVID and stimulant prescribing in the United States.

OBJECTIVES: This study sought to determine the association between suspected long-COVID and receipt of a stimulant prescription among persons diagnosed with COVID-19 and to describe clinical and demographic factors associated with receiving a stimulant prescription. METHODS: US patients 18 and older who had a COVID-19 diagnosis or a positive COVID-19 PCR test from April 1st, 2020 through December 21st, 2022 recorded in a national electronic health record data set obtained from TriNetX were assessed. Comparison subjects were propensity score matched on baseline covariates to those with a symptom of or diagnosis of long-COVID. A Cox Proportional Hazards models was used to estimate the influence of long-COVID on stimulant prescription receipt. RESULTS: Those with long-COVID (n = 65,329) were twice as likely to be prescribed a stimulant as persons with only acute COVID-19 (n = 189,438, HR=2.162; 1.929-2.423). Among persons with long-COVID, persons with new onset ADHD (HR=7.196; 5.749- 9.007), opioid-related disorders (HR=2.140; 1.264-3.621) and mood disorders (HR=1.649; 1.336-2.035) were more likely to be prescribed a stimulant. CONCLUSION: Further research describing the risks associated with increased stimulant use among persons with long-COVID is warranted.