Trends in prescribing pattern of opioid and benzodiazepine substitutes among Medicare part D beneficiaries from 2013 to 2018: a retrospective study.

OBJECTIVE: Opioid and benzodiazepine co-prescribing is associated with a substantial increase in opioid overdose deaths. In this study, we examine the prescribing trends of substitutes of opioids and benzodiazepines alone or in combination, compared with opioids and benzodiazepines. DESIGN: Retrospective cohort study. SETTING: Data were collected using a 20% national sample of Medicare beneficiaries from 2013 to 2018. PARTICIPANTS: 4.1-4.3 million enrollees each year from 2013 to 2018. INTERVENTION: None. PRIMARY OUTCOME: We employ a generalised linear mixed models to calculate ORs for opioid use, benzodiazepine or Z-drug (benzos/Z-drugs) use, opioid/benzos/Z-drugs 30-day use, gabapentinoid use and (selective serotonin reuptake inhibitors (SSRI) and serotonin norepinephrine reuptake inhibitors (SNRIs)) use, adjusted for the repeated measure of patient. We then created two models to calculate the ORs for each year and comparing to 2013. RESULTS: Opioid and benzos/Z-drugs use decreased by 2018 (aOR 0.626; 95% CI 0.622 to 0.630) comparing to 2013. We demonstrate a 36.3% and 9.9% increase rate of gabapentinoid and SSRI/SNRI use, respectively. Furthermore, combined gabapentinoid and SSRI/SNRI use increased in 2018 (aOR 1.422; 95% CI 1.412 to 1.431). CONCLUSION: Little is known about the prescribing pattern and trend of opioid and benzodiazepine alternatives as analgesics. There is a modest shift from prescribing opioid and benzos/Z-drugs (alone or in combination) towards prescribing non-opioid analgesics-gabapentinoids with and without non-benzos/Z-drugs that are indicated for anxiety. It is unclear if this trend towards opioid/benzos/Z-drugs alternatives is associated with fewer drug overdose death, better control of pain and comorbid anxiety, and improved quality of life.

Assessment of vascular permeability in an ovine model of acute lung injury and pneumonia-induced Pseudomonas aeruginosa sepsis.

OBJECTIVE: To assess the time changes and mechanism of pulmonary and peripheral vascular permeability in sheep with acute lung injury and sepsis. DESIGN: Prospective, controlled, randomized trial. SETTING: University research laboratory. SUBJECTS: A total of 21 chronically instrumented, adult female sheep. INTERVENTIONS: Sheep were instrumented with lung and prefemoral lymph fistulas and allocated to either an uninjured control group (n = 5) or sepsis group (n = 5). The sheep in the sepsis group received cotton smoke inhalation injury followed by instillation of Pseudomonas aeruginosa into the lungs. All sheep were mechanically ventilated and fluid resuscitated for the entire duration of the 24-hr experiment. Additional sheep (n = 11) received injury and were killed at different time points for the measurement of vascular endothelial growth factor in lung tissue. MEASUREMENTS AND MAIN RESULTS: The injury induced a hypotensive-hyperdynamic circulation; increases in pulmonary capillary pressure, net fluid balance, lung and prefemoral lymph flow and protein content, lung water content, abdominal and thoracic fluid and protein content, neutrophil accumulation in the lung, and vascular endothelial growth factor expression in lung tissue; and decreases in PaO2/FiO2 ratio, plasma protein concentration, plasma oncotic pressure, and myocardial contractility. CONCLUSIONS: Lung edema formation in this model was the result of marked increases in both pulmonary microvascular permeability and pressure. Pulmonary vascular hyperpermeability peaked 12 hrs postinjury and was related to vascular endothelial growth factor overexpression. Early myocardial failure was a potential contributor to the constant increase in pulmonary capillary pressure. The sepsis-induced increase in peripheral microvascular permeability was associated with significant accumulation of fluid and protein in the third space.