Lovelace Medical Center

To analyze device safety and clinical outcomes of ventral hernia repair with the GORE SYNECOR Preperitoneal Biomaterial (PRE device), a permanent high-strength mesh with bioabsorbable web scaffold technology. This multicenter retrospective review analyzed device/procedure endpoints and patient-reported outcomes in patients treated for hernia repair ≥1 year from study enrollment. Included in this analysis were 148 patients with a mean age of 56 years; 66.2% met the Ventral Hernia Working Group grade 2 classification. Median hernia size was 30.0cm 2 and 58.8% of patients had an incisional hernia. Repairs were primarily a robotic (53.4%) or open approach (41.9%). All meshes were placed extraperitoneal. Procedure-related adverse events within 30 days occurred in 13 (8.8%) patients and included 7 (4.8%) patients with surgical site infection, 2 (1.4%) with surgical site occurrence (SSO), 4 (2.7%) requiring readmission, and 3 (2.0%) who had reoperation. The rate of SSO events requiring procedural intervention was 2.7% (4 patients) through 30 days and 3.4% (5 patients) at 12 months. The rate of procedure-related surgical site infection remained at 4.8% through 12 months (no further reports after 30d) and 3.4% for SSO (2 reports after 30d). There were no site-reported clinically diagnosed hernia recurrences throughout the study. Median patient follow-up including in-person visit, physical examination, reported adverse event, explant, death, and questionnaire response was 28 months (n = 148). Median patient follow-up with patient questionnaire was 36 months (n = 88). Use of the PRE device, which incorporates the proven advantages of both an absorbable synthetic mesh and the long-term durability of a permanent macroporous mesh, is safe and effective in complex ventral hernia repairs. When used in the retromuscular space, the combination of these 2 materials had lower wound complications and recurrence rates than either type of material alone.

Acute respiratory viral infections, such as pneumovirus and respiratory picornavirus infections, exacerbate disease in COPD and asthma patients. A research program targeting respiratory syncytial virus (RSV) led to the discovery of GS-7682 (1), a novel phosphoramidate prodrug of a 4'-CN-4-aza-7,9-dideazaadenosine C-nucleoside GS-646089 (2) with broad antiviral activity against RSV (EC50 = 3-46 nM), human metapneumovirus (EC50 = 210 nM), human rhinovirus (EC50 = 54-61 nM), and enterovirus (EC50 = 83-90 nM). Prodrug optimization for cellular potency and lung cell metabolism identified 5'-methyl [(S)-hydroxy(phenoxy)phosphoryl]-l-alaninate in combination with 2',3'-diisobutyrate promoieties as being optimal for high levels of intracellular triphosphate formation in vitro and in vivo. 1 demonstrated significant reductions of viral loads in the lower respiratory tract of RSV-infected African green monkeys when administered once daily via intratracheal nebulized aerosol. Together, these findings support additional evaluation of 1 and its analogues as potential therapeutics for pneumo- and picornaviruses.

Introduction: Minor cannabinoids are increasingly being consumed in oral formulations (i.e., edibles, tinctures) for medical and nonmedical purposes. This study examined the pharmacokinetics (PKs) of cannabinoids tetrahydrocannabivarin (THCV), cannabichromene (CBC), cannabinol (CBN), and delta-8-tetrahydrocannabinol (D8-THC) after the first and last oral dose during a 14-day administration period. Materials and Methods: Sprague-Dawley rats (N=6 animals/dose, 50% female) were given an assigned dose of one of four cannabinoids (THCV=3.2-100 mg/kg, CBC=3.2-100 mg/kg, CBN=1-100 mg/kg, or D8-THC=0.32-10 mg/kg) or vehicle (medium-chain triglyceride oil) through oral gavage once daily for 14 days. Blood was collected 45 min and 1.5, 3, and 24 h following the first dose (day 1) and the last dose (day 14) of repeated oral cannabinoid treatment for PK analysis. Outcomes of interest included time to maximum concentration (Tmax), maximum concentration (Cmax), and area under the concentration versus time curve (AUClast). Dose-normalized (DN) Cmax and DN AUClast were also calculated. Brain tissue was collected 24 h post-administration of the first (day 1) and the last (day 14) dose of each cannabinoid to determine concentrations in brain. Results: All cannabinoids tested were detectable in plasma after single and 14-day repeated dosing. DN Cmax and DN AUClast were highest for D8-THC, followed by CBC, CBN, and THCV. There was no sex difference observed in cannabinoid kinetics. Accumulation of D8-THC in plasma was observed after 14 days of administration. THCV levels in plasma were lower on day 14 compared to day 1, indicating potential adaptation of metabolic pathways and increased drug elimination. Cannabinoids were detected in brain tissue 24 h post-administration of the first and the last dose of 17-100 mg/kg THCV, 3.2-100 mg/kg CBC, 10-100 mg/kg CBN, and 10 mg/kg D8-THC. Conclusions: THCV, CBC, CBN, and D8-THC produced detectable levels in plasma and translocated to brain tissue after the first dose (day 1) and the last dose (day 14) of repeated oral dosing. Examination of PKs of these minor cannabinoids in blood and brain provides a critical step for informing target dose ranges and dosing schedules in future studies that evaluate the potential effects of these compounds.

The American Heart Association Mission: Lifeline program objectives are to improve the quality of care and outcomes for patients with ST-segment-elevation myocardial infarction. Every minute of delay in treatment adversely affects 1-year mortality. Transfer of patients safely and timely to hospitals with primary percutaneous coronary intervention capability is needed to improve outcomes. But treatment times continue to show delays, especially during interhospital transfers. A simple 3-step process of an interhospital "Call 9-1-1" protocol may expedite this process. This STAT TRANSFER process uses a systems approach that considers diverse ways in which patients access care, how EMS responds and determines destinations, how referring hospital transfers are performed, urban and rural differences, and how receiving hospitals prepare for an incoming patient with ST-segment-elevation myocardial infarction. This initiative suggests a strategy to reduce variability in interhospital transfer times using a STAT TRANSFER and a Call 9-1-1 process in a system of care that involves all stakeholders.

For oral drugs, theformulator and discovery chemist have a toolavailable to them that can be used to navigate the risks associatedwith the selection and development of immediate release oral drugsand drug products. This tool is the biopharmaceutics classificationsystem (giBCS). Unfortunately, no such classification system existsfor inhaled drugs. The perspective outlined in this manuscript providesthe foundational principles and framework for a classification systemfor inhaled drugs. The proposed classification system, an inhalation-basedbiopharmaceutics classification system (iBCS), is based on fundamentalbiopharmaceutics principles adapted to an inhalation route of administrationframework. It is envisioned that a classification system for orallyinhaled drugs will facilitate an understanding of the technical challengesassociated with the development of new chemical entities and theirassociated new drug products (device and drug formulation combinations).Similar to the giBCS, the iBCS will be based on key attributes describingthe drug substance (solubility and permeability) and the drug product(dose and dissolution). This manuscript provides the foundationalaspects of an iBCS, including the proposed scientific principles andframework upon which such a system can be developed.

Introduction: Pneumocystis Pneumonia (PCP) is a common opportunistic infection among people living with the human immunodeficiency virus (HIV). This study’s objective was to assess temporal trends in PCP epidemiology among hospitalized patients with HIV/AIDS in the US and to compare data for hospitalizations with HIV with PCP to those without PCP. Methods: The national inpatient sample (NIS) data were analyzed from 2002–2014. The discharge coding identified hospitalized patients with HIV or AIDS and with or without PCP. Results: We identified 3,011,725 hospitalizations with HIV/AIDS during the study period; PCP was present in 5% of the patients with a diagnosis of HIV. The rates of PCP progressively declined from 6.7% in 2002 to 3.5 % in 2014 (p < 0.001). Overall mortality in patients with HIV was 3.3% and was significantly higher in those with PCP than without PCP (9.9% vs. 2.9%; p < 0.001). After adjusting for demographics and other comorbidities, PCP had higher odds of hospital mortality 3.082 (OR 3.082; 95% CI, 3.007 to 3.159; p < 0.001). Conclusion: From 2002 to 2014, the rate of PCP in HIV patients has decreased significantly in the United States but is associated with substantially higher mortality.