Pharmacokinetics of cysteamine bitartrate following intraduodenal delivery

Cysteamine is approved for the treatment of cystinosis and is being evaluated for Huntington's disease and non‐alcoholic fatty liver disease. Little is known about the bioavailability and biodistribution of the drug. The aim was to determine plasma, cerebrospinal fluid (CSF), and tissue (liver, kidney, muscle) cysteamine levels following intraduodenal delivery of the drug in rats pretreated and naïve to cysteamine and to estimate the hepatic first‐pass effect on cysteamine. Healthy male rats (n = 66) underwent intraduodenal and portal (PV) or jugular (JVC) venous catheterization. Half were pretreated with cysteamine, and half were naïve. Following intraduodenal cysteamine (20 mg/kg), serial blood samples were collected from the PV or the JVC. Animals were sacrificed at specific time points, and CSF and tissue were collected. Cysteamine levels were determined in plasma, CSF, and tissue. The C_max was achieved in 5–10 min from PV and 5–22.5 min from JVC. The PV‐C_max (P = 0.08), PV‐AUC_0–t (P = 0.16), JVC‐C_max (P = 0.02) and JVC‐AUC_0–t (P = 0.03) were higher in naive than in pretreated animals. Plasma cysteamine levels returned to baseline in ≤120 min. The hepatic first‐pass effect was estimated at 40%. Peak tissue and CSF cysteamine levels occurred ≤22.5 min, but returned to baseline levels ≤180 min. There was no difference in CSF and tissue cysteamine levels between naïve and pretreated groups, although cysteamine was more rapidly cleared in the pretreated group. Cysteamine is rapidly absorbed from the small intestine, undergoes significant hepatic first‐pass metabolism, crosses the blood brain barrier, and is almost undetectable in plasma, CSF, and body tissues 2 h after ingestion. Sustained‐release cysteamine may provide prolonged tissue exposure.     

Pulmonary artery pulsatility index predicts prolonged inotrope/pulmonary vasodilator use after implantation of continuous flow left ventricular assist device

Objective: Predictors of right ventricle (RV) dysfunction after continuous‐flow left ventricular assist device (CF‐LVAD) implantation in children are not well described. We explored the association of preimplantation Pulmonary Artery Pulsatility index (PAPi) and other hemodynamic parameters as predictors of prolonged postoperative inotropes/pulmonary vasodilator use after CF‐LVAD implantation.
Design: Retrospective chart review.
Setting: Single tertiary care pediatric referral center.
Patients: Patients who underwent CF‐LVAD implantation from January 2012 to October 2017.
Interventions: Preimplantation invasive hemodynamic parameters were analyzed to evaluate the association with post‐CF‐LVAD need for prolonged (>72 hours) use of inotropes/pulmonary vasodilators.
Measurements and main results: Preimplantation cardiac catheterization data was available for 12 of 44 patients who underwent CF‐LVAD implant during the study period. Median (IQR) age and BSA of the cohort were 15.3 years (10.2, 18) and 1.74 m2 (0.98, 2.03). Group 1 (n = 6) included patients with need for prolonged inotropes/pulmonary vasodilator use after CF‐LVAD implantation and Group 2 (n = 6) included those without. Baseline demographic parameters, cardiopulmonary bypass time, and markers of RV afterload (pulmonary vascular resistance, PA compliance and elastance) were similar among the two groups. PAPi was significantly lower in group 1 compared to group 2 (0.96 vs 3.6, respectively; P = .004). Post‐LVAD stay in the intensive care unit was longer for patients in group 1 (46 vs 23 days, P = .52). Brain natriuretic peptide was significantly higher at 3 months after implantation in group 1; P = .01.
Conclusions: The need for inotropes/pulmonary vasodilators in the postoperative period can be predicted by the preimplantation intrinsic RV contractile reserve as assessed by PAPi rather than the markers of RV afterload. Further investigation and correlation with clinical outcomes is needed.     

Programa de atención farmacéutica integrada en pacientes con enfermedades crónicas

ObjectivesTo assess whether an integrated pharmaceutical care programme (IPCP) improves clinical evolution, patient quality of life, and reduces health costs in chronic patients.Material and methodsA parallel, open, and multi-centre clinical trial of an IPCP in patients with heart failure (HF) and/or chronic obstructive pulmonary disease (COPD) in 8 different health areas in Cataluña. The intervened patient was monitored for pharmacotherapeutic evolution by hospital pharmacists, primary care physicians, and community pharmacists. Controls received normal follow-up. All patients were monitored for 12 months, with quality of life tests administered at the beginning and end of follow-up.ResultsWe had the participation of 8 different hospitals, 8 primary care centres, and 109 community pharmacies. 238 patients completed the study, with 2.9% of participants lost during the study period. There were no significant differences in terms of readmissions, visits to the doctors, or to emergency services. We detected 50 different medication-related problems (MRP) in 37 patients, with a statistically significant difference in terms of MRP between the control and treatment groups of patients with HF, and almost significant differences in COPD patients. MRP were moderate-severe in 36% of cases. MRP were avoidable in 94% of cases, and the pharmacist resolved the issue in 90% of cases. There were no differences in terms of patient quality of life or health costs between the start and end of the study.ConclusionsIntegrated pharmaceutical care programs facilitate an improvement in the quality of patient care, but electronic registries are necessary to promote communication between sections of the health care network.     

Addition of platelet‐rich plasma supports immune modulation and improved mechanical integrity in Alloderm mesh for ventral hernia repair in a rat model

The recurrence of ventral hernias continues to be a problem faced by surgeons, in spite of efforts toward implementing novel repair techniques and utilizing different materials to promote healing. Cadaveric acellular dermal matrices (Alloderm) have shown some promise in numerous surgical subspecialties, but these meshes still suffer from subsequent failure and necessitation of re‐intervention. Here, it is demonstrated that the addition of platelet rich plasma to Alloderm meshes temporally modulates both the innate and cytotoxic inflammatory responses to the implanted material. This results in decreased inflammatory cytokine production at early time points, decreased matrix metalloproteinase expression, and decreased CD8+ T cell infiltration. Collectively, these immune effects result in a healing phenotype that is free from mesh thinning and characterized by increased material stiffness.     

Movimiento de alumnos ayudantes: experiencia de una institución cubana

The teaching-support student movement arose out of the necessity to cover the lack of teachers caused by the massive exodus of professionals at the beginning of the Cuban Revolution. Five decades later it is still alive and continuously perfects and adjusts itself according to the dynamic social requirements of the country. This article intends to describe the experience acquired at the University Hospital “Arnaldo Milián Castro” based on the work of teaching-support students in the period from 2011 to 2016, emphasising its achievements and challenges in the fulfilment of its main objectives in Cuban higher medical education such as: to support the development of the instructional and educational process, to address the professional orientation towards specialities deficient in professionals and to quickly acquire skills for teaching, research, and those related to specialities.