Clinical trial evaluating apomorphine oromucosal solution in Parkinson's disease patients.

Apomorphine, used to treat OFF episodes in patients with Parkinson's disease (PD), is typically administered via subcutaneous injections. Administration of an oromucosal solution could offer a non-invasive and user-friendly alternative. This two-part clinical study evaluated the safety, tolerability, pharmacokinetics (PK), and dose proportionality of a novel apomorphine hydrochloride oromucosal solution, as well as its relative bioavailability to subcutaneous apomorphine injection and apomorphine sublingual film. In part A of the study, 12 patients with PD received 2 mg oromucosal apomorphine (4% weight/volume) and 2 mg subcutaneous apomorphine in a randomized order, followed by 4 and 8 mg oromucosal apomorphine. In part B of the study, 13 patients with PD received 7 mg oromucosal apomorphine (7% weight/volume) and 30 mg sublingual apomorphine in a randomized order, followed by 14 mg oromucosal apomorphine. Washout between dose administrations in both study parts was at least 2 days. Safety, tolerability, and PK were assessed pre- and post-dose. Both study parts showed that oromucosal apomorphine was generally well-tolerated. Observed side effects were typical for apomorphine administration and included asymptomatic orthostatic hypotension, yawning, fatigue, and somnolence. Oromucosal apomorphine exposure increased with dose, although less than dose proportional. The mean (SD) maximum exposure reached with 14 mg oromucosal apomorphine was 753.0 (298.6) ng*min/mL (area under the plasma concentration-time curve from zero to infinity) and 8.0 (3.3) ng/mL (maximum plasma concentration). This was comparable to exposure reached after 2 mg subcutaneous apomorphine and approximately half of the exposure observed with 30 mg sublingual apomorphine. In summary, clinically relevant plasma concentrations could be reached in PD patients without tolerability issues.

High on-treatment platelet reactivity in peripheral arterial disease: A systematic review.

OBJECTIVES: To highlight current evidence pertaining to the measurement methods and prevalence of high on-treatment platelet reactivity (HTPR) in patients with PAD, as well as to evaluate the relationship between HTPR and recurrent adverse cardiovascular and limb events in PAD patients. METHODS: A systematic review of English-language literature on HTPR in patients with PAD. An electronic literature search of PubMed and Medline was performed in May 2021. RESULTS: A total of 29 studies with a total number of 11,201 patients with PAD were identified. HTPR during clopidogrel treatment ranges from 9.8 to 77%, and during aspirin treatment ranges from 4.1 to 50% of PAD patients. HTPR was associated with adverse clinical outcomes. The need for limb revascularisation was higher in patients with HTPR during clopidogrel use. Similarly, HTPR during aspirin use in the PAD population was predictive of adverse cardiovascular events (HR 3.73; 95% CI, 1.43-9.81; p = .007). A wide range of techniques were applied to measure platelet resistance, without consensus on cut-off values. Furthermore, differing patient populations, a variety of antiplatelet regimens, and differing clinical endpoints highlight the high degree of heterogeneity in the studies included in this review. CONCLUSION: No consensus on technique or cut-off values for HTPR testing has been reached. Patients with HTPR are potentially at a greater risk of adverse limb-related and cardiovascular events than patients sensitive to antiplatelet therapy illustrating the need for clinical implementation of HTPR testing. Future research must aim for consistent methodology. Adaptation of antiplatelet therapy based on HTPR results requires further exploration.

Late-onset sepsis due to urinary tract infection in very preterm neonates is not uncommon.

Urinary tract infection (UTI) is a common cause of sepsis in infants. Premature infants hospitalized at a neonatal intensive care unit often have risk factors for infection. In this group, the risk of UTI is not clearly known, and guidelines for urine analysis are not unanimous. We aimed to identify the risk of UTI in premature infants with central lines, suspected of late-onset sepsis. We analyzed all 1402 infants admitted to our hospital between 2006 and 2014 with a gestational age less than 32 weeks. Six hundred sixty-two episodes of sepsis evaluations were found with an unknown source of infection based on clinical symptoms. In half of this group, urine analysis was performed identifying UTI in 11.3% (24/212). In 13 of these infants (54%) with a UTI, infection was due to Candida albicans. In at least four episodes, the diagnosis and treatment would have been delayed if urine analysis had not been performed. CONCLUSION: Based on these findings, we conclude that in premature infants with central lines, urine analysis should be performed routinely when signs of infection occur beyond 72 h after birth. Urine collection should not be delayed and cultures should preferably be performed before the start of the antibiotic treatment. What is known: • In preterm infants, the presence of other risk factors for infection might make clinicians reluctant to obtain urine cultures during sepsis evaluation. • An internal survey demonstrated that there is no consensus within the NICUs in The Netherlands regarding urine analysis as part of LOS work-up. What is new: • The risk of UTI in the NICU population (11.3%) is comparable to term infants; therefore, urine analysis should be performed routinely when LOS is suspected. • Candida albicans was the most frequently (54%) detected pathogen causing UTI in this population.