Pharmacokinetics and pharmacodynamics of the novel daily rivastigmine transdermal patch compared with twice-daily capsules in Alzheimer's disease patients

A transdermal patch has been developed for the cholinesterase inhibitor rivastigmine. This study investigated the pharmacokinetics and pharmacodynamics of rivastigmine and NAP226-90, and compared drug exposure between patch and capsule administrations. This was an open-label, parallel-group study in Alzheimer's disease patients randomized to receive either capsule (1.5-6 mg Q12H, i.e., 3-12 mg/day) or patch (5-20 cm2) in ascending doses through four 14-day periods. The patch showed lower Cmax (ca. 30% lower at 20 cm2, 19.5 versus 29.3 ng/ml), longer tmax (8.0 versus 1.0 h), and greater AUC (ca. 1.8-fold at 20 cm2, 345 versus 191 ng x h/ml) compared with the 6 mg Q12H capsule dose, with markedly less fluctuation between peak and trough plasma levels (80% at 20 cm2 versus 620% at 1.5 mg Q12H). Plasma butyrylcholinesterase inhibition rose slowly after patch administration, whereas two distinct peaks were seen after capsule administration. Average exposure with the 10 cm2 patch was comparable to the highest capsule dose (6 mg Q12H, i.e., 12 mg/day).     

A US policy perspective on oral preexposure prophylaxis for HIV

Orally administered preexposure prophylaxis is an innovative and controversial HIV prevention strategy involving the regular use of antiretroviral medications by uninfected individuals. Antiretroviral medications protect against potential HIV infection by reducing susceptibility to the virus. Recent clinical trial results indicate that preexposure prophylaxis can be safe and efficacious for men who have sexual intercourse with men, yet there remain policy considerations surrounding costs, opportunity costs, and ethical issues that must be addressed before broad implementation in the United States.     

Measurement of wall thickness alone does not accurately assess the presence of left ventricular hypertrophy

Clinical echocardiographic assessment of left ventricular hypertrophy (LVH) is generally performed by measuring wall thickness alone (WT). The objective of this study was to compare the assessment of LVH using the measurement of WT to that using indexed LV mass. Hypertensive patients underwent echocardiography with the measurement of LV WT and LV mass. For each patient, the presence of LVH was assessed by both methods with WT compared to the gold standard of LV mass index. In all, 92 patients (51M/41F) were entered, and in only 55 patients (60%) were the two methods concordant. There was a tendency for WT to underestimate LVH in females (sensitivity 37%, specificity 79%) and overestimate LVH in males (sensitivity 88%, specificity 56%). The measurement of WT alone overestimates LVH in males and underestimates LVH in females and should not be used as a surrogate marker for increased LV mass.     

Papillary muscle masquerading as a vegetation

We describe a case of an elderly man with an unusual post-operative complication after mitral valve replacement. The final diagnosis was discovered on reoperation. To our knowledge, this phenomenon has not been described in the literature previously.     

The Delta Delta: Gaps in screening and patient assessment for hepatitis D virus infection

Hepatitis D virus (HDV) infection is highly prevalent in patients with chronic hepatitis B (CHB). AASLD guidelines recommend a risk-based screening approach. Our aim was to ascertain if the risk-based approach leads to appropriate HDV screening, identify targets to improve screening rates, and study HDV clinical burden. CHB patients screened for HDV from 01/2016 to 12/2021 were identified. Level of training and specialty of providers ordering HDV screening tests were determined. HDV seropositive (HDV+) patient charts were reviewed for the presence of individual risk factors per the AASLD guidelines to determine if they met screening criteria. The severity of liver disease at the time of HDV screening was compared between the HDV+ group and a matched (based on age, hepatitis B e antigen status, BMI and sex) HDV seronegative (HDV−) group. During the study period, 1444/11,190 CHB patients were screened for HDV. Most screening tests were ordered by gastroenterology (90.2%) specialists and attending physicians (80.5%). HDV+ rate was 88/1444 (6%), and 72 HDV+ patients had complete information for analysis. 18% of HDV+ patients would be missed by a risk-based screening approach due to unreported or negative risk factors (see Table). A significantly higher number of HDV+ patients had developed significant fibrosis (p = 0.001) and cirrhosis (p < 0.01) by the time of screening than HDV− (n = 67) patients. In conclusion, targeted interventions are needed towards trainees and primary care clinics to improve screening rates. Current risk-based criteria do not appropriately screen for HDV. It is time for universal screening of HDV in CHB patients.