Systematic review of drug–drug interactions between rifamycins and anticoagulant and antiplatelet agents and considerations for management

Rifamycins (rifampin, rifabutin, and rifapentine) play an essential role in the treatment of mycobacterial and some nonmycobacterial infections. They also induce the activity of various drug transporting and metabolizing enzymes, which can impact the concentrations and efficacy of substrates. Many anticoagulant and antiplatelet (AC/AP) agents are substrates of these enzymes and have narrow therapeutic indices, leading to risks of thrombosis or bleeding when coadministered with rifamycins. The objective of this systematic review was to evaluate the effects on AC/AP pharmacokinetics, laboratory markers, and clinical safety and efficacy of combined use with rifamycins. A systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidance was performed. The PubMed, Embase, and Web of Science databases were queried for English-language reports on combination use of rifamycins and AC/AP agents from database inception through August 2021. The 29 studies identified examined warfarin (n = 17), direct oral anticoagulants (DOACs) (n = 8), and antiplatelet agents (n = 4) combined with rifampin (n = 28) or rifabutin (n = 1). Eleven studies were case reports or small case series; 14 reported on pharmacokinetic or laboratory markers in healthy volunteers. Rifampin-warfarin combinations led to reductions in warfarin area under the curve (AUC) of 15%–74%, with variability by warfarin isomer and study. Warfarin dose increases of up to 3–5 times prerifampin doses were required to maintain coagulation parameters in the therapeutic range. DOAC AUCs were decreased by 20%–67%, with variability by individual agent and with rifampin versus rifabutin. The active metabolite of clopidogrel increased substantially with rifampin coadministration, whereas prasugrel was largely unaffected and ticagrelor saw decreases. Our review suggests most combinations of AC/AP agents and rifampin are problematic. Further studies are required to determine whether rifabutin or rifapentine could be safe alternatives for coadministration with AC/AP drugs.     

Studies by electron microscopy on the assembly of duck hepatitis B virus in the liver

Liver specimens from 1-day-old ducklings infected in ovo with maternally transmitted duck hepatitis B virus (DHBV) were examined by electron microscopy. Complete and incomplete DHBV particles were located within hypertrophied cisternae of the endoplasmic reticulum of the hepatocytes. The complete viral particles found intracellularly have inner cores with a diameter ranging from 35 to 37.5 nm and an outer coat or envelope. The whole particle measures approximately 45-65 nm in diameter. Naked core particles were located in the nuclei, free in the cytoplasm, and also near or on the cisternal membrane of the endoplasmic reticulum on the cytoplasmic face. Duck hepatitis B virions appear to share morphological characteristics with the viral coat and core of human hepatitis B virus (HBV). Electron microscopy suggested that the core particles of DHBV migrate from the nucleus into the cytoplasm through the nuclear pores. The complete viral particles are probably formed by protrusion of the core particles through the endoplasmic reticulum and by simultaneous encapsulation with a coat derived from the endoplasmic reticulum.     

Experimental in ovo transmission of duck hepatitis B virus

Inoculation of fertile Pekin duck eggs with diluted serum containing DHBV into eggs incubated for 24 h and into the extra-embryonic cavities of 14-day-old embryos resulted in a high proportion of viraemic ducklings irrespective of the route of inoculation. Long-term observation of som of the ducks established that the viraemia induced experimentally is long-lasting and has persisted for periods up to 16 mth post-hatch. Separation of DHBV from the plasma of carrier ducks by rate zonal centrifugation was examined by DNA polymerase (DNAP) activity. Particles in the fraction with peak DNAP activity had a buoyant density of 1.16 g X cm-3 in sucrose and an estimated sedimentation coefficient, S20.w of 77. DHBV particles, the morphology of which could be resolved under the electron microscope, consisted of a coat (about 10 nm in thickness) surrounding a core with a diameter measuring 40 nm but not 27 nm as previously reported. Spike-like projections were found on the surface of the core as described previously by W.S. Mason, G. Seal and J. Summers, 1980, J. Virol. 36, 829-836.     

Hip fracture rates in South Australia: into the next century

BACKGROUND: Fractures of the femoral neck already represent a major public health problem in Australia. This situation is set to worsen as the population ages. The present study estimates the number of patients over 50 years of age with femoral neck fractures that is expected to impact on the South Australian healthcare service into the next century. METHODS: Population projections from the Australian Bureau of Statistics 1996 census were combined with age- and gender-specific incidence rates for fractures of the femoral neck for persons over the age of 50 in South Australia. Projections for the expected number of hip fractures in this State were then calculated. RESULTS: Assuming there are no changes in the age- and gender-specific incidence of fracture rates, the number of fractures in South Australia is estimated to increase by approximately 66% by the year 2021 and 190% by 2051. CONCLUSION: Based on the population projections and the assumption that conditions contributing to hip fractures remain constant, the number of fractured neck of femurs will increase in far greater proportion than the overall population in the next century. The results of the present study indicate the serious implications for the South Australian healthcare system if there is no reduction in incidence rates.     

Management of tumour spillage during parotid surgery for pleomorphic adenoma

Over the decades parotid surgery for benign tumours has developed into a reproducible, conservative operation with low morbidity. Despite the advances tumour spillage can still occur, and its management remains controversial. Since no universal consensus exists the aim of this article is to review the approach to tumour spillage and derive a protocol for its management based on existing evidence.     

Psychophysiological Effects of Oral Ethanol in Alcoholics and Social Drinkers

The acute and extended effects of ethanol ingestion were examined in five alcoholic subjects, and five "social" drinkers. Six physiological and four subjective report measures were taken before, during and up to 90 min after the ingestion of ethanol in three doses and placebo. Findings showed that alcohol exerted significant dose-related physiological effects in the initial minutes of ingestion, and in extended analyses of physiological and subjective measures in both groups of drinkers. Alcoholics and social drinkers generally did not differ in their physiological responses to alcohol doses and placebo, while some evidence for tolerance to reported euphoric effects of alcohol in the alcoholic subjects was found. The possibility is raised that early physiological responses observed during ethanol ingestion may arise not only from pharmacological effects of the drink, but may also be evidence for conditional predrink responses.