Rapid rituximab administration: Safety of 60-minute infusions in malignant and benign haematological disease.

INTRODUCTION: Rituximab is a chimeric monoclonal antibody used to treat a range of malignant and benign haematological conditions. To minimise the risk of infusion-related toxicity, initial infusions are administered slowly over 4-6 h. In the absence of significant reactions, subsequent doses are often administered over an off-label rate of 90 min. In response to emergent data, our site adopted the use of rapid 60-min infusions for third and subsequent doses. This study aimed to review the safety and ongoing feasibility of 60-min rituximab infusions following institutional practice change. METHODS: Pharmacy dispensing records were used to identify all rituximab infusions dispensed under the direction of a haematologist between 1 January 2023 and 30 June 2023. Electronic medical records were reviewed retrospectively to characterise the incidence of infusion reactions. RESULTS: Eight-two patients received a total of 262 rituximab infusions, including 54 patients who received a total of 113 rapid 60-min infusions. No infusion-related reactions were observed with 60-min administration. Five patients who experienced grade 1-2 infusion reactions with their first or second dose of rituximab safely received 60-min infusions for third and subsequent doses without additional premedication. Indications for treatment included non-Hodgkin's lymphoma (76.99%), non-malignant disease states (17.70%), chronic lymphocytic leukaemia (3.54%) and post-transplant lymphoproliferative disorder (1.77%). CONCLUSION: In the absence of severe reactions to initial and second doses, administration of rituximab over 60 min is well tolerated in patients with malignant and benign haematological disease.

A survey of operating theatre staff on the impact of automated medication dispensing systems in operating theatres in an Australian hospital.

There is a lack of published literature investigating the impact of anaesthesia-specific automated medication dispensing systems on theatre staff. This study aimed to investigate the perspectives of theatre staff from multiple disciplines on their experience using anaesthesia stations three years after implementation at our Western Australian quaternary hospital institution. A web-based survey was distributed to 440 theatre staff, which included consultant anaesthetists, anaesthetic trainees, nurses, anaesthetic technicians and pharmacists, and 118 responses were received (response rate 26.8%). Eighty-one percent of the anaesthetic medical staff responders reported that the anaesthesia stations were fit for purpose and 66.67% of the anaesthetic medical staff reported that they were user friendly. Sixty-seven percent of anaesthetic medical staff agreed that controlled medication (e.g. schedule 8 and schedule 4 recordable) transactions were more efficient with the anaesthesia stations, and 66.67% agreed that the anaesthesia stations improved accountability for these transactions. Sixty-seven percent of anaesthetic medical staff preferred to use anaesthesia stations and 21.2% of all the responders preferred a manual medication trolley (P ≤ 0.001). This survey of user experience with anaesthesia stations was found to be predominantly positive with the majority of theatre staff and anaesthetic medical staff preferring anaesthesia stations.

A Survey of Australian Hospital Pharmacy Staff Knowledge, Practices, and Assessment of Animal-derived Medications.

This study aims to determine the knowledge and practices of Australian hospital pharmacy staff regarding animal-derived ingredients in medications and reviewing whether commonly used medications contain animal-derived ingredients. The study surveyed 67 pharmacy staff and reviewed 20 medications. Ninety-eight percent of staff were aware patients may have religious or cultural restrictions on ingesting animal-derived products; 33% discussed this issue with patients. Information on animal-derived ingredients was readily accessible for 1.6% of medications, with information unavailable for 14%. Staff demonstrated awareness that medications may contain animal-derived ingredients, but challenges exist in discussion with patients and in accessing information on animal-derived ingredients.

An evaluation of automated dispensing cabinets and inventory robots for centralised distribution of medication in an Australian hospital.

ObjectiveIn Australian hospitals, a central distribution system is often utilised to supply medication to clinical areas. This study investigated the impact of automated dispensing cabinets (ADCs) and inventory robots in medication distribution within an Australian hospital.MethodsA prospective observational study of pharmacy technician medication supply to clinical areas was conducted over a 2-week period pre- and post-implementation of ADCs and inventory robots. Information was collected on the time taken to perform all tasks required to provide a weekly medication supply service for medication other than drugs of addiction.ResultsThere was no significant reduction of total duration for medication supply, pre-implementation mean 73.08min versus post-implementation 68.59min (P=0.567). An instance of automation downtime occurred during the post-implementation period for which manual downtime procedures were implemented. Without downtime, a significant reduction in overall time taken was observed, 74.25min versus 63.18min (P=0.019). Pre-restocking medication selection errors were reduced non-significantly after implementation of inventory robots, 11 (0.43%) versus 4 (0.21%) errors (P=0.090).ConclusionsImplementation of ADCs and robots did not significantly reduce the total time to provide a weekly medication supply service when downtime occurred, although a significant reduction was observed when downtime did not occur. Pharmacy medication selection errors were non-significantly lower.What is known about the topic?Australian hospitals are increasingly implementing automated technology such as ADCs and inventory robotics in an attempt to improve efficiency and accuracy of medication supply; however, limited literature is available in an Australian setting.What does this paper add?This paper describes the impact of implementing ADCs in clinical areas (e.g. inpatient wards) and inventory robots in a main store pharmacy on the medication supply process. This paper highlights the benefit of improved efficiency and accuracy in selecting medication in pharmacy for distribution and identifies time to restock the ADCs is significantly increased.What are the implications for practitioners?Implementing ADCs and inventory robotics in Australian hospitals can provide benefits in efficiency and accuracy; however, robust downtime procedures are essential.

Landscape analyses using eDNA metabarcoding and Earth observation predict community biodiversity in California.

Ecosystems globally are under threat from ongoing anthropogenic environmental change. Effective conservation management requires more thorough biodiversity surveys that can reveal system-level patterns and that can be applied rapidly across space and time. Using modern ecological models and community science, we integrate environmental DNA and Earth observations to produce a time snapshot of regional biodiversity patterns and provide multi-scalar community-level characterization. We collected 278 samples in spring 2017 from coastal, shrub, and lowland forest sites in California, a complex ecosystem and biodiversity hotspot. We recovered 16,118 taxonomic entries from eDNA analyses and compiled associated traditional observations and environmental data to assess how well they predicted alpha, beta, and zeta diversity. We found that local habitat classification was diagnostic of community composition and distinct communities and organisms in different kingdoms are predicted by different environmental variables. Nonetheless, gradient forest models of 915 families recovered by eDNA analysis and using BIOCLIM variables, Sentinel-2 satellite data, human impact, and topographical features as predictors, explained 35% of the variance in community turnover. Elevation, sand percentage, and photosynthetic activities (NDVI32) were the top predictors. In addition to this signal of environmental filtering, we found a positive relationship between environmentally predicted families and their numbers of biotic interactions, suggesting environmental change could have a disproportionate effect on community networks. Together, these analyses show that coupling eDNA with environmental predictors including remote sensing data has capacity to test proposed Essential Biodiversity Variables and create new landscape biodiversity baselines that span the tree of life.

The risk of intramuscular haematoma is low following injection of benzathine penicillin G in patients receiving concomitant anticoagulant therapy.

The use of intramuscular injections is widely recommended to be avoided in patients who are prescribed anticoagulant agents, both oral and parenteral due to concerns of haematoma. Benzathine penicillin G (BPG), administered via intramuscular injection, is a vital treatment component for patients with rheumatic heart disease. BPG must be administered long term (for at least a decade) as part of treatment and alternative options to intramuscular injection are currently limited. Many of these patients with rheumatic heart disease will also require long term or lifelong anticoagulation. Our retrospective, single centre study of 48 adult and paediatric hospitalised patients, 29 of which were receiving concomitant anticoagulants, demonstrates no significant bleeding complications from intramuscular administration of BPG on the day of intramuscular injection and for 7 days post injection or until hospital discharge. In the absence of practical alternatives for patients with rheumatic heart disease, our local data supports continuing intramuscular injection of BPG in patients with rheumatic heart disease receiving anticoagulant medication.Letter to the editor.

Pharmacokinetics of flucloxacillin during prolonged intermittent renal replacement therapy in a 76-year-old man.

Prolonged intermittent renal replacement therapy (PIRRT) use has been increasing in critically ill patients with kidney dysfunction. PIRRT can affect the pharmacokinetics of many drugs, although no data is available to guide flucloxacillin dosing in this clinical scenario. Herein, we describe the pharmacokinetics of flucloxacillin, given at 1 g every 4 h during PIRRT, in a 76-year-old, critically ill patient with a methicillin-susceptible Staphylococcus aureus (MSSA) prosthetic joint infection complicated by bacteraemia. Blood samples were taken over 2 days including during a 9-h PIRRT session. A two-compartment model was developed to describe differences in clearance of flucloxacillin during PIRRT and off-PIRRT (9.45 vs. 6.89 L/h). A flucloxacillin dose of 1 g every 4 h during PIRRT therapy appeared to attain adequate exposures for MSSA sepsis in this patient, however higher doses may be required for infection sites with poor drug penetration.

Pharmacokinetics of Benzylpenicillin (Penicillin G) during Prolonged Intermittent Renal Replacement Therapy.

Prolonged intermittent renal replacement therapy (PIRRT) is an increasingly adopted method of renal replacement in critically ill patients. Like continuous renal replacement therapy, PIRRT can alter the pharmacokinetics (PK) of many drugs. In this setting, dosing data for antibiotics like benzylpenicillin are lacking. In order to enable clinicians to prescribe benzylpenicillin safely and effectively, knowledge of the effects of PIRRT on the plasma PK of benzylpenicillin is required. Herein, we describe the PK of benzylpenicillin in 2 critically ill patients on PIRRT for the treatment of penicillin-susceptible Staphylococcus aureus bacteremia complicated by infective endocarditis. Blood samples were taken for each patient taken over dosing periods during PIRRT and off PIRRT. Two-compartment PK models described significant differences in the mean clearance of benzylpenicillin with and without PIRRT (6.61 vs. 3.04 L/h respectively). We would suggest a benzylpenicillin dose of 1,800 mg (3 million units) every 6-h during PIRRT therapy as sufficient to attain PK/pharmacodynamic target.

ngsLD: evaluating linkage disequilibrium using genotype likelihoods.

MOTIVATION: Linkage disequilibrium (LD) measures the correlation between genetic loci and is highly informative for association mapping and population genetics. As many studies rely on called genotypes for estimating LD, their results can be affected by data uncertainty, especially when employing a low read depth sequencing strategy. Furthermore, there is a manifest lack of tools for the analysis of large-scale, low-depth and short-read sequencing data from non-model organisms with limited sample sizes. RESULTS: ngsLD addresses these issues by estimating LD directly from genotype likelihoods in a fast, reliable and user-friendly implementation. This method makes use of the full information available from sequencing data and provides accurate estimates of linkage disequilibrium patterns compared with approaches based on genotype calling. We conducted a case study to investigate how LD decays over physical distance in two avian species. AVAILABILITY AND IMPLEMENTATION: The methods presented in this work were implemented in C/C and are freely available for non-commercial use from https://github.com/fgvieira/ngsLD. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Development of a tool to assess beliefs about mythical causes of cancer: the Cancer Awareness Measure Mythical Causes Scale.

OBJECTIVES: We aimed to develop a reliable and valid measure to assess public beliefs in mythical causes of cancer: the Cancer Awareness Measure-MYthical Causes Scale (CAM-MYCS). DESIGN AND SETTING: Cancer myth items were generated from a literature review, social media and interviews (n=16). The CAM-MYCS was prepared by reducing items using (a) an online sample (n=527) with exploratory factor analysis and (b) cancer experts with Delhpi methodology (n=13). To assess test-retest reliability and sensitivity to change, students (n=91) completed the CAM-MYCS at baseline and 1 week after exposure to information on lifestyle-related cancer causes or control information. Construct validity was tested by comparing CAM-MYCS scores between cancer experts (n=25) and students (n=91). Factor structure and internal reliability were investigated in a national sample (n=1993). RESULTS: Out of 42 items generated, 12 were retained based on factor loadings, prevalence of endorsement and expert consensus. CAM-MYCS scores improved (fewer myths endorsed) among students exposed to information on cancer causes compared with the control group (p<0.001) and showed high test-retest reliability (r=0.90, p<0.001). Cancer experts reported higher CAM-MYCS scores (fewer myths endorsed) than students (p<0.001). The factor structure of the CAM-MYCS was confirmed in the national sample and internal reliability was high (α=0.86). Inclusion of the CAM-MYCS alongside items assessing knowledge of actual cancer causes did not affect responses. CONCLUSIONS: The CAM-MYCS tool is a reliable and valid tool assessing beliefs in mythical causes of cancer, and it can be used alongside items assessing known causes of cancer.

A multiscale approach to balance trade-offs among dam infrastructure, river restoration, and cost.

Aging infrastructure and growing interests in river restoration have led to a substantial rise in dam removals in the United States. However, the decision to remove a dam involves many complex trade-offs. The benefits of dam removal for hazard reduction and ecological restoration are potentially offset by the loss of hydroelectricity production, water supply, and other important services. We use a multiobjective approach to examine a wide array of trade-offs and synergies involved with strategic dam removal at three spatial scales in New England. We find that increasing the scale of decision-making improves the efficiency of trade-offs among ecosystem services, river safety, and economic costs resulting from dam removal, but this may lead to heterogeneous and less equitable local-scale outcomes. Our model may help facilitate multilateral funding, policy, and stakeholder agreements by analyzing the trade-offs of coordinated dam decisions, including net benefit alternatives to dam removal, at scales that satisfy these agreements.

Brief Report: Metformin for Antipsychotic-Induced Weight Gain in Youth with Autism Spectrum Disorder.

Antipsychotic treatment in youth with autism spectrum disorder (ASD) is becoming increasingly common, placing individuals at risk for antipsychotic-induced weight gain and associated complications. Metformin hydrochloride, a biguanide medication FDA-approved for treatment of type-2 diabetes in youth, may hold promise for treatment of antipsychotic-induced weight gain in youth with ASD. In this report we assess the long-term impact of metformin on antipsychotic-associated weight gain in a naturalistic sample of 53 youth with ASD. Results indicate that treatment with metformin stabilized BMI z-score over a nearly 2 year mean treatment period. Further work is indicated to determine the safety and efficacy of metformin treatment in youth with ASD, as well as predictors of response as a treatment for antipsychotic-induced weight gain.

The neurobehavioral and molecular phenotype of Angelman Syndrome.

Angelman Syndrome (AS) is a rare neurodevelopmental disorder associated with developmental delay, speech impairment, gait ataxia, and a unique behavioral profile. AS is caused by loss of maternal expression of the paternally imprinted UBE3A gene. In this study we aim to contribute to understanding of the neurobehavioral phenotype of AS with particular focus on the neuropsychiatric presentation of the disorder. We also undertake initial exploration of brain-derived neurotrophic factor (BDNF) plasma levels in AS. Twelve individuals ages 3 years or older with a confirmed genetic diagnosis of AS underwent detailed medical history, phenotypic characterization, and BDNF plasma sampling. The results of this study demonstrate that individuals with AS suffer from significant developmental delay, impaired adaptive behavior, and sleep disruption. Additionally, hyperactivity/impulsivity appears to be the primary behavioral domain noted in these individuals. The majority of individuals in this project met criteria for autism spectrum disorder on the Autism Diagnostic Observation Schedule (ADOS); however, a negative correlation was noted between ADOS score and developmental age. BDNF plasma levels in AS individuals were significantly elevated compared to neurotypical controls. This is the first report of abnormal BDNF levels in AS, and one that necessitates larger future studies. The results provide a clue to understanding abnormal neuronal development in AS and may help guide future AS research.

Artemisinin and a series of novel endoperoxide antimalarials exert early effects on digestive vacuole morphology.

Artermisinin and its derivatives are now the mainstays of antimalarial treatment; however, their mechanism of action is only poorly understood. We report on the synthesis of a novel series of epoxy-endoperoxides that can be prepared in high yields from simple starting materials. Endoperoxides that are disubstituted with alkyl or benzyl side chains show efficient inhibition of the growth of both chloroquine-sensitive and -resistant strains of Plasmodium falciparum. A trans-epoxide with respect to the peroxide linkage increases the activity compared to that of its cis-epoxy counterpart or the parent endoperoxide. The novel endoperoxides do not show a strong interaction with artemisinin. We have compared the mechanism of action of the novel endoperoxides with that of artemisinin. Electron microscopy reveals that the novel endoperoxides cause the early accumulation of endocytic vesicles, while artemisinin causes the disruption of the digestive vacuole membrane. At longer incubation times artemisinin causes extensive loss of organellar structures, while the novel endoperoxides cause myelin body formation as well as the accumulation of endocytic vesicles. An early event following endoperoxide treatment is the redistribution of the pH-sensitive probe LysoSensor Blue from the digestive vacuole to punctate structures. By contrast, neither artemisinin nor the novel endoperoxides caused alterations in the morphology of the endoplasmic reticulum nor showed antagonistic antimalarial activity when they were used with thapsigargin. Analysis of rhodamine 123 uptake by P. falciparum suggests that disruption of the mitochondrial membrane potential occurs as a downstream effect rather than as an initiator of parasite killing. The data suggest that the digestive vacuole is an important initial site of endoperoxide antimalarial activity.

Primaquine synergises the activity of chloroquine against chloroquine-resistant P. falciparum.

In recent years, resistance to the antimalarial drug, chloroquine, has become widespread. It is, therefore, imperative to find compounds that could replace chloroquine or work synergistically with this drug to overcome chloroquine resistance. We have examined the interaction between chloroquine, a 4-aminoquinoline, and a number of 8-aminoquinolines, including primaquine, a drug that is widely used to treat Plasmodium vivax infections. We find that primaquine is a potent synergiser of the activity of chloroquine against chloroquine-resistant Plasmodium falciparum. Analysis of matched transfectants expressing mutant and wild-type alleles of the P. falciparum chloroquine resistance transporter (PfCRT) indicate that primaquine exerts its activity by blocking PfCRT, and thus enhancing chloroquine accumulation. Our data suggest that a novel formulation of two antimalarial drugs already licensed for use in humans could be used to treat chloroquine-resistant parasites.

Novel endoperoxide antimalarials: synthesis, heme binding, and antimalarial activity.

We report the synthesis of a series of novel epoxy endoperoxide compounds that can be prepared in high yields in one to three steps from simple starting materials. Some of these compounds inhibit the growth of Plasmodium falciparum in vitro. Structure-activity studies indicate that an endoperoxide ring bisubstituted with saturated cyclic moieties is the pharmacophore. To study the molecular basis of the action of these novel antimalarial compounds, we examined their ability to interact with oxidized and reduced forms of heme. Some of the compounds interact with oxidized heme in a fashion similar to chloroquine and other 4-aminoquinolines, while some of the compounds interact with reduced heme. However, the level of antimalarial potency is not well correlated with these activities, suggesting that some of the endoperoxides may exert their antimalarial activities by a novel mechanism of action.

Differences in presentation and follow-up between HIV-1 antibody positive teenagers and adults: the need for a more focused approach to care?

Our findings show a high rate of loss to follow-up in HIV-positive teenagers compared with adults. Of concern is the fact that this group also have high rates of sexually transmitted infections, unprotected sex and pregnancy. There is an urgent need to examine the reasons for this and adopt strategies to minimize risk-taking behaviour and to improve access to appropriate healthcare.

Treatment of tuberculosis in HIV-infected persons in the era of highly active antiretroviral therapy.

OBJECTIVE: To assess the risks and benefits of administering highly active antiretroviral therapy (HAART) during the treatment of tuberculosis (TB) in HIV-infected patients. DESIGN AND METHODS: HIV-1 patients presenting to 12 HIV centres in Greater London and south-east England with culture-proven TB were identified from January 1996 to June 1999. Case-notes were reviewed retrospectively. RESULTS: Patients (n = 188) were severely immunocompromised with a median CD4 cell count at TB diagnosis of 90 x 106 cells/l (IQR: 30-180). At presentation, 85% (n = 159) were not taking antiretrovirals. A total of 45% commenced HAART during TB treatment, which was associated with significant reductions in viral load, AIDS-defining illness (ADI) [3.5 versus 24.5%; relative risk (RR) = 0.14] and mortality. Only nine of 91 (10%) patients with a CD4 count > 100 x 106 cells/l at TB diagnosis experienced a further ADI, whereas 18 of 92 (20%) patients with a CD4 count < 100 x 106 cells/l developed this complication. Adverse events (AE) occurred in 99 (54%) of 183 patients, one-third of whom changed or interrupted HIV and/or TB medication. The majority of AE occurred within the first 2 months, with peripheral neuropathy (21%), rash (17%) and gastrointestinal upset (10%) occurring most commonly. CONCLUSIONS: Many physicians delay HAART in patients presenting with TB because of pill burden, drug/drug interactions and toxicity. Although the use of HAART led to significant reductions in viral load, ADI and mortality, co-infected patients commonly experienced AE leading to interruptions in TB/HIV therapy. We therefore recommend starting HAART early for patients with advanced HIV disease (CD4 < 100 x 106 cells/l) and deferring HAART until the continuation phase of TB therapy (i.e. after 2 months) for patients who are clinically stable (CD4 > 100 x 106 cells/l).