Lessons from isavuconazole therapeutic drug monitoring at a United Kingdom Reference Center.

We determined isavuconazole serum concentrations for 150 UK patients receiving standard isavuconazole dosing regimens, including serial therapeutic drug monitoring for several patients on prolonged therapy. Mean trough isavuconazole concentrations in these patients were virtually identical to those reported previously from clinical trials, although greater variability was seen in patients below 18 years of age. Serial monitoring in patients receiving prolonged therapy suggested gradual, near-linear accumulation of the drug over many weeks.

The association between benzodiazepine use and sleep quality in residential aged care facilities: a cross-sectional study.

BACKGROUND: Benzodiazepines are commonly prescribed in residential aged care facilities (RACFs) for their sedative and anxiolytic effects. The objective of this study was to investigate the association between benzodiazepine use and sleep quality in residents of RACFs. METHODS: A cross-sectional study involving 383 participants was conducted in six Australian RACFs. Night-time sleep quality, day-time drowsiness and day-time napping behavior were assessed using a validated questionnaire. Logistic regression was used to compute adjusted odds ratios (AORs) and 95% confidence intervals (CIs) for the association between benzodiazepine use and sleep quality. Covariates included pain, dementia severity, depression, insomnia and other sedative use. RESULTS: Of the 383 residents (mean age 87.5 years, 77.5% female), 96(25.1%) used a benzodiazepine on a regular basis. Residents who used long-acting benzodiazepines on a regular basis had higher night-time sleep quality than non-users (AOR = 4.00, 95%CI 1.06 - 15.15). Residents who used short-acting benzodiazepines on a PRN only basis had longer daytime napping times than non-users (AOR = 1.77, 95%CI 1.01 - 3.08). No benzodiazepine category was associated with day-time drowsiness. CONCLUSIONS: The association between benzodiazepine use and sleep quality is dependent on the half-life and prescribing pattern of the benzodiazepine. Short-acting PRN benzodiazepines were associated with lower night time sleep quality and longer day-time napping compared to long-acting regular benzodiazepines. Longitudinal studies are needed to determine whether these findings reflect channeling of short-acting agents to residents at higher risk of sleep disorders.

Infection with antiretroviral-susceptible HIV in an individual adherent to pre-exposure prophylaxis: strategies for treatment initiation.

HIV pre-exposure prophylaxis (PrEP) is effective at preventing sexual acquisition of HIV, and failures in clinical trials are largely attributable to medication nonadherence. We report here a case of infection with a fully susceptible strain of HIV in an individual adherent to PrEP as demonstrated by pharmacy records and intracellular tenofovir diphosphate levels. At diagnosis, the viral load was 90 copies/mL precluding initial genotype testing due to low copy number. While PrEP failure is rare, this case underscores the importance of regular HIV testing for patient on PrEP and prompts discussion regarding the approach to treatment following failure where an initial genotype is not yet available or not possible due to low viral load. Few other case reports of PrEP failure exist in the literature and approaches to treatment varied widely. We suggest the initial viral copy number may guide next steps and discuss the risks and benefits of stopping PrEP, escalating therapy with integrase inhibitors or boosted protease inhibitors, or switching to non-nucleoside antiretroviral treatment regimens.

Analgesic Use and Daytime Sleepiness in Residents With and Without Dementia in Residential Aged Care Facilities.

BACKGROUND: Managing pain in residents of residential aged care facilities (RACFs) is challenging, especially for people with dementia. Clinicians must weigh the benefits of analgesic use against the potential for adverse events, particularly daytime sleepiness. OBJECTIVES: The aim was to investigate the association between analgesic use and daytime sleepiness in residents with and without dementia in RACFs. METHODS: This was a cross-sectional study of 383 permanent residents from six low-level and high-level RACFs in South Australia. Main measures included analgesic use in the previous 24 h, analgesic load and self-reported daytime sleepiness. Covariates included relevant comorbidities (insomnia, depression, painful conditions), Charlson's Comorbidity Index, sedative load, self-reported and clinician-observed pain and dementia severity. Logistic regression was used to compute odds ratios (ORs) and confidence intervals (CIs) for the association between analgesic use and daytime sleepiness. RESULTS: Analgesics were used by 288 residents (75.2%) in the previous 24 h. These included paracetamol (n = 264, 68.9%), opioids (n = 110, 28.7%) and oral NSAIDs (n = 14, 3.7%). Overall, 116 (30.3%) residents were categorized as having daytime sleepiness. Of those with dementia, 77 (45.6%) were categorized as having daytime sleepiness. Opioid use in the previous 24 h was not associated with daytime sleepiness in unadjusted or adjusted analyses. Paracetamol use was positively associated with daytime sleepiness (OR 2.31; 95% CI 1.20-4.42). CONCLUSION: Although daytime sleepiness occurred in a large number of residents, especially those with dementia, this sleepiness was not necessarily associated with use of opioids. The risk of opioid-induced sedation may have been managed by strategies including preferential prescribing of paracetamol to residents at risk of sleepiness, opioid discontinuation in residents who experienced sleepiness, and use of low doses of opioids.