Inter-Individual Differences in Neurobehavioural Impairment following Sleep Restriction Are Associated with Circadian Rhythm Phase

Although sleep restriction is associated with decrements in daytime alertness and neurobehavioural performance, there are considerable inter-individual differences in the degree of impairment. This study examined the effects of short-term sleep restriction on neurobehavioural performance and sleepiness, and the associations between individual differences in impairments and circadian rhythm phase. Healthy adults (n = 43; 22 M) aged 22.5 ± 3.1 (mean ± SD) years maintained a regular 8:16 h sleep:wake routine for at least three weeks prior to laboratory admission. Sleep opportunity was restricted to 5 hours time-in-bed at home the night before admission and 3 hours time-in-bed in the laboratory, aligned by wake time. Hourly saliva samples were collected from 5.5 h before until 5 h after the pre-laboratory scheduled bedtime to assess dim light melatonin onset (DLMO) as a marker of circadian phase. Participants completed a 10-min auditory Psychomotor Vigilance Task (PVT), the Karolinska Sleepiness Scale (KSS) and had slow eye movements (SEM) measured by electrooculography two hours after waking. We observed substantial inter-individual variability in neurobehavioural performance, particularly in the number of PVT lapses. Increased PVT lapses (r = -0.468, p < 0.01), greater sleepiness (r = 0.510, p < 0.0001), and more slow eye movements (r = 0.375, p = 0.022) were significantly associated with later DLMO, consistent with participants waking at an earlier circadian phase. When the difference between DLMO and sleep onset was less than 2 hours, individuals were significantly more likely to have at least three attentional lapses the following morning. This study demonstrates that the phase of an individual’s circadian system is an important variable in predicting the degree of neurobehavioural performance impairment in the hours after waking following sleep restriction, and confirms that other factors influencing performance decrements require further investigation

Home-based care of low-risk febrile neutropenia in children-an implementation study in a tertiary paediatric hospital

BACKGROUND: Home-based management of low-risk febrile neutropenia (FN) is safe, improves quality of life and reduces healthcare expenditure. A formal low-risk paediatric program has not been implemented in Australia. We aimed to describe the implementation process and evaluate the clinical impact. METHOD: This prospective study incorporated three phases: implementation, intervention and evaluation. A low-risk FN implementation toolkit was developed, including a care-pathway, patient information, home-based assessment and educational resources. The program had executive-level endorsement, a multidisciplinary committee and a nurse specialist. Children with cancer and low-risk FN were eligible to be transferred home with a nurse visiting daily after an overnight period of observation for intravenous antibiotics. Low-risk patients were identified using a validated decision rule, and suitability for home-based care was determined using disease, chemotherapy and patient-level criteria. Plan-Do-Study-Act methodology was used to evaluate clinical impact and safety. RESULTS: Over 18 months, 292 children with FN were screened: 132 (45%) were low-risk and 63 (22%) were transferred to home-based care. Compared with pre-implementation there was a significant reduction in in-hospital median LOS (4.0 to 1.5 days, p < 0.001) and 291 in-hospital bed days were saved. Eight (13%) patients needed readmission and there were no adverse outcomes. A key barrier was timely screening of all patients and program improvements, including utilising the electronic medical record for patient identification, are planned. CONCLUSION: This program significantly reduces in-hospital LOS for children with low-risk FN. Ongoing evaluation will inform sustainability, identify areas for improvement and support national scale-up of the program

Impact of antibiotic allergy labels on patient outcomes in a tertiary paediatric hospital

Aims Antibiotic allergies are reported in 5–15% of children. This study aimed to evaluate the impact of common β‐lactam antibiotic allergy labels (AALs) on hospital treatment, focusing on length of stay and appropriateness of antibiotic prescribing. Methods This was a retrospective cohort study over 21 months at the Royal Children's Hospital Melbourne, Australia. A subset of children with the most common β‐lactam allergies, and who required admission for intravenous antibiotics over a 12‐month period, was analysed for appropriateness of prescribing. Non‐allergic patients were matched to evaluate associations between AALs and hospital treatment. Results There were 98 912 children admitted over the study period, of whom 938 (1%) had at least one AAL on first admission. Of all encounters, 5145 (2.5%) were for children with AALs. The most common AALs were to amoxicillin and amoxicillin‐clavulanic acid combinations (40.8%), cefalexin (14.4%) and trimethoprim‐sulfamethoxazole (9.7%). For the subset, there were 66 admissions for children who required intravenous antibiotics. Documentation was adequate for 27% of AALs. Inappropriate prescribing occurred in almost half (47%). Hospital stay was longer for children with AALs (median 4.7 days; IQR 2.3–9.2) compared to non‐allergic controls (median 3.9 days; IQR 1.9–6.8; P  = .02). Children with AALs were more likely to receive restricted antibiotics (aOR 3.03; 95% CI, 1.45–6.30; P  = .003). Conclusion This is the first study to demonstrate high rates of inappropriate prescribing in children with AALs. Children with AALs were significantly more likely to receive restricted antibiotics and had a longer length of stay compared with non‐allergic controls.</p

Sleepiness measures two hours after waking following two nights of sleep restriction, as indicated by the number of PVT lapses (A & B; n = 43), Karolinska Sleepiness Scale (C & D; n = 43), and the proportion of EOG epochs containing slow eye movements (E & F; n = 37).

<p>Data are plotted relative to circadian phase represented by (a) the clock hour of an individuals’ DLMO (left panels; A, C, E) and (b) phase angle difference between dim light melatonin onset (DLMO) and mean sleep onset on the 9 nights prior to the laboratory visit (right panels; B, D, F), (e.g., -2 represents someone with a DLMO occurring 2 hours before sleep onset time). Main bar plots represent data categorised into hourly bins (mean ± SEM) to illustrate the relationship between circadian phase and sleepiness. Inserts present the raw data scatterplots.</p

Schematic representation of the relationship between circadian phase and morning performance for individuals with a phase angle < 2 h (black) and individuals with a phase angle ≥ 2 h (grey).

<p>Phase angle of entrainment represents the time between dim light melatonin onset (DLMO) and mean sleep onset on the 9 nights prior to the laboratory visit. Circles illustrate the timing of DLMO; horizontal bars represent sleep times; squares represent the number of PVT lapses two hours after waking.</p

Relationships between dim light melatonin onset and mood states composed-anxious (r = -0.366), agreeable-hostile (r = -0.347) and clearheaded-confused (r = -0.459).

<p>All relationships were significant (p < 0.05). Higher values represent more positive mood.</p

Participant characteristics shown for the entire sample (n = 43) and separately for individuals recording no lapses on the PVT (n = 16) compared to individuals with a high number of lapses (4+, n = 16) two hours after waking.

<p>* Characteristics between groups were compared using Student’s t-test. Gender was compared using Chi-Squared test.</p><p>Participant characteristics shown for the entire sample (n = 43) and separately for individuals recording no lapses on the PVT (n = 16) compared to individuals with a high number of lapses (4+, n = 16) two hours after waking.</p

Study protocol to assess sleepiness following sleep restriction.

<p>The protocol is plotted for a participant maintaining a 00:00–08:00 h sleep schedule (black bars). Following at least 3 weeks of an 8-hour sleep schedule at home, participants restricted their sleep to 5 hours on the last night at home, remaining in dim light for the 3 hours of extended wake (grey bar on study day 1). Participants attended the sleep laboratory on the following evening. Two hours after session start ambient light levels were reduced to < 2 lux (dark grey bar on study day 2). Saliva samples (●) were collected every 30 to 60 minutes for assessment of circadian phase. Sleep was further restricted to three hours duration in the laboratory (0 lux). POMS-Bi (+) was completed 1.75 hours after waking. Two hours after waking participants underwent constant posture (grey diagonal striped bar) and completed a performance battery (▲) including the Karolinska Sleepiness Scale, auditory psychomotor vigilance test, and Karolinksa Drowsiness Test. The test battery was practiced up to three times during constant posture on study night 1.</p