Can insomnia be fatal? An Australian case of fatal familial insomnia.

Fatal familial insomnia (FFI) is a rare prion disease with autosomal dominant inheritance. Currently, there is only one published case study of FFI in Australia. FFI is universally fatal, with the disease duration ranging from 8 to 72 months. Clinically, it manifests with disordered sleep-wake cycle, dysautonomia, motor disturbances and neuropsychiatric disorders. We describe a case of FFI detailing the investigative process, including the importance of sleep assessment and polysomnography in obtaining a diagnosis.

Case report of amiodarone-associated allergic pneumonitis amidst the COVID-19 pandemic.

Amiodarone is a common antiarrhythmic drug that is utilised in clinical practice and is associated with pulmonary toxicity. The most common form of pulmonary complication is interstitial pneumonitis which is treated with discontinuation of amiodarone and initiation of corticosteroids. Amiodarone-induced pulmonary eosinophilia is a rare complication of amiodarone therapy, with blood and pulmonary eosinophilia the predominant features. During the COVID-19 era, the incidence of delay in treatment of pulmonary pathology is also delayed due to the effort of excluding COVID-19 infection. Here we report a case of a 64-year-old man who developed eosinophilic pneumonia after initiation of amiodarone therapy, and the investigations required to exclude other forms of pulmonary toxicity. We also reviewed the effect of COVID-19 testing in the management of patients presenting with respiratory distress.

Exploring the associations between shift work disorder, depression, anxiety and sick leave taken amongst nurses.

This study aimed to evaluate the association between shift work disorder and mental health in hospital-based nurses. Staff completed an online survey comprising demographic questions, the Shift Work Disorder Questionnaire, Patient Health-9 and the General Anxiety Disorder-7 scale. Sick leave data were collected from archival records from the Human Resources Department. Two hundred and two nurses (95% female; age M = 35.28 years ± SD = 12) participated (42% of eligible staff). Those at high risk of shift work disorder had higher depression (M = 7.54 ± SD = 4.28 vs. M = 3.78 ± SD = 3.24; p < 0.001) and anxiety (M = 5.66 ± SD = 3.82 vs. M = 2.83 ± SD = 3.33, p < 0.001) compared to those at low risk. Linear regression models showed that being at high risk of shift work disorder was the most significant predictor of depression, explaining 18.8% of the variance in depression (R2  = 0.188, adjusted R2  = 0.184, F(1, 200) = 46.20, p < 0.001). Shift work disorder combined with the number of night shifts and alcoholic drinks on non-work days accounted for 49.7% of the variance in anxiety scores (R2  = 0.497, adjusted R2  = 0.453, F(3, 35) = 11.51, p < 0.001). Mean sick leave in those with high risk of shift work disorder was 136.17 hr (SD = 113.11) versus 103.98 hr (SD = 94.46) in others (p = 0.057). Depression and years of shift work accounted for 18.9% of the variance in sick leave taken (R2  = 0.189, adjusted R2  = 0.180, F(2, 175) = 20.36, p < 0.001). Shift work disorder is strongly associated with depression and anxiety, providing a potential target to improve mental health in shift workers. Depression, in turn, is a significant contributing factor to sick leave.

Neural correlates of cough hypersensitivity in humans: evidence for central sensitisation and dysfunctional inhibitory control.

INTRODUCTION: Chronic non-productive coughing is a major complication of pulmonary disease and can also occur in many individuals without identifiable underlying pathology. The common clinical link in patients with cough is an enhanced sensitivity of the respiratory system to stimuli that subsequently evoke excessive coughing. The aetiology of this 'cough hypersensitivity syndrome' is unclear but believed to involve hypersensitivity of the sensory neural pathways that innervate the airways and lungs. METHODS: In the present study, we used functional brain imaging to compare central neural responses to airway stimulation using inhaled capsaicin in healthy people and patients with cough hypersensitivity. RESULTS: Hypersensitivity in response to inhaled capsaicin coincided with elevated neural activity in the midbrain in a region encompassing the nucleus cuneiformis (left: p<0.001; right: p<0.001) and periaqueductal gray (p=0.008) in comparison to normal sensitivity in controls. The enhanced activity noted in the midbrain is similar to that occurring in patients with chronic pain, thus providing empirical evidence to support the notion that cough and pain share neurobiological similarities. Furthermore, patients with cough hypersensitivity displayed difficulty controlling their cough, which manifested as a failure to suppress cough during capsaicin challenge (ie, reduced cough frequency) in controls compared with patients with cough hypersensitivity (p=0.046). Cough suppression was associated with reduced activity in a forebrain network that included the dorsomedial prefrontal and anterior mid-cingulate cortices. Additionally, cough frequency was correlated with activity in the right inferior frontal gyrus (R(2)=0.6, p<0.001) and right anterior insula (R(2)=0.6, p<0.001), regions previously implicated in voluntary cough suppression. CONCLUSIONS: These findings provide insight into the central neurobiology of cough hypersensitivity and suggest that both central amplification of cough sensory inputs and reduced capacity to suppress cough motor behaviours define patients with problematic cough.

The relationship between sleep disturbances and endometriosis: A systematic review.

OBJECTIVE: Endometriosis is associated with a range of symptoms that can negatively impact a person's quality of life. While pain and infertility have received at lot of attention, sleep disturbances in individuals with endometriosis has been overlooked in both clinical practice and research. Therefore, the primary aim of this systematic review was to gather evidence from the current literature to illustrate the association between sleep disturbances and endometriosis. STUDY DESIGN: A literature search was conducted using three electronic databases (OVID EMBASE, MEDLINE, and Web of Science). Observational studies, published in English, that involved participants aged 18 years or older that compared sleep outcomes between endometriosis patients and those without a history of endometriosis were included. The quality of each study was assessed using the Joanna Briggs Institute critical appraisal tools. RESULTS: Nine studies (six case-control and three cross-sectional) were included in this review; 7 with low risk of bias and 2 with moderate risk of bias. The studies demonstrated heterogeneity in the assessment of sleep disturbances. However, 7 studies reported a significant positive association between endometriosis and sleep disturbances. Moreover, this impact on sleep was further complicated by the complex interaction between pain, fatigue and quality of life. CONCLUSION: Current studies suggest an association between sleep disturbances and endometriosis, which may provide a blueprint for future clinical recommendations to screen and treat sleep disturbances in individuals with endometriosis to improve their quality of life. Future studies should aim to standardise the methods of assessing sleep disturbances and explore potential contributing factors.

Venous blood gases in the assessment of respiratory failure in patients undergoing sleep studies: a randomized study.

STUDY OBJECTIVES: Venous blood gases (VBGs) are not consistently considered suitable surrogates for arterial blood gases (ABGs) in assessing acute respiratory failure due to variable measurement error. The physiological stability of patients with chronic ventilatory failure may lead to improved agreement in this setting. METHODS: Adults requiring ABGs for sleep or ventilation titration studies had VBGs drawn before or after each ABG, in a randomized order. Veno-arterial correlation and agreement were examined for carbon dioxide tension (PCO2), pH, oxygen tension (PO2) and oxygen saturation (SO2). RESULTS: We analyzed 115 VBG-ABG pairs from 61 patients. Arterial and venous measures were correlated (with p<0.05) for PCO2 (r=0.84) and pH (r=0.72), but not for PO2 or SO2. Adjusted mean veno-arterial differences (95% limits of agreement) were +5.0mmHg (-4.4 to +14.4) for PCO2; -0.02 (-0.09 to +0.04) for pH; -34.3mmHg (-78.5 to +10.0) for PO2; and -23.9% (-61.3 to +13.5) for SO2. VBGs obtained from the dorsal hand demonstrated a lower mean PCO2 veno-arterial difference (p<0.01). A venous PCO2 threshold of ≥45.8mmHg was >95% sensitive for arterial hypercapnia, so measurements below this can exclude the diagnosis without an ABG. A venous PCO2 threshold of ≥53.7mmHg was >95% specific for arterial hypercapnia, so such readings can be assumed diagnostic. The area under the receiver operating characteristic curve of 0.91 indicated high discriminatory capacity. CONCLUSIONS: A venous PCO2 <45.8mmHg or ≥53.7mmHg would exclude or diagnose hypercapnia, respectively, in patients referred for sleep studies, but VBGs are poor surrogates for ABGs where precision is important. CLINICAL TRIAL REGISTRATION: Registry: Australian New Zealand Clinical Trials Register; Name: A comparison of arterial and blood gas analyses in sleep studies; Identifier: ACTRN12617000562370; URL https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=372717.

Brainstem processing of cough sensory inputs in chronic cough hypersensitivity.

BACKGROUND: Chronic cough is a prevalent and difficult to treat condition often accompanied by cough hypersensitivity, characterised by cough triggered from exposure to low level sensory stimuli. The mechanisms underlying cough hypersensitivity may involve alterations in airway sensory nerve responsivity to tussive stimuli which would be accompanied by alterations in stimulus-induced brainstem activation, measurable with functional magnetic resonance imaging (fMRI). METHODS: We investigated brainstem responses during inhalation of capsaicin and adenosine triphosphate (ATP) in 29 participants with chronic cough and 29 age- and sex-matched controls. Psychophysical testing was performed to evaluate individual sensitivities to inhaled stimuli and fMRI was used to compare neural activation in participants with cough and control participants while inhaling stimulus concentrations that evoked equivalent levels of urge-to-cough sensation. FINDINGS: Participants with chronic cough were significantly more sensitive to inhaled capsaicin and ATP and showed a change in relationship between urge-to-cough perception and cough induction. When urge-to-cough levels were matched, participants with chronic cough displayed significantly less neural activation in medullary regions known to integrate airway sensory inputs. By contrast, neural activations did not differ significantly between the two groups in cortical brain regions known to encode cough sensations whereas activation in a midbrain region of participants with chronic cough was significantly increased compared to controls. INTERPRETATION: Cough hypersensitivity in some patients may occur in brain circuits above the level of the medulla, perhaps involving midbrain regions that amplify ascending sensory signals or change the efficacy of central inhibitory control systems that ordinarily serve to filter sensory inputs. FUNDING: Supported in part by a research grant from Investigator-Initiated Studies Program of Merck Sharp & Dohme Pty Ltd. The opinions expressed in this paper are those of the authors and do not necessarily represent those of Merck Sharp & Dohme (Australia) Pty Ltd.

Continuous renal replacement therapy with an automated monitor is superior to a free-flow system during extracorporeal life support.

OBJECTIVES: To determine whether integrated continuous renal replacement therapy provides more accurate fluid management than IV pump free-flow ultrafiltration in pediatric patients on extracorporeal life support. DESIGN: Retrospective study. SETTING: PICU and neonatal ICU in a tertiary academic center. PATIENTS: Infants and children less than 18 years old. INTERVENTIONS: Extracorporeal membrane oxygenation and continuous renal replacement therapy. MEASUREMENTS AND MAIN RESULTS: Clinical data collected on patients who received free-flow or integrated renal replacement therapy while on extracorporeal life support. Normalized ultrafiltration error was calculated as: (physician specified fluid loss per 24-hr period - actual fluid loss per 24-hr period) divided by patient body weight (kg). Mixed linear regression analyses were used to model longitudinal ultrafiltration error trajectories within each mode of ultrafiltration. Based on an analysis of 458 serial ultrafiltration fluid balance measurements, integrated ultrafiltration was significantly more accurate than free-flow ultrafiltration (normalized ultrafiltration error of 1.2 vs 13.1 mL; p < 0.001). After adjusting for patient factors and time, integrated ultrafiltration was associated with a significantly lower normalized ultrafiltration error (variable estimate, -24 ± 6; p < 0.001). The use of integrated ultrafiltration was associated with shorter duration of extracorporeal life support (384 vs 583 hr, p < 0.001) and renal replacement therapy (185 vs 477 hr, p < 0.001) than free-flow patients. Overall ICU and hospital length of stay and in-hospital mortality were similar between the groups. CONCLUSIONS: While free-flow ultrafiltration has the advantages of simplicity and low cost, integrated renal replacement therapy provides more accurate fluid management during extracorporeal life support. Better fluid status management with integrated renal replacement therapy may contribute to shorter duration of extracorporeal life support.

The effectiveness of an individualized sleep and shift work education and coaching program to manage shift work disorder in nurses: a randomized controlled trial.

STUDY OBJECTIVES: While insomnia and sleepiness symptoms are common in shift workers, 20%-30% experience more severe symptoms and meet the criteria for shift work disorder (SWD). SWD can lead to impairments in cognitive function, physical and mental health, and reduced productivity and increased risk of workplace injury. The aim of this study was to deliver and evaluate a shift work individual management coaching program, focusing on sleep education, promoting good sleep hygiene, and providing individualized behavioral strategies to cope with shift schedules. METHODS: A clustered randomized controlled trial of sleep education and sleep disorders screening was undertaken, based on hospital wards at a tertiary hospital in Melbourne, Australia. Participants identified as high risk for SWD underwent one of two 8-week programs, a shift work individualized management program, or an active control. The primary outcome was ward-based sick leave. Secondary outcomes were SWD risk, sleep hygiene, insomnia, depression, and anxiety. A total of 149 nurses, across 16 wards (96% female, 34.66 ± 11.99 years) completed both baseline and follow-up questionnaires (23.9% were high risk SWD). RESULTS: There was no significant reduction in sick leave between intervention and control wards (mean difference = 1.2 days, P = .063). Improvements were seen in insomnia (P < .0001) and depression (intervention, P ≤ .0001, control, P = .023) in both groups, but were not significantly different between programs. Anxiety (P = .001. control P = .079) and Functional Outcomes of Sleep Questionnaire 10 (P = .001 control P = .056) improved only for the intervention. CONCLUSIONS: This SWD intervention trial did not reduce sick leave compared to the active control but there was an improvement. Improvements in sleep hygiene, insomnia, depression, and anxiety severity were seen for both groups. Future intervention trials should consider including both sleep and mental health interventions, strategies to avoid between group contamination and the duration of programs for optimal behavioral modification. CLINICAL TRIAL REGISTRATION: Registry: Australian New Zealand Clinical Trials Registry; Name: Sleep Health Management for Healthcare Workers; URL: https://anzctr.org.au/Trial/Registration/TrialReview.aspx?ACTRN=12616000369426; Identifier: ACTRN12616000369426. CITATION: Booker LA, Sletten TL, Barnes M, et al. The effectiveness of an individualized sleep and shift work education and coaching program to manage shift work disorder in nurses: a randomized controlled trial. J Clin Sleep Med. 2022;18(4):1035-1045.

The role of sleep hygiene in the risk of Shift Work Disorder in nurses.

A high proportion (20%-30%) of shift workers experience Shift Work Disorder (SWD), characterized by chronic sleepiness and/or insomnia associated with work schedules. The reasons for individual variation in shift work tolerance are not well understood, however. The aim of this study was to identify individual factors that contribute to the risk of SWD. Nurses (n = 202) were categorized as low or high risk of SWD based on the Shift Work Disorder Questionnaire. Participants provided demographic and lifestyle information and completed the Sleep Hygiene Index (SHI) and Morningness-Eveningness Questionnaire (MEQ). High risk of SWD was associated with poorer sleep hygiene (SHI, 35.41 ± 6.19 vs. 31.49 ± 7.08, p < .0001) and greater eveningness (MEQ, 34.73 ± 6.13 vs. 37.49 ± 6.45, p = .005) compared to low risk. No other factors, including body mass index, marital status, having children, or caffeine or alcohol intake were significant. Logistic regression showed that SHI was the most significant contributing factor to SWD risk (odds ratio [OR] = 1.09, 95% confidence interval [CI] = 1.04 to 1.14). Standardized odds ratio further revealed that with every unit increase on the SHI score, the odds of being at high risk of SWD increased by 80% (OR = 1.84). Most individuals at high risk of SWD reported "always" or "frequently" going to bed at different times (79%) and waking at different times (83%; compared to 58%, p = .017, and 61%, p = .002, respectively for the low-risk group), as well as going to bed stressed/angry (67% vs. 41%, p < .0001) and/or planning/worrying in bed (54% vs. 22%, p < .0001). Interventions aimed at improving sleep hygiene practices and psychological health of shift workers may help reduce the risk of SWD.

Driver education: Enhancing knowledge of sleep, fatigue and risky behaviour to improve decision making in young drivers.

This study assessed the impact of an education program on knowledge of sleepiness and driving behaviour in young adult drivers and their performance and behaviour during simulated night driving. Thirty-four participants (18-26 years old) were randomized to receive either a four-week education program about sleep and driving or a control condition. A series of questionnaires were administered to assess knowledge of factors affecting sleep and driving before and after the four-week education program. Participants also completed a two hour driving simulator task at 1am after 17 h of extended wakefulness to assess the impact on driving behaviour. There was an increase in circadian rhythm knowledge in the intervention group following the education program. Self-reported risky behaviour increased in the control group with no changes in other aspects of sleep knowledge. There were no significant differences in proportion of intervention and control participants who had microsleeps (p ≤ .096), stopped driving due to sleepiness (p = .107), recorded objective episodes of drowsiness (p = .455), and crashed (p = .761), although there was a trend towards more control participants having microsleeps and stopping driving. Those in the intervention group reported higher subjective sleepiness at the end of the drive [M = 6.25, SD = 3.83, t(31) = 2.15, p = .05] and were more likely to indicate that they would stop driving [M = 3.08, SD = 1.16, t(31) = 2.24, p = .04]. The education program improved some aspects of driver knowledge about sleep and safety. The results also suggested that the education program lead to an increased awareness of sleepiness. Education about sleep and driving could reduce the risk of drowsy driving and associated road trauma in young drivers, but requires evaluation in a broader sample with assessment of real world driving outcomes.

A pilot study of inspiratory capacity and resting dyspnea correlations in exacerbations of COPD and asthma.

Measurement of inspiratory capacity (IC) as a marker of dynamic lung hyperinflation has been shown to correlate with dyspnea and exercise performance in stable COPD, and is therefore of potential utility in the management of this condition. We have examined whether similar relationships exist during acute exacerbations of COPD and asthma in order to determine whether there is a role for IC monitoring in acute management of these conditions. Eight patients with COPD and ten with asthma requiring hospital admission for acute exacerbations were studied with spirometry (including IC) at admission and at discharge and had concurrent self-perceived resting dyspnea ratings recorded. Over the admission there were significant improvements in resting dyspnea for the COPD group only, and improvements in spirometric indices in the asthma group only. No significant correlations were found between changes in dyspnea and changes in IC, in terms of acute responses to bronchodilator and in response to treatment over the hospital admission. These data suggest that dynamic hyperinflation during acute exacerbations of COPD and asthma is not as sensitive an indicator of resting dyspnea as in stable disease. A role for IC monitoring in the management of acute exacerbations of these diseases has not been identified.

Percutaneous versus surgical tracheostomy: A randomized controlled study with long-term follow-up.

OBJECTIVE: To compare the safety, availability, and long-term sequelae of percutaneous vs. surgical tracheostomy. DESIGN: Prospective, randomized, controlled study. SETTING: Combined medical/surgical intensive care unit in a tertiary referral hospital. PATIENTS: Two hundred critically ill mechanically ventilated patients who required tracheostomy. INTERVENTIONS: Tracheostomy by either percutaneous tracheostomy or surgical tracheostomy performed in the intensive care unit. MEASUREMENTS AND MAIN RESULTS: The primary outcome measure was the aggregate incidence of predefined moderate or severe complications. The secondary outcome measures were the incidence of each of the components of the primary outcome. Long-term follow-up included clinical assessment, flow volume loops, and bronchoscopy. Both groups were well matched for age, gender, admission Acute Physiology and Chronic Health Evaluation II score, period of endotracheal intubation, reason for intubation, and admission diagnosis. There was no statistical difference between groups for the primary outcome. Bleeding requiring surgical intervention occurred in three percutaneous tracheostomy patients and in no surgical tracheostomy patient (p = .2). Postoperative infection (p = .044) and cosmetic sequelae (p = .08) were more common in surgical tracheostomy patients. There was a shorter delay from randomization to percutaneous tracheostomy vs. surgical tracheostomy (p = .006). Long-term follow-up revealed no complications in either group. CONCLUSIONS: Both percutaneous tracheostomies and surgical tracheostomies can be safely performed at the bedside by experienced, skilled practitioners.