We examined whether a polymorphism of the PERIOD3 gene (PER3; rs57875989) modulated the sleep-promoting effects of melatonin in Delayed Sleep-Wake Phase Disorder (DSWPD). One hundred and four individuals (53 males; 29.4 ±10.0 years) with DSWPD and a delayed dim light melatonin onset (DLMO) collected buccal swabs for genotyping (PER34/4 n = 43; PER3 5 allele [heterozygous and homozygous] n = 60). Participants were randomised to placebo or 0.5 mg melatonin taken 1 hour before desired bedtime (or ~1.45 hours before DLMO), with sleep attempted at desired bedtime (4 weeks; 5-7 nights/week). We assessed sleep (diary and actigraphy), Pittsburgh Sleep Quality Index (PSQI), Insomnia Severity Index (ISI), Patient-Reported Outcomes Measurement Information System (PROMIS: Sleep Disturbance, Sleep-Related Impairment), Sheehan Disability Scale (SDS) and Patient- and Clinician-Global Improvement (PGI-C, CGI-C). Melatonin treatment response on actigraphic sleep onset time did not differ between genotypes. For PER34/4 carriers, self-reported sleep onset time was advanced by a larger amount and sleep onset latency (SOL) was shorter in melatonin-treated patients compared to those receiving placebo (P = .008), while actigraphic sleep efficiency in the first third of the sleep episode (SE T1) did not differ. For PER3 5 carriers, actigraphic SOL and SE T1 showed a larger improvement with melatonin (P < .001). Melatonin improved ISI (P = .005), PROMIS sleep disturbance (P < .001) and sleep-related impairment (P = .017), SDS (P = .019), PGI-C (P = .028) and CGI-C (P = .016) in PER34/4 individuals only. Melatonin did not advance circadian phase. Overall, PER34/4 DSWPD patients have a greater response to melatonin treatment. PER3 genotyping may therefore improve DSWPD patient outcomes.

Background: Prehabilitation to maximize exercise capacity before lung cancer surgery has the potential to improve operative tolerability and patient outcomes. However, translation of this evidence into clinical practice is limited. Aims: To determine the acceptability and perceived benefit of prehabilitation in lung cancer among thoracic surgeons. Procedure: 198 cardiothoracic surgeons within Australia and New Zealand were surveyed to evaluate their attitudes and perceived benefits of prehabilitation in lung cancer. Results: Response rate was 14%. A moderate proportion of respondents reported that there is a need to refer lung resection patients to preoperative physiotherapy/prehabilitation, particularly high-risk patients or those with borderline fitness for surgery. 91% of surgeons were willing to delay surgery (as indicated by cancer stage/type) to optimize patients via prehabilitation. The main barriers to prehabilitation reported were patient comorbidities and access to allied health professionals, with 33% stating that they were unsure who to refer to for prehabilitation in thoracic surgery. This is despite 60% of the cohort reporting that pulmonary rehabilitation is available as a preoperative resource. 92% of respondents believe that further research into prehabilitation in lung cancer is warranted. Conclusion: The benefits of prehabilitation for the oncology population have been well documented in the literature over recent years and this is reflected in the perceptions surgeons had on the benefits of prehabilitation for their patients. This survey demonstrates an interest among cardiothoracic surgeons in favor of prehabilitation, and therefore further research and demonstration of its benefit is needed in lung cancer to facilitate implementation into practice.

Sleepiness is a major contributor to motor vehicle crashes and shift workers are particularly vulnerable. There is currently no validated objective field-based measure of sleep-related impairment prior to driving. Ocular parameters are promising markers of continuous driver alertness in laboratory and track studies, however their ability to determine fitness-to-drive in naturalistic driving is unknown. This study assessed the efficacy of a pre-drive ocular assessment for predicting sleep-related impairment in naturalistic driving, in rotating shift workers. Fifteen healthcare workers drove an instrumented vehicle for 2 weeks, while working a combination of day, evening and night shifts. The vehicle monitored lane departures and behavioural microsleeps (blinks >500 ms) during the drive. Immediately prior to driving, ocular parameters were assessed with a 4-min test. Lane departures and behavioural microsleeps occurred on 17.5 % and 10 % of drives that had pre-drive assessments, respectively. Pre-drive blink duration significantly predicted behavioural microsleeps and showed promise for predicting lane departures (AUC = 0.79 and 0.74). Pre-drive percentage of time with eyes closed had high accuracy for predicting lane departures and behavioural microsleeps (AUC = 0.73 and 0.96), although was not statistically significant. Pre-drive psychomotor vigilance task variables were not statistically significant predictors of lane departures. Self-reported sleep-related and hazardous driving events were significantly predicted by mean blink duration (AUC = 0.65 and 0.69). Measurement of ocular parameters pre-drive predict drowsy driving during naturalistic driving, demonstrating potential for fitness-to-drive assessment in operational environments.

A neural network model was previously developed to predict melatonin rhythms accurately from blue light and skin temperature recordings in individuals on a fixed sleep schedule. This study aimed to test the generalizability of the model to other sleep schedules, including rotating shift work. Ambulatory wrist blue light irradiance and skin temperature data were collected in 16 healthy individuals on fixed and habitual sleep schedules, and 28 rotating shift workers. Artificial neural network models were trained to predict the circadian rhythm of (i) salivary melatonin on a fixed sleep schedule; (ii) urinary aMT6s on both fixed and habitual sleep schedules, including shift workers on a diurnal schedule; and (iii) urinary aMT6s in rotating shift workers on a night shift schedule. To determine predicted circadian phase, center of gravity of the fitted bimodal skewed baseline cosine curve was used for melatonin, and acrophase of the cosine curve for aMT6s. On a fixed sleep schedule, the model predicted melatonin phase to within ± 1 hour in 67% and ± 1.5 hours in 100% of participants, with mean absolute error of 41 ± 32 minutes. On diurnal schedules, including shift workers, the model predicted aMT6s acrophase to within ± 1 hour in 66% and ± 2 hours in 87% of participants, with mean absolute error of 63 ± 67 minutes. On night shift schedules, the model predicted aMT6s acrophase to within ± 1 hour in 42% and ± 2 hours in 53% of participants, with mean absolute error of 143 ± 155 minutes. Prediction accuracy was similar when using either 1 (wrist) or 11 skin temperature sensor inputs. These findings demonstrate that the model can predict circadian timing to within ± 2 hours for the vast majority of individuals on diurnal schedules, using blue light and a single temperature sensor. However, this approach did not generalize to night shift conditions.

Practical alternatives to gold-standard measures of circadian timing in shift workers are needed. We assessed the feasibility of applying a limit-cycle oscillator model of the human circadian pacemaker to estimate circadian phase in 25 nursing and medical staff in a field setting during a transition from day/evening shifts (diurnal schedule) to 3-5 consecutive night shifts (night schedule). Ambulatory measurements of light and activity recorded with wrist actigraphs were used as inputs into the model. Model estimations were compared to urinary 6-sulphatoxymelatonin (aMT6s) acrophase measured on the diurnal schedule and last consecutive night shift. The model predicted aMT6s acrophase with an absolute mean error of 0.69 h on the diurnal schedule (SD = 0.94 h, 80% within ±1 hour), and 0.95 h on the night schedule (SD = 1.24 h, 68% within ±1 hour). The aMT6s phase shift from diurnal to night schedule was predicted to within ±1 hour in 56% of individuals. Our findings indicate the model can be generalized to a shift work setting, although prediction of inter-individual variability in circadian phase shift during night shifts was limited. This study provides the basis for further adaptation and validation of models for predicting circadian phase in rotating shift workers.

Shift work is associated with impaired alertness and performance due to sleep loss and circadian misalignment. This study examined sleep between shift types (day, evening, night), and alertness and performance during day and night shifts in 52 intensive care workers. Sleep and wake duration between shifts were evaluated using wrist actigraphs and diaries. Subjective sleepiness (Karolinska Sleepiness Scale, KSS) and Psychomotor Vigilance Test (PVT) performance were examined during day shift, and on the first and subsequent night shifts (3rd, 4th or 5th). Circadian phase was assessed using urinary 6-sulphatoxymelatonin rhythms. Sleep was most restricted between consecutive night shifts (5.74 ± 1.30 h), consecutive day shifts (5.83 ± 0.92 h) and between evening and day shifts (5.20 ± 0.90 h). KSS and PVT mean reaction times were higher at the end of the first and subsequent night shift compared to day shift, with KSS highest at the end of the first night. On nights, working during the circadian acrophase of the urinary melatonin rhythm led to poorer outcomes on the KSS and PVT. In rotating shift workers, early day shifts can be associated with similar sleep restriction to night shifts, particularly when scheduled immediately following an evening shift. Alertness and performance remain most impaired during night shifts given the lack of circadian adaptation to night work. Although healthcare workers perceive themselves to be less alert on the first night shift compared to subsequent night shifts, objective performance is equally impaired on subsequent nights.

Introduction: Idiopathic Parkinson's Disease (PD) results in a range of motor and non-motor impairments. Clinical diagnosis commonly occurs after substantial neurophysiological damage limiting the opportunity for neuroprotective treatments. Uncovering sensitive objective markers with the capacity to detect pre-symptomatic disease and track disease progression is therefore a priority. Speech may provide an ideal proxy marker for PD; a quantifiable biometric that displays salient changes in early disease and appears to evolve with disease progression. Areas covered: This review describes the endophenotype of speech, voice, cognition and language modalities in PD and investigates the speech as a 'proxy marker' of PD disease state. Expert opinion: Detailed characterization at different disease stages are needed and must incorporate longitudinal assessment to capture small but significant changes in speech, voice, cognition and language modalities within patient changes over time. Advances in technology are leading to new opportunities for acquiring data remotely and more frequently, offering more ecologically valid testing environments. Combined with automated signal processing and analysis, symptoms may also be tracked in-home readily. Features extracted may provide a 'proxy marker' for early identification of PD and objective monitoring of disease progression.

BACKGROUND: The routine implementation of sternal precautions to prevent sternal complications that restrict the use of the upper limbs is currently worldwide practice following a median sternotomy. However, evidence is limited and drawn primarily from cadaver studies and orthopaedic research. Sternal precautions may delay recovery, prolong hospital discharge and be overly restrictive. Recent research has shown that upper limb exercise reduces post-operative sternal pain and results in minimal micromotion between the sternal edges as measured by ultrasound. The aims of this study are to evaluate the effects of modified sternal precautions on physical function, pain, recovery and health-related quality of life after cardiac surgery. METHODS/DESIGN: This study is a phase II, double-blind, randomised controlled trial with concealed allocation, blinding of patients and assessors, and intention-to-treat analysis. Patients (n = 72) will be recruited following cardiac surgery via a median sternotomy. Sample size calculations were based on the minimal important difference (two points) for the primary outcome: Short Physical Performance Battery. Thirty-six participants are required per group to counter dropout (20%). All participants will be randomised to receive either standard or modified sternal precautions. The intervention group will receive guidelines encouraging the safe use of the upper limbs. Secondary outcomes are upper limb function, pain, kinesiophobia and health-related quality of life. Descriptive statistics will be used to summarise data. The primary hypothesis will be examined by repeated-measures analysis of variance to evaluate the changes from baseline to 4 weeks post-operatively in the intervention arm compared with the usual-care arm. In all tests to be conducted, a p value <0.05 (two-tailed) will be considered statistically significant, and confidence intervals will be reported. DISCUSSION: The Sternal Management Accelerated Recovery Trial (S.M.A.R.T.) is a two-centre randomised controlled trial powered and designed to investigate whether the effects of modifying sternal precautions to include the safe use of the upper limbs and trunk impact patients' physical function and recovery following cardiac surgery via median sternotomy. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry identifier: ACTRN12615000968572 . Registered on 16 September 2015 (prospectively registered).

BACKGROUND: Short-term recovery after colorectal surgery has been traditionally investigated through length of stay (LOS). However, this measure is influenced by several confounding factors. This study aimed to investigate the construct validity and reliability of assessing the time to achieve standardized discharge criteria (time to readiness for discharge, or TRD) as a measure of short-term recovery. In a secondary analysis, we compared sample size requirements for randomized controlled trials (RCTs) using TRD or LOS as outcome measures. METHODS: Seventy patients participated in the construct validity study and 21 patients participated in the reliability study. TRD was defined as the number of days to achieve discharge criteria previously defined by consensus. Construct validity was investigated by testing six hypothesis based on the assumption that TRD measures short-term recovery. Reliability was calculated by comparing measures of TRD by two independent assessors. Variability estimates (standard deviations) of LOS and TRD were used for sample size calculations. RESULTS: Five of the six hypotheses were supported by the data (p < 0.05). Interobserver reliability was excellent (ICC2.1 = 0.99). Sample size estimations showed that RCTs using TRD as an outcome measure require approximately 23 % less participants compared to RCTs using LOS. CONCLUSIONS: The results of this research support the construct-validity and reliability of TRD as a measure of short-term recovery. Using TRD as an alternative to LOS may reduce sample size requirements in future RCTs.

INTRODUCTION: Intensive care unit-acquired weakness (ICU-AW) is a significant problem. There is currently widespread variability in the methods used for manual muscle testing and handgrip dynamometry (HGD) to diagnose ICU-AW. This study was conducted in two parts. The aims of this study were: to determine the inter-rater reliability and agreement of manual muscle strength testing using both isometric and through-range techniques using the Medical Research Council sum score and a new four-point scale, and to examine the validity of HGD and determine a cutoff score for the diagnosis of ICU-AW for the new four-point scale. METHODS: Part one involved evaluation of muscle strength by two physical therapists in 29 patients ventilated >48 hours. Manual strength testing was performed by both physical therapists using two techniques: isometric and through range; and two scoring systems: traditional six-point Medical Research Council scale and a new collapsed four-point scale. Part two involved assessment of handgrip strength conducted on 60 patients. A cutoff score for ICU-AW was identified for the new four-point scoring system. RESULTS: The incidence of ICU-AW was 42% (n = 25/60) in this study (based on HGD). In part one the highest reliability and agreement was observed for the isometric technique using the four-point scale (intraclass correlation coefficient = 0.90: kappa = 0.72 respectively). Differences existed between isometric and through-range scores (mean difference = 1.76 points, P = 0.005). In part two, HGD had a sensitivity of 0.88 and specificity of 0.80 for diagnosing ICU-AW. A cutoff score of 24 out of 36 points was identified for the four-point scale. CONCLUSIONS: The isometric technique is recommended with reporting on a collapsed four-point scale. Because HGD is easy to perform and sensitive, we recommend a new two-tier approach to diagnosing ICU-AW that first tests handgrip strength with follow-up strength assessment using the isometric technique for muscle strength testing if handgrip strength falls below cutoff scores. Whilst our results for the four-point scale are encouraging, further research is required to confirm the findings of this study and determine the validity of the four-point scoring system and cutoff score developed of less than 24 out of 36 before recommending adoption into clinical practice.