Quality assurance standards and their use in the preparation of parenteral systemic anticancer therapy products in healthcare establishments: a scoping review.

OBJECTIVES: The use of parenteral systemic anticancer therapy (SACT) has led to improved cancer survival. A quality assurance (QA) system of the aseptic compounding process is necessary to ensure safe and consistent production of parenteral SACT. This scoping review identifies international evidence and practice relating to QA standards in the preparation of parenteral SACT in healthcare establishments. METHODS: Standards relating to aseptic compounding in hospital pharmacies and literature exploring the aseptic compounding of parenteral SACT were included. Literature relating to the non-aseptic compounding of medicines and records specific to sterile manufacturing in industrial settings were excluded. A search of several electronic databases, trial registries, the grey literature and websites of key European hospital pharmacy groups and accreditation bodies was conducted on 16 March 2022. A narrative discussion was performed by country, and content analysis of articles was conducted. RESULTS: Thirty-seven records were included. Standards reviewed covered the work environment, the preparation process and the safety of the workers who are potentially exposed to hazardous chemicals. It was a common practice to include frequent audits to ensure adherence to standards. Some standards also recommended external inspections to allow for further learnings. Periodic reviews are encouraged to ensure standards maintain relevance. National standards of the countries reviewed were based on international standards, with minor adaptations for local conditions. CONCLUSIONS: The main limitation of this review is that it is limited to countries with a high human development index. The review shows that the use of an internationally recognised standard as a basis for national standards is best practice, and will allow for relevance into the future.

Lapses of responsiveness: Characteristics, detection, and underlying mechanisms.

Lapses in responsiveness ('lapses'), particularly microsleeps and attention lapses, are complete disruptions in performance from approximately 0.5-15 s. They are of particular importance in the transport sector in which there is a need to maintain sustained attention for extended periods and in which lapses can lead to multiple-fatality accidents.

Detection of focal epileptiform events in the EEG by spatio-temporal dipole clustering.

OBJECTIVE: Methods for the detection of epileptiform events can be broadly divided into two main categories: temporal detection methods that exploit the EEG's temporal characteristics, and spatial detection methods that base detection on the results of an implicit or explicit source analysis. We describe how the framework of a spatial detection method was extended to improve its performance by including temporal information. This results in a method that provides (i) automated localization of an epileptogenic focus and (ii) detection of focal epileptiform events in an EEG recording. For the detection, only one threshold value needs to be set. METHODS: The method comprises five consecutive steps: (1) dipole source analysis in a moving window, (2) automatic selection of focal brain activity, (3) dipole clustering to arrive at the identification of the epileptiform cluster, (4) derivation of a spatio-temporal template of the epileptiform activity, and (5) template matching. Routine EEG recordings from eight paediatric patients with focal epilepsy were labelled independently by two experts. The method was evaluated in terms of (i) ability to identify the epileptic focus, (ii) validity of the derived template, and (iii) detection performance. The clustering performance was evaluated using a leave-one-out cross validation. Detection performance was evaluated using Precision-Recall curves and compared to the performance of two temporal (mimetic and wavelet based) and one spatial (dipole analysis based) detection methods. RESULTS: The method succeeded in identifying the epileptogenic focus in seven of the eight recordings. For these recordings, the mean distance between the epileptic focus estimated by the method and the region indicated by the labelling of the experts was 8mm. Except for two EEG recordings where the dipole clustering step failed, the derived template corresponded to the epileptiform activity marked by the experts. Over the eight EEGs, the method showed a mean sensitivity and selectivity of 92 and 77%, respectively. CONCLUSIONS: The method allows automated localization of the epileptogenic focus and shows good agreement with the region indicated by the labelling of the experts. If the dipole clustering step is successful, the method allows a detection of the focal epileptiform events, and gave a detection performance comparable or better to that of the other methods. SIGNIFICANCE: The identification and quantification of epileptiform events is of considerable importance in the diagnosis of epilepsy. Our method allows the automatic identification of the epileptic focus, which is of value in epilepsy surgery. The method can also be used as an offline exploration tool for focal EEG activity, displaying the dipole clusters and corresponding time series.

The influence of volition on breathing-swallowing coordination in healthy adults.

This research was designed to clarify the role of cortical modulation in the coordination of respiration and swallowing. Time-locked recordings of submental surface electromyography, nasal airflow, and thyroid acoustics were used to evaluate nonnutritive breathing-swallowing coordination (BSC) and swallowing apnea duration (SAD) of 20 healthy adults during 3 conditions. These conditions represented a continuum of volitional through nonvolitional swallowing control on the basis of a decreasing level of cortical activation: voluntarily initiated swallows during wakefulness, nonvolitional awake swallows, and reflexively initiated swallows during sleep. Differing proportions of swallows at the cusps between inspiration and expiration were found between the volitional and nonvolitional conditions, irrespective of the level of arousal. SAD was unaltered by condition. In conclusion, BSC is influenced by degree of volition but not by level of arousal. This implies that cortical influence on BSC is limited to conditions in which swallowing is voluntarily initiated and indirectly implicates the recruitment of the supplementary motor or insular cortices. SAD remained stable across conditions and may therefore be considered relatively impervious to suprabulbar influence.

Clinical measurement of pharyngeal surface electromyography: exploratory research.

BACKGROUND: Dysphagia diagnosis is limited by our inability to evaluate the underlying neuromuscular pathology of swallowing. A novel approach using pharyngeal surface electromyography (PsEMG) has been reported in the literature. OBJECTIVE: Three exploratory projects were undertaken to provide data toward the validation of PsEMG as a clinical measure of pharyngeal physiology. The first evaluates laterality of electrode placement in the pharynx. The second and third evaluate PsEMG using a circumferential and unidirectional electrode, respectively, during swallowing maneuvers. METHODS: In experiment 1, a catheter housing 3 manometric sensors and 1 bipolar PsEMG electrode was randomly inserted in each nares of 10 participants. Moving jaw radiographs were taken, and the PsEMG electrode was measured in millimeters from midline. In experiments 2 and 3, the catheter was placed in 22 and 40 research participants, respectively. Waveform characteristics were collected during swallowing maneuvers. The 2 experiments differed by type of electrode (circumferential, unidirectional) and swallowing maneuver (noneffortful and effortful swallow; noneffortful, effortful, and tongue-hold swallow). RESULTS: Midline electrode placement occurred on 20% of trials with deviation of up to 14.7 mm on all other trials. Maneuver-specific differences in amplitude were not detected with PsEMG; unacceptable levels of intrasubject and intersubject variability were identified. Temporal relationships of PsEMG and pharyngeal manometric pressure appeared appropriate. The unidirectional electrode revealed a unique bimodal PsEMG pattern that may reflect sequential contraction of muscles of the posterior pharyngeal wall. CONCLUSIONS: The current PsEMG design and procedures do not validly measure pharyngeal muscle activity. Recommendations for improved methods are provided.

Frequent lapses of responsiveness during an extended visuomotor tracking task in non-sleep-deprived subjects.

We investigated the occurrence of lapses of responsiveness (lapses) in 15 non-sleep-deprived subjects performing a 1D continuous tracking task during normal working hours. Tracking behaviour, facial video, and electroencephalogram (EEG) were recorded simultaneously during two 1-h sessions. Rate and duration were estimated for lapses identified by a tracking flat spot and/or video sleep. Fourteen of the 15 subjects had one or more lapses, with an overall rate of 39.3 +/- 12.9 lapses per hour (mean +/- SE) and a lapse duration of 3.4 +/- 0.5 s. We also found that subjects' performance improved towards the end of the 1-h long session, even though no external temporal cues were available. Spectral power was found to be higher during lapses in the delta, theta, and alpha bands, and lower in the beta, gamma, and higher bands, but correlations between changes in EEG power and lapses were low. In conclusion, lapses are a frequent phenomenon in normal subjects - even when not sleep-deprived - engaged in an extended monotonous continuous visuomotor task. This is of particular importance to the transport sector in which there is a need to maintain sustained attention for extended periods of time and in which lapses can lead to multiple-fatality accidents.

Slow-wave activity arising from the same area as epileptiform activity in the EEG of paediatric patients with focal epilepsy.

OBJECTIVE: The aim of this study was to investigate the presence and characteristics of apparent non-epileptiform activity arising in the same brain area as epileptiform activity in the EEG of paediatric patients with focal epilepsy. METHODS: The EEG from eight patients was analysed by an automated method which detects epochs with a single underlying source having a dipolar potential distribution. The EEG with the highlighted detections was then rated by a clinical neurophysiologist (EEGer) with respect to epileptiform activity. RESULTS: Although EEGer-marked events and computer detections often coincided, in five out of the eight patients, a substantial number of other detections were found to arise from the same area as the marked events. The morphology of a high proportion of these other detections did not resemble typical epileptiform activity and had a frequency content mainly in the delta and theta ranges. CONCLUSIONS: This is, to our knowledge, the first study to use an automated technique to demonstrate the presence of non-epileptiform activity arising from the same area as the epileptiform activity in the EEG of paediatric patients with focal epilepsy. This slow wave activity is likely to be related to the underlying epileptogenic process. SIGNIFICANCE: This paper suggests a technique for automated detection of focal activity arising from epileptogenic foci. It also provides a new perspective on extracting clinical useful information from slow-wave background EEG activity.

Background activity originating from same area as events in the EEG of paediatric patients with focal epilepsy.

The aim of this study was to investigate the presence of apparent non-epileptiform activity arising in the same brain area as epileptiform activity in the EEG of paediatric patients with focal epilepsy. The EEG from eight patients was analyzed by an automated method which detects epochs with a single underlying source having a dipolar potential distribution. The EEG with the highlighted detections was then rated by an EEGer with respect to epileptiform activity. Although EEGer-marked events and computer detections often coincided, in five out of the eight patients a substantial number of other detections were found to arise from the same area as the marked events. The morphology of a high proportion of these other detections did not resemble typical epileptiform activity.

Investigation of lapses of consciousness using a tracking task: preliminary results.

In many high-risk occupations, it is critical that a person remains alert at all times. There is much to be gained by being able to monitor a person on-line and detect lapses of consciousness (LoC) so that remedial action can be taken (e.g., a rest break) to ensure that safety is maintained. In this study, 15 normal subjects were observed on two sessions while they performed a continuous tracking task for a period of 1 hour. EEG, eye movements, tracking performance data and a video of the subject were recorded during the session. This work presents some preliminary results on the phenomenon of lapsing. Only 4 of the 15 subjects did not have a LoC at some stage. Seven subjects had LoCs more than 45 times and 4 more than 100 times during the 2 hours. The mean rate of lapsing over all subjects was 29.1 LoC/h. In contrast, lapses in performance were caused by both lapses of consciousness (30.1%) and attention (69.9%). There was no correlation found between age of subject and number of lapses of consciousness.

Posttraumatic stress disorder: do electrical startle responses and thyroid function usefully supplement self-report? A study of Vietnam War veterans.

OBJECTIVE: To investigate the usefulness of electrical startle responses and thyroid function as supplements to self-report measures of posttraumatic stress disorder (PTSD). METHOD: Invitations were sent to all New Zealand Vietnam War veterans known to be living in North Canterbury; 50 responded and the 35 living in or near Christchurch were included. Self-report measures of PTSD (the Davidson Trauma Scale (DTS) and the Symptom Check List (SCL-90-R) ), an eye blink electrical startle response and thyroid function were measured. The DTS was re-administered one to two weeks later to assess short-term test-retest reliability. Six months later the DTS and the electrical startle response were measured again. RESULTS: The veterans reported a wide range of PTSD severity, with 15/35 reporting prior diagnosis of PTSD. The DTS showed high short-term test-retest reliability (r = 0.93) and a moderate correlation after 6 months (r = 0.73). It also showed sensitivity to change; in one to two weeks the scores increased by nearly half a standard deviation, possibly because of an imminent "homecoming" march. The DTS and a PTSD scale from the SCL-90-R were highly correlated (r = 0.89). The total triiodothyronine (T3) to free thyroxine (T4) ratio measure of thyroid function correlated poorly with self-report (r < or = 0.27). The electrical startle response also correlated poorly with self-report (r < or = 0.26), showed low internal consistency between left and right sides (r = 0.43), and correlated 0.39 over six months. It was disliked by the veterans and had increased slightly at 6 month follow-up, perhaps because of sensitization. CONCLUSIONS: The DTS was reliable and correlated highly with the SCL-90-R PTSD scale. Neither thyroid function nor eye blink electrical startle correlated with each other or with self-report, and reliability was not good for electrical startle. These two measures do not appear to add anything useful to the assessment of PTSD.