Regulatory Agilities in the Time of COVID-19: Overview,Trends, and Opportunities

PurposeCrucial steps have been adopted by health and regulatory authorities around the world to respond to the COVID-19 pandemic. This review aims to highlight these steps by providing an overview of the regulatory approaches adopted during the onset of the pandemic, provide an assessment of observed trends, and offer some reflections and proposals to leverage learnings and opportunities from this current pandemic.MethodsDocuments and informational materials on regulating the development and management of medical products during the COVID-19 pandemic were collected and classified. These materials were sourced from official websites and press releases from health authorities and international bodies from selected markets across the globe, and covered the period between January and July 2020. Additional information to support this study was gathered through a literature review and analysis of related data available from the public domain, and was complemented with the authors' personal experience.FindingsCommunication has been vital in addressing the impact of COVID-19. A total of 1705 documents and informational materials related to health or regulatory response to the COVID-19 pandemic were gathered. Of these, 343 (around 20%) were identified as regulatory agilities. These agile approaches were classified into 3 categories, namely, where health and regulatory authorities had: (1) facilitated product management across the entire lifecycle, notably in expediting medical product use for COVID-19, ensuring the continuity of clinical trials, and addressing supply chain issues; (2) strengthened international cooperation; and (3) addressed regulatory burden with the adoption of electronic and digital tools.ImplicationsWhile many regulatory measures have been introduced temporarily as a response to the COVID-19 crisis, there are opportunities for leveraging an understanding from these approaches in order to collectively achieve more efficient regulatory systems and to mitigate and address the impact of COVID-19 and further future-proof the regulatory environment.     

Directional Deep Brain Stimulation for Parkinson's Disease: Results of an International Crossover Study With Randomized,Double-Blind Primary Endpoint

ObjectivePublished reports on directional deep brain stimulation (DBS) have been limited to small, single-center investigations. Therapeutic window (TW) is used to describe the range of stimulation amplitudes achieving symptom relief without side effects. This crossover study performed a randomized double-blind assessment of TW for directional and omnidirectional DBS in a large cohort of patients implanted with a DBS system in the subthalamic nucleus for Parkinson's disease.Materials and MethodsParticipants received omnidirectional stimulation for the first three months after initial study programming, followed by directional DBS for the following three months. The primary endpoint was a double-blind, randomized evaluation of TW for directional vs omnidirectional stimulation at three months after initial study programming. Additional data recorded at three- and six-month follow-ups included stimulation preference, therapeutic current strength, Unified Parkinson's Disease Rating Scale (UPDRS) part III motor score, and quality of life.ResultsThe study enrolled 234 subjects (62 ± 8 years, 33% female). TW was wider using directional stimulation in 183 of 202 subjects (90.6%). The mean increase in TW with directional stimulation was 41% (2.98 ± 1.38 mA, compared to 2.11 ± 1.33 mA for omnidirectional). UPDRS part III motor score on medication improved 42.4% at three months (after three months of omnidirectional stimulation) and 43.3% at six months (after three months of directional stimulation) with stimulation on, compared to stimulation off. After six months, 52.8% of subjects blinded to stimulation type (102/193) preferred the period with directional stimulation, and 25.9% (50/193) preferred the omnidirectional period. The directional period was preferred by 58.5% of clinicians (113/193) vs 21.2% (41/193) who preferred the omnidirectional period.ConclusionDirectional stimulation yielded a wider TW compared to omnidirectional stimulation and was preferred by blinded subjects and clinicians.     

The affordance of barrier crossing in young children exhibits dynamic,not geometric,similarity

Previous research has shown that adults perceive affordances like the passability of apertures, climbability or crossability of steps and graspability of objects. In this study, the affordance for stepping over or onto barriers was examined in young children. This was done by placing three distinct barriers (a foam obstacle, a gap, and a single step up), which were scaled to body size, in the walking paths of 4- and 6-year olds and adults, and observing how they crossed the barriers. Age-related differences in the scaling of these actions corresponded to levels of movement variability, indicating that children as young as 4 years old are sensitive to their own constraints and scale their actions accordingly. These results indicate that affordances are not directly related to leg geometry, but rather entail the dynamics of the developing perception–action system.     

Clinical usefulness of the Parkinson's disease sleep scale

OBJECTIVE: To test the usefulness of the Parkinson's disease sleep scale (PDSS) in identifying sleep disorders in the clinical practice setting. METHODS: Sixty-two PD patients were evaluated with the PDSS and the Epworth sleepiness scale (ESS). A cut-off of less than five for each PDSS item as an indicator of substantial sleep disturbance was chosen. If the ESS was equal to or greater than eight, patients were referred to a sleep disorder specialist and possible polysomnography. RESULTS: The mean total PDSS score was 104.7+/-21.5,which correlated with the mean Hoehn and Yahr score (1.9+/-0.9) as well as the mean ESS score (9.7+/-4.7). A significant correlation was also found between the ESS score and several items of the PDSS. CONCLUSIONS: The PDSS was useful in identifying sleep disturbances which were not previously diagnosed, such as sleep maintenance insomnia and excessive daytime sleepiness. Problems with the PDSS include ambiguities of some questions, lack of quantification and an inability to identify specific sleep disturbances such as sleep apnea.     

Suppression of Immunodeficiency Virus-Associated Neural Damage by the p75 Neurotrophin Receptor Ligand, LM11A-31, in an In Vitro Feline Model

Feline immunodeficiency virus (FIV) infection like human immunodeficiency virus (HIV), produces systemic and central nervous system disease in its natural host, the domestic cat, that parallels the pathogenesis seen in HIV-infected humans. The ability to culture feline nervous system tissue affords the unique opportunity to directly examine interactions of infectious virus with CNS cells for the development of models and treatments that can then be translated to a natural infectious model. To explore the therapeutic potential of a new p75 neurotrophin receptor ligand, LM11A-31, we evaluated neuronal survival, neuronal damage and calcium homeostasis in cultured feline neurons following inoculation with FIV. FIV resulted in the gradual appearance of dendritic beading, pruning of processes and shrinkage of neuronal perikarya in the neurons. Astrocytes developed a more activated appearance and there was an enhanced accumulation of microglia, particularly at longer times post-inoculation. Addition of 10?nM LM11A-31, to the cultures greatly reduced or eliminated the neuronal pathology as well as the FIV effects on astrocytes and microglia. LM11A-31 also, prevented the development of delayed calcium deregulation in feline neurons exposed to conditioned medium from FIV treated macrophages. The suppression of calcium accumulation prevented the development of foci of calcium accumulation and beading in the dendrites. FIV replication was unaffected by LM11A-31. The strong neuroprotection afforded by LM11A-31 in an infectious in vitro model indicates that LM11A-31 may have excellent potential for the treatment of HIV-associated neurodegeneration.     

Learning a coordinated rhythmic movement with task-appropriate coordination feedback

A common perception–action learning task is to teach participants to produce a novel coordinated rhythmic movement, e.g. 90° mean relative phase. As a general rule, people cannot produce these novel movements stably without training. This is because they are extremely poor at discriminating the perceptual information required to coordinate and control the movement, which means people require additional (augmented) feedback to learn the novel task. Extant methods (e.g. visual metronomes, Lissajous figures) work, but all involve transforming the perceptual information about the task and thus altering the perception–action task dynamic being studied. We describe and test a new method for providing online augmented coordination feedback using a neutral colour cue. This does not alter the perceptual information or the overall task dynamic, and an experiment confirms that (a) feedback is required for learning a novel coordination and (b) the new feedback method provides the necessary assistance. This task-appropriate augmented feedback therefore allows us to study the process of learning while preserving the perceptual information that constitutes a key part of the task dynamic being studied. This method is inspired by and supports a fully perception–action approach to coordinated rhythmic movement.     

The relationship between lifestyle,occupational health,and work-related factors with presenteeism amongst general practitioners

There is evidence that general practitioners (GPs) are more likely to exhibit sickness presenteeism than other health professional groups or other high-income earners and less likely to take sick leave. This study aims to examine the relationship between lifestyle, occupational health, and work-related factors with presenteeism amongst GPs. A cross-sectional study was conducted amongst GPs in 2011. Logistic regression was used to determine crude and adjusted odds ratios between lifestyle, occupational health, and work-related factors with presenteeism. Whilst adjusting for age and gender, exercising 1 to 3 times a week (odds ratio [OR] = 4.88), not having a good work-life balance (OR = 4.2), work-related sleep problems (OR = 2.55), moderate psychological distress (OR = 3.94), and poor or fair health (OR = 6.22) were associated with presenteeism. Increased burnout and reduced job satisfaction and workability due to the physical demands of the job were also associated with presenteeism. In conclusion, presenteeism amongst GPs can be addressed by implementing interventions in relation to physical activity, stress reduction, and sleep hygiene and improving work-life balance and the physical demands of the job.