Polypharmacy and drug interactions in older patients with cancer receiving chemotherapy: associated factors.

BACKGROUND: Polypharmacy in older adults with cancer receiving chemotherapy leads to increased risks of drug interactions, translating in potential hazardous health outcomes. This study aims to assess the prevalence of polypharmacy, drug-drug interactions (DDIs), and severe-drug interactions (SDIs) in older patients with cancer. Antineoplastic agents (ANAs) involvement and possible risk contexts (comorbidities with cardiac risk, and high-risk medications) were also analysed. METHODS: Observational study with older adults (≥ 65 years) diagnosed with cancer, who were treated with antineoplastic agents (ANAs); it was conducted in three hospitals from the north of Portugal. Data collection was obtained using self-reports and medical records. DDIs were identified and classified using Micromedex® software. Descriptive and association analyze statistics were performed. Statistical hypothesis tests with p value less than 0.05 were considered significant. All statistical procedures and analysis were performed with R version 4.1.3. RESULTS: We enrolled 552 patients. Polypharmacy prevalence was 88.40%; 76.45% and 56.16% of the patients presented with DDIs and SDIs, respectively. SDIs with ANAs were found in 21.20% of the patients. High-risk medications were associated with a higher risk of polypharmacy, DDIs, and SDIs. Polypharmacy and DDIs were higher in patients with hypertension or diabetes. SDIs were higher in patients with diabetes. CONCLUSION: Polypharmacy, potential DDIs and SDIs were highly prevalent in older adults with cancer. A careful review of the medication administered is necessary to decrease it. These findings warrant further research to optimize medication in this population and decrease problems related to medication, which may lead to emergency room visits and hospitalisations, compromising patient safety and/or ongoing treatments.

Perceptual-motor recalibration is intact in older adults.

From an ecological perspective, perceptual-motor recalibration should be a robust and adaptable process, but there are suggestions that older adults may recalibrate slower. Therefore, this study investigated the age-related temporal effects in perceptual-motor recalibration after motor disturbances. In three experiments, we disturbed young and older adults' perception-action by fitting weights around their ankles and asking them to climb stairs or cross obstacles repeatedly. In Experiment 1, participants (n = 26) climbed stairs with different ankle weights. An innovative methodology was applied, identifying the timeline of recalibration as the point where a stable movement pattern emerged. Experiment 1 showed that older adults recalibrated slower than young adults in lighter (but not heavier) weight conditions. In Experiment 2, participants (n = 24) crossed obstacles with different ankle weights. Results showed that older adults recalibrated faster than young adults. Finally, in Experiment 3, participants (n = 24) crossed obstacles of unpredictable and varying heights with heavy ankle weights. Again, results showed that older adults recalibrated faster than young adults. Taken together these results show that although older adults had reduced muscle strength and flexibility, they recalibrated quickly, especially when the task was more challenging.

Switch rates vary due to expected payoff but not due to individual risk tendency.

When switching between different tasks, the initiation of task switches may depend on task characteristics (difficulty, salient cues, etc.) or reasons within the person performing the task (decisions, behavioral variability, etc.). The reasons for variance in switching strategies, especially in paradigms where participants are free to choose the order of tasks and the amount of switching between tasks, are not well researched. In this study, we follow up the recent discussion that variance in switching strategies might be partly explained by the characteristics of the person fulfilling the task. We examined whether risk tendency and impulsiveness differentiate individuals in their response (i.e., switch rates and time spent on tasks) to different task characteristics on a tracking-while-typing paradigm. In detail, we manipulated two aspects of loss prospect (i.e., "payoff" as the amount of points that could be lost when tracking was unattended for too long, and "cursor speed" determining the likelihood of such a loss occurring). To account for between-subject variance and within-subject variability in the data, we employed linear mixed effect analyses following the model selection procedure (Bates, Kliegl, et al., 2015). Besides, we tested whether risk tendency can be transformed into a decision parameter which could predict switching strategies when being computationally modelled. We transferred decision parameters from the Decision Field Theory to model "switching thresholds" for each individual. Results show that neither risk tendency nor impulsiveness explain between-subject variance in the paradigm, nonetheless linear mixed-effects models confirmed that within-subject variability plays a significant role for interpreting dual-task data. Our computational model yielded a good model fit, suggesting that the use of a decision threshold parameter for switching may serve as an alternative means to classify different strategies in task switching.

Ways to Improve Multitasking: Effects of Predictability after Single- and Dual-Task Training.

In this study we investigated the effect of predictability on dual-task performance in two experiments. In the first experiment 33 participants separately practiced a continuous tracking task and an auditory reaction time task. Both tasks had a repeating element that made them predictable; in the tracking task this was a repeating segment, and in the auditory task this was an auditory sequence. In addition, one group obtained explicit knowledge about the repeating sequence in the tracking task while the other group trained implicitly. After training, single- and dual-task performance was tested at a post test and retention test. Results showed that predictability only improved performance in the predictable tasks themselves and dual-task costs disappeared for the tracking task. To see whether the task-specific effect of predictability was the results of task prioritization, or because task representations did not have much chance to interact with each other, we conducted a second experiment. Using the same tasks as in Experiment 1, 39 participants now trained both tasks simultaneously. Results largely mirrored those of the first experiment, demonstrating that freed-up resources due to predictability in one task could not be re-invested to improve in the other task. We conclude that predictability has a positive but task-specific effect on dual-task performance.

Azadirachta indica A. Juss. In Vivo Toxicity-An Updated Review.

The Neem tree, Azadirachta indica A. Juss., is known for its large spectrum of compounds with biological and pharmacological interest. These include, among others, activities that are anticancer, antibacterial, antiviral, and anti-inflammatory. Some neem compounds are also used as insecticides, herbicides, and/or antifeedants. The safety of these compounds is not always taken into consideration and few in vivo toxicity studies have been performed. The current study is a literature review of the latest in vivo toxicity of A. indica. It is divided in two major sections-aquatic animals toxicity and mammalian toxicity-each related to neem's application as a pesticide or a potential new therapeutic drug, respectively.

The impact of predictability on dual-task performance and implications for resource-sharing accounts.

The aim of this study was to examine the impact of predictability on dual-task performance by systematically manipulating predictability in either one of two tasks, as well as between tasks. According to capacity-sharing accounts of multitasking, assuming a general pool of resources two tasks can draw upon, predictability should reduce the need for resources and allow more resources to be used by the other task. However, it is currently not well understood what drives resource-allocation policy in dual tasks and which resource allocation policies participants pursue. We used a continuous tracking task together with an audiomotor task and manipulated advance visual information about the tracking path in the first experiment and a sound sequence in the second experiments (2a/b). Results show that performance predominantly improved in the predictable task but not in the unpredictable task, suggesting that participants did not invest more resources into the unpredictable task. One possible explanation was that the re-investment of resources into another task requires some relationship between the tasks. Therefore, in the third experiment, we covaried the two tasks by having sounds 250 ms before turning points in the tracking curve. This enabled participants to improve performance in both tasks, suggesting that resources were shared better between tasks.

No impact of instructions and feedback on task integration in motor learning.

This study examined the effect of instructions and feedback on the integration of two tasks. Task-integration of covarying tasks are thought to help dual-task performance. With complete task integration of covarying dual tasks, a dual task becomes more like a single task and dual-task costs should be reduced as it is no longer conceptualized as a dual task. In the current study we tried to manipulate the extent to which tasks are integrated. We covaried a tracking task with an auditory go/no-go task and tried to manipulate the extent of task-integration by using two different sets of instructions and feedback. A group receiving task-integration promoting instructions and feedback (N = 18) and a group receiving task-separation instructions and feedback (N = 20) trained on a continuous tracking task. The tracking task covaried with the auditory go/no-go reaction time task because high-pitch sounds always occurred 250 ms before turns, which has been demonstrated to foster task integration. The tracking task further contained a repeating segment to investigate implicit learning. Results showed that instructions, feedback, or participants' conceptualization of performing a single task versus a dual task did not significantly affect task integration. However, the covariation manipulation improved performance in both the tracking and the go/no-go task, exceeding performance in non-covarying and single tasks. We concluded that task integration between covarying motor tasks is a robust phenomenon that is not influenced by instructions or feedback.

Additive Effects of Prior Knowledge and Predictive Visual Information in Improving Continuous Tracking Performance.

Visual information and prior knowledge represent two different sources of predictability for tasks which each have been reported to have a beneficial effect on dual-task performance. What if the two were combined? Adding multiple sources of predictability might, on the one hand, lead to additive, beneficial effects on dual-tasking. On the other hand, it is conceivable that multiple sources of predictability do not increase dual-task performance further, as they complicate performance due to having to process information from multiple sources. In this study, we combined two sources of predictability, predictive visual information and prior knowledge (implicit learning and explicit learning) in a dual-task setup. 22 participants performed a continuous tracking task together with an auditory reaction time task over three days. The middle segment of the tracking task was repeating to promote motor learning, but only half of the participants was informed about this. After the practice blocks (day 3), we provided participants with predictive visual information about the tracking path to test whether visual information would add to beneficial effects of prior knowledge (additive effects of predictability). Results show that both predictive visual information and prior knowledge improved dual-task performance, presented simultaneously or in absence of each other. These results show that processing of information relevant for enhancement of task performance is unhindered by dual-task demands.

Biological Activities of Gedunin-A Limonoid from the Meliaceae Family.

Gedunin is an important limonoid present in several genera of the Meliaceae family, mainly in seeds. Several biological activities have been attributed to gedunin, including antibacterial, insecticidal, antimalarial, antiallergic, anti-inflammatory, anticancer, and neuroprotective effects. The discovery of gedunin as a heat shock protein (Hsp) inhibitor represented a very important landmark for its application as a biological therapeutic agent. The current study is a critical literature review based on the several biological activities so far described for gedunin, its therapeutic effect on some human diseases, and future directions of research for this natural compound.

Chemistry, bioactivities, extraction and analysis of azadirachtin: State-of-the-art.

Azadirachta indica A. Juss. (Neem) is an Indian tree recognized for its activity as pesticide, as well as several pharmacological properties. Among the various compounds already isolated and studied from Neem tree, azadirachtin (AZA) was identified as the main bioactive compound. Azadirachtin can be found at different parts of the Neem plant but assumes its maximum concentration at the seed level. This compound features a quite complex chemical structure, which justifies the 20-plus-year difficulty to identify the synthetic pathway that subsequently permitted to carry out its artificial synthesis. Azadirachtin is widely used as a basis for production of biopesticides; nevertheless, other properties have been recognized for this substance, among which the anticancer and antimalarial activity stand out. The methods available for azadirachtin extraction are diverse, including solid-liquid extraction and extraction with solvents at high or low temperatures. Alcohol based solvents are associated with higher extraction yields and are therefore preferred for the isolation of azadirachtin from plant parts. Clean-up of the extracts is generally required for further purification. The highest azadirachtin levels have been obtained from Neem seeds but concentration values present a large variation between batches. Therefore, in addition to extraction procedures, it is essential to establish routine methods for azadirachtin identification and quantification. Chromatography-based techniques are preferably selected for detection and quantification of azadirachtin in plant matrices. Overall, this process will guarantee a future reproducible, safe and effective use of the extracts in formulations for commercial applications.

The Organization of Working Memory Networks is Shaped by Early Sensory Experience.

Early deafness results in crossmodal reorganization of the superior temporal cortex (STC). Here, we investigated the effect of deafness on cognitive processing. Specifically, we studied the reorganization, due to deafness and sign language (SL) knowledge, of linguistic and nonlinguistic visual working memory (WM). We conducted an fMRI experiment in groups that differed in their hearing status and SL knowledge: deaf native signers, and hearing native signers, hearing nonsigners. Participants performed a 2-back WM task and a control task. Stimuli were signs from British Sign Language (BSL) or moving nonsense objects in the form of point-light displays. We found characteristic WM activations in fronto-parietal regions in all groups. However, deaf participants also recruited bilateral posterior STC during the WM task, independently of the linguistic content of the stimuli, and showed less activation in fronto-parietal regions. Resting-state connectivity analysis showed increased connectivity between frontal regions and STC in deaf compared to hearing individuals. WM for signs did not elicit differential activations, suggesting that SL WM does not rely on modality-specific linguistic processing. These findings suggest that WM networks are reorganized due to early deafness, and that the organization of cognitive networks is shaped by the nature of the sensory inputs available during development.

Multitasking as a choice: a perspective.

Performance decrements in multitasking have been explained by limitations in cognitive capacity, either modelled as static structural bottlenecks or as the scarcity of overall cognitive resources that prevent humans, or at least restrict them, from processing two tasks at the same time. However, recent research has shown that individual differences, flexible resource allocation, and prioritization of tasks cannot be fully explained by these accounts. We argue that understanding human multitasking as a choice and examining multitasking performance from the perspective of judgment and decision-making (JDM), may complement current dual-task theories. We outline two prominent theories from the area of JDM, namely Simple Heuristics and the Decision Field Theory, and adapt these theories to multitasking research. Here, we explain how computational modelling techniques and decision-making parameters used in JDM may provide a benefit to understanding multitasking costs and argue that these techniques and parameters have the potential to predict multitasking behavior in general, and also individual differences in behavior. Finally, we present the one-reason choice metaphor to explain a flexible use of limited capacity as well as changes in serial and parallel task processing. Based on this newly combined approach, we outline a concrete interdisciplinary future research program that we think will help to further develop multitasking research.

Perception, Action, and Cognition of Football Referees in Extreme Temperatures: Impact on Decision Performance.

Different professional domains require high levels of physical performance alongside fast and accurate decision-making. Construction workers, police officers, firefighters, elite sports men and women, the military and emergency medical professionals are often exposed to hostile environments with limited options for behavioral coping strategies. In this (mini) review we use football refereeing as an example to discuss the combined effect of intense physical activity and extreme temperatures on decision-making and suggest an explicative model. In professional football competitions can be played in temperatures ranging from -5°C in Norway to 30°C in Spain for example. Despite these conditions, the referee's responsibility is to consistently apply the laws fairly and uniformly, and to ensure the rules are followed without waning or adversely influencing the competitiveness of the play. However, strenuous exercise in extreme environments imposes increased physiological and psychological stress that can affect decision-making. Therefore, the physical exertion required to follow the game and the thermal strain from the extreme temperatures may hinder the ability of referees to make fast and accurate decisions. Here, we review literature on the physical and cognitive requirements of football refereeing and how extreme temperatures may affect referees' decisions. Research suggests that both hot and cold environments have a negative impact on decision-making but data specific to decision-making is still lacking. A theoretical model of decision-making under the constraint of intense physical activity and thermal stress is suggested. Future naturalistic studies are needed to validate this model and provide clear recommendations for mitigating strategies.

Task Integration Facilitates Multitasking.

The aim of this study was to investigate multi-task integration in a continuous tracking task. We were particularly interested in how manipulating task structure in a dual-task situation affects learning of a constant segment embedded in a pursuit-tracking task. Importantly, we examined if dual-task effects could be attributed to task integration by varying the structural similarity and difficulty of the primary and secondary tasks. In Experiment 1 participants performed a pursuit tracking task while counting high-pitched tones and ignoring low-pitched tones. The tones were either presented randomly or structurally 250 ms before each tracking turn. Experiment 2 increased the motor load of the secondary tasks by asking participants to tap their feet to the tones. Experiment 3 further increased motor load of the primary task by increasing its speed and having participants tracking with their non-dominant hand. The results show that dual-task interference can be moderated by secondary task conditions that match the structure of the primary task. Therefore our results support proposals of task integration in continuous tracking paradigms. We conclude that multi-tasking is not always detrimental for motor learning but can be facilitated through task-integration.

Implicit and Explicit Knowledge Both Improve Dual Task Performance in a Continuous Pursuit Tracking Task.

The goal of this study was to investigate the effect of predictability on dual-task performance in a continuous tracking task. Participants practiced either informed (explicit group) or uninformed (implicit group) about a repeated segment in the curves they had to track. In Experiment 1 participants practices the tracking task only, dual-task performance was assessed after by combining the tracking task with an auditory reaction time task. Results showed both groups learned equally well and tracking performance on a predictable segment in the dual-task condition was better than on random segments. However, reaction times did not benefit from a predictable tracking segment. To investigate the effect of learning under dual-task situation participants in Experiment 2 practiced the tracking task while simultaneously performing the auditory reaction time task. No learning of the repeated segment could be demonstrated for either group during the training blocks, in contrast to the test-block and retention test, where participants performed better on the repeated segment in both dual-task and single-task conditions. Only the explicit group improved from test-block to retention test. As in Experiment 1, reaction times while tracking a predictable segment were no better than reaction times while tracking a random segment. We concluded that predictability has a positive effect only on the predictable task itself possibly because of a task-shielding mechanism. For dual-task training there seems to be an initial negative effect of explicit instructions, possibly because of fatigue, but the advantage of explicit instructions was demonstrated in a retention test. This might be due to the explicit memory system informing or aiding the implicit memory system.

An adaptive toolbox approach to the route to expertise in sport.

Expertise is characterized by fast decision-making which is highly adaptive to new situations. Here we propose that athletes use a toolbox of heuristics which they develop on their route to expertise. The development of heuristics occurs within the context of the athletes' natural abilities, past experiences, developed skills, and situational context, but does not pertain to any of these factors separately. This is a novel approach because it integrates separate factors into a comprehensive heuristic description. The novelty of this approach lies within the integration of separate factors determining expertise into a comprehensive heuristic description. It is our contention that talent identification methods and talent development models should therefore be geared toward the assessment and development of specific heuristics. Specifically, in addition to identifying and developing separate natural abilities and skills as per usual, heuristics should be identified and developed. The application of heuristics to talent and expertise models can bring the field one step away from dichotomized models of nature and nurture toward a comprehensive approach to the route to expertise.

Optimal use of visual information in adolescents and young adults with developmental coordination disorder.

Recent reports offer contrasting views on whether or not the use of online visual control is impaired in individuals with developmental coordination disorder (DCD). This study explored the optimal temporal basis for processing and using visual information in adolescents and young adults with DCD. Participants were 22 adolescents and young adults (12 males and 10 females; M = 19 years, SD = 3). Half had been diagnosed with DCD as children and still performed poorly on the movement assessment battery for children (DCD group; n = 11), and half reported typical development (TD group; n = 11) and were age- and gender-matched with the DCD group. We used performance on a steering task as a measure of information processing and examined the use of advance visual information. The conditions varied the duration of advance visual information: 125, 250, 500, 750, and 1,000 ms. With increased duration of advance visual information, the TD group showed a pattern of linear improvement. For the DCD group, however, the pattern was best described by a U-curve where optimal performance occurred with about 750 ms of advance information. The results suggest that the DCD group has an underlying preference for immediate online processing of visual information. The exact timing for optimal online control may depend crucially on the task, but too much advance information is detrimental to performance.

Adaptation of motor control strategies to environmental cues in a pursuit-tracking task.

Visually guided tracking paradigms can provide insight into the adaptability of motor control strategies. We argue that the question of whether a sensorimotor process, or its absence, is beneficial or detrimental for performance is one that needs to be answered relative to the sensory cues available in the environment and the given task constraints. In this paper, we describe how and when environmental cues have task-dependent benefits. We used a new pursuit-tracking paradigm and added, removed, or replaced cues within the same tracking task in either predictable or unpredictable environments to investigate the use and adaptability of different control strategies. Participants were invited to perform a tracking task over six blocks in six different conditions. Compared to a condition where both target and control cursor (cues) were visible, performance was maintained when a cue was added and decreased when a cue was removed. Our results show that participants only learned to use new cues if the old one was removed and the replacement was valid. This means that the sensorimotor system adapts only if forced to do so instead of constantly exploiting optimization strategies.

Driving skills of young adults with developmental coordination disorder: Maintaining control and avoiding hazards.

In this study we assess for the first time the driving skills of young adults with developmental coordination disorder (DCD). We use a virtual city and a driving simulator to examine steering control, speed regulation and the responses to pedestrians on the road. Participants were adolescents and young adults who had been diagnosed with the disorder as children. For most participants the symptoms were maintained (DCD group) but for others they had largely dissipated (AD group). We also invited typically developing (control) participants matched in age, gender, and driving experience to the DCD and AD participants. Compared to their matched controls, the DCD group showed difficulties in steering when turning bends but not when driving along straight roads. Although the average speed of the DCD group was similar to their controls this may have been too fast for them to steer effectively around the bends. The DCD group also took 50% more time to react to pedestrians who walked towards their path. We found no such differences between the AD and their matched controls. We discuss the results in terms of visual information processing and suggest further applied and fundamental research on this topic.

Driving skills of young adults with developmental coordination disorder: regulating speed and coping with distraction.

In two experiments, we used an automatic car simulator to examine the steering control, speed regulation and response to hazards of young adults with developmental coordination disorder (DCD) and limited driving experience. In Experiment 1 participants either used the accelerator pedal to regulate their speed, or used the brake pedal when they needed to slow down from a pre-set speed. In Experiment 2, we introduced an auditory distraction condition that shared similarities with maintaining a conversation. Overall, the DCD group produced a larger variance in heading and needed more steering adjustments on straight roads, compared to age-matched controls. When turning bends, the DCD group showed greater difficulty in controlling steering while regulating their speed with the accelerator pedal but this was less problematic when using the brake. The DCD group also responded slower than the control group to pedestrians who walked towards their path. The auditory distraction in Experiment 2 had no visible effects on steering control but increased the reaction times to pedestrians in both groups. We discuss the results in terms of the visuomotor control in steering and the learning of optimal mappings between optic flow and vehicle control.