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Surgery Aug 2020Surgical patients incur preventable harm from cognitive and judgment errors made under time constraints and uncertainty regarding patients' diagnoses and predicted...
BACKGROUND
Surgical patients incur preventable harm from cognitive and judgment errors made under time constraints and uncertainty regarding patients' diagnoses and predicted response to treatment. Decision analysis and techniques of reinforcement learning theoretically can mitigate these challenges but are poorly understood and rarely used clinically. This review seeks to promote an understanding of decision analysis and reinforcement learning by describing their use in the context of surgical decision-making.
METHODS
Cochrane, EMBASE, and PubMed databases were searched from their inception to June 2019. Included were 41 articles about cognitive and diagnostic errors, decision-making, decision analysis, and machine-learning. The articles were assimilated into relevant categories according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews guidelines.
RESULTS
Requirements for time-consuming manual data entry and crude representations of individual patients and clinical context compromise many traditional decision-support tools. Decision analysis methods for calculating probability thresholds can inform population-based recommendations that jointly consider risks, benefits, costs, and patient values but lack precision for individual patient-centered decisions. Reinforcement learning, a machine-learning method that mimics human learning, can use a large set of patient-specific input data to identify actions yielding the greatest probability of achieving a goal. This methodology follows a sequence of events with uncertain conditions, offering potential advantages for personalized, patient-centered decision-making. Clinical application would require secure integration of multiple data sources and attention to ethical considerations regarding liability for errors and individual patient preferences.
CONCLUSION
Traditional decision-support tools are ill-equipped to accommodate time constraints and uncertainty regarding diagnoses and the predicted response to treatment, both of which often impair surgical decision-making. Decision analysis and reinforcement learning have the potential to play complementary roles in delivering high-value surgical care through sound judgment and optimal decision-making.
Topics: Attitude to Health; Clinical Decision-Making; Decision Making, Shared; Decision Support Techniques; Decision Trees; Electronic Health Records; Humans; Machine Learning; Numbers Needed To Treat; Patient Preference; Patient-Centered Care; Surgical Procedures, Operative
PubMed: 32540036
DOI: 10.1016/j.surg.2020.04.049 -
The Cochrane Database of Systematic... Aug 2016Malabsorption of fat and protein contributes to poor nutritional status in people with cystic fibrosis. Impaired pancreatic function may also result in increased gastric... (Review)
Review
BACKGROUND
Malabsorption of fat and protein contributes to poor nutritional status in people with cystic fibrosis. Impaired pancreatic function may also result in increased gastric acidity, leading in turn to heartburn, peptic ulcers and the impairment of oral pancreatic enzyme replacement therapy. The administration of gastric acid-reducing agents has been used as an adjunct to pancreatic enzyme therapy to improve absorption of fat and gastro-intestinal symptoms in people with cystic fibrosis. It is important to establish the evidence regarding potential benefits of drugs that reduce gastric acidity in people with cystic fibrosis. This is an update of a previously published review.
OBJECTIVES
To assess the effect of drug therapies for reducing gastric acidity for: nutritional status; symptoms associated with increased gastric acidity; fat absorption; lung function; quality of life and survival; and to determine if any adverse effects are associated with their use.
SEARCH METHODS
We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register which comprises references identified from comprehensive electronic database searches, handsearches of relevant journals, abstract books and conference proceedings.Most recent search of the Group's Trials Register: 12 May 2016.
SELECTION CRITERIA
All randomised and quasi-randomised trials involving agents that reduce gastric acidity compared to placebo or a comparator treatment.
DATA COLLECTION AND ANALYSIS
Both authors independently selected trials, assessed trial quality and extracted data.
MAIN RESULTS
The searches identified 39 trials; 17 of these, with 273 participants, were suitable for inclusion, but the number of trials assessing each of the different agents was small. Seven trials were limited to children and four trials enrolled only adults. Meta-analysis was not performed, 14 trials were of a cross-over design and we did not have the appropriate information to conduct comprehensive meta-analyses. All the trials were run in single centres and duration ranged from five days to six months. The included trials were generally not reported adequately enough to allow judgements on risk of bias.However, one trial found that drug therapies that reduce gastric acidity improved gastro-intestinal symptoms such as abdominal pain; seven trials reported significant improvement in measures of fat malabsorption; and two trials reported no significant improvement in nutritional status. Only one trial reported measures of respiratory function and one trial reported an adverse effect with prostaglandin E2 analogue misoprostol. No trials have been identified assessing the effectiveness of these agents in improving quality of life, the complications of increased gastric acidity, or survival.
AUTHORS' CONCLUSIONS
Trials have shown limited evidence that agents that reduce gastric acidity are associated with improvement in gastro-intestinal symptoms and fat absorption. Currently, there is insufficient evidence to indicate whether there is an improvement in nutritional status, lung function, quality of life, or survival. Furthermore, due to the unclear risks of bias in the included trials, we are unable to make firm conclusions based on the evidence reported therein. We therefore recommend that large, multicentre, randomised controlled clinical trials are undertaken to evaluate these interventions.
Topics: Abdominal Pain; Adult; Child; Cystic Fibrosis; Dietary Fats; Gastric Acid; Gastrointestinal Agents; Histamine H2 Antagonists; Humans; Intestinal Absorption; Pancreas; Proton Pump Inhibitors; Randomized Controlled Trials as Topic
PubMed: 27546383
DOI: 10.1002/14651858.CD003424.pub4 -
International Journal of Psychiatry in... Sep 2022Mental capacity for treatment decisions in psychiatry inpatients is an important ethical and legal concern, especially in light of changes in mental capacity legislation... (Review)
Review
BACKGROUND
Mental capacity for treatment decisions in psychiatry inpatients is an important ethical and legal concern, especially in light of changes in mental capacity legislation in many jurisdictions.
AIMS
To conduct a systematic review of literature examining the prevalence of mental capacity for treatment decisions among voluntary and involuntary psychiatry inpatients, and to assess any correlations between research tools used to measure mental capacity and binary judgements using criteria such as those in capacity legislation.
METHOD
We searched PsycINFO, Ovid MEDLINE and EMBASE for studies assessing mental capacity for treatment decisions in people admitted voluntarily and involuntarily to psychiatric hospitals.
RESULTS
Forty-five papers emanating from 33 studies were identified. There was huge variability in study methods and often selective populations, but the prevalence of decision-making capacity varied between 5% and 83.7%. These figures resulted from studies using cut-off scores or categorical criteria only. The prevalence of decision-making capacity among involuntary patients ranged from 7.7% to 42%, and among voluntary patients ranged from 29% to 97.9%. Two papers showed positive correlations between clinicians' judgement of decision-making capacity and scores on the MacArthur Competence Assessment Tool for Treatment; two papers showed no such correlation.
CONCLUSIONS
Not all voluntary psychiatry inpatients possess mental capacity and many involuntary patients do. This paradox needs to be clarified and resolved in mental health legislation; supported decision-making can help with this task.Key PointsLegislative changes for mental capacity are taking place in many jurisdictions.This is an important human rights issue for many people, including psychiatry inpatients.In our review, we found the prevalence of decision-making capacity varies between 5% and 83.7% in psychiatry inpatients.Not all voluntary inpatients have decision-making capacity.Many involuntary inpatients have mental capacity to make decisions.Supported decision-making can help those with impairments in their mental capacity.
Topics: Humans; Mental Competency; Inpatients; Decision Making; Informed Consent; Psychiatry; Mental Disorders
PubMed: 34941467
DOI: 10.1080/13651501.2021.2017461 -
The Cochrane Database of Systematic... Jun 2019Diabetic peripheral neuropathy (DPN) is a common and severe complication that affects 50% of people with diabetes. Painful DPN is reported to occur in 16% to 24% of... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Diabetic peripheral neuropathy (DPN) is a common and severe complication that affects 50% of people with diabetes. Painful DPN is reported to occur in 16% to 24% of people with diabetes. A complete and comprehensive management strategy for the prevention and treatment of DPN, whether painful or not, has not yet been defined.Research into treatment for DPN has been characterised by a series of failed clinical trials, with few noteworthy advances. Strategies that support peripheral nerve regeneration and restore neurological function in people with painful or painless DPN are needed. The amino acid acetyl-L-carnitine (ALC) plays a role in the transfer of long-chain fatty acids into mitochondria for β-oxidation. ALC supplementation also induces neuroprotective and neurotrophic effects in the peripheral nervous system. Therefore, ALC supplementation targets several mechanisms relevant to potential nerve repair and regeneration, and could have clinical therapeutic potential. There is a need for a systematic review of the evidence from clinical trials.
OBJECTIVES
To assess the effects of ALC for the treatment of DPN.
SEARCH METHODS
On 2 July 2018, we searched the Cochrane Neuromuscular Specialised Register, CENTRAL, MEDLINE, Embase, LILACS, ClinicalTrials.gov, and the World Health Organization International Clinical Trials Registry Platform. We checked references, searched citations, and contacted study authors to identify additional studies.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) and quasi-RCTs of ALC compared with placebo, other therapy, or no intervention in the treatment of DPN. Participants could be of any sex and age, and have type 1 or type 2 diabetes mellitus, of any severity, with painful or painless DPN. We accepted any definition of minimum criteria for DPN, in accordance with the Toronto Consensus. We imposed no language restriction.Pain was the primary outcome, measured as the proportion of participants with at least 30% (moderate) or 50% (substantial) decrease in pain over baseline, or as the score on a visual analogue scale (VAS) or Likert scale for pain.
DATA COLLECTION AND ANALYSIS
We followed standard Cochrane methods.
MAIN RESULTS
We included four studies with 907 participants, which were reported in three publications. Three trials studied ALC versus placebo (675 participants); in one trial the dose of ALC was 2000 mg/day, and in the other two trials, it was 1500 mg/day or 3000 mg/day. The fourth trial studied ALC 1500 mg/day versus methylcobalamin 1.5 mg/day (232 participants). The risk of bias was high in both trials of different ALC doses and low in the other two trials.No included trial measured the proportion of participants with at least moderate (30%) or substantial (50%) pain relief. ALC reduced pain more than placebo, measured on a 0- to 100-mm VAS (MD -9.16, 95% CI -16.76 to -1.57; three studies; 540 participants; P = 0.02; I² = 56%; random-effects; very low-certainty evidence; a higher score indicating more pain). At doses of 1500 mg/day or less, the VAS score after ALC treatment was little different from placebo (MD -0.05, 95% CI -10.00 to 9.89; two studies; 159 participants; P = 0.99; I² = 0%), but at doses greater than 1500 mg/day, ALC reduced pain more than placebo (MD -14.93, 95% CI -19.16 to -10.70; three studies; 381 participants; P < 0.00001; I² = 0%). This subgroup analysis should be viewed with caution as the evidence was even less certain than the overall analysis, which was already of very low certainty.Two placebo-controlled studies reported that vibration perception improved after 12 months. We graded this evidence as very low certainty, due to inconsistency and a high risk of bias, as the trial authors did not provide any numerical data. The placebo-controlled studies did not measure functional impairment and disability scores. No study used validated symptom scales. One study performed sensory testing, but the evidence was very uncertain.The fourth included study compared ALC with methylcobalamin, but did not report effects on pain. There was a reduction from baseline to 24 weeks in functional impairment and disability, based on the change in mean Neuropathy Disability Score (NDS; scale from zero to 10), but there was no important difference between the ALC group (mean score 1.66 ± 1.90) and the methylcobalamin group (mean score 1.35 ± 1.65) groups (P = 0.23; low-certainty evidence).One placebo-controlled study reported that six of 147 participants in the ALC > 1500 mg/day group (4.1%) and two of 147 participants in the placebo group (1.4%) discontinued treatment because of adverse events (headache, facial paraesthesia, and gastrointestinal disorders) (P = 0.17). The other two placebo-controlled studies reported no dropouts due to adverse events, and more pain, paraesthesia, and hyperaesthesias in the placebo group than the 3000 mg/day ALC group, but provided no numerical data. The overall certainty of adverse event evidence for the comparison of ALC versus placebo was low.The study comparing ALC with methylcobalamin reported that 34/117 participants (29.1%) experienced adverse events in the ALC group versus 33/115 (28.7%) in the methylcobalamin group (P = 0.95). Nine participants discontinued treatment due to adverse events (ALC: 4 participants, methylcobalamin: 5 participants), which were most commonly gastrointestinal symptoms. The certainty of the adverse event evidence for ALC versus methylcobalamin was low.Two studies were funded by the manufacturer of ALC and the other two studies had at least one co-author who was a consultant for an ALC manufacturer.
AUTHORS' CONCLUSIONS
We are very uncertain whether ALC causes a reduction in pain after 6 to 12 months' treatment in people with DPN, when compared with placebo, as the evidence is sparse and of low certainty. Data on functional and sensory impairment and symptoms are lacking, or of very low certainty. The evidence on adverse events is too uncertain to make any judgements on safety.
Topics: Acetylcarnitine; Adult; Aged; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Female; Humans; Male; Middle Aged; Neuralgia; Pain Measurement; Placebos; Randomized Controlled Trials as Topic; Sensation; Vibration; Vitamin B 12
PubMed: 31201734
DOI: 10.1002/14651858.CD011265.pub2 -
European Journal of Pediatrics Mar 2018We aimed to describe the experiences of children and adolescents with congenital heart disease (CHD). Electronic databases were searched until August 2016. Qualitative... (Review)
Review
UNLABELLED
We aimed to describe the experiences of children and adolescents with congenital heart disease (CHD). Electronic databases were searched until August 2016. Qualitative studies of children's perspectives on CHD were included. Data was extracted using thematic synthesis. From 44 studies from 12 countries involving 995 children, we identified 6 themes: disrupting normality (denying the diagnosis, oscillating between sickness and health, destabilizing the family dynamic), powerlessness in deteriorating health (preoccupation with impending mortality, vulnerability to catastrophic complications, exhaustion from medical testing), enduring medical ordeals (traumatized by invasive procedures, disappointed by treatment failure, displaced by transition, valuing empathy and continuity in care, overcoming uncertainty with information), warring with the body (losing stamina, distressing inability to participate in sport, distorted body image, testing the limits), hampering potential and goals (feeling disabled, unfair judgment and exclusion, difficulties with academic achievement, limiting attainment and maintenance of life milestones), and establishing one's own pace (demarcating disease from life, determination to survive, taking limitations in their stride, embracing the positives, finding personal enrichment, relying on social or spiritual support).
CONCLUSION
Children with CHD feel vulnerable and burdened by debilitating physical symptoms, unpredictable complications, and discrimination. Clinicians may support patients by sharing recognition of these profound psychosocial consequences. What is Known: • CHD is associated with difficulties in learning and attention, school absenteeism, decreased endurance, poor body image, and peer socialization • What is lesser known is how young patients cope with the symptoms, prognostic uncertainty, and treatment burden What is New: • We found that children are challenged by lifestyle restrictions, fear of invasive procedures, impaired body image, discrimination, and uncertainty about the future. Feelings of disempowerment are intensified by the unpredictability of disease progression • Thus, strategies to improve outcomes include improved patient education on disease and lifestyle management and partnership with school teachers and counselors for unique psychosocial support.
Topics: Activities of Daily Living; Attitude to Health; Child; Family Relations; Heart Defects, Congenital; Humans; Qualitative Research; Quality of Life; Social Participation; Social Support; Spirituality
PubMed: 29327140
DOI: 10.1007/s00431-017-3081-y -
Dementia & Neuropsychologia 2018Metamemory is the awareness of one's own knowledge and control of memory, and refers to the online ability to gather information about the current state of the memory...
UNLABELLED
Metamemory is the awareness of one's own knowledge and control of memory, and refers to the online ability to gather information about the current state of the memory system.
OBJECTIVE
Metamemory is one's own knowledge and control of memory. A systematic review was performed to identify the types of tasks used for evaluating metamemory monitoring, the stimuli used in these tasks, their limitations and the outcomes in people with Alzheimer's disease (PwAD).
METHODS
This systematic review followed PRISMA methodology. A search of Pubmed, Scopus and Web of Science electronic databases was carried out in September, 2018, identifying experimental investigations of metamemory and dementia.
RESULTS
We included 21 studies. The most common tasks used were judgement of learning, feeling of knowing, judgement of confidence and global prediction. The rates of discrepancy between PwAD and caregivers still need further research. The Rey Auditory Verbal Learning Test was the most used list of words. PwAD are able to accurately rate their memory functioning and performance, when the evaluation is done soon afterwards. PwAD tend to overestimate their functioning and performance when the judgement involves forward-looking vision.
CONCLUSION
In the context of metamemory impairment, clinicians and caregivers should seek interventions aiming to identify compensatory styles of functioning. This systematic review provides initial evidence for the use of metamemory measures as part of broader assessments evaluating Alzheimer's disease.
PubMed: 30546843
DOI: 10.1590/1980-57642018dn12-040002 -
Journal of Oral Rehabilitation May 2024Patients with chronic headaches and chronic oro-facial pain commonly present psychosocial issues that can affect social interactions. A possible reason could be that... (Review)
Review
Facial recognition, laterality judgement, alexithymia and resulting central nervous system adaptations in chronic primary headache and facial pain-A systematic review and meta-analysis.
INTRODUCTION
Patients with chronic headaches and chronic oro-facial pain commonly present psychosocial issues that can affect social interactions. A possible reason could be that patients with these disorders might present impairments in facial recognition, laterality judgement and also alexithymia. However, a systematic review summarizing the effects of facial emotion recognition, laterality judgement and alexithymia in individuals with headaches and oro-facial pain is still not available.
AIM
The main objective of this systematic review (SR) and meta-analysis (MA) was to compile and synthesize the evidence on the occurrence of alexithymia, deficits in laterality or left-right (LR) recognition and/or facial emotion recognition (FER) in patients with chronic headache and facial pain.
METHODS
Electronic searches were conducted in five databases (up to September 2023) and a manual search to identify relevant studies. The outcomes of interest were alexithymia scores, speed and accuracy in LR and/or FER, or any other quantitative data assessing body image distortions. The screening process, data extraction, risk of bias and data analysis were performed by two independent assessors following standards for systematic reviews.
RESULTS
From 1395 manuscripts found, only 34 studies met the criteria. The overall quality/certainty of the evidence was very low. Although the results should be interpreted carefully, individuals with chronic headaches showed significantly higher levels of alexithymia when compared to healthy individuals. No conclusive results were found for the other variables of interest.
CONCLUSION
Although the overall evidence from this review is very low, people with chronic primary headaches and oro-facial pain could be regularly screened for alexithymia to guarantee appropriate management.
PubMed: 38803203
DOI: 10.1111/joor.13742 -
Psychogeriatrics : the Official Journal... Nov 2017Choto-san is a traditional medicine used for hypertension and headaches in Japan and China. Some studies have shown its effectiveness in the treatment of dementia. The... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Choto-san is a traditional medicine used for hypertension and headaches in Japan and China. Some studies have shown its effectiveness in the treatment of dementia. The present review aimed to assess the effectiveness and acceptability of Choto-san in the treatment of adults with cognitive impairment.
METHODS
We included randomized controlled trials comparing Choto-san with placebo for patients with dementia or mild cognitive impairment.
RESULTS
Three randomized controlled trials evaluating 219 participants were included. Two were studies on vascular dementia, and the other was on Alzheimer's dementia. There was no difference between Choto-san and placebo in terms of short-term dichotomous judgement of improvement, but Choto-san was more effective than placebo in terms of short-term improvement of cognitive function as measured by continuous outcomes. Also, dropouts judged it to be acceptable. However, the results were imprecise and/or heterogeneous. The number of participants included in the analysis was small (n = 199 in the primary analysis) and sometimes inconsistent, as indicated by the large I (72% in the primary analysis).
CONCLUSION
Low-quality evidence was suggestive of Choto-san's efficacy for vascular dementia, but the present results may be overestimated. Studies with a larger sample size and conducted over longer periods should be performed. Regardless, Choto-san can be one of the choices for the treatment of vascular dementia as it is well tolerated.
Topics: Cognition Disorders; Dementia; Drugs, Chinese Herbal; Humans; Placebos; Plant Extracts; Plants, Medicinal; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 28589702
DOI: 10.1111/psyg.12275 -
International Journal of Nursing Studies Oct 2021Mild cognitive impairment is an age-related cognitive disorder which is associated with frequent memory lapses, impaired judgement, and progressive functional decline.... (Meta-Analysis)
Meta-Analysis Review
The effect of dance interventions on cognition, neuroplasticity, physical function, depression, and quality of life for older adults with mild cognitive impairment: A systematic review and meta-analysis.
BACKGROUND
Mild cognitive impairment is an age-related cognitive disorder which is associated with frequent memory lapses, impaired judgement, and progressive functional decline. If untreated early, 39.2% of people with mild cognitive impairment could progress to develop dementia. However, there are currently no approved pharmacological interventions to treat the condition, which lead researchers to explore non-pharmacological options, such as dance therapy.
OBJECTIVES
This systematic review aimed to examine the effectiveness of dance interventions on cognition, neuroplasticity, physical function, depression, and quality of life in older adults with mild cognitive impairment.
METHODS
Seven databases were systematically searched from their respective inception dates to 31 March 2020. Relevant randomized controlled trials (RCTs) were screened and assessed for risk of bias. Eight RCTs evaluating dance interventions were included.
RESULTS
Results showed that dance interventions had a significant moderate effect on global cognition (SMD=0.54, Z = 3.55, p<0.001), significantly improved memory (SMD=0.33, Z = 3.97, p<0.001), visuospatial function (SMD=0.42, Z = 2.41, p = 0.02), and language (SMD=0.39, Z = 2.69, p = 0.007). We found that dance interventions produced a significant moderate effect on physical function (SMD=0.55, Z = 3.43, p<0.001), and a significant effect on quality of life (SMD=0.93, Z = 5.04, p<0.0.001).
CONCLUSION
Dance is a non-pharmacological and inexpensive intervention that can be implemented for older adults on a large scale. It can slow down the cognitive deterioration of older adults with mild cognitive impairment. However, the findings should be interpreted with caution due to the heterogeneity in intervention designs. Rigorous design studies with long-term follow-ups, neuroimaging, biological markers, and comprehensive neuropsychological assessment are required to understand the mechanism of dance interventions and demonstrate its efficacy for older adults with mild cognitive impairment. The protocol was registered on PROSPERO (CRD42020173659).
Topics: Aged; Cognition; Cognitive Dysfunction; Depression; Humans; Neuronal Plasticity; Quality of Life
PubMed: 34298320
DOI: 10.1016/j.ijnurstu.2021.104025 -
Behavioural Brain Research Jul 2021Performance on timing tasks changes with age. Whether these changes reflect a real "clock" problem due to aging or a secondary effect of the reduced cognitive resources... (Meta-Analysis)
Meta-Analysis
Performance on timing tasks changes with age. Whether these changes reflect a real "clock" problem due to aging or a secondary effect of the reduced cognitive resources of older adults is still an unsettled question. Research on processing of time in aged populations marked by severe mnemonic and/or attentional deficits, such as patients with Alzheimer's disease (AD) and Mild Cognitive Impairment (MCI), may help elucidate the role of cognitive resources in age-related temporal distortions. To this end, we conducted a systematic review and meta-analysis of timing studies in AD and MCI patients; both prospective and retrospective timing tasks were considered and analysed separately. As concerns prospective timing, a first random-effect model showed a medium overall effect of neurodegeneration on timing performance. When considering the role of moderator variables(i.e., neurodegenerative condition, type of measure, participants' age and years of education, interval length, and type of timing task), mean score appeared to be a less sensitive measure than accuracy and variability, and the observed temporal impairment was smaller in older samples. In addition, AD patients only exhibited medium-to-high impairment on prospective timing tasks, whereas MCI patients did not significantly differ from controls. However, assuming a mean age of 70 years old and absolute error as dependent variable, a second fitted meta-regression model predicted a significant outcome also for MCI patients. Concerning retrospective timing, a significant but small effect of neurodegeneration was observed for retrospective judgments. None of the moderators, however, explained between-studies variability. Collectively, our findings highlight a clear deficit in prospective timing for AD patients and underscore several issues that future work should carefully consider to better investigate the effect of MCI on prospective temporal judgements. Results from retrospective timing also point to a possible impairment of retrospective judgments in neurodegenerative conditions, albeit more studies are needed to substantiate this finding.
Topics: Alzheimer Disease; Cognitive Dysfunction; Humans; Time Perception
PubMed: 33989726
DOI: 10.1016/j.bbr.2021.113354