Neuromuscular adaptations to perturbation-based balance training using treadmill belt accelerations do not transfer to an obstacle trip in older people: A cross-over randomised controlled trial.

BACKGROUND: This study examined (i) adaptations in muscle activity following perturbation-based balance training (PBT) using treadmill belt-accelerations or PBT using walkway trips and (ii) whether adaptations during treadmill PBT transfer to a walkway trip. METHODS: Thirty-eight older people (65+ years) undertook two PBT sessions, including 11 treadmill belt-accelerations and 11 walkway trips. Surface electromyography (EMG) was measured bilaterally on the rectus femoris (RF), tibialis anterior (TA), semitendinosus (ST) and gastrocnemius medial head (GM) during the first (T1) and eleventh (T11) perturbations. Adaptations (within-subjects - 1st vs 11th perturbations for treadmill and walkway PBT) and their transfer (between-subjects - 1st walkway trip after treadmill PBT vs 1st walkway trip with no prior training) effects were examined for the EMG parameters. RESULTS: Treadmill PBT reduced post-perturbation peak muscle activation magnitude (left RF, TA, ST, right RF, ST, GM), onset latency (right TA), time to peak (right RF) and co-contraction index (knee muscles) (P < 0.05). Walkway PBT reduced post-trip onset latencies (right TA, ST), peak magnitude (left ST, right GM), time to peak (right RF, ST) and pre-perturbation muscle activity (right TA) (P < 0.05). Those who undertook treadmill PBT were not different to those without prior training during the first walkway trip (P > 0.05). CONCLUSIONS: Both treadmill and walkway PBT induced earlier initiation and peak activation of right limb muscles responsible for the first recovery step. Treadmill PBT also reduced co-contraction of the knee muscles. Adaptations in muscle activity following treadmill PBT did not transfer to a walkway trip.

A Wrist-Worn Wearable Device Can Identify Frailty in Middle-Aged and Older Adults: The UK Biobank Study.

OBJECTIVES: Digital gait biomarkers collected from body-worn devices can remotely and continuously collect movement types, quantity, and quality in real life. This study assessed whether digital gait biomarkers from a wrist-worn device could identify people with frailty in a large sample of middle-aged and older adults. DESIGN: Cross-sectional study. SETTING AND PARTICIPANTS: A total of 5822 middle-aged (43-64 years) and 4344 older adults (65-81 years) who participated in the UK Biobank study. MEASURES: Frailty was assessed using a modified Fried's frailty assessment and was defined as having ≥3 of the 5 frailty criteria (weakness, low activity levels, slowness, exhaustion, and weight loss). Fourteen digital gait biomarkers were extracted from accelerometry data collected from wrist-worn sensors worn continuously by participants for up to 7 days. RESULTS: A total of 238 (4.1%) of the middle-aged group and 196 (4.5%) of the older group were categorized as frail. Multivariable logistic regression analysis revealed that less daily walking (as assessed by step counts), slower maximum walking speed, and increased step time variability best-identified people with frailty in the middle-aged group [area under the curve (95% CI): 0.70 (0.66-0.73)]. Less daily walking, slower maximum walking speed, increased step time variability, and a lower proportion of walks undertaken with a manual task best-identified people with frailty in the older group [0.73 (0.69-0.76)]. CONCLUSIONS AND IMPLICATIONS: Our findings indicate that measures obtained from wrist-worn wearable devices worn in everyday life can identify individuals with frailty in both middle-aged and older people. These digital gait biomarkers may facilitate screening programs and the timely implementation of frailty-prevention interventions.

Cerebral activation caused by dental sounds: a functional magnetic resonance imaging study.

Dental drilling sounds can induce anxiety in some patients. This study aimed to use functional magnetic resonance imaging (fMRI) to assess the relationship between dental fear and auditory stimuli. Thirty-four right-handed individuals (21 women and 13 men; average age, 31.2 years) were selected. The level of dental fear was assessed using the dental fear survey (DFS). Based on a threshold DFS score > 52, participants were categorized into two groups: dental fear (DF) group (n = 12) and control group (n = 22). Two types of stimuli were presented in a single session: dental and neutral sounds. Cerebral activation during the presentation of these sounds was evaluated using contrast-enhanced blood oxygenation level-dependent fMRI. In the DF group, dental sounds induced significantly stronger activation in the left inferior frontal gyrus and left caudate nucleus (one-sample t test, P < 0.001). In contrast, in the control group, significantly stronger activation was observed in the bilateral Heschl's gyri and left middle frontal gyrus (one-sample t test, P < 0.001). Additionally, a two-sample t test revealed that dental sounds induced a significantly stronger activation in the left caudate nucleus in the DF group than in the control group (P < 0.005). These findings suggest that the cerebral activation pattern in individuals with DF differs from that in controls. Increased activation of subcortical regions may be associated with sound memory during dental treatment.

Treadmill induced belt-accelerations may not accurately evoke the muscle responses to obstacle trips in older people.

BACKGROUND: Treadmill belt-accelerations are a commonly utilised surrogate for tripping, but their physiological validity is unknown. This study examined if a treadmill belt-acceleration induces lower limb muscle activation responses similar to a trip on a walkway. METHODS: 38 older people (65+ years) experienced one treadmill belt-acceleration and one walkway obstacle trip in random order. Muscle responses were assessed bilaterally using surface electromyography on the rectus femoris (RF), tibialis anterior (TA), semitendinosus (ST) and gastrocnemius medial head (GM). Unperturbed muscle activity, post-perturbation onset latency, peak magnitude, time to peak and co-contraction index (CCI) were examined. RESULTS: Muscle activity in the right ST was greater during unperturbed walking on the treadmill compared to walkway (P=0.011). Compared to a treadmill belt-acceleration, a walkway trip elicited faster onset latencies in all muscles; greater peak magnitudes in the left RF, TA, GM and right GM; faster time to peaks in the left TA and right GM; and lower knee and ankle muscle CCI (P<0.05). CONCLUSIONS: Walkway trips and treadmill belt-accelerations elicit distinct muscle activation patterns. While walkway trips induced faster and larger muscle responses, treadmill belt-accelerations involved greater co-contraction. Therefore, treadmill belt-accelerations may not accurately simulate the muscle responses to trips.

Immediate Effects of Lower Limb Sensory Simulation Using Smart Socks to Stabilize Gait in People with Parkinson's Disease.

People with Parkinson's disease (PD) experience gait impairment that can lead to falls and poor quality of life. Here we investigate the feasibility of using smart socks to stimulate the lower limbs of people with PD to reduce excessive step time variability during walking. We hypothesised that rythmic excitation of lower limb afferents, matched to a participant's comfortable pace, would entrain deficient neuro-muscular signals resulting in improved gait. Five people with mild to moderate PD symptoms (70 ± 9 years) were tested on medication before and after a 30-minute familierization session. Paired t-tests and Cohen's d were used to assess gait changes and report effect sizes. Participant experiences were recorded through structured interviews. Lower limb stimulation resulted in an acute 15% increase in gait speed (p=0.006, d=0.62), an 11% increase in step length (p=0.04, d=0.35), a 44% reduction in step time variability (p=0.03, d=0.91), a 22% increase in perceived gait quality (p=0.04, d=1.17), a 24% reduction in mental effort to walk (p=0.02, d=0.79) and no statistical difference for cadence (p=0.16). Participants commented positively on the benefit of stimulation during training but found that stimulation could be distracting when not walking and the socks hard to put on. While the large effects for step time variability and percieved gait quality (Cohen's d > 0.8) are promising, limitations regarding sample size, potential placebo effects and translation to the home environment should be addressed by future studies.Clinical Relevance- This study demonstrates the feasibility of using smart stimulating socks to reduce excessive step time variability in people with PD. As step time variability is a risk factor for falls, the use of smart textiles to augment future rehabilitation programs warrants further investigation.

Effect of driving training on car crashes and driving skills in older people: A systematic review and meta-analysis.

The primary aim of this systematic review was to examine the efficacy of driving interventions with regard to a reduction in motor vehicle crashes and improvements in driving skills among older people. The secondary aim was to identify the optimal type (on-road or off-road) and dosage (period, sessions, and duration) of driving interventions for improving driving skills in older people. We searched MEDLINE, EMBASE, PsycINFO, and Scopus of Systematic Reviews for papers published from their inception to December 1, 2020, as well as the reference lists of the included papers. The selected studies were randomized controlled trials examining the effects of driving interventions among community-dwelling older drivers aged 65 years and over. A meta-analysis of two studies (n = 960) showed that driving interventions significantly reduced the number of motor vehicle crashes per person-years. Ten studies (n = 575) were included in the meta-analysis showing that the interventions significantly improved the driving skill scores. Driving skill scores significantly improved after on-road training, and in interventions of at least 3 h, 3 sessions, and 3 weeks. Driving interventions significantly improve driving skills and reduce motor vehicle crashes among older drivers aged 65 years and over. On-road training is more efficacious than off-road training and driving interventions of at least 3 h taking place in 3 sessions over a period of 3 weeks may be required to improve driving skills in older drivers. Geriatr Gerontol Int 2023; 23: 771-778.

Combined Reactive and Volitional Step Training Improves Balance Recovery and Stepping Reaction Time in People With Parkinson's Disease: A Randomised Controlled Trial.

BACKGROUND: Falls are frequent and devastating events for people with Parkinson's disease (PD). Here, we investigated whether laboratory-based reactive step training combined with home-based volitional step training was effective in improving balance recovery and stepping ability in people with PD. METHODS: Forty-four people with idiopathic PD were randomized into intervention or control groups. Intervention participants performed unsupervised volitional step training using home-based exergames (80+ minutes/week) for 12 weeks and attended reactive step training sessions in which they were exposed to slip and trip perturbations at 4 and 8 weeks. Control participants continued their usual activities. Primary outcomes were balance recovery following an induced-trip/slip and choice stepping reaction time (CSRT) at the 12-week reassessment. Secondary outcomes comprised sensorimotor, balance, cognitive, psychological, complex stepping (inhibitory CSRT and Stroop Stepping Test [SST]), gait measures, and falls experienced in everyday life. RESULTS: At reassessment, the intervention group had significantly fewer total laboratory-induced falls and faster CSRT compared to the control group (P < .05). The intervention group also had significantly faster inhibitory CSRT and SST movement times and made fewer mistakes in the SST (P < .05). There were no significant differences in the rate of every day falls or other secondary outcome measures between the groups. CONCLUSION: Combined volitional and reactive step training improved balance recovery from an induced-perturbation, voluntary stepping time, and stepping accuracy in cognitively challenging tests in people with PD. Further research is required to determine whether such combined step training can prevent daily-life falls in this population.

Impact of mobile phone use on accidental falls risk in young adult pedestrians.

Background: Mobile phone use is known to be a distraction to pedestrians, increasing their likelihood of crossing into oncoming traffic or colliding with other people. However, the effect of using a mobile phone to text while walking on gait stability and accidental falls in young adults remains inconclusive. This study uses a 70 cm low friction slip hazard and the threat of hazard to investigate the effects of texting while walking on gait stability, the ability to recover balance after a slip hazard and accidental falls. Methods: Fifty healthy young adults performed six walking tasks, and one seated texting task in random order. The walks were conducted over a 10-m walkway. Four progressive hazard levels were used: 1) Seated; 2) Normal Walk (walking across the walkway with no threat of a slip); 3) Threat (walking with the threat of a slip); and 4) Slip (walking with an actual 70 cm slip hazard). The three walking conditions were repeated twice with and without the mobile phone texting dual-task. Gait kinematics and trunk posture were recorded using wearable sensors attached to the head, trunk, pelvis and feet. Study outcomes were analyzed using repeated measures analysis of variance with significance set to P≤.05. Results: Mobile phone use significantly impaired postural balance recovery when slipping, as demonstrated by increased trunk sway. Mobile phone use negatively impacted gait stability as demonstrated by increased step time variability and decreased harmonic ratios. Increased hazard levels also led to reduced texting accuracy. Conclusions: Using a mobile phone to text while walking may compete with locomotor tasks, threat assessment and postural balance control mechanisms, which leads to an increased risk of accidental falls in young adults. Pedestrians should therefore be discouraged through new educational and technology-based initiatives (for example a "texting lock" on detection of walking) from texting while walking on roadside footpaths and other environments where substantial hazards to safety exist.

Risk Factors for Falls and Fall-Related Fractures in Community-Living Older People with Pain: A Prospective Cohort Study.

(1) Background: This prospective study aimed to identify predictors of falls and fall-related fractures in community-dwelling older people with pain; (2) Methods: Participants comprised 389 community-dwelling older people aged 70+ years who had musculoskeletal pain in the neck, back, hip, leg/knee and/or feet. Demographic, anthropometric, balance, mobility, cognitive function, psychological status and physical activity level measures were obtained at baseline. Falls were monitored with monthly falls calendars for 12 months. Logistic regression analyses were performed to identify predictors of falls and fall-related fractures during a 12-month follow-up; (3) Results: Of the 389 participants, 175 (45.0%) and 20 (5.1%) reported falls and fall-related fractures during the 12-month follow-up, respectively. Greater postural sway on foam, more depressive symptoms and lower physical activity levels at baseline were associated with falls during the 12-month follow-up. Slower walking speed at baseline was associated with fall-related fractures during the 12-month follow-up. These associations remained significant after adjusting for age, sex, body mass index, comorbidities and medication use; (4) Conclusions: This study suggests poor balance, low mood and a less active lifestyle are predictors of falls, and slower walking speed predicts fall-related fractures among community-dwelling older people with pain.

Depression as a Prodromal Symptom of Neurodegenerative Diseases.

Neurodegenerative diseases can manifest as psychiatric symptoms in the prodromal phase, before the onset of core symptoms such as neurological, motor, and cognitive symptoms. Positron emission tomography (PET) has made it possible to detect the pathology of some neurodegenerative diseases in vivo. Many studies have indicated that depression is a preclinical symptom of neurodegenerative diseases. Approximately 10% of non-demented participants with depression developed Alzheimer's disease (AD) during the follow-up period. The prevalence of depression/dysphoria was 42.9% in the preclinical stage of dementia with Lewy bodies. Depression was present in 33.3% of patients with preclinical behavioral-variant frontotemporal lobar degeneration. Approximately 10% of patients had a history of depression at the time of diagnosis with Parkinson's disease. PET studies have revealed the pathology of neurodegenerative diseases in some cases of geriatric depression. Increased brain amyloid-beta deposition in late-onset depression is a possible reflection of prodromal AD. The severity of depression was significantly associated with greater inferior temporal tau and marginally associated with greater entorhinal cortex tau, and depression was associated with significantly greater mean cortical tau deposition. Thus, the presence of depression as a preclinical/prodromal symptom of neurodegenerative diseases has been demonstrated by epidemiological, pathological, and biomarker studies. A growing body of evidence from PET studies indicates that some cases of geriatric depression have pathologies of degenerative neurological disease. In the future, it is expected that PET will be utilized as an imaging biomarker for diagnosis of psychiatric disorders and development of new therapeutic agents.

Training reactive balance using trips and slips in people with multiple sclerosis: A blinded randomised controlled trial.

BACKGROUND: This study examined the feasibility and efficacy of reactive balance training for improving stepping performance and reducing laboratory-induced falls in people with multiple sclerosis (MS). METHODS: Thirty people diagnosed with MS (18-70 years) participated in a blinded randomized controlled trial (ACTRN12618001436268). The intervention group (n = 14) underwent two 50-minute sessions (total 100 min) that exposed them to a total of 24 trips and 24 slips in mixed order, over one week. The control group (n = 16) received sham training (stepping over foam obstacles) with equivalent dosage. The primary outcome was falls into the harness (defined as >30% body weight) when exposed to trips and slips that were unpredictable in timing, location and type at post-assessment. Physical and psychological measures were also assessed at baseline and post assessments. RESULTS: The intervention and control groups completed 86% and 95% of the training protocols respectively. Incidence rate ratios (95% confidence intervals) of the intervention group relative to the control group were 0.57 (0.25, 1.26) for all falls, 0.80 (0.30, 2.11) for slip falls and 0.20 (0.04, 0.96) for trip falls in the laboratory. Kinematic analyses indicated the intervention participants improved dynamic stability, with higher centre of mass position and reduced trunk sway during recovery steps following a trip, compared to control. There were no significant differences between the intervention and control participants at post-assessment for other secondary outcome measures. CONCLUSIONS: Reactive balance training improved trip-induced dynamic stability, limb support, trunk control and reduced falls in people with MS. More research is required to optimise the training protocol and determine whether the beneficial effects of reactive balance training can be retained long term and generalize to fewer daily-life falls.

The role of left insula mediating impaired error processing in response inhibition in adult heavy drinkers.

Identification of neurobiological mechanisms underlying development of alcohol use disorder is critical to ensuring the appropriate early-phase treatment and prevention of the disorder. To this aim, we tried to elucidate the disturbance of neural functions in heavy drinking, which can lead to alcohol use disorder. Because response inhibition is affected by alcohol use disorder, we examined neural activation and task performance for response inhibition using the Go/No-Go task in an fMRI paradigm in adult non-dependent heavy and light drinkers. We examined the neural activation for error processing and inhibitory control, components of response inhibition. We then investigated the mediating effect of the relevant neural substrate on the relationship between the level of alcohol drinking and task performance using mediation analysis. We found that heavy drinking significantly decreased activation in the left insula during error processing and increased the mean commission error rate for No-Go trials compared with light drinking. Mediation analysis demonstrated full mediation of the left insula activation during error processing for the relationship between drinking level and commission error rate. Our results suggested that left insula activation may be a neural marker pivotal for potential conversion to alcohol use disorder in individuals with high clinical risk such as heavy drinking.

Perturbation-based balance training: Principles, mechanisms and implementation in clinical practice.

Since the mid-2000s, perturbation-based balance training has been gaining interest as an efficient and effective way to prevent falls in older adults. It has been suggested that this task-specific training approach may present a paradigm shift in fall prevention. In this review, we discuss key concepts and common issues and questions regarding perturbation-based balance training. In doing so, we aim to provide a comprehensive synthesis of the current evidence on the mechanisms, feasibility and efficacy of perturbation-based balance training for researchers and practitioners. We address this in two sections: "Principles and Mechanisms" and "Implementation in Practice." In the first section, definitions, task-specificity, adaptation and retention mechanisms and the dose-response relationship are discussed. In the second section, issues related to safety, anxiety, evidence in clinical populations (e.g., Parkinson's disease, stroke), technology and training devices are discussed. Perturbation-based balance training is a promising approach to fall prevention. However, several fundamental and applied aspects of the approach need to be further investigated before it can be widely implemented in clinical practice.

Factors Regarding Suicide Decline in Japan: A Longitudinal Study on Psychiatric Diagnosis of Serious Suicide Attempters.

BACKGROUND: The number of suicides in Japan decreased during the period from 2012 through 2019. Because data on factors associated with this decline are limited, we conducted a retrospective longitudinal study of psychiatric diagnoses of serious suicide attempters before 2012 and after 2019. METHODS: Serious suicide attempters admitted to the critical care medicine (CCM) department of Nippon Medical School Hospital between 2006 and 2017 were included and classified as those before and after the suicide decline in 2012. Chi-square test and residual analysis were used to analyze changes in the proportion of suicide attempters among all patients admitted to CCM and to examine differences in the proportion of psychiatric diagnoses. RESULTS: The proportion of suicide attempters among CCM hospitalized patients decreased overall (χ2 (1) =18.29, p<.01). The proportion of psychiatric diagnoses changed significantly (χ2 (8) =62.21, p<0.001); specifically, it decreased for schizophrenia (residual: -2.28), depressive disorders (residual: -5.39), persistent mood disorders (residual: -3.58), and reaction to stress disorders (residual: -2.73). Depressive disorders decreased and had a large contribution ratio in both sexes. CONCLUSIONS: The decrease in the proportion of attempted suicides among patients admitted to CCM was consistent with the decline in suicides in Japan. Analysis by psychiatric diagnosis confirmed a significant decrease in the proportion of suicide attempts associated with depressive disorders, schizophrenia, and reaction to stress disorders, which were the most common disorders associated with attempted suicide. Depressive disorders made the greatest contribution to the reduction in suicide attempts.

Effect of DL-Methylephedrine on Dopamine Transporter Using Positron Emission Tomography With [18F]FE-PE2I.

Rationale: Since ephedrine has a dopamine transporter (DAT) inhibitory effect similar to amphetamine, dl-methylephedrine, a derivative of ephedrine, is considered to have the characteristics of a central nervous system stimulant due to the DAT inhibitory effect. For example, the World Anti-Doping Agency categorizes dl-methylephedrine as a stimulant in the prohibited list for competitions. Assuming to have the same effect as ephedrine, the urinary concentration of dl-methylephedrine is regulated below 10 µg/mL, as is ephedrine. However, the extent to which dl-methylephedrine affects brain function is not yet fully understood. Objectives: The purpose of this study was to evaluate DAT occupancy by a single oral administration of a daily dose of dl-methylephedrine using positron emission tomography (PET) with [18F]FE-PE2I to characterize its stimulatory effect on the central nervous system. Methods: Nine healthy male volunteers were enrolled in the study. The experiments were designed as a placebo-controlled randomized double-blind crossover comparative study. After the first PET scan in a drug-free state, the second and third PET scans were performed with randomized dosing at 60 mg of dl-methylephedrine or placebo. The plasma and urine concentrations of dl-methylephedrine were measured just before and after the PET scans, respectively. Results: Mean urine and plasma concentrations of dl-methylephedrine were 13.9 µg/mL and 215.2 ng/mL, respectively. Mean DAT occupancy in the caudate was 4.4% for dl-methylephedrine and 1.2% for placebo. Mean DAT occupancy in the putamen was 3.6% for dl-methylephedrine and 0.5% for placebo. There was no significant difference of DAT occupancies between the groups. Conclusion: In this study, the urinary concentration of dl-methylephedrine (13.9 µg/mL) was higher than the prohibited reference value (10.0 µg/mL), and there was no significant difference in DAT occupancy between dl-methylephedrine and placebo. These findings suggest that a clinical daily dose of dl-methylephedrine may exceed the doping regulation value according to urine concentration; however, it was considered that at least the central excitatory effect mediated by DAT inhibition was not observed at the daily dose of dl-methylephedrine.

Impact of pathological conditions on postural reflex latency and adaptability following unpredictable perturbations: A systematic review and meta-analysis.

BACKGROUND: Pathological conditions can impair responses to postural perturbations and increase risk of falls. RESEARCH QUESTION: To what extent are postural reflexes impaired in people with pathological conditions and can exercise interventions shorten postural reflexes? METHODS: MEDLINE, EMBASE, Scopus, SportDiscus and Web of Science were systematically searched for articles comparing muscle activation onset latency in people with pathological conditions to healthy controls following unpredictable perturbations including the effect of exercise interventions (registration: CRD42020170861). RESULTS: Fifty-three articles were included for systematic review. Significant delays in muscle activity onset following perturbations were evident in people with multiple sclerosis (n = 7, mean difference [MD]: 22 ms, 95% confidence interval [CI]: 11, 33), stroke (n = 10, MD: 34 ms, 95% CI: 19, 49), diabetes (n = 2, MD: 19 ms, 95% CI: 10, 27), HIV (n = 3, MD: 9 ms, 95% CI: 4, 14), incomplete spinal cord injury (n = 2, MD: 57 ms, 95% CI: 33, 80) and back and knee pain (n = 7, MD: 12 ms, 95% CI: 6, 18), but not in people with Parkinson's disease (n = 10) or cerebellar dysfunction (n = 4). Following exercise interventions, the paretic limb of stroke survivors (n = 3) displayed significantly faster muscle activation onset latency compared to pre-exercise (MD: -13 ms, 95% CI: -24, -4), with no significant changes in Parkinson's disease (n = 3). CONCLUSIONS: This systematic review demonstrated that postural reflexes are significantly delayed in people with multiple sclerosis (+22 ms), stroke (+34 ms), diabetes (+19 ms), HIV (+9 ms), incomplete spinal cord injury (+57 ms), back and knee pain (+12 ms); pathological conditions characterized by impaired sensation or neural function. In contrast, timing of postural reflexes was not impaired in people with Parkinson's disease and cerebellar dysfunction, confirming the limited involvement of supraspinal structures. The meta-analysis showed exercise interventions can significantly shorten postural reflex latencies in stroke survivors (-14 ms), but more research is needed to confirm this finding and in people with other pathological conditions.

Prediction of Corresponding Dose of Transdermal Blonanserin to Oral Dose Based on Dopamine D2 Receptor Occupancy: Unique Characteristics of Blonanserin Transdermal Patch.

BACKGROUND/PURPOSE: Blonanserin is an atypical antipsychotic, a potent selective antagonist of dopamine D2 receptor (D2), prescribed as oral formulations in patients with schizophrenia. Blonanserin transdermal patch was developed to provide a new treatment option, but the corresponding dose to oral blonanserin was not clear. The aims of this study were to clarify the pharmacokinetic (PK)-pharmacodynamic characteristics of blonanserin after transdermal patch application and to evaluate the corresponding dose to oral formulation based on striatal D2 occupancy. METHODS: The relationship between D2 occupancy and plasma blonanserin concentration was analyzed using an Emax model based on data from positron emission tomography study with oral and transdermal blonanserin. D2 occupancy was simulated using Emax models based on the observed plasma concentrations and the simulated plasma concentrations obtained from population PK model. RESULTS: Plasma blonanserin concentration levels after repeated patch applications were nearly stable throughout the day and no effect of sex, advanced age, or application site was detected. The concentration at half maximal D2 occupancy during transdermal patch applications, 0.857 ng/mL, was higher than that after oral doses, 0.112 ng/mL, suggesting metabolite contribution after oral doses. The median predicted D2 occupancy during blonanserin patch applications at doses of 40 and 80 mg/d was 48.7% and 62.5%, respectively, and the distribution of D2 occupancy at these doses could cover most of that at oral doses of 8 to 24 mg/d. CONCLUSIONS: Predicted D2 occupancy suggested that a 40- to 80-mg/d blonanserin transdermal patch dose corresponds to an 8- to 24-mg/d oral dose for the treatment of schizophrenia.

Suicide decline and improved psychiatric treatment status: longitudinal survey of suicides and serious suicide attempters in Tokyo.

BACKGROUND: Connecting individuals in need of psychiatric treatment with adequate medical services has been a major strategy for suicide prevention in Japan. By investigating serious suicide attempters admitted to our Critical Care Medical Center (CCM), we aimed to examine longitudinal changes in the psychiatric treatment status of high-risk suicidal individuals, and to explore the association between any improvement in psychiatric treatment status and suicide decline. METHODS: Subjects from two periods, 2006-2011 and 2012-2017, were enrolled. We collected the data of 32,252 suicides in Tokyo from police reports and the data of 942 suicide attempters admitted to CCM from medical records. Data were annually collected by both age and gender for the number of suicide completers, the number of suicide attempters, and the psychiatric treatment rates, respectively. ANOVA and t-test were used to examine whether there were differences in the number of suicides and attempers between the two periods. The difference in psychiatric treatment rate between the two periods was examined by chi-square test. Additionally, we used Pearson's correlation coefficient to analyze any correlation between annual treatment rate and the number of suicide completers in subgroups with altered psychiatric treatment rates. RESULTS: The number of suicide attempters in the 20-39-year age group of decreased together with the number of suicides. Psychiatric treatment rates of male attempters aged 20-59 years improved significantly from 48.7 to 70.6% and this improvement correlated with a decrease in suicides. However, psychiatric treatment rates in the elderly, which have the highest number of suicides in both genders, did not improve and remain low. CONCLUSIONS: The number of suicide attempters, as well as that of suicides, decreased in Tokyo. Improvement of psychiatric treatment status in high-risk suicidal male adults may have contributed to the reduction of suicides in Tokyo. However, the continuing low rate of psychiatric treatment in the elderly is a pressing issue for future suicide prevention.

Modifiable intrinsic factors related to occupational falls in older workers.

AIM: Identification of modifiable intrinsic factors for occupational falls is required for initiating effective fall prevention strategies for older workers. This study aimed to identify modifiable intrinsic factors related to falls during occupational activities among older workers. METHODS: This retrospective study involved 1164 older workers (aged ≥60 years, workdays ≥4/month) sampled from 18 public employment agencies for seniors in Saitama, Japan. Participants were assessed regarding the following 10 modifiable intrinsic factors: multimorbidity, polypharmacy, fall-risk-increasing medication use, self-rated vision and hearing, functional strength, bilateral stepping, standing balance, executive function and visuospatial ability. The number of falls during occupational activities in the past year was also recorded. RESULTS: In total, 111 falls occurred in 73 of the 1164 participants during occupational activities in the past year. A negative binomial regression model showed that use of fall-risk-increasing medications (incidence rate ratio [IRR]: 2.23, 95% confidence interval [CI]: 1.08, 4.60, P = 0.031), reduced functional strength (IRR: 1.81, 95% CI: 1.02, 3.21, P = 0.042), poor standing balance (IRR: 1.83, 95% CI: 1.09, 3.09, P = 0.023) and poor visuospatial ability (IRR: 1.56, 95% CI: 1.03, 2.36, P = 0.034) were independently associated with occupational falls. CONCLUSIONS: Our findings suggest that the assessment of medication use, functional strength, standing balance and visuospatial ability in regular health checks in the workplace may be useful for screening older workers at risk of occupational falls. Geriatr Gerontol Int 2022; 22: 338-343.