Effects of immersive virtual reality training on balance, gait and mobility in older adults: A systematic review and meta-analysis.

OBJECTIVE: To examine whether immersive virtual reality (VR) can improve balance, gait, mobility and fear of falling in older people. DATA SOURCES: MEDLINE, EMBASE, CINAHL, PsycINFO, ProQuest Central (Engineering and Computer Science) and reference lists of included articles. STUDY SELECTION: Randomised controlled trials that administered immersive VR training and assessed balance, gait and mobility outcomes in older adults without neurological disorders (mean age ≥ 65). Primary outcomes were standing balance (e.g. postural sway), multi-item balance scales (e.g. Berg Balance Scale), gait (e.g. gait speed) and mobility (e.g. Timed Up and Go test). Secondary outcomes comprised measures of enjoyment, fear of falling, adherence (e.g. dropout rate), feasibility/usability and adverse effects (e.g. motion sickness). RESULTS: Meta-analyses showed that immersive VR training significantly improved standing balance (SMD: 0.51, 95% CI: .15, 0.86, p = 0.005, I2 = 28% - 3 studies, n = 79) and performance on the Berg Balance Scale (MD: 2.36, 95% CI: 1.17, 3.56, p=0.0001, I2=0% - 4 studies, n = 190). No significant improvement in gait, mobility or fear of falling was found. Subgroup analyses revealed higher training doses (≥4.5 total hours) and VR interventions using non-head mounted displays were more likely to improve standing balance. No meta-analyses were conducted for enjoyment, adherence, feasibility/usability and adverse events. CONCLUSIONS: The findings indicate immersive VR has beneficial effects on balance, but not gait, mobility or fear of falling. Further research is required to examine these outcomes in trials that also include quantitative measurements of enjoyment, adherence, clinical feasibility, usability and adverse effects.

Efficacy of spesolimab for the treatment of generalized pustular psoriasis flares across pre-specified patient subgroups in the Effisayil 1 study.

Effisayil 1 was a multicentre, randomized, double-blind, placebo-controlled study of the anti-interleukin (IL)-36 receptor monoclonal antibody, spesolimab, in patients presenting with a generalized pustular psoriasis (GPP) flare. Previously published data from this study revealed that within 1 week, rapid pustular and skin clearance were observed in patients receiving spesolimab versus placebo. In this pre-specified subgroup analysis, the efficacy of spesolimab was evaluated according to patient demographic and clinical characteristics at baseline in patients receiving spesolimab (n = 35) or placebo (n = 18) on Day 1. Efficacy was by assessed by achievement of primary endpoint (Generalized Pustular Psoriasis Physician Global Assessment [GPPGA] pustulation subscore of 0 at Week 1) and key secondary endpoint (GPPGA total score of 0 or 1 at Week 1). Safety was assessed at Week 1. Spesolimab was found to be efficacious and had a consistent and favourable safety profile in patients presenting with a GPP flare, regardless of patient demographics and clinical characteristics at baseline.

Occupational Fall Risk Assessment Tool for older workers.

BACKGROUND: No easy-to-use fall risk assessment tools have been devised to assess occupational fall risk in older workers. AIMS: To develop an Occupational Fall Risk Assessment Tool (OFRAT) and report its predictive validity and reliability in older workers. METHODS: The baseline fall risk assessment was completed by 1113 participants aged ≥60 years who worked ≥4 days/month in Saitama, Japan. Participants were followed up for falls during occupational activities for 1 year, and 30 participants were assessed twice for test-retest reliability. The following assessment measures were summed to form the OFRAT risk score: older age, male sex, history of falls, physical work participation, diabetes, use of medications increasing fall risk, reduced vision, poor hearing, executive dysfunction and slow stepping. The scores were then classified into four grades (0-2 points: very low, 3 points: low, 4 points: moderate and ≥5 points: high). RESULTS: During follow-up, 112 participants fell 214 times during work. The negative binomial regression model showed that participants with higher grades had a higher incidence rate ratio [95% confidence interval] for falls than those with very low grades (low: 1.64 [1.08-2.47], moderate: 4.23 [2.82-6.34] and high: 6.12 [3.83-9.76]). The intraclass correlation coefficient for risk score was 0.86 [0.72-0.93], and the weighted kappa coefficient for grade assessment was 0.74 [0.52-0.95]. CONCLUSIONS: The OFRAT is a valid and reliable tool for estimating the occupational fall risk in older workers. It may assist occupational physicians implement strategies to prevent falls in this group.

Financial incentives for infection prevention and antimicrobial stewardship to reduce antibiotic use: Japan's nationwide observational study.

BACKGROUND: The Japanese government introduced financial incentives to reduce nationwide antibiotic use in hospital settings. AIM: This study aimed to determine whether the nationwide financial incentives for creating infection prevention and control (IPC) teams introduced in 2012 and antimicrobial stewardship (ASP) teams introduced in 2018 were associated with changes in antibiotic use and health resource utilization at a national level. METHODS: We conducted time-series analyses and a difference-in-differences study consisting of 3,057,517 inpatients with infectious diseases from 472 medical facilities during fiscal years 2011-2018 using a nationally representative inpatient database in Japan. The primary outcome was the days of therapy (DOT) of antibiotic use per 100 patient-days (PDs). The secondary outcomes consisted of types of antibiotic used, health resource utilization, and mortality. RESULTS: A total of 5,201,304 financial incentives were observed during 2012-2018, which resulted in a total of 12.1 billion JPY (≈110 million USD). Time-series analyses found decreasing trends in total antibiotic use (79.3-72.5 DOTs/100 PDs (8.6% reduction)) and carbapenem use (9.0-7.0 DOTs/100 PDs (7.8% reduction)) from 2011 to 2018 without adversely affecting other healthcare outcomes (e.g., mortality). In the difference-in-differences analyses, we did not observe meaningful changes in total antibiotic use between the incentivized and unincentivized hospitals for ASP teams, except for the northern part of Japan. No dose-response relationships were observed between the amount of financial incentives and reductions in antibiotic use during 2011-2019. CONCLUSIONS: Further research and efforts are needed to accelerate antimicrobial stewardship in hospital settings in Japan.

Impact of ageing, fall history and exercise on postural reflexes following unpredictable perturbations: A systematic review and meta-analyses.

INTRODUCTION: This review examined the impact of ageing, fall history and exercise on postural reflexes and adaptation to unpredictable perturbations. METHODS: MEDLINE, EMBASE, Scopus, SportDiscus and Web of Science were systematically searched for cross-sectional and intervention studies that assessed muscle onset latency following unpredictable postural perturbations in adults (CRD42020170861). RESULTS: Thirty-seven articles (n = 1257) were included in this review. Older adults had slower onset latencies compared to young adults (mean difference 14 ms, 95% CI: 10, 18, P < 0.001). Regular exercisers had faster onset latencies compared to sedentary/untrained participants (mean difference 11 ms, 95%CI: -19, -4, P = 0.002). Exercise interventions delivered in randomised control trials (RCTs) led to faster onset latencies (mean difference -4 ms, 95%CI: -9, 0, P = 0.04) compared to controls. Uncontrolled clinical trials of exercise (mainly short-term) did not show changes in onset latency in pre-post tests (mean difference -2 ms, 95%CI: -5, 1, P = 0.36). CONCLUSION: This review demonstrated that in response to postural perturbation, muscle activation is significantly delayed in older compared to young adults, and that adults who regularly exercised had faster muscle activation compared to their less active counterparts. No significant changes in onset latencies were evident in uncontrolled clinical trials of short duration, but longer-term RCTs indicated postural reflexes are responsive to training.

Cortical activation during gait adaptability in people with Parkinson's disease.

BACKGROUND: People with Parkinson's disease (PD) have difficulties adapting their gait. While underlying neural mechanisms involving the prefrontal cortex (PFC) have been studied across various complex walking tasks, less is known about the premotor cortex (PMC) and supplementary motor area (SMA), key cortical regions for motor planning. This study compared frontal cortical regions activation patterns using functional near-infrared spectroscopy (fNIRS), between people with PD and healthy controls (HC) during gait adaptability tasks. METHODS: Forty-nine people with PD (mean (SD) age: 69.5 (7.9) years) and 21 HC (69.0 (5.9) years) completed a simple walk and three randomly presented gait adaptability tasks: (i) stepping on targets, (ii) avoiding obstacles and (iii) negotiating both targets and obstacles. Cortical activity in the dorsolateral PFC (DLPFC), SMA and PMC were recorded using fNIRS. Step length, velocity and accuracy and cortical activity were contrasted between the groups and walking conditions. RESULTS: Compared with the HC, the PD group exhibited greater PMC activation and walked significantly slower and took shorter steps in all conditions. A statistically significant group by condition interaction indicated an increase in DLPFC cortical activation in the HC participants when undertaking the obstacle avoidance task compared with the simple walk but no increase in cortical activation in the PD group when undergoing this more challenging gait task. CONCLUSIONS: Our findings suggest people with PD have little or no DLPFC, SMA and PMC capacity beyond what they need for simple walking and in consequence need to slow their gait velocity to meet the demands of target stepping and obstacle avoidance tasks. Such behavioral and neural patterns appear consistent with concepts of compensatory over-activation and capacity limitation.

Primary solitary fibrous tumour of the prostate: A case report and literature review.

INTRODUCTION: Solitary fibrous tumour (SFT) is a rare mesenchymal tumour with intermediate malignant potential. Although this tumour arises in several sites, prostatic SFT is an extremely rare neoplasm and may prove confusing owing to the lack of clinical experience because of tumour rarity. The diagnosis may be further difficult because SFTs can manifest positive immunoreactivity for CD34 and progesterone receptor, which are known markers of prostatic stromal tumours. Herein, we describe a case of prostatic SFT that was difficult to differentiate from a prostatic stromal tumour of uncertain malignant potential because of positive immunoreactivity to CD34 and progesterone receptor. CASE REPORT: A 40-year-old Japanese man presented with lower abdominal pain. Computed tomography revealed a prostatic mass; furthermore, prostate core needle biopsy revealed proliferating bland spindle cells, without necrosis or prominent mitoses. Tumour cells were positive for CD34 and progesterone receptor on immunohistochemical analysis; thus, a prostatic stromal tumour of uncertain malignant potential was initially suspected. However, as the tumour cells showed positive immunoreactivity for STAT6, the final diagnosis was an SFT of the prostate. The patient underwent tumour resection, and at the 6-month postoperative follow-up, neither local recurrence nor distant metastasis occurred. CONCLUSION: For an accurate diagnosis of an SFT of the prostate, STAT6 immunohistochemistry should be conducted for all mesenchymal tumours of the prostate. When STAT6 immunohistochemical analysis is unfeasible, pathologists should be aware that the morphological and immunohistochemical characteristics of SFT variable from case to case and diagnose with combined analysis of several immunohistochemical markers.

Mobility performance predicts incident depression: A systematic review and meta-analysis.

Impaired mobility often co-occurs with depression. However, there is no systematic review evidence as to whether mobility impairments precede the onset of depression. The objective of this systematic review and meta-analysis was to evaluate whether mobility impairment could predict incident depression. A systematic search of cohort studies were performed in MEDLINE, EMBASE, CINAHL and PsycINFO. The target population was people with no depressive symptoms at baseline and follow-up for depression or depressive symptoms of at least three months. Of 1061 identified abstracts, 13 studies met the review eligibility criteria. The majority of included studies (8 out of 13) were of high methodological quality. Follow-up periods ranged from 12 months to 16 years. Gait speed was the most consistently reported mobility measure. Participants with slow gait speed were at higher risk of developing depressive symptoms (pooled OR = 1.93, 95%CI: 1.54 to 2.42, 11 studies). This review shows that slow gait speed is predictive of the onset of depressive symptoms. Systematic review registration number: CRD42020153791.

The risk of interstitial lung disease during biological treatment in Japanese patients with psoriasis.

BACKGROUND: With the increasing use of biological agents for the treatment of psoriasis, the numbers of patients with interstitial lung disease (ILD) associated with biologics have also increased. Many of these cases were associated with tumour necrosis factor (TNF)-α inhibitors, but cases associated with other families of biologics have also been reported in Japan. AIM: To analyse the background factors of patients who developed ILD, and to discuss better management of biological treatment. METHOD: We reviewed 246 patients with psoriasis who were treated with biological agents in our department to identify any pulmonary adverse events (AEs). Data on patients who developed ILD were extracted to analyse background factors, clinical type of psoriasis, time to onset of ILD, pre-existing ILD, smoking habit and prescribed drugs. RESULTS: Pulmonary AEs were seen in 22 cases, of which 11 were diagnosed as drug-induced ILD. The causative drugs were mainly TNF-α inhibitors, accounting for eight cases (six treated with infliximab, two with adalimumab). The remaining three cases were associated with secukinumab, ustekinumab and ixekizumab (n = 1 each). Notably, these three cases also had a history of drug-induced ILD. CONCLUSION: Patients with a history of drug-induced ILD seem to be more susceptible to developing another ILD induced by biologics, even if treated with interleukin-17 inhibitors. Thorough screening of risk factors and evaluation for eligibility, and careful monitoring during treatment are the best solutions to avoid serious pulmonary AE. Early detection and precise diagnosis of pulmonary AEs, especially differentiation from infectious diseases, is essential for managing biological treatment.

Efficacy of influenza vaccine (Fluvax) in cancer patients on treatment: a prospective single arm, open-label study.

PURPOSE: Influenza virus infection has significant morbidity and mortality in patients with medical co-morbidities who are also immunosuppressed. The efficacy of the seasonal influenza vaccine has not been well studied in patients receiving chemotherapy. We assessed the efficacy of seasonal influenza vaccine in patients with non-haematological malignancy on active treatment (chemotherapy and targeted therapy). METHODS: A prospective single arm, open label study with 53 patients with non-haematological cancers recruited during the 2011 and 2012 influenza seasons. Participants had one dose of 2011/2012 trivalent vaccine containing strains A/California/7/2009(H1N1), A/Perth/16/2009 (H3N2) and B/Brisbane/60/2008 (Fluvax) prior to or in-between treatment cycles. Haemagglutination inhibition antibody (HIA) titres in serum were measured at baseline 3, 6 and 24 weeks. Primary endpoint: seroconversion rate (SCR) at 3 weeks. Secondary endpoints: late SCR at 6 weeks. rate of sustained sero-protection titres (SPR) at 24 weeks. Seroconversion was defined as postvaccination ≥ 4-fold increase in HIA titre and sero-protection defined as a HIA ≥ 1:40. RESULTS: The SCR at 3 weeks were 35%, 30% and 22.5% to the H1N1, H3N2 and B/Bris strains, respectively. There were no new cases of late SC at 6 weeks or 24 weeks. The SPR at 3 weeks were 72.5%, 65% and 40%, respectively, to H1N1, H3N2 and B/Bris. The SPR at 24 weeks to H1N1, H3N2 and B/Bris were 40%, 52.5% and 17.5%, respectively. CONCLUSIONS: Patients on various solid tumour treatments achieve sero-protection rate congruent with the general population. The sero-protection HIA titres were not sustained at 24 weeks postvaccination.

Molecular detection of fungal and bacterial DNA from pustules in patients with palmoplantar pustulosis: special focus on Malassezia species.

BACKGROUND: Palmoplantar pustulosis (PPP) is a distinct, chronic skin disorder characterized by intraepidermal pustules on the palms and soles. It is hypothesized that microorganisms on the skin might induce the symptoms of PPP via inflammatory cell activation. However, the microbiota has not been studied in detail because of the assumption that the pustules in PPP are sterile. AIM: To elucidate the role of microorganisms in pathogenesis of PPP. METHODS: PCR analysis was performed of microbial DNA fragments in the pustules of patients with PPP. The sequence of the D1/D2 LSU 26s rRNA gene and that of the 16S rRNA gene was used for fungal and bacterial DNA detection, respectively. RESULTS: In total, 71 samples were carefully collected from the pustules of patients with PPP. Fungal DNA bands were detected in 68 samples, and fungi including Malassezia spp. were identified in 30 of 71 samples (42.3%). Malassezia restricta was the most frequently encountered fungus (14/71; 19.7%). However, bacterial DNA was not detected by the methods used. Furthermore, identical fungal DNA was not detected in the outer lid of the pustules, suggesting that the fungi detected within the pustule did not derive from contamination via the skin surface. CONCLUSIONS: In the present study, we demonstrated for the first time that certain pustules in patients with PPP contain fungal DNA fragments, especially those of Malassezia spp. Our findings provide new insights on the role of skin microbiota in the pathogenesis of PPP.

Long-term efficacy and safety of ixekizumab in Japanese patients with erythrodermic or generalized pustular psoriasis: subgroup analyses of an open-label, phase 3 study (UNCOVER-J).

BACKGROUND: Erythrodermic and generalized pustular psoriasis are rare, difficult to treat forms of psoriasis. In previous reports, we documented 24- and 52-week findings of an open-label, phase 3 trial (UNCOVER-J) of ixekizumab in Japanese patients with erythrodermic or generalized pustular psoriasis; most patients responded to treatment and maintained response through 52 weeks. OBJECTIVE: To assess the long-term (>3 years) efficacy and safety of ixekizumab in Japanese patients with erythrodermic or generalized pustular psoriasis. METHODS: These subgroup analyses were of a partial population of patients from UNCOVER-J (NCT01624233; Sponsored by Eli Lilly and Company), specifically those with erythrodermic psoriasis (N = 8) or generalized pustular psoriasis (N = 5). These patients received 160 mg ixekizumab at Week 0, ixekizumab 80 mg every 2 weeks through Week 12, and ixekizumab 80 mg every 4 weeks thereafter up to Week 244. This regimen is consistent with the regimen approved in Japan for plaque, erythrodermic, and generalized pustular psoriasis and psoriatic arthritis. Efficacy assessments included Global Improvement Score (GIS), Psoriasis Area and Severity Index (PASI), dermal symptoms (for patients with generalized pustular psoriasis), Dermatology Life Quality Index (DLQI) and Itch Numeric Rating Scale (NRS). Safety assessments included treatment-emergent adverse events and adverse events of special interest. RESULTS: Most patients had a GIS of resolved or improved from Week 12 onwards, and all patients had early and sustained improvement in PASI and dermal symptom (generalized pustular psoriasis only) scores. Mean improvements in DLQI and Itch NRS at Week 12 were sustained through Week 244. Ixekizumab was well tolerated over 3 years of treatment in patients with erythrodermic psoriasis or generalized pustular psoriasis, and no new safety concerns were identified. CONCLUSION: These findings suggest that ixekizumab can be an effective long-term treatment option for erythrodermic or generalized pustular psoriasis.

Development of the Nutrition and Functionality Assessment (NFA) among Older Adults in Japan.

OBJECTIVE: Develop and evaluate the feasibility and validity of the Nutrition and Functionality Assessment (NFA) which identifies "target" older adults who could benefit from a personalized program following evaluation of their nutrition status and physical functionality. DESIGN: Cross-sectional study. SETTING: Community and geriatric day-care centers and university in Japan. PARTICIPANTS: 267 older adults aged 65-90. MEASUREMENTS: The "target" individuals were screened based on gait speed (0.6-1.5 m/s). Nutrition (Mini Nutrition Assessment-short form and protein intake), strength (30s chair sit-to-stand and hand-grip strength) and endurance (6-minute walk) were assessed. Physical activity was monitored using a tri-axil accelerometer for a week. Fried frailty phenotype was also assessed. RESULTS: Out of 267 individuals, 185 (69%) had gait speed between 0.6-1.5 m/s, corresponding to our "target" group from which, 184 (95%) completed the nutrition and physical functionality assessments with the physical activity monitoring. The NFA was completed in approximately 30 minutes. No adverse events directly due to the NFA were reported. NFA physical functionality and global scores were significantly related to frailty phenotype but nutrition score was not related to frailty phenotype. CONCLUSION: The study demonstrated that the NFA is a safe and feasible tool to screen target older adults and simultaneously evaluate their nutritional status and physical functionality. Validity of the NFA was partially confirmed by the significant association of the global and physical functionality scores with frailty phenotype. More studies are required to validate and maximize the applicability of the NFA in communities and institutions in Japan and elsewhere.

Sézary syndrome managed with histone deacetylase inhibitor followed by anti-CCR4 monoclonal antibody.

A 70-year-old man presented to our clinic with a 10-year history of recurrent pruritic erythema and plaques on his trunk and limbs. Based on the pathological findings and monoclonal rearrangement of the T-cell receptor (TCR)-Cß1 gene, mycosis fungoides (T2N0M0B0 stage IB) was diagnosed. Despite combination therapy including histone deacetylase inhibitor (vorinostat), the symptoms slowly evolved into Sézary syndrome (SS; T4N1M0B2) over 4 years, with dense infiltrates due to atypical lymphocytes expressing CCR4 developing in the entire dermis. Anti-CCR4 monoclonal antibody (mogamulizumab) treatment was started. After seven courses, the CCR4-positive atypical lymphocytes decreased in the dermis to levels below those seen at the outset of treatment. To our knowledge, there is no previous report of a case of SS managed with vorinostat followed by mogamulizumab demonstrating such a remarkable change in the pathological state following treatment.

Analysis of treatment goal alignment between Japanese psoriasis patients and their paired treating physicians.

BACKGROUND: Appropriate goal-oriented treatment strategies are important for optimal treatment outcomes and may prevent under-treatment. As treatment goals vary by patient, a study to examine treatment goals is more meaningful when patients and their physicians are paired. There has not been any study that examines alignment between paired psoriasis patients and physicians in real-world clinical practice using skin clearance as a treatment goal indicator. OBJECTIVES: To evaluate treatment goal alignment between psoriasis patients and their paired physicians, and to quantitatively identify factors associated with goal misalignment. METHODS: The study was a nationwide multicenter cross-sectional observational study. Subjects were physician-reported moderate-to-severe psoriasis patients with a history of systemic treatments, directly paired with their treating physicians. Subjects completed surveys independently. Treatment goals included seven categories, and patient-physician pairs were grouped as 'aligned' or 'misaligned' when the answers were the same or different, respectively. RESULTS: A total of 425 pairs (mean response rate, 94.7%) of responses were collected from 54 sites (64.8% general practitioners or clinics; 35.2% university or large hospitals). Treatment goal misalignment was found in 67.9% of the patient-physician pairs. The misalignment was mainly 'patient predominant' (60.9%) indicating that patients had higher goals ('complete clearance') than physicians. In the multivariate logistic regression analyses, patients' treatment expectation for 'complete clearance' [odds ratio (OR): 1.927; 95% confidential interval (CI): 1.232-3.016] and physician rating of 'level of understanding on treatment options' being low (OR: 1.552, 95% CI; 1.082-2.227) were significant factors for treatment goal misalignment. CONCLUSIONS: The majority of treatment goal misalignment was found between paired psoriasis patients and their treating physicians in Japan. The most important contributing factors to misalignment were patients' treatment expectation for 'complete clearance' and physicians' rating of their patients' 'level of understanding on treatment options' being low.