Non-invasive vagus nerve stimulation for prevention of migraine: The multicenter, randomized, double-blind, sham-controlled PREMIUM II trial

Aim Evaluate the efficacy and safety of non-invasive vagus nerve stimulation for migraine prevention. Methods After completing a 4-week diary run-in period, adults who had migraine with or without aura were randomly assigned to receive active non-invasive vagus nerve stimulation or sham therapy during a 12-week double-blind period. Results Of 336 enrolled participants, 113 (active, n = 56; sham, n = 57) completed ≥70 days of the double-blind period and were ≥66% adherent with treatment, comprising the prespecified modified intention-to-treat population. The COVID-19 pandemic led to early trial termination, and the population was ∼60% smaller than the statistical target for full power. Mean reduction in monthly migraine days (primary endpoint) was 3.12 for the active group and 2.29 days for the sham group (difference, −0.83; p = 0.2329). Responder rate (i.e. the percentage of participants with a ≥50% reduction in migraine days) was greater in the active group (44.87%) than the sham group (26.81%; p = 0.0481). Prespecified subgroup analysis suggested that participants with aura responded preferentially. No serious device-related adverse events were reported. Conclusions These results suggest clinical utility of non-invasive vagus nerve stimulation for migraine prevention, particularly for patients who have migraine with aura, and reinforce the well-established safety and tolerability profile of this therapy. Trial Registration: ClinicalTrials.gov (NCT03716505).

Differences in Park Walking, Comparing the Physically Inactive and Active Groups: Data from mHealth Monitoring System in Seoul

Despite the overall increase in physical activities and park uses, the discrepancies between physically inactive and active people have increasing widened in recent times. This paper aims to empirically measure the differences in walking activity in urban parks between the physically inactive and active. As for the dataset, 22,744 peoples’ 550,234 walking bouts were collected from the mHealth system of the Seoul government, using the smartphone healthcare app, WalkOn, from September to November 2019, in Seocho-gu district, Seoul, Korea. We classified the physically inactive and active sample groups, based on their regular walking (≥150 min of moderate-to-vigorous walking activity a week), and analyzed their park walking activities. We found that while there was no significant difference in walking measures of non-park walking between the sample groups, the difference did exist in park walking. The park walking average in the physically active group had more steps (p = 0.021), longer time (p = 0.008), and higher intensity (p < 0.001) of walking than that in the inactive group. Each park also revealed differences in its on-site park walking quantity and quality, based on which we could draw the list of ‘well-walked parks’, which held more bouts and more moderate-to-vigorous physical activities (MVPAs) than other parks in Seocho-gu district. This paper addresses how park walking of physically inactive and active people is associated with multiple differences in everyday urban walking.

Associations of Exercise Habits in Adolescence and Old Age with Risk of Osteoporosis in Older Adults: The Bunkyo Health Study

We investigated effects of exercise habits (EHs) in adolescence and old age on osteoporosis prevalence and hip joint and lumbar spine bone mineral density (BMD). Body composition and BMD in 1596 people aged 65–84 years living in Bunkyo-ku, Tokyo, were measured using dual-energy X-ray absorptiometry. We divided participants into four groups by a combination of EHs in adolescence and old age: none in either period (None-None), only in adolescence (Active-None), only in old age (None-Active), and in both periods (Active-Active). Logistic regression models were employed to estimate multivariable-adjusted odds ratios (ORs) for osteoporosis determined by T-score (less than −2.5 SD) using the None-None reference group. In men, the combination of EHs in adolescence and old age was not associated with osteoporosis prevalence. However, the lumbar spine’s BMD was significantly higher in the Active-Active than the None-Active group (p = 0.043). In women, the Active-Active group had lower lumbar spine osteoporosis prevalence than the None-None group (OR 0.65; 95% CI, 0.42–1.00, p = 0.049). Furthermore, hip BMD was significantly higher in the Active-Active group than in the other three groups (p = 0.001). Older women with EHs in adolescence and old age had higher lumbar BMD and lower risk of osteoporosis.

Physical Activity Impacts Walking Distances and Energy Consumption of Patients with Peripheral Artery Disease

Lower extremity peripheral artery disease (PAD) is attributed to buildup of atherosclerotic plaques preventing adequate blood flow, leading to pain during walking, and ultimately physical inactivity. Normal day-to-day levels of physical activity may impact the distance a subject can walk before claudication pain onset, as well as their energy consumption capabilities. This study compared walking performance (initial claudication distance (ICD) and absolute claudication distance (ACD)), and energy consumption (EC) between active and inactive subjects with PAD. The distinction between groups was made using previous research that declared the average PAD patient walks 3586 steps/day. Ten subjects were classified as active (□3586 average steps/day) and sixteen participants as inactive (&lt;3586 steps/day) based on a 7-day accelerometer measurement. The Gardner progressive treadmill test was used to asses ICD, ACD, and EC. EC was measured using a metabolic cart and calculated from the second minute of walking and the last minute prior to stopping due to claudication pain. The average ICD and ACD for the active group were 130.6±106.7 meters and 306.0±184.7 meters, respectively and 143.8±119.0 meters and 248.0±156.0 meters, respectively for the inactive group. The average EC for the second minute and last minute were 9.6±1.9 mlkg-1min-1 and 11.5±2.4 mlkg-1min-1 respectively for active group and 7.0±3.1 mlkg-1min-1 and 8.1±3.8 mlkg-1min-1 respectively for inactive group. The data suggests that the active group had better walking performance and greater energy consumption indicating increased efficiency of oxygen transport and extraction capability in the leg muscles.

ENGAGE Model as an Innovation in Teaching Speaking: A Case of Cognitively More and Less Active EFL Learners

This study investigated the effect of using the ENGAGE Model on the speaking performance of cognitively more and less active EFL learners. The participants of the study were 60 intermediate level male EFL learners who were non-randomly selected from a pool of intermediate students (N=80) based on their performance on a standard version of Preliminary English Test (PET). The selected participants were assigned to the two groups of the ENGAGE Model and Task-based Language Teaching (TBLT). They were also specified in terms of their cognitive ability as cognitively more or less active learners based on their answers to a validated cognitive profile questionnaire. The results revealed that learners in the ENGAGE Model group outperformed students in the TBLT group in terms of their L2 speaking, regardless of whether they belonged to the cognitively less or more active group. It was also concluded students with a cognitively more active profile benefit more from the ENGAGE Model. Keywords: Cognition, ENGAGE Model, Speaking Performance, TBLT, EFL Learners.

Prevalence of Ischemia, Health-Related Quality of Life, Medical use and Expenses by Physical Activity and Ischemia Status in Korean Adults

PURPOSE: The purpose of this study is to analyze the different prevalence of ischemia of Korea adults, and to compare the HealthRelated Quality of Life (HRQoL), annual personal medical use and expenses according to physical activity and ischemia status.METHODS: The 2018 Korea Medical Panel data was used (13,791 adults and 604 ischemia). Physical activity was measured with IPAQ and converted to MET-minutes per week. The physical activity group was classified as less than 600 MET-min per week in the inactive group, 600-3,000 MET-min per week in the minimally active group, and 3,000 MET-min more per week in the active group.RESULTS: The prevalence of ischemia was low in the inactive group compared to the minimally active group and the active group (OR=0.75, p<.01) and the active group (OR=0.36, p<.001). In both ischemic and non-ischemic groups, HRQoL was the lowest in the inactive group (p<.05). Inpatient days and emergency days showed no significant difference in according to the physical activity level and the ischemia status. However, within the group with ischemia, the outpatient days of inactive group were 42.8% higher (p<.05) and minimally active group was 4.3% higher (p>.05) compared to the active group (32.5±32.1 days) respectively. Within the group with ischemia, the medical expenses of inactive group were 5.2% lower (p>.05) and minimally active group was 33.9% lower (p<.05) compared to the active group ($1,738±2,457) respectively.CONCLUSIONS: Higher physical activity results in a lower prevalence of ischemia, and higher physical activity results in positive HRQoL and outpatient days in ischemia group. However Annual personal medical expenses showed a significant difference according to the level of physical activity in ischemia group.

Effect of Physical Activity on Cardiovascular Event Risk in a Population-Based Cohort of Patients with Type 2 Diabetes

Cardiovascular disease (CVD) is the most common cause of morbidity and mortality among patients with type 2 diabetes (T2D). Physical activity (PA) is one of the few modifiable factors that can reduce this risk. The aim of this study was to estimate to what extent PA can contribute to reducing CVD risk and all-cause mortality in patients with T2D. Information from a population-based cohort including 26,587 patients with T2D from the Navarre Health System who were followed for five years was gathered from electronic clinical records. Multivariate Cox regression models were fitted to estimate the effect of PA on CVD risk and all-cause mortality, and the approach was complemented using conditional logistic regression models within a matched nested case–control design. A total of 5111 (19.2%) patients died during follow-up, which corresponds to 37.8% of the inactive group, 23.9% of the partially active group and 12.4% of the active group. CVD events occurred in 2362 (8.9%) patients, which corresponds to 11.6%, 10.1% and 7.6% of these groups. Compared with patients in the inactive group, and after matching and adjusting for confounders, the OR of having a CVD event was 0.84 (95% CI: 0.66–1.07) for the partially active group and 0.71 (95% CI: 0.56–0.91) for the active group. A slightly more pronounced gradient was obtained when focused on all-cause mortality, with ORs equal to 0.72 (95% CI: 0.61–0.85) and 0.50 (95% CI: 0.42–0.59), respectively. This study provides further evidence that physically active patients with T2D may have a reduced risk of CVD-related complications and all-cause mortality.

Physical Activity Improves Outcomes of Combined Lenvatinib Plus Anti-PD-1 Therapy In Patients With Unresectable Hepatocellular Carcinoma

Background: Adaptive resistance is one of the major hinderances for unresectable hepatocellular carcinoma (HCC) treated with lenvatinib and anti-programmed cell death protein 1 (anti-PD-1) therapy. Physical activity is known to have anti-cancer effects, including immunomodulatory actions, influencing patients’ outcomes. This study investigated the hypothesis that physical activity synergizes with combined lenvatinib plus anti-PD-1 therapy to enhance efficacy in patients with unresectable HCC.Methods: The physical activity levels of patients with unresectable HCC treated with combination therapy using lenvatinib plus anti-PD-1 antibodies were recorded by questionnaire. Patients were categorized according to physical activity levels (active vs. sedentary). The primary outcome was overall survival (OS), analyzed using the Kaplan-Meier method with a log-rank test. Secondary outcomes included objective response rate (ORR) and progression-free survival (PFS). Factors associated with survival and ORR were analyzed using regression analyses. A subcutaneous syngeneic HCC model was generated in C57BL/6 mice. Mice were randomized to receive placebo, combined lenvatinib plus anti-PD-1 antibodies or combination therapy plus physical activity. Tumors were measured every 3 days and harvested for immunohistochemistry analysis at 20 mm maximum diameter. Results: Fifty-nine patients with unresectable HCC were categorized to active (n=28) or sedentary (n=31) groups. The active group had higher albumin and des-γ-carboxy prothrombin levels and lower hepatitis B virus load at baseline; other clinical and oncologic characteristics were comparable between the two groups. Patients in the active group had significantly longer OS (HR = 0.220, 95% CI, 0.060-0.799) and PFS (HR = 0.158, 95% CI, 0.044-0.562) and higher ORR (OR = 4.571, 95% CI, 1.482-14.102) than patients in the sedentary group. Regular physical activity was independently associated with OS, PFS and ORR. The mouse model showed that physical activity significantly suppressed tumor growth and prolonged survival of tumor-bearing mice. Furthermore, physical activity inhibited Treg cell infiltration and immune checkpoint expression (including CTLA4, TIGIT and TIM3) induced by long-term combined lenvatinib plus anti-PD-1 therapy, improving efficacy. Conclusions: Regular physical activity was associated with improved outcomes in patients receiving combined lenvatinib plus anti-PD-1 therapy for unresectable HCC. Physical activity may improve therapeutic efficacy by reprograming the tumor microenvironment from an immunosuppressive to immunostimulatory phenotype.