The Quantitative Impact of Visual Function on Accelerometer-measured Physical Activity in Older United States Adults: A Nationwide Cross-sectional Analysis.

Purpose: To explore the impact of objective vision measures on novel metrics of objectively-measured physical activity (PA) in a nationally representative sample of United States (US) older adults. Design: Cross-sectional analysis using data from the National Health and Aging Trends Study. Participants: Adults had their distance and near visual acuity (VA) and contrast sensitivity (CS) tested. Any objective vision impairment (VI), defined as any VI in distance VA, near VA, or CS, was the primary exposure. Physical activity data were collected using the Actigraph CentrePoint Insight Watch worn for 7 days. Methods: Multivariable regression models were used to investigate the association between vision and PA measures. All analyses accounted for the survey design and models were adjusted for age, sex, race, living arrangement, education, and comorbidities. Main Outcome Measures: Physical activity metrics included (1) total daily activity (active minutes per day, number of active bouts, and mean length of active bouts), (2) activity fragmentation, and (3) time until 75% activity. An active bout was defined as ≥ 1 consecutive active minute. Activity fragmentation was defined as the probability of an active minute being followed by a sedentary minute, with higher values indicating more fragmented activity. Time until 75% activity was defined as the time taken to complete 75% of daily PA starting from their first active bout. Results: Among 723 participants, sampled from 10 443 338 older adults in the US, 30% had any objective VI. Any objective VI was significantly associated with lower number of active minutes per day (7.8% fewer [95% confidence interval {CI}: -13.6% to -1.7%]), shorter active bouts (7.0% shorter [95% CI: -12.3% to -1.4%]), and greater activity fragmentation (2.5% [95% CI: 0.8% to 4.2%]), while no associations were found with number of active bouts. Time until 75% activity did not significantly differ between adults with any objective VI and those without (P = 0.34). Conclusions: Older US adults with any objective VI displayed lower total daily activity, as well as more fragmented, shorter periods of PA, despite having a similar number of active bouts compared to their normally sighted counterparts. Implementing interventions that increase bout duration may help promote PA in adults with VI. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Visual Impairment and Real-World Home Physical Activity With Home Environment in an Older Population.

Importance: Physical activity levels are lower in visual impairment. However, additional factors, such as home environmental features, which can modify physical activity in this group, are unknown. Objective: To investigate the association between home environment features and home physical activity in patients with visual impairment. Design, Setting, and Participants: This cross-sectional study of clinical patients included participants with glaucoma suspect and primary glaucoma who were 60 years or older with varying degrees of visual field damage. Study participants were recruited from the Johns Hopkins Wilmer Eye Institute Glaucoma Clinic, Baltimore, Maryland, from September 2013 through March 2015. Data were analyzed from December 19, 2022, through December 25, 2022. Main Outcomes and Measures: Total in-home steps taken per day was the primary outcome measure; time in daily home physical activity and nonsedentary activity were secondary outcomes. Results: A total of 153 participants were included in analyses with mean age of 71 (SD, 7.8) years and 71 were female (46%). Sixty percent had more than 1 comorbid illness, about one-third took 5 or more prescription drugs, and median daily home steps were 1137. Median integrated visual field sensitivity was 28 dB. Better-eye median visual acuity in logMAR was 0.05 (20/22 Snellen equivalent). For every 0.1-log unit increment in average measured home lighting, participants took 5% more daily steps (rate ratio [RR], 1.05; 95% CI, 1.00-1.10; P = .04) and had a 3% faster average daily peak cadence (RR, 1.03; 95% CI, 1.01-1.05; P = .01). The average number of nonsedentary activity minutes (RR, 1.04; 95% CI, 1.00-1.07; P = .06), average bout duration (ß = 0.03; 95% CI, 0.00-.07; P = .06), and activity fragmentation (ß = -0.06; 95% CI, -0.13 to 0.00; P = .06) showed associations with home lighting. The number of hazards was not associated with any activity metric (steps: RR, 1.14; 95% CI, 0.96-1.34; P = .13; peak cadence: RR, 1.00; 95% CI, 0.93-1.08; P = .98; and nonsedentary time: RR, 1.11; 95% CI, 0.98-1.26; P = .11), nor was the frequency of hazards. Conclusions and Relevance: In this study, results demonstrated that home environment features, particularly lighting, may influence home activity metrics in older adults with visual impairment. Further prospective studies would be needed to confirm if home modifications can improve at-home activity.

Treatment Patterns and Healthcare Resource Use in Medicare Beneficiaries with Parkinson's Disease.

Background: Studies on real-world treatment patterns and long-term economic burden of Parkinson's disease (PD) have been limited. Objective: To assess treatment patterns, healthcare resource utilization (HRU), and costs associated with PD symptoms and treatment-related adverse events (AEs) among Medicare beneficiaries in the United States. Methods: A 100% Medicare Fee-For-Service data (2006-2020) of patients with PD were analyzed. PD treatment patterns were described for the subset of patients who had no previously observed PD treatments or diagnoses (ie, the incident cohort). HRU and healthcare costs associated with PD symptoms were assessed for all patients with PD (ie, the overall cohort) and that associated with treatment-related AEs were assessed for the subset of patients who received PD treatments after PD diagnosis (ie, the active treatment cohort), using longitudinal models with repeated measures. Results: Overall, 318,582 patients were included (mean age at PD diagnosis: 77.4 years; 53.3% female). Among patients in the incident cohort (N=214,829), 51.1% initiated levodopa monotherapy and 5.9% initiated dopamine agonists (DAs) monotherapy as first-line treatment. The proportion of incident patients treated with DAs and other PD therapies generally increased from post-diagnosis years 1 to 10. The median time from diagnosis to PD treatment initiation was 2.0 months; the median time to treatment discontinuation was the longest with levodopa (18.7 months), followed by DAs (9.5 months). In the overall cohort, PD symptoms, especially motor symptoms and severe motor symptoms, were associated with significantly higher rates of HRU and costs. In the active treatment cohort (N=234,298), treatment-related AEs were associated with significantly higher rates of HRU and medical costs. Conclusion: While levodopa is still the mainstay of PD management, considerable heterogeneity exists in real-world treatment patterns. Overall, PD symptoms and AEs were associated with significantly higher HRU and healthcare costs, suggesting unmet medical needs for PD treatments with better tolerability profiles.

Device-modified trabeculectomy for glaucoma.

BACKGROUND: Glaucoma is an optic neuropathy that leads to visual field defects and vision loss. It is the second leading cause of irreversible blindness in the world. Treatment for glaucoma aims to reduce intraocular pressure (IOP) to slow or prevent further vision loss. IOP can be lowered with medications, laser, or incisional surgery. Trabeculectomy is a surgical approach which lowers IOP by shunting aqueous humor to a subconjunctival bleb. Device-modified trabeculectomy techniques are intended to improve the durability and safety of this bleb-forming surgery. Trabeculectomy-modifying devices include the Ex-PRESS, the XEN Gel Stent, the PreserFlo MicroShunt, as well as antifibrotic materials such as Ologen, amniotic membrane, expanded polytetrafluoroethylene (ePTFE) membrane, Gelfilm and others. However, the comparative effectiveness and safety of these devices are uncertain. OBJECTIVES: To evaluate the benefits and harms of different devices as adjuncts to trabeculectomy on IOP control in eyes with glaucoma compared to standard trabeculectomy. SEARCH METHODS: We used standard, extensive Cochrane search methods. The latest search was August 2021. SELECTION CRITERIA: We included randomized controlled trials in participants with glaucoma comparing device-modified trabeculectomy techniques with standard trabeculectomy. We included studies that used antimetabolites in either or both treatment groups. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes were 1. change in IOP and 2. mean postoperative IOP at one year. Our secondary outcomes were 3. mean change in IOP from baseline, 4. mean postoperative IOP at any time point, 5. mean best-corrected visual acuity (BCVA), 6. visual field change, 7. quality of life, 8. proportion of participants who are drop-free at one year, 9. mean number of IOP lowering medications at one year, and 10. proportion of participants with complications. MAIN RESULTS: Eight studies met our inclusion criteria, of which seven were full-length journal articles and one was a conference abstract. The eight studies included 961 participants with glaucoma, and compared two types of devices implanted during trabeculectomy versus standard trabeculectomy. Seven studies (462 eyes, 434 participants) used the Ex-PRESS, and one study (527 eyes, 527 participants) used the PreserFlo MicroShunt. No studies using the XEN Gel Stent implantation met our criteria. The studies were conducted in North America, Europe, and Africa. Planned follow-up periods ranged from six months to five years. The studies were reported poorly, which limited our ability to judge risk of bias for many domains. None of the studies explicitly masked outcome assessment. We rated seven studies at high risk of detection bias. Low-certainty of evidence from five studies showed that using the Ex-PRESS plus trabeculectomy compared with standard trabeculectomy may be associated with a slightly lower IOP at one year (mean difference (MD) -1.76 mmHg, 95% confidence interval (CI) -2.81 to -0.70; 213 eyes). Moderate-certainty of evidence from one study showed that using the PreserFlo MicroShunt may be associated with a slightly higher IOP than standard trabeculectomy at one year (MD 3.20 mmHg, 95% CI 2.29 to 4.11). Participants who received standard trabeculectomy may have a higher risk of hypotony compared with those who received device-modified trabeculectomy, but the evidence is uncertain (RR 0.73, 95% CI 0.46 to 1.17; I² = 38%; P = 0.14). In the subgroup of participants who received the PreserFlo MicroShunt, there was a lower risk of developing hypotony or shallow anterior chamber compared with those receiving standard trabeculectomy (RR 0.44, 95% CI 0.25 to 0.79; 526 eyes). Device-modified trabeculectomy may lead to less subsequent cataract surgery within one year (RR 0.46, 95% CI 0.27 to 0.80; I² = 0%). AUTHORS' CONCLUSIONS: Use of an Ex-PRESS plus trabeculectomy may produce greater IOP reduction at one-year follow-up than standard trabeculectomy; however, due to potential biases and imprecision in effect estimates, the certainty of evidence is low. PreserFlo MicroShunt may be inferior to standard trabeculectomy in lowering IOP. However, PreserFlo MicroShunt may prevent postoperative hypotony and bleb leakage. Overall, device-modified trabeculectomy appears associated with a lower risk of cataract surgery within five years compared with standard trabeculectomy. Due to various limitations in the design and conduct of the included studies, the applicability of this evidence synthesis to other populations or settings is uncertain. Further research is needed to determine the effectiveness and safety of other devices in subgroup populations, such as people with different types of glaucoma, of various races and ethnicity, and with different lens types (e.g. phakic, pseudophakic).

The Impact of Neighborhood Factors on Physical Activity in Older Adults With Visual Impairment.

PURPOSE: To investigate the associations of neighborhood-level socioeconomic and environmental characteristics with physical activity in persons with glaucoma. DESIGN: Cross-sectional study (N = 230). METHODS: Home addresses were used to extract neighborhood factors (NFs): Area Deprivation Index, crime rate, and the proportion of racial and ethnic minorities, poverty, college graduates, and park area in their census tract. Participants' average number of daily steps and nonsedentary minutes were collected over 7 days using an accelerometer. Visual field (VF) loss was quantified as integrated VF sensitivity. Multivariable negative binomial regression models and additional models with an interaction term evaluated the effect of NF on physical activity and whether these relationships differed by VF loss severity. RESULTS: Participants were on average 70.6 years of age, 51.7% were male, and 27.8% were black. A higher Area Deprivation Index or poverty share was associated with fewer NSM (incidence rate ratio [IRR] = 0.96 per 1 Area Deprivation Index decile increment, P = .01; IRR = 0.92 per 10% poverty share increment, P = .02), while higher share of college graduates was associated with greater NSM (IRR = 1.03 per 10% increment; P = .03). Stronger associations were noted between both high crime rate and poverty share with NSM in individuals with severe VF damage as opposed to no/mild VF damage (IRR = 0.44, P = .001; IRR = 0.81, P = .02). CONCLUSIONS: Select NFs (poverty share and crime rate) may disproportionately affect physical activity in patients with severe VF loss. Interventions to overcome activity limitations within the context of poverty and high socioeconomic disadvantage are important for addressing glaucoma-related disability, particularly in those with severe VF loss.

Motor and Physical Function Impairments as Contributors to Slow Gait Speed and Mobility Difficulty in Middle-Aged and Older Adults.

BACKGROUND: Motor function affects ability to perform daily activities and maintain independence. Yet, the interrelatedness of upper and lower extremity motor impairments and the magnitude of their contribution to slow gait and mobility difficulty are not well investigated. METHODS: Participants in the Baltimore Longitudinal Study of Aging (N = 728, aged 50-99) completed motor and physical function tests including grip and knee extension strength, pegboard, finger tapping, standing balance, chair stands, fast-paced 400-m walk, and usual gait speed. Slow gait was defined as usual gait speed <1.0 m/s. Mobility difficulty was defined as self-reported difficulty walking » mile or climbing stairs. Structural equation modeling examined the interrelationships of motor measures and their contributions to slow gait and mobility difficulty, adjusting for demographics and comorbidities. RESULTS: Poorer manual dexterity (-0.571 standard deviation [SD] units, p < .001) and lower muscle strength (upper and lower extremity; -0.447 SD units, p = .014) were most strongly associated with slow gait speed, followed by slower chair stand pace (-0.195 SD units, p = .002) and greater lap time variation (0.102 SD units, p = .028). Lower muscle strength (-0.582 SD units, p = .001) was most strongly associated with mobility difficulty, followed by slower chair stand pace (-0.322 SD units, p < .001), slower gait speed (-0.247 SD units, p < .001), and poorer standing balance (-0.190 SD units, p = .043). CONCLUSIONS: Components of manual dexterity and strength were the strongest correlates of slow gait and mobility difficulty in mid-to-late life. Longitudinal studies examining relationships between changes in these motor parameters and mobility are needed to elucidate possible causal effects.

Patterns of Prevalence of Multiple Sensory Impairments Among Community-dwelling Older Adults.

BACKGROUND: Much is known about individual sensory deficits among older adults, but there is a dearth of information about the prevalence of multiple concurrent sensory deficits in this population. METHODS: We evaluated the prevalence of individual and multiple sensory impairments at the most recent clinic visit among participants aged 24 years and older in the Baltimore Longitudinal Study of Aging (BLSA) (hearing, vision, olfaction, proprioception, and vestibular function) and Atherosclerosis Risk in Communities Study (ARIC) (hearing, vision, olfaction). We compared observed prevalence of multiple sensory impairments with expected prevalence based on compounded probabilities of multiple impairments using Fisher Exact Tests. Also, we evaluated the comparability of different measures used between these two studies. RESULTS: In both studies, the prevalence of each individual sensory impairment was common (>10%), and higher with older age, and the most common pattern of co-occurring sensory impairments was hearing and visual impairments (17.4% [BLSA]; 50.2% [ARIC]). In BLSA, the pattern that differed the most between observed and expected prevalence was combined hearing, vision, and olfactory impairments (observed 5.2% vs 1.4% expected, p = .01). In ARIC, this difference was much smaller (observed 8.1% vs 7.2% expected, p = .49). CONCLUSIONS: Although concurrent hearing and vision impairments were the most common co-occurring deficits, combined hearing, vision, and olfactory impairments are most likely to co-occur above chance, especially at older ages.

Longitudinal changes in daily patterns of objectively measured physical activity after falls in older adults with varying degrees of glaucoma.

BACKGROUND: Visually impaired older adults have a greater risk of falling, making them particularly susceptible to fall-related health consequences and restricted physical activity. Unclear however, is the relationship between having falls and longitudinal changes in daily patterns of objectively measured physical activity in older adults with visual impairments. METHODS: We created a three-year prospective cohort study (Falls in Glaucoma Study) of older adults with primary or suspected glaucoma at the Johns Hopkins Wilmer Eye Institute from 2013 to 2015. Cumulative incidence of falls was determined through self-reported fall calendars over 12 months. Participants were then classified into one of three groups: multiple fallers (≥2 falls), single fallers (1 fall), and non-fallers (0). Daily physical activity was measured over 1 week using a waist-bound accelerometer during baseline and three-year follow-ups. Activity fragmentation was defined as the reciprocal of the mean activity bout length, with higher fragmentation reflecting shorter, more fractured bouts of continuous activity. Multivariate linear mixed-effects models were used to assess three-year longitudinal changes in: 1) activity fragmentation, and 2) accumulation of activity across six three-hour intervals from 5 AM to 11 PM. FINDINGS: In adjusted models accounting for visual field damage and other factors, multiple fallers demonstrated greater annual declines (per year) in daily active bouts (-1.79 bouts/day, 95% confidence interval [CI]: -3.35, -0.22), daily active minutes (-17.15 min/day, 95% CI: -26.35, -7.94), and increased fragmentation (1%, 95% CI: 0, 2%) over the three-year follow-up period as compared to non-fallers; no such changes were seen when comparing single fallers and non-fallers. In time-of-day analyses, multiple fallers experienced greater annual declines in average hourly steps over all periods of the day, though the rate of decline was only significant between 5 PM and 8 PM (-27.07 steps/hour, 95% CI: -51.15, -2.99) compared to non-fallers. INTERPRETATION: In an older population with visual impairment, multiple falls over 12 months were associated with more transient and fragmented activity over a subsequent three-year period, and activity declines during evening hours, compared to non-fallers. These findings suggest that multiple fallers with visual impairment may be at high risk for a decline in physical capacity and endurance, warranting clinical interventions. FUNDING: The research was supported in part by National Institutes of Health Grant EY022976.

Genomic and transcriptomic profiling of hepatoid adenocarcinoma of the stomach.

Hepatoid adenocarcinoma of the stomach (HAS), a rare subtype of gastric cancer (GC), has a low incidence but a high mortality rate. Little is known about the molecular features of HAS. Here we applied whole-exome sequencing (WES) on 58 tumours and the matched normal controls from 54 HAS patients, transcriptome sequencing on 30 HAS tumours, and single-cell RNA sequencing (scRNA-seq) on one HAS tumour. Our results reveal that the adenocarcinomatous component and hepatocellular-like component of the same HAS tumour originate monoclonally, and HAS is likely to initiate from pluripotent precursor cells. HAS has high stemness and high methionine cycle activity compared to classical GC. Two genes in the methionine cycle, MAT2A, and AHCY are potential targets for HAS treatments. We provide the first integrative genomic profiles of HAS, which may facilitate its diagnosis, prognosis, and treatment.

Non-ketotic Hyperglycemia Chorea-Ballismus and Intracerebral Hemorrhage: A Case Report and Literature Review.

Non-ketotic hyperglycemia chorea-ballismus (NKH-CB) is a rare metabolical syndrome secondary to the hyperglycemic condition, which is characterized by a triad of acute or subacute hemichorea-hemiballismus, hyperglycemic state, and unique abnormalities limited to the striatum on neuroimaging. Several related case studies on this disorder have been reported previously, but NKH-CB had never been associated with intracerebral hemorrhage (ICH). Herein, we report an uncommon case of NKH-CB and ICH that occurred simultaneously in one patient, which provides a challenge for clinicians in making a correct diagnosis. An 88-year-old woman with a long-term history of poor-controlled type 2 diabetes mellitus and hypertension, who presented with a sudden-onset headache, restlessness, severe bilateral choreiform and ballistic movements, elevated levels of glucose and osmolality in the serum, an increased white blood cell count, and two-type hyperdense signs on CT imaging, was finally diagnosed with NKH-CB and ICH. Despite administrated active treatments, the patient's clinical status did not improve and ultimately passed away. This case is reported to remind clinicians to consider the possibility of NKH-CB when patients present sudden-onset choreiform and ballistic movements. It is also the first entity with two-type hyperdense signs on CT imaging simultaneously, which helps us distinguish NKH-CB from ICH more intuitively.

Association Between Visual Field Damage and Gait Dysfunction in Patients With Glaucoma.

IMPORTANCE: Gait dysfunction is common in older people with visual impairment and is a major cause of falls. OBJECTIVE: To compare 3-year longitudinal changes in gait measures across the spectrum of baseline visual field (VF) damage in glaucoma. DESIGN, SETTING, AND PARTICIPANTS: A post hoc analysis was designed on September 1, 2018, following a prospective cohort study, which enrolled older adults with glaucoma or suspected glaucoma from September 2013 to March 2015 and followed up for up to 3 years. Baseline VF damage was defined by integrated VF (IVF) sensitivity and categorized as normal/mild (IVF >28 dB), moderate (IVF, 23-28 dB), and severe (IVF, <23 dB). Each participant walked on an electronic walkway back and forth twice at normal pace each study year. Linear mixed-effects models evaluated longitudinal change in gait outcomes (1) stratified within each VF severity category and (2) across the range of IVF sensitivity. Analysis took place from October 2019 to October 2020. MAIN OUTCOMES AND MEASURES: Three-year changes in 7 gait assessments under usual-pace walking, including base support and its coefficient of variation, stride length and its coefficient of variation, stride velocity and its coefficient of variation, and cadence. RESULTS: Of 241 participants, the mean (SD) age was 70.8 (7.7) years, 116 (48.2%) were women, and 70 (29.0%) were African American. When comparing longitudinal gait changes over 3 years across the spectrum of IVF sensitivity, each 5-unit (dB) decrement was associated with more rapid declines in stride velocity (-0.05 z score unit/y; 95% CI, -0.09 to -0.01; P = .01) and cadence (-0.07 z score unit/y; 95% CI, -0.10 to -0.03; P < .001). When evaluating gait changes within each glaucoma severity group, shorter stride length was associated with persons with normal/mild (-0.06 z score unit/y; 95% CI, -0.10 to -0.03; P = .001), moderate (-0.08 z score unit/y; 95% CI, -0.12 to -0.04; P < .001), and severe VF damage (-0.16 z score unit/y; 95% CI, -0.24 to -0.07; P < .001), while stride velocity (-0.18 z score unit; 95% CI, -0.28 to -0.07; P = .002) and slower cadence (-0.15 z score unit; 95% CI, -0.25 to -0.04; P = .006) were associated with those with severe VF damage. CONCLUSIONS AND RELEVANCE: At worse levels of baseline VF damage, patients with glaucoma in this study demonstrated an exacerbated decline in walking speeds (ie, stride velocity and cadence), indicating that mobility speeds decrease faster over time in older adults with glaucoma.

Perioperative or postoperative adjuvant oxaliplatin with S-1 versus adjuvant oxaliplatin with capecitabine in patients with locally advanced gastric or gastro-oesophageal junction adenocarcinoma undergoing D2 gastrectomy (RESOLVE): an open-label, superiority and non-inferiority, phase 3 randomised controlled trial.

BACKGROUND: The optimal perioperative chemotherapeutic regimen for locally advanced gastric cancer remains undefined. We evaluated the efficacy and safety of perioperative and postoperative S-1 and oxaliplatin (SOX) compared with postoperative capecitabine and oxaliplatin (CapOx) in patients with locally advanced gastric cancer undergoing D2 gastrectomy. METHODS: We did this open-label, phase 3, superiority and non-inferiority, randomised trial at 27 hospitals in China. We recruited antitumour treatment-naive patients aged 18 years or older with historically confirmed cT4a N+ M0 or cT4b Nany M0 gastric or gastro-oesophageal junction adenocarcinoma, with Karnofsky performance score of 70 or more. Patients undergoing D2 gastrectomy were randomly assigned (1:1:1) via an interactive web response system, stratified by participating centres and Lauren classification, to receive adjuvant CapOx (eight postoperative cycles of intravenous oxaliplatin 130 mg/m2 on day one of each 21 day cycle plus oral capecitabine 1000 mg/m2 twice a day), adjuvant SOX (eight postoperative cycles of intravenous oxaliplatin 130 mg/m2 on day one of each 21 day cycle plus oral S-1 40-60 mg twice a day), or perioperative SOX (intravenous oxaliplatin 130 mg/m2 on day one of each 21 day plus oral S-1 40-60 mg twice a day for three cycles preoperatively and five cycles postoperatively followed by three cycles of S-1 monotherapy). The primary endpoint, assessed in the modified intention-to-treat population, 3-year disease-free survival to assess the superiority of perioperative-SOX compared with adjuvant-SOX and the non-inferiority (hazard ratio non-inferiority margin of 1·33) of adjuvant-SOX compared with adjuvant-CapOx. Safety analysis were done in patients who received at least one dose of the assigned treatment. This study is registered with ClinicalTrials.gov, NCT01534546. FINDINGS: Between Aug 15, 2012, and Feb 28, 2017, 1094 patients were screened and 1022 (93%) were included in the modified intention-to-treat population, of whom 345 (34%) patients were assigned to the adjuvant-CapOx, 340 (33%) patients to the adjuvant-SOX group, and 337 (33%) patients to the perioperative-SOX group. 3-year disease-free survival was 51·1% (95% CI 45·5-56·3) in the adjuvant-CapOx group, 56·5% (51·0-61·7) in the adjuvant-SOX group, and 59·4% (53·8-64·6) in the perioperative-SOX group. The hazard ratio (HR) was 0·77 (95% CI 0·61-0·97; Wald p=0·028) for the perioperative-SOX group compared with the adjuvant-CapOx group and 0·86 (0·68-1·07; Wald p=0·17) for the adjuvant-SOX group compared with the adjuvant-CapOx group. The most common grade 3-4 adverse events was neutropenia (32 [12%] of 258 patients in the adjuvant-CapOx group, 21 [8%] of 249 patients in the adjuvant-SOX group, and 30 [10%] of 310 patients in the perioperative-SOX group). Serious adverse events were reported in seven (3%) of 258 patients in adjuvant-CapOx group, two of which were related to treatment; eight (3%) of 249 patients in adjuvant-SOX group, two of which were related to treatment; and seven (2%) of 310 patients in perioperative-SOX group, four of which were related to treatment. No treatment-related deaths were reported. INTERPRETATION: Perioperative-SOX showed a clinically meaningful improvement compared with adjuvant-CapOx in patients with locally advanced gastric cancer who had D2 gastrectomy; adjuvant-SOX was non-inferior to adjuvant-CapOx in these patients. Perioperative-SOX could be considered a new treatment option for patients with locally advanced gastric cancer. FUNDING: National Key Research and Development Program of China, Beijing Scholars Program 2018-2024, Peking University Clinical Scientist Program, Taiho, Sanofi-Aventis, and Hengrui Pharmaceutical. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

The Impact of Weather and Seasons on Falls and Physical Activity among Older Adults with Glaucoma: A Longitudinal Prospective Cohort Study.

Understanding periods of the year associated with higher risk for falling and less physical activity may guide fall prevention and activity promotion for older adults. We examined the relationship between weather and seasons on falls and physical activity in a three-year cohort of older adults with glaucoma. Participants recorded falls information via monthly calendars and participated in four one-week accelerometer trials (baseline and per study year). Across 240 participants, there were 406 falls recorded over 7569 person-months, of which 163 were injurious (40%). In separate multivariable regression models incorporating generalized estimating equations, temperature, precipitation, and seasons were not significantly associated with the odds of falling, average daily steps, or average daily active minutes. However, every 10 °C increase in average daily temperature was associated with 24% higher odds of a fall being injurious, as opposed to non-injurious (p = 0.04). The odds of an injurious fall occurring outdoors, as opposed to indoors, were greater with higher average temperatures (OR per 10 °C = 1.46, p = 0.03) and with the summer season (OR = 2.69 vs. winter, p = 0.03). Falls and physical activity should be understood as year-round issues for older adults, although the likelihood of injury and the location of fall-related injuries may change with warmer season and temperatures.

Environmental Features Contributing to Falls in Persons With Vision Impairment: The Role of Home Lighting and Home Hazards.

PURPOSE: To evaluate whether home hazards and lighting levels are associated with higher fall rates in adults with varying degrees of visual field (VF) damage from glaucoma. METHODS: Participants with diagnosed or suspected glaucoma provided three years of prospective falls data via monthly falls diaries. A post-fall telephone questionnaire determined fall locations. Seven home areas were evaluated for hazards and lighting via an in-home assessment. Multivariate models adjusting for relevant confounders, including age, sex, comorbidity, and severity of VF damage, evaluated the influence of hazards and lighting on fall rates in each home region. RESULTS: Mean baseline age for the 170 participants was 71.0 (7.6) years and 78 (46%) of participants were female. Fifty-nine participants experienced a total of 83 home falls, with the greatest number of falls occurring on the indoor stairs (n = 24, 29%) and bedroom (n = 17, 21%). Neither the number nor the percentage of hazardous items graded as hazardous was associated with the rate of falls (P > .26). Each 10-fold increase in room lighting was associated with 35% fewer falls in that home region (P = .02). The relation between lighting and the rate of falls did not differ with the degree of visual field damage (P > .3), and a lower fall rate was noted with better lighting even in participants with mild or no VF damage (rate ratio = 0.52/10-fold better lighting; P = 0.01). CONCLUSIONS: Fewer home falls were found with better lighting, but not with fewer home hazards. Lighting improvements at home may reduce fall rates in older adults. NOTE: Publication of this article is sponsored by the American Ophthalmological Society.

Importance and Severity Dependence of Physical Activity by GPS-Tracked Location in Glaucoma Patients.

PURPOSE: To quantify the association of visual field (VF) damage on physical activity away-from-home, per away-from-home excursion, and at-home. DESIGN: Prospective cohort study. METHODS: Among 229 participants with glaucoma or suspected glaucoma, the severity of VF damage was defined as average sensitivity within the integrated VF (IVF). Participants wore accelerometers and global positioning system trackers for 7 days to measure physical activity and characterize activity location. Multivariable negative binomial regressions were used to test whether away-from-home activity per day, physical activity per away-from-home excursion, and at-home activity per day varied by the severity of VF damage. RESULTS: Each 5-dB decrement in IVF sensitivity was associated with a lower number of away-from-home activities per day (18% less moderate and vigorous physical activity [MVPA] minutes/d, 95% confidence interval, 0.69-0.97) and physical activities per away-from-home excursion (20% less MVPA minutes/excursion, 95% confidence interval, 0.65-0.98). Similar findings were noted for other away-from-home activity measures (including active minutes/steps per day, or active minutes/steps per excursion). However, worse IVF sensitivity was not associated with measures of at-home activities (MVPA minutes/d, active minutes/d, and steps/d), time spent at or away from home, or excursions/wk (P > .1 for all). CONCLUSIONS: Restriction of physical activity in more patients with severe glaucoma results mostly from activity restriction outside the home environment. These findings highlight the importance of maintaining a safe home environment (where activity is less restricted) and increasing confidence to perform activity, particular high-intensity activity, when leaving the home amongst patients with glaucoma.

Visual Impairment and Objectively Measured Physical Activity in Middle-Aged and Older Adults.

BACKGROUND: Vision loss is associated with increased risk of falls and restricted physical activity, yet the relationship between multiple vision measures and objectively measured physical activity, especially activity patterns, in mid-to-late life is not well understood. METHOD: This study included 603 participants aged 50 years and older (mean age = 73.5) in the Baltimore Longitudinal Study of Aging who had the following assessments: presenting and best-corrected visual acuity, contrast sensitivity, visual fields, stereo acuity, and free-living physical activity using a wrist-worn ActiGraph accelerometer for 7 days. Linear regression models were used to examine the association between vision measures and daily activity counts, active minutes, and activity fragmentation (defined as an active-to-sedentary transition probability), adjusting for potential confounders. Mixed-effects models estimated differences in activity by time of day comparing those with and without each visual impairment. RESULTS: In the fully adjusted model, worse presenting visual acuity, contrast sensitivity, and visual fields were associated with fewer activity counts, less active time, and more fragmented activity patterns (p < .05 for all). Participants with presenting or best-corrected visual acuity impairment had 19.2 and 29.3 fewer active minutes (p = .05 and p = .03, respectively) per day. Visual field impairment was associated with 268 636 fewer activity counts (p = .02), 46.2 fewer active minutes (p = .02) per day, and 3% greater activity fragmentation (p = .009). Differences in activity levels tended to be greatest from 6 am to 6 pm (p < .05). CONCLUSIONS: Older adults with visual impairment have restricted and more fragmented patterns of daily activity. Longitudinal studies to quantify the long-term impacts of visual impairments on activity decline are warranted.

Characterizing Longitudinal Changes in Physical Activity and Fear of Falling after Falls in Glaucoma.

BACKGROUND: Older adults with visual impairments experience a higher risk of falling, and are more vulnerable to adverse health consequences associated with falls than those with normal vision. This study characterizes longitudinal changes in objectively measured physical activity and fear of falling (FoF) occurring after various types of falls in visually impaired older adults. DESIGN: Prospective cohort study. SETTING: Hospital-based enrollment. PARTICIPANTS: People with glaucoma or suspected glaucoma. MEASUREMENTS: Falls were defined as unintentionally coming to rest on the ground or a lower level, and injurious falls were determined though follow-up calls. Study participants were categorized into three groups-fallers with injurious consequences, fallers without injurious consequences, and non-fallers based on fall status in the first year. Physical activity was assessed by waist-bound accelerometer. FoF was evaluated by questionnaire, with Rasch modeling generating FoF scores where higher scores reflected worse FoF. The 3-year longitudinal changes of physical activity and FoF were modeled using mixed-effects models. RESULTS: In linear models fully adjusted for visual field damage and other covariates, physical activity among injurious fallers showed greater annual (per year) declines in daily steps (-425 steps/d, 95% confidence interval (CI) = -793, -57), daily active minutes (-13 min/d, 95% CI = -21, -6), and daily moderate and vigorous physical activity (MVPA) minutes (-3 MVPA minutes/d, 95% CI = -5, 0) over the 3-year period as compared to non-fallers; however, physical activity did not significantly decline among non-injurious fallers. No longitudinal increases in FoF scores were observed in injurious or non-injurious fallers when compared to non-fallers. CONCLUSION: Among visually impaired older adults, injurious falls identified prospectively over 12 months contributed to a significant decline in physical activity over a 3-year period, while minimal changes were observed in FoF.

Patterns of Daily Physical Activity across the Spectrum of Visual Field Damage in Glaucoma Patients.

PURPOSE: To define and quantify patterns of objectively measured daily physical activity by level of visual field (VF) damage in glaucoma patients including: (1) activity fragmentation, a metric of health and physiologic decline, and (2) diurnal patterns of activity, a measure of rest and activity rhythms. DESIGN: Prospective cohort study. PARTICIPANTS: Older adults diagnosed with glaucoma or suspected glaucoma. METHODS: Degree of VF damage was defined by the average VF sensitivity within the integrated VF (IVF). Each participant wore a hip accelerometer for 1 week to measure daily minute-by-minute activity for 7 consecutive days. Activity fragmentation was calculated as the reciprocal of the average activity bout duration in minutes, with higher fragmentation indicating more transient, rather than sustained, activity. Multivariate linear regression was used to test for cross-sectional associations between VF damage and activity fragmentation. Multivariate linear mixed-effects models were used to assess the associations between VF damage and accumulation of activity across 6 3-hour intervals from 5 am to 11 pm. MAIN OUTCOME MEASURES: Activity fragmentation and amount of activity (steps) over the course of the day. RESULTS: Each 5-dB decrement in IVF sensitivity was associated with 16.3 fewer active minutes/day (P < 0.05) and 2% higher activity fragmentation (P < 0.05), but not with the number of active bouts per day (P = 0.30). In time-of-day analyses, lower IVF sensitivity was associated with fewer steps over the 11 am to 2 pm, 2 pm to 5 pm, and 5 pm to 8 pm periods (106.6, 93.1, and 89.2 fewer steps, respectively; P < 0.05 for all), but not over other periods. The activity midpoint (the time at which half of the daily activity is completed) did not vary across level of VF damage. CONCLUSIONS: At worse levels of VF damage, glaucoma patients demonstrate shorter, more fragmented bouts of physical activity throughout the day and lower activity levels during typical waking hours, reflecting low physiologic functioning. Further work is needed to establish the temporality of this association and whether glaucoma patients with such activity patterns are at a greater risk of adverse health outcomes associated with activity fragmentation.

Visual Impairment and Eye Diseases in HIV-infected People in the Antiretroviral Therapy (ART) Era in Rakai, Uganda.

PURPOSE: Antiretroviral therapy reduced infectious eye diseases (EDs) in HIV-infected people. There is limited data on age-related EDs and visual impairment (VI) in people living with HIV. We report prevalence of VI and spectrum of EDs in HIV-infected people in an ART era in Rakai, Uganda. METHODS: A philanthropic campaign during 2009-2012 provided ophthalmic services to HIV+ patients in care. Unilateral presenting visual acuity (VA) was assessed by a trained staff in HIV clinics using a 6-m Snellen chart. A slit-lamp examination by an ophthalmologist evaluated eyes with impaired acuity. A retrospective chart review was later conducted retrieving data of patients participating the ophthalmic service. VI was defined referencing WHO's ICD-11. Ophthalmic diagnosis was summarized by VI level. Logistic regressions estimated demographic associations with cataract diagnosis. RESULTS: 688 HIV+ patients were evaluated, median age was 44 (IQR: 37-50) years, 69% were female. Fifty-one percent were on ART (median duration 4, IQR: 2-5 years). Crude prevalence of moderate/severe VI and blindness were both 2%. The main diagnoses were refractive error (55%), conjunctivitis (18%), cataract (15%), and pterygium (11%). Cataract prevalences were 10%, 12%, and 26% among age groups of 19-34, 35-49, and ≥50 years, respectively. Cataract was found in 73% of the HIV+s with blindness and in 63% of those with moderate/severe VI. Older age and male sex were significantly associated with higher cataract prevalence. CONCLUSION: VI in HIV+ patients in Rakai was mainly due to refractive error and cataract. Cataract was common in all age groups.