Prevalence and Distribution of Intrinsic Capacity and Its Associations with Health Outcomes in Older People: The Jockey Club Community eHealth Care Project in Hong Kong.

OBJECTIVE: To determine the prevalence and distribution of intrinsic capacity (IC) impairments and examine their associations with health outcomes. METHODS: Community-dwelling people aged 60 years and older were interviewed at baseline and followed up for one to three years. IC domains including cognitive, locomotor, vitality, sensory (vision, hearing), and psychological capacities were assessed at baseline. Incident polypharmacy, incontinence, poor/fair self-rated health, and instrumental activities of daily living (IADL) difficulty were ascertained at each follow-up. FINDINGS: 10,007 participants were interviewed at baseline. Overall mean age was 75.7±7.9 years. At baseline, 85.3% had impairments in one or more IC domains, where cognitive capacity was the domain that was most frequently affected (71.3%). The prevalence of impairments in one or more domains increased with age (p<0.001) and was higher among women than men (p<0.001). Among the 1,601 participants who were interviewed at each follow-up, those with impairments in three or more domains had the greatest risk for the incidence of polypharmacy (adjusted OR 2.2, 95%CI 1.1-4.2), incontinence (adjusted OR 3.0, 95%CI 1.8-5.0), poor/fair self-rated health (adjusted OR 3.7, 95%CI 1.9-7.2), and IADL difficulty (adjusted OR 3.3, 95%CI 1.8-6.1) compared with those without IC impairments. CONCLUSION: IC impairments are highly prevalent and those with IC impairments had increased risks of polypharmacy, incontinence, poor/fair self-rated health, and IADL difficulty. The findings could potentially lead to a refinement and the adoption of IC as a screening measure which could be served as a target of intervention in the care for older people.

Patient-reported outcome (PRO) results from the AGITG DOCTOR trial: a randomised phase 2 trial of tailored neoadjuvant therapy for resectable oesophageal adenocarcinoma.

BACKGROUND: AGITG DOCTOR was a randomised phase 2 trial of pre-operative cisplatin, 5 fluorouracil (CF) followed by docetaxel (D) with or without radiotherapy (RT) based on poor early response to CF, detected via PET, for resectable oesophageal adenocarcinoma. This study describes PROs over 2 years. METHODS: Participants (N = 116) completed the EORTC QLQ-C30 and oesophageal module (QLQ-OES18) before chemotherapy (baseline), before surgery, six and 12 weeks post-surgery and three-monthly until 2 years. We plotted PROs over time and calculated the percentage of participants per treatment group whose post-surgery score was within 10 points (threshold for clinically relevant change) of their baseline score, for each PRO scale. We examined the relationship between Grade 3+ adverse events (AEs) and PROs. This analysis included four groups: CF responders, non-responders randomised to DCF, non-responders randomised to DCF + RT, and "others" who were not randomised. RESULTS: Global QOL was clinically similar between groups from 6 weeks post-surgery. All groups had poorer functional and higher symptom scores during active treatment and shortly after surgery, particularly the DCF and DCF + RT groups. DCF + RT reported a clinically significant difference (-13points) in mean overall health/QOL between baseline and pre-surgery. Similar proportions of patients across groups scored +/- 10 points of baseline scores within 2 years for most PRO domains. Instance of grade 3+ AEs were not related to PROs at baseline or 2 years. CONCLUSIONS: By 2 years, similar proportions of patients scored within 10 points of baseline for most PRO domains, with the exception of pain and insomnia for the DCF + RT group. Non-responders randomised to DCF or DCF + RT experienced additional short-term burden compared to CF responders, reflecting the longer duration of neoadjuvant treatment and additional toxicity. This should be weighed against clinical benefits reported in AGITG DOCTOR. This data will inform communication of the trajectory of treatment options for early CF non-responders. TRIAL REGISTRATION: Australia New Zealand Clinical Trials Registry (ANZCTR), ACTRN12609000665235 . Registered 31 July 2009.

Processed electroencephalography: impact of patient age and surgical position on intraoperative processed electroencephalogram monitoring of burst-suppression.

We previously reported that processed EEG underestimated the amount of burst suppression compared to off-line visual analysis. We performed a follow-up study to evaluate the reasons for the discordance. Forty-five patients were monitored intraoperatively with processed EEG. A computer algorithm was used to convert the SedLine® (machine)-generated burst suppression ratio into a raw duration of burst suppression. The reference standard was a precise off-line measurement by two neurologists. We measured other potential variables that may affect machine accuracy such as age, surgery position, and EEG artifacts. Overall, the median duration of bust suppression for all study subjects was 15.4 min (Inter-quartile Range [IQR] = 1.0-20.1) for the machine vs. 16.1 min (IQR = 0.3-19.7) for the neurologists' assessment; the 95% limits of agreement fall within - 4.86 to 5.04 s for individual 30-s epochs. EEG artifacts did not affect the concordance between the two methods. For patients in prone surgical position, the machine estimates had significantly lower overall sensitivity (0.86 vs. 0.97; p = 0.038) and significantly wider limits of agreement ([- 4.24, 3.82] seconds vs. [- 1.36, 1.13] seconds, p = 0.001) than patients in supine position. Machine readings for younger patients (age < 65 years) had higher sensitivity (0.96 vs 0.92; p = 0.021) and specificity (0.99 vs 0.88; p = 0.007) for older patients. The duration of burst suppression estimated by the machine generally had good agreement compared with neurologists' estimation using a more precise off-line measurement. Factors that affected the concordance included patient age and position during surgery, but not EEG artifacts.

KRAS mutation effects on the 2-[18F]FDG PET uptake of colorectal adenocarcinoma metastases in the liver.

BACKGROUND: Deriving individual tumor genomic characteristics from patient imaging analysis is desirable. We explore the predictive value of 2-[18F]FDG uptake with regard to the KRAS mutational status of colorectal adenocarcinoma liver metastases (CLM). METHODS: 2-[18F]FDG PET/CT images, surgical pathology and molecular diagnostic reports of 37 patients who underwent PET/CT-guided biopsy of CLM were reviewed under an IRB-approved retrospective research protocol. Sixty CLM in 39 interventional PET scans of the 37 patients were segmented using two different auto-segmentation tools implemented in different commercially available software packages. PET standard uptake values (SUV) were corrected for: (1) partial volume effect (PVE) using cold wall-corrected contrast recovery coefficients derived from phantom spheres with variable diameter and (2) variability of arterial tracer supply and variability of uptake time after injection until start of PET scan derived from the tumor-to-blood standard uptake ratio (SUR) approach. The correlations between the KRAS mutational status and the mean, peak and maximum SUV were investigated using Student's t test, Wilcoxon rank sum test with continuity correction, logistic regression and receiver operation characteristic (ROC) analysis. These correlation analyses were also performed for the ratios of the mean, peak and maximum tumor uptake to the mean blood activity concentration at the time of scan: SURMEAN, SURPEAK and SURMAX, respectively. RESULTS: Fifteen patients harbored KRAS missense mutations (KRAS+), while another 3 harbored KRAS gene amplification. For 31 lesions, the mutational status was derived from the PET/CT-guided biopsy. The Student's t test p values for separating KRAS mutant cases decreased after applying PVE correction to all uptake metrics of each lesion and when applying correction for uptake time variability to the SUR metrics. The observed correlations were strongest when both corrections were applied to SURMAX and when the patients harboring gene amplification were grouped with the wild type: p ≤ 0.001; ROC area under the curve = 0.77 and 0.75 for the two different segmentations, respectively, with a mean specificity of 0.69 and sensitivity of 0.85. CONCLUSION: The correlations observed after applying the described corrections show potential for assigning probabilities for the KRAS missense mutation status in CLM using 2-[18F]FDG PET images.

Hip fractures are preventable: a proposal for osteoporosis screening and fall prevention in older people.

Osteoporosis is highly prevalent but underdiagnosed and undertreated in Hong Kong. Fragility fractures associated with osteoporosis often result in loss of independence and increased mortality for home-dwelling patients, imposing a high socio-economic burden on society. This issue requires urgent attention given the rapid growth of the elderly population in Hong Kong by approximately 4.3% each year. To address this situation, a group of experts convened to discuss practical ways to reduce the burden of fractures and formulated three recommendations: first, all men (aged ≥70 years) and women (aged ≥65 years) should receive universal dual-energy X-ray absorptiometry assessment for osteoporosis. Second, all men (aged ≥70 years) and women (aged ≥65 years) with a fracture-risk assessment-derived 10-year risk (hip fracture with bone mineral density) ≥3% should receive ≥3 years of anti-osteoporotic treatment. Third, comprehensive structured assessment (including dual-energy X-ray absorptiometry) should be conducted in older patients with a history of falling. By implementing these recommendations, we estimate that we could prevent 5234 hip fractures in 10 years, an annual incidence reduction of approximately 7%, and save HK$425 million in direct medical costs plus substantial indirect savings. Ample clinical and cost-effectiveness data support these recommendations, and studies in Hong Kong and abroad could serve as models on how to implement them. We are confident that by applying these recommendations rigorously and systematically, a significant reduction in hip fractures in Hong Kong is achievable.

A clinical prediction score using age at diagnosis and saline infusion test parameters can predict aldosterone-producing adenoma from idiopathic adrenal hyperplasia.

PURPOSE: Accurate subtyping of the primary aldosteronism into aldosterone-producing adenoma (APA) and idiopathic adrenal hyperplasia (IAH) is important to direct for specific treatment modalities. The objective of the study was to compare the clinical and biochemical parameters of APA and IAH patients to derive a Clinical Prediction Score reliably predicting APA from IAH. METHODS: This was a retrospective multi-centre study recruiting 38 APA patients and 42 IAH patients from four major hospitals in Hong Kong using database from Surgical Outcomes Monitoring and Improvement Programme and Clinical Data Analysis and Reporting System. Their clinical and biochemical parameters were evaluated. RESULTS: Patients in APA group were younger than IAH group (mean age 48.6 ± 9.2 vs. 57.1 ± 7.3 years old, p < 0.001), had more suppressed renin before saline infusion in saline infusion test (SIT) (median 0.19 [IQR 0.15-0.37] vs. 0.39 [IQR 0.19-0.69] ng/mL/h, p = 0.01), and higher aldosterone level after saline infusion in SIT (median 674 [IQR 498-1000] vs. 327 [IQR 242-483] pmol/L, p < 0.001). A clinical prediction score using three parameters was devised, comprising age at diagnosis < 50 years, PRA before saline infusion in SIT ≤ 0.26 ng/mL/h, and aldosterone level after saline infusion in SIT ≥ 424 pmol/L. A score of 2 would predict APA with a sensitivity of 84.2% and specificity of 88.1%, and a score of 3 would predict APA with a sensitivity of 31.6% and specificity of 100%. CONCLUSIONS: Clinical Prediction Score based on the combination of age at diagnosis, PRA, and aldosterone level in the saline infusion tests could reliably predict APA from IAH.

High Protein Intake Is Associated with Lower Risk of All-Cause Mortality in Community-Dwelling Chinese Older Men and Women.

OBJECTIVES: To examine the association of the quantity and the source of protein intake with mortality risk in Chinese older adults. DESIGN: Prospective cohort study. SETTING: Community. PARTICIPANTS: Community-dwelling Chinese adults aged >=65 (1,480 men, 1,540 women) in Hong Kong. MEASUREMENTS: Food frequency questionnaire was used to capture baseline dietary intakes including protein, fiber, total grains, vegetables and fruit intakes. Primary outcome measures, identified from the death registry, were death from all causes, cancer and cardiovascular disease (CVD). Other demographic and lifestyle risk factors were also collected. Multivariate Cox proportion hazards regression was used to examine the association of protein intake with mortality risk. RESULTS: During a median of 13.8 follow-up years, 963 all-cause deaths, 336 cancer deaths, and 205 CVD deaths were identified. Among men in the highest quintile of total protein intake, all-cause mortality and cancer mortality decreased by 29% [95% confidence interval (CI): 0.55-0.92, p-trend=0.017] and 38% [95% CI: 0.39-0.97, p-trend=0.041] respectively compared with men in the lowest quintile after adjustment for demographics, lifestyle factors and medical conditions. Men in the highest quintile of animal protein intake showed 20% reduced risk of all-cause mortality than men in the lowest quintile (p-trend=0.042). Women in the highest quintile of plant protein intake showed 39% decreased risk of all-cause mortality [95% CI: 0.44-0.85, p-trend=0.019] than those in the lowest quintile. In women, protein intake was not associated with cancer mortality. In both men and women, protein intake was not associated with CVD morality. Further adjustment for other dietary variables attenuated the significant associations. CONCLUSIONS: Contrary to findings from Caucasian populations of all ages, among Chinese older adults, higher total protein intake was associated with lower all-cause and cancer mortality in Chinese older men. While higher animal protein intake was associated with reduced all-cause mortality in Chinese older men, higher plant protein intake was protective against all-cause mortality in Chinese women. The attenuated associations between protein intake and mortality risk after adjustment for other dietary variables also highlight the role of whole diet approach in mortality risk reduction among older adults.

A prospective RCT comparing combined chromoendoscopy with water exchange (CWE) vs water exchange (WE) vs air insufflation (AI) in adenoma detection in screening colonoscopy.

Background: A low adenoma detection rate (ADR) increases risks of interval cancers (ICs). Proximal colon flat polyps, e.g. serrated lesions (SLs), are difficult to find. Missed proximal colon flat lesions likely contribute to IC. Aims: We compared chromoendoscopy with water exchange (CWE), water exchange (WE) and air insufflation (AI) in detecting adenomas in screening colonoscopy. Methods: After split-dose preparation, 480 veterans were randomized to AI, WE and CWE. Results: Primary outcome of proximal ADR (55.6% vs 53.4% vs 52.2%, respectively) were similar in all groups. Adenoma per colonoscopy (APC) and adenoma per positive colonoscopy (APPC) were comparable. Detection rate of proximal colon SLs was significantly higher for CWE and WE than AI (26.3%, 23.6% and 11.3%, respectively, p = 0.002). Limitations: single operator; SLs only surrogate markers of but not IC. Conclusions: When an endoscopist achieves high-quality AI examinations with overall ADR twice (61.6%) the recommended standard (30%), use of WE and CWE does not produce further improvement in proximal or overall ADR. Comparable APC and APPC confirm equivalent withdrawal inspection techniques. WE alone is sufficient to significantly improve detection of proximal SLs. The impact of increased detection of proximal SLs by WE on prevention of IC deserves to be studied. This study is registered at ClinicalTrial.gov (NCT#01607255).

How Dietary Patterns are Related to Inflammaging and Mortality in Community-Dwelling Older Chinese Adults in Hong Kong - A Prospective Analysis.

INTRODUCTION: Studies examining dietary patterns and inflammageing in relation to mortality are limited. OBJECTIVE: We examined the influence of various dietary patterns on all-cause and cardiovascular disease (CVD) mortality, taking into account demographics, lifestyle factors, and serum inflammatory markers. METHODS: We conducted multivariate Cox regression analyses using data from a cohort of community-dwelling older Chinese adults (1,406 men, 1,396 women) in Hong Kong. Baseline interviewer administered questionnaires covered dietary intake estimation and dietary pattern generation from the food frequency questionnaire, demographic and lifestyle factors, cognitive function and depressive symptoms. Serum high-sensitivity C-reactive protein (hsCRP) and 25-hydroxyvitamin D (25OHD) were measured. All-cause and CVD mortality data at 14-year follow up were retrieved from an official database. RESULTS: In men, higher hsCRP level was associated with lower Diet Quality Index-International (DQI-I) score, Mediterranean-DASH Intervention for Neurodegenerative Delay Diet (MIND) score, Okinawan diet score, "vegetables-fruits" pattern score and "snacks-drinks-milk" pattern score. Higher serum 25OHD level was associated with higher Mediterranean Diet Score (MDS) but lower "snacks-drinks-milk" pattern score. None of the dietary pattern scores was associated with all-cause or CVD mortality after adjusting for all covariates. In women, hsCRP level and serum 25OHD level were not associated with any dietary patterns. Higher DQI-I score (HR=0.77 (95% CIs: 0.59, 0.99) highest vs. lowest tertile, p-trend=0.038) and Okinawan diet score (HR=0.78 (95% CIs: 0.61, 1.00) highest vs lowest tertile, p-trend=0.046) was associated with a lower risk of all-cause mortality, whereas higher MIND score (HR=0.63 (95% CI: 0.36, 1.09) highest vs. lowest tertile, p-trend=0.045) was associated with a reduced risk of CVD morality in the multivariate adjusted model. CONCLUSION: Higher DQI-I score and Okinawan diet score were associated with a lower risk of all-cause mortality, and higher adherence to the MIND diet was related to a reduced risk of CVD mortality in community-dwelling Chinese older women.

Underwater polypectomy without submucosal injection for colorectal lesions ≤ 20 mm in size-a multicenter retrospective observational study.

BACKGROUND: Underwater polypectomy (UWP) of large (≥ 20 mm) colorectal lesions is well described, but reports of UWP for lesions ≤ 20 mm in size, which account for > 95% of polyps encountered in routine clinical practice, are limited. We assessed the feasibility of UWP in routine practice across various sites for colorectal lesions ≤ 20 mm in size. METHODS: A multicenter retrospective study was performed on pooled data from nine colonoscopists at 3 U.S., 1 Taiwanese and 2 Italian sites. Outcomes related to UWP on lesions ≤ 20 mm in size were analyzed. RESULTS: In 117 patients, UWP netted 169 lesions. Polypectomy by hot (HSP, 54%) or cold (CSP, 41%) snare, and cold forceps (CFP, 5%) were performed successfully without endoscopic evidence of residual neoplasia or immediate clinically significant adverse events. The majority (74.6%) were tubular adenomas; 60.9% were from the proximal colon. Histopathologic margins were positive in 4 and unavailable in 26 CSP and 24 HSP specimens. The remainder had negative resection margins on pathologic reports. CONCLUSION: UWP for colorectal lesions ≤ 20 mm in routine practice across multiple sites confirms the feasibility and acceptability of this technique. Improvement of resection outcomes by UWP in routine practice deserves further evaluation in a randomized controlled trial.

Breath-Hold Blood Oxygen Level-Dependent MRI: A Tool for the Assessment of Cerebrovascular Reserve in Children with Moyamoya Disease.

BACKGROUND AND PURPOSE: There is a critical need for a reliable and clinically feasible imaging technique that can enable prognostication and selection for revascularization surgery in children with Moyamoya disease. Blood oxygen level-dependent MR imaging assessment of cerebrovascular reactivity, using voluntary breath-hold hypercapnic challenge, is one such simple technique. However, its repeatability and reliability in children with Moyamoya disease are unknown. The current study sought to address this limitation. MATERIALS AND METHODS: Children with Moyamoya disease underwent dual breath-hold hypercapnic challenge blood oxygen level-dependent MR imaging of cerebrovascular reactivity in the same MR imaging session. Within-day, within-subject repeatability of cerebrovascular reactivity estimates, derived from the blood oxygen level-dependent signal, was computed. Estimates were associated with demographics and intellectual function. Interrater reliability of a qualitative and clinically applicable scoring scheme was assessed. RESULTS: Twenty children (11 males; 12.1 ± 3.3 years) with 30 MR imaging sessions (60 MR imaging scans) were included. Repeatability was "good" on the basis of the intraclass correlation coefficient (0.70 ± 0.19). Agreement of qualitative scores was "substantial" (κ = 0.711), and intrarater reliability of scores was "almost perfect" (κ = 0.83 and 1). Younger participants exhibited lower repeatability (P = .027). Repeatability was not associated with cognitive function (P > .05). However, abnormal cerebrovascular reactivity was associated with slower processing speed (P = .015). CONCLUSIONS: Breath-hold hypercapnic challenge blood oxygen level-dependent MR imaging is a repeatable technique for the assessment of cerebrovascular reactivity in children with Moyamoya disease and is reliably interpretable for use in clinical practice. Standardization of such protocols will allow further research into its application for the assessment of ischemic risk in childhood cerebrovascular disease.

Cost-effectiveness of osteoporosis screening strategies for hip fracture prevention in older Chinese people: a decision tree modeling study in the Mr. OS and Ms. OS cohort in Hong Kong.

Despite the high costs of hip fracture, many governments provide limited support for osteoporosis screening. We demonstrated that osteoporosis screening by dual-energy X-ray absorptiometry (DXA) with or without pre-screening by Fracture Risk Assessment Tool (FRAX) or calcaneal ultrasound are more cost-effective than no screening in Chinese people aged 65 or over in Hong Kong. INTRODUCTION: To examine the cost-effective potential osteoporosis screening strategies for hip fracture prevention in Hong Kong. METHODS: Decision tree models were constructed to evaluate the cost per quality-adjusted life years (QALYs) of the different osteoporosis screening strategies followed by subsequent 5-year treatment with alendronate compared to no screening (but treat if a hip fracture occurs). The multiple osteoporosis screening strategies were composed of alternative tests and initiation age groups were evaluated with a 10-year horizon, and treatment were assigned if central dual-energy X-ray absorptiometry (DXA) T-score (at either the hip or spine) is - 2.5 or less. Strategies included DXA for all people and pre-screening with the Fracture Risk Assessment Tool (FRAX) at specific thresholds or by calcaneal quantitative ultrasonography (QUS) before taking DXA examination. All the model inputs were based on the Mr. OS and Ms. OS Hong Kong cohort; data are obtained from the Social Welfare Department or the published literature. RESULTS: All of the screening strategies, including the universal screening with DXA and the pre-screening with FRAX or QUS before DXA, were consistently more cost-effective than no screening for people aged 65 years old or over. One-way sensitivity analysis with a more optimistic assumption on treatment adherence or inclusion of other major osteoporotic fractures did not change the results materially. Probabilistic sensitivity analyses showed a dominant role of pre-screening with FRAX followed by subsequent osteoporosis drug treatment in people aged 70 years old or over in Hong Kong. CONCLUSIONS: Osteoporosis screening strategies based on DXA with or without pre-screening are more cost-effective compared to no screening for Chinese people aged 65 or over in Hong Kong.

Influence of Dietary Patterns and Inflammatory Markers on Atherosclerosis Using Ankle Brachial Index as a Surrogate.

OBJECTIVE: To examine the influence of various dietary patterns on ankle-brachial index (ABI) as a surrogate of atherosclerosis, taking into account serum levels of C-reactive protein (CRP) and factors that predispose to inflammation and/or endothelial damage (homocysteine) or may be protective (tryptophan, vitamin D), as well as age, gender, and lifestyle risk factors. DESIGN: Cross sectional analysis. SETTING: Cohort of 4000 men and women aged 65 years living in the community in Hong Kong SAR China. MEASUREMENTS: Interviewer administered questionnaire that includes dietary intake estimation by the food frequency records (from which various dietary patterns can be characterized), socioeconomic status, smoking habit, alcohol consumption, physical activity. Clinical measurements include body weight and height, and ankle-brachial index using hand-held Doppler machine. Laboratory measurements include assays of serum 25 hydroxyvitamin D, CRP, homocysteine, and tryptophan using LC/MC methods. RESULT: Compared with the lowest quintile of vitamin D level, higher quintile was associated with lower prevalence of ABI <0.9 in women only after multiple adjustments of covariates. In men the low score group of the vegetables-fruits dietary pattern was associated with increased odds of having ABI<0.9 after adjusting for all covariates (OR=16.51 (95% CI: 2.21, 123.26)). Similar findings apply to the low score group in the MIND (Mediterranean-DASH Intervention for Neurodegenerative Delay Diet) pattern (OR=2.6 (95% CI: 1.24, 5.42)). In women, ABI<0.9 was associated with low Dietary Quality Index (DQI) score (OR=2.05 (95% CI: 1.22, 3.43)), and low score group of snacks-drinks-milk products dietary pattern (OR=3.07 (95% CI: 1.05, 9.04)). No association was observed for the Mediterranean Dietary Pattern (MDS), Dietary Approaches to Stop Hypertension (DASH), Okinawan and "meat-fish" dietary patterns in either men or women. CONCLUSION: We conclude that any dietary patterns emphasizing fruit and vegetable intake are associated with better vascular health using ABI as an indicator.