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"Chao, David"
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30-day mortality after systemic anticancer treatment for breast and lung cancer in England: a population-based, observational study
by
Bomb, Martine
,
Dodwell, David
,
Smittenaar, Rebecca
in
Aged
,
Antineoplastic Combined Chemotherapy Protocols - therapeutic use
,
Breast cancer
2016
30-day mortality might be a useful indicator of avoidable harm to patients from systemic anticancer treatments, but data for this indicator are limited. The Systemic Anti-Cancer Therapy (SACT) dataset collated by Public Health England allows the assessment of factors affecting 30-day mortality in a national patient population. The aim of this first study based on the SACT dataset was to establish national 30-day mortality benchmarks for breast and lung cancer patients receiving SACT in England, and to start to identify where patient care could be improved.
In this population-based study, we included all women with breast cancer and all men and women with lung cancer residing in England, who were 24 years or older and who started a cycle of SACT in 2014 irrespective of the number of previous treatment cycles or programmes, and irrespective of their position within the disease trajectory. We calculated 30-day mortality after the most recent cycle of SACT for those patients. We did logistic regression analyses, adjusting for relevant factors, to examine whether patient, tumour, or treatment-related factors were associated with the risk of 30-day mortality. For each cancer type and intent, we calculated 30-day mortality rates and patient volume at the hospital trust level, and contrasted these in a funnel plot.
Between Jan 1, and Dec, 31, 2014, we included 23 228 patients with breast cancer and 9634 patients with non-small cell lung cancer (NSCLC) in our regression and trust-level analyses. 30-day mortality increased with age for both patients with breast cancer and patients with NSCLC treated with curative intent, and decreased with age for patients receiving palliative SACT (breast curative: odds ratio [OR] 1·085, 99% CI 1·040–1·132; p<0·0001; NSCLC curative: 1·045, 1·013–1·079; p=0·00033; breast palliative: 0·987, 0·977–0·996; p=0·00034; NSCLC palliative: 0·987, 0·976–0·998; p=0·0015). 30-day mortality was also significantly higher for patients receiving their first reported curative or palliative SACT versus those who received SACT previously (breast palliative: OR 2·326 99% CI 1·634–3·312; p<0·0001; NSCLC curative: 3·371, 1·554–7·316; p<0·0001; NSCLC palliative: 2·667, 2·109–3·373; p<0·0001), and for patients with worse general wellbeing (performance status 2–4) versus those who were generally well (breast curative: 6·057, 1·333–27·513; p=0·0021; breast palliative: 6·241, 4·180–9·319; p<0·0001; NSCLC palliative: 3·384, 2·276–5·032; p<0·0001). We identified trusts with mortality rates in excess of the 95% control limits; this included seven for curative breast cancer, four for palliative breast cancer, five for curative NSCLC, and seven for palliative NSCLC.
Our findings show that several factors affect the risk of early mortality of breast and lung cancer patients in England and that some groups are at a substantially increased risk of 30-day mortality. The identification of hospitals with significantly higher 30-day mortality rates should promote review of clinical decision making in these hospitals. Furthermore, our results highlight the importance of collecting routine data beyond clinical trials to better understand the factors placing patients at higher risk of 30-day mortality, and ultimately improve clinical decision making. Our insights into the factors affecting risk of 30-day mortality will help treating clinicians and their patients predict the balance of harms and benefits associated with SACT.
Public Health England.
Journal Article
Prognostic value of nocturnal blood pressure dipping on cardiovascular outcomes in Chinese patients with hypertension in primary care
by
Chan, Sara S. W.
,
Chan, Pang‐Fai
,
Lo, Ling
in
ambulatory blood pressure monitoring
,
Blood Pressure
,
Blood Pressure Monitoring, Ambulatory
2021
Meta‐analyses showed that non‐dipping of nocturnal blood pressure on ambulatory blood pressure monitoring (ABPM) was associated with adverse cardiovascular prognosis. However, these prognostic studies were mainly conducted in Caucasian and Japanese populations. Whether this association applies to Chinese patients remained uninvestigated. A total of 1199 Chinese patients with hypertension undergoing ABPM between January 2012 and December 2014 were recruited retrospectively from five public hypertension referral clinics in Hong Kong. Patients were followed up for a mean 6.42 years for cardiovascular morbidity and mortality and all‐cause mortality. Time to event of different dipping patterns was compared by Kaplan‐Meier curves. Hazard ratios (HR) were obtained by Cox proportional hazard models with patient demographics and confounding factors adjusted in multivariate regression. A total of 163 end point events occurred in the period. Normal dipping was observed in 446 patients (37.2%), non‐dipping in 490 (40.9%), reverse dipping in 161 (13.4%), and extreme dipping in 102 (8.5%). Kaplan‐Meier analyses showed inferior survival in non‐dippers and reverse dippers for total cardiovascular events and coronary events but not cerebrovascular events. After adjusting for confounding factors, Cox regressions showed HRs 1.166 (CI 0.770‐1.764) and 1.173 (CI 0.681‐2.021) in non‐dippers and reverse dippers for total cardiovascular events, and HRs 1.320 (CI 0.814‐2.141) and 1.476 (CI 0.783‐2.784) for coronary events. Nocturnal blood pressure non‐dipping, and to a greater extent reverse dipping, demonstrated adverse cardiovascular prognosis in a cohort of Chinese patients with hypertension in Hong Kong. Further focused studies on cerebrovascular events and reverse dippers were warranted to refine risk stratification.
Journal Article
Combined nicotine patch with gum versus nicotine patch alone in smoking cessation in Hong Kong primary care clinics: a randomised controlled trial
2019
Background
The prevalence of daily cigarette smoking has dropped to 10% in Hong Kong (HK) in 2017, however, smoking still kills 5700 persons per year. Studies suggest that abstinence rates are higher with combined NRT than single NRT, although local data on safety and benefits of combined NRT are lacking. The aim of this study is to compare the effectiveness of combined NRT with single NRT among HK Chinese.
Methods
This is a one-year, two-arm, parallel randomised trial. Five hundred sixty smokers, who smoked ≥10 cigarettes/day for ≥1 year, were randomized to combined and single NRT. Combined NRT group received counseling and nicotine patch & gum. Single NRT group received counselling and nicotine patch. Primary outcome was abstinence rate measured as self-reported 7-day point prevalence with CO validated at 52 weeks. Secondary outcomes included smoking abstinence rates at 4, 12, & 26 weeks. Crude odds ratio and
p
-value were reported from logistic regression without adjustment; for trend analysis, adjusted odds ratio (AOR) and p-value were reported from Generalized Estimating Equation (GEE) (controlling for time). All AORs were adjusted for age, sex, baseline CO and clusters.
Results
Abstinence rates at 4, 12, 26 and 52 weeks were all higher in the combined NRT group (35.8, 21.9, 16.8, 20.1%) compared with the single NRT group (28, 16.8, 11.2, 14.3%). At 4 weeks, combined NRT group was more likely to quit smoking (OR 1.43, 95% CI, 1.00 to 2.05) than the single NRT group. From GEE analysis, combined NRT group had a significantly higher abstinence rate (23.6%) than the single NRT group (17.6%) across repeated measures at all-time points. Combined NRT group was more likely to quit smoking (OR 1.43, 95% CI, 1.15 to 1.77). No significant difference in the side effect profile was detected between groups.
Conclusions
Smokers given 8 weeks of combined NRT were more likely to quit smoking at 4, 12, 26 and 52 weeks compared with single NRT. Combined NRT was as well tolerated as single NRT and it should be further promoted in our community.
Trial registration
NCT03836560 from
ClinicalTrial.gov
, 9 Feb 2019.
Journal Article
External validation of the Hong Kong Chinese non‐laboratory risk models and scoring algorithm for case finding of prediabetes and diabetes mellitus in primary care
2024
Aims/Introduction Two Hong Kong Chinese non‐laboratory‐based prediabetes/diabetes mellitus (pre‐DM/DM) risk models were developed using logistic regression (LR) and machine learning, respectively. We aimed to evaluate the models' validity in case finding of pre‐DM/DM in a Chinese primary care (PC) population. We also evaluated the validity of a risk‐scoring algorithm derived from the LR model. Materials and Methods This was a cross‐sectional external validation study on Chinese adults, without a prior DM diagnosis, who were recruited from public/private PC clinics in Hong Kong. A total of 1,237 participants completed a questionnaire on the models' predictors. Of that, 919 underwent blood glucose testing. The primary outcome was the models' and the algorithm's sensitivity in finding pre‐DM/DM cases. The secondary outcomes were the models' and the algorithm's specificity, positive/negative predictive values, discrimination and calibration. Results The models' sensitivity were 0.70 (machine learning) and 0.72 (LR). Both showed good external discrimination (area under the receiver operating characteristic curve: machine learning 0.744, LR 0.739). The risks estimated by the models were lower than the observed incidence, indicating poor calibration. Both models were more effective among participants with lower pretest probabilities; that is, age 18–44 years. The algorithm's sensitivity was 0.77 at the cut‐off score of ≥16 out of 41. Conclusion This study showed the validity of the models and the algorithm for finding pre‐DM/DM cases in a Chinese PC population in Hong Kong. They can facilitate more cost‐effective identification of high‐risk individuals for blood testing to diagnose pre‐DM/DM in PC. Further studies should recalibrate the models for more precise risk estimation in PC populations. A cross‐sectional external validation study on 919 Chinese adults without a prior diabetes diagnosis recruited from public/private primary care clinics in Hong Kong. Our findings supported the external validity of the new non‐laboratory‐based models and the derived risk‐scoring algorithm in finding pre‐DM/DM cases in a primary care population.
Journal Article
First-line erlotinib in patients with advanced non-small-cell lung cancer unsuitable for chemotherapy (TOPICAL): a double-blind, placebo-controlled, phase 3 trial
by
Boshoff, Chris
,
Khan, Iftekhar
,
Falk, Stephen
in
Aged
,
Aged, 80 and over
,
Antineoplastic Combined Chemotherapy Protocols
2012
Many patients with advanced non-small-cell lung cancer (NSCLC) receive only active supportive care because of poor performance status or presence of several comorbidities. We investigated whether erlotinib improves clinical outcome in these patients.
TOPICAL was a double-blind, randomised, placebo-controlled, phase 3 trial, done at 78 centres in the UK. Eligibility criteria were newly diagnosed, pathologically confirmed NSCLC; stage IIIb or IV; chemotherapy naive; no symptomatic brain metastases; deemed unsuitable for chemotherapy because of poor (≥2) Eastern Cooperative Oncology Group performance status or presence of several comorbidities, or both; and estimated life expectancy of at least 8 weeks. Patients were randomly assigned (by phone call, in a 1:1 ratio, stratified by disease stage, performance status, smoking history, and centre, block size 10) to receive oral placebo or erlotinib (150 mg per day) until disease progression or unacceptable toxicity. Investigators, clinicians, and patients were masked to assignment. The primary endpoint was overall survival. Analyses were by intention to treat, and prespecified subgroup analyses included development of a rash due to erlotinib within 28 days of starting treatment. This study is registered, number ISRCTN 77383050.
Between April 14, 2005, and April 1, 2009, we randomly assigned 350 patients to receive erlotinib and 320 to receive placebo. We followed up patients until March 31, 2011. 657 patients died; median overall survival did not differ between groups (erlotinib, 3·7 months, 95% CI 3·2–4·2, vs placebo, 3·6 months, 3·2–3·9; unadjusted hazard ratio [HR] 0·94, 95% CI 0·81–1·10, p=0·46). 59% (178 of 302) of patients assigned erlotinib and who were assessable at 1 month developed first-cycle rash, which was the only independent factor associated with overall survival. Patients with first-cycle rash had better overall survival (HR 0·76, 95% CI 0·63–0·92, p=0·0058), compared with placebo. Compared with placebo, overall survival seemed to be worse in the group that did not develop first-cycle rash (1·30, 1·05–1·61, p=0·017). Grade 3 or 4 diarrhoea was more common with erlotinib than placebo (8% [28 of 334] vs 1% [four of 313], p=0·0001), as was high-grade rash (23% [79 of 334] vs 2% [five of 313], p<0·0001); other adverse events were much the same between groups.
Patients with NSCLC who are deemed unsuitable for chemotherapy could be given erlotinib. Patients who develop a first-cycle rash should continue to receive erlotinib, whereas those who do not have a rash after 28 days should discontinue erlotinib, because of the possibility of decreased survival.
Cancer Research UK, Roche.
Journal Article
Genome-wide analysis of enhancer RNA in gene regulation across 12 mouse tissues
by
Tsai, Huai-Kuang
,
Pan, David Zhi-Chao
,
Tsai, Zing Tsung-Yeh
in
631/114
,
631/208/726/2102
,
631/337/384/2568
2015
Enhancers play a crucial role in gene regulation but the participation of enhancer transcripts (i.e. enhancer RNA, eRNAs) in regulatory systems remains unclear. We provide a computational analysis on eRNAs using genome-wide data across 12 mouse tissues. The expression of genes targeted by transcribing enhancer is positively correlated with eRNA expression and significantly higher than expression of genes targeted by non-transcribing enhancers. This result implies eRNA transcription indicates a state of enhancer that further increases gene expression. This state of enhancer is tissue-specific, as the same enhancer differentially transcribes eRNAs across tissues. Therefore, the presence of eRNAs describes a tissue-specific state of enhancer that is generally associated with higher expressed target genes, surmising as to whether eRNAs have gene activation potential. We further found a large number of eRNAs contain regions in which sequences and secondary structures are similar to microRNAs. Interestingly, an increasing number of recent studies hypothesize that microRNAs may switch from their general repressive role to an activating role when targeting promoter sequences. Collectively, our results provide speculation that eRNAs may be associated with the selective activation of enhancer target genes.
Journal Article
Hong Kong Academy of Medicine position paper on postgraduate medical education 2023
2023
[...]CBME requires trainers to master teaching skills that may not be well-known. [...]the alignment of learning and assessment methods with CBME approaches requires educational standards and procedures to be redesigned. [...]PGME is a relatively new discipline with limited academic presence. [...]there is a need to empower Fellows and CME/CPD providers to use methods that support adult learning, and online learning is a particularly promising method for this learning.11Finally, many learners lack the skills and personal attributes needed for self-directed learning; they require support to acquire these abilities.12 Recommendation 5: HKAM and the Colleges should undertake actions to transform CME/CPD, including: (1) devise and deliver a comprehensive communication plan to effectively engage all stakeholders; (2) reform the structure and redesign the standards and procedures of CME requirements and accreditation to align with the new CME paradigm; (3) design and implement FDPs to empower Fellows and possibly other CME providers to use learning methods which support adult learning; (4) nurture the capacities of learners to practise self-directed learning; (5) support the development of online learning through the provision of technology and relevant training in educational practices; and (6) establish partnerships with overseas CME/CPD accreditation bodies.
Journal Article
Assessment of Hypertension Complications and Health Service Use 5 Years After Implementation of a Multicomponent Intervention
by
Yu, Esther Y. T.
,
Li, Yim Chu
,
Luk, Wan
in
Adult
,
Aged
,
Cardiovascular Diseases - epidemiology
2023
There is a lack of information regarding the impact of implementing a protocol-driven, team-based, multicomponent intervention in public primary care settings on hypertension-related complications and health care burden over the long term.
To compare hypertension-related complications and health service use at 5 years among patients managed with Risk Assessment and Management Program for Hypertension (RAMP-HT) vs usual care.
In this population-based prospective matched cohort study, patients were followed up until the date of all-cause mortality, an outcome event, or last follow-up appointment before October 2017, whichever occurred first. Participants included 212 707 adults with uncomplicated hypertension managed at 73 public general outpatient clinics in Hong Kong between 2011 and 2013. RAMP-HT participants were matched to patients receiving usual care using propensity score fine stratification weightings. Statistical analysis was conducted from January 2019 to March 2023.
Nurse-led risk assessment linked to electronic action reminder system, nurse intervention, and specialist consultation (as necessary), in addition to usual care.
Hypertension-related complications (cardiovascular diseases, end-stage kidney disease), all-cause mortality, public health service use (overnight hospitalization, attendances at accident and emergency department, specialist outpatient clinic, and general outpatient clinic).
A total of 108 045 RAMP-HT participants (mean [SD] age: 66.3 [12.3] years; 62 277 [57.6%] female) and 104 662 patients receiving usual care (mean [SD] age 66.3 [13.5] years; 60 497 [57.8%] female) were included. After a median (IQR) follow-up of 5.4 (4.5-5.8) years, RAMP-HT participants had 8.0% absolute risk reduction in cardiovascular diseases, 1.6% absolute risk reduction in end-stage kidney disease, and 10.0% absolute risk reduction in all-cause mortality. After adjusting for baseline covariates, the RAMP-HT group was associated with lower risk of cardiovascular diseases (hazard ratio [HR], 0.62; 95% CI, 0.61-0.64), end-stage kidney disease (HR, 0.54; 95% CI, 0.50-0.59), and all-cause mortality (HR, 0.52; 95% CI, 0.50-0.54) compared with the usual care group. The number needed to treat to prevent 1 cardiovascular disease event, end-stage kidney disease, and all-cause mortality was 16, 106, and 17, respectively. RAMP-HT participants had lower hospital-based health service use (incidence rate ratios ranging from 0.60 to 0.87) but more general outpatient clinic attendances (IRR, 1.06; 95% CI, 1.06-1.06) compared with usual care patients.
In this prospective matched cohort study involving 212 707 primary care patients with hypertension, participation in RAMP-HT was associated with statistically significant reductions in all-cause mortality, hypertension-related complications, and hospital-based health service use after 5 years.
Journal Article
Realtime phase-amplitude coupling analysis of micro electrode recorded brain signals
by
Sachs, Adam J.
,
Lu, David Chao-Chia
,
Boulay, Chadwick
in
Algorithms
,
Amplitudes
,
Biology and Life Sciences
2018
To demonstrate a method to calculate phase amplitude coupling (PAC) quickly and robustly for realtime applications.
We designed and implemented a multirate PAC algorithm with efficient filter bank processing and efficient computation of PAC for many frequency-pair combinations. We tested the developed algorithm for computing PAC on simulated data and on intraoperative neural recording data obtained during deep brain stimulation (DBS) electrode implantation surgery.
A combination of parallelized frequency-domain filtering and modulation index for PAC estimation provided robust results that could be calculated in real time on modest computing hardware.
The standard methods for calculating PAC can be optimized for quick and robust performance.
These results demonstrated that PAC can be extracted in real time and is suitable for neurofeedback applications.
Journal Article
Recalibration of a Non-Laboratory-Based Risk Model to Estimate Pre-Diabetes/Diabetes Mellitus Risk in Primary Care in Hong Kong
2024
Introduction/Objectives:
A non-laboratory-based pre-diabetes/diabetes mellitus (pre-DM/DM) risk prediction model developed from the Hong Kong Chinese population showed good external discrimination in a primary care (PC) population, but the estimated risk level was significantly lower than the observed incidence, indicating poor calibration. This study explored whether recalibrating/updating methods could improve the model’s accuracy in estimating individuals’ risks in PC.
Methods:
We performed a secondary analysis on the model’s predictors and blood test results of 919 Chinese adults with no prior DM diagnosis recruited from PC clinics from April 2021 to January 2022 in HK. The dataset was randomly split in half into a training set and a test set. The model was recalibrated/updated based on a seven-step methodology, including model recalibrating, revising and extending methods. The primary outcome was the calibration of the recalibrated/updated models, indicated by calibration plots. The models’ discrimination, indicated by the area under the receiver operating characteristic curves (AUC-ROC), was also evaluated.
Results:
Recalibrating the model’s regression constant, with no change to the predictors’ coefficients, improved the model’s accuracy (calibration plot intercept: −0.01, slope: 0.69). More extensive methods could not improve any further. All recalibrated/updated models had similar AUC-ROCs to the original model.
Conclusion:
The simple recalibration method can adapt the HK Chinese pre-DM/DM model to PC populations with different pre-test probabilities. The recalibrated model can be used as a first-step screening tool and as a measure to monitor changes in pre-DM/DM risks over time or after interventions.
Journal Article