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Background. Epidermal growth factor receptor is overexpressed in most pediatric high-grade gliomas (HGG). Since erlotinib had shown activity in adults with HGG, we conducted a phase II trial of erlotinib and local radiotherapy in children with newly diagnosed HGG. Methods. Following maximum surgical resection, patients between 3 and 21 years with nonmetastatic HGG received local radiotherapy at 59.4 Gy (54 Gy for spinal tumors and those with ≥70% brain involvement). Erlotinib started on day 1 of radiotherapy (120 mg/m2 per day) and continued for 2 years unless there was tumor progression or intolerable toxicities. The 2-year progression-free survival (PFS) was estimated for patients with intracranial anaplastic astrocytoma (AA) and glioblastoma.Results. Median age at diagnosis for 41 patients with intracranial tumors (21 with glioblastoma and 20 with AA) was 10.9 years (range, 3.3 to 19 years). The 2-year PFS for patients with AA and glioblastoma was 15% ± 7% and 19% ± 8%, respectively. Only five patients remained alive without tumor progression. Twenty-six patients had at least one grade 3 or 4 toxicity irrespective of association with erlotinib; only four required dose modifications. The main toxicities were gastrointestinal (n=11), dermatologic (n=5), and metabolic (n=4). One patient with gliomatosis cerebri who required prolonged corticosteroids died of septic shock associated with pancreatitis. Conclusions. Although therapy with erlotinib was mostly well tolerated, it did not change the poor outcome of our patients. Our results showed that erlotinib is not a promising medication in the treatment of children with intracranial AA and glioblastoma.

RNA thermometers are temperature-sensing non-coding RNAs that regulate the expression of downstream genes. A well-characterized RNA thermometer motif discovered in bacteria is the ROSE-like element (repression of heat shock gene expression). ATP-binding cassette (ABC) transporters are a superfamily of transmembrane proteins that harness ATP hydrolysis to facilitate the export and import of substrates across cellular membranes. Through structure-guided bioinformatics, we discovered that ROSE-like RNA thermometers are widespread upstream of ABC transporter genes in bacteria. X-ray crystallography, biochemistry, and cellular assays indicate that these RNA thermometers are functional regulatory elements. This study expands the known biological role of RNA thermometers to these key membrane transporters., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Single-cell nanopore sequencing of full-length mRNAs transforms single-cell multi-omics studies. However, challenges include high sequencing errors and dependence on short-reads and/or barcode whitelists. To address these, we develop scNanoGPS to calculate same-cell genotypes (mutations) and phenotypes (gene/isoform expressions) without short-read nor whitelist guidance. We apply scNanoGPS onto 23,587 long-read transcriptomes from 4 tumors and 2 cell-lines. Standalone, scNanoGPS deconvolutes error-prone long-reads into single-cells and single-molecules, and simultaneously accesses both phenotypes and genotypes of individual cells. Our analyses reveal that tumor and stroma/immune cells express distinct combination of isoforms (DCIs). In a kidney tumor, we identify 924 DCI genes involved in cell-type-specific functions such as PDE10A in tumor cells and CCL3 in lymphocytes. Transcriptome-wide mutation analyses identify many cell-type-specific mutations including VEGFA mutations in tumor cells and HLA-A mutations in immune cells, highlighting the critical roles of different mutant populations in tumors. Together, scNanoGPS facilitates applications of single-cell long-read sequencing technologies., (© 2023. The Author(s).)

Single-cell nanopore sequencing of full-length mRNAs (scNanoRNAseq) is transforming singlecell multi-omics studies. However, challenges include computational complexity and dependence on short-read curation. To address this, we developed a comprehensive toolkit, scNanoGPS to calculate same-cell genotypes-phenotypes without short-read guidance. We applied scNanoGPS onto 23,587 long-read transcriptomes from 4 tumors and 2 cell lines. Standalone, scNanoGPS accurately deconvoluted error-prone long-reads into single-cells and single-molecules. Further, scNanoGPS simultaneously accessed both phenotypes (expressions/isoforms) and genotypes (mutations) of individual cells. Our analyses revealed that tumor and stroma/immune cells often expressed significantly distinct combinations of isoforms (DCIs). In a kidney tumor, we identified 924 genes with DCIs involved in cell-type-specific functions such as PDE10A in tumor cells and CCL3 in lymphocytes. Moreover, transcriptome-wide mutation analyses identified many cell-type-specific mutations including VEGFA mutations in tumor cells and HLA-A mutations in immune cells, highlighting critical roles of different populations in tumors. Together, scNanoGPS facilitates applications of single-cell long-read sequencing.

Objective: Arthroscopy with lavage and synovectomy can remove tissue debris from the joint space and the synovial lining to provide pain relief to patients with osteoarthritis (OA). Here, we developed an in vitro model to study the interaction of cartilage wear particles with fibroblast-like synoviocytes (FLS) to better understand the interplay of cartilage particulates with cytokines on cells of the synovium., Method: In this study sub-10 μm cartilage particles or 1 μm latex particles were co-cultured with FLS ±10 ng/mL interleukin-1α (IL-1α) or tumor necrosis factor-α (TNF-α). Samples were analyzed for DNA, glycosaminoglycan (GAG), and collagen, and media samples were analyzed for media GAG, nitric oxide (NO) and prostaglandin-E2 (PGE2). The nature of the physical interaction between the particles and FLS was determined by microscopy., Results: Both latex and cartilage particles could be phagocytosed by FLS. Cartilage particles were internalized and attached to the surface of both dense monolayers and individual cells. Co-culture of FLS with cartilage particulates resulted in a significant increase in cell sheet DNA and collagen content as well as NO and PGE2 synthesis compared to control and latex treated groups., Conclusion: The proliferative response of FLS to cartilage wear particles resulted in an overall increase in extracellular matrix (ECM) content, analogous to the thickening of the synovial lining observed in OA patients. Understanding how cartilage particles interface with the synovium may provide insight into how this interaction contributes to OA progression and may guide the role of lavage and synovectomy for degenerative disease., (Copyright © 2017 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)

Objective: To determine the demographic characteristics, prognostic factors, and optimal treatment modalities of patients diagnosed with malignant primary tumors of the sublingual gland., Materials and Methods: The Surveillance, Epidemiology, and End Results (SEER) registry contains 210 patients diagnosed with sublingual gland tumors in the SEER database. Kaplan-Meier and multivariate Cox regression analysis were performed on age, sex, race, histologic subtype, stage, and treatment modality., Results: Kaplan-Meier analysis found an overall survival and disease-specific survival at 5 years of 69% and 83%, respectively. Multivariate analysis demonstrated that age, sex, stage, and surgery were predictors of overall survival, whereas stage was a predictor of disease-specific survival., Conclusions: Here we report, to our knowledge, the largest study to date investigating demographic characteristics, prognostic factors, and treatment modalities of patients diagnosed with primary malignant tumors of the sublingual gland. Increased age and stage correlated with decreased survival, whereas female gender and surgical therapy correlated with increased survival in the overall population. Radiation therapy for patients diagnosed with adenoid cystic carcinoma in the sublingual gland was correlated with increased survival., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objective: To determine the demographic characteristics, prognostic factors, and management for patients diagnosed with a malignant odontogenic tumor (MOT)., Study Design: The Surveillance, Epidemiology, and End Results (SEER) registry was reviewed for patients diagnosed with MOT from 1973 to 2011. Kaplan-Meier and multivariate Cox regression analyses were performed on patient demographic characteristics and pathologic variables., Results: The SEER database identified 295 MOT patients. The mean age at diagnosis was 50.5 years (range 5-89 years). Of these patients, 61.7% were male and 38.3% were female. The racial composition was 66.4% White, 22% Black, 6.1% Asian, 3.1% Pacific Islander, 0.3% Native American, and 2.1% Other/Unknown. Kaplan-Meier analysis found an overall survival (OS) and disease-specific survival (DSS) at 5 years of 54% and 67%, respectively. Multivariate analysis of the entire cohort found that age and stage were predictors of OS and that age was a predictor for DSS. For stage I/II MOTs, age and surgical therapy were predictors of OS and DSS, respectively., Conclusions: Here we report the largest study to date investigating demographic characteristics, prognostic factors, and management of MOT patients. Determinants of survival for OS and DSS include age, stage, and surgical therapy., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Importance: Malignant tumors of the submandibular gland are uncommon, leading to limited information regarding prognostic factors and difficulty in evaluating treatment modalities., Objective: To investigate the correlates of survival in patients with primary malignant tumors of the submandibular gland., Design, Setting, and Participants: Data from 2626 patients with a diagnosis of primary tumors of the submandibular gland between 1973 and 2011 in the Surveillance, Epidemiology, and End Results database were used in a retrospective population-based cohort analysis. Kaplan-Meier analysis along with multivariate Cox regression analysis was performed to determine prognostic factors in overall survival (OS) and disease-specific survival (DSS)., Interventions: Patients were treated with surgery, radiation therapy, both, or neither., Main Outcomes and Measures: Overall and disease-specific survival., Results: We identified 2626 patients with a diagnosis of primary malignant tumors of the submandibular gland, 52.9% male and 47.1% female, with a mean (range) age of 61.3 (7-101) years. Adenoid cystic carcinoma (36.0%) was the most prevalent histologic subtype, followed by squamous cell carcinoma (18.1%), mucoepidermoid carcinoma (16.9%), and adenocarcinoma (13.7%). Kaplan-Meier analysis demonstrated an OS and DSS of 65% and 74%at 2 years, 54% and 67% at 5 years, and 40% and 60% at 10 years, respectively. Multivariate Cox regression analysis revealed independent predictors of OS and DSS to be age (HR, 1.04 [95% CI, 1.03-1.04], P < .001; HR, 1.02 [95% CI, 1.01-1.03], P < .001), sex (HR, 0.69 [95% CI, 0.57-0.84], P < .001; HR, 0.73 [95% CI, 0.56-0.96], P = .02), tumor grade (HR, 1.47 [95% CI, 1.19-1.81], P < .001; HR, 1.67 [95% CI, 1.25-2.25], P = .001), stage at presentation (HR, 1.56 [95% CI, 1.41-1.72], P < .001; HR, 1.96 [95% CI, 1.69-2.28], P < .001), and surgical resection (HR, 0.55 [95% CI, 0.41-0.74], P < .001; HR, 0.51 [95% CI, 0.35-0.75], P = .001)., Conclusions and Relevance: We report, to our knowledge, the largest study to date focused on correlates of survival in submandibular gland malignant neoplasms. Multivariate analysis found that older age at diagnosis, high tumor grade, and later stage at presentation were correlated with decreased survival whereas female sex and surgical resection were correlated with increased survival. In addition, a 3-cm tumor cutoff size was demonstrated above which was associated with a significantly less favorable prognosis. Radiation therapy had mixed association with survival, dependent on tumor size and subtype.

Aim: To determine angle closure agreements between gonioscopy and anterior segment optical coherence tomography (AS-OCT), as well as gonioscopy and spectral domain OCT (SD-OCT). A secondary objective was to quantify inter-observer agreements of AS-OCT and SD-OCT assessments., Methods: Seventeen consecutive subjects (33 eyes) were recruited from the study hospital's Glaucoma clinic. Gonioscopy was performed by a glaucomatologist masked to OCT results. OCT images were read independently by 2 other glaucomatologists masked to gonioscopy findings as well as each other's analyses of OCT images., Results: Totally 84.8% and 45.5% of scleral spurs were visualized in AS-OCT and SD-OCT images respectively (P<0.01). The agreement for angle closure between AS-OCT and gonioscopy was fair at k=0.31 (95% confidence interval, CI: 0.03-0.59) and k=0.35 (95% CI: 0.07-0.63) for reader 1 and 2 respectively. The agreement for angle closure between SD-OCT and gonioscopy was fair at k=0.21 (95% CI: 0.07-0.49) and slight at k=0.17 (95% CI: 0.08-0.42) for reader 1 and 2 respectively. The inter-reader agreement for angle closure in AS-OCT images was moderate at 0.51 (95% CI: 0.13-0.88). The inter-reader agreement for angle closure in SD-OCT images was slight at 0.18 (95% CI: 0.08-0.45)., Conclusion: Significant proportion of scleral spurs were not visualised with SD-OCT imaging resulting in weaker inter-reader agreements. Identifying other angle landmarks in SD-OCT images will allow more consistent angle closure assessments. Gonioscopy and OCT imaging do not always agree in angle closure assessments but have their own advantages, and should be used together and not exclusively.

Background: Optimal adherence with antihypertensive medications is crucial to prevent hypertension-related complications. This study evaluated whether the duration of initial antihypertensive prescription is associated with better medication adherence in a large sample of Chinese hypertensive patients., Methods and Results: From a validated clinical database which consists of all patients in the public healthcare sector in Hong Kong, all patients on their first-ever antihypertensive agent from 2001 to 2005 (N=203,259) were included and followed-up for 12 months (and up to 5 years in separate analyses). The average age was 58.7 years (SD 17.3), and the overall rate of optimal adherence (as measured by having the Proportion of Days Covered≥0.80) was 32.4%. The proportion of patients whose initial prescriptions lasted for ≤6 days; 7-14 days; 15-28 days and ≥29 days was 23.7%, 24.3%, 15.1% and 37.0%, respectively. The corresponding proportion of optimal adherence was 18.1%, 20.1%, 31.0% and 50.3%. The binary logistic regression analysis showed that after controlling for age, sex, socioeconomic status, service type, drug class, and district of residence, those whose initial prescription was 7-14 days (adjusted odds ratio [AOR]=1.17, 95% C.I. 1.12-1.22); 15-28 days (AOR=1.90, 95% C.I. 1.82-1.99) and ≥29 days (AOR=4.13, 95% C.I. 3.96-4.31) were significantly more likely to be adherent than those who were prescribed for ≤6 days (all p<0.001). These findings remained significant in separate analyses where the period of follow-up was extended to 5 years., Conclusions: Shorter duration of first antihypertensive prescriptions was associated with poorer medication adherence, and this practice should be avoided if possible., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Current evidence is mixed regarding the association between antihypertensive prescriptions and cancer mortality. We evaluated this association in a large Chinese hypertensive population. We followed for five years all patients who were prescribed their first-ever antihypertensive agents between 2001 and 2005 in a public healthcare sector of Hong Kong. The association between antihypertensive drug class and cancer mortality was evaluated by Cox proportional hazard models with propensity score matching. Age, gender, socioeconomic status, service settings, district of residence, proportion of days covered reflecting medication adherence, and the number of comorbidities were adjusted. From 217,910 eligible patients, 9500 (4.4%) died from cancer within five years after their first-ever antihypertensive prescription. Most cancer deaths occurred in the digestive (38.9%) and respiratory system (30.4%); the breast (6.2%); and the lympho-hematopoietic tissues (5.3%). The proportion of patients who died from cancer was the highest in the calcium channel blocker (CCB) group (6.5%), followed by thiazide diuretics (4.4%), angiotensin converting enzyme inhibitors (4.2%) and β-blockers (2.6%). When compared with β-blockers, patients prescribed CCBs (Adjusted Hazard Ratio [AHR]=1.406, 95% C.I. 1.334-1.482, p<0.001) were more likely to die from cancer. Thiazide users were also more likely to suffer from cancer deaths (AHR=1.364, 95% C.I. 1.255-1.483, p<0.001), but became insignificant in stratified analysis. The association between cancer mortality and use of CCB, and perhaps thaizide, may alert physicians to the need for more meticulous and comprehensive care of these patients in clinical practice. We recommend prospective studies to evaluate cause-and-effect relationships of these associations., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Multimorbidity has become the norm worldwide as populations age. It remains, however, infrequently researched. This study evaluated factors associated with multimorbidity in a predominantly Chinese hypertensive population. We included all adult patients prescribed their first antihypertensive agents in the entire public sector in Hong Kong from a validated database. Multimorbidity was defined as having one or more medical conditions (cardiovascular diseases; respiratory diseases; diabetes or impaired fasting glucose; renal disease) in addition to hypertension. We studied the prevalence of multimorbidity and performed multinomial regression analyses to evaluate factors independently associated with multimorbidity. 223,286 hypertensive patients (average age of 59.9 years, SD 17.6) were included. The prevalence of having 0, 1 and ≥ 2 additional conditions was 59.6%, 32.8% and 7.5%, respectively. The most common conditions were cardiovascular disease (24.2%) and diabetes (23.0%), followed by respiratory disorders (14.6%) and renal disease (10.9%). Older age (>50 years), male sex, lower household income, receipt of social security allowance and suboptimal blood pressure control (>140 mmHg or >90 mmHg; >130 mmHg or >80 mmHg for diabetes patients; AOR = 3.38-4.49) were significantly associated with multimorbidity. There exists a synergistic effect among these variables as older (≥ 70 years), male patients receiving security allowance had substantially higher prevalence of multimorbidity (19.9% vs 7.5% among all patients). Multimorbidity is very common in hypertensive patients and its prevalence increased markedly with the presence of risk factors identified in this study. Hypertensive patients with multimorbidities should receive more meticulous clinical care as their blood pressure control tends to be poorer., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Background: Perindopril and lisinopril are two common ACE inhibitors prescribed for management of hypertension. Few studies have evaluated their comparative effectiveness to reduce mortality. This study compared the all-cause and cardiovascular related mortality among patients newly prescribed ACE inhibitors., Methods: All adult patients newly prescribed perindopril or lisinopril from 2001 to 2005 in all public clinics or hospitals in Hong Kong were retrospectively evaluated, and followed up until 2010. Patients prescribed the ACE inhibitors for less than a month were excluded. The all-cause mortality and cardiovascular-specific (i.e. coronary heart disease, heart failure and stroke) mortality were compared. Cox proportional hazard regression model was used to assess the mortality, controlling for age, sex, socioeconomic status, patient types, the presence of comorbidities, and medication adherence as measured by the proportion of days covered. An additional model using propensity scores was performed to minimize indication bias., Results: A total of 15,622 patients were included in this study, in which 6910 were perindopril users and 8712 lisinopril users. The all-cause mortality (22.2% vs. 20.0%, p<0.005) and cardiovascular mortality (6.5% vs. 5.6%, p<0.005) were higher among lisinopril users than perindopril users. From regression analyses, lisinopril users were 1.09-fold (95% C.I. 1.01-1.16) and 1.18-fold (95% C.I. 1.02-1.35) more likely to die from any-cause and cardiovascular diseases, respectively. Age-stratified analysis showed that this significant difference was observed only among patients aged >70 years. The additional models controlled for propensity scores yielded comparable results., Conclusions: The long-term all-cause and cardiovascular related mortality rates of lisinopril users was significantly different from those of perindopril users. These findings showed that intra-class variation on mortality exists among ACE inhibitors among those aged 70 years or older. Future studies should consider a longer, large-scale randomized controlled trial to compare the effectiveness between different medications in the ACEI class, especially among the elderly., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

This study evaluated whether short term exposures to NO2, O3, particulate matter <10 mm in diameter (PM10) were associated with higher risk of mortality. A total of 223,287 hypertensive patients attended public health-care services and newly prescribed at least 1 antihypertensive agent were followed-up for up to 5 years. A time-stratified, bi-directional case-crossover design was adopted. For all-cause mortality, significant positive associations were observed for NO2 and PM10 at lag 0-3 days per 10 μg/m(3) increase in concentration (excess risks 1.187%-2.501%). Significant positive associations were found for O3 at lag 1 and 2 days and the excess risks were 1.654% and 1.207%, respectively. We found similarly positive associations between these pollutants and respiratory disease mortality. These results were significant among those aged ≥65 years and in cold seasons only. Older hypertensive patients are susceptible to all-cause and respiratory disease-specific deaths from these air pollutants in cold weather., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Background: Existing trials almost exclusively used atenolol to represent the entire β-blocker class, and it is unknown whether there are intra-class differences. We compared the incidence of all-cause and cardiovascular mortality, blood pressure (BP) control and adherence levels between patients newly prescribed atenolol vs. metoprolol tartrate., Methods: This cohort study included all public, clinical settings in Hong Kong between 2001 and 2005, followed up till 2010. We compared outcomes between 22,479 new atenolol users and 29,972 new metoprolol tartrate users. Cox proportional hazard regression analysis was used to evaluate the difference in mortality between drugs. Binary logistic regression analyses were used to compare the BP control rates and adherence levels., Results: 7.0% and 13.1% died of any causes among atenolol and metoprolol users, respectively (p<0.005). The incidence of cardiovascular mortality among atenolol users was lower than metoprolol users (1.4% vs. 3.7%, p<0.001). When compared with atenolol users, metoprolol users were 1.13-fold (95% C.I. 1.06-1.20) and 1.56-fold (95% C.I. 1.27-1.90), respectively, more likely to experience all-cause and cardiovascular mortality; less likely to be drug adherent (adjusted relative risk [aRR]: 0.95, 95% C.I. 0.90-0.99, p=0.013); and less likely to achieve optimal overall BP control (aRR 0.94, 95% C.I. 0.90-0.99, p=0.023) and diastolic BP control (aRR 0.86, 95% C.I. 0.77-0.97, p=0.013)., Conclusions: These findings imply an intra-class difference for beta-blockers when used as first-line antihypertensive prescriptions in real-life clinical settings which inform future clinical guidelines. More outcome studies on the effectiveness of different subtypes within other major antihypertensive drug classes are warranted., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Background: Randomized trials have shown that the major antihypertensive drug classes are similarly effective to reduce mortality, but whether these drug class difference exists in clinical practice has been scarcely explored. This study evaluated the association between antihypertensive drug class, all-cause mortality and deaths due to diabetes or renal disease in real-life clinical settings., Methods: A clinical database in Hong Kong included all patients who were prescribed their first-ever antihypertensive agents between 2001 and 2005 from the public healthcare sector. All patients were followed up for five years, and grouped according to the initial antihypertensive prescription. The associations between antihypertensive drug class, all-cause mortality or combined diabetes and renal mortality, respectively, were evaluated by Cox proportional hazard models., Results: From 218,047 eligible patients, 33,288 (15.3%) died within five years after their first-ever antihypertensive prescription and among which 1055 patients (0.48%) died of diabetes or renal disease. After adjusted for age, gender, socioeconomic status, service settings, district of residence, medication adherence, and the number of comorbidities, each drug class was similarly likely to be associated with mortality due to diabetes or renal disease [Adjusted Hazard Ratios (AHR) ranged from 0.92 to 1.73, p=0.287-0.939] and all-cause mortality (AHR ranged from 0.83 to 1.02) except for beta-blockers (AHR=0.815, 95% C.I. 0.68-0.87, p=0.024) when ACEI was used as a reference group in propensity score-adjusted analysis., Conclusions: These findings provide real-life evidence reinforcing that any major antihypertensive drug class is suitable as a first-line agent for management of hypertension as recommended by international guidelines., (© 2013.)

Background: Randomized trials have shown that optimal adherence to antihypertensive agents could protect against cardiovascular diseases, but whether adherence reduces cardiovascular deaths in community settings has not been explored so fully. This study evaluates the association between antihypertensive adherence and cardiovascular (coronary heart disease and stroke) mortality in the primary care settings., Methods: From a territory-wide database in Hong Kong, we included all patients who were prescribed their first-ever antihypertensive agents in the years between 2001 and 2005 from the public healthcare sector. All patients were followed up for five years, and assigned as having poor (Proportion of Days Covered [PDC]<40%), intermediate (40-79%), and high (≥ 80%) adherence to antihypertensive agents. The association between antihypertensive adherence and cardiovascular mortality was evaluated by using the Cox proportional hazard models., Results: From a total of 218,047 eligible patients, 3825 patients (1.75%) died of cardiovascular disease within five years after having received their first-ever antihypertensive agents. The proportions of patients having poor, intermediate, and high medication adherence were 32.9%, 12.1%, and 55.0%, respectively. Higher adherence levels at PDC 40%-79% (HR=0.46, 95% C.I. 0.41-0.52, p<0.001) and ≥ 80% (HR=0.91, 95% C.I. 0.85-0.98, p=0.012) were significantly less likely to be associated with mortality than the poor adherence (PDC0.040) group., Conclusions: Better antihypertensive adherence was associated with lower cardiovascular mortality. This highlights the need to promote adherence through strategies which have been proved to be effective in clinical settings., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Background: A territory-wide Internet-based electronic patient record allows better patient care in different sectors. The engagement of private physicians is one of the major facilitators for implementation, but there is limited information about the current adoption level of electronic medical record (eMR) among private primary care physicians., Objective: This survey measured the adoption level, enabling factors, and hindering factors of eMR, among private physicians in Hong Kong. It also evaluated the key functions and the popularity of electronic systems and vendors used by these private practitioners., Methods: A central registry consisting of 4324 private practitioners was set up. Invitations for self-administered surveys and the completed questionnaires were sent and returned via fax, email, postal mail, and on-site clinic visits. Current users and non-users of eMR system were compared according to their demographic and practice characteristics. Student's t tests and chi-square tests were used for continuous and categorical variables, respectively., Results: A total of 524 completed surveys (response rate 524/4405 11.90%) were collected. The proportion of using eMR in private clinics was 79.6% (417/524). When compared with non-users, the eMR users were younger (users: 48.4 years SD 10.6 years vs non-users: 61.7 years SD 10.2 years, P<.001); more were female physicians (users: 80/417, 19.2% vs non-users: 14/107, 13.1%, P=.013); possessed less clinical experience (with more than20 years of practice: users: 261/417, 62.6% vs non-user: 93/107, 86.9%, P<.001); fewer worked under a Health Maintenance Organization (users: 347/417, 83.2% vs non-users: 97/107, 90.7%, P<.001) and more worked with practice partners (users: 126/417, 30.2% vs non-users: 4/107, 3.7%, P<.001). Efficiency (379/417, 90.9%) and reduction of medical errors (229/417, 54.9%) were the major enabling factors, while patient-unfriendliness (58/107, 54.2%) and limited consultation time (54/107, 50.5%) were the most commonly reported hindering factors. The key functions of computer software among eMR users consisted of electronic patient registration system (376/417, 90.2%), drug dispensing system (328/417, 78.7%) and electronic drug labels (296/417, 71.0%). SoftLink Clinic Solution was the most popular vendor (160/417, 38.4%)., Conclusions: These findings identified several physician groups who should be targeted for more assistance on eMR installation and its adoption. Future studies should address the barriers of using Internet-based eMR to enhance its adoption.

Purpose: Suboptimal adherence to antihypertensive agents leads to adverse clinical outcomes. This study aims to evaluate the association between first-line antihypertensive drug class and medication adherence in a large Chinese population., Methods: All patients prescribed ≥ one antihypertensive drug in 2001-2003 and 2005 who have paid at least two consecutive clinic visits in the public healthcare system of Hong Kong were included. We excluded patients who have followed-up in the clinics for ≤ 30 days. Interval-based Proportion of Days Covered (PDC) was used to assess medication adherence. All patients were followed-up for up to 5 years. Binary logistic regression analysis was used to evaluate the factors associated with optimal adherence, defined as PDC ≥ 80%., Results: From 147,914 eligible patients, 69.2% were adherent to the antihypertensive prescriptions. When compared with angiotensin converting enzyme inhibitors (ACEIs), patients initially prescribed α-blockers (adjusted odds ratio [AOR]=0.234, 95% C.I. 0.215-0.256), β-blockers (AOR=0.447, 95% C.I. 0.420, 0.477), thiazide diuretics (AOR=0.431 95% C.I. 0.399, 0.466) and calcium channel blockers (AOR=0.451, 95% C.I. 0.423, 0.481) were significantly less likely to be drug adherers. Angiotensin receptor blockers (ARBs) and fixed-dose combination therapies were similarly likely to be medication adherent. Older age, male gender, visits in general out-patient clinics, residence in urbanized regions, and the presence of comorbidity were positively associated with optimal drug adherence., Conclusion: Patients receiving initial prescriptions of ACEIs, ARB and combination therapy had more favorable adherence profiles than the other major antihypertensive classes in real-life clinical practice., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Background: International guidelines recommending antihypertensive prescriptions for the management of hypertension have been published in the past decade. Beta-blocker use was discouraged by a significant body of evidence and angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) were found more effective among younger patients. This study aims to evaluate the trends in prescription profiles in a large Chinese population because patterns of antihypertensive agent dispensation represent important information for physicians and policymakers., Methods: From clinical databases consisting of all patient records in the public health-care system of Hong Kong, we examined all antihypertensive prescriptions according to the drug classes (thiazide diuretics, alpha-blockers, beta-blockers, calcium channel blockers (CCBs), ACEIs, ARBs, fixed-dose combinations, and polytherapy (2, ≥3)) between 2001 and 2010. We retrieved >6.3 million prescription episodes for 223,287 patients., Results: The average age of the patients was 59.9 years (SD = 17.6), and 54.8% were women. According to prescription episodes, the most commonly prescribed medications were beta-blockers (31.7%) and CCBs (29.2%), followed by ACEIs (13.9%), thiazide diuretics (5.0%), and alpha-blockers (4.5%). Between 2001 and 2010, the prescription proportions of beta-blockers decreased from 41.5% to 21.5%, whereas that of ARBs increased from 0.5% to 1.0% (P < 0.001, χ(2) test for trend). It was found that the decline of beta-blockers (71.0% to 35.4%) and increase in ARB prescriptions (0.4% to 1.0%) were particularly marked among younger subjects aged <55 years., Conclusions: These findings provided information on the prescription patterns of antihypertensive agents in a large Chinese population. It sets a future research direction to study the various reasons influencing these drug class-specific trends.

Purpose: Adverse effects of antihypertensive therapy incur substantial cost. We evaluated whether any major classes of antihypertensive drugs were significantly associated with switching as a proxy measure of medication side effects in a large Chinese population in Hong Kong., Methods: From a clinical database, all adult patients newly prescribed an antihypertensive mono-therapy in Hong Kong between the years 2001-2003 and 2005 were included. Those who paid only one visit, died or stayed in the cohort for <180 days after the prescription, or prescribed more than one antihypertensive agent were excluded. The factors associated with switching at 180 days were evaluated by multivariate regression analyses. Age, gender, payment status, service type, district of residence, drug class, systolic and diastolic blood pressure levels were predictor variables., Results: From 250,851 subjects, 159,813 patients were eligible. A total of 6,163 (3.9%) switched their medications within 180 days. Patients prescribed thiazide diuretics had the highest switching rate (5.6%), followed by ACEIs (4.5%), CCBs (4.4%) and beta-blockers (3.2%). When compared with ACEIs, patients on thiazide diuretics were significantly more likely to be switchers (adjusted odds ratio [AOR] 1.49, 95% C.I. 1.31-1.69, p<0.001), whilst patients prescribed CCBs and beta-blockers were similarly likely to have switching. Following these patients up for 5 years showed that thiazide had the most marked increase in switching rate., Conclusions: The higher rates of switching among thiazide diuretics in this study might raise a probably greater incidence of their adverse effects in this Chinese population, yet other factors might also influence switching rates. Patients prescribed thiazide diuretics for longer term should be observed for their intolerability.