Paclitaxel-Containing Extract Exerts Anti-Cancer Activity through Oral Administration in A549-Xenografted BALB/C Nude Mice: Synergistic Effect between Paclitaxel and Flavonoids or Lignoids.

Taxus yunnanensis is a paclitaxel-containing herb with traditional usage in cancer treatment, and its extract possesses great oral bioavailability of paclitaxel. However, it is elusive whether paclitaxel-containing extract (HDS-1) can exert anti-tumor effect through oral administration and how other components contribute to its efficacy. Therefore, we investigate the oral-route anti-tumor effect of HDS-1 in A549-bearing mice. HDS-1-derived flavonoids (HDS-2) and lignoids (HDS-3) are hypothesized to contribute to HDS-1's efficacy, and their effects of enhancing enterocytic absorption and cytotoxicity of paclitaxel are validated in 2 permeability experiments and apoptosis-related assay, respectively. In vivo, A549 growth is significantly inhibited by 86.1 ± 12.94% (P < 0.01) at 600 mg/kg of HDS-1 and 65.7 ± 38.71% (P < 0.01) at 200 mg/kg. HDS-2 and HDS-3 significantly reduce the efflux ratio of paclitaxel to 2.33 and 3.70, respectively, in Caco-2 permeability experiment and reduce paclitaxel reflux in MDCK-MDR1 experiment. Furthermore, HDS-2 and HDS-3 potentiated paclitaxel-induced cytotoxicity by 19.1-22.45% (P < 0.05) and 10.52-18.03% (P < 0.05), respectively, inhibited the expression of cyclinB1, Bcl-2, and pMCL-1, and increased the percentage of necrosis cell in the condition of paclitaxel exposure. Conclusively, paclitaxel-containing extracts exert anti-cancer effects through oral administration, and flavonoid and lignoids contribute to its anti-cancer effect through simultaneously improving enterocytic absorption of paclitaxel and the cytotoxic effect of paclitaxel.

Persistence and clearance of oral human papillomavirus infections: A prospective population-based cohort study.

OBJECTIVE: This study aimed to evaluate the incidence of and factors associated with persistence and clearance of oral human papillomavirus (HPV) infections. METHOD: A prospective cohort study invited 458 subjects (231 HPV-positive and 227 HPV-negative at baseline) to attend follow-ups at 12 months. Those 231 HPV-positive subjects and 10 new infections were invited to reassessment at 24 months. We used next-gen sequencing for detection and genotyping of HPV. RESULTS: α-HPV infections showed higher persistence rates than ß/γ-HPV (22.7% vs 9.2% at 12 months [P < .05], 10.6% vs 6.8% at 24 months [P = .30]). Clearance rates of α-HPV were lower than ß/γ-HPV at 12 months (31.8% vs 45.1%; P = .05) and higher at 24 months (7.6% vs 4.8%; P = .36). Persistence of ß/γ-HPV was positively associated with males (crude odds ratio [COR] = 3.8, 95% confidence interval [CI] = 1.3-11.2), elderly (51-65 vs 16-50 years; COR = 5.1, 95% CI = 1.2-22.3), and smoking (COR = 4.3, 95% CI = 1.9-9.6). Drinking (COR = 0.5, 95% CI = 0.3-0.9), handwashing less than 90% of times before meals (COR = 0.6, 95% CI = 0.3-0.9), and using public bath more than once per month (COR = 0.5, 95% CI = 0.2-0.9) were risk factors hindering ß/γ-HPV clearance. CONCLUSIONS: This study identified factors associated with persistence and clearance of oral HPV infections among Chinese. Studies on other ethnogeographic groups may further inform prevention strategies of oral HPV infection and immunization programmes.

The adoption of hypertension reference framework: An investigation among primary care physicians of Hong Kong.

BACKGROUND: The Hong Kong Government released a Reference Framework (RF-HT) for Hypertension Care for Adults in Primary Care Settings since 2010. No studies have evaluated its adoption by primary care physicians (PCPs) since its release. AIM: We aimed to evaluate the level of PCPs' adoption of the RF-HT and the potential barriers of its use in family practice. DESIGN AND SETTING: A cross-sectional study was conducted by a self-administered validated survey among all PCPs in Hong Kong through various means. METHODS: We assessed the level of and factors associated with its adoption by multivariate logistic regression modelling. RESULT: A total of 3,857 invitation episodes were sent to 2,297 PCPs in 2014-2015. We received 383 completed questionnaires. The average score of adoption was 3.43 out of 4.00, and 47.5% of PCPs highly adopted RF-HT in their daily consultations. Male practitioners (adjusted odds ratio [aOR] = 0.524, 95% CI = 0.290-0.948, p = 0.033) and PCPs of public sector (aOR = 0.524, 95% CI = 0.292-0.940, p = 0.030) were significantly less likely to adopt the RF-HT. PCPs with higher training completion or being academic fellow are more likely to adopt RF-HT than those who were "nil to basic training completion" (aOR = 0.479, 95% CI = 0.269-0.853, p = 0.012) or "higher trainee" (aOR = 0.302, 95% CI = 0.093-0.979, p = 0.046). Three most-supported suggestions on RF-HT improvement were simplification of RF-HT, provision of pocket version and promoting in patients. CONCLUSION: Among PCP respondents, the adoption level of the RF-HT was high. These findings also highlighted some factors associated with its adoption that could inform targeted interventions for enhancing its use in clinical practice.

Prevalence and Epidemiologic Profile of Oral Infection with Alpha, Beta, and Gamma Papillomaviruses in an Asian Chinese Population.

Background: Knowledge of the prevalence of and risk factors for oral human papillomavirus (HPV) infection, especially cutaneous types, is limited. Methods: A population-based study using next-generation sequencing consecutively recruited asymptomatic individuals aged 18-64 years from a proportional sampling of the general population of Hong Kong, according to age groups, gender, and regions of residence. We examined associations of alpha-, beta-, and gamma-HPVs from oral rinse samples with participants' sociodemographics by logistic regression models. Results: The prevalence of oral HPV infection among 1426 ethnic Chinese was 15.5% (95% confidence interval [CI], 13.7%-17.5%), 2.5% (95% CI, 1.8%-3.5%), 11.9% (95% CI, 10.3%-13.6%), and 2.9% (95% CI, 2.1%-3.9%) for any type, alpha-, beta-, and gamma-HPV, respectively. Prevalence of any high-risk HPV was 0.8% (95% CI, 0.4%-1.4%), and that of HPV-16 was 0.4% (95% CI, 0.2%-0.8%). HPV-8 and HPV-98 were the most common beta types detected, while HPV-4 and HPV-SD2R were the most common gamma types. Prevalence of alpha- and beta/gamma-HPV infection showed a similar pattern of increase with age, and was higher in men than women. Smoking, drinking, oral sex, and more sexual partners were associated with alpha-HPV. Teeth brushing before sleep was protective for beta/gamma-HPVs. Discussion: The epidemiologic factors associated with oral infection with alpha-HPVs are different from those of beta/gamma-HPVs, suggesting different modes of acquisition and persistence.

Benefits and limitations of implementing Chronic Care Model (CCM) in primary care programs: A systematic review.

BACKGROUND: Chronic Care Model (CCM) has been developed to improve patients' health care by restructuring health systems in a multidimensional manner. This systematic review aims to summarize and analyse programs specifically designed and conducted for the fulfilment of multiple CCM components. We have focused on programs targeting diabetes mellitus, hypertension and cardiovascular disease. METHOD AND RESULTS: This review was based on a comprehensive literature search of articles in the PubMed database that reported clinical outcomes. We included a total of 25 eligible articles. Evidence of improvement in medical outcomes and the compliance of patients with medical treatment were reported in 18 and 14 studies, respectively. Two studies demonstrated a reduction of the medical burden in terms of health service utilization, and another two studies reported the effectiveness of the programs in reducing the risk of heart failure and other cardiovascular diseases. However, CCMs were still restricted by limited academic robustness and social constraints when they were implemented in primary care. Higher professional recognition, tighter system collaborations and increased financial support may be necessary to overcome the limitations of, and barriers to CCM implementation. CONCLUSION: This review has identified the benefits of implementing CCM, and recommended suggestions for the future development of CCM.

Association between investigator-measured body-mass index and colorectal adenoma: a systematic review and meta-analysis of 168,201 subjects.

The objective of this meta-analysis is to evaluate the odds of colorectal adenoma (CRA) in colorectal cancer screening participants with different body mass index (BMI) levels, and examine if this association was different according to gender and ethnicity. The EMBASE and MEDLINE were searched to enroll high quality observational studies that examined the association between investigator-measured BMI and colonoscopy-diagnosed CRA. Data were independently extracted by two reviewers. A random-effects meta-analysis was conducted to estimate the summary odds ratio (SOR) for the association between BMI and CRA. The Cochran's Q statistic and I2 analyses were used to assess the heterogeneity. A total of 17 studies (168,201 subjects) were included. When compared with subjects having BMI < 25, individuals with BMI 25-30 had significantly higher risk of CRA (SOR 1.44, 95% CI 1.30-1.61; I2 = 43.0%). Subjects with BMI ≥ 30 had similarly higher risk of CRA (SOR 1.42, 95% CI 1.24-1.63; I2 = 18.5%). The heterogeneity was mild to moderate among studies. The associations were significantly higher than estimates by previous meta-analyses. There was no publication bias detected (Egger's regression test, p = 0.584). Subgroup analysis showed that the magnitude of association was significantly higher in female than male subjects (SOR 1.43, 95% CI 1.30-1.58 vs. SOR 1.16, 95% CI 1.07-1.24; different among different ethnic groups (SOR 1.72, 1.44 and 0.88 in White, Asians and Africans, respectively) being insignificant in Africans; and no difference exists among different study designs. In summary, the risk conferred by BMI for CRA was significantly higher than that reported previously. These findings bear implications in CRA risk estimation.

Complete Genome Sequence of a Novel Human Papillomavirus Isolated from Oral Rinse.

A novel human papillomavirus (HPV TG550) isolated from the oral rinse of a Chinese male resident was fully characterized. The L1 open reading frame of HPV TG550 shares 82.5% nucleotide sequence similarity with its closest relative, HPV166, and clusters within the species group Gammapapillomavirus 19.

Systematic Review of Guidelines on Managing Patients with Harmful Use of Alcohol in Primary Healthcare Settings.

AIM: To appraise existing alcohol guidelines for identifying and managing harmful alcohol use in primary healthcare settings. METHODS: Seven databases and 18 health organization or medical society websites were systematically searched from inception to 31 October 2016. Guidelines in English language, developed by a national or international medical specialty society, government or health organization, and containing recommendations for identifying and managing harmful use of alcohol in primary healthcare settings, were included. The Appraisal of Guidelines Research and Evaluation II (AGREE II) instrument was used to appraise the guidelines. RESULTS: Of the 970 literature identified, 17 were included for review, with 13 guidelines developed for use in Western countries and 4 for international use. The AGREE II scores ranged from 2.0 to 5.3, out of 7. Variations in terminology of harmful alcohol use were seen, with 'harmful drinking' and 'problem drinking' being mostly used. All guidelines were in favor of screening and brief interventions due to their effectiveness and cost-effectiveness. Potential benefits and costs of applying screening and brief interventions were found, but there was a lack of evidence for long-term effects or specific populations. CONCLUSIONS: All 17 guidelines recommended screening and brief interventions due to its associated health and financial benefits. Policy makers are highly encouraged to integrate these practices into primary healthcare settings taking the drinking status, culture and resources into account. SHORT SUMMARY: Screening and brief interventions were recommended by all 17 guidelines on managing patients with harmful use of alcohol in primary healthcare settings. Policy makers and healthcare practitioners are highly encouraged to implement these recommendations.

Global temporal patterns of pancreatic cancer and association with socioeconomic development.

Pancreatic cancer induces a substantial global burden. We examined its global incidence/mortality rates and their correlation with socioeconomic development (Human Development Index [HDI] and Gross Domestic Product [GDP] in 2000 as proxy measures). Data on age-standardized incidence/mortality rates in 2012 were retrieved from the GLOBOCAN database. Temporal patterns in 1998-2007 were assessed for 39 countries according to gender. The Average Annual Percent Change (AAPC) of the incidence/mortality trends was evaluated using joinpoint regression analysis. The age-standardized incidence ranged between 0.8-8.9/100,000. When compared among countries, Brazil (AAPC = 10.4, 95%C.I. = 0.8,21) and France (AAPC = 4.7, 95%C.I. = 3.6,5.9) reported the highest incidence rise in men. The greatest increase in women was reported in Thailand (AAPC = 7, 95%C.I. = 2.1,12.1) and Ecuador (AAPC = 4.3, 95%C.I. = 1.3,7.3). For mortality, the Philippines (APCC = 4.3, 95%C.I. = 2,6.6) and Croatia (AAPC = 2, 95% C.I. = 0,3.9) reported the biggest increase among men. The Philippines (AAPC = 5.8, 95% C.I. 4.5,7.2) and Slovakia (AAPC = 3.1, 95% C.I. 0.9,5.3) showed the most prominent rise among women. Its incidence was positively correlated with HDI (men: r = 0.66; women: r = 0.70) and GDP (men: r = 0.29; women: r = 0.28, all p < 0.05), and similarly for mortality (men: r = 0.67; women: r = 0.72 [HDI]; men: r = 0.23; women: r = 0.28 [GDP]). In summary, the incidence and mortality of pancreatic cancer were rising in many countries, requiring regular surveillance.

International incidence and mortality trends of liver cancer: a global profile.

We examined the global incidence and mortality rates of liver cancer, and evaluated the association between incidence/mortality and socioeconomic development (Human Development Index [HDI] and Gross Domestic Product [GDP]) using linear regression analysis. The average annual percent change (AAPC) of the trends was evaluated from join-point regression analysis. The global incidence of liver cancer varied widely by nine-fold, and was negatively correlated with HDI (men: r = -0.232, p = 0.003; women: r = -0.369, p < 0.001) and GDP per capita (men: r = -0.164, p = 0.036; women: r = -0.212, p = 0.007). Its mortality showed a similarly negative correlation with both indices. The greatest incidence rise in men was observed in Poland (AAPC = 17.5, 95% C.I. = 5.6, 30.9) and Brazil (AAPC = 13.2, 95% C.I. = 5.9, 21.0), whereas Germany (AAPC = 6.6, 95% C.I = 2.0, 11.5) and Norway (AAPC = 6.5, 95% C.I. = 3.2, 10.0) had the greatest increase in women. The mortality rates paralleled the incidence rates in most countries. For mortality, Malta (AAPC = 11.5, 95% C.I. = 3.9, 19.8), Australia (AAPC = 6.8, 95% C.I. = 2.2, 11.5) and Norway (APCC = 5.6, 95% C.I. = 2.8, 8.5) reported the biggest increase among men; whilst Australia (AAPC = 13.4, 95% C.I. = 7.8, 19.4) and Singapore (AAPC = 7.7, 95% C.I. = 4.1, 11.5) showed the most prominent rise among women. These epidemiological data identified countries with potentially increasing trends of liver cancer for preventive actions.

Approaching the Hard-to-Reach in Organized Colorectal Cancer Screening: an Overview of Individual, Provider and System Level Coping Strategies.

BACKGROUND: Despite the proven effectiveness of colorectal cancer (CRC) screening on reduction of CRC mortality, the uptake of CRC screening remains low. Participation rate is one of determinants for the success of organized population-based screening program. This review aims to identify those who are hard-to-reach, and summarize the strategies to increase their screening rate from individual, provider and system levels. METHODS: A systematic search of electronic English databases was conducted on the factors and strategies of uptake in CRC screening for the hard-to-reach population up to May 2017. DISCUSSION: The coverage rate and participation rate are two indexes to identify the hard-to-reach population in organized CRC screening program. However, the homeless, new immigrants, people with severe mental illness, the jail intimates, and people with characteristics including lower education levels and/or low socioeconomic status, living in rural/remote areas, without insurance, and racial minorities are usually recognized as hard-to-reach populations. For them, organized screening programs offer a better coverage, while novel invitation approaches for eligible individuals and multiple strategies from primary care physicians are still needed to enhance screening rates among subjects who are hard-to-reach. Suggestions implied the effectiveness of interventions at the system level, including linkages to general practice; use of decision making tools; enlisting supports from coalition; and the continuum from screening to diagnosis and treatment. CONCLUSION: Organized CRC screening offers a system access to approach the hard-to-reach populations. To increase their uptake, multiple and novel strategies from individual, provider and system levels should be applied. For policymakers, public healthcare providers and community stakeholders, it is a test to tailor their potential needs and increase their participation rates through continuous efforts to eliminate disparities and inequity in CRC screening service.

The effectiveness of Dietary Approaches to Stop Hypertension (DASH) counselling on estimated 10-year cardiovascular risk among patients with newly diagnosed grade 1 hypertension: A randomised clinical trial.

BACKGROUND: The Dietary Approaches to Stop Hypertension (DASH) has been shown to lower blood pressure in the West. However, the real-life impact of DASH on reducing cardiovascular (CV) risk in routine clinical setting has not been studied. METHODS: A parallel-group, open-labelled, physician-blinded, randomised controlled trial was conducted in January-June 2013 and followed up for 6- and 12-months in primary care settings in Hong Kong. Patients newly diagnosed with grade 1 hypertension (aged 40-70years) who had no concomitant medical conditions requiring dietary modifications were consecutively recruited. Subjects were randomised to standard education (usual care) (n=275), or usual care plus dietitian-delivered DASH-based dietary counselling in a single one-to-one session (intervention) (n=281). Primary outcomes were the changes in estimated 10-year CV risk. RESULTS: Outcome data were available for 504 (90.6%) and 485 (87.2%) patients at 6 and 12months, respectively. There was no difference in the reduction of 10-year CV risk between the two groups at 6months (-0.13%, 95% confidence interval [95% CI] -0.50% to 0.23%, p=0.477) and 12months (-0.08%, 95% CI -0.33% to 0.18%, p=0.568). Multivariate regression analyses showed that male subjects, younger patients, current smokers, subjects with lower educational level, and those who dined out for main meals for ≥4 times in a typical week were significantly associated with no improvements in CV risk. CONCLUSIONS: The findings may not support automatic referral of newly diagnosed grade 1 hypertensive patients for further one-to-one dietitian counselling on top of primary care physician's usual care. Patients with those risk factors identified should receive more clinical attention to reduce their CV risk. CLINICAL TRIAL REGISTRATION: ChiCTR-TRC-13003014 (http://www.chictr.org.cn/enindex.aspx).

The adoption of the Reference Framework for diabetes care among primary care physicians in primary care settings: A cross-sectional study.

The prevalence of diabetes mellitus has been increasing both globally and locally. Primary care physicians (PCPs) are in a privileged position to provide first contact and continuing care for diabetic patients. A territory-wide Reference Framework for Diabetes Care for Adults has been released by the Hong Kong Primary Care Office in 2010, with the aim to further enhance evidence-based and high quality care for diabetes in the primary care setting through wide adoption of the Reference Framework.A valid questionnaire survey was conducted among PCPs to evaluate the levels of, and the factors associated with, their adoption of the Reference Framework.A total of 414 completed surveys were received with the response rate of 13.0%. The average adoption score was 3.29 (SD 0.51) out of 4. Approximately 70% of PCPs highly adopted the Reference Framework in their routine practice. Binary logistic regression analysis showed that the PCPs perceptions on the inclusion of sufficient local information (adjusted odds ratio [aOR] = 4.748, 95%CI 1.597-14.115, P = 0.005) and reduction of professional autonomy of PCPs (aOR = 1.859, 95%CI 1.013-3.411, P = 0.045) were more likely to influence their adoption level of the Reference Framework for diabetes care in daily practices.The overall level of guideline adoption was found to be relatively high among PCPs for adult diabetes in primary care settings. The adoption barriers identified in this study should be addressed in the continuous updating of the Reference Framework. Strategies need to be considered to enhance the guideline adoption and implementation capacity.