Risks and impacts of thromboembolism in patients with pancreatic cancer.

INTRODUCTION: Patients with pancreatic cancer have a high risk of thromboembolism (TE), which may increase mortality. Most relevant studies have been conducted in Western populations. We investigated risk factors for TE in a predominantly Chinese population of patients with pancreatic cancer, along with effects of TE on overall survival. METHODS: This retrospective cohort study included patients diagnosed with exocrine pancreatic cancer in Prince of Wales Hospital in Hong Kong between 2010 and 2015. Data regarding patient demographics, World Health Organization performance status, stage, treatment, TE-related information, and time of death (if applicable) were retrieved from electronic medical records. Univariate and multivariable logistic regression analyses were performed to identify risk factors for TE. Survival analyses were performed using Kaplan-Meier analysis and Cox proportional hazards regression. RESULTS: In total, 365 patients were included in the study. The overall incidence of TE (14.8%) was lower than in Western populations. In univariate logistic regression analysis, stage IV disease and non-head pancreatic cancer were significantly associated with TE (both P=0.01). Multivariable logistic regression analysis showed that stage IV disease was a significant risk factor (odds ratio=1.08, 95% confidence interval [CI]=1.00-1.17; P=0.046). Median overall survival did not significantly differ between patients with and without TE (4.88 months vs 7.80 months, hazard ratio=1.08, 95% CI=0.80-1.49; P=0.58) and between patients with TE who received anticoagulation treatment or not (5.63 months vs 4.77 months, hazard ratio=0.72, 95% CI=0.40-1.29; P=0.27). CONCLUSION: The incidence of TE was low in our Chinese cohort. Stage IV disease increased the risk of TE. Overall survival was not affected by TE or its treatment.

Clinical standards for the diagnosis and management of asthma in low- and middle-income countries.

BACKGROUND: The aim of these clinical standards is to aid the diagnosis and management of asthma in low-resource settings in low- and middle-income countries (LMICs).METHODS: A panel of 52 experts in the field of asthma in LMICs participated in a two-stage Delphi process to establish and reach a consensus on the clinical standards.RESULTS: Eighteen clinical standards were defined: Standard 1, Every individual with symptoms and signs compatible with asthma should undergo a clinical assessment; Standard 2, In individuals (>6 years) with a clinical assessment supportive of a diagnosis of asthma, a hand-held spirometry measurement should be used to confirm variable expiratory airflow limitation by demonstrating an acute response to a bronchodilator; Standard 3, Pre- and post-bronchodilator spirometry should be performed in individuals (>6 years) to support diagnosis before treatment is commenced if there is diagnostic uncertainty; Standard 4, Individuals with an acute exacerbation of asthma and clinical signs of hypoxaemia or increased work of breathing should be given supplementary oxygen to maintain saturation at 94-98%; Standard 5, Inhaled short-acting beta-2 agonists (SABAs) should be used as an emergency reliever in individuals with asthma via an appropriate spacer device for metered-dose inhalers; Standard 6, Short-course oral corticosteroids should be administered in appropriate doses to individuals having moderate to severe acute asthma exacerbations (minimum 3-5 days); Standard 7, Individuals having a severe asthma exacerbation should receive emergency care, including oxygen therapy, systemic corticosteroids, inhaled bronchodilators (e.g., salbutamol with or without ipratropium bromide) and a single dose of intravenous magnesium sulphate should be considered; Standard 8, All individuals with asthma should receive education about asthma and a personalised action plan; Standard 9, Inhaled medications (excluding dry-powder devices) should be administered via an appropriate spacer device in both adults and children. Children aged 0-3 years will require the spacer to be coupled to a face mask; Standard 10, Children aged <5 years with asthma should receive a SABA as-needed at step 1 and an inhaled corticosteroid (ICS) to cover periods of wheezing due to respiratory viral infections, and SABA as-needed and daily ICS from step 2 upwards; Standard 11, Children aged 6-11 years with asthma should receive an ICS taken whenever an inhaled SABA is used; Standard 12, All adolescents aged 12-18 years and adults with asthma should receive a combination inhaler (ICS and rapid onset of action long-acting beta-agonist [LABA] such as budesonide-formoterol), where available, to be used either as-needed (for mild asthma) or as both maintenance and reliever therapy, for moderate to severe asthma; Standard 13, Inhaled SABA alone for the management of patients aged >12 years is not recommended as it is associated with increased risk of morbidity and mortality. It should only be used where there is no access to ICS.The following standards (14-18) are for settings where there is no access to inhaled medicines. Standard 14, Patients without access to corticosteroids should be provided with a single short course of emergency oral prednisolone; Standard 15, Oral SABA for symptomatic relief should be used only if no inhaled SABA is available. Adjust to the individual's lowest beneficial dose to minimise adverse effects; Standard 16, Oral leukotriene receptor antagonists (LTRA) can be used as a preventive medication and is preferable to the use of long-term oral systemic corticosteroids; Standard 17, In exceptional circumstances, when there is a high risk of mortality from exacerbations, low-dose oral prednisolone daily or on alternate days may be considered on a case-by-case basis; Standard 18. Oral theophylline should be restricted for use in situations where it is the only bronchodilator treatment option available.CONCLUSION: These first consensus-based clinical standards for asthma management in LMICs are intended to help clinicians provide the most effective care for people in resource-limited settings.

Risk of hospitalised bronchiectasis exacerbation based on blood eosinophil counts.

SETTING: There has been growing recognition on the importance of phenotyping of airway diseases. The eosinophilic phenotype was proposed in bronchiectasis; however, there has not been any evidence on its association with the risk of hospitalised bronchiectasis exacerbations.OBJECTIVE: To investigate the association between baseline blood eosinophil count (BEC) and bronchiectasis exacerbations requiring hospitalisation with validation by an independent cohort.DESIGN: This was a retrospective cohort study.RESULTS: Over a 24-month period, 37/318 (11.6%) study participants experienced an exacerbation requiring hospitalisation. The mean baseline serum eosinophil was 135 ± 92 cells/µL in those who had exacerbations, and 188 ± 161 cells/µL in those who did not. A serum eosinophil level of 250 cells/µL at stable state was the most significant cut-off for predicting hospitalised bronchiectasis exacerbation, which was validated by the independent cohort.CONCLUSIONS: Patients with BEC below 250 cells/µL at stable state are at increased risk of having hospitalised bronchiectasis exacerbations.

Efficacy of postoperative oral metronidazole for haemorrhoidectomy pain: a randomized double-blind, placebo-controlled trial.

AIM: The aim of this work was to examine the efficacy of oral metronidazole in reducing posthaemorrhoidectomy pain versus placebo. METHOD: Forty patients were randomized to either metronidazole and standard care or placebo and standard care (21 metronidazole, 19 placebo) in a double-blinded, randomized controlled trial. The main outcome measure was posthaemorrhoidectomy pain scores over 21 days, measured on a 10-point Likert scale. RESULTS: There were no significant differences between groups with regards to age, gender, smoking status, self-reported general health or quality of life, haemorrhoid-related pain, haemorrhoid-related impact on quality of life, reported satisfaction with surgery, experience of surgery, median overall pain score or likelihood of recommending surgery to others. For reported median worst pain scores and defaecation-related pain, a trend to significance was identified between groups on days 16 and 18-21, with the metronidazole group reporting less pain. However, these differences were not significant when prespecified Bonferroni correction criteria were used. Using multilevel mixed effects modelling, the impact of time on median worst pain score was identified to be highly significant (P < 0.0001) whereas treatment allocation (placebo versus metronidazole) did not significantly affect the improvement in patients' reported pain (P = 0.8837). CONCLUSION: Our data do not support the hypothesis that postoperative metronidazole has a clinically meaningful effect on posthaemorrhoidectomy pain. This study adds to the previous literature, and implies that it should not be routinely used as an adjunct to analgesia.

Integrating postradiotherapy plasma Epstein-Barr virus DNA and TNM stage for risk stratification of nasopharyngeal carcinoma to adjuvant therapy.

BACKGROUND: After curative radiotherapy (RT) or chemoradiation (CRT), there is no validated tool to accurately identify patients for adjuvant therapy in nasopharyngeal carcinoma (NPC). Post-RT circulating plasma Epstein-Barr virus (EBV) DNA can detect minimal residual disease and is associated with recurrence and survival independent of TNM (tumor-lymph node-metastasis) stage. We aimed to develop and validate a risk model for stratification of NPC patients after completion of RT/CRT to observation or adjuvant therapy. PATIENTS AND METHODS: The prospective multicenter 0502 EBV DNA screening cohort (Hong Kong NPC Study Group 0502 trial) enrolled from 2006 to 2015 (n = 745) was used for model development. For internal validation, we pooled independent patient cohorts from prospective clinical studies enrolled from 1997 to 2006 (n = 340). For external validation, we used retrospective cohort of NPC patients treated at Sun Yat-sen University Cancer Center from 2009 to 2012 (n = 837). Eligible patients had histologically confirmed NPC of Union for International Cancer Control (UICC) 7th Edition stage II-IVB who completed curative RT/CRT with or without neoadjuvant chemotherapy, had post-RT EBV DNA tested within 120 days after RT and received no adjuvant therapy. The primary end point was overall survival (OS). We used recursive-partitioning analysis (RPA) to classify patients into groups of low, intermediate, and high risk of death. RESULTS: Combining post-RT EBV DNA level (0, 1-49, 50-499, and ≥500 copies/ml) and TNM stage (II, III, IVAB), RPA model classified patients into low-, intermediate-, and high-risk groups with 5-year OS of 89.4%, 78.5% and 37.2%, respectively. The RPA low-risk group had comparable OS to TNM stage II (5-year OS 88.5%) but identified more patients (64.8% versus stage II 28.1%) that could potentially be spared adjuvant therapy toxicity. The RPA model (c-index 0.712) showed better risk discrimination than either the TNM stage (0.604) or post-RT EBV DNA alone (0.675) with improved calibration and consistence. These results were validated in both internal and external cohorts. CONCLUSION: Combining post-RT EBV DNA and TNM stage improved risk stratification in NPC.

FEV3, FEV6 and their derivatives for detecting airflow obstruction in adult Chinese.

BACKGROUND: Forced expiratory volume in 3 seconds (FEV(3)) and 6 seconds (FEV(6)) could complement FEV(1) and forced vital capacity (FVC) for detecting airflow obstruction. OBJECTIVE: To compare FEV(1)/ FEV(6) and FEV(3)/FVC with FEV(1)/FVC in the detection of airflow obstruction. METHOD: Previous lung function data were re-analysed to establish reference values for FEV(3) and FEV(6). Data from a separate cohort of male smokers were used as test set. FEV(1), FEV(3), FEV(6), FVC, FEV(1)/FVC, FEV(1)/ FEV(6) and FEV(3)/FVC were regressed against age, standing height, weight and body mass index, and the mean and 95% confidence intervals for the lower limit of normal (LLN) values for these parameters were determined. RESULTS: The percentage of smokers with airflow obstruction in the test population using FEV(1)/FVC < LLN was 15.0%, while using FEV(1)/ FEV(6) < LLN and FEV(3)/FVC < LLN they were respectively 18.5% and 18.1%. Using FEV(1)/FVC < LLN as reference, the sensitivity and specificity of FEV(1)/ FEV(6) < LLN in identifying airflow obstruction were 82.3% and 92.8%, while those for FEV(3)/FVC < LLN were 78.5% and 92.6%; the positive and negative predictive values were 67% and 96.7% for FEV(1)/ FEV(6) < LLN and 65.3% and 96% for FEV(3)/FVC < LLN. CONCLUSION: FEV(3)/FVC < LLN and FEV(1)/ FEV(6) < LLN are comparable to FEV(1)/FVC < LLN for detecting airflow obstruction. FEV(3)/FVC < LLN could be useful in screening for airflow obstruction, while FEV(1)/ FEV(6) < LLN is useful in detecting airflow limitation in the elderly or in subjects with severe airflow obstruction.

Effects of azithromycin in bronchiolitis obliterans syndrome after hematopoietic SCT--a randomized double-blinded placebo-controlled study.

Bronchiolitis obliterans syndrome (BOS) is an important complication after hematopoietic SCT (HSCT). Recent observations suggested that azithromycin might improve lung function in BOS after HSCT. We conducted a randomized double-blinded placebo-controlled study on azithromycin in patients with BOS after HSCT. The treatment group (n=10) received oral azithromycin 250 mg daily while the control group (n=12) received placebo daily for 12 weeks. Respiratory symptoms were assessed by the St George Respiratory Questionnaires and spirometry at baseline (drug commencement), 1, 2, 3 (drug cessation) and 4 months (1 month after drug cessation). There was no significant difference in the baseline demographic characteristics between the treatment and the control groups in age, gender, time from HSCT to BOS, time since diagnosis of BOS, chronic GVHD, baseline respiratory symptom scores and baseline forced expiratory volume in 1 s (FEV(1)). Throughout and after 3 months of treatment, there were no significant changes in respiratory symptom scores and FEV(1) measurements between the treatment and the control groups. In conclusion, there was no significant benefit of 3 months of oral azithromycin on the respiratory symptoms and lung function in patients with relatively late BOS after HSCT in this randomized placebo-controlled study.

Serum adipocyte-fatty acid binding protein level is elevated in severe OSA and correlates with insulin resistance.

Obstructive sleep apnoea (OSA) is associated with insulin resistance and metabolic syndrome. There is evidence that adipocyte-fatty acid binding protein (A-FABP) may be involved in the development of cardiometabolic dysfunction. The present authors hypothesise that A-FABP is upregulated in OSA. A total of 124 males without hypertension, diabetes mellitus, hyperlipidaemia or cardiovascular disease were recruited and underwent polysomnography. Serum A-FABP levels showed significant positive correlations with duration of oxygen desaturation and minimal oxygen saturation, fasting insulin and insulin resistance index by homeostasis model assessment. When subjects were divided into tertiles according to apnoea/hypopnoea index (AHI), serum A-FABP levels were significantly higher in the group with AHI >/=34.4 events.h(-1) than the groups with AHI 13.2-34.4 events.h(-1) or with AHI <13.2 events.h(-1). Serum A-FABP levels were significantly higher in the AHI >/=34.4 group than obesity-matched subjects with AHI <34.4 events.h(-1). Serum adipocyte-fatty acid binding protein levels correlated with obstructive sleep apnoea and insulin resistance, independently of obesity, and were significantly higher in severe obstructive sleep apnoea. Adipocyte-fatty acid binding protein may play a role in obstructive sleep apnoea and metabolic dysfunction.

Obstructive sleep apnoea in Asia.

Obstructive sleep apnoea (OSA) syndrome is the commonest sleep-related breathing disorder worldwide. In Asia, the prevalence of symptomatic OSA in middle-aged men and women is 4.1-7.5% and 2.1-3.2%, respectively. These prevalence rates are similar to those reported in Caucasian populations. Obesity, an established major risk factor for OSA, is less common among Asians, and the reported values of body mass indices (BMIs) of Asians with OSA are lower than in their Caucasian counterparts. However, these population-based studies have consistently demonstrated that obesity is still the major risk factor for OSA in Asians, while other studies have suggested that craniofacial structural factors may make a greater contribution towards development of OSA in Asians than in Caucasians. Sleep medicine is in a developmental stage in many Asian countries, and the condition is likely under-recognised. Although sleep laboratories have been set up in various countries in Asia, the availability of this service is very limited. Continuous positive airway pressure is available in most parts of Asia, but financial constraints may limit its utility. Oral appliances have been postulated to have a greater role in the management of OSA in Asian patients, as they are likely to have more modifiable factors in their craniofacial structures, but this is yet to be proven. There is a great need for research and health care development on sleep disordered breathing in Asia, and the solution will only come with efforts towards promotion of awareness of this condition in both professional and lay communities.

The clinical value of autofluorescence bronchoscopy for the diagnosis of lung cancer.

The aim of this study was to evaluate the role of autofluorescence bronchoscopy (AFB) in the routine work-up of lung cancer. Consecutive patients with atypical or suspicious cells in sputum or bronchial aspirate, no localising abnormality on chest radiography and nondiagnostic white-light bronchoscopic (WLB) results were recruited. WLB and AFB were performed sequentially during the same session. All abnormal areas detected by WLB, AFB or both were sampled and the biopsy specimens sent for histological examination. Sixty-two patients were recruited within the 32-month study period. Seventeen had no endobronchial lesion detected. Among the 45 patients with endobronchial lesions, 37 had lesions with a histopathological grade of mild dysplasia or less; of the eight patients who had a lesion with a histological grade of moderate dysplasia or worse, five were found to have lung cancer, two invasive lung cancer and three an intra-epithelial neoplasm (severe dysplasia). Lesions showing moderate dysplasia or worse were more commonly found in patients with suspicious cells than in those with atypical cells on sputum examination. AFB was more sensitive than WLB (91 versus 58%) at detecting these lesions, but less specific (26 versus 50%). A combination of white-light and autofluorescence bronchoscopy can increase the diagnostic yield of this invasive procedure in patients exhibiting abnormal sputum cytology.

Application of four watershed acidification models to Batchawana Watershed, Canada.

Four watershed acidification models (TMWAM, ETD, ILWAS, and RAINS) are reviewed and a comparison of model performance is presented for a common watershed. The models have been used to simulate the dynamics of water quantity and quality at Batchawana Watershed, Canada, a sub-basin of the Turkey Lakes Watershed. The computed results are compared with observed data for a four-year period (Jan. 1981-Dec. 1984). The models exhibit a significant range in the ability to simulate the daily, monthly and seasonal changes present in the observed data. Monthly watershed outflows and lake chemistry predictions are compared to observed data. pH and ANC are the only two chemical parameters common to all four models. Coefficient of efficiency (E), linear (r) and rank (R) correlation coefficients, and regression slope (s) are used to compare the goodness of fit of the simulated with the observed data. The ILWAS, TMWAM and RAINS models performed very well in predicting the monthly flows, with values of r and R of approximately 0.98. The ETD model also showed strong correlations with linear (r) and rank (R) correlation coefficients of 0.896 and 0.892, respectively. The results of the analyses showed that TMWAM provided the best simulation of pH (E=0.264, r=0.648), which is slightly better than ETD (E=0.240, r=0.549), and much better than ILWAS (E=-2.965, r=0.293), and RAINS (E=-4.004, r=0.473). ETD was found to be superior in predicting ANC (E=0.608, r=0.781) as compared to TMWAM (E=0.340, r=0.598), ILWAS (E=0.275, r=0.442), and RAINS (E=-1.048, r=0.356). The TMWAM model adequately simulated SO4 over the four-year period (E=0.423, r=0.682) but the ETD (E=-0.904, r=0.274), ILWAS (E=-4.314, r=0.488), and RAINS (E=-6.479, r=0.126) models all performed poorer than the benchmark model (mean observed value).

An expert system for water quality modelling.

The RAISON-micro (Regional Analysis by Intelligent System ON a micro-computer) expert system is being used to predict the effects of mine effluents on receiving waters in Ontario. The potential of this system to assist regulatory agencies and mining industries to define more acceptable effluent limits was shown in an initial study. This system has been further developed so that the expert system helps the model user choose the most appropriate model for a particular application from a hierarchy of models. The system currently contains seven models which range from steady state to time dependent models, for both conservative and nonconservative substances in rivers and lakes. The menu driven expert system prompts the model user for information such as the nature of the receiving water system, the type of effluent being considered, and the range of background data available for use as input to the models. The system can also be used to determine the nature of the environmental conditions at the site which are not available in the textual information database, such as the components of river flow. Applications of the water quality expert system are presented for representative mine sites in the Timmins area of Ontario.

An expert system for assessing safety and security of heterogeneous public water sources.

We have implemented a diagnostic system designed to advise on the likely causes of sanitary problems with public water sources. The approach to the problem makes extensive use of rule based expert systems and multi media information (maps, data, text, expert knowledge). The rules were based on actual water survey data, with a weighting scheme designed to highlight causes of health risks approximately in reverse order of importance (where such order may be presumed to exist). Out put is a vailable in one of several languages.

Evaluation of the effects of acid precipitation in eastern Canada using the raison system.

Evaluations have been made of the key chemical factors in the aquatic effects upon surface waters due to acidic precipitation in eastern Canada. The region of Canada east of the Manitoba/Ontario border was divided into 22 aggregates and assessments of inorganic and organic ion chemistry appraised relative to sulphate deposition rates and distributions. Aquatic sensitivity is largely dominated by the concentration, distribution and magnitude of SO inf4 (sup2-) (sulphate) deposition and by the prevalent geology and derived soils found in each aggregate. The RAISON system provided an adaptable and highly flexible platform to evaluate interactively, multiple data sets of divergent characteristics. Attributes usually associated with geographical information systems are significantly augmented by quantitative numerical and stochastic capabilities that were used extensively in this study.

A knowledge-based approach to regional acidification modelling.

Data from over 2000 stations and knowledge from experts on atmospheric transport, soil geochemistry, lake chemistry, wetland processes and acidification modelling were assembled in an expert system. The data were grouped by aggregates of tertiary watersheds based on water chemistry knowledge. A set of expert rules was used to determine which of six existing models was most appropriate for a given set of data. Comparison of computed and observed alkalinity indicated median relative errors from 11.3-17.9%, with regression slopes ranging from 0.91-1.18 and regression coefficients between 0.82 and 0.99. The expert model performance was further confirmed with paleolimnological data and other independent sets of data. The sensitivity of the predicted alkalinity was illustrated by changing some of the rules. Given that the rules were acceptable by experts and produced reasonable agreement with observations, the knowledge-based system seemed a viable approach to the impact assessment of acidic deposition.

The predicted effect of SO2 emission controls on the water quality of eastern Canadian lakes.

Changes in SO inf4 (sup2-) deposition predicted to occur in response to implementation of announced SO2 emission control programs in Canada and the U.S.A. have been used as input to water chemistry models thereby giving an estimate of the changes in lake acid neutralizing capacity (ANC) and pH that can be expected from these programs. Eastern Canada has been divided into 22 subregions for the purpose of this analysis. Relative to the current level (1982-86) of SO inf4 (sup2-) deposition (Scenario 1), the effect of the Canadian SO2 emission control program alone (Scenario 2) is compared to that obtained when controls are implemented throughout North America (Scenarios 3 and 4). SO2 emission reduction will effect a shrinkage of the high wet SO inf4 (sup2-) deposition field in NE North America such that under Scenario 4 conditions, almost no area will remain in Canada that receives >20 kg ha(-1) yr(-1). The greatest decrease in deposition and resulting change in lake chemistry occurs in southern Ontario and southwestern Quebec. ANC distributions shift to higher concentrations and the percentage of lakes having pH<6 decreases in these areas. The Atlantic Provinces will obtain only a minor benefit from the control programs, i.e. experiencing only a small decrease in deposition and improvement in water quality. High sensitivity of the terrain in many parts of Atlantic Canada means that large numbers of lakes will remain acidic (i.e. ANC<0) and/or have pH<6 (an important biological threshold) even after full implementation of the current plans for SO2 control in Canada and the U.S.