Hospitalized acute exacerbation in chronic obstructive pulmonary disease - impact on long-term renal outcomes.

INTRODUCTION: Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is a common and preventable event in patients with chronic obstructive pulmonary disease (COPD). Data regarding the impact of AECOPD on short- and long-term renal outcomes are lacking. METHODS: We included all COPD patients who were followed at Queen Mary Hospital (QMH) in year 2015 and reviewed their clinical/renal outcomes in subsequent five years. Relationships between AECOPD and adverse renal outcomes were evaluated. RESULTS: 371 COPD patients were included. 169 patients had hospitalized AECOPD in past one year (HAE group) while 202 patients did not (non-HAE group). 285 patients (76.8%) had renal progression/death and 102 (27.5%) patients developed acute kidney injury (AKI). HAE group showed a more rapid eGFR decline than non-HAE group (-4.64 mL/min/1.73m2/year vs. -2.40 mL/min/1.73m2/year, p = 0.025). HAE group had significantly higher risk for renal progression/death at 5 years [adjusted OR (aOR) 2.380 (95% CI = 1.144-4.954), p = 0.020]. The frequency of hospitalized AECOPD in past 3 years, any AECOPD in past 3 years, hospitalized AECOPD in past 3 years were also predictive of renal progression/death at 5 years [aOR were 1.176 (95% CI = 1.038- 1.331), 2.998 (95% CI = 1.438-6.250) and 2.887 (95% CI = 1.409-5.917) respectively; p = 0.011, 0.003 and 0.004]. HAE group also showed significantly higher risk of AKI [adjusted HR (aHR) 2.430; 95% CI = 1.306-4.519, p = 0.005]. CONCLUSIONS: AECOPD, in particular HAE, was associated with increased risk of renal progression/death and AKI. Prevention of AECOPD, especially HAE, may potentially improve short- and long-term renal outcomes in COPD patients.

Cardiovascular outcomes in obstructive sleep apnoea and implications of clinical phenotyping on effect of CPAP treatment.

BACKGROUND: There is a growing awareness of the heterogeneity of obstructive sleep apnoea (OSA). Clinical trials of CPAP treatment on cardiovascular protection have been mostly negative. We aimed to assess the association between polysomnographic parameters and incident major adverse cardiovascular events (MACEs), and to investigate if the CPAP effect could be better delineated among clinical subgroups. METHODS: This sleep cohort study was conducted using a clinical database and territory-wide electronic health administration data in Hong Kong. Cox regressions were used to calculate HRs. Latent class analysis was used to cluster patients with OSA according to clinical and polysomnographic features. RESULTS: Of 1860 eligible Chinese subjects who underwent polysomnography (2006-2013), 1544 (83%) had OSA. Over median follow-up of 8.3 years, 278 (14.9%) experienced MACEs. Apnoea-hypopnoea index (AHI) did not predict MACEs (HR: 0.95; 95% CI 0.76 to 1.17), whereas sleep time with oxygen saturation <90% (TST90) (HR: 1.41; 95% CI 1.10 to 1.81) was an independent predictor of MACEs, as were wake and nocturnal heart rate. In moderate-severe OSA (n=1108) who were indicated for CPAP treatment, regular CPAP was not associated with reduction of incident MACEs. Further cluster analysis identified a subgroup (n=333) who was younger, more obese, had more severe OSA (higher AHI and TST90) and more cardiovascular risks, in whom regular CPAP was associated with a lower risk of MACEs (HR:0.49, 95% CI 0.25 to 0.95). CONCLUSIONS: OSA-related TST90 and mean heart rate, but not AHI, were robust predictors of MACEs. A clinical phenotype subgroup who demonstrated beneficial effect of CPAP treatment was identified.

USPSTF2013 versus PLCOm2012 lung cancer screening eligibility criteria (International Lung Screening Trial): interim analysis of a prospective cohort study.

BACKGROUND: Lung cancer is a major health problem. CT lung screening can reduce lung cancer mortality through early diagnosis by at least 20%. Screening high-risk individuals is most effective. Retrospective analyses suggest that identifying individuals for screening by accurate prediction models is more efficient than using categorical age-smoking criteria, such as the US Preventive Services Task Force (USPSTF) criteria. This study prospectively compared the effectiveness of the USPSTF2013 and PLCOm2012 model eligibility criteria. METHODS: In this prospective cohort study, participants from the International Lung Screening Trial (ILST), aged 55-80 years, who were current or former smokers (ie, had ≥30 pack-years smoking history or ≤15 quit-years since last permanently quitting), and who met USPSTF2013 criteria or a PLCOm2012 risk threshold of at least 1·51% within 6 years of screening, were recruited from nine screening sites in Canada, Australia, Hong Kong, and the UK. After enrolment, patients were assessed with the USPSTF2013 criteria and the PLCOm2012 risk model with a threshold of at least 1·70% at 6 years. Data were collected locally and centralised. Main outcomes were the comparison of lung cancer detection rates and cumulative life expectancies in patients with lung cancer between USPSTF2013 criteria and the PLCOm2012 model. In this Article, we present data from an interim analysis. To estimate the incidence of lung cancers in individuals who were USPSTF2013-negative and had PLCOm2012 of less than 1·51% at 6 years, ever-smokers in the Prostate Lung Colorectal and Ovarian Cancer Screening Trial (PLCO) who met these criteria and their lung cancer incidence were applied to the ILST sample size for the mean follow-up occurring in the ILST. This trial is registered at ClinicalTrials.gov, NCT02871856. Study enrolment is almost complete. FINDINGS: Between June 17, 2015, and Dec 29, 2020, 5819 participants from the International Lung Screening Trial (ILST) were enrolled on the basis of meeting USPSTF2013 criteria or the PLCOm2012 risk threshold of at least 1·51% at 6 years. The same number of individuals was selected for the PLCOm2012 model as for the USPSTF2013 criteria (4540 [78%] of 5819). After a mean follow-up of 2·3 years (SD 1·0), 135 lung cancers occurred in 4540 USPSTF2013-positive participants and 162 in 4540 participants included in the PLCOm2012 of at least 1·70% at 6 years group (cancer sensitivity difference 15·8%, 95% CI 10·7-22·1%; absolute odds ratio 4·00, 95% CI 1·89-9·44; p<0·0001). Compared to USPSTF2013-positive individuals, PLCOm2012-selected participants were older (mean age 65·7 years [SD 5·9] vs 63·3 years [5·7]; p<0·0001), had more comorbidities (median 2 [IQR 1-3] vs 1 [1-2]; p<0·0001), and shorter life expectancy (13·9 years [95% CI 12·8-14·9] vs 14·8 [13·6-16·0] years). Model-based difference in cumulative life expectancies for those diagnosed with lung cancer were higher in those who had PLCOm2012 risk of at least 1·70% at 6 years than individuals who were USPSTF2013-positive (2248·6 years [95% CI 2089·6-2425·9] vs 2000·7 years [1841·2-2160·3]; difference 247·9 years, p=0·015). INTERPRETATION: PLCOm2012 appears to be more efficient than the USPSTF2013 criteria for selecting individuals to enrol into lung cancer screening programmes and should be used for identifying high-risk individuals who benefit from the inclusion in these programmes. FUNDING: Terry Fox Research Institute, The UBC-VGH Hospital Foundation and the BC Cancer Foundation, the Alberta Cancer Foundation, the Australian National Health and Medical Research Council, Cancer Research UK and a consortium of funders, and the Roy Castle Lung Cancer Foundation for the UK Lung Screen Uptake Trial.

Implementation of evidence on management of pleural diseases: insights from a territory-wide survey of clinicians in Hong Kong.

BACKGROUND: Major advances in management of common pleural diseases have taken place in the past decade. However, pleural diseases are often managed by physicians of diverse training background and research on implementation of new knowledge is scanty. We aim to evaluate the practice pattern in pleural medicine among physicians in Hong Kong, for identification of possible gaps for clinical service improvement. METHODS: The Hong Kong Thoracic Society undertook a cross-sectional questionnaire survey in 2019, targeting clinicians of various subspecialties in internal medicine and levels of experience (basic and higher trainees, specialists) from twelve regional hospitals of diverse service scopes throughout Hong Kong. Respondents were selected by non-probability quota sampling. The questionnaire tool consisted of 46 questions covering diagnostic and therapeutic aspects of common pleural diseases. The responses were anonymous, and analysed independently using SPSS statistics software. RESULTS: The survey collected 129 responses, 47(36%) were from clinicians specialized in respiratory medicine. Majority of the respondents (98%) managed pleural diseases, including performing pleural procedures in their practice. Fifty-five percent of all the respondents had not received any formal training in transthoracic ultrasonography. A significant proportion of clinicians were unaware of pleuroscopy for investigation of exudative pleural effusion, indwelling pleural catheter for recurrent malignant pleural effusion, and combined intra-pleural Alteplase plus DNase for treatment of pleural infection (30%, 15% and 70% of non-respiratory clinicians respectively). Significant heterogeneity was found in the management of pleural infection, malignant pleural effusion and pneumothorax among respiratory versus non-respiratory clinicians. Contributing factors to the observed heterogeneity included lack of awareness or training, limited accessibility of drugs, devices, or dedicated service support. CONCLUSION: Significant heterogeneity in management of pleural diseases was observed among medical clinicians in Hong Kong. Continuous medical education and training provision for both specialists and non-specialists has to be strengthened to enhance the implementation of advances, improve quality and equity of healthcare provision in pleural medicine.

A New Contact Lens Sensor System for Continuous Intraocular Pressure Monitoring: Evaluation of Safety and Tolerability.

PURPOSE: To assess the safety and tolerability of a new contact lens sensor (CLS) system for continuous 3- and 24-hr intraocular pressure (IOP) monitoring in human eyes. METHODS: Twenty-five subjects were recruited for 3-hr IOP measurement by CLS. Corneal fluorescein staining (CFS) scores were evaluated before and after measurement. Then, 30 participants (10 normal subjects and 20 glaucoma patients) were recruited for 24-hr IOP monitoring. Ocular surface disease index (OSDI) was assessed before and one day after measurement. Contact lens dry eye questionnaire-8 was assessed immediately after measurement. Visual analog scale of discomfort was measured before, immediately after, and one day after measurement. Best-corrected visual acuity (BCVA), tear break-up time (TBUT), and CFS were assessed before, immediately after, and 1 day after measurement. RESULTS: All participants completed 3- or 24-hr IOP measurement by CLS. Corneal fluorescein staining increased from 0.6±0.7 to 2.4±1.5 after 3-hr IOP measurement ( P <0.001). For participants undergoing 24-hr IOP monitoring, OSDI increased from 9.1±9.7 to 18.0±12.4 ( P =0.001). CLDEQ-8 score was 11.6±5.8. Visual analog scale increased from 11.1±14.2 to 35.2±21.8 after measurement ( P <0.001) and decreased to 26.7±18.4 one day later ( P <0.001 compared with baseline). BCVA decreased from 1.0±0.01 to 0.8±0.1 ( P <0.001) and returned to 0.9±0.1 after one day ( P <0.001 compared with baseline). TBUT decreased from 5.1±3.9 to 2.6±1.5 s ( P =0.001) and returned to 4.8±2.5 s ( P =0.465 compared with baseline). Corneal fluorescein staining increased from 0.7±0.9 to 4.3±0.8 ( P <0.001) and dropped to 0.8±0.7 ( P =0.599 compared with baseline). No significant difference was found for all variations of indicators between normal subjects and glaucoma patients ( P >0.1 for all comparisons). CONCLUSIONS: The CLS shows a great potential for a safe and tolerable 24-hr IOP monitoring in normal subjects and glaucoma patients. Clinical attention to the worsening signs and symptoms after measurement is required.

Circulating adipocyte fatty acid-binding protein is reduced by continuous positive airway pressure treatment for obstructive sleep apnea-a randomized controlled study.

PURPOSE: The circulating level of adipocyte fatty acid-binding protein (AFABP), a biomarker with prognostic and therapeutic importance in metabolic disorders, has been shown to be elevated in obstructive sleep apnea (OSA). This randomized controlled study aimed to investigate the effect of continuous positive airway pressure (CPAP) treatment for OSA on AFABP levels. METHODS: Consecutive subjects attending sleep study were invited if they were confirmed to have severe OSA and were free of metabolic diseases. Participants were randomized (1:1) into CPAP or observation group for 4 weeks. Demographics, anthropometric data, and circulating biomarkers were checked at baseline and after the 4-week study period. RESULTS: Ninety subjects were randomized. The mean age was 46 ± 9 years old; 82% were male. Their mean body mass index (BMI) was 29 ± 5 kg/m2. By intention-to-treat approach, the CPAP group showed significant reductions in Epworth sleepiness scale and morning systolic blood pressure (- 7.2 mmHg, - 12.7 to - 1.7 mmHg, p = 0.011), but no significant difference in AFABP, adiponectin, C-reactive protein (CRP), and 8-isoprostane levels. In the per-protocol analysis, when only those who were compliant to CPAP were included, a significant reduction in AFABP (- 7.32 ng/ml, - 13.58, - 1.06, p = 0.023) were found in the CPAP-treated group compared with the control group, along with improvements in clinical parameters. Changes in AFABP were independently associated with both systolic blood pressure (ß = 0.289, p = 0.028) and diastolic blood pressure (ß = 0.217, p = 0.030). CONCLUSION: CPAP therapy used regularly over 4 weeks for severe OSA lowered circulating AFABP level, suggesting a potential beneficial effect of OSA treatment on alleviating metabolic risks. TRIAL REGISTRATION: The research protocol was registered at the National Institutes of Health clinical trials registry (NCT01173432).

Rapid versus gradual lung function decline in bronchiolitis obliterans syndrome after haematopoietic stem cell transplantation is associated with survival outcome.

BACKGROUND AND OBJECTIVE: Bronchiolitis obliterans syndrome (BOS) after haematopoietic stem cell transplantation (HSCT) presents with lung function decline. The pattern of lung function decline after BOS diagnosis could impact prognostication of BOS as a complication after HSCT. The aim of this study was to assess the impact of lung function decline on overall survival (OS) in BOS subjects. METHODS: Subjects with BOS were compared to those without BOS and matched for age, gender, primary diagnoses, conditioning regimes and chronic graft versus host disease. Lung function tests at baseline, at BOS diagnosis and every 3 months after HSCT were evaluated. RESULTS: Of the 1461 subjects undergoing allogeneic HSCT (allo-HSCT) between 1998 and 2015, 95 (6.5%) were diagnosed with BOS. A total of 159 matched HSCT recipients without BOS were identified. A 25% decline in FEV1 within the first 3 months after BOS diagnosis would separate BOS subjects into a subgroup with initial rapid decline and another subgroup with initial gradual decline in lung function. The rapid decline group showed lower subsequent lung function parameters and significantly worse OS compared to the gradual decline group (P = 0.013). CONCLUSION: Post-HSCT BOS subjects with initial rapid lung function decline within 3 months after BOS diagnosis will have significantly poorer lung function and worse OS compared to those with initial gradual decline in lung function after BOS diagnosis. HSCT BOS patients with rapid initial decline in lung function warrant closer monitoring for the development of other post-HSCT complications that could affect their survival.

High myopes have lower normalised corneal tangent moduli (less 'stiff' corneas) than low myopes.

PURPOSE: To compare corneal tangent moduli between low and high myopes. METHODS: Corneal hysteresis (CH) and corneal resistance factor (CRF) of 32 low and 32 high myopes were obtained using an Ocular Response Analyzer, followed by a corneal indentation device that measured corneal stiffness. Corneal topography, pachymetry, Goldmann applanation tonometry intraocular pressure (GAT-IOP), and corneal compensated intraocular pressure (IOPcc) were also obtained. Corneal tangent modulus was calculated on the basis of corneal stiffness, central corneal thickness and corneal radius. Comparisons between groups and associations between corneal biomechanical and ocular parameters were performed. RESULTS: Corneal tangent moduli were positively correlated with GAT-IOP (R2 = 0.078, p = 0.025), and IOPcc (R2 = 0.12, p = 0.006). Despite similarity in corneal thickness and radius, high myopes exhibited a significantly higher IOPcc (16.4 ± 2.51 mmHg) than low myopes (13.1 ± 1.96 mmHg; t(62) = -5.57, p < 0.0001). Both groups had similar corneal stiffness (0.063 ± 0.0085 and 0.063 ± 0.0079 N mm-1 for low and high myopes, respectively) and CRF (9.6 ± 1.58 and 9.5 ± 1.90 mmHg for low and high myopes, respectively). Moreover, high myopes exhibited a significantly lower CH (9.5 ± 1.51 mmHg) than low myopes (10.6 ± 1.38 mmHg; t(62) = 2.92, p = 0.005). After normalising corneal tangent moduli to the mean intraocular pressure in normal eyes (15.5 mmHg) using IOPcc, high myopes showed a significantly lower corneal tangent moduli (0.47 ± 0.087 MPa) than low myopes (0.57 ± 0.099 MPa; t(62) = 4.17, p < 0.0001). CONCLUSIONS: High myopes had lower normalised corneal tangent moduli than low myopes, which indicated that their corneas were less stiff. This is the first in vivo study comparing elastic moduli of the cornea in different refractive groups. Further studies are warranted to understand whether a less stiff cornea is a cause for or an outcome from myopia development.

Effect of an Indwelling Pleural Catheter vs Talc Pleurodesis on Hospitalization Days in Patients With Malignant Pleural Effusion: The AMPLE Randomized Clinical Trial.

Importance: Indwelling pleural catheter and talc pleurodesis are established treatments for malignant pleural effusions among patients with poor prognosis. Objective: To determine whether indwelling pleural catheters are more effective than talc pleurodesis in reducing total hospitalization days in the remaining lifespan of patients with malignant pleural effusion. Design, Setting, and Participants: This open-label, randomized clinical trial included participants recruited from 9 centers in Australia, New Zealand, Singapore, and Hong Kong between July 2012 and October 2014; they were followed up for 12 months (study end date: October 16, 2015). Patients (n = 146) with symptomatic malignant pleural effusion who had not undergone indwelling pleural catheter or pleurodesis treatment were included. Interventions: Participants were randomized (1:1) to indwelling pleural catheter (n = 74) or talc pleurodesis (n = 72), minimized by malignancy (mesothelioma vs others) and trapped lung (vs not), and stratified by region (Australia vs Asia). Main Outcomes and Measures: The primary end point was the total number of days spent in hospital from procedure to death or to 12 months. Secondary outcomes included further pleural interventions, patient-reported breathlessness, quality-of-life measures, and adverse events. Results: Among the 146 patients who were randomized (median age, 70.5 years; 56.2% male), 2 withdrew before receiving the randomized intervention and were excluded. The indwelling pleural catheter group spent significantly fewer days in hospital than the pleurodesis group (median, 10.0 [interquartile range [IQR], 3-17] vs 12.0 [IQR, 7-21] days; P = .03; Hodges-Lehmann estimate of difference, 2.92 days; 95% CI, 0.43-5.84). The reduction was mainly in effusion-related hospitalization days (median, 1.0 [IQR, 1-3] day with the indwelling pleural catheter vs 4.0 (IQR, 3-6) days with pleurodesis; P < .001; Hodges-Lehmann estimate, 2.06 days; 95% CI, 1.53-2.58). Fewer patients randomized to indwelling pleural catheter required further ipsilateral invasive pleural drainages (4.1% vs 22.5%; difference, 18.4%; 95% CI, 7.7%-29.2%). There were no significant differences in improvements in breathlessness or quality of life offered by indwelling pleural catheter or talc pleurodesis. Adverse events were seen in 22 patients in the indwelling pleural catheter group (30 events) and 13 patients in the pleurodesis group (18 events). Conclusions and Relevance: Among patients with malignant pleural effusion, treatment with an indwelling pleural catheter vs talc pleurodesis resulted in fewer hospitalization days from treatment to death, but the magnitude of the difference is of uncertain clinical importance. These findings may help inform patient choice of management for pleural effusion. Trial Registration: anzctr.org.au Identifier: ACTRN12611000567921.

Obstructive sleep apnoea, insulin resistance and adipocytokines.

Obstructive sleep apnoea (OSA) is associated with multiple cardiometabolic abnormalities. Obesity is considered a major risk factor for the development of OSA, and it is also an established risk factor for insulin resistance and other cardiometabolic disorders. The enigma remains whether OSA has any causal role in the adverse metabolic profile, independent of or beyond that due to obesity. Sleep apnoeas and hypopnoeas result directly in intermittent hypoxaemia and cerebral arousals, both of which may evoke a cascade of downstream biologic responses in various body tissues and cells. Adipose tissue is a major source of adipocytokines many of which play important roles in the regulation of various metabolic functions. It is hypothesized that OSA may, through its unique pathophysiology, affect metabolic function through modulation of production or action of adipocytokines. This review focuses on insulin resistance, glucose metabolism and relevant adipocytokines in the context of OSA.

The effectiveness of lung cancer MDT and the role of respiratory physicians.

There is an increasing trend for the use of multi-disciplinary teams (MDT) in the management of complex medical conditions. The latter may include various cancers, including lung cancer. However, the use of MDT is not restricted to cancer management, but may include complex conditions like diabetes and other non-malignant disorders. There is an increasing trend to use MDT in the investigation and management of patients with suspected or proven lung cancer. This review examines the evidence that supports the efficacy, or otherwise, of lung cancer management in a MDT as opposed to individual care, who should be a member of a lung cancer MDT, and the specific role of the respiratory physician in a lung cancer MDT. Although it may seem to make common sense to manage lung cancer in a MDT setting, there is actually little in the way of high quality data to support this concept. The logistic and ethical difficulties in researching this issue are highlighted in this review.

Electronic cigarettes. A position statement of the forum of international respiratory societies.

BACKGROUND: Awareness and usage of electronic cigarettes has exponentially increased during the last few years, especially among young people and women in some countries. The rapid acceptance of electronic cigarettes may be attributed in part to the perception created by marketing and the popular press that they are safer than combustible cigarettes. GOALS: To alert and advise policy makers about electronic cigarettes and their potential hazards. METHODS: Using The Union's position paper on electronic cigarettes as the starting template, the document was written using an iterative process. Portions of the manuscript have been taken directly from the position papers of participating societies. RESULTS: Because electronic cigarettes generate less tar and carcinogens than combustible cigarettes, use of electronic cigarettes may reduce disease caused by those components. However, the health risks of electronic cigarettes have not been adequately studied. Studies looking at whether electronic cigarettes can aid smoking cessation have had inconsistent results. Moreover, the availability of electronic cigarettes may have an overall adverse health impact by increasing initiation and reducing cessation of combustible nicotine delivery products. CONCLUSIONS: The health and safety claims regarding electronic nicotine delivery devices should be subject to evidentiary review. The potential benefits of electronic cigarettes to an individual smoker should be weighed against potential harm to the population of increased social acceptability of smoking and use of nicotine, the latter of which has addictive power and untoward effects. As a precaution, electronic nicotine delivery devices should be restricted or banned until more information about their safety is available. If they are allowed, they should be closely regulated as medicines or tobacco products.

Repeatability of a novel corneal indentation device for corneal biomechanical measurement.

PURPOSE: The aim of the study was to evaluate the repeatability of a new device for measuring corneal biomechanics. METHODS: Twenty-nine normal subjects aged 20-28 years (23.4 ± 1.7 years) underwent measurements of corneal stiffness and tangent elastic modulus using a novel corneal indentation device. Corneal topography, axial biometry and Goldmann applanation tonometry were also performed during the visit. Subjects returned after about 1 week, at approximately the same time, and with the corneal biomechanics, corneal topography and Goldmann applanation tonometry measured again. Both the intrasession and intersession repeatability was assessed. RESULTS: Both the corneal stiffness and tangent elastic modulus demonstrated good intrasession repeatability (corneal stiffness: coefficient of variation = 7.32%, intraclass correlation coefficient = 0.75; tangent elastic modulus: coefficient of variation = 7.34%, intraclass correlation coefficient = 0.84). The mean modulus after normalised to normal intraocular pressure of 15.5 mmHg was 0.755 ± 0.159 MPa. There was no significant difference between the two visits (paired t-tests: p > 0.05). The repeatability [1.96 times the standard deviation (S.D.) of the intersession difference] of the corneal stiffness and the tangent elastic modulus was 0.0022 N mm(-1) and 0.197 MPa, respectively. CONCLUSION: The corneal indentation device has good intrasession and intersession repeatability. It has good potential to measure corneal biomechanics clinically, even at different corneal regions.

Continuous 24-hour intraocular pressure monitoring in normal Chinese adults using a novel contact lens sensor system.

AIMS: To investigate the physiological nyctohemeral intraocular pressure (IOP) rhythms of normal Chinese adults using a novel contact lens sensor system (CLS) that can output IOP in millimetres of mercury (mm Hg) continuously. METHODS: Fifty-nine eyes of 59 normal Chinese adults completed 24-hour IOP monitoring using the novel CLS. A descriptive analysis was conducted on the 24-hour IOP mean, peak and acrophase, trough and bathyphase, fluctuation, and mean amplitude of intraocular pressure excursion (MAPE). The continuous data were analysed at several periods (diurnal period, 08:00-20:00 hours; nocturnal period, 22:00-06:00 hours; sleep time, 0:00-06:00 hours), and compared between right and left eyes, males and females, and different age ranges (<30, and ≥30), respectively. RESULTS: Normal adults had a lower peak, higher trough, smaller fluctuation and smaller MAPE (p<0.05 for all comparisons) but non-significantly different mean (p=0.695) in the nocturnal period or sleep time compared with the diurnal period. The 24-hour IOP peak and trough showed the frequency of occurrence ranging from 1.69% to 15.25% at an interval of 2 hours. No IOP parameter showed significant difference between right and left eyes (p>0.1 for all comparisons). The male group had larger 24-hour and diurnal IOP fluctuation and MAPE (p<0.05 for all comparisons). Subjects aged 30 or over had higher 24-hour and diurnal mean, higher peak, and larger MAPE (p<0.05 for all comparisons). CONCLUSION: Continuous 24-hour IOP output from the CLS in normal Chinese was stable with a comparable mean level between day and night, as well as scattered acrophase and bathyphase. The 24-hour IOP mean increased with age, and IOP variations were positively correlated to age and male sex.

Clinical testing for molecular targets for personalized treatment in lung cancer.

Lung cancer is the leading cause of cancer mortality worldwide. Over the past decades, the management of advanced stage lung cancer has been revolutionized from very limited options of systemic chemotherapy with limited efficacy to the present stage of testing for biomarkers (epidermal growth factor receptor (EGFR), gene mutations) to guide therapeutic decision and to improve efficacy of treatment. Relevant advancement in understanding of lung cancer biology also revealed that different lung tumours may carry different cancer driver gene mutations and thus adopt different carcinogenic pathways. These cancer driver gene mutations were found to be mutually exclusive in individual lung tumour further supporting the rationale of testing tumour sample for the presence of these mutations, especially when there could be corresponding specific agents against these molecular targets. The aim of this article is to review the current understanding of molecular targets that are important in the personalized therapy of lung cancer and how the testing for these molecular targets, namely EGFR, KRAS and ALK, will guide therapeutic decision in advanced stage lung cancer.