Detection of EGFR mutations in patients with suspected lung cancer using paired tissue-plasma testing: a prospective comparative study with plasma ddPCR assay.

Detecting EGFR mutations in plasma using droplet digital PCR (ddPCR) assay offers a promising diagnostic tool for lung cancer patients. The performance of plasma-based ddPCR assay relative to traditional EGFR mutation testing in tissue biopsies among Asian patients with suspected lung cancer remains underexplored. Consecutive patients admitted for diagnostic workup for suspected lung cancer were recruited. Peripheral blood samples were collected on the same day of tissue biopsies. Tissue samples were subjected to EGFR mutation analysis via real-time PCR, whereas plasma samples were processed for ddPCR assay to evaluate for EGFR mutation status. The tissue re-biopsy rate was 43.8% while 0.7% of patients failed blood taking. Despite repeat biopsy, 15.2% of patients could not achieve histological diagnosis. Of the 202 patients newly diagnosed with lung cancer, EGFR mutations were detected in 13.4% of plasma samples, compared to 44.3% in tissue samples. Plasma ddPCR for EGFR mutations detection were barely detectable in stages I and II non-small cell lung cancer (NSCLC), but the sensitivity was 25.0%, 56.3%, and 75.0% in stages III, IVA, and IVB NSCLC, respectively. Plasma EGFR mutations were highly specific among all stages of lung cancer. Concordance rates of plasma ddPCR assay also rose with more advanced stages, recorded at 41.9% for stages I and II, 71.9% for stage III, 86.3% for stage IV. In stage IV lung cancer, the false negative rate for the plasma ddPCR assay was 34.4%, whereas that for the tissue testing was 19.2% due to insufficient tissue samples. Plasma-based EGFR genotyping using ddPCR is a non-invasive method that offers early diagnosis and serves as a valuable adjunct to tissue-based testing for patients with advanced-stage lung cancer. However, its usefulness is limited in the context of early-stage lung cancer, indicating a need for further research to improve its accuracy in these patients.

The Impact of Intraocular Pressure Changes on Corneal Biomechanics in Primary Open-angle Glaucoma.

PURPOSE: To investigate the relationship between intraocular pressure (IOP) changes and corneal biomechanical properties, determine the quantitative relationship between IOP changes and corneal biomechanical properties in patients with glaucoma and observe the differences among different types of glaucoma when the effects of high-level IOP were excluded. DESIGN: Prospective clinical cohort study. METHODS: Setting: Institutional. PATIENTS: Treatment-naive patients with primary open-angle glaucoma or ocular hypertension (OHT) were included. OBSERVATION PROCEDURES: IOP was measured using a Goldmann applanation tonometer. Corneal biomechanics were evaluated using a corneal indentation device and corneal visualization Scheimpflug technology. Medication therapy was used for IOP reduction. Repeated measurements were taken at the baseline visit and each week thereafter within a month. Paired t tests were used to compare IOP and corneal biomechanical metrics before and after IOP-lowering therapy. One-way analysis of variance was employed to investigate potential differences across groups, with a Bonferroni post hoc correction administered for multiple intergroup comparisons. MAIN OUTCOME MEASURES: Corneal biomechanical parameters following IOP changes. RESULTS: Eighty-one participants (mean age, 41.63 ± 17.33 years) were included in this study. The cohort comprised 20 patients with normal-tension glaucoma (NTG), 47 with high-tension glaucoma (HTG), and 14 with OHT. The baseline corneal stiffness (88.58 ± 18.30 N/m) and corneal modulus (0.71 ± 0.16 MPa) were greater than the post-IOP reduction values (67.15 ± 9.24 N/m and 0.54 ± 0.08 MPa, respectively; P < .001). The relationships between changes in IOP and changes in corneal biomechanical parameters were Δ corneal stiffness = 2.06*ΔIOP+6.47 (P < .001) and Δ corneal modulus = 0.017*ΔIOP+0.051 (P < .001). After IOP reduction, the mean corneal stiffness at the 4th week in the NTG group was significantly lower (60.97 ± 6.36 N/m) than that in the HTG (67.25 ± 9.01 N/m) and OHT (75.62 ± 6.52 N/m, P < .001) groups. Additionally, the stiffness of HTG patients was lower than that of OHT patients (P = .003). CONCLUSIONS: Changes in IOP have an impact on corneal biomechanical parameters. Decreases in corneal stiffness and modulus were observed after IOP reduction. When the effect of high-level IOP was excluded, corneal biomechanics varied according to the type of glaucoma. The HTG corneas were softer than the OHT corneas, and the NTG corneas were even softer.

Impact of sleep disturbance on longitudinal cognitive performance in patients with transient ischemic attack or mild stroke.

INTRODUCTION: Sleep disturbances including obstructive sleep apnea (OSA) and poor sleep quality are common after stroke, while its association with cognitive changes following transient ischemic attack (TIA) or mild stroke remains unclear. We aim to determine whether sleep duration, OSA parameters, or nocturnal hypoxemia is associated with a greater cognitive decline after stroke. METHODS: We prospectively followed-up patients with acute TIA/mild stroke [National Institute Health Stroke Scale (NIHSS) < 7] who underwent baseline sleep questionnaire [Pittsburgh Sleep Quality Index (PSQI)], and serial cognitive assessments [Montreal Cognitive Assessment (MoCA) 5-min, Stroop Test] at baseline and one-year. We also evaluated apnea-hypopnea index (AHI) and nocturnal hypoxemia by Home Sleep Apnea Test (HSAT) at one-year. Primary outcome was one-year change in MoCA 5-min score. RESULTS: One hundred and five patients with TIA/mild stroke (mean age 63 years, 65 % male) were included. Baseline short sleep (< 6 hour/night) and AHI ≥ 20/hour at one-year were independently associated with a decline in the MoCA 5-min total score after covariates adjustment [short sleep: ß = -2.36 95 % confidence interval (CI) (-4.13, -0.59), p = 0.009; AHI ≥ 20/hour: ß = -1.79 (-3.26, -0.32), p = 0.017; remained significant after multiple comparisons correction]. A lower mean MinSpO2 was associated with a decline in executive function [Stroop interference index: ß = 0.29 (0.04, 0.53), p = 0.021], but not with MoCA 5-min score at one-year. Moderation analysis indicated AHI ≥ 20/hour was associated with a pronounced decline in executive function only in men. CONCLUSIONS: Short sleep after stroke onset, AHI ≥ 20/hour and nocturnal hypoxemia at one-year contributed to an impaired cognitive trajectory at one-year following stroke in patients with TIA/mild stroke.

Tobacco and COPD: presenting the World Health Organization (WHO) Tobacco Knowledge Summary.

The WHO recently published a Tobacco Knowledge Summary (TKS) synthesizing current evidence on tobacco and COPD, aiming to raise awareness among a broad audience of health care professionals. Furthermore, it can be used as an advocacy tool in the fight for tobacco control and prevention of tobacco-related disease. This article builds on the evidence presented in the TKS, with a greater level of detail intended for a lung-specialist audience. Pulmonologists have a vital role to play in advocating for the health of their patients and the wider population by sharing five key messages: (1) Smoking is the leading cause of COPD in high-income countries, contributing to approximately 70% of cases. Quitting tobacco is an essential step toward better lung health. (2) People with COPD face a significantly higher risk of developing lung cancer. Smoking cessation is a powerful measure to reduce cancer risk. (3) Cardiovascular disease, lung cancer and type-2 diabetes are common comorbidities in people with COPD. Quitting smoking not only improves COPD management, but also reduces the risk of developing these coexisting conditions. (4) Tobacco smoke also significantly impacts children's lung growth and development, increasing the risk of respiratory infections, asthma and up to ten other conditions, and COPD later in life. Governments should implement effective tobacco control measures to protect vulnerable populations. (5) The tobacco industry's aggressive strategies in the marketing of nicotine delivery systems and all tobacco products specifically target children, adolescents, and young adults. Protecting our youth from these harmful tactics is a top priority.

Draw & Doodle Simulation: A colorful strategy to prepare medical teams for electronic dance music festival emergencies.

EDUCATIONAL CHALLENGE: Electronic dance music (EDM) festivals - crowded, loud, low-resource environments - pose unique challenges to event medical teams. Simulation can prepare teams to manage clinical presentations in this unconventional context. Without access to simulation infrastructure, a low-technological, low-fidelity simulation modality is warranted. SOLUTION: Draw & Doodle Simulation (D&D SIM) is a low-fidelity simulation where patients are hand-drawn (i.e. on paper, whiteboard, or digitally) instead of utilizing manikins or live actors. Facilitators draw all patient findings, while participants doodle any possible interventions. SOLUTION IMPLEMENTATION: Two D&D SIM cases (serotonin toxicity and refractory anaphylaxis) were piloted in classrooms. Participants included paramedics, medical students, lifeguards, and first aiders. Facilitators conducted simulations using chart paper, with each participant doodling contributions using differently colored markers. LESSONS LEARNED: Participants responded positively, rating the serotonin toxicity case 4.31/5 (n = 13) and refractory anaphylaxis case 4.53/5 (n = 15). Participants appreciated the 'low-stakes', useful 'visual' representation of progress, 'fun and [interactivity]', and appropriate '[realism]' of D&D SIM. However, D&D SIM was perceived as 'less life threatening', would not be appropriate for physical skills (e.g. CPR), required everyone to be 'oriented in the same direction to see the drawing', and the chart paper risked becoming cluttered. NEXT STEPS: Next steps include writing new cases, implementing D&D SIM in other teaching contexts, exploring its use in digital platforms, and studying its effectiveness against higher-fidelity simulation.

Changes in the incidence, clinical features and outcomes of tuberculosis during COVID-19 pandemic.

BACKGROUND: COVID-19 pandemic has disrupted tuberculosis (TB) services in many countries, but the impacts on sites of involvement, drug susceptibility, smear positivity and clinical outcomes, and clinical outcomes of co-infection with influenza and COVID-19 remain unclear. METHODS: Descriptive epidemiological study using episode-based and patient unique data of tuberculosis from Hospital Authority's territory-wide electronic medical record database, comparing baseline (January 2015-December 2019) and COVID-19 period (January 2020-December 2022), followed by univariate and multivariate analyses. Effects of co-infection with influenza and COVID-19 were investigated. RESULTS: The study included 10,473 episodes of laboratory-confirmed TB, with 6818 in baseline period and 3655 during COVID-19 period. During COVID-19 period, TB patients had a lower proportion of smear positivity (49.2 % vs 54.7 %, P < 0.001), and fewer cases of extrapulmonary TB (7.0 % vs 8.0 %, P = 0.078) and multidrug resistant TB (1.0 % vs 1.6 %, P = 0.020). Mortality was higher in TB patients with COVID-19 coinfection (OR 1.7, P = 0.003) and influenza coinfection (OR 2.6, P = 0.004). During COVID-19 period, there were higher rates of treatment delay (20.5 % vs 15.5 %, P < 0.001) and episodic death (15.1 % vs 13.3 %, P = 0.006). Factors associated with higher mortality included age ≥ 70 years (OR 7.24), treatment delay (OR 2.16), extrapulmonary TB (OR 2.13). smear positivity (OR 1.71) and Charlson comorbidity index score ≥ 3 (OR 1.37). Higher mortality was observed with co-infection by influenza (OR 1.18) and COVID-19 (OR 1.7). CONCLUSIONS: The epidemiology and outcomes of TB were changed during COVID-19 period. Mortality was higher during COVID-19 period and with co-infection by influenza and COVID-19.

Protective Effects from Prior Pneumococcal Vaccination in Patients with Chronic Airway Diseases during Hospitalization for Influenza-A Territory-Wide Study.

Influenza is an important respiratory viral pathogen in adults, with secondary bacterial pneumonia being a common complication. While pneumococcal vaccines can prevent pneumococcal pneumonia and invasive pneumococcal disease, whether they can also prevent the severe in-hospital outcomes among patients hospitalized for influenza has not been examined. A territory-wide retrospective study was conducted in Hong Kong, which included all adult patients having chronic airway diseases (asthma, bronchiectasis, and chronic obstructive pulmonary disease) hospitalized for influenza and who had received seasonal influenza vaccine. The occurrence of secondary bacterial pneumonia, mortality, and other severe in-hospital outcomes were compared among subjects with or without pneumococcal vaccination. There was a total of 3066 eligible patients who were hospitalized for influenza in public hospitals in Hong Kong from 1 January 2016 to 30 June 2023. Completed pneumococcal vaccination with PSV23/PCV13 conferred protection against secondary bacterial pneumonia, all-cause mortality, and respiratory cause of mortality with adjusted odds ratios of 0.74 (95% CI = 0.57-0.95, p = 0.019), 0.12 (95% CI = 0.03-0.53, p = 0.005), and 0.04 (95% CI = 0.00-0.527, p = 0.0038), respectively.

Baseline neutrophil-to-lymphocyte ratio as a predictor of response to hospitalized bronchiectasis exacerbation risks.

Background: Bronchiectasis is a disease with predominantly neutrophilic inflammation. As a readily available biomarker, there is little evidence to support the use of blood neutrophil-to-lymphocyte ratio (NLR) to predict bronchiectasis exacerbation severe enough to warrant hospitalization. Methods: A registry-based retrospective cohort study was conducted at a in Hong Kong. Chinese patients with non-cystic fibrosis (CF) bronchiectasis were retrospectively reviewed and subsequently followed up to investigate the association of NLR and the need for hospitalization for bronchiectasis exacerbation. Data on the NLR for patients in a clinically stable state in 2018 were collected and patients followed up from 1 January 2019 to 31 December 2022. The primary outcome was the need for hospitalization due to bronchiectasis exacerbation over the next 4 years. Results: We reviewed 473 Chinese patients with non-CF bronchiectasis, of whom 94 required hospitalization for bronchiectasis exacerbation during the 4-year follow-up period. Multi-variable logistic regression adjusted for E-FACED score (Exacerbation, Forced expiratory volume in 1 s (FEV1), Age, Chronic colonization, Extension, and Dyspnea score), gender, age, smoking status, and presence of co-existing chronic obstructive pulmonary disease (COPD) was conducted to compare patients with highest and lowest quartile NLR. Results revealed that those with NLR at the highest quartile were at increased risk of hospitalization for bronchiectasis exacerbation with an adjusted odds ratio (aOR) of 2.02 (95% confidence interval = 1.00-4.12, p = 0.05). Conclusion: Blood NLR may serve as a marker to predict the need for hospitalization due to bronchiectasis exacerbation.

Systemic immune-inflammation index in predicting hospitalized bronchiectasis exacerbation risks and disease severity.

Background: Bronchiectasis is a common respiratory disease with neutrophilic inflammation being the predominant pathophysiology. Systemic immune-inflammation index (SII) is a simple and readily available biomarker being studied in various conditions including asthma, chronic obstructive pulmonary disease, and interstitial lung disease, but not in bronchiectasis. We aim to investigate the prognostic role of SII in bronchiectasis with this study. Methods: A retrospective cohort study in Chinese patients with non-cystic fibrosis (CF) bronchiectasis was conducted in Hong Kong, to investigate the association between baseline SII and of hospitalized bronchiectasis exacerbation risk over 4.5 years of follow-up, as well as correlating with disease severity in bronchiectasis. The baseline SII in 2018 was calculated based on stable-state complete blood count. Results: Among 473 Chinese patients with non-CF bronchiectasis were recruited, 94 of the patients had hospitalized bronchiectasis exacerbation during the follow-up period. Higher SII was associated with increased hospitalized bronchiectasis exacerbation risks with adjusted odds ratio (aOR) of 1.001 [95% confidence interval (CI): 1.000-1.001, P=0.003] for 1 unit (cells/µL) increase in SII count and aOR of 1.403 (95% CI: 1.126-1.748, P=0.003) for 1 standard deviation (SD) increase in SII. SII was found to have significant negative association with baseline forced expiratory volume in the first second (FEV1) (in litre and percentage predicted), forced vital capacity (FVC) in percentage; and significant positive correlation with the extent of bronchiectasis and baseline neutrophil to lymphocyte ratio (NLR). Conclusions: SII could serve as biomarker to predict the risks of hospitalized exacerbation in bronchiectasis patients, as well as correlating with the disease severity.

Effectiveness of a self-determination theory-based smoking cessation intervention plus instant messaging via mobile application for smokers with cancer: Protocol for a pragmatic randomized controlled trial.

BACKGROUND AND AIMS: Despite evidence that patients living with cancer who continue to smoke after diagnosis are at higher risk for all-cause mortality and reduced treatment efficacy, many cancer patients continue to smoke. This protocol is for a study to test the effectiveness of a self-determination theory-based intervention (quit immediately or progressively) plus instant messaging (WhatsApp or WeChat) to help smokers with cancer to quit smoking. DESIGN: This will be a multi-centre, two-arm (1:1), single-blind, pragmatic, individually randomized controlled trial. SETTING: Taking part will be specialist outpatient clinics in five major hospitals in different location-based clusters in Hong Kong. PARTICIPANTS: The sample will include 1448 Chinese smokers living with cancer attending medical follow-ups at outpatient clinics. INTERVENTIONS: The intervention group will receive brief advice (approximately 5-8 minutes) from research nurses in the outpatient clinics and then be invited to choose their own quit schedules (immediate or progressive). During the first 6-month follow-up period they will receive instant messaging with smoking cessation advice once per week for the first 3 months, and thereafter approximately once per month. They will also receive four videos, and those opting to quit progressively will receive a smoking reduction leaflet. The control group will also receive brief advice but be advised to quit immediately, and instant messaging with general health advice during the first 6-month follow-up period using the same schedule as the intervention group. Participants in both groups will receive smoking cessation leaflets. MEASUREMENTS: The primary outcome is biochemically validated smoking abstinence at 6 months, as confirmed by saliva cotinine level and carbon monoxide level in expired air. Secondary outcomes include biochemically validated smoking abstinence at 12 months, self-reported 7-day point prevalence of smoking abstinence at 6 and 12 months, self-reported ≥ 50% reduction of cigarette consumption at 6 and 12 months and quality of life at 6 and 12 months. All time-points for outcomes measures are set after randomization. COMMENTS: The results could inform research, policymaking and health-care professionals regarding smoking cessation for patients living with cancer, and therefore have important implications for clinical practice and health enhancement.

SABINA + Hong Kong: a territory wide study of prescribing trends and outcomes associated with the use of short-acting ß2 agonists in the Chinese population.

BACKGROUND: Excessive use of short-acting ß2 agonists (SABA) in patients with asthma continues to be a notable concern due to its link to higher mortality rates. Global relevance of SABA overuse in asthma management cannot be understated, it poses significant health risk to patients with asthma and imposes burden on healthcare systems. This study, as part of global SABINA progamme, aimed to describe the prescribing patterns and clinical outcomes associated with SABA use in the Chinese population. METHODS: Retrospective cohort study was conducted using anonymized electronic healthcare records of Clinical Data Analysis and Reporting System (CDARS) from Hong Kong Hospital Authority (HA). Patients newly diagnosed with asthma between 2011 and 2018 and aged ≥12 years were included, stratified by SABA use (≤2, 3-6, 7-10, or ≥11 canisters/year) during one-year baseline period since asthma diagnosis date. Patients were followed up from one-year post-index until earliest censoring of events: outcome occurrence and end of study period (31 December 2020). Cox proportional regression and negative binomial regression were used to estimate the mortality risk and frequency of hospital admissions associated with SABA use respectively, after adjusting for age, sex, Charlson Comorbidity Index (CCI), and inhaled corticosteroid (ICS) dose. Outcomes include all-cause, asthma-related, and respiratory-related mortality, frequency of hospital admissions for any cause, and frequency of hospital admissions due to asthma. RESULTS: 17,782 patients with asthma (mean age 46.7 years, 40.8% male) were included and 59.1% of patients were overusing SABA (≥ 3 canisters per year). Each patient was prescribed a median of 5.61 SABA canisters/year. SABA overuse during baseline period was associated with higher all-cause mortality risk compared to patients with ≤2 canisters/year. Association was dose-dependent, highest risk in those used ≥11 canisters/year (adjusted hazard ratio: 1.42, 95% CI: 1.13, 1.79) and 3-6 canisters/year (adjusted hazard ratio: 1.22, 95% CI: 1.00, 1.50). Higher SABA prescription volume associated with increased frequency of hospital admissions with greatest risk observed in 7-10 canisters/year subgroup (adjusted rate ratio: 4.81, 95% CI: 3.66, 6.37). CONCLUSIONS: SABA overuse is prevalent and is associated with increased all-cause mortality risk and frequency of hospital admissions among the patients with asthma in Hong Kong.

Histological assessment of microtia cartilage, a potential source of autograft tissue in ear reconstruction.

Cartilage is a strong and flexible connective tissue that has many forms and functions in our body. While cartilage exhibits some forms of limited repair, for the most part, it is not particularly regenerative. Thus, in situations where patients require cartilage reconstruction, surgeons may use autografts to replace missing or damaged tissue. Cartilage tissues from different regions of the body exhibit histological differences and are in limited supply. Thus, it is important to characterize these differences to determine the most appropriate autograft source. In the case of microtia, a congenital deformity where the pinna is underdeveloped, reconstruction commonly utilizes cartilage sourced from a patient's own costal cartilage. This presents a potential morbidity risk. In this study, we evaluate the histological characteristics of microtia cartilage compared with normal auricular and costal cartilage obtained from human patients undergoing surgical resection. Histochemistry was used to evaluate cellularity, lipid content, and ECM content. Using a Bayesian statistical approach, we determined that while costal cartilage is the standard tissue donor, the microanatomy of microtia cartilage more closely reflects normal auricular cartilage than costal cartilage. Therefore, microtia cartilage may serve as an additional reservoir for cartilage during reconstruction.

Prophylactic negative pressure wound therapy to improve wound healing rates following ileostomy closure: a randomized controlled trial.

BACKGROUND: Reversal of ileostomy is associated with morbidity including wound infection and prolonged wound healing. Negative pressure wound therapy (NPWT) has been shown to reduce time to wound healing by secondary intention. The aim of this study was to determine whether NPWT improved wound healing rates, compared with simple wound dressings, in patients undergoing reversal of ileostomy where the skin wound is closed with a purse-string suture. METHODS: This was a dual-centre, open-label, randomized controlled trial with two parallel intervention arms. Patients undergoing elective loop ileostomy reversal were randomized 1:1 to receive NPWT or simple wound dressings. The primary endpoint of the study was assessment of complete wound healing at day 42 post reversal of ileostomy and the secondary endpoints were patient-reported wound cosmesis using a visual analogue scale and rates of surgical site infection (SSI). RESULTS: The study was conducted from June 2018 to December 2021. The trial was approved by the local ethics committee. We enrolled 40 patients, 20 in each arm. One patient in each arm was lost to follow up. Nine patients (9/19, 47.36%) in the simple dressing group had wound healing vs. 13 patients (13/19, 68.42%) in the NPWT group (P = 0.188). There was no significant difference in patient- reported wound cosmesis or SSI. CONCLUSION: There was no difference in wound healing rates when comparing NPWT to simple wound dressings at early and late time points post reversal of ileostomy, where the skin wound was closed with a purse-string suture.

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.

Prevalence, incidence, and survival analysis of interstitial lung diseases in Hong Kong: a 16-year population-based cohort study.

Background: Published data on the epidemiology of interstitial lung disease (ILD) in Asia is scarce. Understanding the epidemiology is important for authorities in the health management planning. This study aimed to estimate the prevalence, incidence, and survival of ILD in Hong Kong from 2005 to 2020 and evaluate the change of trend over time. Methods: In this retrospective cohort study, we identified ILD patients between 2005 and 2020 using a territory-wide electronic health record database. Prevalence, incidence rates, and age- and sex-standardised incidence rates with United Nations population in 2020 as a reference were estimated. Trends in prevalence and incidence were analysed using joinpoint regression and the average annual percent change (AAPC) was estimated. Median survival, and risk factors of mortality were evaluated using Cox proportional hazard regression. Findings: We identified 5924 patients and included 5884 of them for analysis. The prevalence of ILD increased from 24.7 to 33.6 per 100,000 population from 2005 to 2020 with an AAPC of 1.94 (95% confidence interval, CI: 1.69-2.34). The standardized incidence rate decreased from 5.36 to 2.57 per 100,000 person from 2005 to 2020 (AAPC -3.56, 95% CI, -4.95 to -1.78). The median survival of ILD was 2.50 (95% CI, 2.32-2.69) years. Male, older age, higher Charlson comorbidity index, and IIP subtype were associated with increased mortality with statistical significance. Interpretation: This study provided the first epidemiological evaluation of ILD in Hong Kong. Further studies on ILD in multiple Asian cities and countries are warranted. Funding: None.

Inhalable paclitaxel nanoagglomerate dry powders for lung cancer chemotherapy: Design of experiments-guided development, characterization and in vitro evaluation.

Conventional intravenous chemotherapy for lung cancer frequently results in inefficient drug penetration into primary lung tumors and severe systemic toxicities. This study reports the development of inhalable paclitaxel (PTX) nanoagglomerate dry powders (PTX-NADP) for enhanced pulmonary delivery of PTX chemotherapy to lung tumors using full factorial Design of Experiments. PTX nanoparticles were fabricated by flash nanoprecipitation with the aid of N-polyvinylpyrrolidone (PVP) and curcumin (CUR) as stabilizer and co-stabilizer respectively, and subsequently agglomerated into inhalable dry powders via co-spray drying with methylcellulose. The optimized PTX-NADP formulation exhibited acceptable aqueous redispersibility (redispersibility index = 1.17 ± 0.02) into âˆ¼ 150 nm nanoparticles and superb in vitro aerosol performance [mass median aerodynamic diameter (MMAD) = 1.69 ± 0.05 µm and fine particle fraction (FPF) of 70.89 ± 1.72 %] when dispersed from a Breezhaler® at 90 L/min. Notably, adequate aerosolization (MMAD < 3.5 µm and FPF > 40 %) of the optimized formulation was maintained when dispersed at reduced inspiratory flow rates of 30 - 60 L/min. Redispersed PTX nanoparticles from PTX-NADP demonstrated enhanced in vitro antitumor efficacy and cellular uptake in A549 lung adenocarcinoma cells without compromising tolerability of BEAS-2B normal lung epithelial cells towards PTX chemotherapy. These findings highlight the potential of inhaled PTX-NADP therapy to improve therapeutic outcomes for lung cancer patients with varying levels of pulmonary function impairment.

A Real-World Precision Medicine Program Including the KidneyIntelX Test Effectively Changes Management Decisions and Outcomes for Patients With Early-Stage Diabetic Kidney Disease.

INTRODUCTION/OBJECTIVE: The KidneyIntelX is a multiplex, bioprognostic, immunoassay consisting of 3 plasma biomarkers and clinical variables that uses machine learning to predict a patient's risk for a progressive decline in kidney function over 5 years. We report the 1-year pre- and post-test clinical impact on care management, eGFR slope, and A1C along with engagement of population health clinical pharmacists and patient coordinators to promote a program of sustainable kidney, metabolic, and cardiac health. METHODS: The KidneyIntelX in vitro prognostic test was previously validated for patients with type 2 diabetes and diabetic kidney disease (DKD) to predict kidney function decline within 5 years was introduced into the RWE study (NCT04802395) across the Health System as part of a population health chronic disease management program from [November 2020 to April 2023]. Pre- and post-test patients with a minimum of 12 months of follow-up post KidneyIntelX were assessed across all aspects of the program. RESULTS: A total of 5348 patients with DKD had a KidneyIntelX assay. The median age was 68 years old, 52% were female, 27% self-identified as Black, and 89% had hypertension. The median baseline eGFR was 62 ml/min/1.73 m2, urine albumin-creatinine ratio was 54 mg/g, and A1C was 7.3%. The KidneyIntelX risk level was low in 49%, intermediate in 40%, and high in 11% of cases. New prescriptions for SGLT2i, GLP-1 RA, or referral to a specialist were noted in 19%, 33%, and 43% among low-, intermediate-, and high-risk patients, respectively. The median A1C decreased from 8.2% pre-test to 7.5% post-test in the high-risk group (P < .001). UACR levels in the intermediate-risk patients with albuminuria were reduced by 20%, and in a subgroup treated with new scripts for SGLT2i, UACR levels were lowered by approximately 50%. The median eGFR slope improved from -7.08 ml/min/1.73 m2/year to -4.27 ml/min/1.73 m2/year in high-risk patients (P = .0003), -2.65 to -1.04 in intermediate risk, and -3.26 ml/min/1.73 m2/year to +0.45 ml/min/1.73 m2/year in patients with low-risk (P < .001). CONCLUSIONS: Deployment and risk stratification by KidneyIntelX was associated with an escalation in action taken to optimize cardio-kidney-metabolic health including medications and specialist referrals. Glycemic control and kidney function trajectories improved post-KidneyIntelX testing, with the greatest improvements observed in those scored as high-risk.

Increased exacerbations of bronchiectasis following recovery from mild COVID-19 in patients with non-cystic fibrosis bronchiectasis.

BACKGROUND AND OBJECTIVE: Respiratory viral infection is a common trigger of bronchiectasis exacerbation. Knowledge of the intermediate to long-term effect of COVID-19 on bronchiectasis is poor. METHODS: A retrospective cohort study of patient records was conducted to assess the frequency of bronchiectasis exacerbation following recovery from mild-to-moderate COVID-19. The exacerbation frequency at baseline, using 2019 and 2019-2021 data, was compared with that during the 1 year following recovery. RESULTS: A total of 234 adult patient records who had a confirmed diagnosis of bronchiectasis were identified, of whom 52 (22.2%) were classified as the COVID-19 group. Patients with COVID-19 had significantly more frequent annual exacerbations of bronchiectasis (total exacerbations and hospitalizations). Compared with 2019-2021 data, the total exacerbation frequency decreased by 0.1 ± 0.51 per year among non-COVID-19 patients but increased by 0.68 ± 1.09 per year among the COVID-19 group (p < 0.001). Compared with 2019 only data, exacerbation frequency decreased by 0.14 ± 0.79 per year among non-COVID-19 patients but increased by 0.76 ± 1.17 per year in the COVID-19 group, p < 0.001. The annual frequency of hospitalization for bronchiectasis increased by 0.01 ± 0.32 per year among non-COVID-19 patients and increased by 0.39 ± 1.06 per year in the COVID-19 group (p < 0.001) compared with 2019 to 2021 data. When compared with only 2019 data, it remained unchanged at 0 ± 0.43 per year among non-COVID-19 patients but increased to 0.38 ± 1.12 per year among COVID-19 patients (p < 0.001). CONCLUSION: Mild-to-moderate COVID-19 was associated with an increase in frequency of bronchiectasis exacerbation and frequency of hospitalizations following recovery.