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Sharifah Saffinas Syed Soffian,1 Azmawati Mohammed Nawi,1 Rozita Hod,1 Mohd Rizal Abdul Manaf,1 Huan-Keat Chan,2 Muhammad Radzi Abu Hassan2 1Department of Community Health, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur, 56000, Malaysia; 2Clinical Research Center, Sultanah Bahiyah Hospital, Alor Setar, 05400, Kedah, MalaysiaCorrespondence: Azmawati Mohammed Nawi, Department of Community Health, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur, 56000, Malaysia, Tel +60 3 9145 8408, Email azmawati@ppukm.ukm.edu.myAbstract: Regardless of the high global burden of colorectal cancer (CRC), the uptake of CRC screening varies across countries. This systematic review aimed to provide a picture of the disparities in recommendations for CRC screening in average-risk individuals using an ecobiosocial approach. It was reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The literature search was conducted through Scopus, Web of Science, PubMed, and EBSCOHost. Full-text guidelines which were published between 2011 and 2021, along with guidelines which provided recommendations on CRC screening in average-risk individuals, were included in the review. However, guidelines focusing only on a single screening modality were excluded. Fourteen guidelines fulfilling the eligibility criteria were retained for the final review and analysis. Quality assessment of each guideline was performed using the AGREE II instrument. Disparities in guidelines identified in this review were classified into ecological (screening modalities and strategies), biological (recommended age, gender and ethnicities), and social (smoking history, socioeconomic status, and behavior) factors. In general, unstandardized practices in CRC screening for average-risk individuals are likely attributable to the inconsistent and non-specific recommendations in the literature. This review calls on stakeholders and policymakers to review the existing colorectal cancer screening practices and pursue standardization.Keywords: colorectal cancer, screening, guidelines, ecology, biology, social, disparities

Kamaruddin Mardhiah,1,2 Nadiah Wan-Arfah,2 Nyi Nyi Naing,3 Muhammad Radzi Abu Hassan,4 Huan-Keat Chan,4 Hazriah Hasan1 1Faculty of Entrepreneurship and Business, Universiti Malaysia Kelantan, Kota Bharu, Kelantan, Malaysia; 2Faculty of Health Sciences, Universiti Sultan Zainal Abidin, Kuala Terengganu, Terengganu, Malaysia; 3Faculty of Medicine, Universiti Sultan Zainal Abidin, Kuala Terengganu, Terengganu, Malaysia; 4Clinical Research Center, Hospital Sultanah Bahiyah, Ministry of Health Malaysia, Alor Setar, Kedah, MalaysiaCorrespondence: Nadiah Wan-ArfahFaculty of Health Sciences, Universiti Sultan Zainal Abidin, Gong Badak Campus, Kuala Nerus, Kuala Terengganu, Terengganu, 21300, MalaysiaTel +6012-6260508Email wanwaj@unisza.edu.myPurpose: This study was conducted to determine the direct medical cost of treating melioidosis patients. The calculation was made according to the variables extracted from medical records.Materials and Methods: Data collection was performed retrospectively on a total of 293 cases from Hospital Sultanah Bahiyah, Kedah, Malaysia. The data consisted of personal information, treatment history, and investigation findings, including blood results, USG abdomen results, and CT scan results. The site of culture and sensitivity were also obtained. The total direct medical cost was based on the antibiotics/treatments received by the patients, diagnostic test and investigations performed. The trend analysis used to see the pattern of costs from 2014 to 2017. All the costs were compared based on patients’ status and duration of stay at the hospital using the independent t-test.Results: The overall mean of direct medical cost for melioidosis amounted to US $233.61 (RM931.33). Overall, the finding confirms a huge reduction (44.7%) of direct medical cost from 2014 to 2017 (P = 0.001). From 2015 to 2016, there was a 19.1% reduction of direct medical cost (P> 0.95), followed by a 38.8% reduction in costs from 2016 to 2017 (P = 0.019). In the case of the duration of stay, the mean of total direct medical cost among patients with ≥ 14 duration of stay was higher compared to those with < 14 duration of stay (p < 0.001). There was no significant mean difference of direct medical cost between patients who were cured and died.Conclusion: Despite the higher mortality of melioidosis cases compared to other infectious diseases, there is a limitation in the amount of published data on the management cost of melioidosis. The importance of cost in managing this disease should be underlined to perform a fully prepared management toward the disease.Keywords: melioidosis, direct medical cost, trend analysis

Nguyen Hoai An Le,1 Hoang Van Phan,1 Jiaqi Yu,2 Hak-Kim Chan,2 Adrian Neild,1 Tuncay Alan1 1Department of Mechanical and Aerospace Engineering, Monash University, Melbourne, VIC, 2The Advanced Drug Delivery Group, Faculty of Pharmacy, University of Sydney, Sydney, NSW, Australia Background: This article presents an acoustically enhanced microfluidic mixer to generate highly uniform and ultra-fine nanoparticles, offering significant advantages over conventional liquid antisolvent techniques.Methods: The method employed a 3D microfluidic geometry whereby two different phases – solvent and antisolvent – were introduced at either side of a 1 µm thick resonating membrane, which contained a through-hole. The vibration of the membrane rapidly and efficiently mixed the two phases, at the location of the hole, leading to the formation of nanoparticles.Results: The versatility of the device was demonstrated by synthesizing budesonide (a common asthma drug) with a mean diameter of 135.7 nm and a polydispersity index of 0.044.Conclusion: The method offers a 40-fold reduction in the size of synthesized particles combined with a substantial improvement in uniformity, achieved without the need of stabilizers. Keywords: microfluidics, nanodrugs, budesonide, liquid antisolvent method

Satomi Onoue,1 Shizuo Yamada,1 Hak-Kim Chan2 1Department of Pharmacokinetics and Pharmacodynamics, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan; 2Advanced Drug Delivery Group, Faculty of Pharmacy, The University of Sydney, Sydney, NSW, Australia Abstract: To date, various nanodrug systems have been developed for different routes of administration, which include dendrimers, nanocrystals, emulsions, liposomes, solid lipid nanoparticles, micelles, and polymeric nanoparticles. Nanodrug systems have been employed to improve the efficacy, safety, physicochemical properties, and pharmacokinetic/pharmacodynamic profile of pharmaceutical substances. In particular, functionalized nanodrug systems can offer enhanced bioavailability of orally taken drugs, prolonged half-life of injected drugs (by reducing immunogenicity), and targeted delivery to specific tissues. Thus, nanodrug systems might lower the frequency of administration while providing maximized pharmacological effects and minimized systemic side effects, possibly leading to better therapeutic compliance and clinical outcomes. In spite of these attractive pharmacokinetic advantages, recent attention has been drawn to the toxic potential of nanodrugs since they often exhibit in vitro and in vivo cytotoxicity, oxidative stress, inflammation, and genotoxicity. A better understanding of the pharmacokinetic and safety characteristics of nanodrugs and the limitations of each delivery option is necessary for the further development of efficacious nanodrugs with high therapeutic potential and a wide safety margin. This review highlights the recent progress in nanodrug system development, with a focus on the pharmacokinetic advantages and safety challenges. Keywords: nanoparticles, nanotechnology, nanotoxicity, solubilization, targeted delivery

Background: Inadequacies of drug labeling have been frequently reported among Malaysian healthcare institutes, in which the Hospital Information System (HIS) is used. Objective: To identify potential areas to improve the existing labels used for pediatric liquid medications. Methods: This study was qualitative in nature, whereby focus group discussions (FGDs), face-to-face interviews (FTFIs), and onsite observation were used for data collection. Pharmacists stationed at three units (outpatient, inpatient and clinical pharmacy) of a tertiary hospital were targeted. Both FGDs and FTFIs were facilitated using a semi-structured interview guide, video-recorded and transcribed verbatim. All transcripts were thematically analyzed using content analysis approach. Results: Thirteen pharmacists participated in FGDs, while five were approached for FTFIs. Data analysis resulted in four major themes: format of labels, presentation of medication instructions, insufficiency of information, and the need for external aids and education. Participants unanimously agreed on the need for enlarging font sizes of key information. Suggestions were made to use more specific instructions for administration times and pictograms to illustrate important directions. The absence of information about storage, stability and handling of liquid medications was also highlighted. While discussion mainly focused on improving drug labeling, participants consistently stressed the need for an instruction sheet and pharmacist-based, one-to-one education regarding medication instructions. Conclusion: This study provides important insights into critical shortcomings in current labeling practice, underlying the need for developing a new label that incorporates a new format, additional information and pictograms for pediatric liquid medications.

Therapeutic communication is central to mental health nursing and through this process nurse-client relationships can be enhanced. In Hong Kong, mental health nurses are educated in 'western' theories and strategies in using therapeutic communication and the field of communication is predominantly Eurocentric. However, the majority of people in Hong Kong are Chinese and little research has been conducted into how Hong Kong nurses communicate with their Chinese clients. This qualitative study focused on identifying the therapeutic communication strategies used by mental health nurses with Chinese clients in Hong Kong. Three case study vignettes with some of the characteristics of Chinese culture were developed to elicit information about the strategies that respondents used in therapeutic communication. The purposive sample of 20 comprised 10 admission ward nurses and 10 community nurses from two psychiatric hospitals. All participants had at least five years postregistration experience. Content analysis revealed categories of communication and theme clusters for the nurses' response to the vignettes. The result showed a unique cultural influence emerged in communication patterns. In view of the scant nature of existing literature and studies in this area, this research provided some valuable data for further studies. Implications for mental health nursing education and practice in Hong Kong are raised, as are implications for nurses working in multicultural countries such as Australia, the UK and the USA, where there are significant numbers of Chinese clients who would benefit from nurses practising with a deeper understanding of communication strategies which are culturally bound. [ABSTRACT FROM AUTHOR]

Background: Children with intravenous immunoglobulin (IVIG) resistant Kawasaki disease (KD) are at higher risk of developing coronary artery (CA) aneurysm. Early identification of high-risk patients using a predictive tool would allow for earlier interventions to prevent cardiac complications., Methods: Children with KD who were admitted to five selected hospitals in Malaysia between 2008 and 2018 and received 2 g/kg of IVIG within 10 days from the onset of illness were included. Predictors of IVIG resistance in KD were determined using multiple logistic regression analysis. An optimal cut-off point was set using receiver operative characteristic curve and a final multiple logistic regression analysis was performed entering these cut-off points. A new scoring system was constructed., Results: A total of 276 patients were included. IVIG resistance occurred in 9.1 % of them. Total bilirubin [OR 7.37; 95 % CI (2.18, 24.83)], male sex [OR 0.34; 95 % CI (0.10, 1.19)], C-reactive protein (CRP) [OR 0.17; 95 % CI (0.02, 1.38)] and neutrophils [OR 0.25; 95 % CI (0.05, 1.21)] were found to be significant predictors for IVIG resistance. The findings led to the development of a new predictive tool called the Hibiscus score, which scored 1 point each for neutrophils ≥60 %, CRP ≥80 mg/L, and male sex, while total bilirubin ≥9.4 μmol/L scored 2 points. A cut-off point of ≥4 with this prediction score yielded a sensitivity of 78.9 % and specificity of 80.5 %, with area under the curve of 0.835 [95 % CI (0.752, 0.919)]. CA aneurysms occurred in 6.7 % of IVIG responders and 32 % of IVIG-resistant children (p < 0.001)., Conclusion: The findings suggest that the Hibiscus score has a higher predictive power than the existing scoring systems for IVIG resistance in children with KD in Malaysia. However, external validation is required to enable its use to guide treatment decisions., Competing Interests: Declaration of competing interest The authors declare that there is no conflict of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Phase contrast x-ray imaging (PCXI) provides high-contrast images of weakly-attenuating structures like the lungs. PCXI, when paired with 4D X-ray Velocimetry (XV), can measure regional lung function and non-invasively assess the efficacy of emerging therapeutics. Bacteriophage therapy is an emerging antimicrobial treatment option for lung diseases such as cystic fibrosis (CF), particularly with increasing rates of multi-drug-resistant infections. Current efficacy assessment in animal models is highly invasive, typically requiring histological assessment. We aim to use XV techniques as non-invasive alternatives to demonstrate efficacy of bacteriophage therapy for treating Pseudomonas aeruginosa CF lung infections, measuring functional changes post-treatment. Time-resolved in vivo PCXI-CT scans of control, Pseudomonas-infected, and phage-treated mouse lungs were taken at the Australian Synchrotron Imaging and Medical Beamline. Using XV we measured local lung expansion and ventilation throughout the breath cycle, analysing the skew of the lung expansion distribution. CT images allowed visualisation of the projected air volume in the lungs, assessing structural lung damage. XV analysis demonstrated changes in lung expansion between infection and control groups, however there were no statistically significant differences between treated and placebo groups. In some cases where structural changes were not evident in the CT scans, XV successfully detected changes in lung function., Competing Interests: Declaration. Competing interests: Martin Donnelley and Stephen Dubsky own shares in 4DMedical. Stephanie A. Harker, Melissa Preissner, Rachel Yoon Chang, David Trevascus, Chengxi Liu, Yuncheng Wang, Michael Yee Chow, Patricia Cmielewski, Nicole Reyne, Ying Ying How, James A. Pollock, Mitzi Klein, Christopher A. Wright, Hak-Kim Chan, and Kaye S. Morgan have no competing interests., (© 2024. The Author(s).)

The emergence of multidrug-resistant Acinetobacter baumannii (MDR-AB), which most commonly manifests as pneumonia, has posed significant clinical challenges and called for novel treatment strategies. Phage depolymerases, which degrade bacterial surface carbohydrates, have emerged as potential antimicrobial agents. However, their preclinical application is limited to systemic infections due to their dependency on serum-mediated bacterial killing. To extend the treatment paradigm of depolymerase to low-serum lung infections, we explored the feasibility of applying phage depolymerase to potentiate antibiotic efficacy in controlling MDR-AB pneumonia. Using a model depolymerase, Dpo71, we observed that it could effectively potentiate antibiotic efficacy against MDR-AB2 bacteria in low-serum conditions mimicking lung milieu but showed no adjuvant effect in serum-free conditions. Unprecedentedly, we reported this low-serum-dependent mechanism that polysaccharide-degrading enzyme Dpo71 exposed bacteria to serum-induced membrane permeabilization and oxidative phosphorylation pathway inhibition, leading to a weakened ATP-dependent efflux pump and strengthened ROS-induced membrane permeabilization. These joint effects facilitated antibiotic (ceftazidime, CFZ) binding, ultimately exerting bactericidal effects. Resultantly, the bacterial load in the lungs of the Dpo71-CFZ combination group was significantly reduced compared with the Dpo71-alone and CFZ-alone groups. Overall, this study unravels the low-serum-dependent mechanisms by which depolymerase potentiated antibiotic efficacy, highlighting its potential as a novel strategy to enhance antibiotic activity against severe pneumonia., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Substance abuse admission to health facilities following the pandemic is often met with challenges. COVID-19 is causing an insurmountable psychosocial impact on the whole of mankind. Marginalized communities, particularly those with substance use disorders (SUDs), are also likely to suffer from greater psychosocial burden., Objectives: This study sought to evaluate substance abuse trends before and during the pandemic., Methods: A cross-sectional study was conducted among patients attending selected government hospitals in Malaysia. Data from the year 2018 to 2021 was utilized., Results: A total of 9,606 patients consisting of 7881 males and 1725 females were identified. Most of the patients involved with substance abuse from 2018 to 2021 were males, aged between 26 and 44 years old, Malays, high school students, singles, workers of private sectors and those residing in urban areas. The most abused substances over the four years were tobacco (61.8%), followed by amphetamine-type stimulants (ATS) (43.1%), alcohol (39.7%), cannabis (17.2%), opioids (13.0%), and kratom (8.8%). Those who worked in the private sector and were self-employed or unemployed were more associated with substance abuse during the pandemic compared to those who worked in the government sector. Those with a history of psychiatric illness were more associated with abuse of substances during the pandemic than those without the history (adjusted OR: 1.18, 95% CI 1.09-1.29, p <0.001)., Conclusions: Targeted exploration of factors affecting substance abuse in Malaysia is essential. The results of this study assist in identifying variations in substance abuse treatment characteristics for those admitted to treatment in Malaysia., Competing Interests: The authors report no conflicts of interest., (Copyright: © 2024 Muhamad et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: The use of probiotic bacteria to improve lung health has been gaining interest. Although the oral delivery of probiotics and their effects are well documented, there is currently limited knowledge on the respiratory delivery of probiotics., Objectives: This study aimed to investigate whether nebulisation is suitable for delivering Lacticaseibacillus rhamnosus GG (LGG) into the lungs for the potential treatment of bacterial pulmonary infections., Methods: It compared the dose output and aerosol performance of a vibrating-mesh nebuliser (VMN) and a jet nebuliser (JN) in nebulising LGG suspended in de Man Rogosa Sharpe (MRS) broth, phosphate-buffered saline (PBS), or normal saline (0.9% w / v sodium chloride in water)., Results: The VMN consistently produced a higher output than the JN for all liquid media, indicating that VMN was more efficient. The fine-particle fractions of both nebulisers were comparable for a given medium. The highest fine-particle fraction was achieved with LGG suspended in MRS broth for both nebulisers (20.5 ± 2.8% for VMN; 18.7 ± 3.4% for JN). This suggests that the aerosol performance of nebulised probiotics may depend on the medium in which the probiotic bacteria were suspended., Conclusions: Therefore, this study demonstrated that the nebulisation efficiency of LGG depended on the nebuliser type and liquid medium of the probiotic suspension.

Introduction: Deprescribing serves as a pivotal measure to mitigate the drug-related problem due to polypharmacy. This study aimed to map the factors influencing healthcare providers' deprescribing decision using the Behaviour Change Wheel framework and develop an innovative conceptual model to support deprescribing practice., Methods: A cross-sectional online survey targeting doctors and pharmacists was conducted to assess the influence of various factors on healthcare providers' comfort in recommending deprescribing. The conceptual model was formulated, based on the existing deprescribing framework and the Behaviour Change Wheel. The model's robustness was scrutinised through Partial Least Squares Structural Equation Modeling (PLS-SEM), and model-fitting indices were employed to obtain the best-fit model., Results: A total of 736 responses were analysed with the final best-fit model consisting of 24 items in 5 constructs ( R 2 : 0.163; SRMR: 0.064; rho&#95;c: 0.750-0.862; AVE: 0.509-0.627) and three independent factors. Based on the results, we proposed that deprescribing could be promoted through strategies aimed at enhancing healthcare providers internal capabilities such as knowledge levels, when patients' condition deteriorated and previous experiences with adverse events of drugs. Organisational support in providing such educational opportunities is important, with the empowerment of patient and healthcare providers through policy enhancements, guideline development, and effective communication., Conclusion: The deprescribing behaviours of healthcare professionals are influenced by an intricate interplay of patient, prescriber, and system factors. Enhancing deprescribing practices necessitates a comprehensive strategy that encompasses providers and patients' education, the development of structured deprescribing guidelines, the implementation of deprescribing support tools, and the enhancement of communication between healthcare providers., Competing Interests: No potential conflict of interest was reported by the author(s)., (© 2024 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

Objectives: Airway management is a fundamental skill that Emergency Medical Services (EMS) clinicians must be prepared to perform on patients of any age. We performed one of the first epidemiological studies of out-of-hospital pediatric airway management utilizing the ESO data set., Methods: We used the 2019 ESO Data Collaborative public release research data set. We performed a descriptive analysis of all patients <18 years receiving at least one of the following airway management interventions: nasopharyngeal airway, oropharyngeal airway, noninvasive positive pressure ventilation (NIPPV), airway suctioning, bag-valve-mask ventilation (BVM), tracheal intubation (TI), supraglottic airway (SGA) or surgical airway placement. We determined the success rates for BVM, TI and SGA., Results: Among 7,422,710 911 EMS activations, there were 346,912 pediatric encounters that resulted in patient care. Airway management occurred in 27,071 encounters (7,803 per 100,000 pediatric EMS patient care events). Use of BVM, intubation or supraglottic airway insertion occurred in 3,496 encounters (1,007 per 100,000 pediatric EMS patient care events). Ventilation with BVM occurred in 2,226 encounters (642 per 100,000 pediatric EMS patient care events), TI in 935 pediatric EMS patient care encounters (270 per 100,000 patient care encounters), and supraglottic airway insertion in 335 patient encounters (97 per 100,000 patient care encounters). Overall TI success was 71.4%, rapid sequence intubation success was 86.3%, and SGA success was 87.2%. Overall TI first pass success rate was 63.1%., Conclusions: In the ESO cohort, advanced airway management of children occurred in only 5.9 in 10,000 911 emergency encounters. Overall and first pass success rates for TI were low. These data provide contemporary perspectives of pediatric prehospital airway management in the United States.

Limited attempts have been made previously to develop high-loading CBD inhalable powders, which are essential for high dose delivery. Therefore, this study aimed to develop and characterise inhalable powders with ≥ 95 % w/w CBD by wet ball milling. The effects of magnesium stearate (2 % and 5 %) and inhaler resistance (low-resistance and high-resistance RS01 inhalers) on aerosol performance were also compared. Wet ball milling produced CBD powders with > 50 % production yield. The milled particles showed irregular shapes. The powders were crystalline with minimal amorphous content, low residual solvent level (<1%), and low moisture sorption (<4%). Magnesium stearate improved both the emitted and fine particle fractions. The aerodynamic particle size distribution of the formulations differed between the low-resistance and high-resistance RS01 inhalers. The latter decreased throat deposition but increased inhaler retention. The dissolution profiles showed that all three formulations released CBD steadily and plateaued at 30 min. The best scenario was CBD with 5 % magnesium stearate dispersed from the high resistance RS01 inhaler, showing the highest FPF with the lowest throat deposition. This combination may be tested in vivo in the future to investigate its pharmacokinetic profile., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Pulmonary delivery is an efficient route of administration to deliver cannabidiol (CBD) due to the high bioavailability and fast onset of action. The major formulation challenge is the poor aqueous solubility of CBD. This study aimed to produce inhalable CBD powders with enhanced solubility and characterise their solid-state properties. CBD was spray freeze dried with mannitol or trehalose dihydrate with and without dipalmitoylphosphatidylcholine (DPPC). All four powders had acceptable yields at > 70 % with porous and spherical particles. The two crystalline mannitol powders contained less residual solvent than both amorphous trehalose ones. The addition of DPPC did not affect the crystallinity and residual solvent level of the powders. Instead, DPPC made the particles more porous, decreased the particle size from 19-23 µm to 11-13 µm, and increased CBD solubility from 0.36 µg/mL to over 2 µg/mL. The two DPPC powders were dispersed from a low resistance RS01 inhaler, showing acceptable aerosol performance with emitted fractions at 91-93 % and fine particle fractions < 5 µm at 34-43 %. These formulations can be used as a platform to deliver CBD and other cannabinoids by inhalation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

COVID-19 self-testing is essential for enabling individuals to self-care, screen themselves and, if positive, isolate themselves. Since 2021, COVID-19 self-tests have been extensively used in high-income countries, however, their programmatic implementation in low- and middle-income countries has been delayed. An implementation pilot, mixed-methods study, was conducted in four industrial manufacturing companies, in Kedah State between November 2022 and May 2023. Participants were asked to take COVID-19 self-tests home for themselves and their household members and to use the tests according to national guidelines. At enrolment and at the end of the study, participants completed an online sociodemographic, knowledge and satisfaction survey. Data were cleaned and analysed using SPSS Statistics V28.0. Qualitative data were collected through semi-structured interviews and focus group discussions. Thematic analysis was conducted. A total of 1768 employees from four manufacturing industries enrolled in the pilot, representing 60% of the total employees and more than 50% of employees at each site. There were 40 COVID-19-positive cases detected in participants from the manufacturing industries, and 100 positive household members. Participants reported 27 invalid test results. Individuals aged 30 or less [adjusted odds ratio (AOR): 2.65; 95% CI: 1.63 to 4.31; p<0.001] and males (AOR: 1.54; 95% CI: 1.09 to 2.17; p = 0.014) showed a significant higher likelihood of self-testing compared to older and female participants. Additionally, individuals who received three or more doses of a COVID-19 vaccine had higher odds of using self-tests (OR 1.56 (95% CI: 1.03 to 2.36, p = 0.037)). There was a significant increase in participants' knowledge on how to correctly collect a self-sample using a nasal swab from 36,9% at baseline to 43,6% post-implementation (p = 0.004) and correct interpretation of a positive result from 80,5% at baseline to 87,6% post-implementation (p<0.001). Furthermore, there was a notable increase in the correct understanding of actions following a positive result, especially regarding self-isolation, which rose from 59.1% to 71.9% (p<0.001). A total of 44 SSIs, and 4 FGDs with a total of 14 participants, were performed. The five main themes explored were: 1) previous experiences with COVID-19, 2) COVID-19 ST experiences during the pilot study, 3) advantages of COVID-19 ST, 4) feelings related to COVID-19 ST, 5) willingness to use COVID-19 ST again, and 6) ST for other diseases. This research shows the feasibility of a self-testing model in the community through workplaces due to participants' high acceptability to enrol and high self-tests' uptake. Lessons learnt can inform operational aspects of the introduction and scale-up of self-care strategies in low- and middle-income countries, in particular the South-East Asia region., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Chan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Aerosol drug delivery in the human airway is significantly affected by the morphology and size of the airway. This work developed a CFD-DEM model to simulate and analyze air flow and powder dynamics in combined inhaler-airway systems with different degrees of airway deformation (non-deformed, 50%, and 75% deformed) and sizes (adult, 0.80, and 0.62 scaled). The airways were generated based on a regular airway constructed from the MRI images through finite element method (for deformed airways) or scaling-down (for smaller airways). The airways were connected to Turbuhaler® through a connector. The results showed that under the same flow rate, the variation in the airway geometry and size had a minimum impact on the flow field and powder deposition in the device and the connector. However, deformation caused more particle deposition in the deformed region. Notably, the airway with 50% deformation had the most particles passing through the airway with the largest particle sizes due to its lower air velocity in the deformed area. Reducing airway size resulted in more powder deposition on the airway, particularly at the pharynx and mouth regions. This was because, with the same flow rate, the flow velocity in the smaller airway was higher, causing more particle-wall collisions in the mouth and pharynx regions. More importantly, the deposition efficiency in the 0.62-scaled airway was significantly higher than the other two airways, highlighting the importance of the different administration of aerosol drugs for young children., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: To fulfil the diagnostic criteria of Attention Deficit Hyperactivity Disorder in the Fifth Edition of Diagnostic and Statistical Manual of Mental Disorders (DSM-5), symptoms should be observed in two or more settings. This implies that diagnostic procedures require observations reported from informants in different settings, such as teachers in school and caregivers at home. This study examined parent-teacher agreement in reporting hyperactivity/inattention and its relationship with child's, parent's, and family's characteristics., Method: We used data from the 2004 United Kingdom Mental Health of Children and Young People survey, including 7977 children aged 4-17, to investigate cross-informant agreement between parents and teachers on the hyperactivity-inattention subscale of the Strengths and Difficulties Questionnaire. The characteristics of different patterns of informant agreement were assessed using multinomial logistic regression., Results: Cross-informant agreement of parent and teacher was low (weighted kappa = .34, 95% C.I.: .31, .37). Some characteristics, such as male child and parental emotional distress, were associated with higher likelihood of parent-teacher discrepancy., Conclusion: We found low informant agreement in the hyperactive/inattention subscale, as hypothesised and consistent with previous studies. The current study has found several factors that predict discrepancy, which were partly consistent with previous research. Possible explanation, implications, and further research on parent-teacher informant discrepancy in reporting hyperactivity/inattention were discussed., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Chan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: Although COVID-19 has entered the endemic phase, individuals infected with COVID-19 are required to adhere to home quarantine measures. By exploring the public's knowledge and attitude towards recommended home quarantine measures, their readiness in containing potential COVID-19 outbreak can be determined. This study aimed to assess the public knowledge and attitude towards home quarantine instructions and their association with history of COVID-19 infections., Methods: This was a web-based cross-sectional study conducted among the public in Malaysia between August to October 2022. All Malaysian adults over 18 years of age were included. Knowledge on home quarantine instructions and COVID-19 warning signs were measured using "True," "False," or "I'm not sure", while attitude towards home quarantine instructions was measured using a five-point Likert Scale. The questionnaire was initially constructed in English and then translated into the national language, Bahasa Malaysia. Face and content validation were performed. The internal consistency of the questionnaire was found to be satisfactory., Results: 1,036 respondents were analyzed, comprised mostly of females (743, 71.6%) with a history of COVID-19 (673, 64.9%). In the knowledge domain, more than 80% of the respondents answered 9 out of 11 home quarantine instructions statements correctly. 457 (44.1%) were unaware or unsure about the minimum distance of the infected individual's bed from the rest of the occupants in a shared bedroom. The respondents reported relatively weaker knowledge in identifying uncommon warning signs of COVID-19 deterioration, including anuria (162, 44.5%), ingestion problems (191, 52.5%), and immobility (195, 53.6%). In the attitude domain, more than 90% of respondents answered correctly in 8 out of 9 questions. Respondents with a previous history of COVID-19 infections had better knowledge than COVID-19 infection-naïve individuals towards both home quarantine instructions and COVID-19 warning signs., Conclusion: Most respondents had good knowledge and attitude towards home quarantine instructions, with those previously infected with COVID-19 showing greater awareness of uncommon warning signs. However, there was a notable lack of awareness regarding physical distancing within shared rooms, appropriate disinfectant use and mobility limitation within the household. This study highlights the knowledge gaps to be improved in future educational campaigns., (© 2024. The Author(s).)

Inhalation of pharmaceutical aerosol formulations is widely used to treat respiratory diseases. Spatially resolved thermal characterization offers promise for better understanding drug release rates from particles; however, this has been an analytical challenge due to the small particle size (from a few micrometers down to nanometers) and the complex composition of the formulations. Here, we employ nano-thermal analysis (nanoTA) to probe the nanothermal domain of a pharmaceutical aerosol formulation containing a mixture of fluticasone propionate (FP), salmeterol xinafoate (SX), and excipient lactose, which is widely used to treat asthma and chronic obstructive pulmonary disease (COPD). Furthermore, atomic force microscopy-infrared spectroscopy (AFM-IR) and AFM force measurements are performed to provide nanochemical and nanomechanical information to complement the nanothermal data. The colocalized thermal and chemical mapping clearly reveals the surface heterogeneity of the drugs in the aerosol particles and demonstrates the contribution of the surface chemical composition to the variation in the thermal properties of the particles. We present a powerful analytical approach for in-depth characterization of thermal/chemical/morphological properties of dry powder inhaler particles at micro- and nanometer scales. This approach can be used to facilitate the comparison between generics and reference inhalation products and further the development of high-performance pharmaceutical formulations., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Asthma is a common chronic disease amongst children. Epidemiological studies showed that the mortality rate of asthma in children is still high worldwide. Asthma control is therefore essential to minimize asthma exacerbations, which can be fatal if the condition is poorly controlled. Frequent monitoring could help to detect asthma progression and ensure treatment effectiveness. Although subjective asthma monitoring tools are available, the results vary as they rely on patients' self-perception. Emerging evidence suggests several objective tools could have the potential for monitoring purposes. However, there is no consensus to standardise the use of objective monitoring tools. In this review, we start with the prevalence and severity of childhood asthma worldwide. Then, we detail the latest available objective monitoring tools, focusing on their effectiveness in paediatric asthma management. Publications of spirometry, fractional exhaled nitric oxide (FeNO), hyperresponsiveness tests and electronic monitoring devices (EMDs) between 2016 and 2023 were included. The potential advantages and limitations of each tool were also discussed. Overall, this review provides a summary for researchers dedicated to further improving objective paediatric asthma monitoring and provides insights for clinicians to incorporate different objective monitoring tools in clinical practices., (© 2024. The Author(s).)

Respiratory infection caused by multi-drug resistant (MDR) Pseudomonas aeruginosa is challenging to treat. In this study, we investigate the optimal dose of anti-pseudomonas phage PEV31 (10 3 , 10 5 , and 10 8 PFU/mL) combined with ciprofloxacin (ranging from 1/8× MIC to 8× MIC) to treat the MDR P. aeruginosa strain FADD1-PA001 using time-kill studies. We determined the impact of phage growth kinetics in the presence of ciprofloxacin through one-step growth analysis. Single treatments with either phage PEV31 or ciprofloxacin (except at 8× MIC) showed limited bactericidal efficiency, with bacterial regrowth observed at 48 h. The most effective treatments were PEV31 at multiplicity of infection (MOI) of 0.1 and 100 combined with ciprofloxacin at concentrations above 1× MIC, resulting in a >4 log 10 reduction in bacterial counts. While the burst size of phage PEV31 was decreased with increasing ciprofloxacin concentration, robust antimicrobial effects were still maintained in the combination treatment. Aerosol samples collected from vibrating mesh nebulization of the combination formulation at phage MOI of 100 with 2× MIC effectively inhibited bacterial density. In summary, our combination treatments eradicated in vitro bacterial growth and sustained antimicrobial effects for 48 h. These results indicated the potential application of nebulization-based strategies for the combination treatment against MDR lung infections., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Introduction: Equitable healthcare delivery is essential and requires resources to be distributed, which include assets and healthcare workers. To date, there is no gold standard for measuring the correct number of physicians to meet healthcare needs. This rapid review aims to explore measurement tools employed to optimise the distribution of hospital physicians, with a focus on ensuring fair resource allocation for equitable healthcare delivery., Materials and Methods: A literature search was performed across PubMed, EMBASE, Emerald Insight and grey literature sources. The key terms used in the search include 'distribution', 'method', and 'physician', focusing on research articles published in English from 2002 to 2022 that described methods or tools to measure hospital-based physicians' distribution. Relevant articles were selected through a two-level screening process and critically appraised. The primary outcome is the measurement tools used to assess the distribution of hospital-based physicians. Study characteristics, tool advantages and limitations were also extracted. The extracted data were synthesised narratively., Results: Out of 7,199 identified articles, 13 met the inclusion criteria. Among the selected articles, 12 were from Asia and one from Africa. The review identified eight measurement tools: Gini coefficients and Lorenz curve, Robin Hood index, Theil index, concentration index, Workload Indicator of Staffing Need method, spatial autocorrelation analysis, mixed integer linear programming model and cohortcomponent model. These tools rely on fundamental data concerning population and physician numbers to generate outputs. Additionally, five studies employed a combination of these tools to gain a comprehensive understanding of physician distribution dynamics., Conclusion: Measurement tools can be used to assess physician distribution according to population needs. Nevertheless, each tool has its own merits and limitations, underscoring the importance of employing a combination of tools. The choice of measuring tool should be tailored to the specific context and research objectives.

There are many modeling works that aim to explain people's behaviors that violate classical economic theories. However, these models often do not take into full account the multi-stage nature of real-life problems and people's tendency in solving complicated problems sequentially. In this work, we propose a descriptive decision-making model for multi-stage problems with perceived post-decision information. In the model, decisions are chosen based on an entity which we call the 'anticipated surprise'. The reference point is determined by the expected value of the possible outcomes, which we assume to be dynamically changing during the mental simulation of a sequence of events. We illustrate how our formalism can help us understand prominent economic paradoxes and gambling behaviors that involve multi-stage or sequential planning. We also discuss how neuroscience findings, like prediction error signals and introspective neuronal replay, as well as psychological theories like affective forecasting, are related to the features in our model. This provides hints for future experiments to investigate the role of these entities in decision-making., (© 2024. The Author(s).)

Hepatitis C self-testing (HCVST) is emerging as an additional strategy that could help to expand access to HCV testing. We conducted a study to assess the usability and acceptability of two types of HCVST, oral fluid- and blood-based, among the general population and men who have sex with men (MSM) in Malaysia. An observational study was conducted in three primary care centres in Malaysia. Participants who were layman users performed the oral fluid- and blood-based HCVST sequentially. Usability was assessed by calculating the rate of errors observed, the rate of difficulties faced by participants as well as inter-reader (self-test interpreted by self-tester vs interpreted by trained user) and inter-operator concordances (self-test vs test performed by trained user). The acceptability of HCV self-testing was assessed using an interviewer-administered semi-structured questionnaire. Participants were also required to read contrived test results which included "positive", "negative", and "invalid". There was a total of 200 participants (100 general population, 100 MSM; mean age 33.6 ± 14.0 years). We found a high acceptability of oral fluid- and blood-based HCVST across both general population and MSM. User errors, related to timekeeping and reading within stipulated time, were common. However, the majority of the participants were still able to obtain and interpret results correctly, including that of contrived results, although there was substantial difficulty interpreting weak positive results. The high acceptability of HCVST among the participants did not appreciably change after they had experienced both tests, with 97.0% of all participants indicating they would be willing to use HCVST again and 98.5% of them indicating they would recommend it to people they knew. There was no significant difference between the general population and MSM in these aspects. Our study demonstrates that both oral fluid- and blood-based HCVST are highly acceptable among both the general population and MSM. Both populations also showed comparable ability to conduct the tests and interpret the results. Overall, this study suggests that HCVST could be introduced as an addition to existing HCV testing services in Malaysia. Further studies are needed to establish the optimal positioning of self-testing alongside facility-based testing to expand access to HCV diagnosis in the country., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Chan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objective: Familial hypercholesterolaemia (FH) variant positive subjects have over double the cardiovascular risk of low-density-lipoprotein-cholesterol (LDL-C) matched controls. It is desirable to optimise FH variant detection., Methods: We identified 213 subjects with FH gene panel reports ( LDLR , APOB , PCSK9 , and APOE ) based on total cholesterol >310 mg/dL; excluding triglycerides >400 mg/dL, cascade screening, and patients without pre-treatment LDL-C recorded. Demographic, clinical and lipid parameters were recorded., Results: A 31/213 (14.6%) patients had pathogenic or likely pathogenic FH variants. 10/213 (4.7%) had variants of uncertain significance. Compared with patients without FH variants, patients with FH variants were younger (median age, 39 years vs. 48 years), had more tendon xanthomata (25.0% vs. 11.4%), greater proportion of first degree relatives with total cholesterol >95th percentile (40.6% vs. 16.5%), higher LDL-C (median, 271 mg/dL vs. 236 mg/dL), and lower triglycerides (median, 115 mg/dL vs. 159 mg/dL). The Besseling et al. model (c-statistic 0.798) improved FH variant discrimination over Friedewald LDL-C (c-statistic 0.724), however, Dutch Lipid Clinic Network Score (DLCNS) did not (c-statistic 0.665). Sampson LDL-C (c-statistic 0.734) had similar discrimination to Friedewald., Conclusion: Although tendon xanthomata and first degree relatives with high total cholesterol >95th percentile were associated with FH variants, DLCNS or Simon Broome criteria did not improve FH detection over LDL-C. Sampson LDL-C did not significantly improve discrimination over Friedewald. Although lower triglycerides and younger age of presentation are positively associated with presence of FH variants, this information is not commonly used in FH detection algorithms apart from Besseling et al., Competing Interests: Conflict of Interest: The authors have no conflicts of interest to declare., (Copyright © 2024 The Korean Society of Lipid and Atherosclerosis.)

Objective: We sought to describe prehospital ultrasound (PHUS) use and trends in PHUS utilization over time using a national database., Methods: Using the 2018 - 2021 National Emergency Medical Services Information System databases, we identified those EMS activations where PHUS was performed. We evaluated the association between year and number of PHUS exams performed using univariable and multivariable regression analysis. Analysis was performed on the overall group and various subgroups., Results: In total, there were 148,709,000 EMS activations by 13,899 agencies over the 4 years. Of these, 3,291 unique activations (0.002%) involved PHUS, performed by 71 EMS agencies (0.5%). The annual rate of ultrasound evaluations per 1 million EMS activations significantly increased over the study period: 5.2 in 2018, 14.8 in 2019, 18.6 in 2020, and 38.9 in 2021 ( p  < 0.01). The number of agencies performing PHUS each year increased over the study period from 11 in 2018 to 54 in 2021 ( p  < 0.05). Each year after 2018 had an increased odds of PHUS use demonstrated with logistic regression ( p  < 0.01). PHUS was used in each US census region, and paramedics performed most of the PHUS exams (75.5%). We identified 1,060 out-of-hospital cardiac arrest, 820 trauma, and 427 respiratory PHUS cases. These three cohorts accounted for 70.1% of all PHUS cases., Conclusion: Prehospital ultrasound use in the United States increased significantly over the study period, but remains exceedingly rare. The performance of PHUS was recorded throughout the United States, with paramedics performing the majority of PHUS studies included in this database.

This study evaluates the scale-free network assumption commonly used in COVID-19 epidemiology, using empirical social network data from SARS-CoV-2 Delta variant molecular local clusters in Houston, Texas. We constructed genome-informed social networks from contact and co-residence data, tested them for scale-free power-law distributions that imply highly connected hubs, and compared them to alternative models (exponential, log-normal, power-law with exponential cutoff, and Weibull) that suggest more evenly distributed network connections. Although the power-law model failed the goodness of fit test, after incorporating social network ties, the power-law model was at least as good as, if not better than, the alternatives, implying the presence of both hub and non-hub mechanisms in local SARS-CoV-2 transmission. These findings enhance our understanding of the complex social interactions that drive SARS-CoV-2 transmission, thereby informing more effective public health interventions., (© 2023. The Author(s).)

Background and Objective: Understanding the impact of inhaler resistance on particle transport and deposition in the human upper airway is essential for optimizing inhaler designs, thereby contributing to the enhancement of the therapeutic efficacy of inhaled drug delivery. This study demonstrates the potential effects of inhaler resistance on particle deposition characteristics in an anatomically realistic human oropharynx and the United States Pharmacopeia (USP) throat using computational fluid dynamics (CFD)., Method: Magnetic resonance (MR) imaging was performed on a healthy volunteer biting on a small mockup inhaler mouthpiece. Three-dimensional geometry of the oropharynx and mouthpiece were reconstructed from the MR images. CFD simulations coupled with discrete phase modelling were conducted. Inhaled polydisperse particles under two different transient flow profiles with peak inspiratory flow rates (PIFR) of 30 L/min and 60 L/min were investigated. The effect of inhaler mouthpiece resistance was modelled as a porous medium by varying the initial resistance (Ri) and viscous resistance (Rv). Three resistance values, 0.02 kPa 0.5 minL -1 , 0.035 kPa 0.5 minL -1 and 0.05 kPa 0.5 minL -1 , were simulated. The inhaler outlet velocity was set to be consistent across all models for both flow rate conditions to enable a meaningful comparison of models with different inhaler resistances., Result: The results from this study demonstrate that investigating the effect of inhaler resistance by solely relying on the USP throat model may yield misleading results. For the geometrically realistic oropharyngeal model, both the pressure and kinetic energy profiles at the mid-sagittal plane of the airway change dramatically when connected to a higher-resistance inhaler. In addition, the geometrically realistic oropharyngeal model appears to have a resistance threshold. When this threshold is surpassed, significant changes in flow dynamics become evident, which is not observed in the USP throat model. Furthermore, this study also reveals that the impact of inhaler resistance in a geometrically realistic throat model extends beyond the oral cavity and affects particle deposition downstream of the oral cavity, including the oropharynx region., Conclusion: Results from this study suggest that key mechanisms underpinning the working principles of inhaler resistance are intricately connected to their complex interaction with the pharynx geometry, which affects the local pressure, local variation in velocity and kinetic energy profile in the airway., Competing Interests: Declaration of competing interest All authors report no potential competing interests. The content of the manuscript has not been published or submitted for publication elsewhere, and all authors have approved the manuscript for the submission to Computers in Biology and Medicine., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Colorectal cancer (CRC) is a major cause of cancer-related mortality worldwide. It is the second leading cause of cancer death in men and women in Malaysia and poses a major burden on society., Aims: To determine the overall survival rate of patients diagnosed with CRC and factors contributing to survival., Methods: Data were obtained from the Malaysia National Cancer Registry. All patients with CRC were identified, and a total of 15,515 patients were screened. A total of 5,675 CRC patients were included from January 1, 2012, to December 31, 2016. Sex, age groups, ethnic groups, stage at diagnosis, cancer sites, and status of treatment received were analysed. The Kaplan-Meier analysis was performed to estimate the 1-, 3-, and 5-year survival of CRC. The log-rank test was conducted to compare the survival between sex, age groups, ethnic groups, stage at diagnosis, cancer sites, and status of treatment received. Multiple Cox regression was conducted to determine the risk of CRC death., Results: Of 5,675, a total of 2,055 had died, 3,534 were censored, and another 86 were still alive within 5 years of CRC diagnosis. The 1-, 3-, and 5-year survival rates were 68.5%, 34.7%, and 18.4%, respectively with a median survival time of 24 months. Significant differences in survival rates of CRC were observed between age groups ( p < 0.001), ethnic groups ( p < 0.001), stages at diagnosis ( p < 0.001), treatment status ( p = 0.003), and treatment modalities ( p < 0.001). No significant difference was observed in survival rates of CRC between sex ( p = 0.235) and cancer sites ( p = 0.410). Those who were 80 years old and above were found to be at higher risk of CRC death compared to those below 80 years old (adjusted hazard ratio (HR): 1.24, 95% CI 1.14-1.36). The risk of CRC death was also found four times higher among those with stage IV compared to those with stage 0 (adjusted HR: 4.28, 95% CI 3.26-5.62)., Conclusion: In general, Malaysian patients with CRC had low survival rates. National health policies should focus on enhancing awareness of CRC, encouraging early screening, and developing strategies for early detection and management to reduce CRC-associated mortality., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Muhamad, Ma’amor, Rosli, Leman, Abdul Mutalip, Chan, Yusof, Tamin, Aris, Lai and Abu Hassan.)

Capsule based dry powder inhalers (DPIs) often require piercing of the capsule before inhalation, and the characteristics of the apertures (punctured holes) affect air flow and the release of powders from the capsule. This work develops a numerical model based on the two-way coupling of computational fluid dynamics and discrete element method (CFD-DEM) to investigate the effect of aperture size on powder dispersion in the Aerolizer® device loaded with only carrier particles (lactose). Powders (carrier particles) in the size range 60-140 μm (d 50 : 90 μm and span: 0.66) were initialized in a capsule which had a circular aperture at each end. Boundary conditions corresponding to an air flow rate of 45 L/min were specified at each inlet to the mixing chamber (i.e., a total flow rate 90 L/min), and a capsule spin speed of ∼ 4050 rpm. The velocity magnitudes inside the capsule were considerably lower than those in the mixing chamber in the vicinity of the rotating capsule, with the exception of the capsules featuring 2.5 mm and 4 mm apertures. Larger apertures reduced the capsule emptying time and increased the particle evacuation velocity; the fluid drag force on the particles issuing from the capsule peaked for an aperture of 1.3 mm. Inside the capsule, particle-particle (PP) collisions were more frequent than particle-wall (PW) collisions due to high concentration of powder, but PP collisions had smaller (median) impact energy than PW collisions. Larger apertures resulted in fewer collisions in the capsule with higher PW and virtually unchanged PP collision energies. Outside the capsule (i.e., in the inhaler mixing chamber), PW collisions occurred more frequently than PP collisions with median collision energies typically two orders of magnitude higher than inside the capsule. Larger apertures resulted in more collisions with slightly reduced collision energy, but this effect plateaued for aperture sizes larger than 1.3 mm. Powder dispersion, expressed as the fine particle fraction (FPF) of the powder, was predicted using an empirical equation based on carrier PW collisions. Therefore, consistent with the model prediction of the effect of aperture sizes on the chamber collision frequency, FPF increased with aperture size but plateaued beyond 1.3 mm., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)