Towards advancing Out-of-Hospital cardiac arrest (OHCA) registries globally: Considerations from the global OHCA registry (GOHCAR) collaborative.

A growing number out-of-hospital cardiac arrest (OHCA) registries have been developed across the globe. A few of these are national, while others cover larger geographical regions. These registries have common objectives; continuous quality improvement, epidemiological research and providing infrastructure for clinical trials. OHCA registries make performance comparison across Emergency Medical Services systems possible for benchmarking, hypothesis generation and further research. Changes in OHCA incidence and outcomes provide insights about the effects of secular trends or health services interventions. These registries, therefore, have become a mainstay of OHCA management and research. However, developing and maintaining these registries is challenging. Coordination of different service providers to support data collection, sustainable resourcing, data quality and data security are the key challenges faced by these registries. Despite all these challenges, noteworthy progress has been made and further standardization and co-ordination across registries can result in great international benefit. In this paper we present a 'why' and 'how to' model for setting up OHCA registries, and suggestions for better international co-ordination through a Global OHCA Registries Collaborative (GOHCAR). We draw together the knowledge of a cohort of international researchers, with experience and expertise in OHCA registry development, management, and data synthesis.

Increasing neurologically intact survival after out-of-hospital cardiac arrest among elderly: Singapore Experience.

Objectives: With more elderly presenting with Out-of-Hospital Cardiac Arrests (OHCAs) globally, neurologically intact survival (NIS) should be the aim of resuscitation. We aimed to study the trend of OHCA amongst elderly in a large Asian registry to identify if age is independently associated with NIS and factors associated with NIS. Methods: All adult OHCAs aged ≥18 years attended by emergency medical services (EMS) from April 2010 to December 2019 in Singapore was extracted from the Pan-Asian Resuscitation Outcomes Study (PAROS) registry. Cases pronounced dead at scene, non-EMS transported, traumatic OHCAs and OHCAs in ambulances were excluded. Patient characteristics and outcomes were compared across four age categories (18-64, 65-79, 80-89, ≥90). Multivariable logistic regression analysis determined the factors associated with NIS. Results: 19,519 eligible cases were analyzed. OHCA incidence increased with age almost doubling in octogenarians (from 312/100,000 in 2011 to 652/100,000 in 2019) and tripling in those ≥90 years (from 458/100,000 in 2011 to 1271/100,000 in 2019). The proportion of patients with NIS improved over time for the 18-64, 65-79- and 80-89-years age groups, with the greatest improvement in the youngest group. NIS decreased with each increasing year of age and minute of response time. NIS increased in the arrests of presumed cardiac etiology, witnessed and bystander CPR. Conclusions: Survival with good outcomes has increased even amongst the elderly. Regardless of age, NIS is possible with good-quality CPR, highlighting its importance. End-of-life planning is a complex yet necessary decision that requires qualitative exploration with elderly, their families and care providers.

Assertive community treatment for high-utilizing alcohol misuse patients: a before-and-after cohort study protocol.

BACKGROUND: The challenge posed by Alcohol-Related Frequent Attenders (ARFAs) in Emergency Departments (EDs) is growing in Singapore, marked by limited engagement with conventional addiction treatment pathways. Recognizing this gap, this study aims to explore the potential benefits of Assertive Community Treatment (ACT) - an innovative, community-centered, harm-reduction strategy-in mitigating the frequency of ED visits, curbing Emergency Medical Services (EMS) calls, and uplifting health outcomes across a quartet of Singaporean healthcare institutions. METHODS: Employing a prospective before-and-after cohort design, this investigation targeted ARFAs aged 21 years and above, fluent in English or Mandarin. Eligibility was determined by a history of at least five ED visits in the preceding year, with no fewer than two due to alcohol-related issues. The study contrasted health outcomes of patients integrated into the ACT care model versus their experiences under the exclusive provision of standard emergency care across Hospitals A, B, C and D. Following participants for half a year post-initial assessment, the evaluation metrics encompassed socio-demographic factors, ED, and EMS engagement frequencies, along with validated health assessment tools, namely Christo Inventory for Substance-misuse Services (CISS) scores, University of California, Los Angeles (UCLA) Loneliness scores, and Centre for Epidemiologic Studies Depression Scale Revised (CESD-R-10) scores. DISCUSSION: Confronted with intricate socio-economic and medical challenges, the ARFA cohort often grapples with heightened vulnerabilities in relation to alcohol misuse. Pioneering the exploration of ACT's efficacy with ARFAs in a Singaporean context, our research is anchored in a patient-centered approach, designed to comprehensively address these multifaceted clinical profiles. While challenges, like potential high attrition rates and sporadic data collection, are anticipated, the model's prospective contribution towards enhancing patient well-being and driving healthcare efficiencies in Singapore is substantial. Our findings have the potential to reshape healthcare strategies and policy recommendations. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04447079. Initiated on 25 June 2020.

Technology activated community first responders in Singapore: Real-world care delivery & outcome trends.

BACKGROUND: Community first responders (CFRs) strengthen the Chain of Survival for out-of-hospital cardiac arrest (OHCA) care. Considerable efforts have been invested in Singapore's CFR program, during the years 2016-2020, by developing an app-based activation system called myResponder. This paper reports on national CFR response indicators to evaluate the real-world impact of these efforts. METHODS: We matched data from the Singapore Civil Defence Force's CFR registry with the Pan Asian Resuscitation Outcomes Study (PAROS) registry data to calculate performance indicators. These included the number of CFRs receiving and accepting an issued alert per OHCA event. Also calculated were the fraction of OHCA events where CFRs received an issued alert, or accepted the alert, and arrived at the scene either before or after EMS. We also present trends of these indicators and compare the prevalence of these fractions between the CFR-attended and CFR-unattended OHCA events. RESULTS: Of 6577 alerted OHCA events, 42.7% accepted an alert, 50% of these arrived at the scene and 71% of them arrived before EMS. Almost all CFR response indicators improved over time even for the pandemic year (2020). The fraction of OHCA events where >2 CFRs received an alert increased from 62% to 96%; the same figure for accepting an alert did not change much but >2 CFRs arriving at the scene increased from 0% to 7.5%. The fraction of OHCA events with an automated external defibrillator applied and defibrillation performed by CFR increased from 4.2% to 10.3% and 1.6% to 3%, respectively. Statistically significant differences were observed in these indicators when CFR-attended and CFR-unattended OHCA events were compared. CONCLUSION: This real-world study shows that activating CFRs using mobile technology can improve community response to OHCA and are bearing fruit in Singapore at a national level. Some targets for improvement and future research are highlighted in this report.

Risk of wound infection with use of sterile versus clean gloves in wound repair at the Emergency Department: A systematic review and meta-analysis.

STUDY OBJECTIVE: Sterile gloves are widely used during wound repair procedures in Emergency Departments (ED) worldwide. It is unclear whether sterile gloves protect against postoperative wound infections. We conducted a systematic review and meta-analysis to determine if sterile gloves offer significant protection against wound infections compared to clean gloves for wound repair in the ED. METHODS: Ovid MEDLINE, Ovid Embase, Cochrane Library and Web Of Science were searched for randomised controlled trials (RCTs) or non-randomized studies of intervention (NRSIs) from their dates of inception to January 2023. RCTs or NRSIs comparing sterile (control) vs. clean/no (intervention) glove use for wound repair procedures in the ED and reporting postoperative wound infections were included. Two investigators independently extracted data and assessed risk-of-bias of each report on a standardised form. Wound infection incidence was pooled using a random effects model. Subgroup analysis was performed to explore heterogeneity. RESULTS: 7 studies were included in the review, with 6 included in the meta-analysis. Of 3227 patients, 115/1608 (7.2%) patients in the intervention group and 135/1619 (8.3%) patients in the control group had postoperative wound infections. Overall RR was 0.86 (95% CI,0.67-1.10, I2=3.6%), and of high evidence certainty (GRADE). Absence of a protective effect was invariant in sensitivity analyses, leave-one-out analysis and subgroup analyses. CONCLUSION: No evidence of additional protection against wound infections with the use of sterile gloves for wound repair in the ED compared to clean gloves was found. However, the review was limited by nonreporting of antibiotic history and time between wound repair and follow-up amongst included studies. Considering the ergonomics, potential cost-savings and environmental impact, clean gloves are a viable alternative to sterile gloves, without compromising wound infection risk in this setting.

Formulation development, in vivo bioequivalence and pediatric PBPK modeling studies of taste-masked ciprofloxacin chewable tablets.

A taste-masked chewable tablet of ciprofloxacin using ion exchange resin Kyron T-134 for enhancing compliance for the paediatric population was developed. The drug-to-resin ratio was optimized for maximum taste masking by studying the effects of soaking time (X1) and mixing time (X2) on complexation (%) using Central Composite Rotatable Design (CCRD). The resin complexes were characterized by bitterness score, DSC, FTIR, and PXRD. The complex was further formulated and optimized into chewable tablets through full factorial design, The optimized formulation was subjected to a bioequivalence study, and a virtual approach of PBPK modelling was adapted to predict the pharmacokinetics of the drug in the paediatric group. The drug resin ratio of 1:1.5 yielded an optimum drug loading of 99.05%. The optimized formulation shows minimum disintegration time with more than 99% drug release within 30 min. The formulation F-9 was found to be bioequivalent with a geometric mean ratio of Cmax, Tmax, AUC0-t, and AUC0-∞ within 90% CI. It was concluded that quality by design approach can successfully be applied to optimize the drug resin ratio and PBPK modeling is a successful predictive tool for estimating the pharmacokinetics of ciprofloxacin HCl in the paediatric population.

Artificial intelligence and machine learning in prehospital emergency care: A scoping review.

Our scoping review provides a comprehensive analysis of the landscape of artificial intelligence (AI) applications in prehospital emergency care (PEC). It contributes to the field by highlighting the most studied AI applications and identifying the most common methodological approaches across 106 included studies. The findings indicate a promising future for AI in PEC, with many unique use cases, such as prognostication, demand prediction, resource optimization, and the Internet of Things continuous monitoring systems. Comparisons with other approaches showed AI outperforming clinicians and non-AI algorithms in most cases. However, most studies were internally validated and retrospective, highlighting the need for rigorous prospective validation of AI applications before implementation in clinical settings. We identified knowledge and methodological gaps using an evidence map, offering a roadmap for future investigators. We also discussed the significance of explainable AI for establishing trust in AI systems among clinicians and facilitating real-world validation of AI models.

Halloysite nanotubes-cellulose ether based biocomposite matrix, a potential sustained release system for BCS class I drug verapamil hydrochloride: Compression characterization, in-vitro release kinetics, and in-vivo mechanistic physiologically based pharmacokinetic modeling studies.

This study investigated the ability of natural nanotubular clay mineral (Halloysite) and cellulose ether based biocomposite matrix as a controlled release agent for Verapamil HCl (BCS Class-I). Drug-loaded halloysite was prepared and tablet formulations were designed by varying amount of hydroxy propyl methyl cellulose (HPMC K4M). Physical characterization was carried out using SEM, FTIR, and DSC. Tabletability profiles were evaluated using USP1062 guidelines. Drug release kinetics were studied, and physiologically based pharmacokinetic (PBPK) modeling was performed. Compressed tablets possess satisfactory yield pressure of 625 MPa with adequate hardness and disintegration within 30 min. The initial release of the drug was due to surface drug on tablets, while the prolonged release at later time points (around 80 % drug release at 12 h) were due to halloysite loading. The FTIR spectra exhibited electrostatic attraction between the positively charged drug and the negatively charged Si-O-Si functional group of halloysite, while the thermogram showed Verapamil HCl melting point at ~146 °C with enthalpy change of -126.82 J/g. PBPK modeling exhibited PK parameters of optimized matrix formulation (VER-HNT3%) comparable to in vivo data. The study effectively demonstrated the potential of prepared biocomposite matrix as a commercially viable oral release modifying agent for highly soluble drugs.

Impact of time-to-compression on out-of-hospital cardiac arrest survival outcomes: A national registry study.

OBJECTIVE: We aimed to quantify the association of no-flow interval in out-of-hospital cardiac arrests (OHCA) with the odds of neurologically favorable survival and survival to hospital discharge/ 30th day. Our secondary aim was to explore futility thresholds to guide clinical decisions, such as prehospital termination of resuscitation. METHODS: All OHCAs from 2012 to 2017 in Singapore were extracted. We examined the association between no-flow interval (continuous variable) and survival outcomes using univariate and multivariable logistic regressions. The primary outcome was survival with favorable cerebral performance (Glasgow-Pittsburgh Cerebral Performance Categories 1/2), the secondary outcome was survival to hospital discharge/ 30th day if not discharged. To determine futility thresholds, we plotted the adjusted probability of good neurological outcomes to no-flow interval. RESULTS: 12,771 OHCAs were analyzed. The per-minute adjusted OR when no-flow interval was incorporated as a continuous variable in the multivariable model was: good neurological function- aOR 0.98 (95%CI: 0.97-0.98); survival to discharge- aOR 0.98 (95%CI: 0.98-0.99). Taking the 1% futility of survival line gave a no-flow interval cutoff of 12 mins (NPV 99%, sensitivity 85% and specificity 42%) overall and 7.5 mins for witnessed arrests. CONCLUSION: We demonstrated that prolonged no-flow interval had a significant effect on lower odds of favorable neurological outcomes, with medical futility occurring when no-flow interval was >12 mins (>7.5 mins for witnessed arrest). Our study adds to the literature of the importance of early CPR and EMS response and provided a threshold beyond traditional 'down-times', which could aid clinical decisions in TOR or OHCA management.

Automated mandatory bolus versus basal infusion for maintenance of epidural analgesia in labour.

BACKGROUND: Epidural analgesia is often used for pain relief during labour and childbirth, and involves administration of local anaesthetics (LA) into the epidural space resulting in sensory blockade of the abdomen, pelvis, and perineum. Epidural opioids are often co-administered to improve analgesia. Administration of epidural medications can be accomplished by basal infusion (BI) or automated mandatory bolus (AMB). With BI, medications are administered continuously, while AMB involves injecting medications at set time intervals. Patient-controlled epidural analgesia (PCEA) on top of AMB or BI enables patients to initiate additional boluses of epidural medications.  The superior method of delivering epidural medications would result in lower incidence of pain requiring anaesthesiologist intervention (breakthrough pain). Also, it should be associated with lower incidence of epidural-related adverse effects including caesarean delivery, instrumental delivery (use of forceps or vacuum devices), prolonged duration of labour analgesia, and LA consumption. However, clear evidence of the superiority of one technique over the other is lacking. Also, differences in the initiation of epidural analgesia such as combined spinal-epidural (CSE) (medications given into the intrathecal space in addition to the epidural space) compared to epidural only, and medications used (types and doses of LA or opioids) may not have been accounted for in previous reviews.  Our prior systematic review suggested that AMB reduces the incidence of breakthrough pain compared to BI with no significant difference in the incidence of caesarean delivery or instrumental delivery, duration of labour analgesia, and LA consumption. However, several studies comparing AMB and BI have been performed since then, and inclusion of their data may improve the precision of our effect estimates. OBJECTIVES: To assess the benefits and harms of AMB versus BI for maintaining labour epidural analgesia in women at term. SEARCH METHODS: We searched CENTRAL, Wiley Cochrane Library), MEDLINE, (National Library of Medicine), Embase(Elseiver), Web of Science (Clarivate), the WHO-ICTRP (World Health Organization) and ClinicalTrials.gov (National Library of Medicine) on 31 December 2022. Additionally, we screened the reference lists of relevant trials and reviews for eligible citations, and we contacted authors of included studies to identify unpublished research and ongoing trials. SELECTION CRITERIA: We included all randomised controlled studies that compared bolus dosing AMB with continuous BI during epidural analgesia. We excluded studies of women in preterm labour, with multiple pregnancies, with fetal malposition, intrathecal catheters, those that did not use automated delivery of medications, and those where AMB and BI were combined. DATA COLLECTION AND ANALYSIS: We used standard methodology for systematic review and meta-analysis described by Cochrane. Primary outcomes included: incidence of breakthrough pain requiring anaesthesiologist intervention; incidence of caesarean delivery; and incidence of instrumental delivery. Secondly, we assessed the duration of labour; hourly LA consumption in bupivacaine equivalents, maternal satisfaction after fetal delivery, and neonatal Apgar scores.  The following subgroup analyses were chosen a priori: epidural alone versus CSE technique; regimens that used PCEA versus those that did not; and nulliparous versus combination of nulli- and multi-parous women. We used the GRADE system to assess the certainty of evidence associated with our outcome measures. MAIN RESULTS: We included 18 studies of 4590 women, of which 13 enrolled healthy nulliparous women and five included healthy nulli- and multiparous women. All studies excluded women with preterm or complicated pregnancies. Techniques used to initiate epidural analgesia differed between the studies: seven used combined spinal epidural, 10 used epidural, and one used dural puncture epidural (DPE). There was also variation in analgesics used. Eight studies utilised ropivacaine with fentanyl, three used ropivacaine with sufentanil, two utilised levobupivacaine with sufentanil, one used levobupivacaine with fentanyl, and four utilised bupivacaine with fentanyl. Most of the studies were assessed to have low risk of randomisation, blinding, attrition, and reporting biases, except for allocation concealment where eight studies were assessed to have uncertain risk and three with high risk. Our results showed that AMB was associated with lower incidence of breakthrough pain compared to BI (risk ratio (RR) 0.71; 95% confidence interval (CI) 0.55 to 0.91; I2 = 57%) (16 studies, 1528 participants), and lower hourly LA consumption in bupivacaine equivalents (mean difference (MD) -0.84 mg/h; 95% CI -1.29 to -0.38, I2 = 87%) (16 studies, 1642 participants), both with moderate certainty. AMB was associated with an estimated reduction in breakthrough pain incidence of 29.1% (incidence 202 per 1000, 95% CI 157 to 259), and was therefore considered clinically significant. The incidence of caesarean delivery (RR 0.85; 95% CI 0.69 to 1.06; I2 = 0%) (16 studies, 1735 participants) and instrumental delivery (RR 0.85; 95% CI 0.71 to 1.01; I2 = 0%) (17 studies, 4550 participants) were not significantly, both with moderate certainty. There was no significant difference in duration of labour analgesia (MD -8.81 min; 95% CI -19.38 to 1.77; I2 = 50%) (17 studies, 4544 participants) with moderate certainty. Due to differences in the methods and timing of outcome measurements, we did not pool data for maternal satisfaction and Apgar scores. Results reported narratively suggest AMB may be associated with increased maternal satisfaction (eight studies reported increased satisfaction and six reported no difference), and all studies showed no difference in Apgar scores. WIth the exception of epidural alone versus CSE which found significant subgroup differences in LA consumption between AMB and BI, no significant differences were detected in the remaining subgroup analyses. AUTHORS' CONCLUSIONS: Overall, AMB is associated with lower incidence of breakthrough pain, reduced LA consumption, and may improve maternal satisfaction. There were no significant differences between AMB and BI in the incidence of caesarean delivery, instrumental delivery, duration of labour analgesia, and Apgar scores. Larger studies assessing the incidence of caesarean and instrumental delivery are required.

Does witness type affect the chance of receiving bystander CPR in out-of-hospital cardiac arrest?

OBJECTIVES: The relationship between the bystander witness type and receipt of bystander CPR (BCPR) is not well understood. Herein we compared BCPR administration between family and non-family witnessed out-of-hospital cardiac arrest (OHCA). BACKGROUND: In many communities, interventions in the past decade have contributed to an increased receipt of BCPR, for example in Singapore from 15% to 60%. However, BCPR rates have plateaued despite sustained and ongoing community-based interventions, which may be related to gaps in education or training for various witness types. The purpose of this study was to investigate the association between witness type and BCPR administration. METHODS: Singapore data from 2010-2020 was extracted from the Pan-Asian Resuscitation Outcomes Study (PAROS) network registry (n = 25,024). All adult, layperson witnessed, non-traumatic OHCAs were included in this study. RESULTS: Of 10,016 eligible OHCA cases, 6,895 were family witnessed and 3,121 were non-family witnessed. After adjustment for potential confounders, BCPR administration was less likely for non-family witnessed OHCA (OR 0.83, 95% CI 0.75, 0.93). After location stratification, non-family witnessed OHCAs were less likely to receive BCPR in residential settings (OR 0.75, 95% CI 0.66, 0.85). In non-residential settings, there was no statistically significant association between witness type and BCPR administration (OR 1.11, 95% CI 0.88, 1.39). Details regarding witness type and bystander CPR were limited. CONCLUSION: This study found differences in BCPR administration between family and non-family witnessed OHCA cases. Elucidation of witness characteristics may be useful to determine populations that would benefit most from CPR education and training.

SeDeM expert system with I-optimal mixture design for oral multiparticulate drug delivery: An encapsulated floating minitablets of loxoprofen Na and its in silico physiologically based pharmacokinetic modeling.

Introduction: A SeDeM expert tool-driven I-optimal mixture design has been used to develop a directly compressible multiparticulate based extended release minitablets for gastro-retentive drug delivery systems using loxoprofen sodium as a model drug. Methods: Powder blends were subjected to stress drug-excipient compatibility studies using FTIR, thermogravimetric analysis, and DSC. SeDeM diagram expert tool was utilized to assess the suitability of the drug and excipients for direct compression. The formulations were designed using an I-optimal mixture design with proportions of methocel K100M, ethocel 10P and NaHCO3 as variables. Powder was compressed into minitablets and encapsulated. After physicochemical evaluation lag-time, floating time, and drug release were studied. Heckel analysis for yield pressure and accelerated stability studies were performed as per ICH guidelines. The in silico PBPK Advanced Compartmental and Transit model of GastroPlus™ was used for predicting in vivo pharmacokinetic parameters. Results: Drug release follows first-order kinetics with fickian diffusion as the main mechanism for most of the formulations; however, a few formulations followed anomalous transport as the mechanism of drug release. The in-silico-based pharmacokinetic revealed relative bioavailability of 97.0%. Discussion: SeDeM expert system effectively used in QbD based development of encapsulated multiparticulates for once daily administration of loxoprofen sodium having predictable in-vivo bioavailability.

Implementation of Prediction Models in the Emergency Department from an Implementation Science Perspective-Determinants, Outcomes, and Real-World Impact: A Scoping Review.

STUDY OBJECTIVE: Prediction models offer a promising form of clinical decision support in the complex and fast-paced environment of the emergency department (ED). Despite significant advancements in model development and validation, implementation of such models in routine clinical practice remains elusive. This scoping review aims to survey the current state of prediction model implementation in the ED and to provide insights on contributing factors and outcomes from an implementation science perspective. METHODS: We searched 4 databases from their inception to May 20, 2022: MEDLINE (through PubMed), Embase, Scopus, and CINAHL. Articles that reported implementation outcomes and/or contextual determinants under the Reach, Effectiveness, Adoption, Implementation Maintenance (RE-AIM)/Practical, Robust, Implementation, and Sustainability Model (PRISM) framework were included. Characteristics of studies, models, and results of the RE-AIM/PRISM domains were summarized narratively. RESULTS: Thirty-six reports on 31 implementations were included. The most common prediction models implemented were early warning scores. The most common implementation strategies used were training stakeholders, infrastructural changes, and using evaluative or iterative strategies. Only one report examined ED patients' perspectives, whereas the rest were focused on the experience of health care workers or organizational stakeholders. Key determinants of successful implementation include strong stakeholder engagement, codevelopment of workflows and implementation strategies, education, and usability. CONCLUSION: Examining ED prediction models from an implementation science perspective can provide valuable insights and help guide future implementations.

SeDeM tool-driven full factorial design for osmotic drug delivery of tramadol HCl: Formulation development, physicochemical evaluation, and in-silico PBPK modeling for predictive pharmacokinetic evaluation using GastroPlus™.

The study is based on using SeDeM expert system in developing controlled-release tramadol HCl osmotic tablets and its in-silico physiologically based pharmacokinetic (PBPK) modeling for in-vivo pharmacokinetic evaluation. A Quality by Design (QbD) based approach in developing SeDEM-driven full factorial osmotic drug delivery was applied. A 24 Full-factorial design was used to make the trial formulations of tramadol HCl osmotic tablets using NaCl as osmogen, Methocel K4M as rate controlling polymer, and avicel pH 101 as diluent. The preformulation characteristics of formulations (F1-F16) were determined by applying SeDeM Expert Tool. The formulation was optimized followed by in-vivo predictive pharmacokinetic assessment using PBPK "ACAT" model of GastroPlus™. The FTIR results showed no interaction among the ingredients. The index of good compressibility (ICG) values of all trial formulation blends were ≥5, suggesting direct compression is the best-suited method. Formulation F3 and F4 were optimized based on drug release at 2, 10, and 16 h with a zero-order kinetic release (r 2 = 0.992 and 0.994). The SEM images confirmed micropores formation on the surface of the osmotic tablet after complete drug release. F3 and F4 were also stable (shelf life 29.41 and 23.46 months). The in vivo simulation of the pharmacokinetics of the PBPK in-silico model revealed excellent relative bioavailability of F3 and F4 with reference to tramadol HCl 50 mg IR formulations. The SeDeM expert tool was best utilized to evaluate the compression characteristics of selected formulation excipients and their blends for direct compression method in designing once-daily osmotically controlled-release tramadol HCl tablets. The in-silico GastroPlus™ PBPK modeling provided a thorough pharmacokinetic assessment of the optimized formulation as an alternative to tramadol HCl in vivo studies.

Management of Out-of-Hospital Cardiac Arrest during COVID-19: A Tale of Two Cities.

Variations in the impact of the COVID-19 pandemic on out-of-hospital cardiac arrest (OHCA) have been reported. We aimed to, using population-based registries, compare community response, Emergency Medical Services (EMS) interventions and outcomes of adult, EMS-treated, non-traumatic OHCA in Singapore and metropolitan Atlanta, before and during the pandemic. Associations of OHCA characteristics, pre-hospital interventions and pandemic with survival to hospital discharge were analyzed using logistic regression. There were 2084 cases during the pandemic (17 weeks from the first confirmed COVID-19 case) and 1900 in the pre-pandemic period (corresponding weeks in 2019). Compared to Atlanta, OHCAs in Singapore were older, received more bystander interventions (cardiopulmonary resuscitation (CPR): 65.0% vs. 41.4%; automated external defibrillator application: 28.6% vs. 10.1%), yet had lower survival (5.6% vs. 8.1%). Compared to the pre-pandemic period, OHCAs in Singapore and Atlanta occurred more at home (adjusted odds ratio (aOR) 2.05 and 2.03, respectively) and were transported less to hospitals (aOR 0.59 and 0.36, respectively) during the pandemic. Singapore reported more witnessed OHCAs (aOR 1.96) yet less bystander CPR (aOR 0.81) during pandemic, but not Atlanta (p < 0.05). The impact of COVID-19 on OHCA outcomes did not differ between cities. Changes in OHCA characteristics and management during the pandemic, and differences between Singapore and Atlanta were likely the result of systemic and sociocultural factors.

Nanoclay-Based Composite Films for Transdermal Drug Delivery: Development, Characterization, and in silico Modeling and Simulation.

Purpose: Halloysite nanotubes (HNTs) are a versatile and highly investigated clay mineral due to their natural availability, low cost, strong mechanical strength, biocompatibility, and binding properties. The present work explores its role for retarding and controlling the drug release from the composite polymer matrix material. Methods: For this purpose, nanocomposite films comprising propranolol HCl and different concentrations of HNTs were formulated using the "solution casting method". The menthol in a concentration of 1% w/v was used as a permeation enhancer, and its effect on release and permeation was also determined. Quality characteristics of the nanocomposite were determined, and in vitro release and permeation studies were performed using the Franz diffusion system. The data was analyzed using various mathematical models and permeation parameters. Optimized formulation was also subjected to skin irritation test, FTIR, DSC, and SEM study. Systemic absorption and disposition of propranolol HCl from the nanocomposites were predicted using the GastroPlus TCAT® model. Results: The control in drug release rate was associated with the higher concentration of HNTs. F8 released 50% of propranolol within 8 hours (drug, HNTs ratio, 1:2). The optimized formulation (F6) with drug: HNTs (2:1), exhibited drug release 80% in 4 hours, with maximum flux of 145.812 µg/cm2hr. The optimized formulation was found to be a non-irritant for skin with a shelf life of 35.46 months (28-30 ℃). The in silico model predicted Cmax, Tmax, AUCt , and AUCinf as 32.113 ng/mL, 16.58 h, 942.34 ng/mL×h, and 1102.9 ng/mL×h, respectively. Conclusion: The study demonstrated that HNTs could be effectively used as rate controlling agent in matrix type transdermal formulations.

An Agile Systems Modeling Framework for Bed Resource Planning During COVID-19 Pandemic in Singapore.

Background: The COVID-19 pandemic has had a major impact on health systems globally. The sufficiency of hospitals' bed resource is a cornerstone for access to care which can significantly impact the public health outcomes. Objective: We describe the development of a dynamic simulation framework to support agile resource planning during the COVID-19 pandemic in Singapore. Materials and Methods: The study data were derived from the Singapore General Hospital and public domain sources over the period from 1 January 2020 till 31 May 2020 covering the period when the initial outbreak and surge of COVID-19 cases in Singapore happened. The simulation models and its variants take into consideration the dynamic evolution of the pandemic and the rapidly evolving policies and processes in Singapore. Results: The models were calibrated against historical data for the Singapore COVID-19 situation. Several variants of the resource planning model were rapidly developed to adapt to the fast-changing COVID-19 situation in Singapore. Conclusion: The agility in adaptable models and robust collaborative management structure enabled the quick deployment of human and capital resources to sustain the high level of health services delivery during the COVID-19 surge.

Emergency department utilisation among older adults-Protocol for a systematic review of determinants and conceptual frameworks.

BACKGROUND: Older adults aged 65 years and above have a disproportionately higher utilization of emergency healthcare, of which Emergency Department (ED) visits are a key component. They experience higher degree of multimorbidity and mobility issues compared to younger patients, and are consequently more likely to experience a health event which requires an ED visit. During their visit, older adults tend to require more extensive workup, therefore spending a greater amount of time in the ED. Compared to the younger population, older adults are more susceptible to adverse events following discharge. Considering these factors, investigating the determinants of ED utilisation would be valuable. In this paper, we present a protocol for a systematic review of the determinants of ED utilisation among communitydwelling older adults aged 65 years and above, applying Andersen and Newman's model of healthcare utilisation. Furthermore, we aim to present other conceptual frameworks for healthcare utilisation and propose a holistic approach for understanding the determinants of ED utilisation by older persons. METHODS: The protocol is developed in accordance with the standards of Campbell Collaboration guidelines for systematic reviews, with reference to the Cochrane Handbook for Systematic Review of Interventions. Medline, Embase and Scopus will be searched for studies published from 2000 to 2020. Studies evaluating more than one determinant for ED utilisation among older adults aged 65 years and above will be included. Search process and selection of studies will be presented in a PRISMA flow chart. Statistically significant (p < 0.05) determinants of ED utilisation will be grouped according to individual and societal determinants. Quality of the studies will be assessed using Newcastle Ottawa Scale (NOS). DISCUSSION: In Andersen and Newman's model, individual determinants include predisposing factors, enabling and illness factors, and societal determinants include technology and social norms. Additional conceptual frameworks for healthcare utilisation include Health Belief Model, Social Determinants of Health and Big Five personality traits. By incorporating the concepts of these models, we hope to develop a holistic approach of conceptualizing the factors that influence ED utilisation among older people. SYSTEMATIC REVIEW REGISTRATION: This protocol is registered on 8 May 2021 with PROSPERO's International Prospective Register of Systematic Reviews (CRD42021253770).