Monitoring temperature and humidity in ambulance service rapid-response vehicles and paramedics medication bags: A pilot study

Background: In the pre-hospital context, paramedics carry medications in multi-compartment medication bags. However, these medications are occasionally subjected to temperature and humidity variations as they are being carried around by paramedics during their operational duties. 1,2 To develop a protocol to investigate medications’ stability inside these bags, a pilot study was needed to build a basic understanding of the temperature and humidity variations within both vehicles and bags and to guide the development of such a protocol. Methods: Data loggers, pre-programmed to record temperature and humidity every 5 minutes, were inserted inside two operational rapid-response vehicles and their respective medication bags for two full days (16-17/09/2020) when the outside temperature ranged from 30 to 40°C and the humidity ranged from 39% to 74%. 3 Following this, 4 data loggers were installed for one month inside 4 different medication bags (28/09/2020-28/10/2020) in similar operational vehicles when the outside temperature ranged from 23 to 42°C and the humidity ranged from 18% to 80%. 3 Logging data were extracted using special software (ElitechLog V6.0.3). Results: For the two-day study, temperature and humidity recordings were obtained (Figure 1). The mean (SD) temperature differences between both medication bags and their respective vehicles were -1.04°C (3.01) and 0.09°C (2.64)

A protocol to investigate the stability of 0.9% sodium chloride IV fluid bags in the prehospital setting of Qatar

Background: 0.9% sodium chloride (NaCl) fluid bags are commonly stored in ambulances. Despite that the ambulances normally use air-conditioning during operational shifts, NaCl bags are exposed to deviations from the controlled environmental conditions that could affect their integrity 1,2 , as all ambulances are not constantly in use. Although stress tests performed in a laboratory Binder Convection Oven 3 showed that NaCl maintained its stability, these findings need to be validated. This study aims to develop a protocol to evaluate the thermal stability of NaCl under real-life conditions in Qatar. Methods: Key aspects were considered to subject the research samples to the routine environmental conditions under which NaCl bags are stored in ambulances. The study bags are used for research purposes only, thus should not be used on patients (to avoid hindering the work of paramedics) and need to be tested after various exposure durations. Results: The agreed-upon study protocol is to be replicated on 5 ambulances over 12 months and includes 4 collection cycles of three 500 mL NaCl study bags and three 10 ml NaCl vials following different exposure durations (Table 1). Hence, 12 NaCl bags and 12 vials marked “for research-use-only” will be stored in a locked cabinet in the ambulance patient compartment alongside a temperature and humidity data logger taking measurements every 30 minutes (Figure 1). Control samples will be stored under manufacturer's recommended conditions. Following each collection cycle from the 5 ambulances and controls, samples will be stored at 4°C and protected from light until being visually inspected (for discoloration, turbidity, bulging), diluted, and tested using ion-exchange chromatography to measure sodium and chloride levels. Conclusion: This study performed under real-life conditions will help determine the effect of exposure to actual ambulance operational conditions on NaCl bags and may have a significant impact on how they are handled in the prehospital setting in countries with a hot/arid climate

Creation of an inventory of quality markers used to evaluate pharmacokinetic literature: A systematic review

What is known and objective: Robust critical appraisal tools for clinical pharmacokinetic studies are limited. Before development of such a tool is possible, quality markers (items deemed important for credibility of study results) must be identified. We aim to create an inventory of quality markers intended for the appraisal of clinical pharmacokinetic studies and to categorize identified markers into associated domains of study quality. Methods: Medline via ProQuest central (1946–Sep 2020, EMBASE (1974–Sep 2020), Cochrane database of systematic reviews, Google and Google Scholar were searched using the following search categories: pharmacokinetics, reporting guidelines and quality markers. Reference lists of the identified articles were searched manually. Any article (review, study or guideline) reporting quality markers related to the appraisal of pharmacokinetic literature was eligible for inclusion. Articles were further screened and limited to those reported in English on human subjects only. Cell-based and animal-based pharmacokinetic studies were excluded. Extracted data from included articles included identified or perceived markers of quality and baseline article data. Identified quality markers were then categorized according to manuscript reporting domains (abstract, introduction/background, methodology, results, discussion and conclusion). Results and discussion: Of 789 studies identified, 17 articles were included for extraction of quality markers. A total of 35 quality markers were identified across eight categories. The most frequently reported quality markers were related to method (13/35) and result sections (6/35). Quality markers encompassed all aspects of study design and reporting and were both similar and different to established reporting checklists for clinical pharmacokinetic studies. What is new and conclusion: The inventory of quality markers is now suitable to undergo further testing for inclusion in a tool designed for the appraisal of clinical pharmacokinetic studies

The use of a modified Delphi technique to develop a critical appraisal tool for clinical pharmacokinetic studies.

Critical appraisal aids in assessing the quality of scientific literature, which is central to the practice of evidence-based medicine. Several tools and guidelines are available for critiquing and assessing the quality of specific study types. However, limited guidance exists for critical appraisal of clinical pharmacokinetic studies. We aimed to achieve experts' consensus regarding the quality markers for clinical pharmacokinetic studies in an attempt to develop a critical appraisal tool. Quality markers related to clinical pharmacokinetic studies, were derived from the published literature and categorized according to manuscript reporting domains (abstract, introduction/background, methodology, results, discussion, and conclusion). Questions that aid in appraising pharmacokinetic studies were formulated from these quality markers. Experts were involved in a modified Delphi process to achieve a consensus regarding the formulated questions. The proposed tool was pilot tested on 30 recently published clinical pharmacokinetic studies. Inter-observer agreement was measured to determine the reliability of the included items. Twenty-five experts consented to participate. Three rounds of a modified Delphi survey were required to generate a consensus for a 21-item tool aimed at appraising the quality of clinical pharmacokinetic studies. When applied to 30 recently published clinical pharmacokinetic studies, most items scored fair to moderate levels of agreement (61.90-95.24%). The clinical pharmacokinetic critical appraisal tool (CACPK) developed in this study consisted of 21 items aimed at helping an end-user to determine the quality of a pharmacokinetic study. Further studies are warranted to reaffirm the validity and reliability of the CACPK tool.Open Access funding provided by the Qatar National Library

Intravenous fluids in hot pre-hospital environments: Thermal and physical stability of normal saline after exposure to simulated stress conditions

Background: Normal saline 0.9 % (NS) is the most widespread crystalloid used as a life-saving intravenous (IV) fluid. 1 NS contains sodium and chloride in equal concentrations and is subject to thermal stress conditions while stored and transported by clinicians in the pre-hospital environment. 2 This study aimed to investigate the effect of high-temperature exposure on NS bags used by the Hamad Medical Corporation Ambulance Service in Qatar. Methods: Five-hundred mL polyolefin NS soft bags (Qatar-Pharma, BN:1929013008) were divided into 4 groups of 24 each and stored at constant temperature (22, 50, or 70°C), or subjected to a temperature of 70°C for 8 hours followed by 22°C for 16 hours repeatedly over 28 days. Inspection and chromatographic analysis of the bags was performed at 0, 12, 24, 48, and 72 hours in the 72-hour study, and at 1, 2, 3, and 4 weeks in the 28-day study. Results: NS bags slightly bulged at 50°C and significantly bulged at 70°C or in the long experiment with temperature variation (Figure 1). During the exposure period, there was no discoloration, turbidity, or leaching of plastic components observed in the NS fluid. The pH readings were 5.59 ± 0.08 (22°C-Control sample), 5.73 ± 0.04 (50°C), 5.86 ± 0.02 (70°C), and 5.79 ± 0.03 following prolonged temperature variation. The sodium and chloride levels for the short-term study ranged from 100.2 ± 0.26% to 107.9 ± 0.75% and from 99.04 ± 0.76 to 102.11 ± 1.71%, and for the long-term study they ranged from 101.93 ± 0.90% to 111.27 ± 2.61 and from 99.05 ± 0.94% to 110.95 ± 1.63%; respectively (Figure 2) in comparison to manufacturer stated concentrations. Conclusion: There was no evidence to suggest that the NS fluid inside the PO bags is physically and chemically different when exposed up to 28 days to 50°C, 70°C, and prolonged temperature variations compared to 22°C. These simulated conditions are subject to further testing under real-life pre-hospital care emergency conditions in a hot country

PLGA-Gold Nanocomposite: Preparation and Biomedical Applications

A composite system consisting of both organic and inorganic nanoparticles is an approach to prepare a new material exhibiting “the best of both worlds”. In this review, we highlight the recent advances in the preparation and applications of poly(lactic-co-glycolic acid)-gold nanoparticles (PLGA-GNP). With its current clinically use, PLGA-based nanocarriers have promising pharmaceutical applications and can “extract and utilize” the fascinating optical and photothermal properties of encapsulated GNP. The resulting “golden polymeric nanocarrier” can be tracked, analyzed, and visualized using the encapsulated gold nanoprobes which facilitate a better understanding of the hosting nanocarrier’s pharmacokinetics and biological fate. In addition, the “golden polymeric nanocarrier” can reveal superior nanotherapeutics that combine both the photothermal effect of the encapsulated gold nanoparticles and co-loaded chemotherapeutics. To help stimulate more research on the development of nanomaterials with hybrid and exceptional properties, functionalities, and applications, this review provides recent examples with a focus on the available chemistries and the rationale behind encapsulating GNP into PLGA nanocarriers that has the potential to be translated into innovative, clinically applicable nanomedicine.A.M.A. acknowledge funding support from the University of Jordan. The APC was funded by the University of Illinois at Urbana-Champaign

A systematic review of stability of medicines used in emergency medical service settings

Background: Temperature, among several environment conditions like humidity, is known to impact medicine stability 1,2 . In emergency medical service (EMS) settings, it is often challenging to control these conditions. In the GCC region including Qatar, temperature and relative humidity values may rise over 50°C and 80%, respectively, according to climate data from the Qatar Civil Aviation Authority 3 . The aim of this systematic review is to collate and analyze data on the stability of EMS medicines exposed to temperature excursions beyond recommended limits (20-25°C with excursions up to 15-30°C) and provide evidence-based best practice recommendations on storage of medicines in EMS settings. Method: Literature on stability studies in EMS settings were obtained from PubMed, Embase, Web of Science and grey literature. Data from articles that met inclusion and exclusion criteria were collected using developed data collection forms then analyzed following PRISMA statement. The quality of articles were assessed using the Health Evidence Tool. Results: Thirteen studies were included (Table 1). Results were variable depending on the region and whether the study was done in an EMS setting or simulated in laboratory. Studies affirmed that medicines were exposed to temperatures beyond limits in EMS settings (Table 2). Medicines recommended to be refrigerated were not stable in a temperature-dependent manner. Although many medicines were stable, temperature-sensitive medicines degraded faster, while extreme cold produced various effects. No study has explored the biological effects of degradation and degradation products. Conclusion: EMS medicines are exposed to temperature extremes which may affect their stability and decrease their shelf-life. Therefore, routine stability testing during storage, replacement of exposed medicines and inclusion of temperature monitoring devices are paramount to validate the content of EMS medicines administered to end-users. We aim to collaborate with Hamad Medical Corporation Ambulance Service in Qatar to study the stability of EMS medicines in several settings including ambulances and paramedic bags of indoor and outdoor bike units.qscienc

Substantial cell apoptosis provoked by naked PAMAM dendrimers in HER2-positive human breast cancer via JNK and ERK1/ERK2 signalling pathways

HER2-positive breast cancer is one of its most challenging subtypes, forming around 15–25% of the total cases. It is characterized by aggressive behavior and treatment resistance. On the other hand, poly (amidoamine) (PAMAM) dendrimers are widely used in drug delivery systems and gene transfection as carriers. PAMAMs can modulate gene expression and interfere with transactivation of the human epidermal growth factor receptor family members (HER1-4). Nevertheless, the outcome of PAMAMs on HER2-positive breast cancer remains unknown. Thus, in this study, we investigated the anti-cancer effects of different generations of PAMAM dendrimers (G4 and G6) and the outcome of their surface chemistries (cationic, neutral, and anionic) on HER2-positive breast cancer cell lines, SKBR3 and ZR75. Our data showed that PAMAM dendrimers, mainly cationic types, significantly reduce cell viability in a dose-dependent manner. More significantly, PAMAMs induce substantial cell apoptosis, accompanied by the up-regulation of apoptotic markers (Bax, Caspases-3, 8 and 9) in addition to down-regulation of Bcl-2. Moreover, our data pointed out that cationic PAMAMs inhibit colony formation compared to controls and other types of PAMAMs. The molecular pathway analysis of PAMAM exposed cells revealed that PAMAMs enhance JNK1/2/3 expression while blocking ERK1/2, in addition to EGFR1 (HER1) and HER2 activities, which could be the major molecular pathway behind these events. These observed effects were comparable to lapatinib treatment, a clinically used inhibitor of HER1 and 2 receptors phosphorylation. Our findings implicate that PAMAMs may possess important therapeutic effects against HER2-positive breast cancer via JNK1/2/3, ERK1/2, and HER1/2 signalling pathways

Pharmaceutical Characterization of MyoNovin, a Novel Skeletal Muscle Regenerator: in silico, in vitro and in vivo Studies.

MyoNovin is a novel skeletal muscle-regenerating compound developed through synthesis of two nitro groups onto a guaifenesin backbone to deliver nitric oxide to skeletal muscle with a potential to treat muscle atrophy. The purpose of this study was to utilize in silico, in vitro, and in vivo approaches to characterize MyoNovin and examine its safety, biodistribution, and feasibility for drug delivery. In silico software packages were used to predict the physicochemical and biopharmaceutical properties of MyoNovin. In vitro cardiotoxicity was assessed using human cardiomyocytes (RL-14) while effects on CYP3A4 metabolic enzyme and antioxidant activity were examined using commercial kits. A novel HPLC assay was developed to measure MyoNovin concentration in serum, and delineate initial pharmacokinetic and acute toxicity after intravenous administration (20 mg/kg) to male Sprague-Dawley rats. MyoNovin showed relatively high lipophilicity with a LogP value of 3.49, a 20-fold higher skin permeability (19.89 cm/s*107) compared to guaifenesin (0.66 cm/s*107), and ~10-fold higher effective jejunal permeability (2.24 cm/s*104) compared to guaifenesin (0.26 cm/s*104). In vitro, MyoNovinwas not cytotoxic to cardiomyocytes at concentrations below 8 μM and did not inhibit CYP3A4 or show antioxidant activity. In vivo, MyoNovin had a short half-life (t1/2) of 0.16 h, and a volume of distribution Vss of 0.62 L/kg. Biomarkers of MyoNovincardiac and renal toxicity did not differ significantly from baseline control levels. The predicted high lipophilicity and skin permeability of MyoNovin render it a potential candidate for transdermal administration while its favourable intestinal permeation suggests it may be suitable for oral administration. Pharmacokinetics following IV administration of MyoNovin were delineated for the first time in a rat model. Preliminary single 20 mg/kg dose assessment of MyoNovin suggest no influenceon cardiac troponin or β-N-Acetylglucosaminidase. This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page

Trends in prescribing and outcomes in obese versus non-obese patients receiving rivaroxaban therapy: an observational study using real-world data

Purpose To investigate real-world prescribing trends and clinical outcomes based on body mass index (BMI) categorization in patients who received rivaroxaban therapy. Methods This was a retrospective cohort study involving all patients who received rivaroxaban therapy across all Hamad Medical Corporation (HMC) hospitals from 2015 to 2020. Results The number of patients initiated on rivaroxaban therapy significantly increased from 152 (3.3%) in 2015 to 1342 (28.9%) in 2020 (p <0.001). Within BMI categories, a similar increasing trend was observed in underweight, normal, and overweight patients, while from 2018 to 2020, there was a decreasing trend in rivaroxaban prescribing in all obese classes. The prevalence rate of all-cause mortality differed significantly between the BMI groups, with the highest mortality being among morbidly obese patients (BMI ≥ 40 kg/m2) (p< 0.001). On the other hand, no significant differences were found between the BMI groups in terms of bleeding, pulmonary embolism, deep vein thrombosis and stroke incidences. Multivariate logistic regression analyses showed that the likelihood of all-cause mortality was significantly higher in overweight and all categories of obese patients compared to underweight patients: overweight (OR: 5.3, 95% CI: 2.3–11.9, p< 0.001); obese class 1 (OR: 5.4, 95% CI: 2.3 – 12.2, p< 0.001); obese class 2 (OR: 6.5, 95% CI: 2.7 – 15.6, p< 0.001); and obese class 3 (OR: 3.7, 95% CI: 1.6 – 8.7, p = 0.003). Conclusions Rivaroxaban prescribing has significantly increased over the years across general population, with a noticeable decline in obese population during the last few years (from 2018 onwards). Furthermore, an appreciable association was evident between all-cause mortality and BMI of these patients.The study protocol and other associated study documents were approved by the HMC's Medical Research Centre (MRC-01-22-102) and the Institutional Review Board (IRB) at Qatar University before study initiation (QU-IRB1743-E/22).Scopu