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By ensuring optimal dosing, therapeutic drug monitoring (TDM) improves outcomes in critically ill patients by maximizing effectiveness while minimizing toxicity. Current methods for measuring plasma drug concentrations, however, can be challenging, time-consuming, and slow to return an answer, limiting the extent to which TDM is used to optimize drug exposure. A potentially promising solution to this dilemma is provided by biosensors, molecular sensing devices that employ biorecognition elements to recognize and quantify their target molecules rapidly and in a single step. This paper reviews the current state of the art for biosensors regarding their application to TDM of antibiotics in the critically ill, both as ex vivo point-of-care devices supporting single timepoint measurements and in vivo devices supporting continuous real-time monitoring in situ in the body. This paper also discusses the clinical development of biosensors for TDM, including regulatory challenges and the need for standardized performance evaluation. We conclude by arguing that, through precise and real-time monitoring of antibiotics, the application of biosensors in TDM holds great promise for enhancing the optimization of drug exposure in critically ill patients, offering the potential for improved outcomes.

BackgroundElectronic consultation (eConsult) programs are crucial components of modern healthcare that facilitate communication between primary care providers (PCPs) and specialists. eConsults between PCPs and specialists. They also provide a unique opportunity to use real-world patient scenarios for reflective learning as part of professional development. However, tools that guide and document learning from eConsults are limited. The purpose of this study was to develop and pilot two eConsult reflective learning tools (RLTs), one for PCPs and one for specialists, for those participating in eConsults.MethodsWe performed a four-phase pragmatic mixed methods study recruiting PCPs and specialists from two public health systems located in two countries: eConsult BASE in Canada and San Francisco Health Network eConsult in the United States. In phase 1, subject matter experts developed preliminary RLTs for PCPs and specialists. During phase 2, a Delphi survey among 20 PCPs and 16 specialists led to consensus on items for each RLT. In phase 3, we conducted cognitive interviews with three PCPs and five specialists as they applied the RLTs on previously completed consults. In phase 4, we piloted the RLTs with eConsult users.ResultsThe RLTs were perceived to elicit critical reflection among participants regarding their knowledge and practice habits and could be used for quality improvement and continuing professional development.ConclusionPCPs and specialists alike perceived that eConsult systems provided opportunities for self-directed learning wherein they were motivated to investigate topics further through the course of eConsult exchanges. We recommend the RLTs be subject to further evaluation through implementation studies at other sites.

Biomedical science students need to learn to code. Graduates face a future where they will be better prepared for research higher degrees and the workforce if they can code. Embedding coding in a biomedical curriculum comes with challenges. First, biomedical science students often experience anxiety learning quantitative and computational thinking skills and second biomedical faculty often lack expertise required to teach coding. In this study, we describe a creative coding approach to building coding skills in students using the packages of Processing and Arduino. Biomedical science students were taught by an interdisciplinary faculty team from Medicine and Health, Science and Architecture, Design and Planning. We describe quantitative and qualitative responses of students to this approach. Cluster analysis revealed a diversity of student responses, with a large majority of students who supported creative coding in the curriculum, a smaller but vocal cluster, who did not support creative coding because either the exercises were not sufficiently challenging or were too challenging and believed coding should not be in a Biomedical Science curriculum. We describe how two creative coding platforms, Processing and Arduino, embedded and used to visualize human physiological data, and provide responses to students, including those minority of students, who are opposed to coding in the curriculum This study found a variety of students responses in a final year capstone course of an undergraduate Biomedical Science degree where future pathways for students are either in research higher degrees or to the workforce with a future which will be increasingly data driven.

INTRODUCTION/AIMS: Facioscapulohumeral muscular dystrophy (FSHD) is a slowly progressive muscular dystrophy without approved therapies. In this study we evaluated whether locally acting ACE-083 could safely increase muscle volume and improve functional outcomes in adults with FSHD. METHODS: Participants were at least 18 years old and had FSHD1/FSHD2. Part 1 was open label, ascending dose, assessing safety and tolerability (primary objective). Part 2 was randomized, double-blind for 6 months, evaluating ACE-083240 mg/muscle vs placebo injected bilaterally every 3 weeks in the biceps brachii (BB) or tibialis anterior (TA) muscles, followed by 6 months of open label. Magnetic resonance imaging measures included total muscle volume (TMV; primary objective), fat fraction (FF), and contractile muscle volume (CMV). Functional measures included 6-minute walk test, 10-meter walk/run, and 4-stair climb (TA group), and performance of upper limb midlevel/elbow score (BB group). Strength, patient-reported outcomes (PROs), and safety were also evaluated. RESULTS: Parts 1 and 2 enrolled 37 and 58 participants, respectively. Among 55 participants evaluable in Part 2, the least-squares mean (90% confidence interval, analysis of covariance) treatment difference for TMV was 16.4% (9.8%-23.0%) in the BB group (P

This phase 2, double-blind, placebo-controlled, hypothesis-generating study evaluated the effects of oral reldesemtiv, a fast skeletal muscle troponin activator, in patients with spinal muscular atrophy (SMA). Patients ≥ 12 years of age with type II, III, or IV SMA were randomized into 2 sequential, ascending reldesemtiv dosing cohorts (cohort 1: 150 mg bid or placebo [2:1]; cohort 2: 450 mg bid or placebo [2:1]). The primary objective was to determine potential pharmacodynamic effects of reldesemtiv on 8 outcome measures in SMA, including 6-minute walk distance (6MWD) and maximum expiratory pressure (MEP). Changes from baseline to weeks 4 and 8 were determined. Pharmacokinetics and safety were also evaluated. Patients were randomized to reldesemtiv 150 mg, 450 mg, or placebo (24, 20, and 26, respectively). The change from baseline in 6MWD was greater for reldesemtiv 450 mg than for placebo at weeks 4 and 8 (least squares [LS] mean difference, 35.6 m [p = 0.0037] and 24.9 m [p = 0.058], respectively). Changes from baseline in MEP at week 8 on reldesemtiv 150 and 450 mg were significantly greater than those on placebo (LS mean differences, 11.7 [p = 0.038] and 13.2 cm H2O [p = 0.03], respectively). For 6MWD and MEP, significant changes from placebo were seen in the highest reldesemtiv peak plasma concentration quartile (Cmax > 3.29 μg/mL; LS mean differences, 43.3 m [p = 0.010] and 28.8 cm H2O [p = 0.0002], respectively). Both dose levels of reldesemtiv were well tolerated. Results suggest reldesemtiv may offer clinical benefit and support evaluation in larger SMA patient populations.

A practical focusing on the synthesis, isolation, and hydrolysis of ammonia borane (AB), H[subscript 3]N·BH[subscript 3], was developed for first-year undergraduate students. By requiring students to propose their own experimental setup to measure the amount of gas produced upon hydrolysis, experimental design skills were introduced and developed during the practical. As a result of the COVID-19 pandemic, remote and face-to-face versions of the practical were created to enable inclusivity in which experimental design skills were a key feature. Students identified and reported an appreciable increase in their experimental design skills. The multifaceted nature of the practical allows for flexibility in its implementation, dependent on students' prior knowledge, local logistical considerations, and the learning objectives of an institution.

Teaching practical laboratory skills is a key component of preparing undergraduate students for future careers in chemistry and elsewhere. In this paper, we present our new strategy to teach practical skills to undergraduate chemistry students. We report a Skills Inventory, a list of the suggested practical skills a graduate chemist should possess; this list was compiled by chemists across the UK. In our new practical course we begin by decoupling the practical skill from the theoretical background, compelling students to first master the basic processes needed to carry out a specific technique. In what we have termed a ‘spiral curriculum’ approach, skills are revisited on multiple occasions, with increasing complexity and greater emphasis on underlying theory. The new course makes links across traditional subdisciplines of chemistry to avoid compartmentalisation of ideas.

Since the sudden emergence of COVID-19 global pandemic, all educational institutions have looked to move resources and delivery online. Some institutions had already embraced delivering instruction in this way; however, broader adaptation to this teaching style is new to many educators. While the teaching of theoretical concepts is more easily transferred to a blended learning environment, the teaching of practical chemistry poses significant challenges, yet it is crucial to the chemist's identity. Here we describe the establishment of a new, international, network to consider how practical chemistry can be taught outside of the traditional laboratory environment and invite readers of this special edition of the journal to join. Meeting fortnightly and maintaining links through a shared networked drive between meetings, the network has been accessed by over 100 delegates in the U.K., mainland Europe, North America, and Australasia. The traditional siloes of chemistry have not defined the discussions, which have instead focused on logistical aspects such as social distancing and the pastoral role of the laboratory environment. Initial evaluation shows the network is valued by its members and is making progress toward its aims.

Data-handling, processing, and analysis skills are an integral part of a chemist's skill set and, more generally, are highly sought by employers. We report a self-directed workshop to develop and advance these key skills using the popular spreadsheet program Microsoft Excel. Making use of its accessible user interface, various contextualized problems relevant to chemistry are introduced, linking theory to practical applications and providing insight and understanding of processes that operate behind-the-scenes in many specialized data processing packages. The workshop has been delivered as a remote exercise for both our first and second year undergraduate cohorts (216 students completed). Students reported a positive impact from the workshop, including the development of a wide range of important skills, the utility for future practical work, and the effectiveness of communication remotely to address their issues.

Earth's field nuclear magnetic resonance (EFNMR) spectroscopy offers students a unique opportunity to consolidate their understanding of NMR spectroscopic theory through hands-on practice with a simple spectrometer. A comprehensive, 6 h experiment is presented for the introduction of low-field NMR techniques, covering spectroscopy, relaxivity, and imaging experiments in the Earth's magnetic field. This multifaceted practical session explores the concepts of free induction decay, pulse sequences, field homogeneity, relaxation times, J-coupling, and magnetic resonance imaging (MRI), which are reinforced through a series of experiments carried out within an undergraduate teaching laboratory. Students are required to alter parameters as they see fit in order to obtain data, ensuring their understanding of the theory behind NMR spectroscopy. The challenges overcome for the implementation of EFNMR spectroscopy in a modern undergraduate laboratory are also discussed, and detailed instructions are included for spectrometer setup.

BACKGROUND: Trials in rare diseases have many challenges, among which are the need to set up multiple sites in different countries to achieve recruitment targets and the divergent landscape of clinical trial regulations in those countries. Over the past years, there have been initiatives to facilitate the process of international study set-up, but the fruits of these deliberations require time to be operationally in place. FOR-DMD (Finding the Optimum Steroid Regimen for Duchenne Muscular Dystrophy) is an academic-led clinical trial which aims to find the optimum steroid regimen for Duchenne muscular dystrophy, funded by the National Institutes of Health (NIH) for 5 years (July 2010 to June 2015), anticipating that all sites (40 across the USA, Canada, the UK, Germany and Italy) would be open to recruitment from July 2011. However, study start-up was significantly delayed and recruitment did not start until January 2013. METHOD: The FOR-DMD study is used as an example to identify systematic problems in the set-up of international, multi-centre clinical trials. The full timeline of the FOR-DMD study, from funding approval to site activation, was collated and reviewed. Systematic issues were identified and grouped into (1) study set-up, e.g. drug procurement; (2) country set-up, e.g. competent authority applications; and (3) site set-up, e.g. contracts, to identify the main causes of delay and suggest areas where anticipatory action could overcome these obstacles in future studies. RESULTS: Time from the first contact to site activation across countries ranged from 6 to 24 months. Reasons of delay were universal (sponsor agreement, drug procurement, budgetary constraints), country specific (complexity and diversity of regulatory processes, indemnity requirements) and site specific (contracting and approvals). The main identified obstacles included (1) issues related to drug supply, (2) NIH requirements regarding contracting with non-US sites, (3) differing regulatory requirements in the five participating countries, (4) lack of national harmonisation with contracting and the requirement to negotiate terms and contract individually with each site and (5) diversity of languages needed for study materials. Additionally, as with many academic-led studies, the FOR-DMD study did not have access to the infrastructure and expertise that a contracted research organisation could provide, organisations often employed in pharmaceutical-sponsored studies. This delay impacted recruitment, challenged the clinical relevance of the study outcomes and potentially delayed the delivery of the best treatment to patients. CONCLUSION: Based on the FOR-DMD experience, and as an interim solution, we have devised a checklist of steps to not only anticipate and minimise delays in academic international trial initiation but also identify obstacles that will require a concerted effort on the part of many stakeholders to mitigate.

ObjectiveTo conduct a randomized trial to test the primary hypothesis that once-daily tadalafil, administered orally for 48 weeks, lessens the decline in ambulatory ability in boys with Duchenne muscular dystrophy (DMD).MethodsThree hundred thirty-one participants with DMD 7 to 14 years of age taking glucocorticoids were randomized to tadalafil 0.3 mg·kg-1·d-1, tadalafil 0.6 mg·kg-1·d-1, or placebo. The primary efficacy measure was 6-minute walk distance (6MWD) after 48 weeks. Secondary efficacy measures included North Star Ambulatory Assessment and timed function tests. Performance of Upper Limb (PUL) was a prespecified exploratory outcome.ResultsTadalafil had no effect on the primary outcome: 48-week declines in 6MWD were 51.0 ± 9.3 m with placebo, 64.7 ± 9.8 m with low-dose tadalafil (p = 0.307 vs placebo), and 59.1 ± 9.4 m with high-dose tadalafil (p = 0.538 vs placebo). Tadalafil also had no effect on secondary outcomes. In boys >10 years of age, total PUL score and shoulder subscore declined less with low-dose tadalafil than placebo. Adverse events were consistent with the known safety profile of tadalafil and the DMD disease state.ConclusionsTadalafil did not lessen the decline in ambulatory ability in boys with DMD. Further studies should be considered to confirm the hypothesis-generating upper limb data and to determine whether ambulatory decline can be slowed by initiation of tadalafil before 7 years of age.Clinicaltrialsgov identifierNCT01865084.Classification of evidenceThis study provides Class I evidence that tadalafil does not slow ambulatory decline in 7- to 14-year-old boys with Duchenne muscular dystrophy.

Despite corticosteroids being the only treatment documented to improve strength and function in boys with Duchenne muscular dystrophy (DMD) corticosteroid prescription is inconsistent and in some countries, corticosteroids are not prescribed. We are conducting a clinical trial that (1) compares the 3 most frequently prescribed corticosteroid regimes; (2) standardizes treatment of DMD complications; and (3) standardizes prevention of corticosteroid side effects. Investigators at 38 sites in 5 countries plan to recruit 300 boys aged 4-7 who are randomly assigned to one of three regimens: daily prednisone; daily deflazacort; or intermittent prednisone (10days on/10days off). Boys are followed for a minimum of 3years to assess the relative effectiveness and adverse event profiles of the different regimens. The primary outcome is a 3-dimensional variable consisting of log-transformed time to rise from the floor, forced vital capacity, and subject/parent satisfaction with treatment, each averaged over all post-baseline visits. The study protocol includes evidence- and consensus-based treatment of DMD complications and of corticosteroid side effects. This study seeks to establish a standard corticosteroid regimen for DMD. Since all new interventions for DMD are being developed as add-on therapies to corticosteroids, defining the optimum regimen is of importance for all new treatments.

Rationale Methods Results Conclusions Mass spectrometry (MS) is introduced to high school students in the UK in many pre‐university course syllabi. As such, we have identified the use of MS as a key technique that should be taught practically to undergraduates from the outset of their studies. This mini‐review describes how we introduce and develop students' use of MS throughout our three‐year undergraduate spiral curriculum practical programme, using atmospheric pressure chemical ionization MS (APCI‐MS).We have used an Advion ExpressionL spectrometer, fitted with an atmospheric solids analysis probe or a Plate Express TLC sampler for sample introduction.We have successfully demonstrated the use of APCI‐MS in a range of practicals and experiments covering organic and organometallic chemistries, with large cohorts of students gaining hands‐on instrumental experience in authentic research settings.APCI‐MS has proven to be an easy‐to‐use and valuable addition to our undergraduate practical course. The robustness of the spectrometer enables routine use by large cohorts of students with minimal supervision, and routine maintenance can be carried out by non‐specialist technicians. Students can readily process and interpret results for a series of routine analyses, as well as demonstrate uses in problem‐solving exercises. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Dystrophinopathy is a rare, severe muscle disorder, and nonsense mutations are found in 13% of cases. Ataluren was developed to enable ribosomal readthrough of premature stop codons in nonsense mutation (nm) genetic disorders. METHODS: Randomized, double-blind, placebo-controlled study; males ≥ 5 years with nm-dystrophinopathy received study drug orally 3 times daily, ataluren 10, 10, 20 mg/kg (N=57); ataluren 20, 20, 40 mg/kg (N=60); or placebo (N=57) for 48 weeks. The primary endpoint was change in 6-Minute Walk Distance (6MWD) at Week 48. RESULTS: Ataluren was generally well tolerated. The primary endpoint favored ataluren 10, 10, 20 mg/kg versus placebo; the week 48 6MWD Δ=31.3 meters, post hoc P=0.056. Secondary endpoints (timed function tests) showed meaningful differences between ataluren 10, 10, 20 mg/kg, and placebo. CONCLUSIONS: As the first investigational new drug targeting the underlying cause of nm-dystrophinopathy, ataluren offers promise as a treatment for this orphan genetic disorder with high unmet medical need.

Since 1970, Middle East and North African (MENA) countries have witnessed evolutionary industrial development and long-running terrorist and inter-country conflicts. Additionally, the risk of accidental, deliberate or natural chemical, biological, radiological, and nuclear (CBRN) threats has also increased, requiring a collaborative review of the health sectors' preparedness for potential CBRN risks within the region. This study aimed to explore the opinion of multidisciplinary experts interested in disaster management research in MENA about perspectives and challenges on readiness for potential CBRN incidents. A modified interview online link was sent to the participants. A qualitative thematic analysis was performed on the responses using Nvivo®12 software, following semistructured modified interviews using the Phonic® application. A total of 29 participants were sufficient to reach the data saturation. Through an inductive coding approach, five themes were identified: 'CBRN-Related Incidents are a Threat', 'Inadequate National Practice and Policy', 'Need for International Cooperation', 'Importance of Better Mass Gathering Management', and 'Ineffective Hospital Preparedness'. With the assistance of the World Health Organization, there is a consensus on the need for cooperation between the MENA countries to ensure adequate healthcare preparedness for CBRN threats. Suggested measures should be considered, such as creating a unified database and liaison officer designation. [ABSTRACT FROM AUTHOR]

Introduction Children with Duchenne muscular dystrophy (DMD) are at risk of experiencing fatigue that negatively impacts their health-related quality of life (HRQoL). This study aimed to assess the association between fatigue and HRQoL, by examining fatigue trajectories over 48 weeks, and assessing factors associated with these fatigue trajectories. Methods The study sample consisted of 173 DMD subjects enrolled in a 48-week-long phase 2 clinical trial (NCT00592553) for a novel therapeutic who were between the ages of 5 and 16 years. Results The results of regression modeling show baseline fatigue and baseline HRQoL (R2 = 0. 54 for child self-report and 0.51 for parent proxy report) and change in fatigue and HRQoL over 48 weeks (R2 = 0.47 for child self-report and 0.36 for parent proxy report) were significantly associated with one another. Three unique fatigue trajectories using Latent Class Growth Models were identified for child and parent proxy reported fatigue. The risk of being in the high fatigue group as compared to the low fatigue group increased by 24% with each year increase in age and also with decreasing walking distance, as reported by children and parent proxy, respectively. Conclusion This study identified fatigue trajectories and risk factors associated with greater fatigue, helping clinicians and researchers identify the profile of fatigue in DMD children. [ABSTRACT FROM AUTHOR]