The role of the surface ligand on the performance of electrochemical SARS-CoV-2 antigen biosensors.

Point-of-care (POC) technologies and testing programs hold great potential to significantly improve diagnosis and disease surveillance. POC tests have the intrinsic advantage of being able to be performed near the patient or treatment facility, owing to their portable character. With rapid results often in minutes, these diagnostic platforms have a high positive impact on disease management. POC tests are, in addition, advantageous in situations of a shortage of skilled personnel and restricted availability of laboratory-based analytics. While POC testing programs are widely considered in addressing health care challenges in low-income health systems, the ongoing pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections could largely benefit from fast, efficient, accurate, and cost-effective point-of-care testing (POCT) devices for limiting COVID-19 spreading. The unrestrained availability of SARS-CoV-2 POC tests is indeed one of the adequate means of better managing the COVID-19 outbreak. A large number of novel and innovative solutions to address this medical need have emerged over the last months. Here, we critically elaborate the role of the surface ligands in the design of biosensors to cope with the current viral outbreak situation. Their notable effect on electrical and electrochemical sensors' design will be discussed in some given examples. Graphical abstract.

I'm dreaming of a COVID-free Christmas.

BioTechniques Editors explore the evolution of point-of-care testing over the past 2 years, inside and outside of the COVID-19 pandemic.

Sample Preparation and Diagnostic Methods for a Variety of Settings: A Comprehensive Review.

Sample preparation is an essential step for nearly every type of biochemical analysis in use today. Among the most important of these analyses is the diagnosis of diseases, since their treatment may rely greatly on time and, in the case of infectious diseases, containing their spread within a population to prevent outbreaks. To address this, many different methods have been developed for use in the wide variety of settings for which they are needed. In this work, we have reviewed the literature and report on a broad range of methods that have been developed in recent years and their applications to point-of-care (POC), high-throughput screening, and low-resource and traditional clinical settings for diagnosis, including some of those that were developed in response to the coronavirus disease 2019 (COVID-19) pandemic. In addition to covering alternative approaches and improvements to traditional sample preparation techniques such as extractions and separations, techniques that have been developed with focuses on integration with smart devices, laboratory automation, and biosensors are also discussed.

Bedside Electrophysiological Study Using a Temporary Pacemaker May Predict Recurrence of Atrioventricular Block After Transcatheter Aortic Valve Replacement.

High-degree atrioventricular block (HAVB) or complete heart block (CHB) is a common complication associated with transcatheter aortic valve replacement (TAVR). However, some patients with HAVB/CHB recover with time. The results of electrophysiological studies (EPSs) using permanent pacemaker implantation (PPI) in patients with suspicious HAVB/CHB are considered controversial.This study aimed to evaluate whether HAVB/CHB induction at the bedside using a temporary pacemaker can predict recurrence in patients who had recovered from HAVB/CHB after TAVR.We enrolled a total of 11 patients who had recovered from HAVB/CHB and evaluated their electrophysiology using right ventricular pacing and/or procainamide administration.HAVB/CHB induction was positive. Three patients tested positive for HAVB/CHB, whereas 8 tested negative. The ejection fraction and the interval between HAVB/CHB onset and EPS were found to be significant. HAVB/CHB positive patients underwent PPI. A patient with a balloon-expandable valve tested positive just before recovery of CHB, but tested negative 5 days later and was included in the negative group. The 4 patients who tested negative received a cardiovascular implantable electric device (CIED). We observed HAVB/CHB in 2 patients who had previously tested positive after 3 months. Among those who tested negative, those with CIED had no HAVB/CHB, and others showed neither HAVB/CHB on electrocardiogram nor experienced syncope or sudden death.Our EPS revealed that HAVB/CHB induction may predict HAVB/CHB recurrence after TAVR. Valve type and EPS timing may affect the results.

Recent progress on rapid SARS-CoV-2/COVID-19 detection by CRISPR-Cas13-based platforms.

The limitations of conventional diagnostic procedures, such as real-time PCR-based methods and serological tests, have led the scientific community to innovate alternative nucleic acid detection approaches for SARS-CoV-2 RNA, thereby addressing the dire need for increased testing. Such approaches aim to provide rapid, accurate, cost-effective, sensitive, and high-throughput detection of SARS-CoV-2 RNA, on multiple specimen types, and without specialized equipment and expertise. The CRISPR-Cas13 system functions as a sequence-specific RNA-sensing tool that has recently been harnessed to develop simplified and flexible testing formats. This review recapitulates technical advances in the most recent CRISPR-Cas13-based methods for SARS-CoV-2/COVID-19 diagnosis. The challenges and opportunities for implementing mass testing using these novel CRISPR-Cas13 platforms are critically analyzed.

Emerging applications of clinical ultrasonography.

In this work, we introduce the numerous emerging areas and frontiers in the use of point-of-care ultrasonography. Of these, we review the following three: 1) the use of clinical ultrasonography in infectious and tropical diseases (we address its usefulness in the diagnosis and follow-up of the main syndromes, in tropical diseases, and in areas with scarce resources); 2) the usefulness of clinical ultrasonography in the assessment of response to volume infusion in severely ill patients (we review basic concepts and the main static and dynamic variables used for this evaluation); and 3) the use of clinical ultrasonography in the assessment of muscle mass in elderly patients with primary sarcopenia (we review the main muscles and measurements used for it).

Automatic real-time analysis and interpretation of arterial blood gas sample for Point-of-care testing: Clinical validation.

BACKGROUND: Point-of-care arterial blood gas (ABG) is a blood measurement test and a useful diagnostic tool that assists with treatment and therefore improves clinical outcomes. However, numerically reported test results make rapid interpretation difficult or open to interpretation. The arterial blood gas algorithm (ABG-a) is a new digital diagnostics solution that can provide clinicians with real-time interpretation of preliminary data on safety features, oxygenation, acid-base disturbances and renal profile. The main aim of this study was to clinically validate the algorithm against senior experienced clinicians, for acid-base interpretation, in a clinical context. METHODS: We conducted a prospective international multicentre observational cross-sectional study. 346 sample sets and 64 inpatients eligible for ABG met strict sampling criteria. Agreement was evaluated using Cohen's kappa index, diagnostic accuracy was evaluated with sensitivity, specificity, efficiency or global accuracy and positive predictive values (PPV) and negative predictive values (NPV) for the prevalence in the study population. RESULTS: The concordance rates between the interpretations of the clinicians and the ABG-a for acid-base disorders were an observed global agreement of 84,3% with a Cohen's kappa coefficient 0.81; 95% CI 0.77 to 0.86; p < 0.001. For detecting accuracy normal acid-base status the algorithm has a sensitivity of 90.0% (95% CI 79.9 to 95.3), a specificity 97.2% (95% CI 94.5 to 98.6) and a global accuracy of 95.9% (95% CI 93.3 to 97.6). For the four simple acid-base disorders, respiratory alkalosis: sensitivity of 91.2 (77.0 to 97.0), a specificity 100.0 (98.8 to 100.0) and global accuracy of 99.1 (97.5 to 99.7); respiratory acidosis: sensitivity of 61.1 (38.6 to 79.7), a specificity of 100.0 (98.8 to 100.0) and global accuracy of 98.0 (95.9 to 99.0); metabolic acidosis: sensitivity of 75.8 (59.0 to 87.2), a specificity of 99.7 (98.2 to 99.9) and a global accuracy of 97.4 (95.1 to 98.6); metabolic alkalosis sensitivity of 72.2 (56.0 to 84.2), a specificity of 95.5 (92.5 to 97.3) and a global accuracy of 93.0 (88.8 to 95.3); the four complex acid-base disorders, respiratory and metabolic alkalosis, respiratory and metabolic acidosis, respiratory alkalosis and metabolic acidosis, respiratory acidosis and metabolic alkalosis, the sensitivity, specificity and global accuracy was also high. For normal acid-base status the algorithm has PPV 87.1 (95% CI 76.6 to 93.3) %, and NPV 97.9 (95% CI 95.4 to 99.0) for a prevalence of 17.4 (95% CI 13.8 to 21.8). For the four-simple acid-base disorders and the four complex acid-base disorders the PPV and NPV were also statistically significant. CONCLUSIONS: The ABG-a showed very high agreement and diagnostic accuracy with experienced senior clinicians in the acid-base disorders in a clinical context. The method also provides refinement and deep complex analysis at the point-of-care that a clinician could have at the bedside on a day-to-day basis. The ABG-a method could also have the potential to reduce human errors by checking for imminent life-threatening situations, analysing the internal consistency of the results, the oxygenation and renal status of the patient.

CRISPR-based detection of SARS-CoV-2: A review from sample to result.

The current pandemic of the 2019 novel coronavirus (COVID-19) caused by SARS-CoV-2 (severe acute respiratory syndrome coronavirus-2) has raised significant public health concern. Rapid, affordable, and accurate diagnostics of SARS-CoV-2 is essential for early treatment and control of the disease spread. In the past few years, CRISPR technology has shown great potential for highly sensitive and specific molecular diagnostics. Amid the ongoing COVID-19 pandemic, there is an increasing interest in implementing CRISPR-based diagnostic principles to develop fast and precise methods for detecting SARS-CoV-2. In this work, we reviewed and summarized these CRISPR-based diagnostic systems as well as their characteristics and challenges. We also provided future perspectives of CRISPR-based sensing towards point-of-care molecular diagnosis applications.

A critical review of point-of-care diagnostic technologies to combat viral pandemics.

The COVID-19 global pandemic of 2019-2020 pointedly revealed the lack of diagnostic solutions that are able to keep pace with the rapid spread of the virus. Despite the promise of decades of lab-on-a-chip research, no commercial products were available to deliver rapid results or enable testing in the field at the onset of the pandemic. In this critical review, we assess the current state of progress on the development of point-of-care technologies for the diagnosis of viral diseases that cause pandemics. While many previous reviews have reported on progress in various lab-on-a-chip technologies, here we address the literature from the perspective of the testing needs of a rapidly expanding pandemic. First, we recommend a set of requirements to heed when designing point-of-care diagnostic technologies to address the testing needs of a pandemic. We then review the current state of assay technologies with a focus on isothermal amplification and lateral-flow immunoassays. Though there is much progress on assay development, we argue that the largest roadblock to deployment exists in sample preparation. We summarize current approaches to automate sample preparation and discuss both the progress and shortcomings of these developments. Finally, we provide our recommendations to the field of specific challenges to address in order to prepare for the next pandemic.

A Novel Approach to Hematology Testing at the Point of Care.

BACKGROUND: The need for rapid point-of-care (POC) diagnostics is now becoming more evident due to the increasing need for timely results and improvement in healthcare service. With the recent COVID-19 pandemic outbreak, POC has become critical in managing the spread of disease. Applicable diagnostics should be readily deployable, easy to use, portable, and accurate so that they fit mobile laboratories, pop-up treatment centers, field hospitals, secluded wards within hospitals, or remote regions, and can be operated by staff with minimal training. Complete blood count (CBC), however, has not been available at the POC in a simple-to-use device until recently. The HemoScreen, which was recently cleared by the FDA for POC use, is a miniature, easy-to-use instrument that uses disposable cartridges and may fill this gap. CONTENT: The HemoScreen's analysis method, in contrast to standard laboratory analyzers, is based on machine vision (image-based analysis) and artificial intelligence (AI). We discuss the different methods currently used and compare their results to the vision-based one. The HemoScreen is found to correlate well to laser and impedance-based methods while emphasis is given to mean cell volume (MCV), mean cell hemoglobin (MCH), and platelets (PLT) that demonstrate better correlation when the vision-based method is compared to itself due to the essential differences between the underlying technologies. SUMMARY: The HemoScreen analyzer demonstrates lab equivalent performance, tested at different clinical settings and sample characteristics, and might outperform standard techniques in the presence of certain interferences. This new approach to hematology testing has great potential to improve quality of care in a variety of settings.

Community Pharmacists: On the frontline of health service against COVID-19 in LMICs.

The COVID-19 outbreak is a global public health crisis which has affected healthcare practice across professions. In the context of this pandemic, there is a need to highlight the roles and responsibilities of pharmacists. Community pharmacists are the most accessible healthcare professionals to the general public and have a lot to offer amid the COVID-19 response. This have led to significant changes in the health systems of many countries. This article seeks to highlight additional roles and activities relating to the public health response that can be undertaken by community pharmacists that could help to reduce pressure on general practice and other areas of the health service.

Use of ultrasound for assessment of musculoskeletal disease in persons with haemophilia: Results of an International Prophylaxis Study Group global survey.

AIM: The objective of this survey was to understand the global trends of imaging assessments in persons with haemophilia, focusing on point-of-care ultrasound (POCUS). Insights into the barriers impeding its widespread proliferation as a frontline imaging modality were obtained. METHODS: The survey opened in September of 2017 and closed in May of 2018. Haemophilia Treatment Centres (HTCs) treating both paediatric/adult patients were the population of interest. A REDCap survey of 25 questions was disseminated to 232 clinical staff in 26 countries. RESULTS: The majority of respondents (88.3%, 91/103) reported that POCUS is most useful to confirm or rule out a presumed acute joint bleed. European HTCs reported the highest routine use of POCUS at 59.5% (22/37) followed by HTCs in the "Other" countries of the world at 46.7% (7/15) and North American HTCs at 43.9% (25/57). At the time of the survey, physiotherapists were identified as the clinical staff who perform POCUS 52.8% (28/53) of the time, in contrast with nurses/nurse practitioners who represent only 5.7% (3/53) of users. The greatest perceived barriers to the implementation of POCUS are the lack of trained healthcare professionals who can perform POCUS at 69.2% (74/107) and the overall time commitment required at 68.2% (73/107). CONCLUSION: Despite POCUS being used in 49.5% (54/109) of sampled HTCs, it is still utilized almost 30% less globally than full diagnostic ultrasound. A list of barriers has been identified to inform HTCs which challenges they will likely need to overcome should they choose to incorporate this imaging modality into their practice.

Cytokine and Cancer Biomarkers Detection: The Dawn of Electrochemical Paper-Based Biosensor.

Although the established ELISA-based sensing platforms have many benefits, the importance of cytokine and cancer biomarkers detection for point-of-care diagnostics has propelled the search for more specific, sensitive, simple, accessible, yet economical sensor. Paper-based biosensor holds promise for future in-situ applications and can provide rapid analysis and data without the need to conduct in a laboratory. Electrochemical detection plays a vital role in interpreting results obtained from qualitative assessment to quantitative determination. In this review, various factors affecting the design of an electrochemical paper-based biosensor are highlighted and discussed in depth. Different detection methods, along with the latest development in utilizing them in cytokine and cancer biomarkers detection, are reviewed. Lastly, the fabrication of portable electrochemical paper-based biosensor is ideal in deliberating positive societal implications in developing countries with limited resources and accessibility to healthcare services.

Designing and implementing an all Wales postpartum haemorrhage quality improvement project: OBS Cymru (the Obstetric Bleeding Strategy for Wales).

BACKGROUND: Postpartum haemorrhage (PPH) contributes to substantial maternal morbidity. Research into PPH has led to improvements in care which have been incorporated into the Obstetric Bleeding Strategy for Wales. INTERVENTION: A national quality improvement team supported local teams in implementing multiple interventions including risk assessment, objective measurement of blood loss, multiprofessional assessment (at the bedside at 1000 mL blood loss) and point-of-care (POC) testing of coagulation to guide blood product resuscitation during PPH. The project was rolled out to all 12 obstetric units in 2017. The interventions were reinforced by an All Wales Guideline, PPH proforma and standardised training. A national database, biannual audits, and patient and staff surveys reported process and outcome measures. RESULTS: Process measures: during 2017, there was an increase in the percentage of maternities with documented risk assessment (0%-76%), objective measurement of blood loss (52%-88%) and POC testing for coagulation for PPH ≥1500 mL (38%-59%). Maternity staff survey indicated that 94% were aware of the project and 87% stated that it had changed their unit's management of PPH. Interim outcome measures: the incidence (95% CI) of PPH ≥2500 mL per 1000 maternities in 2017 was 6.03 (5.23-6.95). The annual number of women receiving any red blood cell transfusion, level 3 intensive care admission and hysterectomy for PPH was 19.7 (18.2 to 21.3), 0.702 (0.464 to 1.06) and 0.255 (0.129 to 0.504) per 1000 maternities, respectively. CONCLUSIONS: A high level of project awareness across Welsh maternity units has been achieved. Measurement of blood loss was reported to be the most important early change in practice, while PPH documentation and POC testing continue to be embedded. Combining qualitative and quantitative measures to inform implementation has improved project delivery and allowed teams to adapt to local contexts.

Microfluidic Point-of-Care Devices: New Trends and Future Prospects for eHealth Diagnostics.

Point-of-care (PoC) diagnostics is promising for early detection of a number of diseases, including cancer, diabetes, and cardiovascular diseases, in addition to serving for monitoring health conditions. To be efficient and cost-effective, portable PoC devices are made with microfluidic technologies, with which laboratory analysis can be made with small-volume samples. Recent years have witnessed considerable progress in this area with "epidermal electronics", including miniaturized wearable diagnosis devices. These wearable devices allow for continuous real-time transmission of biological data to the Internet for further processing and transformation into clinical knowledge. Other approaches include bluetooth and WiFi technology for data transmission from portable (non-wearable) diagnosis devices to cellphones or computers, and then to the Internet for communication with centralized healthcare structures. There are, however, considerable challenges to be faced before PoC devices become routine in the clinical practice. For instance, the implementation of this technology requires integration of detection components with other fluid regulatory elements at the microscale, where fluid-flow properties become increasingly controlled by viscous forces rather than inertial forces. Another challenge is to develop new materials for environmentally friendly, cheap, and portable microfluidic devices. In this review paper, we first revisit the progress made in the last few years and discuss trends and strategies for the fabrication of microfluidic devices. Then, we discuss the challenges in lab-on-a-chip biosensing devices, including colorimetric sensors coupled to smartphones, plasmonic sensors, and electronic tongues. The latter ones use statistical and big data analysis for proper classification. The increasing use of big data and artificial intelligence methods is then commented upon in the context of wearable and handled biosensing platforms for the Internet of things and futuristic healthcare systems.

Sideline Concussion Assessment: The Current State of the Art.

More than 200 million American adults and children participate in organized physical activity. Growing awareness has highlighted that concussion, especially when repeated, may be associated with prolonged neurological, cognitive, and/or neuropsychiatric sequelae. Objective diagnosis of concussion remains challenging. Although some concussion symptoms may be apparent even to nonmedical observers, diagnosis and removal from play for evaluation depend on validated assessment tools and trained, vigilant healthcare personnel. Over the past 2 decades, sideline concussion measures have undergone significant revision and augmentation to become more comprehensive batteries in order to detect a wide spectrum of symptomatology, eg, neurocognitive function, postconcussive symptoms, gait/balance, and saccadic eye movements. This review summarizes the current state-of-the-art concussion evaluation instruments, ranging from the Sports Concussion Assessment Tool (SCAT) and tools that may enhance concussion detection, to near-term blood-based biomarkers and emerging technology (eg, head impact sensors, vestibulo-ocular/eye-tracking, and mobile applications). Special focus is directed at feasibility, utility, generalizability, and challenges to implementation of each measure on-field and on the sidelines. This review finds that few instruments beyond the SCAT provide guidance for removal from play, and establishing thresholds for concussion detection and removal from play in qualification/validation of future instruments is of high importance. Integration of emerging sideline concussion evaluation tools should be supported by resources and education to athletes, caregivers, athletic staff, and medical professionals for standardized administration as well as triage, referral, and prevention strategies. It should be noted that concussion evaluation instruments are used to assist the clinician in sideline diagnosis, and no single test can diagnose concussion as a standalone investigation.